Immunogenic composition for modulating the immune system and methods to treat bacterial infections in a subject
10213504 ยท 2019-02-26
Inventors
Cpc classification
C12N2710/24134
CHEMISTRY; METALLURGY
A61K39/102
HUMAN NECESSITIES
C12N2710/16734
CHEMISTRY; METALLURGY
A61K47/10
HUMAN NECESSITIES
C12N2710/16634
CHEMISTRY; METALLURGY
A61K39/0002
HUMAN NECESSITIES
C12N2760/18434
CHEMISTRY; METALLURGY
A61K39/05
HUMAN NECESSITIES
C12N2770/32334
CHEMISTRY; METALLURGY
C12N2770/36234
CHEMISTRY; METALLURGY
C12N2770/24134
CHEMISTRY; METALLURGY
C12N2730/10134
CHEMISTRY; METALLURGY
A61K45/06
HUMAN NECESSITIES
A61K39/105
HUMAN NECESSITIES
A61K39/292
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
A61K9/0019
HUMAN NECESSITIES
International classification
A61K39/00
HUMAN NECESSITIES
A61K9/00
HUMAN NECESSITIES
A61K39/09
HUMAN NECESSITIES
A61K39/05
HUMAN NECESSITIES
A61K39/102
HUMAN NECESSITIES
Abstract
The present invention refers to pharmaceutical products comprising immunogenic compositions for modulating the immune system, which comprise a therapeutically effective amount of a Immunological Response Shifter (IRS) comprising two or more immunoactive antigenic agents presenting pathogen-associated molecular patterns (PAMPS) and/or danger associated molecular patterns (DAMPS) and/or Stress Response Signals (SRS), in association with an antibiotic and one or more physiologically acceptable carriers, excipients, diluents or solvents. IN other embodiments, the present invention refers to methods to treat severe bacterial infections, sepsis and modulating the immune system.
Claims
1. A pharmaceutical product comprising one or more antibiotics and one or more immunological response shifter (IRS) immunogenic compositions for modulating the immune system comprising a therapeutically effective amount of three or more synthetic antigenic agents or natural antigenic agents, or fractions and combinations thereof, comprising pathogen-associated molecular patterns (PAMPS) and/or danger associated molecular patterns (DAMPS) selected from at least two groups consisting of: (A) antigenic agents with molecular patterns associated with bacteria, (B) antigenic agents with molecular patterns associated with viruses, (C) antigenic agents with molecular patterns associated with fungi and yeasts, (D) antigenic agents with molecular patterns associated with protozoa, (E) antigenic agents with molecular patterns associated with helminths, and (F) antigenic agents with molecular patterns associated with prions; and one or more physiologically acceptable carriers, excipients, diluents or solvents.
2. The pharmaceutical product of claim 1 wherein the antigenic agents are selected from at least four groups (A), (B), (C), (D), (E) and (F).
3. The pharmaceutical product of claim 1, wherein the antibiotic is a beta-Lactam.
4. The pharmaceutical product of claim 1 wherein the antibiotics are selected from the following classes: Amino Acid Derivatives, Aminoglycosides, Aureolic Acids, Aziridines, Ansamycins, Benzenoids, Benzimidazoles, Carbapenems, Cephalosporins, Coumarin-glycosides, Diphenyl Ether Derivatives, Epipolythiodioxopiperazines, Fatty Acid Derivatives, Glucosamine, Imidazoles, Indol Derivatives, Macrolactams, Macrolides, Nucleosides, Penicillins Peptides, Peptidyl Nucleosides, Phenicoles, Polyenes, Polyethers, Pyridines, Pyrimidines, Quinolones, Fluoroquinolones, Statins, Steroids, Sulfonamides, Taxoides and Tetracyclines.
5. The pharmaceutical product of claim 4 wherein the antibiotics are selected from the following classes: ansamycins, Penicillins, Cephalosporins, Carbapenems and Lipopeptides.
