COMPOSITION FOR ENHANCING INDUCTION OF HUMORAL IMMUNITY, AND VACCINE PHARMACEUTICAL COMPOSITION
20170216429 · 2017-08-03
Assignee
Inventors
- Takuya SHISHIDO (Osaka, JP)
- Daisuke ASARI (Osaka, JP)
- Kyohei MATSUSHITA (Osaka, JP)
- Mitsuhiko HORI (Osaka, JP)
Cpc classification
C12N2720/12334
CHEMISTRY; METALLURGY
C12N2760/20134
CHEMISTRY; METALLURGY
C12N2710/16734
CHEMISTRY; METALLURGY
A61K2039/6037
HUMAN NECESSITIES
C12N2760/18434
CHEMISTRY; METALLURGY
C12N2760/18734
CHEMISTRY; METALLURGY
C12N2770/32634
CHEMISTRY; METALLURGY
C12N2770/36234
CHEMISTRY; METALLURGY
C12N2770/24134
CHEMISTRY; METALLURGY
C12N2760/16134
CHEMISTRY; METALLURGY
C12N2730/10134
CHEMISTRY; METALLURGY
A61K39/39
HUMAN NECESSITIES
A61K2039/52
HUMAN NECESSITIES
A61K39/00
HUMAN NECESSITIES
Y02A50/30
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
C12N2710/20034
CHEMISTRY; METALLURGY
International classification
Abstract
The present invention aims to provide a composition for promoting humoral immunity induction and a vaccine pharmaceutical composition that can be universally used for various antigens in inducing humoral immunity to antigens, contain a Th2 reaction promoter, and exerts a high humoral immunity inducing effect. The present invention relates to a vaccine pharmaceutical composition containing an antigen for humoral immunity induction and at least one Th2 reaction promoter.
Claims
1. A composition for promoting humoral immunity induction, comprising: a Th2 reaction promoter.
2. The composition for promoting humoral immunity induction according to claim 1, wherein the Th2 reaction promoter is at least one of a phosphodiesterase inhibitor or a G protein-coupled receptor ligand.
3. The composition for promoting humoral immunity induction according to claim 1, wherein the Th2 reaction promoter is at least one selected from the group consisting of a drug that promotes synthesis of cyclic AMP (cAMP), a drug that reduces decomposition of cyclic AMP (cAMP), and a drug that suppresses a stimulus to phospholipase C (PLC).
4. The composition for promoting humoral immunity induction according to claim 3, wherein the drug that promotes synthesis of cyclic AMP (cAMP) is at least one selected from the group consisting of an adrenergic receptor ligand, a muscarinic receptor ligand, a dopamine receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, and a vasopressin receptor ligand; the drug that reduces decomposition of cyclic AMP (cAMP) is at least one selected from the group consisting of a phosphodiesterase inhibitor, an adrenergic receptor ligand, a muscarinic receptor ligand, a dopamine receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, a PAF receptor ligand, a purine receptor ligand, an opioid receptor ligand, a leukotriene receptor ligand, and an angiotensin receptor ligand; and the drug that suppresses a stimulus to phospholipase C (PLC) is at least one selected from the group consisting of an adrenergic receptor ligand, a muscarinic receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, a PAF receptor ligand, a vasopressin receptor ligand, a leukotriene receptor ligand, and an angiotensin receptor ligand.
5. A vaccine pharmaceutical composition, comprising: an antigen for humoral immunity induction; and the composition for promoting humoral immunity induction according to claim 1.
6. The vaccine pharmaceutical composition according to claim 5, which is administered to a body surface.
7. The vaccine pharmaceutical composition according to claim 5, which is administered by intradermal injection, subcutaneous injection, or intramuscular injection.
8. A method for promoting humoral immunity induction in a subject in need thereof, comprising: administering to the subject an effective amount of a Th2 reaction promoter.
9. The method for promoting humoral immunity induction according to claim 8, wherein the Th2 reaction promoter is at least one of a phosphodiesterase inhibitor or a G protein-coupled receptor ligand.
10. The method for promoting humoral immunity induction according to claim 8, wherein the Th2 reaction promoter is at least one selected from the group consisting of a drug that promotes synthesis of cyclic AMP (cAMP), a drug that reduces decomposition of cyclic AMP (cAMP), and a drug that suppresses a stimulus to phospholipase C (PLC).
11. The method for promoting humoral immunity induction according to claim 10, wherein the drug that promotes synthesis of cyclic AMP (cAMP) is at least one selected from the group consisting of an adrenergic receptor ligand, a muscarinic receptor ligand, a dopamine receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, and a vasopressin receptor ligand; the drug that reduces decomposition of cyclic AMP (cAMP) is at least one selected from the group consisting of a phosphodiesterase inhibitor, an adrenergic receptor ligand, a muscarinic receptor ligand, a dopamine receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, a PAF receptor ligand, a purine receptor ligand, an opioid receptor ligand, a leukotriene receptor ligand, and an angiotensin receptor ligand; and the drug that suppresses a stimulus to phospholipase C (PLC) is at least one selected from the group consisting of an adrenergic receptor ligand, a muscarinic receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, a PAF receptor ligand, a vasopressin receptor ligand, a leukotriene receptor ligand, and an angiotensin receptor ligand.
12. The method for promoting humoral immunity induction according to claim 8, wherein the Th2 reaction promoter is at least one drug that promotes synthesis of cyclic AMP (cAMP) selected from the group consisting of an adrenergic receptor ligand, a muscarinic receptor ligand, a dopamine receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, and a vasopressin receptor ligand.
13. The method for promoting humoral immunity induction according to claim 8, wherein the Th2 reaction promoter is at least one drug that reduces decomposition of cyclic AMP (cAMP) selected from the group consisting of a phosphodiesterase inhibitor, an adrenergic receptor ligand, a muscarinic receptor ligand, a dopamine receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, a PAF receptor ligand, a purine receptor ligand, an opioid receptor ligand, a leukotriene receptor ligand, and an angiotensin receptor ligand.
14. The method for promoting humoral immunity induction according to claim 8, wherein the Th2 reaction promoter is at least one drug that suppresses a stimulus to phospholipase C (PLC) selected from the group consisting of an adrenergic receptor ligand, a muscarinic receptor ligand, a histamine receptor ligand, a serotonin receptor ligand, a PAF receptor ligand, a vasopressin receptor ligand, a leukotriene receptor ligand, and an angiotensin receptor ligand.
15. A method for promoting humoral immunity induction in a subject in need thereof, comprising: administering to the subject an effective amount of a pharmaceutical composition comprising: an antigen for humoral immunity induction; and a Th2 reaction promoter.
Description
BRIEF DESCRIPTION OF DRAWINGS
[0147]
[0148]
[0149]
[0150]
[0151]
DESCRIPTION OF EMBODIMENTS
[0152] The present invention will be specifically described with reference to examples below. The present invention, however, is not limited to these examples.
Examples 1 to 30, Comparative Examples 1 to 8
[0153] (Preparation of solution for transmucosal administration) A solution for transmucosal administration was prepared according to the formulation shown in Tables 2 and 3. Specifically, an antigen and a Th2 reaction promoter were blended in the amounts specified in Tables 2 and 3, and 10 uL of saline was added thereto, followed by mixing to provide a vaccine composition.
[0154] Substances used are listed below.
Examples: resveratrol (Wako Pure Chemical Industries, Ltd.), vinpocetine (Yodogawa Seiyaku K.K.), pimobendan (LKT Laboratories), BRL50481 (Tocris Bioscience), dipyridamole (Wako Pure Chemical Industries, Ltd.), methoxyphenamine hydrochloride (MP Biomedicals), fenoldopam mesylate (LKT Laboratories), cisapride (Sigma-Aldrich), desmopressin (Sigma-Aldrich), prazosin hydrochloride (Wako Pure Chemical Industries, Ltd.), pirenzepine hydrochloride (Wako Pure Chemical Industries, Ltd.), oxybutynin hydrochloride (LKT Laboratories), tolterodine tartrate (HELM JAPAN), fluphenazine (Sigma-Aldrich), droperidol (Sigma-Aldrich), sulpiride (Wako Pure Chemical Industries, Ltd.), azelastine hydrochloride (AdooQ BioScience), levocetirizine (Sigma-Aldrich), mequitazine (Wako Pure Chemical Industries, Ltd.), thioperamide (Sigma-Aldrich), sarpogrelate hydrochloride (Sigma-Aldrich), clopidogrel (M/s LEE Pharma), ticlopidine (Wako Pure Chemical Industries, Ltd.), prasugrel (Sigma-Aldrich), apafant (Sigma-Aldrich), naloxone (Wako Pure Chemical Industries, Ltd.), zafirlukast (Sigma-Aldrich), montelukast (LG Life Sciences), pranlukast (Cayman Chemical), candesartan (AdooQ BioScience) Comparative Examples: propranolol hydrochloride (Sigma-Aldrich), butaclamol hydrochloride (Sigma-Aldrich), piboserod hydrochloride (Axon Medchem), tolvaptan (Sigma-Aldrich), metaraminol (Sigma-Aldrich), cevimeline (Sigma-Aldrich), cabergoline (Toronto Research Chemicals)
Model antigen: ovalbumin (OVA)
(Mouse Immunity Test of Solution for Transmucosal Administration)
[0155] A mouse immunity test using an animal model for immunity evaluation was performed with the solution prepared as described above. A Mouse (BALB/c mouse, female, 7 weeks old) was provided in advance. After the mouse was anesthetized, the solution was administered to the mouse by transnasal administration (10 uL) or sublingual administration (30 uL). One week after the administration, the mouse was anesthetized again, and the solution was administered again in the same manner.
[0156] One week after the second administration, the mouse serum and nasal wash were taken, and the OVA-specific IgG antibody titer in the serum was determined by ELISA.
ELISA
[0157] The systemic immune response was evaluated by determining the OVA-specific IgG antibody titer in the mouse serum.
<Method for Determining Antigen-Specific IgG Antibody Titer in Mouse Serum (ELISA)>
[0158] To each well of a 96-well plate for ELISA was added 100 uL of an OVA-containing solution (100 ug/mL) diluted with carbonate buffer, followed by standing overnight.
[0159] The wells were washed three times with preliminarily prepared wash (Tween 20-containing PBS), and to each well was added 200 uL of a blocking solution prepared by diluting a blocking agent (Block Ace, Sumitomo Dainippon Pharma Co., Ltd.) in purified water to 4 g/100 mL. This was followed by standing for 2 hours at room temperature. The wells were then washed three times with wash.
[0160] The serum taken from the mouse was centrifuged at 4° C. and 3000 g for 10 minutes, and the supernatant was recovered. The supernatant or nasal wash was diluted in two-fold increments using a solution prepared by diluting a blocking agent in a phosphate buffer (Nacalai Tesque, Inc.) to 0.4 g/100 mL. The diluted solution was added to wells (50 μL for each well), followed by standing for 2 hours at room temperature.
[0161] The wells were then washed three times with wash. An HRP-labeled anti-mouse IgG antibody (Goat-anti mouse IgG Fc HRP, BETHYL) was diluted 10000-fold using a solution prepared by diluting a blocking agent in a phosphate buffer (Nacalai Tesque, Inc.) to 0.4 g/100 mL. To each well was added 100 uL of the resulting solution, followed by standing for 1 hour at room temperature.
[0162] The wells were then washed three times with wash, and 100 uL of a TMB solution (ELISA POD TMB kit, Nacalai Tesque, Inc.) was added to each well, followed by standing for 30 minutes at dark place.
[0163] Thereafter, 100 uL of a 1M sulfuric acid solution was added to each well, and the 96-well plate was subjected to measurement of absorbance at 450 nm with a microplate reader (Spectra Max M2.sup.e, molecular device). The IgG antibody titer in the mouse serum was determined as Log 2 titer based on the absorbance at the incremental dilution. The results are shown in
TABLE-US-00002 TABLE 2 Antigen Th2 reaction promoter IgG anti- Administration Dosage Amount Amount Pharmacological body titer No. route form Name [ug] Name [ug] effect [Log2 titer] Comp. Transnasal Solution OVA 1 — — — 5.4 Ex. 1 Comp. Transnasal Solution OVA 1 Propranolol 20 β1-3 5.1 Ex. 2 hydrochloride antagonization Comp. Transnasal Solution OVA 1 Butaclamol 20 D1 5.3 Ex. 3 hydrochloride antagonization Comp. Transnasal Solution OVA 1 Piboserod 20 5-HT4 5.4 Ex. 4 hydrochloride antagonization Comp. Transnasal Solution OVA 1 Tolvaptan 40 V2 5.5 Ex. 5 antagonization Ex. 1 Transnasal Solution OVA 1 Resveratrol 40 PDE 10.8 inhibition Ex. 2 Transnasal Solution OVA 1 Vinpocetine 20 PDE 10.1 inhibition Ex. 3 Transnasal Solution OVA 1 Pimobendan 20 PDE 10.8 inhibition Ex. 4 Transnasal Solution OVA 1 BRL50481 20 PDE 9.4 inhibition Ex. 5 Transnasal Solution OVA 1 Dipyridamole 40 PDE 12.1 inhibition Ex. 6 Transnasal Solution OVA 1 Methoxyphenamine 20 β2 11.6 hydrochloride activation Ex. 7 Transnasal Solution OVA 1 Fenoldopam 20 D1 11.8 mesylate activation Ex. 8 Transnasal Solution OVA 1 Cisapride 20 5-HT4 9.9 activation Ex. 9 Transnasal Solution OVA 1 Desmopressin 20 V2 11.3 activation
TABLE-US-00003 TABLE 3 Antigen Th2 reaction promoter IgG anti- Administration Dosage Amount Amount Pharmacological body titer No. route form Name [ug] Name [ug] effect [Log2 titer] Comp. Transnasal Solution OVA 1 Metaraminol 20 α1,2 4.6 Ex. 6 activation Comp. Transnasal Solution OVA 1 Cevimeline 20 M1,3 4.6 Ex. 7 activation Comp. Transnasal Solution OVA 1 Cabergoline 20 D2 5.0 Ex. 8 activation Ex. 10 Transnasal Solution OVA 1 Prazosin 80 α1,2 11.3 hydrochloride antagonization Ex. 11 Transnasal Solution OVA 1 Pirenzepine 20 M1 10.8 hydrochloride antagonization Ex. 12 Transnasal Solution OVA 1 Oxybutynin 40 M2 12.6 hydrochloride antagonization Ex. 13 Transnasal Solution OVA 1 Tolterodine 80 M3 11.9 tartrate antagonization Ex. 14 Transnasal Solution OVA 1 Fluphenazine 10 D2 12.6 Ex. 15 Transnasal Solution OVA 1 Droperidol 20 antagonization 10.5 Ex. 16 Transnasal Solution OVA 1 Sulpiride 20 11.3 Ex. 17 Transnasal Solution OVA 1 Azelastine 40 H1 11.3 hydrochloride antagonization Ex. 18 Transnasal Solution OVA 1 Levocetirizine 20 12.3 Ex. 19 Transnasal Solution OVA 1 Mequitazine 20 10.0 Ex. 20 Transnasal Solution OVA 1 Thioperamide 20 H3 10.5 antagonization Ex. 21 Transnasal Solution OVA 1 Sarpogrelate 20 5-HT2 10.0 hydrochloride antagonization Ex. 22 Transnasal Solution OVA 1 Clopidogrel 20 P2Y12 13.4 Ex. 23 Transnasal Solution OVA 1 Ticlopidine 40 antagonization 11.6 Ex. 24 Transnasal Solution OVA 1 Prasugrel 20 11.6 Ex. 25 Transnasal Solution OVA 1 Apafant 20 PAF 11.0 antagonization Ex. 26 Transnasal Solution OVA 1 Naloxone 20 μ, κ, σ 10.0 antagonization Ex. 27 Transnasal Solution OVA 1 Zafirlukast 20 CysLT 10.1 Ex. 28 Transnasal Solution OVA 1 Montelukast 20 antagonization 10.4 Ex. 29 Transnasal Solution OVA 1 Pranlukast 20 11.6 Ex. 30 Transnasal Solution OVA 1 Candesartan 20 AT1 9.3 antagonization
Examples 31 to 55, Comparative Examples 9 to 16
(Preparation of Injection for Subcutaneous Administration)
[0164] An injection for subcutaneous administration was prepared according to the formulation shown in Table 4 and 5 below. Specifically, an antigen and a Th2 reaction promoter were blended in the amounts shown in Tables 4 and 5, and 100 uL of saline was added thereto, followed by mixing to provide a vaccine composition.
[0165] Substances used are listed below.
Example: resveratrol (Wako Pure Chemical Industries, Ltd.), EHNA (Wako Pure Chemical Industries, Ltd.), cilostazol (LKT Laboratories), pimobendan (LKT Laboratories), BRL50481 (Tocris Bioscience), dipyridamole (Wako Pure Chemical Industries, Ltd.), methoxyphenamine hydrochloride (MP Biomedicals), fenoldopam mesylate (LKT Laboratories), cisapride (Sigma-Aldrich), desmopressin (Sigma-Aldrich), prazosin hydrochloride (Wako Pure Chemical Industries, Ltd.), pirenzepine hydrochloride (Wako Pure Chemical Industries, Ltd.), tolterodine tartrate (HELM JAPAN), scopolamine (Wako Pure Chemical Industries, Ltd.), perphenazine (Sigma-Aldrich), droperidol (Sigma-Aldrich), sulpiride (Wako Pure Chemical Industries, Ltd.), azelastine hydrochloride (AdooQ BioScience), thioperamide (Sigma-Aldrich), sarpogrelate hydrochloride (Sigma-Aldrich), clopidogrel (M/s LEE Pharma), ticlopidine (Wako Pure Chemical Industries, Ltd.), prasugrel (Sigma-Aldrich), apafant (Sigma-Aldrich), naloxone (Wako Pure Chemical Industries, Ltd.), montelukast (LG Life Sciences), candesartan (AdooQ BioScience)
Comparative Example: propranolol hydrochloride (Sigma-Aldrich), butaclamol hydrochloride (Sigma-Aldrich), piboserod hydrochloride (Axon Medchem), tolvaptan (Sigma-Aldrich), metaraminol (Sigma-Aldrich), cevimeline (Sigma-Aldrich), cabergoline (Toronto Research Chemicals)
Model antigen: ovalbumin (OVA)
(Mouse Immunity Test of Injection for Subcutaneous Administration)
[0166] A mouse immunity test using an animal model for immunity evaluation was performed with the solution prepared as described above. A mouse (BALB/c mouse, female, 7 weeks old) was provided in advance, and 200 uL of the injection was subcutaneously injected to the back of the mouse. One week after the administration, the injection was administered again in the same manner.
[0167] One week after the second administration, the mouse serum was taken, and the OVA-specific IgG antibody titer in the serum was determined by ELISA. The results are shown in
TABLE-US-00004 TABLE 4 Antigen Th2 reaction promoter IgG anti- Administration Dosage Amount Amount Pharmacological body titer No. route form Name [ug] Name [ug] effect [Log2 titer] Comp. Subcutaneous Solution OVA 0.05 — — — 6.5 Ex. 9 Comp. Subcutaneous Solution OVA 0.05 Propranolol 200 β1-3 5.5 Ex. 10 hydrochloride antagonization Comp. Subcutaneous Solution OVA 0.05 Butaclamol 200 D1 5.8 Ex. 11 hydrochloride antagonization Comp. Subcutaneous Solution OVA 0.05 Piboserod 200 5-HT4 5.9 Ex. 12 hydrochloride antagonization Comp. Subcutaneous Solution OVA 0.05 Tolvaptan 200 V2 5.4 Ex. 13 antagonization Ex. 31 Subcutaneous Solution OVA 0.05 Resveratrol 200 PDE 12.4 inhibition Ex. 32 Subcutaneous Solution OVA 0.05 EHNA 200 PDE 11.3 inhibition Ex. 33 Subcutaneous Solution OVA 0.05 Cilostazol 200 PDE 10.6 inhibition Ex. 34 Subcutaneous Solution OVA 0.05 Pimobendan 200 PDE 10.0 inhibition Ex. 35 Subcutaneous Solution OVA 0.05 BRL50481 200 PDE 11.0 inhibition Ex. 36 Subcutaneous Solution OVA 0.05 Dipyridamole 200 PDE 12.5 inhibition Ex. 37 Subcutaneous Solution OVA 0.05 Methoxyphenamine 200 β2 9.6 hydrochloride activation Ex. 38 Subcutaneous Solution OVA 0.05 Fenoldopam 200 D1 10.3 mesylate activation Ex. 39 Subcutaneous Solution OVA 0.05 Cisapride 200 5-HT4 10.8 activation Ex. 40 Subcutaneous Solution OVA 0.05 Desmopressin 200 V2 9.9 activation
TABLE-US-00005 TABLE 5 Antigen Th2 reaction promoter IgG anti- Administration Dosage Amount Amount Pharmacological body titer No. route form Name [ug] Name [ug] effect [Log2 titer] Comp. Subcutaneous Solution OVA 1 Metaraminol 200 α1,2 5.1 Ex. 14 activation Comp. Subcutaneous Solution OVA 1 Cevimeline 200 M1,3 5.5 Ex. 15 activation Comp. Subcutaneous Solution OVA 1 Cabergoline 200 D2 5.6 Ex. 16 activation Ex. 41 Subcutaneous Solution OVA 1 Prazosin 200 α1,2 13.9 hydrochloride antagonization Ex. 42 Subcutaneous Solution OVA 1 Pirenzepine 200 M1 10.8 hydrochloride antagonization Ex. 43 Subcutaneous Solution OVA 1 Tolterodine 200 M3 11.6 tartrate antagonization Ex. 44 Subcutaneous Solution OVA 1 Scopolamine 200 M1-5 10.6 antagonization Ex. 45 Subcutaneous Solution OVA 1 Perphenazine 200 D2 block 10.9 Ex. 46 Subcutaneous Solution OVA 1 Droperidol 200 10.9 Ex. 47 Subcutaneous Solution OVA 1 Sulpiride 200 10.0 Ex. 48 Subcutaneous Solution OVA 1 Azelastine 200 H1 10.3 hydrochloride antagonization Ex. 49 Subcutaneous Solution OVA 1 Clopidogrel 200 P2Y12 9.8 Ex. 50 Subcutaneous Solution OVA 1 Ticlopidine 200 antagonization 10.5 Ex. 51 Subcutaneous Solution OVA 1 Prasugrel 200 10.8 Ex. 52 Subcutaneous Solution OVA 1 Apafant 200 PAF 10.8 antagonizstion Ex. 53 Subcutaneous Solution OVA 1 Naloxone 200 μ, κ, σ 9.5 antagonization Ex. 54 Subcutaneous Solution OVA 1 Montelukast 200 CysLT1 10.1 antagonization Ex. 55 Subcutaneous Solution OVA 1 Candesartan 200 AT1 11.5 antagonization
Examples 56 to 69, Comparative Examples 17 to 23
(Preparation of Cream for Transdermal Administration)
[0168] A cream for transdermal administration was prepared according to the formulation shown in Table 6 below. Specifically, an antigen and a Th2 reaction promoter were blended in the amounts shown in Table 6. To the mixture was added a base (base cream) to achieve a total amount of 100 parts by weight, followed by mixing to provide a cream. The base cream was prepared by blending and mixing the materials according to the formulation shown in Table 48.
[0169] A composite base was prepared by bonding a PET film/PET nonwoven fabric laminate (area: 0.7 cm.sup.2) to the center portion of an adhesive tape for attachment such that the PET film side faced the adhesive side of the tape. The cream in an amount of 4 mg was applied to the nonwoven fabric portion of the composite base to provide a sample for an immunity test.
[0170] Substances used are listed below.
Example: resveratrol (Wako Pure Chemical Industries, Ltd.), dipyridamole (Wako Pure Chemical Industries, Ltd.), methoxyphenamine hydrochloride (MP Biomedicals), fenoldopam mesylate (LKT Laboratories), cisapride (Sigma-Aldrich), prazosin hydrochloride (Wako Pure Chemical Industries, Ltd.), oxybutynin hydrochloride (LKT Laboratories), tolterodine tartrate (HELM JAPAN), perphenazine (Sigma-Aldrich), azelastine hydrochloride (AdooQ BioScience), clopidogrel (M/s LEE Pharma), apafant (Sigma-Aldrich), montelukast (LG Life Sciences), candesartan (AdooQ BioScience) Comparative Example: propranolol hydrochloride (Sigma-Aldrich), butaclamol hydrochloride (Sigma-Aldrich), piboserod hydrochloride (Axon Medchem), metaraminol (Sigma-Aldrich), cevimeline (Sigma-Aldrich), cabergoline (Toronto Research Chemicals)
Model antigen: ovalbumin (OVA)
(Mouse Immunity Test of Cream for Transdermal Administration)
[0171] A mouse immunity test using an animal model for immunity evaluation was performed with the cream prepared as described above. The right back of a mouse (C57BL6 NCr mice, female, 7 weeks old) was shaved in advance. After a rearing period for recovery from the skin damage caused by the shaving, 4 mg of the cream was administered to the skin of the right back of the mouse, and the left back was shaved at the same time. Twenty-four hours later, the formulation was removed. One week after the administration, the cream was administered to the skin of the left back of the mouse, and removed 24 hours later.
[0172] One week after the second administration, the mouse serum was taken and the OVA-specific IgG antibody titer in the serum was determined by ELISA. The results are shown in
[0173] White Vaseline, sorbitan monostearate, isostearic acid, benzyl alcohol, stearyl alcohol, polysorbate 60, and concentrated glycerin were purchased from Wako Pure Chemical Industries, Ltd. Cetanol was purchased from Tokyo Chemical Industry Co., Ltd.
TABLE-US-00006 TABLE 6 Antigen Th2 reaction promoter Amount Amount IgG anti- Administration Dosage [Parts [Parts Pharmacological body titer No. route form Name by weight] Name by weight] effect [Log2 titer] Comp. Transdermal Cream OVA 5.0 — — — 5.3 Ex. 17 Comp. Transdermal Cream OVA 5.0 Propranolol 5.0 β1-3 5.0 Ex. 18 hydrochloride antagonization Comp. Transdermal Cream OVA 5.0 Butaclamol 5.0 D1 5.0 Ex. 19 hydrochloride antagonization Comp. Transdermal Cream OVA 5.0 Piboserod 5.0 5-HT4 5.3 Ex. 20 hydrochloride antagonization Comp. Transdermal Cream OVA 5.0 Metaraminol 5.0 α1,2 5.1 Ex. 21 activation Comp. Transdermal Cream OVA 5.0 Cevimeline 5.0 M1,3 5.0 Ex. 22 activation Comp. Transdermal Cream OVA 5.0 Cabergoline 5.0 D2 5.0 Ex. 23 activation Ex. 56 Transdermal Cream OVA 5.0 Resveratrol 5.0 PDE 10.1 inhibition Ex. 57 Transdermal Cream OVA 5.0 Dipyridamole 5.0 PDE 9.9 inhibition Ex. 58 Transdermal Cream OVA 5.0 Methoxyphenamine 5.0 β2 9.6 hydrochloride activation Ex. 59 Transdermal Cream OVA 5.0 Fenoldopam 5.0 D1 10.0 mesylate activation Ex. 60 Transdermal Cream OVA 5.0 Cisapride 5.0 5-HT4 9.1 activation Ex. 61 Transdermal Cream OVA 5.0 Prazosin 5.0 α1,2 10.9 hydrochloride antagonization Ex. 62 Transdermal Cream OVA 5.0 Oxybutynin 5.0 M2 10.5 hydrochloride antagonization Ex. 63 Transdermal Cream OVA 5.0 Tolterodine 5.0 M3 10.9 tartrate antagonization Ex. 64 Transdermal Cream OVA 5.0 Perphenazine 5.0 D2 block 8.9 Ex. 65 Transdermal Cream OVA 5.0 Azelastine 5.0 H1 9.1 hydrochloride antagonization Ex. 66 Transdermal Cream OVA 5.0 Clopidogrel 5.0 P2Y12 10.3 antagonization Ex. 67 Transdermal Cream OVA 5.0 Apafant 5.0 PAF 10.1 antagonization Ex. 68 Transdermal Cream OVA 5.0 Montelukast 5.0 CysLT1 10.9 antagonization Ex. 69 Transdermal Cream OVA 5.0 Candesartan 5.0 AT1 8.4 antagonization
Examples 70 to 83, Comparative Example 24
(Preparation of Cream for Transdermal (Minimally Invasive) Administration)
[0174] A cream for transdermal administration according to the formulation shown in Table 7 below was prepared in the same manner as the cream for transdermal administration shown in Table 6. The right back of a mouse (C57BL6 NCr mouse, female, 7 weeks old) was shaved, and after the skin was subjected to a corneum removing treatment five times with an OPP tape (EZ Dunplon No. 3301EZ, Nitto Denko Corporation), the cream was administered to the skin (minimally invasive administration), and the left back was shaved at the same time. Twenty-four hours later, the cream for transdermal administration on the right back was removed. One week after the administration, the skin of the left back of the mouse was subjected to a corneum removing treatment in the same manner as above, and the cream for transdermal administration was administered thereto. The cream was removed 24 hours later. One week after the second administration, the mouse serum was taken, and the antigen (OVA)-specific IgG antibody in the serum was determined by ELISA. Also in this immunization using the minimally invasive administration, humoral immunity specific to the administered antigen can be induced.
[0175] Substances used are listed below.
Example: resveratrol (Wako Pure Chemical Industries, Ltd.), dipyridamole (Wako Pure Chemical Industries, Ltd.), methoxyphenamine hydrochloride (MP Biomedicals), fenoldopam mesylate (LKT Laboratories), cisapride (Sigma-Aldrich), prazosin hydrochloride (Wako Pure Chemical Industries, Ltd.), oxybutynin hydrochloride (LKT Laboratories), tolterodine tartrate (HELM JAPAN), perphenazine (Sigma-Aldrich), azelastine hydrochloride (AdooQ BioScience), clopidogrel (M/s LEE Pharma), apafant (Sigma-Aldrich), montelukast (LG Life Sciences), candesartan (AdooQ BioScience)
Model antigen: ovalbumin (OVA)
TABLE-US-00007 TABLE 7 Antigen Th2 reaction promoter Amount Amount Administration Dosage [Parts by [Parts by Pharmacological No. route form Name weight] Name weight] effect Comp. Transdermal Cream OVA 5.0 — — Ex. 24 (minimally invasive) Ex. 70 Transdermal Cream OVA 5.0 Resveratrol 5.0 PDE (minimally invasive) inhibition Ex. 71 Transdermal Cream OVA 5.0 Dipyridamole 5.0 PDE (minimally invasive) inhibition Ex. 72 Transdermal Cream OVA 5.0 Methoxyphenamine 5.0 β2 (minimally invasive) hydrochloride activation Ex. 73 Transdermal Cream OVA 5.0 Fenoldopam 5.0 D1 (minimally invasive) mesylate activation Ex. 74 Transdermal Cream OVA 5.0 Cisapride 5.0 5-HT4 (minimally invasive) activation Ex. 75 Transdermal Cream OVA 5.0 Prazosin 5.0 α1,2 (minimally invasive) hydrochloride antagonization Ex. 76 Transdermal Cream OVA 5.0 Oxybutynin 5.0 M2 (minimally invasive) hydrochloride antagonization Ex. 77 Transdermal Cream OVA 5.0 Tolterodine 5.0 M3 (minimally invasive) tartrate antagonization Ex. 78 Transdermal Cream OVA 5.0 Perphenazine 5.0 D2 block (minimally invasive) Ex. 79 Transdermal Cream OVA 5.0 Azelastine 5.0 H1 (minimally invasive) hydrochloride antagonization Ex. 80 Transdermal Cream OVA 5.0 Clopidogrel 5.0 P2Y12 (minimally invasive) antagonization Ex. 81 Transdermal Cream OVA 5.0 Apafant 5.0 PAF (minimally invasive) antagonization Ex. 82 Transdermal Cream OVA 5.0 Montelukast 5.0 CysLT (minimally invasive) antagonization Ex. 83 Transdermal Cream OVA 5.0 Candesartan 5.0 AT1 (minimally invasive) antagonization
Example 84 to 1283, Comparative Examples 25 to 64
(Preparation of Solution for Transmucosal Administration)
[0176] A solution for transmucosal administration (transnasal administration or sublingual administration) was prepared according to the formulation shown in Tables 8 to 47 below. Specifically, an antigen and Th2 reaction promoter were blended in the amounts shown in Tables 8 to 47. For transnasal administration, saline was added so that the amount of the resulting mixture was 10 μL. For sublingual administration, saline was added so that the amount of the resulting mixture was 30 μL. This was followed by mixing to provide a solution for transmucosal administration (transnasal administration or sublingual administration).
Model Antigens in Tables 8 to 47
[0177] As influenza vaccine antigens, an influenza vaccine antigen-containing solution H1N1 (A/California/07/2009, The Research Foundation for Microbial Diseases of Osaka University), H3N2 (A/Victoria361/2011, The Research Foundation for Microbial Diseases of Osaka University), Influenza B virus (B/Wisconsin/1/2010, The Research Foundation for Microbial Diseases of Osaka University), Influenza B virus (B/Brisbane/60/2008, The Research Foundation for Microbial Diseases of Osaka University) were used. Also used were a pneumococcal capsular polysaccharide-containing solution (Pneumovax NP, MSD), HPV16 recombinant protein-containing solution (HPV16, PROSPEC), a live attenuated rotavirus-containing solution (RotaTeq Oral Solution, MSD), an inactivated poliovirus-containing solution (IMOVAX POLIO for subcutaneous injection, Sanofi), an inactivated hepatitis A virus-containing solution (Aimmugen, The Chemo-Sero-Therapeutic Research Institute), an inactivated Japanese encephalitis virus-containing solution (Encevac for subcutaneous injection, The Chemo-Sero-Therapeutic Research Institute), a live attenuated mumps virus-containing solution (live mumps vaccine, Kitasato Daiichi Sankyo Vaccine Co., Ltd), a live attenuated measles virus-containing solution (live measles vaccine, Kitasato Daiichi Sankyo Vaccine Co., Ltd), a live attenuated rubella virus-containing solution (dried live attenuated rubella vaccine, Kitasato Daiichi Sankyo Vaccine Co., Ltd), a solution containing tetanus toxoid-conjugated haemophilus influenzae type b polysaccharide (ActHIB, Sanofi), a recombinant HBs antigen protein-containing solution (Bimmugen, The Chemo-Sero-Therapeutic Research Institute), a live attenuated yellow fever virus-containing solution (yellow fever vaccine, Sanofi), a tetanus toxoid-containing solution (tetanus toxoid, Denka Seiken Co., Ltd.), a live attenuated varicella virus-containing solution (dried live attenuated varicella vaccine, The Research Foundation for Microbial Diseases of Osaka University), a live BCG-containing solution (dried BCG vaccine, Japan BCG Laboratory), and an inactivated rabies virus-containing solution (tissue-cultured inactivated rabies vaccine, The Chemo-Sero-Therapeutic Research Institute).
[0178] Substances shown in Tables 8 to 47 are listed below.
Example: resveratrol (Wako Pure Chemical Industries, Ltd.), vinpocetine (Yodogawa Seiyaku K.K.), pimobendan (LKT Laboratories), BRL50481 (Tocris Bioscience), dipyridamole (Wako Pure Chemical Industries, Ltd.), methoxyphenamine hydrochloride (MP Biomedicals), fenoldopam mesylate (LKT Laboratories), cisapride (Sigma-Aldrich), desmopressin (Sigma-Aldrich), prazosin hydrochloride (Wako Pure Chemical Industries, Ltd.), pirenzepine hydrochloride (Wako Pure Chemical Industries, Ltd.), oxybutynin hydrochloride (LKT Laboratories), tolterodine tartrate (HELM JAPAN), fluphenazine (Sigma-Aldrich), droperidol (Sigma-Aldrich), sulpiride (Wako Pure Chemical Industries, Ltd.), azelastine hydrochloride (AdooQ BioScience), levocetirizine (Sigma-Aldrich), mequitazine (Wako Pure Chemical Industries, Ltd.), thioperamide (Sigma-Aldrich), sarpogrelate hydrochloride (Sigma-Aldrich), clopidogrel (M/s LEE Pharma), ticlopidine (Wako Pure Chemical Industries, Ltd.), prasugrel (Sigma-Aldrich), apafant (Sigma-Aldrich), naloxone (Wako Pure Chemical Industries, Ltd.), zafirlukast (Sigma-Aldrich), montelukast (LG Life Sciences), pranlukast (Cayman Chemical), candesartan (AdooQ BioScience)
[0179] A mouse immunity test using an animal model for immunity evaluation was performed with the solution prepared as described above. A mouse was provided in advance. After the mouse was anesthetized, the solution was administered to the mouse by transnasal administration (10 uL) or sublingual administration (30 uL). One week after the administration, the mouse was anesthetized again, and the solution was administered again in the same manner. One week after the second administration, the mouse serum and nasal wash were taken, and the OVA-specific IgG antibody titer in the serum was determined by ELISA. In the immunization by transmucosal administration (transnasal administration and sublingual administration), humoral immunity specific to the administered antigen can be induced.
TABLE-US-00008 TABLE 8 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution A/California/07/2009 1.0 — — 10 Ex. 25 [H1N1] Ex. 84 Transnasal Solution A/California/07/2009 1.0 Resveratrol 40 PDE 10 [H1N1] inhibition Ex. 85 Transnasal Solution A/California/07/2009 1.0 Vinpocetine 20 PDE 10 [H1N1] inhibition Ex. 86 Transnasal Solution A/California/07/2009 1.0 Pimobendan 20 PDE 10 [H1N1] inhibition Ex. 87 Transnasal Solution A/California/07/2009 1.0 BRL50481 20 PDE 10 [H1N1] inhibition Ex. 88 Transnasal Solution A/California/07/2009 1.0 Dipyridamole 40 PDE 10 [H1N1] inhibition Ex. 89 Transnasal Solution A/California/07/2009 1.0 Methoxyphenamine 20 β2 10 [H1N1] hydrochloride activation Ex. 90 Transnasal Solution A/California/07/2009 1.0 Fenoldopam 20 D1 10 [H1N1] mesylate activation Ex. 91 Transnasal Solution A/California/07/2009 1.0 Cisapride 20 5-HT4 10 [H1N1] activation Ex. 92 Transnasal Solution A/California/07/2009 1.0 Desmopressin 20 V2 10 [H1N1] activation Ex. 93 Transnasal Solution A/California/07/2009 1.0 Prazosin 80 α1,2 10 [H1N1] hydrochloride antagonization Ex. 94 Transnasal Solution A/California/07/2009 1.0 Pirenzepine 20 M1 10 [H1N1] hycrochloride antagonization Ex. 95 Transnasal Solution A/California/07/2009 1.0 Oxybutynin 40 M2 10 [H1N1] hydrochloride antagonization Ex. 96 Transnasal Solution A/California/07/2009 1.0 Tolterodine 80 M3 10 [H1N1] tartrate antagonization Ex. 97 Transnasal Solution A/California/07/2009 1.0 Fluphenazine 10 D2 10 [H1N1] antagonization Ex. 98 Transnasal Solution A/California/07/2009 1.0 Droperidol 20 10 [H1N1] Ex. 99 Transnasal Solution A/California/07/2009 1.0 Sulpiride 20 10 [H1N1] Ex. 100 Transnasal Solution A/California/07/2009 1.0 Azelastine 40 H1 10 [H1N1] hydrochloride antagonization Ex. 101 Transnasal Solution A/California/07/2009 1.0 Levocetirizine 20 10 [H1N1] Ex. 102 Transnasal Solution A/California/07/2009 1.0 Mequitazine 20 10 [H1N1] Ex. 103 Transnasal Solution A/California/07/2009 1.0 Thioperamide 20 H3 10 [H1N1] antagonization Ex. 104 Transnasal Solution A/California/07/2009 1.0 Sarpogrelate 20 5-HT2 10 [H1N1] hydrochloride antagonization Ex. 105 Transnasal Solution A/California/07/2009 1.0 Clopidogrel 20 P2Y12 10 [H1N1] antagonization Ex. 106 Transnasal Solution A/California/07/2009 1.0 Tiolopidine 40 10 [H1N1] Ex. 107 Transnasal Solution A/California/07/2009 1.0 Prasugrel 20 10 [H1N1] Ex. 108 Transnasal Solution A/California/07/2009 1.0 Apafant 20 PAF 10 [H1N1] antagonization Ex. 109 Transnasal Solution A/California/07/2009 1.0 Naloxone 20 μ, κ, σ 10 [H1N1] antagonization Ex. 110 Transnasal Solution A/California/07/2009 1.0 Zafirlukast 20 CysLT 10 [H1N1] antagonization Ex. 111 Transnasal Solution A/California/07/2009 1.0 Montelukast 20 10 [H1N1] Ex. 112 Transnasal Solution A/California/07/2009 1.0 Pranlukast 20 10 [H1N1] Ex. 113 Transnasal Solution A/California/07/2009 1.0 Candesartan 20 AT1 10 [H1N1] antagonization
TABLE-US-00009 TABLE 9 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution A/California/07/2009 1.0 — — 30 Ex. 26 [H1N1] Ex. 114 Sublingual Solution A/California/07/2009 1.0 Resveratrol 200 PDE 30 [H1N1] inhibition Ex. 115 Sublingual Solution A/California/07/2009 1.0 Vinpocetine 100 PDE 30 [H1N1] inhibition Ex. 116 Sublingual Solution A/California/07/2009 1.0 Pimobendan 100 PDE 30 [H1N1] inhibition Ex. 117 Sublingual Solution A/California/07/2009 1.0 BRL50481 100 PDE 30 [H1N1] inhibition Ex. 118 Sublingual Solution A/California/07/2009 1.0 Dipyridamole 200 PDE 30 [H1N1] inhibition Ex. 119 Sublingual Solution A/California/07/2009 1.0 Methoxyphenamine 100 β2 30 [H1N1] hydrochloride activation Ex. 120 Sublingual Solution A/California/07/2009 1.0 Fenoldopam 100 D1 30 [H1N1] mesylate activation Ex. 121 Sublingual Solution A/California/07/2009 1.0 Cisapride 100 5-HT4 30 [H1N1] activation Ex. 122 Sublingual Solution A/California/07/2009 1.0 Desmopressin 100 V2 30 [H1N1] activation Ex. 123 Sublingual Solution A/California/07/2009 1.0 Prazosin 400 α1,2 30 [H1N1] hydrochloride antagonization Ex. 124 Sublingual Solution A/California/07/2009 1.0 Pirenzepine 100 M1 30 [H1N1] hycrochloride antagonization Ex. 125 Sublingual Solution A/California/07/2009 1.0 Oxybutynin 200 M2 30 [H1N1] hydrochloride antagonization Ex. 126 Sublingual Solution A/California/07/2009 1.0 Tolterodine 400 M3 30 [H1N1] tartrate antagonization Ex. 127 Sublingual Solution A/California/07/2009 1.0 Fluphenazine 50 D2 30 [H1N1] antagonization Ex. 128 Sublingual Solution A/California/07/2009 1.0 Droperidol 100 30 [H1N1] Ex. 129 Sublingual Solution A/California/07/2009 1.0 Sulpiride 100 30 [H1N1] Ex. 130 Sublingual Solution A/California/07/2009 1.0 Azelastine 200 H1 30 [H1N1] hydrochloride antagonization Ex. 131 Sublingual Solution A/California/07/2009 1.0 Levocetirizine 100 30 [H1N1] Ex. 132 Sublingual Solution A/California/07/2009 1.0 Mequitazine 100 30 [H1N1] Ex. 133 Sublingual Solution A/California/07/2009 1.0 Thioperamide 100 H3 30 [H1N1] antagonization Ex. 134 Sublingual Solution A/California/07/2009 1.0 Sarpogrelate 100 5-HT2 30 [H1N1] hydrochloride antagonization Ex. 135 Sublingual Solution A/California/07/2009 1.0 Clopidogrel 100 P2Y12 30 [H1N1] antagonization Ex. 136 Sublingual Solution A/California/07/2009 1.0 Tiolopidine 200 30 [H1N1] Ex. 137 Sublingual Solution A/California/07/2009 1.0 Prasugrel 100 30 [H1N1] Ex. 138 Sublingual Solution A/California/07/2009 1.0 Apafant 100 PAF 30 [H1N1] antagonization Ex. 139 Sublingual Solution A/California/07/2009 1.0 Naloxone 100 μ, κ, σ 30 [H1N1] antagonization Ex. 140 Sublingual Solution A/California/07/2009 1.0 Zafirlukast 100 CysLT 30 [H1N1] antagonization Ex. 141 Sublingual Solution A/California/07/2009 1.0 Montelukast 100 30 [H1N1] Ex. 142 Sublingual Solution A/California/07/2009 1.0 Pranlukast 100 30 [H1N1] Ex. 143 Sublingual Solution A/California/07/2009 1.0 Candesartan 100 AT1 30 [H1N1] antagonization
TABLE-US-00010 TABLE 10 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution A/Victoria361/2011 1.0 — — 10 Ex. 27 [H3N2] Ex. 144 Transnasal Solution A/Victoria361/2011 1.0 Resveratrol 40 PDE 10 [H3N2] inhibition Ex. 145 Transnasal Solution A/Victoria361/2011 1.0 Vinpocetine 20 PDE 10 [H3N2] inhibition Ex. 146 Transnasal Solution A/Victoria361/2011 1.0 Pimobendan 20 PDE 10 [H3N2] inhibition Ex. 147 Transnasal Solution A/Victoria361/2011 1.0 BRL50481 20 PDE 10 [H3N2] inhibition Ex. 148 Transnasal Solution A/Victoria361/2011 1.0 Dipyridamole 40 PDE 10 [H3N2] inhibition Ex. 149 Transnasal Solution A/Victoria361/2011 1.0 Methoxyphenamine 20 β2 10 [H3N2] hydrochloride activation Ex. 150 Transnasal Solution A/Victoria361/2011 1.0 Fenoldopam 20 D1 10 [H3N2] mesylate activation Ex. 151 Transnasal Solution A/Victoria361/2011 1.0 Cisapride 20 5-HT4 10 [H3N2] activation Ex. 152 Transnasal Solution A/Victoria361/2011 1.0 Desmopressin 20 V2 10 [H3N2] activation Ex. 153 Transnasal Solution A/Victoria361/2011 1.0 Prazosin 80 α1,2 10 [H3N2] hydrochloride antagonization Ex. 154 Transnasal Solution A/Victoria361/2011 1.0 Pirenzepine 20 M1 10 [H3N2] hycrochloride antagonization Ex. 155 Transnasal Solution A/Victoria361/2011 1.0 Oxybutynin 40 M2 10 [H3N2] hydrochloride antagonization Ex. 156 Transnasal Solution A/Victoria361/2011 1.0 Tolterodine 80 M3 10 [H3N2] tartrate antagonization Ex. 157 Transnasal Solution A/Victoria361/2011 1.0 Fluphenazine 10 D2 10 [H3N2] antagonization Ex. 158 Transnasal Solution A/Victoria361/2011 1.0 Droperidol 20 10 [H3N2] Ex. 159 Transnasal Solution A/Victoria361/2011 1.0 Sulpiride 20 10 [H3N2] Ex. 160 Transnasal Solution A/Victoria361/2011 1.0 Azelastine 40 H1 10 [H3N2] hydrochloride antagonization Ex. 161 Transnasal Solution A/Victoria361/2011 1.0 Levocetirizine 20 10 [H3N2] Ex. 162 Transnasal Solution A/Victoria361/2011 1.0 Mequitazine 20 10 [H3N2] Ex. 163 Transnasal Solution A/Victoria361/2011 1.0 Thioperamide 20 H3 10 [H3N2] antagonization Ex. 164 Transnasal Solution A/Victoria361/2011 1.0 Sarpogrelate 20 5-HT2 10 [H3N2] hydrochloride antagonization Ex. 165 Transnasal Solution A/Victoria361/2011 1.0 Clopidogrel 20 P2Y12 10 [H3N2] antagonization Ex. 166 Transnasal Solution A/Victoria361/2011 1.0 Tiolopidine 40 10 [H3N2] Ex. 167 Transnasal Solution A/Victoria361/2011 1.0 Prasugrel 20 10 [H3N2] Ex. 168 Transnasal Solution A/Victoria361/2011 1.0 Apafant 20 PAF 10 [H3N2] antagonization Ex. 169 Transnasal Solution A/Victoria361/2011 1.0 Naloxone 20 μ, κ, σ 10 [H3N2] antagonization Ex. 170 Transnasal Solution A/Victoria361/2011 1.0 Zafirlukast 20 CysLT 10 [H3N2] antagonization Ex. 171 Transnasal Solution A/Victoria361/2011 1.0 Montelukast 20 10 [H3N2] Ex. 172 Transnasal Solution A/Victoria361/2011 1.0 Pranlukast 20 10 [H3N2] Ex. 173 Transnasal Solution A/Victoria361/2011 1.0 Candesartan 20 AT1 10 [H3N2] antagonization
TABLE-US-00011 TABLE 11 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution A/Victoria361/2011 1.0 — — 30 Ex. 28 [H3N2] Ex. 174 Sublingual Solution A/Victoria361/2011 1.0 Resveratrol 200 PDE 30 [H3N2] inhibition Ex. 175 Sublingual Solution A/Victoria361/2011 1.0 Vinpocetine 100 PDE 30 [H3N2] inhibition Ex. 176 Sublingual Solution A/Victoria361/2011 1.0 Pimobendan 100 PDE 30 [H3N2] inhibition Ex. 177 Sublingual Solution A/Victoria361/2011 1.0 BRL50481 100 PDE 30 [H3N2] inhibition Ex. 178 Sublingual Solution A/Victoria361/2011 1.0 Dipyridamole 200 PDE 30 [H3N2] inhibition Ex. 179 Sublingual Solution A/Victoria361/2011 1.0 Methoxyphenamine 100 β2 30 [H3N2] hydrochloride activation Ex. 180 Sublingual Solution A/Victoria361/2011 1.0 Fenoldopam 100 D1 30 [H3N2] mesylate activation Ex. 181 Sublingual Solution A/Victoria361/2011 1.0 Cisapride 100 5-HT4 30 [H3N2] activation Ex. 182 Sublingual Solution A/Victoria361/2011 1.0 Desmopressin 100 V2 30 [H3N2] activation Ex. 183 Sublingual Solution A/Victoria361/2011 1.0 Prazosin 400 α1,2 30 [H3N2] hydrochloride antagonization Ex. 184 Sublingual Solution A/Victoria361/2011 1.0 Pirenzepine 100 M1 30 [H3N2] hycrochloride antagonization Ex. 185 Sublingual Solution A/Victoria361/2011 1.0 Oxybutynin 200 M2 30 [H3N2] hydrochloride antagonization Ex. 186 Sublingual Solution A/Victoria361/2011 1.0 Tolterodine 400 M3 30 [H3N2] tartrate antagonization Ex. 187 Sublingual Solution A/Victoria361/2011 1.0 Fluphenazine 50 D2 30 [H3N2] antagonization Ex. 188 Sublingual Solution A/Victoria361/2011 1.0 Droperidol 100 30 [H3N2] Ex. 189 Sublingual Solution A/Victoria361/2011 1.0 Sulpiride 100 30 [H3N2] Ex. 190 Sublingual Solution A/Victoria361/2011 1.0 Azelastine 200 H1 30 [H3N2] hydrochloride antagonization Ex. 191 Sublingual Solution A/Victoria361/2011 1.0 Levocetirizine 100 30 [H3N2] Ex. 192 Sublingual Solution A/Victoria361/2011 1.0 Mequitazine 100 30 [H3N2] Ex. 193 Sublingual Solution A/Victoria361/2011 1.0 Thioperamide 100 H3 30 [H3N2] antagonization Ex. 194 Sublingual Solution A/Victoria361/2011 1.0 Sarpogrelate 100 5-HT2 30 [H3N2] hydrochloride antagonization Ex. 195 Sublingual Solution A/Victoria361/2011 1.0 Clopidogrel 100 P2Y12 30 [H3N2] antagonization Ex. 196 Sublingual Solution A/Victoria361/2011 1.0 Tiolopidine 200 30 [H3N2] Ex. 197 Sublingual Solution A/Victoria361/2011 1.0 Prasugrel 100 30 [H3N2] Ex. 198 Sublingual Solution A/Victoria361/2011 1.0 Apafant 100 PAF 30 [H3N2] antagonization Ex. 199 Sublingual Solution A/Victoria361/2011 1.0 Naloxone 100 μ, κ, σ 30 [H3N2] antagonization Ex. 200 Sublingual Solution A/Victoria361/2011 1.0 Zafirlukast 100 CysLT 30 [H3N2] antagonization Ex. 201 Sublingual Solution A/Victoria361/2011 1.0 Montelukast 100 30 [H3N2] Ex. 202 Sublingual Solution A/Victoria361/2011 1.0 Pranlukast 100 30 [H3N2] Ex. 203 Sublingual Solution A/Victoria361/2011 1.0 Candesartan 100 AT1 30 [H3N2] antagonization