6. The pharmaceutical product of claim 4, wherein the peptides are Glycopeptides or Lipopeptides.
7. The pharmaceutical product of claim 1 comprising from 4 to 20 antigenic agents selected from the group consisting of antigenic agents derived from: dornase, yeast, oidiomycin, purified protein derivative of Koch's bacillus (PPD), prions, streptokinases, Streptococcus toxoid, diphtheria toxoid, tetanus toxoid, Koch's original tuberculin, Ascaris lumbricoides lysates, Aspergillus spp., Candida albicans, Candida glabrata, Candida parapsilosis, Chlamydia spp., Cryptosporidium spp., Dermatophytes, Entamoeba hystolitica, Enterobius vermicularis, Enterococcus faecalis, Epidermophyton floccosum, Escherichia coli, Giardia lamblia, Haemophilus influenzae, Microsporum canis, Mycobacterium spp., Neisseria gonorrhoeae, Human papillomavirus, Polio virus, Proteus spp., Salmonella spp., Serratia spp., Shigella spp., Staphylococcus spp., Streptococcus spp., Toxoplasma gondii, Trichomonas vaginalis, trichophytin, Trichophyton spp., yellow fever virus, hepatitis B virus, rubella virus, varicella zoster virus, variola virus, mumps virus, measles virus, herpes virus and vaccinia virus.
8. The pharmaceutical product of claim 7, wherein the Aspergillus spp. is Aspergillus flavus, Aspergillus fumigatus, or Aspergillus terreus, the Chlamydia spp. is Chlamydia pneumoniae, Chlamydia psittaci, or Chlamydia trachomatis, the Mycobacterium spp. is Mycobacterium bovis, Mycobacterium leprae, or Mycobacterium tuberculosis, the Proteus spp. is Proteus mirabilis, Proteus penerii, or Proteus vulgaris, the Salmonella spp. is Salmonella bongori, or Salmonella enterica, the Serratia spp. is Serratia liquefaciens, or Serratia marcencens, the Shigella spp. is Shigella flexneri, or Shigella sonnei, the Staphylococcus spp. is Staphylococcus aureus, Staphylococcus epidermidis, or Strongyloides stercoralis, the Streptococcus spp. is Streptococcus bovis, Streptococcus viridans, Streptococcus equinus, Streptococcus pneumoniae, or Streptococcus pyogenes, and the Trichophyton spp. is Trichophyton rubrum, Trichophyton tonsurans, or Trichophyton mentagrophytes.
9. A method to treat sepsis and multi resistant bacterial infection in a human or an animal comprising administering to the human or animal an effective amount of one or more antibiotics and one or more immunological response shifter (IRS immunogenic compositions comprising a therapeutically effective amount of three or more synthetic antigenic agents or natural antigenic agents, or fractions and combinations thereof, comprising pathogen-associated molecular patterns (PAMPS) and/or danger associated molecular patterns (DAMPS) selected from at least two groups consisting of: (A) antigenic agents with molecular patterns associated with bacteria, (B) antigenic agents with molecular patterns associated with viruses, (C) antigenic agents with molecular patterns associated with fungi and yeasts, (D) antigenic agents with molecular patterns associated with protozoa, (E) antigenic agents with molecular patterns associated with helminthes, and (F) antigenic agents with molecular patterns associated with prions; and one or more physiologically acceptable carriers, excipients, diluents or solvents.
10. A method to modulate an immune system response in a human or an animal who has a bacterial infection comprising administering to the human or animal an effective amount of one or more immunological response shifter (IRS) immunogenic compositions comprising a therapeutically effective amount of three or more synthetic antigenic agents or natural antigenic agents, or fractions and combinations thereof, comprising pathogen-associated molecular patterns (PAMPS) and/or danger associated molecular patterns (DAMPS) selected from at least two groups consisting of: (A) antigenic agents with molecular patterns associated with bacteria, (B) antigenic agents with molecular patterns associated with viruses, (C) antigenic agents with molecular patterns associated with fungi and yeasts, (D) antigenic agents with molecular patterns associated with protozoa, (E) antigenic agents with molecular patterns associated with helminthes, and (F) antigenic agents with molecular patterns associated with prions; and one or more physiologically acceptable carriers, excipients, diluents or solvents.