TABLE-US-00012 TABLE 12 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution B/Wisconsin/1/2010 1.0 — — 10 Ex. 29 Ex. 204 Transnasal Solution B/Wisconsin/1/2010 1.0 Resveratrol 40 PDE 10 inhibition Ex. 205 Transnasal Solution B/Wisconsin/1/2010 1.0 Vinpocetine 20 PDE 10 inhibition Ex. 206 Transnasal Solution B/Wisconsin/1/2010 1.0 Pimobendan 20 PDE 10 inhibition Ex. 207 Transnasal Solution B/Wisconsin/1/2010 1.0 BRL50481 20 PDE 10 inhibition Ex. 208 Transnasal Solution B/Wisconsin/1/2010 1.0 Dipyridamole 40 PDE 10 inhibition Ex. 209 Transnasal Solution B/Wisconsin/1/2010 1.0 Methoxyphenamine 20 β2 10 hydrochloride activation Ex. 210 Transnasal Solution B/Wisconsin/1/2010 1.0 Fenoldopam 20 D1 10 mesylate activation Ex. 211 Transnasal Solution B/Wisconsin/1/2010 1.0 Cisapride 20 5-HT4 10 activation Ex. 212 Transnasal Solution B/Wisconsin/1/2010 1.0 Desmopressin 20 V2 10 activation Ex. 213 Transnasal Solution B/Wisconsin/1/2010 1.0 Prazosin 80 α1,2 10 hydrochloride antagonization Ex. 214 Transnasal Solution B/Wisconsin/1/2010 1.0 Pirenzepine 20 M1 10 hycrochloride antagonization Ex. 215 Transnasal Solution B/Wisconsin/1/2010 1.0 Oxybutynin 40 M2 10 hydrochloride antagonization Ex. 216 Transnasal Solution B/Wisconsin/1/2010 1.0 Tolterodine 80 M3 10 tartrate antagonization Ex. 217 Transnasal Solution B/Wisconsin/1/2010 1.0 Fluphenazine 10 D2 10 antagonization Ex. 218 Transnasal Solution B/Wisconsin/1/2010 1.0 Droperidol 20 10 Ex. 219 Transnasal Solution B/Wisconsin/1/2010 1.0 Sulpiride 20 10 Ex. 220 Transnasal Solution B/Wisconsin/1/2010 1.0 Azelastine 40 H1 10 hydrochloride antagonization Ex. 221 Transnasal Solution B/Wisconsin/1/2010 1.0 Levocetirizine 20 10 Ex. 222 Transnasal Solution B/Wisconsin/1/2010 1.0 Mequitazine 20 10 Ex. 223 Transnasal Solution B/Wisconsin/1/2010 1.0 Thioperamide 20 H3 10 antagonization Ex. 224 Transnasal Solution B/Wisconsin/1/2010 1.0 Sarpogrelate 20 5-HT2 10 hydrochloride antagonization Ex. 225 Transnasal Solution B/Wisconsin/1/2010 1.0 Clopidogrel 20 P2Y12 10 antagonization Ex. 226 Transnasal Solution B/Wisconsin/1/2010 1.0 Tiolopidine 40 10 Ex. 227 Transnasal Solution B/Wisconsin/1/2010 1.0 Prasugrel 20 10 Ex. 228 Transnasal Solution B/Wisconsin/1/2010 1.0 Apafant 20 PAF 10 antagonization Ex. 229 Transnasal Solution B/Wisconsin/1/2010 1.0 Naloxone 20 μ, κ, σ 10 antagonization Ex. 230 Transnasal Solution B/Wisconsin/1/2010 1.0 Zafirlukast 20 CysLT 10 antagonization Ex. 231 Transnasal Solution B/Wisconsin/1/2010 1.0 Montelukast 20 10 Ex. 232 Transnasal Solution B/Wisconsin/1/2010 1.0 Pranlukast 20 10 Ex. 233 Transnasal Solution B/Wisconsin/1/2010 1.0 Candesartan 20 AT1 10 antagonization
TABLE-US-00013 TABLE 13 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution B/Wisconsin/1/2010 1.0 — — 30 Ex. 30 Ex. 234 Sublingual Solution B/Wisconsin/1/2010 1.0 Resveratrol 200 PDE 30 inhibition Ex. 235 Sublingual Solution B/Wisconsin/1/2010 1.0 Vinpocetine 100 PDE 30 inhibition Ex. 236 Sublingual Solution B/Wisconsin/1/2010 1.0 Pimobendan 100 PDE 30 inhibition Ex. 237 Sublingual Solution B/Wisconsin/1/2010 1.0 BRL50481 100 PDE 30 inhibition Ex. 238 Sublingual Solution B/Wisconsin/1/2010 1.0 Dipyridamole 200 PDE 30 inhibition Ex. 239 Sublingual Solution B/Wisconsin/1/2010 1.0 Methoxyphenamine 100 β2 30 hydrochloride activation Ex. 240 Sublingual Solution B/Wisconsin/1/2010 1.0 Fenoldopam 100 D1 30 mesylate activation Ex. 241 Sublingual Solution B/Wisconsin/1/2010 1.0 Cisapride 100 5-HT4 30 activation Ex. 242 Sublingual Solution B/Wisconsin/1/2010 1.0 Desmopressin 100 V2 30 activation Ex. 243 Sublingual Solution B/Wisconsin/1/2010 1.0 Prazosin 400 α1,2 30 hydrochloride antagonization Ex. 244 Sublingual Solution B/Wisconsin/1/2010 1.0 Pirenzepine 100 M1 30 hycrochloride antagonization Ex. 245 Sublingual Solution B/Wisconsin/1/2010 1.0 Oxybutynin 200 M2 30 hydrochloride antagonization Ex. 246 Sublingual Solution B/Wisconsin/1/2010 1.0 Tolterodine 400 M3 30 tartrate antagonization Ex. 247 Sublingual Solution B/Wisconsin/1/2010 1.0 Fluphenazine 50 D2 30 antagonization Ex. 248 Sublingual Solution B/Wisconsin/1/2010 1.0 Droperidol 100 30 Ex. 249 Sublingual Solution B/Wisconsin/1/2010 1.0 Sulpiride 100 30 Ex. 250 Sublingual Solution B/Wisconsin/1/2010 1.0 Azelastine 200 H1 30 hydrochloride antagonization Ex. 251 Sublingual Solution B/Wisconsin/1/2010 1.0 Levocetirizine 100 30 Ex. 252 Sublingual Solution B/Wisconsin/1/2010 1.0 Mequitazine 100 30 Ex. 253 Sublingual Solution B/Wisconsin/1/2010 1.0 Thioperamide 100 H3 30 antagonization Ex. 254 Sublingual Solution B/Wisconsin/1/2010 1.0 Sarpogrelate 100 5-HT2 30 hydrochloride antagonization Ex. 255 Sublingual Solution B/Wisconsin/1/2010 1.0 Clopidogrel 100 P2Y12 30 antagonization Ex. 256 Sublingual Solution B/Wisconsin/1/2010 1.0 Tiolopidine 200 30 Ex. 257 Sublingual Solution B/Wisconsin/1/2010 1.0 Prasugrel 100 30 Ex. 258 Sublingual Solution B/Wisconsin/1/2010 1.0 Apafant 100 PAF 30 antagonization Ex. 259 Sublingual Solution B/Wisconsin/1/2010 1.0 Naloxone 100 μ, κ, σ 30 antagonization Ex. 260 Sublingual Solution B/Wisconsin/1/2010 1.0 Zafirlukast 100 CysLT 30 antagonization Ex. 261 Sublingual Solution B/Wisconsin/1/2010 1.0 Montelukast 100 30 Ex. 262 Sublingual Solution B/Wisconsin/1/2010 1.0 Pranlukast 100 30 Ex. 263 Sublingual Solution B/Wisconsin/1/2010 1.0 Candesartan 100 AT1 30 antagonization
TABLE-US-00014 TABLE 14 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution B/Brisbane/60/2008 1.0 — — 10 Ex. 31 Ex. 264 Transnasal Solution B/Brisbane/60/2008 1.0 Resveratrol 40 PDE 10 inhibition Ex. 265 Transnasal Solution B/Brisbane/60/2008 1.0 Vinpocetine 20 PDE 10 inhibition Ex. 266 Transnasal Solution B/Brisbane/60/2008 1.0 Pimobendan 20 PDE 10 inhibition Ex. 267 Transnasal Solution B/Brisbane/60/2008 1.0 BRL50481 20 PDE 10 inhibition Ex. 268 Transnasal Solution B/Brisbane/60/2008 1.0 Dipyridamole 40 PDE 10 inhibition Ex. 269 Transnasal Solution B/Brisbane/60/2008 1.0 Methoxyphenamine 20 β2 10 hydrochloride activation Ex. 270 Transnasal Solution B/Brisbane/60/2008 1.0 Fenoldopam 20 D1 10 mesylate activation Ex. 271 Transnasal Solution B/Brisbane/60/2008 1.0 Cisapride 20 5-HT4 10 activation Ex. 272 Transnasal Solution B/Brisbane/60/2008 1.0 Desmopressin 20 V2 10 activation Ex. 273 Transnasal Solution B/Brisbane/60/2008 1.0 Prazosin 80 α1,2 10 hydrochloride antagonization Ex. 274 Transnasal Solution B/Brisbane/60/2008 1.0 Pirenzepine 20 M1 10 hycrochloride antagonization Ex. 275 Transnasal Solution B/Brisbane/60/2008 1.0 Oxybutynin 40 M2 10 hydrochloride antagonization Ex. 276 Transnasal Solution B/Brisbane/60/2008 1.0 Tolterodine 80 M3 10 tartrate antagonization Ex. 277 Transnasal Solution B/Brisbane/60/2008 1.0 Fluphenazine 10 D2 10 antagonization Ex. 278 Transnasal Solution B/Brisbane/60/2008 1.0 Droperidol 20 10 Ex. 279 Transnasal Solution B/Brisbane/60/2008 1.0 Sulpiride 20 10 Ex. 280 Transnasal Solution B/Brisbane/60/2008 1.0 Azelastine 40 H1 10 hydrochloride antagonization Ex. 281 Transnasal Solution B/Brisbane/60/2008 1.0 Levocetirizine 20 10 Ex. 282 Transnasal Solution B/Brisbane/60/2008 1.0 Mequitazine 20 10 Ex. 283 Transnasal Solution B/Brisbane/60/2008 1.0 Thioperamide 20 H3 10 antagonization Ex. 284 Transnasal Solution B/Brisbane/60/2008 1.0 Sarpogrelate 20 5-HT2 10 hydrochloride antagonization Ex. 285 Transnasal Solution B/Brisbane/60/2008 1.0 Clopidogrel 20 P2Y12 10 antagonization Ex. 286 Transnasal Solution B/Brisbane/60/2008 1.0 Tiolopidine 40 10 Ex. 287 Transnasal Solution B/Brisbane/60/2008 1.0 Prasugrel 20 10 Ex. 288 Transnasal Solution B/Brisbane/60/2008 1.0 Apafant 20 PAF 10 antagonization Ex. 289 Transnasal Solution B/Brisbane/60/2008 1.0 Naloxone 20 μ, κ, σ 10 antagonization Ex. 290 Transnasal Solution B/Brisbane/60/2008 1.0 Zafirlukast 20 CysLT 10 antagonization Ex. 291 Transnasal Solution B/Brisbane/60/2008 1.0 Montelukast 20 10 Ex. 292 Transnasal Solution B/Brisbane/60/2008 1.0 Pranlukast 20 10 Ex. 293 Transnasal Solution B/Brisbane/60/2008 1.0 Candesartan 20 AT1 10 antagonization
TABLE-US-00015 TABLE 15 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution B/Brisbane/60/2008 1.0 — — 30 Ex. 32 Ex. 294 Sublingual Solution B/Brisbane/60/2008 1.0 Resveratrol 200 PDE 30 inhibition Ex. 295 Sublingual Solution B/Brisbane/60/2008 1.0 Vinpocetine 100 PDE 30 inhibition Ex. 296 Sublingual Solution B/Brisbane/60/2008 1.0 Pimobendan 100 PDE 30 inhibition Ex. 297 Sublingual Solution B/Brisbane/60/2008 1.0 BRL50481 100 PDE 30 inhibition Ex. 298 Sublingual Solution B/Brisbane/60/2008 1.0 Dipyridamole 200 PDE 30 inhibition Ex. 299 Sublingual Solution B/Brisbane/60/2008 1.0 Methoxyphenamine 100 β2 30 hydrochloride activation Ex. 300 Sublingual Solution B/Brisbane/60/2008 1.0 Fenoldopam 100 D1 30 mesylate activation Ex. 301 Sublingual Solution B/Brisbane/60/2008 1.0 Cisapride 100 5-HT4 30 activation Ex. 302 Sublingual Solution B/Brisbane/60/2008 1.0 Desmopressin 100 V2 30 activation Ex. 303 Sublingual Solution B/Brisbane/60/2008 1.0 Prazosin 400 α1,2 30 hydrochloride antagonization Ex. 304 Sublingual Solution B/Brisbane/60/2008 1.0 Pirenzepine 100 M1 30 hycrochloride antagonization Ex. 305 Sublingual Solution B/Brisbane/60/2008 1.0 Oxybutynin 200 M2 30 hydrochloride antagonization Ex. 306 Sublingual Solution B/Brisbane/60/2008 1.0 Tolterodine 400 M3 30 tartrate antagonization Ex. 307 Sublingual Solution B/Brisbane/60/2008 1.0 Fluphenazine 50 D2 30 antagonization Ex. 308 Sublingual Solution B/Brisbane/60/2008 1.0 Droperidol 100 30 Ex. 309 Sublingual Solution B/Brisbane/60/2008 1.0 Sulpiride 100 30 Ex. 310 Sublingual Solution B/Brisbane/60/2008 1.0 Azelastine 200 H1 30 hydrochloride antagonization Ex. 311 Sublingual Solution B/Brisbane/60/2008 1.0 Levocetirizine 100 30 Ex. 312 Sublingual Solution B/Brisbane/60/2008 1.0 Mequitazine 100 30 Ex. 313 Sublingual Solution B/Brisbane/60/2008 1.0 Thioperamide 100 H3 30 antagonization Ex. 314 Sublingual Solution B/Brisbane/60/2008 1.0 Sarpogrelate 100 5-HT2 30 hydrochloride antagonization Ex. 315 Sublingual Solution B/Brisbane/60/2008 1.0 Clopidogrel 100 P2Y12 30 antagonization Ex. 316 Sublingual Solution B/Brisbane/60/2008 1.0 Tiolopidine 200 30 Ex. 317 Sublingual Solution B/Brisbane/60/2008 1.0 Prasugrel 100 30 Ex. 318 Sublingual Solution B/Brisbane/60/2008 1.0 Apafant 100 PAF 30 antagonization Ex. 319 Sublingual Solution B/Brisbane/60/2008 1.0 Naloxone 100 μ, κ, σ 30 antagonization Ex. 320 Sublingual Solution B/Brisbane/60/2008 1.0 Zafirlukast 100 CysLT 30 antagonization Ex. 321 Sublingual Solution B/Brisbane/60/2008 1.0 Montelukast 100 30 Ex. 322 Sublingual Solution B/Brisbane/60/2008 1.0 Pranlukast 100 30 Ex. 323 Sublingual Solution B/Brisbane/60/2008 1.0 Candesartan 100 AT1 30 antagonization
TABLE-US-00016 TABLE 16 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Pneumococcal capsular polysaccharide 20 — — 10 Ex. 33 Pneumovax NP Ex. 324 Transnasal Solution Pneumococcal capsular polysaccharide 20 Resveratrol 40 PDE 10 Pneumovax NP inhibition Ex. 325 Transnasal Solution Pneumococcal capsular polysaccharide 20 Vinpocetine 20 PDE 10 Pneumovax NP inhibition Ex. 326 Transnasal Solution Pneumococcal capsular polysaccharide 20 Pimobendan 20 PDE 10 Pneumovax NP inhibition Ex. 327 Transnasal Solution Pneumococcal capsular polysaccharide 20 BRL50481 20 PDE 10 Pneumovax NP inhibition Ex. 328 Transnasal Solution Pneumococcal capsular polysaccharide 20 Dipyridamole 40 PDE 10 Pneumovax NP inhibition Ex. 329 Transnasal Solution Pneumococcal capsular polysaccharide 20 Methoxyphenamine 20 β2 10 Pneumovax NP hydrochloride activation Ex. 330 Transnasal Solution Pneumococcal capsular polysaccharide 20 Fenoldopam 20 D1 10 Pneumovax NP mesylate activation Ex. 331 Transnasal Solution Pneumococcal capsular polysaccharide 20 Cisapride 20 5-HT4 10 Pneumovax NP activation Ex. 332 Transnasal Solution Pneumococcal capsular polysaccharide 20 Desmopressin 20 V2 10 Pneumovax NP activation Ex. 333 Transnasal Solution Pneumococcal capsular polysaccharide 20 Prazosin 80 α1,2 10 Pneumovax NP hydrochloride antagonization Ex. 334 Transnasal Solution Pneumococcal capsular polysaccharide 20 Pirenzepine 20 M1 10 Pneumovax NP hycrochloride antagonization Ex. 335 Transnasal Solution Pneumococcal capsular polysaccharide 20 Oxybutynin 40 M2 10 Pneumovax NP hydrochloride antagonization Ex. 336 Transnasal Solution Pneumococcal capsular polysaccharide 20 Tolterodine 80 M3 10 Pneumovax NP tartrate antagonization Ex. 337 Transnasal Solution Pneumococcal capsular polysaccharide 20 Fluphenazine 10 D2 10 Pneumovax NP antagonization Ex. 338 Transnasal Solution Pneumococcal capsular polysaccharide 20 Droperidol 20 10 Pneumovax NP Ex. 339 Transnasal Solution Pneumococcal capsular polysaccharide 20 Sulpiride 20 10 Pneumovax NP Ex. 340 Transnasal Solution Pneumococcal capsular polysaccharide 20 Azelastine 40 H1 10 Pneumovax NP hydrochloride antagonization Ex. 341 Transnasal Solution Pneumococcal capsular polysaccharide 20 Levocetirizine 20 10 Pneumovax NP Ex. 342 Transnasal Solution Pneumococcal capsular polysaccharide 20 Mequitazine 20 10 Pneumovax NP Ex. 343 Transnasal Solution Pneumococcal capsular polysaccharide 20 Thioperamide 20 H3 10 Pneumovax NP antagonization Ex. 344 Transnasal Solution Pneumococcal capsular polysaccharide 20 Sarpogrelate 20 5-HT2 10 Pneumovax NP hydrochloride antagonization Ex. 345 Transnasal Solution Pneumococcal capsular polysaccharide 20 Clopidogrel 20 P2Y12 10 Pneumovax NP antagonization Ex. 346 Transnasal Solution Pneumococcal capsular polysaccharide 20 Tiolopidine 40 10 Pneumovax NP Ex. 347 Transnasal Solution Pneumococcal capsular polysaccharide 20 Prasugrel 20 10 Pneumovax NP Ex. 348 Transnasal Solution Pneumococcal capsular polysaccharide 20 Apafant 20 PAF 10 Pneumovax NP antagonization Ex. 349 Transnasal Solution Pneumococcal capsular polysaccharide 20 Naloxone 20 μ, κ, σ 10 Pneumovax NP antagonization Ex. 350 Transnasal Solution Pneumococcal capsular polysaccharide 20 Zafirlukast 20 CysLT 10 Pneumovax NP antagonization Ex. 351 Transnasal Solution Pneumococcal capsular polysaccharide 20 Montelukast 20 10 Pneumovax NP Ex. 352 Transnasal Solution Pneumococcal capsular polysaccharide 20 Pranlukast 20 10 Pneumovax NP Ex. 353 Transnasal Solution Pneumococcal capsular polysaccharide 20 Candesartan 20 AT1 10 Pneumovax NP antagonization
TABLE-US-00017 TABLE 17 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Pneumococcal capsular polysaccharide 20 — — 30 Ex. 34 Pneumovax NP Ex. 354 Sublingual Solution Pneumococcal capsular polysaccharide 20 Resveratrol 200 PDE 30 Pneumovax NP inhibition Ex. 355 Sublingual Solution Pneumococcal capsular polysaccharide 20 Vinpocetine 100 PDE 30 Pneumovax NP inhibition Ex. 356 Sublingual Solution Pneumococcal capsular polysaccharide 20 Pimobendan 100 PDE 30 Pneumovax NP inhibition Ex. 357 Sublingual Solution Pneumococcal capsular polysaccharide 20 BRL50481 100 PDE 30 Pneumovax NP inhibition Ex. 358 Sublingual Solution Pneumococcal capsular polysaccharide 20 Dipyridamole 200 PDE 30 Pneumovax NP inhibition Ex. 359 Sublingual Solution Pneumococcal capsular polysaccharide 20 Methoxyphenamine 100 β2 30 Pneumovax NP hydrochloride activation Ex. 360 Sublingual Solution Pneumococcal capsular polysaccharide 20 Fenoldopam 100 D1 30 Pneumovax NP mesylate activation Ex. 361 Sublingual Solution Pneumococcal capsular polysaccharide 20 Cisapride 100 5-HT4 30 Pneumovax NP activation Ex. 362 Sublingual Solution Pneumococcal capsular polysaccharide 20 Desmopressin 100 V2 30 Pneumovax NP activation Ex. 363 Sublingual Solution Pneumococcal capsular polysaccharide 20 Prazosin 400 α1,2 30 Pneumovax NP hydrochloride antagonization Ex. 364 Sublingual Solution Pneumococcal capsular polysaccharide 20 Pirenzepine 100 M1 30 Pneumovax NP hycrochloride antagonization Ex. 365 Sublingual Solution Pneumococcal capsular polysaccharide 20 Oxybutynin 200 M2 30 Pneumovax NP hydrochloride antagonization Ex. 366 Sublingual Solution Pneumococcal capsular polysaccharide 20 Tolterodine 400 M3 30 Pneumovax NP tartrate antagonization Ex. 367 Sublingual Solution Pneumococcal capsular polysaccharide 20 Fluphenazine 50 D2 30 Pneumovax NP antagonization Ex. 368 Sublingual Solution Pneumococcal capsular polysaccharide 20 Droperidol 100 30 Pneumovax NP Ex. 369 Sublingual Solution Pneumococcal capsular polysaccharide 20 Sulpiride 100 30 Pneumovax NP Ex. 370 Sublingual Solution Pneumococcal capsular polysaccharide 20 Azelastine 200 H1 30 Pneumovax NP hydrochloride antagonization Ex. 371 Sublingual Solution Pneumococcal capsular polysaccharide 20 Levocetirizine 100 30 Pneumovax NP Ex. 372 Sublingual Solution Pneumococcal capsular polysaccharide 20 Mequitazine 100 30 Pneumovax NP Ex. 373 Sublingual Solution Pneumococcal capsular polysaccharide 20 Thioperamide 100 H3 30 Pneumovax NP antagonization Ex. 374 Sublingual Solution Pneumococcal capsular polysaccharide 20 Sarpogrelate 100 5-HT2 30 Pneumovax NP hydrochloride antagonization Ex. 375 Sublingual Solution Pneumococcal capsular polysaccharide 20 Clopidogrel 100 P2Y12 30 Pneumovax NP antagonization Ex. 376 Sublingual Solution Pneumococcal capsular polysaccharide 20 Tiolopidine 200 30 Pneumovax NP Ex. 377 Sublingual Solution Pneumococcal capsular polysaccharide 20 Prasugrel 100 30 Pneumovax NP Ex. 378 Sublingual Solution Pneumococcal capsular polysaccharide 20 Apafant 100 PAF 30 Pneumovax NP antagonization Ex. 379 Sublingual Solution Pneumococcal capsular polysaccharide 20 Naloxone 100 μ, κ, σ 30 Pneumovax NP antagonization Ex. 380 Sublingual Solution Pneumococcal capsular polysaccharide 20 Zafirlukast 100 CysLT 30 Pneumovax NP antagonization Ex. 381 Sublingual Solution Pneumococcal capsular polysaccharide 20 Montelukast 100 30 Pneumovax NP Ex. 382 Sublingual Solution Pneumococcal capsular polysaccharide 20 Pranlukast 100 30 Pneumovax NP Ex. 383 Sublingual Solution Pneumococcal capsular polysaccharide 20 Candesartan 100 AT1 30 Pneumovax NP antagonization
TABLE-US-00018 TABLE 18 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution HPV16 10 — — 10 Ex. 35 recombinant protein Ex. 384 Transnasal Solution HPV16 10 Resveratrol 40 PDE 10 recombinant protein inhibition Ex. 385 Transnasal Solution HPV16 10 Vinpocetine 20 PDE 10 recombinant protein inhibition Ex. 386 Transnasal Solution HPV16 10 Pimobendan 20 PDE 10 recombinant protein inhibition Ex. 387 Transnasal Solution HPV16 10 BRL50481 20 PDE 10 recombinant protein inhibition Ex. 388 Transnasal Solution HPV16 10 Dipyridamole 40 PDE 10 recombinant protein inhibition Ex. 389 Transnasal Solution HPV16 10 Methoxyphenamine 20 β2 10 recombinant protein hydrochloride activation Ex. 390 Transnasal Solution HPV16 10 Fenoldopam 20 D1 10 recombinant protein mesylate activation Ex. 391 Transnasal Solution HPV16 10 Cisapride 20 5-HT4 10 recombinant protein activation Ex. 392 Transnasal Solution HPV16 10 Desmopressin 20 V2 10 recombinant protein activation Ex. 393 Transnasal Solution HPV16 10 Prazosin 80 α1,2 10 recombinant protein hydrochloride antagonization Ex. 394 Transnasal Solution HPV16 10 Pirenzepine 20 M1 10 recombinant protein hycrochloride antagonization Ex. 395 Transnasal Solution HPV16 10 Oxybutynin 40 M2 10 recombinant protein hydrochloride antagonization Ex. 396 Transnasal Solution HPV16 10 Tolterodine 80 M3 10 recombinant protein tartrate antagonization Ex. 397 Transnasal Solution HPV16 10 Fluphenazine 10 D2 10 recombinant protein antagonization Ex. 398 Transnasal Solution HPV16 10 Droperidol 20 10 recombinant protein Ex. 399 Transnasal Solution HPV16 10 Sulpiride 20 10 recombinant protein Ex. 400 Transnasal Solution HPV16 10 Azelastine 40 H1 10 recombinant protein hydrochloride antagonization Ex. 401 Transnasal Solution HPV16 10 Levocetirizine 20 10 recombinant protein Ex. 402 Transnasal Solution HPV16 10 Mequitazine 20 10 recombinant protein Ex. 403 Transnasal Solution HPV16 10 Thioperamide 20 H3 10 recombinant protein antagonization Ex. 404 Transnasal Solution HPV16 10 Sarpogrelate 20 5-HT2 10 recombinant protein hydrochloride antagonization Ex. 405 Transnasal Solution HPV16 10 Clopidogrel 20 P2Y12 10 recombinant protein antagonization Ex. 406 Transnasal Solution HPV16 10 Tiolopidine 40 10 recombinant protein Ex. 407 Transnasal Solution HPV16 10 Prasugrel 20 10 recombinant protein Ex. 408 Transnasal Solution HPV16 10 Apafant 20 PAF 10 recombinant protein antagonization Ex. 409 Transnasal Solution HPV16 10 Naloxone 20 μ, κ, σ 10 recombinant protein antagonization Ex. 410 Transnasal Solution HPV16 10 Zafirlukast 20 CysLT 10 recombinant protein antagonization Ex. 411 Transnasal Solution HPV16 10 Montelukast 20 10 recombinant protein Ex. 412 Transnasal Solution HPV16 10 Pranlukast 20 10 recombinant protein Ex. 413 Transnasal Solution HPV16 10 Candesartan 20 AT1 10 recombinant protein antagonization
TABLE-US-00019 TABLE 19 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution HPV16 10 — — 30 Ex. 36 recombinant protein Ex. 414 Sublingual Solution HPV16 10 Resveratrol 200 PDE 30 recombinant protein inhibition Ex. 415 Sublingual Solution HPV16 10 Vinpocetine 100 PDE 30 recombinant protein inhibition Ex. 416 Sublingual Solution HPV16 10 Pimobendan 100 PDE 30 recombinant protein inhibition Ex. 417 Sublingual Solution HPV16 10 BRL50481 100 PDE 30 recombinant protein inhibition Ex. 418 Sublingual Solution HPV16 10 Dipyridamole 200 PDE 30 recombinant protein inhibition Ex. 419 Sublingual Solution HPV16 10 Methoxyphenamine 100 β2 30 recombinant protein hydrochloride activation Ex. 420 Sublingual Solution HPV16 10 Fenoldopam 100 D1 30 recombinant protein mesylate activation Ex. 421 Sublingual Solution HPV16 10 Cisapride 100 5-HT4 30 recombinant protein activation Ex. 422 Sublingual Solution HPV16 10 Desmopressin 100 V2 30 recombinant protein activation Ex. 423 Sublingual Solution HPV16 10 Prazosin 400 α1,2 30 recombinant protein hydrochloride antagonization Ex. 424 Sublingual Solution HPV16 10 Pirenzepine 100 M1 30 recombinant protein hycrochloride antagonization Ex. 425 Sublingual Solution HPV16 10 Oxybutynin 200 M2 30 recombinant protein hydrochloride antagonization Ex. 426 Sublingual Solution HPV16 10 Tolterodine 400 M3 30 recombinant protein tartrate antagonization Ex. 427 Sublingual Solution HPV16 10 Fluphenazine 50 D2 30 recombinant protein antagonization Ex. 428 Sublingual Solution HPV16 10 Droperidol 100 30 recombinant protein Ex. 429 Sublingual Solution HPV16 10 Sulpiride 100 30 recombinant protein Ex. 430 Sublingual Solution HPV16 10 Azelastine 200 H1 30 recombinant protein hydrochloride antagonization Ex. 431 Sublingual Solution HPV16 10 Levocetirizine 100 30 recombinant protein Ex. 432 Sublingual Solution HPV16 10 Mequitazine 100 30 recombinant protein Ex. 433 Sublingual Solution HPV16 10 Thioperamide 100 H3 30 recombinant protein antagonization Ex. 434 Sublingual Solution HPV16 10 Sarpogrelate 100 5-HT2 30 recombinant protein hydrochloride antagonization Ex. 435 Sublingual Solution HPV16 10 Clopidogrel 100 P2Y12 30 recombinant protein antagonization Ex. 436 Sublingual Solution HPV16 10 Tiolopidine 200 30 recombinant protein Ex. 437 Sublingual Solution HPV16 10 Prasugrel 100 30 recombinant protein Ex. 438 Sublingual Solution HPV16 10 Apafant 100 PAF 30 recombinant protein antagonization Ex. 439 Sublingual Solution HPV16 10 Naloxone 100 μ, κ, σ 30 recombinant protein antagonization Ex. 440 Sublingual Solution HPV16 10 Zafirlukast 100 CysLT 30 recombinant protein antagonization Ex. 441 Sublingual Solution HPV16 10 Montelukast 100 30 recombinant protein Ex. 442 Sublingual Solution HPV16 10 Pranlukast 100 30 recombinant protein Ex. 443 Sublingual Solution HPV16 10 Candesartan 100 AT1 30 recombinant protein antagonization
TABLE-US-00020 TABLE 20 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Live attenuated rotavirus 10 — — 10 Ex. 37 (RIX4414 strain) Ex. 444 Transnasal Solution Live attenuated rotavirus 10 Resveratrol 40 PDE 10 (RIX4414 strain) inhibition Ex. 445 Transnasal Solution Live attenuated rotavirus 10 Vinpocetine 20 PDE 10 (RIX4414 strain) inhibition Ex. 446 Transnasal Solution Live attenuated rotavirus 10 Pimobendan 20 PDE 10 (RIX4414 strain) inhibition Ex. 447 Transnasal Solution Live attenuated rotavirus 10 BRL50481 20 PDE 10 (RIX4414 strain) inhibition Ex. 448 Transnasal Solution Live attenuated rotavirus 10 Dipyridamole 40 PDE 10 (RIX4414 strain) inhibition Ex. 449 Transnasal Solution Live attenuated rotavirus 10 Methoxyphenamine 20 β2 10 (RIX4414 strain) hydrochloride activation Ex. 450 Transnasal Solution Live attenuated rotavirus 10 Fenoldopam 20 D1 10 (RIX4414 strain) mesylate activation Ex. 451 Transnasal Solution Live attenuated rotavirus 10 Cisapride 20 5-HT4 10 (RIX4414 strain) activation Ex. 452 Transnasal Solution Live attenuated rotavirus 10 Desmopressin 20 V2 10 (RIX4414 strain) activation Ex. 453 Transnasal Solution Live attenuated rotavirus 10 Prazosin 80 α1,2 10 (RIX4414 strain) hydrochloride antagonization Ex. 454 Transnasal Solution Live attenuated rotavirus 10 Pirenzepine 20 M1 10 (RIX4414 strain) hycrochloride antagonization Ex. 455 Transnasal Solution Live attenuated rotavirus 10 Oxybutynin 40 M2 10 (RIX4414 strain) hydrochloride antagonization Ex. 456 Transnasal Solution Live attenuated rotavirus 10 Tolterodine 80 M3 10 (RIX4414 strain) tartrate antagonization Ex. 457 Transnasal Solution Live attenuated rotavirus 10 Fluphenazine 10 D2 10 (RIX4414 strain) antagonization Ex. 458 Transnasal Solution Live attenuated rotavirus 10 Droperidol 20 10 (RIX4414 strain) Ex. 459 Transnasal Solution Live attenuated rotavirus 10 Sulpiride 20 10 (RIX4414 strain) Ex. 460 Transnasal Solution Live attenuated rotavirus 10 Azelastine 40 H1 10 (RIX4414 strain) hydrochloride antagonization Ex. 461 Transnasal Solution Live attenuated rotavirus 10 Levocetirizine 20 10 (RIX4414 strain) Ex. 462 Transnasal Solution Live attenuated rotavirus 10 Mequitazine 20 10 (RIX4414 strain) Ex. 463 Transnasal Solution Live attenuated rotavirus 10 Thioperamide 20 H3 10 (RIX4414 strain) antagonization Ex. 464 Transnasal Solution Live attenuated rotavirus 10 Sarpogrelate 20 5-HT2 10 (RIX4414 strain) hydrochloride antagonization Ex. 465 Transnasal Solution Live attenuated rotavirus 10 Clopidogrel 20 P2Y12 10 (RIX4414 strain) antagonization Ex. 466 Transnasal Solution Live attenuated rotavirus 10 Tiolopidine 40 10 (RIX4414 strain) Ex. 467 Transnasal Solution Live attenuated rotavirus 10 Prasugrel 20 10 (RIX4414 strain) Ex. 468 Transnasal Solution Live attenuated rotavirus 10 Apafant 20 PAF 10 (RIX4414 strain) antagonization Ex. 469 Transnasal Solution Live attenuated rotavirus 10 Naloxone 20 μ, κ, σ 10 (RIX4414 strain) antagonization Ex. 470 Transnasal Solution Live attenuated rotavirus 10 Zafirlukast 20 CysLT 10 (RIX4414 strain) antagonization Ex. 471 Transnasal Solution Live attenuated rotavirus 10 Montelukast 20 10 (RIX4414 strain) Ex. 472 Transnasal Solution Live attenuated rotavirus 10 Pranlukast 20 10 (RIX4414 strain) Ex. 473 Transnasal Solution Live attenuated rotavirus 10 Candesartan 20 AT1 10 (RIX4414 strain) antagonization
TABLE-US-00021 TABLE 21 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live attenuated rotavirus 10 — — 30 Ex. 38 (RIX4414 strain) Ex. 474 Sublingual Solution Live attenuated rotavirus 10 Resveratrol 200 PDE 30 (RIX4414 strain) inhibition Ex. 475 Sublingual Solution Live attenuated rotavirus 10 Vinpocetine 100 PDE 30 (RIX4414 strain) inhibition Ex. 476 Sublingual Solution Live attenuated rotavirus 10 Pimobendan 100 PDE 30 (RIX4414 strain) inhibition Ex. 477 Sublingual Solution Live attenuated rotavirus 10 BRL50481 100 PDE 30 (RIX4414 strain) inhibition Ex. 478 Sublingual Solution Live attenuated rotavirus 10 Dipyridamole 200 PDE 30 (RIX4414 strain) inhibition Ex. 479 Sublingual Solution Live attenuated rotavirus 10 Methoxyphenamine 100 β2 30 (RIX4414 strain) hydrochloride activation Ex. 480 Sublingual Solution Live attenuated rotavirus 10 Fenoldopam 100 D1 30 (RIX4414 strain) mesylate activation Ex. 481 Sublingual Solution Live attenuated rotavirus 10 Cisapride 100 5-HT4 30 (RIX4414 strain) activation Ex. 482 Sublingual Solution Live attenuated rotavirus 10 Desmopressin 100 V2 30 (RIX4414 strain) activation Ex. 483 Sublingual Solution Live attenuated rotavirus 10 Prazosin 400 α1,2 30 (RIX4414 strain) hydrochloride antagonization Ex. 484 Sublingual Solution Live attenuated rotavirus 10 Pirenzepine 100 M1 30 (RIX4414 strain) hydrochloride antagonization Ex. 485 Sublingual Solution Live attenuated rotavirus 10 Oxybutynin 200 M2 30 (RIX4414 strain) hydrochloride antagonization Ex. 486 Sublingual Solution Live attenuated rotavirus 10 Tolterodine 400 M3 30 (RIX4414 strain) tartrate antagonization Ex. 487 Sublingual Solution Live attenuated rotavirus 10 Fluphenazine 50 D2 30 (RIX4414 strain) antagonization Ex. 488 Sublingual Solution Live attenuated rotavirus 10 Droperidol 100 30 (RIX4414 strain) Ex. 489 Sublingual Solution Live attenuated rotavirus 10 Sulpiride 100 30 (RIX4414 strain) Ex. 490 Sublingual Solution Live attenuated rotavirus 10 Azelastine 200 H1 30 (RIX4414 strain) hydrochloride antagonization Ex. 491 Sublingual Solution Live attenuated rotavirus 10 Levocetirizine 100 30 (RIX4414 strain) Ex. 492 Sublingual Solution Live attenuated rotavirus 10 Mequitazine 100 30 (RIX4414 strain) Ex. 493 Sublingual Solution Live attenuated rotavirus 10 Thioperamide 100 H3 30 (RIX4414 strain) antagonization Ex. 494 Sublingual Solution Live attenuated rotavirus 10 Sarpogrelate 100 5-HT2 30 (RIX4414 strain) hydrochloride antagonization Ex. 495 Sublingual Solution Live attenuated rotavirus 10 Clopidogrel 100 P2Y12 30 (RIX4414 strain) antagonization Ex. 496 Sublingual Solution Live attenuated rotavirus 10 Ticlopidine 200 30 (RIX4414 strain) Ex. 497 Sublingual Solution Live attenuated rotavirus 10 Prasugrel 100 30 (RIX4414 strain) Ex. 498 Sublingual Solution Live attenuated rotavirus 10 Apafant 100 PAF 30 (RIX4414 strain) antagonization Ex. 499 Sublingual Solution Live attenuated rotavirus 10 Naloxone 100 μ, κ, σ 30 (RIX4414 strain) antagonization Ex. 500 Sublingual Solution Live attenuated rotavirus 10 Zafirlukast 100 CysLT 30 (RIX4414 strain) antagonization Ex. 501 Sublingual Solution Live attenuated rotavirus 10 Montelukast 100 30 (RIX4414 strain) Ex. 502 Sublingual Solution Live attenuated rotavirus 10 Pranlukast 100 30 (RIX4414 strain) Ex. 503 Sublingual Solution Live attenuated rotavirus 10 Candesartan 100 AT1 30 (RIX4414 strain) antagonization
TABLE-US-00022 TABLE 22 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Inactivated poliovirus Vaccine — — 10 Ex. 39 (type 1, type 2, and type 3) 100 μL equivalent Ex. 504 Transnasal Solution Inactivated poliovirus Vaccine Resveratrol 40 PDE 10 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 505 Transnasal Solution Inactivated poliovirus Vaccine Vinpocetine 20 PDE 10 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 506 Transnasal Solution Inactivated poliovirus Vaccine Pimobendan 20 PDE 10 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 507 Transnasal Solution Inactivated poliovirus Vaccine BRL50481 20 PDE 10 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 508 Transnasal Solution Inactivated poliovirus Vaccine Dipyridamole 40 PDE 10 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 509 Transnasal Solution Inactivated poliovirus Vaccine Methoxyphenamine 20 β2 10 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride activation Ex. 510 Transnasal Solution Inactivated poliovirus Vaccine Fenoldopam 20 D1 10 (type 1, type 2, and type 3) 100 μL equivalent mesylate activation Ex. 511 Transnasal Solution Inactivated poliovirus Vaccine Cisapride 20 5-HT4 10 (type 1, type 2, and type 3) 100 μL equivalent activation Ex. 512 Transnasal Solution Inactivated poliovirus Vaccine Desmopressin 20 V2 10 (type 1, type 2, and type 3) 100 μL equivalent activation Ex. 513 Transnasal Solution Inactivated poliovirus Vaccine Prazosin 80 α1,2 10 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 514 Transnasal Solution Inactivated poliovirus Vaccine Pirenzepine 20 M1 10 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 515 Transnasal Solution Inactivated poliovirus Vaccine Oxybutynin 40 M2 10 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 516 Transnasal Solution Inactivated poliovirus Vaccine Tolterodine 80 M3 10 (type 1, type 2, and type 3) 100 μL equivalent tartrate antagonization Ex. 517 Transnasal Solution Inactivated poliovirus Vaccine Fluphenazine 10 D2 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 518 Transnasal Solution Inactivated poliovirus Vaccine Droperidol 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 519 Transnasal Solution Inactivated poliovirus Vaccine Sulpiride 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 520 Transnasal Solution Inactivated poliovirus Vaccine Azelastine 40 H1 10 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 521 Transnasal Solution Inactivated poliovirus Vaccine Levocetirizine 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 522 Transnasal Solution Inactivated poliovirus Vaccine Mequitazine 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 523 Transnasal Solution Inactivated poliovirus Vaccine Thioperamide 20 H3 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 524 Transnasal Solution Inactivated poliovirus Vaccine Sarpogrelate 20 5-HT2 10 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 525 Transnasal Solution Inactivated poliovirus Vaccine Clopidogrel 20 P2Y12 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 526 Transnasal Solution Inactivated poliovirus Vaccine Ticlopidine 40 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 527 Transnasal Solution Inactivated poliovirus Vaccine Prasugrel 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 528 Transnasal Solution Inactivated poliovirus Vaccine Apafant 20 PAF 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 529 Transnasal Solution Inactivated poliovirus Vaccine Naloxone 20 μ, κ, σ 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 530 Transnasal Solution Inactivated poliovirus Vaccine Zafirlukast 20 CysLT 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 531 Transnasal Solution Inactivated poliovirus Vaccine Montelukast 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 532 Transnasal Solution Inactivated poliovirus Vaccine Pranlukast 20 10 (type 1, type 2, and type 3) 100 μL equivalent Ex. 533 Transnasal Solution Inactivated poliovirus Vaccine Candesartan 20 AT1 10 (type 1, type 2, and type 3) 100 μL equivalent antagonization
TABLE-US-00023 TABLE 23 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Inactivated poliovirus Vaccine — — 30 Ex. 40 (type 1, type 2, and type 3) 100 μL equivalent Ex. 534 Sublingual Solution Inactivated poliovirus Vaccine Resveratrol 200 PDE 30 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 535 Sublingual Solution Inactivated poliovirus Vaccine Vinpocetine 100 PDE 30 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 536 Sublingual Solution Inactivated poliovirus Vaccine Pimobendan 100 PDE 30 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 537 Sublingual Solution Inactivated poliovirus Vaccine BRL50481 100 PDE 30 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 538 Sublingual Solution Inactivated poliovirus Vaccine Dipyridamole 200 PDE 30 (type 1, type 2, and type 3) 100 μL equivalent inhibition Ex. 539 Sublingual Solution Inactivated poliovirus Vaccine Methoxyphenamine 100 β2 30 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride activation Ex. 540 Sublingual Solution Inactivated poliovirus Vaccine Fenoldopam 100 D1 30 (type 1, type 2, and type 3) 100 μL equivalent mesylate activation Ex. 541 Sublingual Solution Inactivated poliovirus Vaccine Cisapride 100 5-HT4 30 (type 1, type 2, and type 3) 100 μL equivalent activation Ex. 542 Sublingual Solution Inactivated poliovirus Vaccine Desmopressin 100 V2 30 (type 1, type 2, and type 3) 100 μL equivalent activation Ex. 543 Sublingual Solution Inactivated poliovirus Vaccine Prazosin 400 α1,2 30 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 544 Sublingual Solution Inactivated poliovirus Vaccine Pirenzepine 100 M1 30 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 545 Sublingual Solution Inactivated poliovirus Vaccine Oxybutynin 200 M2 30 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 546 Sublingual Solution Inactivated poliovirus Vaccine Tolterodine 400 M3 30 (type 1, type 2, and type 3) 100 μL equivalent tartrate antagonization Ex. 547 Sublingual Solution Inactivated poliovirus Vaccine Fluphenazine 50 D2 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 548 Sublingual Solution Inactivated poliovirus Vaccine Droperidol 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 549 Sublingual Solution Inactivated poliovirus Vaccine Sulpiride 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 550 Sublingual Solution Inactivated poliovirus Vaccine Azelastine 200 H1 30 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 551 Sublingual Solution Inactivated poliovirus Vaccine Levocetirizine 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 552 Sublingual Solution Inactivated poliovirus Vaccine Mequitazine 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 553 Sublingual Solution Inactivated poliovirus Vaccine Thioperamide 100 H3 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 554 Sublingual Solution Inactivated poliovirus Vaccine Sarpogrelate 100 5-HT2 30 (type 1, type 2, and type 3) 100 μL equivalent hydrochloride antagonization Ex. 555 Sublingual Solution Inactivated poliovirus Vaccine Clopidogrel 100 P2Y12 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 556 Sublingual Solution Inactivated poliovirus Vaccine Ticlopidine 200 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 557 Sublingual Solution Inactivated poliovirus Vaccine Prasugrel 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 558 Sublingual Solution Inactivated poliovirus Vaccine Apafant 100 PAF 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 589 Sublingual Solution Inactivated poliovirus Vaccine Naloxone 100 μ, κ, σ 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 560 Sublingual Solution Inactivated poliovirus Vaccine Zafirlukast 100 CysLT 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization Ex. 561 Sublingual Solution Inactivated poliovirus Vaccine Montelukast 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 562 Sublingual Solution Inactivated poliovirus Vaccine Pranlukast 100 30 (type 1, type 2, and type 3) 100 μL equivalent Ex. 563 Sublingual Solution Inactivated poliovirus Vaccine Candesartan 100 AT1 30 (type 1, type 2, and type 3) 100 μL equivalent antagonization
TABLE-US-00024 TABLE 24 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Inactivated Vaccine — — 10 Ex. 41 hepatitis A virus 100 μL equivalent Ex. 564 Transnasal Solution Inactivated Vaccine Resveratrol 40 PDE 10 hepatitis A virus 100 μL equivalent inhibition Ex. 565 Transnasal Solution Inactivated Vaccine Vinpocetine 20 PDE 10 hepatitis A virus 100 μL equivalent inhibition Ex. 566 Transnasal Solution Inactivated Vaccine Pimobendan 20 PDE 10 hepatitis A virus 100 μL equivalent inhibition Ex. 567 Transnasal Solution Inactivated Vaccine BRL50481 20 PDE 10 hepatitis A virus 100 μL equivalent inhibition Ex. 568 Transnasal Solution Inactivated Vaccine Dipyridamole 40 PDE 10 hepatitis A virus 100 μL equivalent inhibition Ex. 569 Transnasal Solution Inactivated Vaccine Methoxyphenamine 20 β2 10 hepatitis A virus 100 μL equivalent hydrochloride activation Ex. 570 Transnasal Solution Inactivated Vaccine Fenoldopam 20 D1 10 hepatitis A virus 100 μL equivalent mesylate activation Ex. 571 Transnasal Solution Inactivated Vaccine Cisapride 20 5-HT4 10 hepatitis A virus 100 μL equivalent activation Ex. 572 Transnasal Solution Inactivated Vaccine Desmopressin 20 V2 10 hepatitis A virus 100 μL equivalent activation Ex. 573 Transnasal Solution Inactivated Vaccine Prazosin 80 α1,2 10 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 574 Transnasal Solution Inactivated Vaccine Pirenzepine 20 M1 10 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 575 Transnasal Solution Inactivated Vaccine Oxybutynin 40 M2 10 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 576 Transnasal Solution Inactivated Vaccine Tolterodine 80 M3 10 hepatitis A virus 100 μL equivalent tartrate antagonization Ex. 577 Transnasal Solution Inactivated Vaccine Fluphenazine 10 D2 10 hepatitis A virus 100 μL equivalent antagonization Ex. 578 Transnasal Solution Inactivated Vaccine Droperidol 20 10 hepatitis A virus 100 μL equivalent Ex. 579 Transnasal Solution Inactivated Vaccine Sulpiride 20 10 hepatitis A virus 100 μL equivalent Ex. 580 Transnasal Solution Inactivated Vaccine Azelastine 40 H1 10 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 581 Transnasal Solution Inactivated Vaccine Levocetirizine 20 10 hepatitis A virus 100 μL equivalent Ex. 582 Transnasal Solution Inactivated Vaccine Mequitazine 20 10 hepatitis A virus 100 μL equivalent Ex. 583 Transnasal Solution Inactivated Vaccine Thioperamide 20 H3 10 hepatitis A virus 100 μL equivalent antagonization Ex. 584 Transnasal Solution Inactivated Vaccine Sarpogrelate 20 5-HT2 10 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 585 Transnasal Solution Inactivated Vaccine Clopidogrel 20 P2Y12 10 hepatitis A virus 100 μL equivalent antagonization Ex. 586 Transnasal Solution Inactivated Vaccine Ticlopidine 40 10 hepatitis A virus 100 μL equivalent Ex. 587 Transnasal Solution Inactivated Vaccine Prasugrel 20 10 hepatitis A virus 100 μL equivalent Ex. 588 Transnasal Solution Inactivated Vaccine Apafant 20 PAF 10 hepatitis A virus 100 μL equivalent antagonization Ex. 589 Transnasal Solution Inactivated Vaccine Naloxone 20 μ, κ, σ 10 hepatitis A virus 100 μL equivalent antagonization Ex. 590 Transnasal Solution Inactivated Vaccine Zafirlukast 20 CysLT 10 hepatitis A virus 100 μL equivalent antagonization Ex. 591 Transnasal Solution Inactivated Vaccine Montelukast 20 10 hepatitis A virus 100 μL equivalent Ex. 592 Transnasal Solution Inactivated Vaccine Pranlukast 20 10 hepatitis A virus 100 μL equivalent Ex. 593 Transnasal Solution Inactivated Vaccine Candesartan 20 AT1 10 hepatitis A virus 100 μL equivalent antagonization
TABLE-US-00025 TABLE 25 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Inactivated Vaccine — — 30 Ex. 42 hepatitis A virus 100 μL equivalent Ex. 594 Sublingual Solution Inactivated Vaccine Resveratrol 200 PDE 30 hepatitis A virus 100 μL equivalent inhibition Ex. 595 Sublingual Solution Inactivated Vaccine Vinpocetine 100 PDE 30 hepatitis A virus 100 μL equivalent inhibition Ex. 596 Sublingual Solution Inactivated Vaccine Pimobendan 100 PDE 30 hepatitis A virus 100 μL equivalent inhibition Ex. 597 Sublingual Solution Inactivated Vaccine BRL50481 100 PDE 30 hepatitis A virus 100 μL equivalent inhibition Ex. 598 Sublingual Solution Inactivated Vaccine Dipyridamole 200 PDE 30 hepatitis A virus 100 μL equivalent inhibition Ex. 599 Sublingual Solution Inactivated Vaccine Methoxyphenamine 100 β2 30 hepatitis A virus 100 μL equivalent hydrochloride activation Ex. 600 Sublingual Solution Inactivated Vaccine Fenoldopam 100 D1 30 hepatitis A virus 100 μL equivalent mesylate activation Ex. 601 Sublingual Solution Inactivated Vaccine Cisapride 100 5-HT4 30 hepatitis A virus 100 μL equivalent activation Ex. 602 Sublingual Solution Inactivated Vaccine Desmopressin 100 V2 30 hepatitis A virus 100 μL equivalent activation Ex. 603 Sublingual Solution Inactivated Vaccine Prazosin 400 α1,2 30 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 604 Sublingual Solution Inactivated Vaccine Pirenzepine 100 M1 30 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 605 Sublingual Solution Inactivated Vaccine Oxybutynin 200 M2 30 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 606 Sublingual Solution Inactivated Vaccine Tolterodine 400 M3 30 hepatitis A virus 100 μL equivalent tartrate antagonization Ex. 607 Sublingual Solution Inactivated Vaccine Fluphenazine 50 D2 30 hepatitis A virus 100 μL equivalent antagonization Ex. 608 Sublingual Solution Inactivated Vaccine Droperidol 100 30 hepatitis A virus 100 μL equivalent Ex. 609 Sublingual Solution Inactivated Vaccine Sulpiride 100 30 hepatitis A virus 100 μL equivalent Ex. 610 Sublingual Solution Inactivated Vaccine Azelastine 200 H1 30 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 611 Sublingual Solution Inactivated Vaccine Levocetirizine 100 30 hepatitis A virus 100 μL equivalent Ex. 612 Sublingual Solution Inactivated Vaccine Mequitazine 100 30 hepatitis A virus 100 μL equivalent Ex. 613 Sublingual Solution Inactivated Vaccine Thioperamide 100 H3 30 hepatitis A virus 100 μL equivalent antagonization Ex. 614 Sublingual Solution Inactivated Vaccine Sarpogrelate 100 5-HT2 30 hepatitis A virus 100 μL equivalent hydrochloride antagonization Ex. 615 Sublingual Solution Inactivated Vaccine Clopidogrel 100 P2Y12 30 hepatitis A virus 100 μL equivalent antagonization Ex. 616 Sublingual Solution Inactivated Vaccine Ticlopidine 200 30 hepatitis A virus 100 μL equivalent Ex. 617 Sublingual Solution Inactivated Vaccine Prasugrel 100 30 hepatitis A virus 100 μL equivalent Ex. 618 Sublingual Solution Inactivated Vaccine Apafant 100 PAF 30 hepatitis A virus 100 μL equivalent antagonization Ex. 619 Sublingual Solution Inactivated Vaccine Naloxone 100 μ, κ, σ 30 hepatitis A virus 100 μL equivalent antagonization Ex. 620 Sublingual Solution Inactivated Vaccine Zafirlukast 100 CysLT 30 hepatitis A virus 100 μL equivalent antagonization Ex. 621 Sublingual Solution Inactivated Vaccine Montelukast 100 30 hepatitis A virus 100 μL equivalent Ex. 622 Sublingual Solution Inactivated Vaccine Pranlukast 100 30 hepatitis A virus 100 μL equivalent Ex. 623 Sublingual Solution Inactivated Vaccine Candesartan 100 AT1 30 hepatitis A virus 100 μL equivalent antagonization
TABLE-US-00026 TABLE 26 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Inactivated Japanese Vaccine — — 10 Ex. 43 encephalitis virus 100 μL equivalent Ex. 624 Transnasal Solution Inactivated Japanese Vaccine Resveratrol 40 PDE 10 encephalitis virus 100 μL equivalent inhibition Ex. 625 Transnasal Solution Inactivated Japanese Vaccine Vinpocetine 20 PDE 10 encephalitis virus 100 μL equivalent inhibition Ex. 626 Transnasal Solution Inactivated Japanese Vaccine Pimobendan 20 PDE 10 encephalitis virus 100 μL equivalent inhibition Ex. 627 Transnasal Solution Inactivated Japanese Vaccine BRL50481 20 PDE 10 encephalitis virus 100 μL equivalent inhibition Ex. 628 Transnasal Solution Inactivated Japanese Vaccine Dipyridamole 40 PDE 10 encephalitis virus 100 μL equivalent inhibition Ex. 629 Transnasal Solution Inactivated Japanese Vaccine Methoxyphenamine 20 β2 10 encephalitis virus 100 μL equivalent hydrochloride activation Ex. 630 Transnasal Solution Inactivated Japanese Vaccine Fenoldopam 20 D1 10 encephalitis virus 100 μL equivalent mesylate activation Ex. 631 Transnasal Solution Inactivated Japanese Vaccine Cisapride 20 5-HT4 10 encephalitis virus 100 μL equivalent activation Ex. 632 Transnasal Solution Inactivated Japanese Vaccine Desmopressin 20 V2 10 encephalitis virus 100 μL equivalent activation Ex. 633 Transnasal Solution Inactivated Japanese Vaccine Prazosin 80 α1,2 10 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 634 Transnasal Solution Inactivated Japanese Vaccine Pirenzepine 20 M1 10 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 635 Transnasal Solution Inactivated Japanese Vaccine Oxybutynin 40 M2 10 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 636 Transnasal Solution Inactivated Japanese Vaccine Tolterodine 80 M3 10 encephalitis virus 100 μL equivalent tartrate antagonization Ex. 637 Transnasal Solution Inactivated Japanese Vaccine Fluphenazine 10 D2 10 encephalitis virus 100 μL equivalent antagonization Ex. 638 Transnasal Solution Inactivated Japanese Vaccine Droperidol 20 10 encephalitis virus 100 μL equivalent Ex. 639 Transnasal Solution Inactivated Japanese Vaccine Sulpiride 20 10 encephalitis virus 100 μL equivalent Ex. 640 Transnasal Solution Inactivated Japanese Vaccine Azelastine 40 H1 10 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 641 Transnasal Solution Inactivated Japanese Vaccine Levocetirizine 20 10 encephalitis virus 100 μL equivalent Ex. 642 Transnasal Solution Inactivated Japanese Vaccine Mequitazine 20 10 encephalitis virus 100 μL equivalent Ex. 643 Transnasal Solution Inactivated Japanese Vaccine Thioperamide 20 H3 10 encephalitis virus 100 μL equivalent antagonization Ex. 644 Transnasal Solution Inactivated Japanese Vaccine Sarpogrelate 20 5-HT2 10 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 645 Transnasal Solution Inactivated Japanese Vaccine Clopidogrel 20 P2Y12 10 encephalitis virus 100 μL equivalent antagonization Ex. 646 Transnasal Solution Inactivated Japanese Vaccine Ticlopidine 40 10 encephalitis virus 100 μL equivalent Ex. 647 Transnasal Solution Inactivated Japanese Vaccine Prasugrel 20 10 encephalitis virus 100 μL equivalent Ex. 648 Transnasal Solution Inactivated Japanese Vaccine Apafant 20 PAF 10 encephalitis virus 100 μL equivalent antagonization Ex. 649 Transnasal Solution Inactivated Japanese Vaccine Naloxone 20 μ, κ, σ 10 encephalitis virus 100 μL equivalent antagonization Ex. 650 Transnasal Solution Inactivated Japanese Vaccine Zafirlukast 20 CysLT 10 encephalitis virus 100 μL equivalent antagonization Ex. 651 Transnasal Solution Inactivated Japanese Vaccine Montelukast 20 10 encephalitis virus 100 μL equivalent Ex. 652 Transnasal Solution Inactivated Japanese Vaccine Pranlukast 20 10 encephalitis virus 100 μL equivalent Ex. 653 Transnasal Solution Inactivated Japanese Vaccine Candesartan 20 AT1 10 encephalitis virus 100 μL equivalent antagonization
TABLE-US-00027 TABLE 27 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Inactivated Japanese Vaccine — — 30 Ex. 44 encephalitis virus 100 μL equivalent Ex. 654 Sublingual Solution Inactivated Japanese Vaccine Resveratrol 200 PDE 30 encephalitis virus 100 μL equivalent inhibition Ex. 655 Sublingual Solution Inactivated Japanese Vaccine Vinpocetine 100 PDE 30 encephalitis virus 100 μL equivalent inhibition Ex. 656 Sublingual Solution Inactivated Japanese Vaccine Pimobendan 100 PDE 30 encephalitis virus 100 μL equivalent inhibition Ex. 657 Sublingual Solution Inactivated Japanese Vaccine BRL50481 100 PDE 30 encephalitis virus 100 μL equivalent inhibition Ex. 658 Sublingual Solution Inactivated Japanese Vaccine Dipyridamole 200 PDE 30 encephalitis virus 100 μL equivalent inhibition Ex. 659 Sublingual Solution Inactivated Japanese Vaccine Methoxyphenamine 100 β2 30 encephalitis virus 100 μL equivalent hydrochloride activation Ex. 660 Sublingual Solution Inactivated Japanese Vaccine Fenoldopam 100 D1 30 encephalitis virus 100 μL equivalent mesylate activation Ex. 661 Sublingual Solution Inactivated Japanese Vaccine Cisapride 100 5-HT4 30 encephalitis virus 100 μL equivalent activation Ex. 662 Sublingual Solution Inactivated Japanese Vaccine Desmopressin 100 V2 30 encephalitis virus 100 μL equivalent activation Ex. 663 Sublingual Solution Inactivated Japanese Vaccine Prazosin 400 α1,2 30 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 664 Sublingual Solution Inactivated Japanese Vaccine Pirenzepine 100 M1 30 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 665 Sublingual Solution Inactivated Japanese Vaccine Oxybutynin 200 M2 30 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 666 Sublingual Solution Inactivated Japanese Vaccine Tolterodine 400 M3 30 encephalitis virus 100 μL equivalent tartrate antagonization Ex. 667 Sublingual Solution Inactivated Japanese Vaccine Fluphenazine 50 D2 30 encephalitis virus 100 μL equivalent antagonization Ex. 668 Sublingual Solution Inactivated Japanese Vaccine Droperidol 100 30 encephalitis virus 100 μL equivalent Ex. 669 Sublingual Solution Inactivated Japanese Vaccine Sulpiride 100 30 encephalitis virus 100 μL equivalent Ex. 670 Sublingual Solution Inactivated Japanese Vaccine Azelastine 200 H1 30 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 671 Sublingual Solution Inactivated Japanese Vaccine Levocetirizine 100 30 encephalitis virus 100 μL equivalent Ex. 672 Sublingual Solution Inactivated Japanese Vaccine Mequitazine 100 30 encephalitis virus 100 μL equivalent Ex. 673 Sublingual Solution Inactivated Japanese Vaccine Thioperamide 100 H3 30 encephalitis virus 100 μL equivalent antagonization Ex. 674 Sublingual Solution Inactivated Japanese Vaccine Sarpogrelate 100 5-HT2 30 encephalitis virus 100 μL equivalent hydrochloride antagonization Ex. 675 Sublingual Solution Inactivated Japanese Vaccine Clopidogrel 100 P2Y12 30 encephalitis virus 100 μL equivalent antagonization Ex. 676 Sublingual Solution Inactivated Japanese Vaccine Ticlopidine 200 30 encephalitis virus 100 μL equivalent Ex. 677 Sublingual Solution Inactivated Japanese Vaccine Prasugrel 100 30 encephalitis virus 100 μL equivalent Ex. 678 Sublingual Solution Inactivated Japanese Vaccine Apafant 100 PAF 30 encephalitis virus 100 μL equivalent antagonization Ex. 679 Sublingual Solution Inactivated Japanese Vaccine Naloxone 100 μ, κ, σ 30 encephalitis virus 100 μL equivalent antagonization Ex. 680 Sublingual Solution Inactivated Japanese Vaccine Zafirlukast 100 CysLT 30 encephalitis virus 100 μL equivalent antagonization Ex. 681 Sublingual Solution Inactivated Japanese Vaccine Montelukast 100 30 encephalitis virus 100 μL equivalent Ex. 682 Sublingual Solution Inactivated Japanese Vaccine Pranlukast 100 30 encephalitis virus 100 μL equivalent Ex. 683 Sublingual Solution Inactivated Japanese Vaccine Candesartan 100 AT1 30 encephalitis virus 100 μL equivalent antagonization
TABLE-US-00028 TABLE 28 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Live attenuated Vaccine — — 10 Ex. 45 mumps virus 100 μL equivalent Ex. 684 Transnasal Solution Live attenuated Vaccine Resveratrol 40 PDE 10 mumps virus 100 μL equivalent inhibition Ex. 685 Transnasal Solution Live attenuated Vaccine Vinpocetine 20 PDE 10 mumps virus 100 μL equivalent inhibition Ex. 686 Transnasal Solution Live attenuated Vaccine Pimobendan 20 PDE 10 mumps virus 100 μL equivalent inhibition Ex. 687 Transnasal Solution Live attenuated Vaccine BRL50481 20 PDE 10 mumps virus 100 μL equivalent inhibition Ex. 688 Transnasal Solution Live attenuated Vaccine Dipyridamole 40 PDE 10 mumps virus 100 μL equivalent inhibition Ex. 689 Transnasal Solution Live attenuated Vaccine Methoxyphenamine 20 β2 10 mumps virus 100 μL equivalent hydrochloride activation Ex. 690 Transnasal Solution Live attenuated Vaccine Fenoldopam 20 D1 10 mumps virus 100 μL equivalent mesylate activation Ex. 691 Transnasal Solution Live attenuated Vaccine Cisapride 20 5-HT4 10 mumps virus 100 μL equivalent activation Ex. 692 Transnasal Solution Live attenuated Vaccine Desmopressin 20 V2 10 mumps virus 100 μL equivalent activation Ex. 693 Transnasal Solution Live attenuated Vaccine Prazosin 80 α1,2 10 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 694 Transnasal Solution Live attenuated Vaccine Pirenzepine 20 M1 10 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 695 Transnasal Solution Live attenuated Vaccine Oxybutynin 40 M2 10 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 696 Transnasal Solution Live attenuated Vaccine Tolterodine 80 M3 10 mumps virus 100 μL equivalent tartrate antagonization Ex. 697 Transnasal Solution Live attenuated Vaccine Fluphenazine 10 D2 10 mumps virus 100 μL equivalent antagonization Ex. 698 Transnasal Solution Live attenuated Vaccine Droperidol 20 10 mumps virus 100 μL equivalent Ex. 699 Transnasal Solution Live attenuated Vaccine Sulpiride 20 10 mumps virus 100 μL equivalent Ex. 700 Transnasal Solution Live attenuated Vaccine Azelastine 40 H1 10 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 701 Transnasal Solution Live attenuated Vaccine Levocetirizine 20 10 mumps virus 100 μL equivalent Ex. 702 Transnasal Solution Live attenuated Vaccine Mequitazine 20 10 mumps virus 100 μL equivalent Ex. 703 Transnasal Solution Live attenuated Vaccine Thioperamide 20 H3 10 mumps virus 100 μL equivalent antagonization Ex. 704 Transnasal Solution Live attenuated Vaccine Sarpogrelate 20 5-HT2 10 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 705 Transnasal Solution Live attenuated Vaccine Clopidogrel 20 P2Y12 10 mumps virus 100 μL equivalent antagonization Ex. 706 Transnasal Solution Live attenuated Vaccine Ticlopidine 40 10 mumps virus 100 μL equivalent Ex. 707 Transnasal Solution Live attenuated Vaccine Prasugrel 20 10 mumps virus 100 μL equivalent Ex. 708 Transnasal Solution Live attenuated Vaccine Apafant 20 PAF 10 mumps virus 100 μL equivalent antagonization Ex. 709 Transnasal Solution Live attenuated Vaccine Naloxone 20 μ, κ, σ 10 mumps virus 100 μL equivalent antagonization Ex. 710 Transnasal Solution Live attenuated Vaccine Zafirlukast 20 CysLT 10 mumps virus 100 μL equivalent antagonization Ex. 711 Transnasal Solution Live attenuated Vaccine Montelukast 20 10 mumps virus 100 μL equivalent Ex. 712 Transnasal Solution Live attenuated Vaccine Pranlukast 20 10 mumps virus 100 μL equivalent Ex. 713 Transnasal Solution Live attenuated Vaccine Candesartan 20 AT1 10 mumps virus 100 μL equivalent antagonization
TABLE-US-00029 TABLE 29 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live attenuated Vaccine — — 30 Ex. 46 mumps virus 100 μL equivalent Ex. 714 Sublingual Solution Live attenuated Vaccine Resveratrol 200 PDE 30 mumps virus 100 μL equivalent inhibition Ex. 715 Sublingual Solution Live attenuated Vaccine Vinpocetine 100 PDE 30 mumps virus 100 μL equivalent inhibition Ex. 716 Sublingual Solution Live attenuated Vaccine Pimobendan 100 PDE 30 mumps virus 100 μL equivalent inhibition Ex. 717 Sublingual Solution Live attenuated Vaccine BRL50481 100 PDE 30 mumps virus 100 μL equivalent inhibition Ex. 718 Sublingual Solution Live attenuated Vaccine Dipyridamole 200 PDE 30 mumps virus 100 μL equivalent inhibition Ex. 719 Sublingual Solution Live attenuated Vaccine Methoxyphenamine 100 β2 30 mumps virus 100 μL equivalent hydrochloride activation Ex. 720 Sublingual Solution Live attenuated Vaccine Fenoldopam 100 D1 30 mumps virus 100 μL equivalent mesylate activation Ex. 721 Sublingual Solution Live attenuated Vaccine Cisapride 100 5-HT4 30 mumps virus 100 μL equivalent activation Ex. 722 Sublingual Solution Live attenuated Vaccine Desmopressin 100 V2 30 mumps virus 100 μL equivalent activation Ex. 723 Sublingual Solution Live attenuated Vaccine Prazosin 400 α1,2 30 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 724 Sublingual Solution Live attenuated Vaccine Pirenzepine 100 M1 30 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 725 Sublingual Solution Live attenuated Vaccine Oxybutynin 200 M2 30 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 726 Sublingual Solution Live attenuated Vaccine Tolterodine 400 M3 30 mumps virus 100 μL equivalent tartrate antagonization Ex. 727 Sublingual Solution Live attenuated Vaccine Fluphenazine 50 D2 30 mumps virus 100 μL equivalent antagonization Ex. 728 Sublingual Solution Live attenuated Vaccine Droperidol 100 30 mumps virus 100 μL equivalent Ex. 729 Sublingual Solution Live attenuated Vaccine Sulpiride 100 30 mumps virus 100 μL equivalent Ex. 730 Sublingual Solution Live attenuated Vaccine Azelastine 200 H1 30 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 731 Sublingual Solution Live attenuated Vaccine Levocetirizine 100 30 mumps virus 100 μL equivalent Ex. 732 Sublingual Solution Live attenuated Vaccine Mequitazine 100 30 mumps virus 100 μL equivalent Ex. 733 Sublingual Solution Live attenuated Vaccine Thioperamide 100 H3 30 mumps virus 100 μL equivalent antagonization Ex. 734 Sublingual Solution Live attenuated Vaccine Sarpogrelate 100 5-HT2 30 mumps virus 100 μL equivalent hydrochloride antagonization Ex. 735 Sublingual Solution Live attenuated Vaccine Clopidogrel 100 P2Y12 30 mumps virus 100 μL equivalent antagonization Ex. 736 Sublingual Solution Live attenuated Vaccine Ticlopidine 200 30 mumps virus 100 μL equivalent Ex. 737 Sublingual Solution Live attenuated Vaccine Prasugrel 100 30 mumps virus 100 μL equivalent Ex. 738 Sublingual Solution Live attenuated Vaccine Apafant 100 PAF 30 mumps virus 100 μL equivalent antagonization Ex. 739 Sublingual Solution Live attenuated Vaccine Naloxone 100 μ, κ, σ 30 mumps virus 100 μL equivalent antagonization Ex. 740 Sublingual Solution Live attenuated Vaccine Zafirlukast 100 CysLT 30 mumps virus 100 μL equivalent antagonization Ex. 741 Sublingual Solution Live attenuated Vaccine Montelukast 100 30 mumps virus 100 μL equivalent Ex. 742 Sublingual Solution Live attenuated Vaccine Pranlukast 100 30 mumps virus 100 μL equivalent Ex. 743 Sublingual Solution Live attenuated Vaccine Candesartan 100 AT1 30 mumps virus 100 μL equivalent antagonization
TABLE-US-00030 TABLE 30 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Live attenuated Vaccine — — 10 Ex. 47 measles virus 100 μL equivalent Ex. 744 Transnasal Solution Live attenuated Vaccine Resveratrol 40 PDE 10 measles virus 100 μL equivalent inhibition Ex. 745 Transnasal Solution Live attenuated Vaccine Vinpocetine 20 PDE 10 measles virus 100 μL equivalent inhibition Ex. 746 Transnasal Solution Live attenuated Vaccine Pimobendan 20 PDE 10 measles virus 100 μL equivalent inhibition Ex. 747 Transnasal Solution Live attenuated Vaccine BRL50481 20 PDE 10 measles virus 100 μL equivalent inhibition Ex. 748 Transnasal Solution Live attenuated Vaccine Dipyridamole 40 PDE 10 measles virus 100 μL equivalent inhibition Ex. 749 Transnasal Solution Live attenuated Vaccine Methoxyphenamine 20 β2 10 measles virus 100 μL equivalent hydrochloride activation Ex. 750 Transnasal Solution Live attenuated Vaccine Fenoldopam 20 D1 10 measles virus 100 μL equivalent mesylate activation Ex. 751 Transnasal Solution Live attenuated Vaccine Cisapride 20 5-HT4 10 measles virus 100 μL equivalent activation Ex. 752 Transnasal Solution Live attenuated Vaccine Desmopressin 20 V2 10 measles virus 100 μL equivalent activation Ex. 753 Transnasal Solution Live attenuated Vaccine Prazosin 80 α1,2 10 measles virus 100 μL equivalent hydrochloride antagonization Ex. 754 Transnasal Solution Live attenuated Vaccine Pirenzepine 20 M1 10 measles virus 100 μL equivalent hydrochloride antagonization Ex. 755 Transnasal Solution Live attenuated Vaccine Oxybutynin 40 M2 10 measles virus 100 μL equivalent hydrochloride antagonization Ex. 756 Transnasal Solution Live attenuated Vaccine Tolterodine 80 M3 10 measles virus 100 μL equivalent tartrate antagonization Ex. 757 Transnasal Solution Live attenuated Vaccine Fluphenazine 10 D2 10 measles virus 100 μL equivalent antagonization Ex. 758 Transnasal Solution Live attenuated Vaccine Droperidol 20 10 measles virus 100 μL equivalent Ex. 759 Transnasal Solution Live attenuated Vaccine Sulpiride 20 10 measles virus 100 μL equivalent Ex. 760 Transnasal Solution Live attenuated Vaccine Azelastine 40 H1 10 measles virus 100 μL equivalent hydrochloride antagonization Ex. 761 Transnasal Solution Live attenuated Vaccine Levocetirizine 20 10 measles virus 100 μL equivalent Ex. 762 Transnasal Solution Live attenuated Vaccine Mequitazine 20 10 measles virus 100 μL equivalent Ex. 763 Transnasal Solution Live attenuated Vaccine Thioperamide 20 H3 10 measles virus 100 μL equivalent antagonization Ex. 764 Transnasal Solution Live attenuated Vaccine Sarpogrelate 20 5-HT2 10 measles virus 100 μL equivalent hydrochloride antagonization Ex. 765 Transnasal Solution Live attenuated Vaccine Clopidogrel 20 P2Y12 10 measles virus 100 μL equivalent antagonization Ex. 766 Transnasal Solution Live attenuated Vaccine Ticlopidine 40 10 measles virus 100 μL equivalent Ex. 767 Transnasal Solution Live attenuated Vaccine Prasugrel 20 10 measles virus 100 μL equivalent Ex. 768 Transnasal Solution Live attenuated Vaccine Apafant 20 PAF 10 measles virus 100 μL equivalent antagonization Ex. 769 Transnasal Solution Live attenuated Vaccine Naloxone 20 μ, κ, σ 10 measles virus 100 μL equivalent antagonization Ex. 770 Transnasal Solution Live attenuated Vaccine Zafirlukast 20 CysLT 10 measles virus 100 μL equivalent antagonization Ex. 771 Transnasal Solution Live attenuated Vaccine Montelukast 20 10 measles virus 100 μL equivalent Ex. 772 Transnasal Solution Live attenuated Vaccine Pranlukast 20 10 measles virus 100 μL equivalent Ex. 773 Transnasal Solution Live attenuated Vaccine Candesartan 20 AT1 10 measles virus 100 μL equivalent antagonization
TABLE-US-00031 TABLE 31 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live attenuated Vaccine — — 30 Ex. 48 measles virus 100 μL equivalent Ex. 774 Sublingual Solution Live attenuated Vaccine Resveratrol 200 PDE 30 measles virus 100 μL equivalent inhibition Ex. 775 Sublingual Solution Live attenuated Vaccine Vinpocetine 100 PDE 30 measles virus 100 μL equivalent inhibition Ex. 776 Sublingual Solution Live attenuated Vaccine Pimobendan 100 PDE 30 measles virus 100 μL equivalent inhibition Ex. 777 Sublingual Solution Live attenuated Vaccine BRL50481 100 PDE 30 measles virus 100 μL equivalent inhibition Ex. 778 Sublingual Solution Live attenuated Vaccine Dipyridamole 200 PDE 30 measles virus 100 μL equivalent inhibition Ex. 779 Sublingual Solution Live attenuated Vaccine Methoxyphenamine 100 β2 30 measles virus 100 μL equivalent hydrochloride activation Ex. 780 Sublingual Solution Live attenuated Vaccine Fenoldopam 100 D1 30 measles virus 100 μL equivalent mesylate activation Ex. 781 Sublingual Solution Live attenuated Vaccine Cisapride 100 5-HT4 30 measles virus 100 μL equivalent activation Ex. 782 Sublingual Solution Live attenuated Vaccine Desmopressin 100 V2 30 measles virus 100 μL equivalent activation Ex. 783 Sublingual Solution Live attenuated Vaccine Prazosin 400 α1,2 30 measles virus 100 μL equivalent hydrochloride antagonization Ex. 784 Sublingual Solution Live attenuated Vaccine Pirenzepine 100 M1 30 measles virus 100 μL equivalent hydrochloride antagonization Ex. 785 Sublingual Solution Live attenuated Vaccine Oxybutynin 200 M2 30 measles virus 100 μL equivalent hydrochloride antagonization Ex. 786 Sublingual Solution Live attenuated Vaccine Tolterodine 400 M3 30 measles virus 100 μL equivalent tartrate antagonization Ex. 787 Sublingual Solution Live attenuated Vaccine Fluphenazine 50 D2 30 measles virus 100 μL equivalent antagonization Ex. 788 Sublingual Solution Live attenuated Vaccine Droperidol 100 30 measles virus 100 μL equivalent Ex. 789 Sublingual Solution Live attenuated Vaccine Sulpiride 100 30 measles virus 100 μL equivalent Ex. 790 Sublingual Solution Live attenuated Vaccine Azelastine 200 H1 30 measles virus 100 μL equivalent hydrochloride antagonization Ex. 791 Sublingual Solution Live attenuated Vaccine Levocetirizine 100 30 measles virus 100 μL equivalent Ex. 792 Sublingual Solution Live attenuated Vaccine Mequitazine 100 30 measles virus 100 μL equivalent Ex. 793 Sublingual Solution Live attenuated Vaccine Thioperamide 100 H3 30 measles virus 100 μL equivalent antagonization Ex. 794 Sublingual Solution Live attenuated Vaccine Sarpogrelate 100 5-HT2 30 measles virus 100 μL equivalent hydrochloride antagonization Ex. 795 Sublingual Solution Live attenuated Vaccine Clopidogrel 100 P2Y12 30 measles virus 100 μL equivalent antagonization Ex. 796 Sublingual Solution Live attenuated Vaccine Ticlopidine 200 30 measles virus 100 μL equivalent Ex. 797 Sublingual Solution Live attenuated Vaccine Prasugrel 100 30 measles virus 100 μL equivalent Ex. 798 Sublingual Solution Live attenuated Vaccine Apafant 100 PAF 30 measles virus 100 μL equivalent antagonization Ex. 799 Sublingual Solution Live attenuated Vaccine Naloxone 100 μ, κ, σ 30 measles virus 100 μL equivalent antagonization Ex. 800 Sublingual Solution Live attenuated Vaccine Zafirlukast 100 CysLT 30 measles virus 100 μL equivalent antagonization Ex. 801 Sublingual Solution Live attenuated Vaccine Montelukast 100 30 measles virus 100 μL equivalent Ex. 802 Sublingual Solution Live attenuated Vaccine Pranlukast 100 30 measles virus 100 μL equivalent Ex. 803 Sublingual Solution Live attenuated Vaccine Candesartan 100 AT1 30 measles virus 100 μL equivalent antagonization
TABLE-US-00032 TABLE 32 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Trasnasal Solution Live attenuated Vaccine — — 10 Ex. 49 rubella virus 100 μL equivalent Ex. 804 Trasnasal Solution Live attenuated Vaccine Resveratrol 40 PDE 10 rubella virus 100 μL equivalent inhibition Ex. 805 Trasnasal Solution Live attenuated Vaccine Vinpocetine 20 PDE 10 rubella virus 100 μL equivalent inhibition Ex. 806 Trasnasal Solution Live attenuated Vaccine Pimobendan 20 PDE 10 rubella virus 100 μL equivalent inhibition Ex. 807 Trasnasal Solution Live attenuated Vaccine BRL50481 20 PDE 10 rubella virus 100 μL equivalent inhibition Ex. 808 Trasnasal Solution Live attenuated Vaccine Dipyridamole 40 PDE 10 rubella virus 100 μL equivalent inhibition Ex. 809 Trasnasal Solution Live attenuated Vaccine Methoxyphenamine 20 β2 10 rubella virus 100 μL equivalent hydrochloride activation Ex. 810 Trasnasal Solution Live attenuated Vaccine Fenoldopam 20 D1 10 rubella virus 100 μL equivalent mesylate activation Ex. 811 Trasnasal Solution Live attenuated Vaccine Cisapride 20 5-HT4 10 rubella virus 100 μL equivalent activation Ex. 812 Trasnasal Solution Live attenuated Vaccine Desmopressin 20 V2 10 rubella virus 100 μL equivalent activation Ex. 813 Trasnasal Solution Live attenuated Vaccine Prazosin 80 α1,2 10 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 814 Trasnasal Solution Live attenuated Vaccine Pirenzepine 20 M1 10 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 815 Trasnasal Solution Live attenuated Vaccine Oxybutynin 40 M2 10 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 816 Trasnasal Solution Live attenuated Vaccine Tolterodine 80 M3 10 rubella virus 100 μL equivalent tartrate antagonization Ex. 817 Trasnasal Solution Live attenuated Vaccine Fluphenazine 10 D2 10 rubella virus 100 μL equivalent antagonization Ex. 818 Trasnasal Solution Live attenuated Vaccine Droperidol 20 10 rubella virus 100 μL equivalent Ex. 819 Trasnasal Solution Live attenuated Vaccine Sulpiride 20 10 rubella virus 100 μL equivalent Ex. 820 Trasnasal Solution Live attenuated Vaccine Azelastine 40 H1 10 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 821 Trasnasal Solution Live attenuated Vaccine Levocetirizine 20 10 rubella virus 100 μL equivalent Ex. 822 Trasnasal Solution Live attenuated Vaccine Mequitazine 20 10 rubella virus 100 μL equivalent Ex. 823 Trasnasal Solution Live attenuated Vaccine Thioperamide 20 H3 10 rubella virus 100 μL equivalent antagonization Ex. 824 Trasnasal Solution Live attenuated Vaccine Sarpogrelate 20 5-HT2 10 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 825 Trasnasal Solution Live attenuated Vaccine Clopidogrel 20 P2Y12 10 rubella virus 100 μL equivalent antagonization Ex. 826 Trasnasal Solution Live attenuated Vaccine Ticlopidine 40 10 rubella virus 100 μL equivalent Ex. 827 Trasnasal Solution Live attenuated Vaccine Prasugrel 20 10 rubella virus 100 μL equivalent Ex. 828 Trasnasal Solution Live attenuated Vaccine Apafant 20 PAF 10 rubella virus 100 μL equivalent antagonization Ex. 829 Trasnasal Solution Live attenuated Vaccine Naloxone 20 μ, κ, σ 10 rubella virus 100 μL equivalent antagonization Ex. 830 Trasnasal Solution Live attenuated Vaccine Zafirlukast 20 CysLT 10 rubella virus 100 μL equivalent antagonization Ex. 831 Trasnasal Solution Live attenuated Vaccine Montelukast 20 10 rubella virus 100 μL equivalent Ex. 832 Trasnasal Solution Live attenuated Vaccine Pranlukast 20 10 rubella virus 100 μL equivalent Ex. 833 Trasnasal Solution Live attenuated Vaccine Candesartan 20 AT1 10 rubella virus 100 μL equivalent antagonization
TABLE-US-00033 TABLE 33 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live attenuated Vaccine — — 30 Ex. 50 rubella virus 100 μL equivalent Ex. 834 Sublingual Solution Live attenuated Vaccine Resveratrol 200 PDE 30 rubella virus 100 μL equivalent inhibition Ex. 835 Sublingual Solution Live attenuated Vaccine Vinpocetine 100 PDE 30 rubella virus 100 μL equivalent inhibition Ex. 836 Sublingual Solution Live attenuated Vaccine Pimobendan 100 PDE 30 rubella virus 100 μL equivalent inhibition Ex. 837 Sublingual Solution Live attenuated Vaccine BRL50481 100 PDE 30 rubella virus 100 μL equivalent inhibition Ex. 838 Sublingual Solution Live attenuated Vaccine Dipyridamole 200 PDE 30 rubella virus 100 μL equivalent inhibition Ex. 839 Sublingual Solution Live attenuated Vaccine Methoxyphenamine 100 β2 30 rubella virus 100 μL equivalent hydrochloride activation Ex. 840 Sublingual Solution Live attenuated Vaccine Fenoldopam 100 D1 30 rubella virus 100 μL equivalent mesylate activation Ex. 841 Sublingual Solution Live attenuated Vaccine Cisapride 100 5-HT4 30 rubella virus 100 μL equivalent activation Ex. 842 Sublingual Solution Live attenuated Vaccine Desmopressin 100 V2 30 rubella virus 100 μL equivalent activation Ex. 843 Sublingual Solution Live attenuated Vaccine Prazosin 400 α1,2 30 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 844 Sublingual Solution Live attenuated Vaccine Pirenzepine 100 M1 30 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 845 Sublingual Solution Live attenuated Vaccine Oxybutynin 200 M2 30 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 846 Sublingual Solution Live attenuated Vaccine Tolterodine 400 M3 30 rubella virus 100 μL equivalent tartrate antagonization Ex. 847 Sublingual Solution Live attenuated Vaccine Fluphenazine 50 D2 30 rubella virus 100 μL equivalent antagonization Ex. 848 Sublingual Solution Live attenuated Vaccine Droperidol 100 30 rubella virus 100 μL equivalent Ex. 849 Sublingual Solution Live attenuated Vaccine Sulpiride 100 30 rubella virus 100 μL equivalent Ex. 850 Sublingual Solution Live attenuated Vaccine Azelastine 200 H1 30 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 851 Sublingual Solution Live attenuated Vaccine Levocetirizine 100 30 rubella virus 100 μL equivalent Ex. 852 Sublingual Solution Live attenuated Vaccine Mequitazine 100 30 rubella virus 100 μL equivalent Ex. 853 Sublingual Solution Live attenuated Vaccine Thioperamide 100 H3 30 rubella virus 100 μL equivalent antagonization Ex. 854 Sublingual Solution Live attenuated Vaccine Sarpogrelate 100 5-HT2 30 rubella virus 100 μL equivalent hydrochloride antagonization Ex. 855 Sublingual Solution Live attenuated Vaccine Clopidogrel 100 P2Y12 30 rubella virus 100 μL equivalent antagonization Ex. 856 Sublingual Solution Live attenuated Vaccine Ticlopidine 200 30 rubella virus 100 μL equivalent Ex. 857 Sublingual Solution Live attenuated Vaccine Prasugrel 100 30 rubella virus 100 μL equivalent Ex. 858 Sublingual Solution Live attenuated Vaccine Apafant 100 PAF 30 rubella virus 100 μL equivalent antagonization Ex. 859 Sublingual Solution Live attenuated Vaccine Naloxone 100 μ, κ, σ 30 rubella virus 100 μL equivalent antagonization Ex. 860 Sublingual Solution Live attenuated Vaccine Zafirlukast 100 CysLT 30 rubella virus 100 μL equivalent antagonization Ex. 861 Sublingual Solution Live attenuated Vaccine Montelukast 100 30 rubella virus 100 μL equivalent Ex. 862 Sublingual Solution Live attenuated Vaccine Pranlukast 100 30 rubella virus 100 μL equivalent Ex. 863 Sublingual Solution Live attenuated Vaccine Candesartan 100 AT1 30 rubella virus 100 μL equivalent antagonization
TABLE-US-00034 TABLE 34 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Haemophilus influenzae Vaccine — — 10 Ex. 51 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 864 Transnasal Solution Haemophilus influenzae Vaccine Resveratrol 40 PDE 10 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 865 Transnasal Solution Haemophilus influenzae Vaccine Vinpocetine 20 PDE 10 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 866 Transnasal Solution Haemophilus influenzae Vaccine Pimobendan 20 PDE 10 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 867 Transnasal Solution Haemophilus influenzae Vaccine BRL50481 20 PDE 10 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 868 Transnasal Solution Haemophilus influenzae Vaccine Dipyridamole 40 PDE 10 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 869 Transnasal Solution Haemophilus influenzae Vaccine Methoxyphenamine 20 β2 10 type b polysaccharide- 100 μL equivalent hydrochloride activation tetanus toxoid conjugate Ex. 870 Transnasal Solution Haemophilus influenzae Vaccine Fenoldopam 20 D1 10 type b polysaccharide- 100 μL equivalent mesylate activation tetanus toxoid conjugate Ex. 871 Transnasal Solution Haemophilus influenzae Vaccine Cisapride 20 5-HT4 10 type b polysaccharide- 100 μL equivalent activation tetanus toxoid conjugate Ex. 872 Transnasal Solution Haemophilus influenzae Vaccine Desmopressin 20 V2 10 type b polysaccharide- 100 μL equivalent activation tetanus toxoid conjugate Ex. 873 Transnasal Solution Haemophilus influenzae Vaccine Prazosin 80 α1,2 10 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 874 Transnasal Solution Haemophilus influenzae Vaccine Pirenzepine 20 M1 10 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 875 Transnasal Solution Haemophilus influenzae Vaccine Oxybutynin 40 M2 10 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 876 Transnasal Solution Haemophilus influenzae Vaccine Tolterodine 80 M3 10 type b polysaccharide- 100 μL equivalent tartrate antagonization tetanus toxoid conjugate Ex. 877 Transnasal Solution Haemophilus influenzae Vaccine Fluphenazine 10 D2 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 878 Transnasal Solution Haemophilus influenzae Vaccine Droperidol 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 879 Transnasal Solution Haemophilus influenzae Vaccine Sulpiride 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 880 Transnasal Solution Haemophilus influenzae Vaccine Azelastine 40 H1 10 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 881 Transnasal Solution Haemophilus influenzae Vaccine Levocetirizine 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 882 Transnasal Solution Haemophilus influenzae Vaccine Mequitazine 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 883 Transnasal Solution Haemophilus influenzae Vaccine Thioperamide 20 H3 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 884 Transnasal Solution Haemophilus influenzae Vaccine Sarpogrelate 20 5-HT2 10 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 885 Transnasal Solution Haemophilus influenzae Vaccine Clopidogrel 20 P2Y12 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 886 Transnasal Solution Haemophilus influenzae Vaccine Ticlopidine 40 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 887 Transnasal Solution Haemophilus influenzae Vaccine Prasugrel 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 888 Transnasal Solution Haemophilus influenzae Vaccine Apafant 20 PAF 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 889 Transnasal Solution Haemophilus influenzae Vaccine Naloxone 20 μ, κ, σ 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 890 Transnasal Solution Haemophilus influenzae Vaccine Zafirlukast 20 CysLT 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 891 Transnasal Solution Haemophilus influenzae Vaccine Montelukast 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 892 Transnasal Solution Haemophilus influenzae Vaccine Pranlukast 20 10 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 893 Transnasal Solution Haemophilus influenzae Vaccine Candesartan 20 AT1 10 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate
TABLE-US-00035 TABLE 35 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Haemophilus influenzae Vaccine — — 30 Ex. 52 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 894 Sublingual Solution Haemophilus influenzae Vaccine Resveratrol 200 PDE 30 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 895 Sublingual Solution Haemophilus influenzae Vaccine Vinpocetine 100 PDE 30 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 896 Sublingual Solution Haemophilus influenzae Vaccine Pimobendan 100 PDE 30 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 897 Sublingual Solution Haemophilus influenzae Vaccine BRL50481 100 PDE 30 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 898 Sublingual Solution Haemophilus influenzae Vaccine Dipyridamole 200 PDE 30 type b polysaccharide- 100 μL equivalent inhibition tetanus toxoid conjugate Ex. 899 Sublingual Solution Haemophilus influenzae Vaccine Methoxyphenamine 100 β2 30 type b polysaccharide- 100 μL equivalent hydrochloride activation tetanus toxoid conjugate Ex. 900 Sublingual Solution Haemophilus influenzae Vaccine Fenoldopam 100 D1 30 type b polysaccharide- 100 μL equivalent mesylate activation tetanus toxoid conjugate Ex. 901 Sublingual Solution Haemophilus influenzae Vaccine Cisapride 100 5-HT4 30 type b polysaccharide- 100 μL equivalent activation tetanus toxoid conjugate Ex. 902 Sublingual Solution Haemophilus influenzae Vaccine Desmopressin 100 V2 30 type b polysaccharide- 100 μL equivalent activation tetanus toxoid conjugate Ex. 903 Sublingual Solution Haemophilus influenzae Vaccine Prazosin 400 α1,2 30 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 904 Sublingual Solution Haemophilus influenzae Vaccine Pirenzepine 100 M1 30 type b polysaccharide- 100 μL equivalent hycrochloride antagonization tetanus toxoid conjugate Ex. 905 Sublingual Solution Haemophilus influenzae Vaccine Oxybutynin 200 M2 30 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 906 Sublingual Solution Haemophilus influenzae Vaccine Tolterodine 400 M3 30 type b polysaccharide- 100 μL equivalent tartrate antagonization tetanus toxoid conjugate Ex. 907 Sublingual Solution Haemophilus influenzae Vaccine Fluphenazine 50 D2 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 908 Sublingual Solution Haemophilus influenzae Vaccine Droperidol 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 909 Sublingual Solution Haemophilus influenzae Vaccine Sulpiride 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 910 Sublingual Solution Haemophilus influenzae Vaccine Azelastine 200 H1 30 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 911 Sublingual Solution Haemophilus influenzae Vaccine Levocetirizine 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 912 Sublingual Solution Haemophilus influenzae Vaccine Mequitazine 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 913 Sublingual Solution Haemophilus influenzae Vaccine Thioperamide 100 H3 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 914 Sublingual Solution Haemophilus influenzae Vaccine Sarpogrelate 100 5-HT2 30 type b polysaccharide- 100 μL equivalent hydrochloride antagonization tetanus toxoid conjugate Ex. 915 Sublingual Solution Haemophilus influenzae Vaccine Clopidogrel 100 P2Y12 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 916 Sublingual Solution Haemophilus influenzae Vaccine Tiolopidine 200 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 917 Sublingual Solution Haemophilus influenzae Vaccine Prasugrel 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 918 Sublingual Solution Haemophilus influenzae Vaccine Apafant 100 PAF 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 919 Sublingual Solution Haemophilus influenzae Vaccine Naloxone 100 μ, κ, σ 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 920 Sublingual Solution Haemophilus influenzae Vaccine Zafirlukast 100 CysLT 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate Ex. 921 Sublingual Solution Haemophilus influenzae Vaccine Montelukast 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 922 Sublingual Solution Haemophilus influenzae Vaccine Pranlukast 100 30 type b polysaccharide- 100 μL equivalent tetanus toxoid conjugate Ex. 923 Sublingual Solution Haemophilus influenzae Vaccine Candesartan 100 AT1 30 type b polysaccharide- 100 μL equivalent antagonization tetanus toxoid conjugate
TABLE-US-00036 TABLE 36 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Recombinant HBs Vaccine — — 10 Ex. 53 antigen protein 100 μL equivalent Ex. 924 Transnasal Solution Recombinant HBs Vaccine Resveratrol 40 PDE 10 antigen protein 100 μL equivalent inhibition Ex. 925 Transnasal Solution Recombinant HBs Vaccine Vinpocetine 20 PDE 10 antigen protein 100 μL equivalent inhibition Ex. 926 Transnasal Solution Recombinant HBs Vaccine Pimobendan 20 PDE 10 antigen protein 100 μL equivalent inhibition Ex. 927 Transnasal Solution Recombinant HBs Vaccine BRL50481 20 PDE 10 antigen protein 100 μL equivalent inhibition Ex. 928 Transnasal Solution Recombinant HBs Vaccine Dipyridamole 40 PDE 10 antigen protein 100 μL equivalent inhibition Ex. 929 Transnasal Solution Recombinant HBs Vaccine Methoxyphenamine 20 β2 10 antigen protein 100 μL equivalent hydrochloride activation Ex. 930 Transnasal Solution Recombinant HBs Vaccine Fenoldopam 20 D1 10 antigen protein 100 μL equivalent mesylate activation Ex. 931 Transnasal Solution Recombinant HBs Vaccine Cisapride 20 5-HT4 10 antigen protein 100 μL equivalent activation Ex. 932 Transnasal Solution Recombinant HBs Vaccine Desmopressin 20 V2 10 antigen protein 100 μL equivalent activation Ex. 933 Transnasal Solution Recombinant HBs Vaccine Prazosin 80 α1,2 10 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 934 Transnasal Solution Recombinant HBs Vaccine Pirenzepine 20 M1 10 antigen protein 100 μL equivalent hycrochloride antagonization Ex. 935 Transnasal Solution Recombinant HBs Vaccine Oxybutynin 40 M2 10 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 936 Transnasal Solution Recombinant HBs Vaccine Tolterodine 80 M3 10 antigen protein 100 μL equivalent tartrate antagonization Ex. 937 Transnasal Solution Recombinant HBs Vaccine Fluphenazine 10 D2 10 antigen protein 100 μL equivalent antagonization Ex. 938 Transnasal Solution Recombinant HBs Vaccine Droperidol 20 10 antigen protein 100 μL equivalent Ex. 939 Transnasal Solution Recombinant HBs Vaccine Sulpiride 20 10 antigen protein 100 μL equivalent Ex. 940 Transnasal Solution Recombinant HBs Vaccine Azelastine 40 H1 10 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 941 Transnasal Solution Recombinant HBs Vaccine Levocetirizine 20 10 antigen protein 100 μL equivalent Ex. 942 Transnasal Solution Recombinant HBs Vaccine Mequitazine 20 10 antigen protein 100 μL equivalent Ex. 943 Transnasal Solution Recombinant HBs Vaccine Thioperamide 20 H3 10 antigen protein 100 μL equivalent antagonization Ex. 944 Transnasal Solution Recombinant HBs Vaccine Sarpogrelate 20 5-HT2 10 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 945 Transnasal Solution Recombinant HBs Vaccine Clopidogrel 20 P2Y12 10 antigen protein 100 μL equivalent antagonization Ex. 946 Transnasal Solution Recombinant HBs Vaccine Tiolopidine 40 10 antigen protein 100 μL equivalent Ex. 947 Transnasal Solution Recombinant HBs Vaccine Prasugrel 20 10 antigen protein 100 μL equivalent Ex. 948 Transnasal Solution Recombinant HBs Vaccine Apafant 20 PAF 10 antigen protein 100 μL equivalent antagonization Ex. 949 Transnasal Solution Recombinant HBs Vaccine Naloxone 20 μ, κ, σ 10 antigen protein 100 μL equivalent antagonization Ex. 950 Transnasal Solution Recombinant HBs Vaccine Zafirlukast 20 CysLT 10 antigen protein 100 μL equivalent antagonization Ex. 951 Transnasal Solution Recombinant HBs Vaccine Montelukast 20 10 antigen protein 100 μL equivalent Ex. 952 Transnasal Solution Recombinant HBs Vaccine Pranlukast 20 10 antigen protein 100 μL equivalent Ex. 953 Transnasal Solution Recombinant HBs Vaccine Candesartan 20 AT1 10 antigen protein 100 μL equivalent antagonization
TABLE-US-00037 TABLE 37 Antigen TH2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Recombinant HBs Vaccine — — 30 Ex. 54 antigen protein 100 μL equivalent Ex. 954 Sublingual Solution Recombinant HBs Vaccine Resveratrol 200 PDE 30 antigen protein 100 μL equivalent inhibition Ex. 955 Sublingual Solution Recombinant HBs Vaccine Vinpocetine 100 PDE 30 antigen protein 100 μL equivalent inhibition Ex. 956 Sublingual Solution Recombinant HBs Vaccine Pimobendan 100 PDE 30 antigen protein 100 μL equivalent inhibition Ex. 957 Sublingual Solution Recombinant HBs Vaccine BRL50481 100 PDE 30 antigen protein 100 μL equivalent inhibition Ex. 958 Sublingual Solution Recombinant HBs Vaccine Dipyridamole 200 PDE 30 antigen protein 100 μL equivalent inhibition Ex. 959 Sublingual Solution Recombinant HBs Vaccine Methoxyphenamine 100 β2 30 antigen protein 100 μL equivalent hydrochloride activation Ex. 960 Sublingual Solution Recombinant HBs Vaccine Fenoldopam 100 D1 30 antigen protein 100 μL equivalent mesylate activation Ex. 961 Sublingual Solution Recombinant HBs Vaccine Cisapride 100 5-HT4 30 antigen protein 100 μL equivalent activation Ex. 962 Sublingual Solution Recombinant HBs Vaccine Desmopressin 100 V2 30 antigen protein 100 μL equivalent activation Ex. 963 Sublingual Solution Recombinant HBs Vaccine Prazosin 400 α1,2 30 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 964 Sublingual Solution Recombinant HBs Vaccine Pirenzepine 100 M1 30 antigen protein 100 μL equivalent hycrochloride antagonization Ex. 965 Sublingual Solution Recombinant HBs Vaccine Oxybutynin 200 M2 30 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 966 Sublingual Solution Recombinant HBs Vaccine Tolterodine 400 M3 30 antigen protein 100 μL equivalent tartrate antagonization Ex. 967 Sublingual Solution Recombinant HBs Vaccine Fluphenazine 50 D2 30 antigen protein 100 μL equivalent antagonization Ex. 968 Sublingual Solution Recombinant HBs Vaccine Droperidol 100 30 antigen protein 100 μL equivalent Ex. 969 Sublingual Solution Recombinant HBs Vaccine Sulpiride 100 30 antigen protein 100 μL equivalent Ex. 970 Sublingual Solution Recombinant HBs Vaccine Azelastine 200 H1 30 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 971 Sublingual Solution Recombinant HBs Vaccine Levocetirizine 100 30 antigen protein 100 μL equivalent Ex. 972 Sublingual Solution Recombinant HBs Vaccine Mequitazine 100 30 antigen protein 100 μL equivalent Ex. 973 Sublingual Solution Recombinant HBs Vaccine Thioperamide 100 H3 30 antigen protein 100 μL equivalent antagonization Ex. 974 Sublingual Solution Recombinant HBs Vaccine Sarpogrelate 100 5-HT2 30 antigen protein 100 μL equivalent hydrochloride antagonization Ex. 975 Sublingual Solution Recombinant HBs Vaccine Clopidogrel 100 P2Y12 30 antigen protein 100 μL equivalent antagonization Ex. 976 Sublingual Solution Recombinant HBs Vaccine Tiolopidine 200 30 antigen protein 100 μL equivalent Ex. 977 Sublingual Solution Recombinant HBs Vaccine Prasugrel 100 30 antigen protein 100 μL equivalent Ex. 978 Sublingual Solution Recombinant HBs Vaccine Apafant 100 PAF 30 antigen protein 100 μL equivalent antagonization Ex. 979 Sublingual Solution Recombinant HBs Vaccine Naloxone 100 μ, κ, σ 30 antigen protein 100 μL equivalent antagonization Ex. 980 Sublingual Solution Recombinant HBs Vaccine Zafirlukast 100 CysLT 30 antigen protein 100 μL equivalent antagonization Ex. 981 Sublingual Solution Recombinant HBs Vaccine Montelukast 100 30 antigen protein 100 μL equivalent Ex. 982 Sublingual Solution Recombinant HBs Vaccine Pranlukast 100 30 antigen protein 100 μL equivalent Ex. 983 Sublingual Solution Recombinant HBs Vaccine Candesartan 100 AT1 30 antigen protein 100 μL equivalent antagonization
TABLE-US-00038 TABLE 38 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Live attenuated Vaccine — — 10 Ex. 55 yellow fever virus 100 μL equivalent Ex. 984 Transnasal Solution Live attenuated Vaccine Resveratrol 40 PDE 10 yellow fever virus 100 μL equivalent inhibition Ex. 985 Transnasal Solution Live attenuated Vaccine Vinpocetine 20 PDE 10 yellow fever virus 100 μL equivalent inhibition Ex. 986 Transnasal Solution Live attenuated Vaccine Pimobendan 20 PDE 10 yellow fever virus 100 μL equivalent inhibition Ex. 987 Transnasal Solution Live attenuated Vaccine BRL50481 20 PDE 10 yellow fever virus 100 μL equivalent inhibition Ex. 988 Transnasal Solution Live attenuated Vaccine Dipyridamole 40 PDE 10 yellow fever virus 100 μL equivalent inhibition Ex. 989 Transnasal Solution Live attenuated Vaccine Methoxyphenamine 20 β2 10 yellow fever virus 100 μL equivalent hydrochloride activation Ex. 990 Transnasal Solution Live attenuated Vaccine Fenoldopam 20 D1 10 yellow fever virus 100 μL equivalent mesylate activation Ex. 991 Transnasal Solution Live attenuated Vaccine Cisapride 20 5-HT4 10 yellow fever virus 100 μL equivalent activation Ex. 992 Transnasal Solution Live attenuated Vaccine Desmopressin 20 V2 10 yellow fever virus 100 μL equivalent activation Ex. 993 Transnasal Solution Live attenuated Vaccine Prazosin 80 α1,2 10 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 994 Transnasal Solution Live attenuated Vaccine Pirenzepine 20 M1 10 yellow fever virus 100 μL equivalent hycrochloride antagonization Ex. 995 Transnasal Solution Live attenuated Vaccine Oxybutynin 40 M2 10 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 996 Transnasal Solution Live attenuated Vaccine Tolterodine 80 M3 10 yellow fever virus 100 μL equivalent tartrate antagonization Ex. 997 Transnasal Solution Live attenuated Vaccine Fluphenazine 10 D2 10 yellow fever virus 100 μL equivalent antagonization Ex. 998 Transnasal Solution Live attenuated Vaccine Droperidol 20 10 yellow fever virus 100 μL equivalent Ex. 999 Transnasal Solution Live attenuated Vaccine Sulpiride 20 10 yellow fever virus 100 μL equivalent Ex. 1000 Transnasal Solution Live attenuated Vaccine Azelastine 40 H1 10 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 1001 Transnasal Solution Live attenuated Vaccine Levocetirizine 20 10 yellow fever virus 100 μL equivalent Ex. 1002 Transnasal Solution Live attenuated Vaccine Mequitazine 20 10 yellow fever virus 100 μL equivalent Ex. 1003 Transnasal Solution Live attenuated Vaccine Thioperamide 20 H3 10 yellow fever virus 100 μL equivalent antagonization Ex. 1004 Transnasal Solution Live attenuated Vaccine Sarpogrelate 20 5-HT2 10 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 1005 Transnasal Solution Live attenuated Vaccine Clopidogrel 20 P2Y12 10 yellow fever virus 100 μL equivalent antagonization Ex. 1006 Transnasal Solution Live attenuated Vaccine Tiolopidine 40 10 yellow fever virus 100 μL equivalent Ex. 1007 Transnasal Solution Live attenuated Vaccine Prasugrel 20 10 yellow fever virus 100 μL equivalent Ex. 1008 Transnasal Solution Live attenuated Vaccine Apafant 20 PAF 10 yellow fever virus 100 μL equivalent antagonization Ex. 1009 Transnasal Solution Live attenuated Vaccine Naloxone 20 μ, κ, σ 10 yellow fever virus 100 μL equivalent antagonization Ex. 1010 Transnasal Solution Live attenuated Vaccine Zafirlukast 20 CysLT 10 yellow fever virus 100 μL equivalent antagonization Ex. 1011 Transnasal Solution Live attenuated Vaccine Montelukast 20 10 yellow fever virus 100 μL equivalent Ex. 1012 Transnasal Solution Live attenuated Vaccine Pranlukast 20 10 yellow fever virus 100 μL equivalent Ex. 1013 Transnasal Solution Live attenuated Vaccine Candesartan 20 AT1 10 yellow fever virus 100 μL equivalent antagonization
TABLE-US-00039 TABLE 39 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live attenuated Vaccine — — 30 Ex. 56 yellow fever virus 100 μL equivalent Ex. 1014 Sublingual Solution Live attenuated Vaccine Resveratrol 200 PDE 30 yellow fever virus 100 μL equivalent inhibition Ex. 1015 Sublingual Solution Live attenuated Vaccine Vinpocetine 100 PDE 30 yellow fever virus 100 μL equivalent inhibition Ex. 1016 Sublingual Solution Live attenuated Vaccine Pimobendan 100 PDE 30 yellow fever virus 100 μL equivalent inhibition Ex. 1017 Sublingual Solution Live attenuated Vaccine BRL50481 100 PDE 30 yellow fever virus 100 μL equivalent inhibition Ex. 1018 Sublingual Solution Live attenuated Vaccine Dipyridamole 200 PDE 30 yellow fever virus 100 μL equivalent inhibition Ex. 1019 Sublingual Solution Live attenuated Vaccine Methoxyphenamine 100 β2 30 yellow fever virus 100 μL equivalent hydrochloride activation Ex. 1020 Sublingual Solution Live attenuated Vaccine Fenoldopam 100 D1 30 yellow fever virus 100 μL equivalent mesylate activation Ex. 1021 Sublingual Solution Live attenuated Vaccine Cisapride 100 5-HT4 30 yellow fever virus 100 μL equivalent activation Ex. 1022 Sublingual Solution Live attenuated Vaccine Desmopressin 100 V2 30 yellow fever virus 100 μL equivalent activation Ex. 1023 Sublingual Solution Live attenuated Vaccine Prazosin 400 α1,2 30 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 1024 Sublingual Solution Live attenuated Vaccine Pirenzepine 100 M1 30 yellow fever virus 100 μL equivalent hycrochloride antagonization Ex. 1025 Sublingual Solution Live attenuated Vaccine Oxybutynin 200 M2 30 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 1026 Sublingual Solution Live attenuated Vaccine Tolterodine 400 M3 30 yellow fever virus 100 μL equivalent tartrate antagonization Ex. 1027 Sublingual Solution Live attenuated Vaccine Fluphenazine 50 D2 30 yellow fever virus 100 μL equivalent antagonization Ex. 1028 Sublingual Solution Live attenuated Vaccine Droperidol 100 30 yellow fever virus 100 μL equivalent Ex. 1029 Sublingual Solution Live attenuated Vaccine Sulpiride 100 30 yellow fever virus 100 μL equivalent Ex. 1030 Sublingual Solution Live attenuated Vaccine Azelastine 200 H1 30 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 1031 Sublingual Solution Live attenuated Vaccine Levocetirizine 100 30 yellow fever virus 100 μL equivalent Ex. 1032 Sublingual Solution Live attenuated Vaccine Mequitazine 100 30 yellow fever virus 100 μL equivalent Ex. 1033 Sublingual Solution Live attenuated Vaccine Thioperamide 100 H3 30 yellow fever virus 100 μL equivalent antagonization Ex. 1034 Sublingual Solution Live attenuated Vaccine Sarpogrelate 100 5-HT2 30 yellow fever virus 100 μL equivalent hydrochloride antagonization Ex. 1035 Sublingual Solution Live attenuated Vaccine Clopidogrel 100 P2Y12 30 yellow fever virus 100 μL equivalent antagonization Ex. 1036 Sublingual Solution Live attenuated Vaccine Tiolopidine 200 30 yellow fever virus 100 μL equivalent Ex. 1037 Sublingual Solution Live attenuated Vaccine Prasugrel 100 30 yellow fever virus 100 μL equivalent Ex. 1038 Sublingual Solution Live attenuated Vaccine Apafant 100 PAF 30 yellow fever virus 100 μL equivalent antagonization Ex. 1039 Sublingual Solution Live attenuated Vaccine Naloxone 100 μ, κ, σ 30 yellow fever virus 100 μL equivalent antagonization Ex. 1040 Sublingual Solution Live attenuated Vaccine Zafirlukast 100 CysLT 30 yellow fever virus 100 μL equivalent antagonization Ex. 1041 Sublingual Solution Live attenuated Vaccine Montelukast 100 30 yellow fever virus 100 μL equivalent Ex. 1042 Sublingual Solution Live attenuated Vaccine Pranlukast 100 30 yellow fever virus 100 μL equivalent Ex. 1043 Sublingual Solution Live attenuated Vaccine Candesartan 100 AT1 30 yellow fever virus 100 μL equivalent antagonization
TABLE-US-00040 TABLE 40 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Tetanus Vaccine — — 10 Ex. 57 toxoid 100 μL equivalent Ex. 1044 Transnasal Solution Tetanus Vaccine Resveratrol 40 PDE 10 toxoid 100 μL equivalent inhibition Ex. 1045 Transnasal Solution Tetanus Vaccine Vinpocetine 20 PDE 10 toxoid 100 μL equivalent inhibition Ex. 1046 Transnasal Solution Tetanus Vaccine Pimobendan 20 PDE 10 toxoid 100 μL equivalent inhibition Ex. 1047 Transnasal Solution Tetanus Vaccine BRL50481 20 PDE 10 toxoid 100 μL equivalent inhibition Ex. 1048 Transnasal Solution Tetanus Vaccine Dipyridamole 40 PDE 10 toxoid 100 μL equivalent inhibition Ex. 1049 Transnasal Solution Tetanus Vaccine Methoxyphenamine 20 β2 10 toxoid 100 μL equivalent hydrochloride activation Ex. 1050 Transnasal Solution Tetanus Vaccine Fenoldopam 20 D1 10 toxoid 100 μL equivalent mesylate activation Ex. 1051 Transnasal Solution Tetanus Vaccine Cisapride 20 5-HT4 10 toxoid 100 μL equivalent activation Ex. 1052 Transnasal Solution Tetanus Vaccine Desmopressin 20 V2 10 toxoid 100 μL equivalent activation Ex. 1053 Transnasal Solution Tetanus Vaccine Prazosin 80 α1,2 10 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1054 Transnasal Solution Tetanus Vaccine Pirenzepine 20 M1 10 toxoid 100 μL equivalent hycrochloride antagonization Ex. 1055 Transnasal Solution Tetanus Vaccine Oxybutynin 40 M2 10 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1056 Transnasal Solution Tetanus Vaccine Tolterodine 80 M3 10 toxoid 100 μL equivalent tartrate antagonization Ex. 1057 Transnasal Solution Tetanus Vaccine Fluphenazine 10 D2 10 toxoid 100 μL equivalent antagonization Ex. 1058 Transnasal Solution Tetanus Vaccine Droperidol 20 10 toxoid 100 μL equivalent Ex. 1059 Transnasal Solution Tetanus Vaccine Sulpiride 20 10 toxoid 100 μL equivalent Ex. 1060 Transnasal Solution Tetanus Vaccine Azelastine 40 H1 10 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1061 Transnasal Solution Tetanus Vaccine Levocetirizine 20 10 toxoid 100 μL equivalent Ex. 1062 Transnasal Solution Tetanus Vaccine Mequitazine 20 10 toxoid 100 μL equivalent Ex. 1063 Transnasal Solution Tetanus Vaccine Thioperamide 20 H3 10 toxoid 100 μL equivalent antagonization Ex. 1064 Transnasal Solution Tetanus Vaccine Sarpogrelate 20 5-HT2 10 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1065 Transnasal Solution Tetanus Vaccine Clopidogrel 20 P2Y12 10 toxoid 100 μL equivalent antagonization Ex. 1066 Transnasal Solution Tetanus Vaccine Tiolopidine 40 10 toxoid 100 μL equivalent Ex. 1067 Transnasal Solution Tetanus Vaccine Prasugrel 20 10 toxoid 100 μL equivalent Ex. 1068 Transnasal Solution Tetanus Vaccine Apafant 20 PAF 10 toxoid 100 μL equivalent antagonization Ex. 1069 Transnasal Solution Tetanus Vaccine Naloxone 20 μ, κ, σ 10 toxoid 100 μL equivalent antagonization Ex. 1070 Transnasal Solution Tetanus Vaccine Zafirlukast 20 CysLT 10 toxoid 100 μL equivalent antagonization Ex. 1071 Transnasal Solution Tetanus Vaccine Montelukast 20 10 toxoid 100 μL equivalent Ex. 1072 Transnasal Solution Tetanus Vaccine Pranlukast 20 10 toxoid 100 μL equivalent Ex. 1073 Transnasal Solution Tetanus Vaccine Candesartan 20 AT1 10 toxoid 100 μL equivalent antagonization
TABLE-US-00041 TABLE 41 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Tetanus Vaccine — — 30 Ex. 58 toxoid 100 μL equivalent Ex. 1074 Sublingual Solution Tetanus Vaccine Resveratrol 200 PDE 30 toxoid 100 μL equivalent inhibition Ex. 1075 Sublingual Solution Tetanus Vaccine Vinpocetine 100 PDE 30 toxoid 100 μL equivalent inhibition Ex. 1076 Sublingual Solution Tetanus Vaccine Pimobendan 100 PDE 30 toxoid 100 μL equivalent inhibition Ex. 1077 Sublingual Solution Tetanus Vaccine BRL50481 100 PDE 30 toxoid 100 μL equivalent inhibition Ex. 1078 Sublingual Solution Tetanus Vaccine Dipyridamole 200 PDE 30 toxoid 100 μL equivalent inhibition Ex. 1079 Sublingual Solution Tetanus Vaccine Methoxyphenamine 100 β2 30 toxoid 100 μL equivalent hydrochloride activation Ex. 1080 Sublingual Solution Tetanus Vaccine Fenoldopam 100 D1 30 toxoid 100 μL equivalent mesylate activation Ex. 1081 Sublingual Solution Tetanus Vaccine Cisapride 100 5-HT4 30 toxoid 100 μL equivalent activation Ex. 1082 Sublingual Solution Tetanus Vaccine Desmopressin 100 V2 30 toxoid 100 μL equivalent activation Ex. 1083 Sublingual Solution Tetanus Vaccine Prazosin 400 α1,2 30 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1084 Sublingual Solution Tetanus Vaccine Pirenzepine 100 M1 30 toxoid 100 μL equivalent hycrochloride antagonization Ex. 1085 Sublingual Solution Tetanus Vaccine Oxybutynin 200 M2 30 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1086 Sublingual Solution Tetanus Vaccine Tolterodine 400 M3 30 toxoid 100 μL equivalent tartrate antagonization Ex. 1087 Sublingual Solution Tetanus Vaccine Fluphenazine 50 D2 30 toxoid 100 μL equivalent antagonization Ex. 1088 Sublingual Solution Tetanus Vaccine Droperidol 100 30 toxoid 100 μL equivalent Ex. 1089 Sublingual Solution Tetanus Vaccine Sulpiride 100 30 toxoid 100 μL equivalent Ex. 1090 Sublingual Solution Tetanus Vaccine Azelastine 200 H1 30 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1091 Sublingual Solution Tetanus Vaccine Levocetirizine 100 30 toxoid 100 μL equivalent Ex. 1092 Sublingual Solution Tetanus Vaccine Mequitazine 100 30 toxoid 100 μL equivalent Ex. 1093 Sublingual Solution Tetanus Vaccine Thioperamide 100 H3 30 toxoid 100 μL equivalent antagonization Ex. 1094 Sublingual Solution Tetanus Vaccine Sarpogrelate 100 5-HT2 30 toxoid 100 μL equivalent hydrochloride antagonization Ex. 1095 Sublingual Solution Tetanus Vaccine Clopidogrel 100 P2Y12 30 toxoid 100 μL equivalent antagonization Ex. 1096 Sublingual Solution Tetanus Vaccine Tiolopidine 200 30 toxoid 100 μL equivalent Ex. 1097 Sublingual Solution Tetanus Vaccine Prasugrel 100 30 toxoid 100 μL equivalent Ex. 1098 Sublingual Solution Tetanus Vaccine Apafant 100 PAF 30 toxoid 100 μL equivalent antagonization Ex. 1099 Sublingual Solution Tetanus Vaccine Naloxone 100 μ, κ, σ 30 toxoid 100 μL equivalent antagonization Ex. 1100 Sublingual Solution Tetanus Vaccine Zafirlukast 100 CysLT 30 toxoid 100 μL equivalent antagonization Ex. 1101 Sublingual Solution Tetanus Vaccine Montelukast 100 30 toxoid 100 μL equivalent Ex. 1102 Sublingual Solution Tetanus Vaccine Pranlukast 100 30 toxoid 100 μL equivalent Ex. 1103 Sublingual Solution Tetanus Vaccine Candesartan 100 AT1 30 toxoid 100 μL equivalent antagonization
TABLE-US-00042 TABLE 42 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Live attenuated Vaccine — — 10 Ex. 59 varicella virus 100 μL equivalent Ex. 1104 Transnasal Solution Live attenuated Vaccine Resveratrol 40 PDE 10 varicella virus 100 μL equivalent inhibition Ex. 1105 Transnasal Solution Live attenuated Vaccine Vinpocetine 20 PDE 10 varicella virus 100 μL equivalent inhibition Ex. 1106 Transnasal Solution Live attenuated Vaccine Pimobendan 20 PDE 10 varicella virus 100 μL equivalent inhibition Ex. 1107 Transnasal Solution Live attenuated Vaccine BRL50481 20 PDE 10 varicella virus 100 μL equivalent inhibition Ex. 1108 Transnasal Solution Live attenuated Vaccine Dipyridamole 40 PDE 10 varicella virus 100 μL equivalent inhibition Ex. 1109 Transnasal Solution Live attenuated Vaccine Methoxyphenamine 20 β2 10 varicella virus 100 μL equivalent hydrochloride activation Ex. 1110 Transnasal Solution Live attenuated Vaccine Fenoldopam 20 D1 10 varicella virus 100 μL equivalent mesylate activation Ex. 1111 Transnasal Solution Live attenuated Vaccine Cisapride 20 5-HT4 10 varicella virus 100 μL equivalent activation Ex. 1112 Transnasal Solution Live attenuated Vaccine Desmopressin 20 V2 10 varicella virus 100 μL equivalent activation Ex. 1113 Transnasal Solution Live attenuated Vaccine Prazosin 80 α1,2 10 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1114 Transnasal Solution Live attenuated Vaccine Pirenzepine 20 M1 10 varicella virus 100 μL equivalent hycrochloride antagonization Ex. 1115 Transnasal Solution Live attenuated Vaccine Oxybutynin 40 M2 10 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1116 Transnasal Solution Live attenuated Vaccine Tolterodine 80 M3 10 varicella virus 100 μL equivalent tartrate antagonization Ex. 1117 Transnasal Solution Live attenuated Vaccine Fluphenazine 10 D2 10 varicella virus 100 μL equivalent antagonization Ex. 1118 Transnasal Solution Live attenuated Vaccine Droperidol 20 10 varicella virus 100 μL equivalent Ex. 1119 Transnasal Solution Live attenuated Vaccine Sulpiride 20 10 varicella virus 100 μL equivalent Ex. 1120 Transnasal Solution Live attenuated Vaccine Azelastine 40 H1 10 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1121 Transnasal Solution Live attenuated Vaccine Levocetirizine 20 10 varicella virus 100 μL equivalent Ex. 1122 Transnasal Solution Live attenuated Vaccine Mequitazine 20 10 varicella virus 100 μL equivalent Ex. 1123 Transnasal Solution Live attenuated Vaccine Thioperamide 20 H3 10 varicella virus 100 μL equivalent antagonization Ex. 1124 Transnasal Solution Live attenuated Vaccine Sarpogrelate 20 5-HT2 10 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1125 Transnasal Solution Live attenuated Vaccine Clopidogrel 20 P2Y12 10 varicella virus 100 μL equivalent antagonization Ex. 1126 Transnasal Solution Live attenuated Vaccine Tiolopidine 40 10 varicella virus 100 μL equivalent Ex. 1127 Transnasal Solution Live attenuated Vaccine Prasugrel 20 10 varicella virus 100 μL equivalent Ex. 1128 Transnasal Solution Live attenuated Vaccine Apafant 20 PAF 10 varicella virus 100 μL equivalent antagonization Ex. 1129 Transnasal Solution Live attenuated Vaccine Naloxone 20 μ, κ, σ 10 varicella virus 100 μL equivalent antagonization Ex. 1130 Transnasal Solution Live attenuated Vaccine Zafirlukast 20 CysLT 10 varicella virus 100 μL equivalent antagonization Ex. 1131 Transnasal Solution Live attenuated Vaccine Montelukast 20 10 varicella virus 100 μL equivalent Ex. 1132 Transnasal Solution Live attenuated Vaccine Pranlukast 20 10 varicella virus 100 μL equivalent Ex. 1133 Transnasal Solution Live attenuated Vaccine Candesartan 20 AT1 10 varicella virus 100 μL equivalent antagonization
TABLE-US-00043 TABLE 43 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live attenuated Vaccine — — 30 Ex. 60 varicella virus 100 μL equivalent Ex. 1134 Sublingual Solution Live attenuated Vaccine Resveratrol 200 PDE 30 varicella virus 100 μL equivalent inhibition Ex. 1135 Sublingual Solution Live attenuated Vaccine Vinpocetine 100 PDE 30 varicella virus 100 μL equivalent inhibition Ex. 1136 Sublingual Solution Live attenuated Vaccine Pimobendan 100 PDE 30 varicella virus 100 μL equivalent inhibition Ex. 1137 Sublingual Solution Live attenuated Vaccine BRL50481 100 PDE 30 varicella virus 100 μL equivalent inhibition Ex. 1138 Sublingual Solution Live attenuated Vaccine Dipyridamole 200 PDE 30 varicella virus 100 μL equivalent inhibition Ex. 1139 Sublingual Solution Live attenuated Vaccine Methoxyphenamine 100 β2 30 varicella virus 100 μL equivalent hydrochloride activation Ex. 1140 Sublingual Solution Live attenuated Vaccine Fenoldopam 100 D1 30 varicella virus 100 μL equivalent mesylate activation Ex. 1141 Sublingual Solution Live attenuated Vaccine Cisapride 100 5-HT4 30 varicella virus 100 μL equivalent activation Ex. 1142 Sublingual Solution Live attenuated Vaccine Desmopressin 100 V2 30 varicella virus 100 μL equivalent activation Ex. 1143 Sublingual Solution Live attenuated Vaccine Prazosin 400 α1,2 30 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1144 Sublingual Solution Live attenuated Vaccine Pirenzepine 100 M1 30 varicella virus 100 μL equivalent hycrochloride antagonization Ex. 1145 Sublingual Solution Live attenuated Vaccine Oxybutynin 200 M2 30 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1146 Sublingual Solution Live attenuated Vaccine Tolterodine 400 M3 30 varicella virus 100 μL equivalent tartrate antagonization Ex. 1147 Sublingual Solution Live attenuated Vaccine Fluphenazine 50 D2 30 varicella virus 100 μL equivalent antagonization Ex. 1148 Sublingual Solution Live attenuated Vaccine Droperidol 100 30 varicella virus 100 μL equivalent Ex. 1149 Sublingual Solution Live attenuated Vaccine Sulpiride 100 30 varicella virus 100 μL equivalent Ex. 1150 Sublingual Solution Live attenuated Vaccine Azelastine 200 H1 30 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1151 Sublingual Solution Live attenuated Vaccine Levocetirizine 100 30 varicella virus 100 μL equivalent Ex. 1152 Sublingual Solution Live attenuated Vaccine Mequitazine 100 30 varicella virus 100 μL equivalent Ex. 1153 Sublingual Solution Live attenuated Vaccine Thioperamide 100 H3 30 varicella virus 100 μL equivalent antagonization Ex. 1154 Sublingual Solution Live attenuated Vaccine Sarpogrelate 100 5-HT2 30 varicella virus 100 μL equivalent hydrochloride antagonization Ex. 1155 Sublingual Solution Live attenuated Vaccine Clopidogrel 100 P2Y12 30 varicella virus 100 μL equivalent antagonization Ex. 1156 Sublingual Solution Live attenuated Vaccine Tiolopidine 200 30 varicella virus 100 μL equivalent Ex. 1157 Sublingual Solution Live attenuated Vaccine Prasugrel 100 30 varicella virus 100 μL equivalent Ex. 1158 Sublingual Solution Live attenuated Vaccine Apafant 100 PAF 30 varicella virus 100 μL equivalent antagonization Ex. 1159 Sublingual Solution Live attenuated Vaccine Naloxone 100 μ, κ, σ 30 varicella virus 100 μL equivalent antagonization Ex. 1160 Sublingual Solution Live attenuated Vaccine Zafirlukast 100 CysLT 30 varicella virus 100 μL equivalent antagonization Ex. 1161 Sublingual Solution Live attenuated Vaccine Montelukast 100 30 varicella virus 100 μL equivalent Ex. 1162 Sublingual Solution Live attenuated Vaccine Pranlukast 100 30 varicella virus 100 μL equivalent Ex. 1163 Sublingual Solution Live attenuated Vaccine Candesartan 100 AT1 30 varicella virus 100 μL equivalent antagonization
TABLE-US-00044 TABLE 44 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Live BCG Vaccine — — 10 Ex. 61 30 μL equivalent Ex. 1164 Transnasal Solution Live BCG Vaccine Resveratrol 40 PDE 10 30 μL equivalent inhibition Ex. 1165 Transnasal Solution Live BCG Vaccine Vinpocetine 20 PDE 10 30 μL equivalent inhibition Ex. 1166 Transnasal Solution Live BCG Vaccine Pimobendan 20 PDE 10 30 μL equivalent inhibition Ex. 1167 Transnasal Solution Live BCG Vaccine BRL50481 20 PDE 10 30 μL equivalent inhibition Ex. 1168 Transnasal Solution Live BCG Vaccine Dipyridamole 40 PDE 10 30 μL equivalent inhibition Ex. 1169 Transnasal Solution Live BCG Vaccine Methoxyphenamine 20 β2 10 30 μL equivalent hydrochloride activation Ex. 1170 Transnasal Solution Live BCG Vaccine Fenoldopam 20 D1 10 30 μL equivalent mesylate activation Ex. 1171 Transnasal Solution Live BCG Vaccine Cisapride 20 5-HT4 10 30 μL equivalent activation Ex. 1172 Transnasal Solution Live BCG Vaccine Desmopressin 20 V2 10 30 μL equivalent activation Ex. 1173 Transnasal Solution Live BCG Vaccine Prazosin 80 α1,2 10 30 μL equivalent hydrochloride antagonization Ex. 1174 Transnasal Solution Live BCG Vaccine Pirenzepine 20 M1 10 30 μL equivalent hycrochloride antagonization Ex. 1175 Transnasal Solution Live BCG Vaccine Oxybutynin 40 M2 10 30 μL equivalent hydrochloride antagonization Ex. 1176 Transnasal Solution Live BCG Vaccine Tolterodine 80 M3 10 30 μL equivalent tartrate antagonization Ex. 1177 Transnasal Solution Live BCG Vaccine Fluphenazine 10 D2 10 30 μL equivalent antagonization Ex. 1178 Transnasal Solution Live BCG Vaccine Droperidol 20 10 30 μL equivalent Ex. 1179 Transnasal Solution Live BCG Vaccine Sulpiride 20 10 30 μL equivalent Ex. 1180 Transnasal Solution Live BCG Vaccine Azelastine 40 H1 10 30 μL equivalent hydrochloride antagonization Ex. 1181 Transnasal Solution Live BCG Vaccine Levocetirizine 20 10 30 μL equivalent Ex. 1182 Transnasal Solution Live BCG Vaccine Mequitazine 20 10 30 μL equivalent Ex. 1183 Transnasal Solution Live BCG Vaccine Thioperamide 20 H3 10 30 μL equivalent antagonization Ex. 1184 Transnasal Solution Live BCG Vaccine Sarpogrelate 20 5-HT2 10 30 μL equivalent hydrochloride antagonization Ex. 1185 Transnasal Solution Live BCG Vaccine Clopidogrel 20 P2Y12 10 30 μL equivalent antagonization Ex. 1186 Transnasal Solution Live BCG Vaccine Tiolopidine 40 10 30 μL equivalent Ex. 1187 Transnasal Solution Live BCG Vaccine Prasugrel 20 10 30 μL equivalent Ex. 1188 Transnasal Solution Live BCG Vaccine Apafant 20 PAF 10 30 μL equivalent antagonization Ex. 1189 Transnasal Solution Live BCG Vaccine Naloxone 20 μ, κ, σ 10 30 μL equivalent antagonization Ex. 1190 Transnasal Solution Live BCG Vaccine Zafirlukast 20 CysLT 10 30 μL equivalent antagonization Ex. 1191 Transnasal Solution Live BCG Vaccine Montelukast 20 10 30 μL equivalent Ex. 1192 Transnasal Solution Live BCG Vaccine Pranlukast 20 10 30 μL equivalent Ex. 1193 Transnasal Solution Live BCG Vaccine Candesartan 20 AT1 10 30 μL equivalent antagonization
TABLE-US-00045 TABLE 45 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Live BCG Vaccine — — 30 Ex. 62 30 μL equivalent Ex. 1194 Sublingual Solution Live BCG Vaccine Resveratrol 200 PDE 30 30 μL equivalent inhibition Ex. 1195 Sublingual Solution Live BCG Vaccine Vinpocetine 100 PDE 30 30 μL equivalent inhibition Ex. 1196 Sublingual Solution Live BCG Vaccine Pimobendan 100 PDE 30 30 μL equivalent inhibition Ex. 1197 Sublingual Solution Live BCG Vaccine BRL50481 100 PDE 30 30 μL equivalent inhibition Ex. 1198 Sublingual Solution Live BCG Vaccine Dipyridamole 200 PDE 30 30 μL equivalent inhibition Ex. 1199 Sublingual Solution Live BCG Vaccine Methoxyphenamine 100 β2 30 30 μL equivalent hydrochloride activation Ex. 1200 Sublingual Solution Live BCG Vaccine Fenoldopam 100 D1 30 30 μL equivalent mesylate activation Ex. 1201 Sublingual Solution Live BCG Vaccine Cisapride 100 5-HT4 30 30 μL equivalent activation Ex. 1202 Sublingual Solution Live BCG Vaccine Desmopressin 100 V2 30 30 μL equivalent activation Ex. 1203 Sublingual Solution Live BCG Vaccine Prazosin 400 α1,2 30 30 μL equivalent hydrochloride antagonization Ex. 1204 Sublingual Solution Live BCG Vaccine Pirenzepine 100 M1 30 30 μL equivalent hycrochloride antagonization Ex. 1205 Sublingual Solution Live BCG Vaccine Oxybutynin 200 M2 30 30 μL equivalent hydrochloride antagonization Ex. 1206 Sublingual Solution Live BCG Vaccine Tolterodine 400 M3 30 30 μL equivalent tartrate antagonization Ex. 1207 Sublingual Solution Live BCG Vaccine Fluphenazine 50 D2 30 30 μL equivalent antagonization Ex. 1208 Sublingual Solution Live BCG Vaccine Droperidol 100 30 30 μL equivalent Ex. 1209 Sublingual Solution Live BCG Vaccine Sulpiride 100 30 30 μL equivalent Ex. 1210 Sublingual Solution Live BCG Vaccine Azelastine 200 H1 30 30 μL equivalent hydrochloride antagonization Ex. 1211 Sublingual Solution Live BCG Vaccine Levocetirizine 100 30 30 μL equivalent Ex. 1212 Sublingual Solution Live BCG Vaccine Mequitazine 100 30 30 μL equivalent Ex. 1213 Sublingual Solution Live BCG Vaccine Thioperamide 100 H3 30 30 μL equivalent antagonization Ex. 1214 Sublingual Solution Live BCG Vaccine Sarpogrelate 100 5-HT2 30 30 μL equivalent hydrochloride antagonization Ex. 1215 Sublingual Solution Live BCG Vaccine Clopidogrel 100 P2Y12 30 30 μL equivalent antagonization Ex. 1216 Sublingual Solution Live BCG Vaccine Tiolopidine 200 30 30 μL equivalent Ex. 1217 Sublingual Solution Live BCG Vaccine Prasugrel 100 30 30 μL equivalent Ex. 1218 Sublingual Solution Live BCG Vaccine Apafant 100 PAF 30 30 μL equivalent antagonization Ex. 1219 Sublingual Solution Live BCG Vaccine Naloxone 100 μ, κ, σ 30 30 μL equivalent antagonization Ex. 1220 Sublingual Solution Live BCG Vaccine Zafirlukast 100 CysLT 30 30 μL equivalent antagonization Ex. 1221 Sublingual Solution Live BCG Vaccine Montelukast 100 30 30 μL equivalent Ex. 1222 Sublingual Solution Live BCG Vaccine Pranlukast 100 30 30 μL equivalent Ex. 1223 Sublingual Solution Live BCG Vaccine Candesartan 100 AT1 30 30 μL equivalent antagonization
TABLE-US-00046 TABLE 46 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Transnasal Solution Inactivated Vaccine — — 10 Ex. 63 rabies virus 200 μL equivalent Ex. 1224 Transnasal Solution Inactivated Vaccine Resveratrol 40 PDE 10 rabies virus 200 μL equivalent inhibition Ex. 1225 Transnasal Solution Inactivated Vaccine Vinpocetine 20 PDE 10 rabies virus 200 μL equivalent inhibition Ex. 1226 Transnasal Solution Inactivated Vaccine Pimobendan 20 PDE 10 rabies virus 200 μL equivalent inhibition Ex. 1227 Transnasal Solution Inactivated Vaccine BRL50481 20 PDE 10 rabies virus 200 μL equivalent inhibition Ex. 1228 Transnasal Solution Inactivated Vaccine Dipyridamole 40 PDE 10 rabies virus 200 μL equivalent inhibition Ex. 1229 Transnasal Solution Inactivated Vaccine Methoxyphenamine 20 β2 10 rabies virus 200 μL equivalent hydrochloride activation Ex. 1230 Transnasal Solution Inactivated Vaccine Fenoldopam 20 D1 10 rabies virus 200 μL equivalent mesylate activation Ex. 1231 Transnasal Solution Inactivated Vaccine Cisapride 20 5-HT4 10 rabies virus 200 μL equivalent activation Ex. 1232 Transnasal Solution Inactivated Vaccine Desmopressin 20 V2 10 rabies virus 200 μL equivalent activation Ex. 1233 Transnasal Solution Inactivated Vaccine Prazosin 80 α1,2 10 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1234 Transnasal Solution Inactivated Vaccine Pirenzepine 20 M1 10 rabies virus 200 μL equivalent hycrochloride antagonization Ex. 1235 Transnasal Solution Inactivated Vaccine Oxybutynin 40 M2 10 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1236 Transnasal Solution Inactivated Vaccine Tolterodine 80 M3 10 rabies virus 200 μL equivalent tartrate antagonization Ex. 1237 Transnasal Solution Inactivated Vaccine Fluphenazine 10 D2 10 rabies virus 200 μL equivalent antagonization Ex. 1238 Transnasal Solution Inactivated Vaccine Droperidol 20 10 rabies virus 200 μL equivalent Ex. 1239 Transnasal Solution Inactivated Vaccine Sulpiride 20 10 rabies virus 200 μL equivalent Ex. 1240 Transnasal Solution Inactivated Vaccine Azelastine 40 H1 10 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1241 Transnasal Solution Inactivated Vaccine Levocetirizine 20 10 rabies virus 200 μL equivalent Ex. 1242 Transnasal Solution Inactivated Vaccine Mequitazine 20 10 rabies virus 200 μL equivalent Ex. 1243 Transnasal Solution Inactivated Vaccine Thioperamide 20 H3 10 rabies virus 200 μL equivalent antagonization Ex. 1244 Transnasal Solution Inactivated Vaccine Sarpogrelate 20 5-HT2 10 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1245 Transnasal Solution Inactivated Vaccine Clopidogrel 20 P2Y12 10 rabies virus 200 μL equivalent antagonization Ex. 1246 Transnasal Solution Inactivated Vaccine Tiolopidine 40 10 rabies virus 200 μL equivalent Ex. 1247 Transnasal Solution Inactivated Vaccine Prasugrel 20 10 rabies virus 200 μL equivalent Ex. 1248 Transnasal Solution Inactivated Vaccine Apafant 20 PAF 10 rabies virus 200 μL equivalent antagonization Ex. 1249 Transnasal Solution Inactivated Vaccine Naloxone 20 μ, κ, σ 10 rabies virus 200 μL equivalent antagonization Ex. 1250 Transnasal Solution Inactivated Vaccine Zafirlukast 20 CysLT 10 rabies virus 200 μL equivalent antagonization Ex. 1251 Transnasal Solution Inactivated Vaccine Montelukast 20 10 rabies virus 200 μL equivalent Ex. 1252 Transnasal Solution Inactivated Vaccine Pranlukast 20 10 rabies virus 200 μL equivalent Ex. 1253 Transnasal Solution Inactivated Vaccine Candesartan 20 AT1 10 rabies virus 200 μL equivalent antagonization
TABLE-US-00047 TABLE 47 Antigen Th2 reaction promoter Administration Dosage Amount Amount Pharmacological Amount route form Name [μg] Name [μg] effect [μL] Comp. Sublingual Solution Inactivated Vaccine — — 30 Ex. 64 rabies virus 200 μL equivalent Ex. 1254 Sublingual Solution Inactivated Vaccine Resveratrol 200 PDE 30 rabies virus 200 μL equivalent inhibition Ex. 1255 Sublingual Solution Inactivated Vaccine Vinpocetine 100 PDE 30 rabies virus 200 μL equivalent inhibition Ex. 1256 Sublingual Solution Inactivated Vaccine Pimobendan 100 PDE 30 rabies virus 200 μL equivalent inhibition Ex. 1257 Sublingual Solution Inactivated Vaccine BRL50481 100 PDE 30 rabies virus 200 μL equivalent inhibition Ex. 1258 Sublingual Solution Inactivated Vaccine Dipyridamole 200 PDE 30 rabies virus 200 μL equivalent inhibition Ex. 1259 Sublingual Solution Inactivated Vaccine Methoxyphenamine 100 β2 30 rabies virus 200 μL equivalent hydrochloride activation Ex. 1260 Sublingual Solution Inactivated Vaccine Fenoldopam 100 D1 30 rabies virus 200 μL equivalent mesylate activation Ex. 1261 Sublingual Solution Inactivated Vaccine Cisapride 100 5-HT4 30 rabies virus 200 μL equivalent activation Ex. 1262 Sublingual Solution Inactivated Vaccine Desmopressin 100 V2 30 rabies virus 200 μL equivalent activation Ex. 1263 Sublingual Solution Inactivated Vaccine Prazosin 400 α1,2 30 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1264 Sublingual Solution Inactivated Vaccine Pirenzepine 100 M1 30 rabies virus 200 μL equivalent hycrochloride antagonization Ex. 1265 Sublingual Solution Inactivated Vaccine Oxybutynin 200 M2 30 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1266 Sublingual Solution Inactivated Vaccine Tolterodine 400 M3 30 rabies virus 200 μL equivalent tartrate antagonization Ex. 1267 Sublingual Solution Inactivated Vaccine Fluphenazine 50 D2 30 rabies virus 200 μL equivalent antagonization Ex. 1268 Sublingual Solution Inactivated Vaccine Droperidol 100 30 rabies virus 200 μL equivalent Ex. 1269 Sublingual Solution Inactivated Vaccine Sulpiride 100 30 rabies virus 200 μL equivalent Ex. 1270 Sublingual Solution Inactivated Vaccine Azelastine 200 H1 30 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1271 Sublingual Solution Inactivated Vaccine Levocetirizine 100 30 rabies virus 200 μL equivalent Ex. 1272 Sublingual Solution Inactivated Vaccine Mequitazine 100 30 rabies virus 200 μL equivalent Ex. 1273 Sublingual Solution Inactivated Vaccine Thioperamide 100 H3 30 rabies virus 200 μL equivalent antagonization Ex. 1274 Sublingual Solution Inactivated Vaccine Sarpogrelate 100 5-HT2 30 rabies virus 200 μL equivalent hydrochloride antagonization Ex. 1275 Sublingual Solution Inactivated Vaccine Clopidogrel 100 P2Y12 30 rabies virus 200 μL equivalent antagonization Ex. 1276 Sublingual Solution Inactivated Vaccine Tiolopidine 200 30 rabies virus 200 μL equivalent Ex. 1277 Sublingual Solution Inactivated Vaccine Prasugrel 100 30 rabies virus 200 μL equivalent Ex. 1278 Sublingual Solution Inactivated Vaccine Apafant 100 PAF 30 rabies virus 200 μL equivalent antagonization Ex. 1279 Sublingual Solution Inactivated Vaccine Naloxone 100 μ, κ, σ 30 rabies virus 200 μL equivalent antagonization Ex. 1280 Sublingual Solution Inactivated Vaccine Zafirlukast 100 CysLT 30 rabies virus 200 μL equivalent antagonization Ex. 1281 Sublingual Solution Inactivated Vaccine Montelukast 100 30 rabies virus 200 μL equivalent Ex. 1282 Sublingual Solution Inactivated Vaccine Pranlukast 100 30 rabies virus 200 μL equivalent Ex. 1283 Sublingual Solution Inactivated Vaccine Candesartan 100 AT1 30 rabies virus 200 μL equivalent antagonization
[0180] The evaluation of the humoral immunity inducing effect shows that the transmucosal administration (transnasal administration) of a solution for transmucosal administration containing a Th2 reaction promoter (Examples 1 to 30) provides a higher antigen-specific IgG antibody titer than the administration of a solution for transmucosal administration free from a Th2 reaction promoter (Comparative Examples 1 to 8). Although the antigen and the Th2 reaction promoter in the examples were administered in the same formulation, the effect mentioned above can be obtained also when they are in separate formulations and administered separately. Not only in the case of the solution for transmucosal administration, but also in the case of other dosage forms such as solutions for subcutaneous administration or creams for transdermal administration, a high antigen-specific IgG antibody titer as mentioned above can be obtained by preparing an antigen and a Th2 reaction promoter as different formulations and administering them separately.
TABLE-US-00048 TABLE 48 Amount Additive [Parts by weight] White Vaseline 60.7 Sorbitan monostearate 0.7 Isostearic acid 12 Benzyl alcohol 2.4 Cetanol 2.4 Stearyl alcohol 3.5 Polysorbate 60 3.5 Concentrated glycerin 2.4 Purified water 12.4 Total 100