Description
DESCRIPTION OF THE FIGURES
(1) The following figures are part of this report and are included here to illustrate certain aspects of the invention. The object of the present invention may be better understood by reference to one or more of these figures in combination with the detailed description of the preferred embodiment presented here.
(2)
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EXAMPLES
(5) In order to allow a better understanding of the invention and clearly demonstrate the technical progress achieved, the results of the various tests conducted with respect to this invention are shown below as examples.
(6) These Examples are presented for illustrative purposes only and should not be regarded in any way as limiting the scope and range of the invention.
Example 1: Immunogenic Compositions
(7) In order to achieve the recontextualizing, renewal and reprogramming of the immune response in real time according to the innovative concepts described in the present invention, an expert skilled in the art can design different and distinct compositions, combinations or formulations of products, which fall within the scope of the invention.
(8) As described, for such compositions to meet the technical requirements for the advantageous or unpublished results in treat a number of diseases and illnesses, they must have a high diversity of antigens from pathogens, so as to get the maximum synergistic effect in binding the PAMPs and DAMPs to their receptors and allowing the achievement of a high degree of activation of the innate immunity in the sentinel cells (with or without ATC function) thereby allowing the recontextualizing, renewal and reprogramming of the immune response in real time.
(9) Such compositions should preferably use antigenic agents for which most people, because of previous contact, would have memory clones of in their immune system capable of inducing a broad anti-inflammatory action in parallel to recontextualization. For this, antigenic agents should preferably be selected that: correspond to the most common infections contracted by the individual from childhood to maturity (when the animal or the human being acquires its repertoire of immunity). are used in immunization programs such as childhood vaccination programs against endemic and/or epidemic diseases. those from organisms of potentially pathogenic microflora, especially of the gastrointestinal tract, where the memory lymphocytes play an active dynamic barrier ensuring the survival of the individual. Ideally each of the antigenic agents should be present in a concentration of 0.001 to 500 micrograms per mL.
(10) In accordance with these concepts, several formulations have been developed, using antigenic agents in their already available, safe, and approved forms for use in human vaccination programs or allergic response tests and immunity assessment tests.
(11) Therefore, we present the following several examples of compositions which fall within the scope of the present invention, without however the intention to limit it, since the present invention and its concepts allow for the design of immunogenic compositions comprising a very large number of combinations of antigenic agents.
(12) Composition 1a (DECA Composition):
(13) TABLE-US-00001 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL PPD 0.004 g/mL Inactivated Staphylococcus lysate (Staphylococcus aureus and 6.94 g/mL Staphylococcus epidermidis in equal parts). Inactivated Steptococcus lysate (Streptococcus pyogenes, 6.94 g/mL Streptococcus pneumoniae and Enterococcus faecalis in equal parts). Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.444 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.111 g/mL purification. Inactivated Candida lysate (Candida albicans and Candida glabrata in 6.94 g/mL equal parts). Inactivated dermatophytes lysate (Epidermophytonfloccosum, 6.94 g/mL Microsporum cannis, Trichophyton mentagrophytes of the interdigitale variety in equal parts). Inactivated enteropathogenic Escherichia coli lysate (EPEC) 6.94 g/mL Inactivated Salmonella lysate (Salmonella bongori, Salmonella 6.94 g/mL enterica and Salmonella subterranea in equal parts). Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 1b (VITER Composition):
(14) TABLE-US-00002 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.0036 ng/mL PPD 0.0036 g/mL Inactivated Staphylococcus lysate (Staphylococcus aureus and 6.31 g/mL Staphylococcus epidermidis in equal parts). Inactivated Steptococcus lysate (Streptococcus pyogenes, 6.31 g/ml Streptococcus pneumoniae and Enterococcus faecalis in equal parts). Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.404 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.101 g/mL purification. Oidiomycin (antigenic extract of Candida albicans 6.31 g/mL Trichophytin (antigenic extract of Tricophyton sp 6.31 g/mL Inactivated enteropathogenic Escherichia coli lysate (EPEC) 6.31 g/mL Inactivated Salmonella lysate (Salmonella bongori, Salmonella 6.31 g/mL enterica and Salmonella subterranea in equal parts). Attenuated yellow fever virus strain 17 D204 20 g/mL Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 2:
(15) TABLE-US-00003 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL PPD 0.004 g/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.444 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.111 g/mL purification. Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 3:
(16) TABLE-US-00004 Component Concentration PPD 0.004 g/mL Inactivated Streptococcus pyogenes lysate, inactivated 6.94 g/mL Streptococcus pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated 6.94 g/mL Staphylococcus epidermidis lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida 6.94 g/mL parapsilosis lysate, inactivated Candida glabrata lysate in equal parts. Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 4:
(17) TABLE-US-00005 Component Concentration Inactivated BCG lysate 50 mg/mL Inactivated Staphylococcus aureus lysate, inactivated 6.94 g/mL Staphylococcus epidermidis lysate in equal parts. Inactivated Streptococcus agalactiae lysate, inactivated 6.94 g/mL Streptococcus mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Candida albincans lysate, inactivated 6.94 g/mL Candida parapsilosis lysate, inactivated Candida glabrata in equal parts. Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 5:
(18) TABLE-US-00006 Component Concentration PPD 0.004 g/mL Inactivated Streptococcus pyogenes lysate, inactivated 6.94 g/mL Streptococcus pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, 6.94 g/mL and Apergillus terreus lysate in equal parts. Inactivated dermatophytes lysate 6.94 g/mL (Epidermophytonfloccosum, Microsporum cannis, Trichophyton mentagrophytes of the interdigitale variety in equal parts). Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 6:
(19) TABLE-US-00007 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis 0.004 ng/mL lysate). Inactivated Streptococcus pyogenes lysate, inactivated 6.94 g/mL Streptococcus pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Neisseria meningitides lysate. 6.94 g/mL Inactivated Apergillus fumigatus, Apergillus flavus, and 6.94 g/mL Apergillus terreus lysate in equal parts. Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 7:
(20) TABLE-US-00008 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Inactivated Streptococcus equinus, Streptococcus bovis and 6.94 g/mL Streptococcus viridans lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 8:
(21) TABLE-US-00009 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL PPD 0.004 g/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.444 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.111 g/mL purification. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Helicobacter pylori lysate. 6.94 g/mL Tetanus toxoid 50 units of Lf/mL Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Sodium Chloride 7.5 mg/mL Sodium phosphate dibasic heptahydrate 0.48 mg/mL Potassium phosphate monobasic 0.06 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 9:
(22) TABLE-US-00010 Component Concentration Inactivated BCG lysate 50 mg/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 10:
(23) TABLE-US-00011 Component Concentration Inactivated Mycobacterium africanum lysate. 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Acinetobacter baumannii lysate. 6.94 g/mL Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated lysate of antigens of the mumps virus (Urabe AM9 strain) 10,000 TDCI50/mL Inactivated Polio virus lysate 40 UD of type I antigens; 1.8 UD of type 2 antigens; 32 UD of type 3 antigens Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 11:
(24) TABLE-US-00012 Component Concentration Inactivated Mycobacterium leprae lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Antigens of the rubella virus (Wistar RA 27/3M strain) 10,000 TDCI50/mL Inactivate antigen of the Varicella zoster virus lysate 149 231 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 12:
(25) TABLE-US-00013 Component Concentration Inactivated Mycobacterium avium lysate 0.004 ng/mL Inactivated Mycobacterium kansasii lysate 0.004 ng/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Neisseria gonorrhoeae lysate. 6.94 g/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Chlamydia trachomatis, Chlamydia psittaci, and Chamydia 6.94 g/mL pneumoniae lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Antigens of the rubella virus (Wistar RA 27/3M strain) 10,000 TDCI50/mL Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 13:
(26) TABLE-US-00014 Component Concentration Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Mycobacterium avium lysate 0.004 ng/mL Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated Serratia marcencense Serratia liquefaciens lysate 6.94 g/mL Inactivated antigen of HSV-I and HSV-II lysate 149 231 PFU/mL Inactivated antigen of the measles virus (Schwarz strain) lysate 10,000 TDCI50/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 14:
(27) TABLE-US-00015 Component Concentration Inactivated Mycobacterium africanum lysate 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Neisseria gonorrhoeae lysate 6.94 mg/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Shigella flexneri and Shigella sonnei lysate in equal parts 6.94 g/mL Inactivated surface antigen of the hepatitis B (HBs AG) virus lysate 200 g/mL Inactivated antigen of the measles virus (Schwarz strain) lysate 10,000 TDCI50/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 15:
(28) TABLE-US-00016 Component Concentration PPD 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Tetanus toxoid 50 units of Lf/mL Diphtheria toxoid 67 units of Lf/mL Inactivated Acinetobacter baumannii lysate. 6.94 g/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated lysate of antigens of the mumps virus (Urabe AM9 strain) 10,000 TDCI50/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 16:
(29) TABLE-US-00017 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Bordetella pertussis toxoid 75 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Tetanus toxoid 50 units of Lf/mL Inactivated Polio virus lysate 40 UD of type I antigens; 1.8 UD of type 2 antigens; 32 UD of type 3 antigens Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 17:
(30) TABLE-US-00018 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated BCG lysate 50 mg/mL PPD 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Klebsiella oxytoca and Klebsiella pneumonia lysate in 6.94 g/mL equal parts Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Diphtheria toxoid 67 units of Lf/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Bordetella pertussis toxoid 75 g/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Inactivated Candida albincans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 18:
(31) TABLE-US-00019 Component Concentration PPD 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.444 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.111 g/mL purification. Inactivated Klebsiella oxytoca and Klebsiella pneumonia lysate in 6.94 g/mL equal parts Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Helicobacter pylori lysate. 6.94 g/mL Tetanus toxoid 50 units of Lf/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 19:
(32) TABLE-US-00020 Component Concentration Inactivated BCG lysate 50 mg/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Serratia marcencens e Serratia liquefaciens lysate 6.94 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Klebsiella oxytoca and Klebsiella pneumonia lysate in 6.94 g/mL equal parts Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 20:
(33) TABLE-US-00021 Component Concentration Inactivated Mycobacterium africanum lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Neisseria meningitides lysate 6.94 g/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Acinetobacter baumannii lysate. 6.94 g/mL Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated lysate of antigens of the mumps virus (Urabe AM9 strain) 50,000 TDCI50/mL Inactivated Polio virus lysate 40 UD of type I antigens; 1.8 UD of type 2 antigens; 32 UD of type 3 antigens Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 21:
(34) TABLE-US-00022 Component Concentration Inactivated Mycobacterium leprae lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Staphylococcus aureuslysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Diphtheria toxoid 67 units of Lf/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Tetanus toxoid 50 units of Lf/mL Inactivated Neisseria meningitides lysate 6.94 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated Serratia marcencens e Serratia liquefaciens lysate 6.94 g/mL Antigens of the rubella virus (Wistar RA 27/3M strain) 10,000 TDCI50/mL Inactivate antigen of the Varicella zoster virus lysate 149 231 PFU/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 22:
(35) TABLE-US-00023 Component Concentration Inactivated Mycobacterium avium lysate 0.004 ng/mL Inactivated Mycobacterium kansasii lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Neisseria gonorrhoeae lysate 6.94 mg/mL Tetanus toxoid 50 units of Lf/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Chlamydia trachomatis, Chlamydia psittaci, and Chamydia 6.94 g/mL pneumoniae lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Klebsiella oxytoca and Klebsiella pneumonia lysate in 6.94 g/mL equal parts Antigens of the rubella virus (Wistar RA 27/3M strain) 10,000 TDCI50/mL Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 23:
(36) TABLE-US-00024 Component Concentration Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Mycobacterium avium lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Tetanus toxoid 50 units of Lf/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated Serratia marcencens e Serratia liquefaciens lysate 6.94 g/mL Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated antigen of HSV-I and HSV-II lysate 149 231 PFU/mL Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 24:
(37) TABLE-US-00025 Component Concentration Inactivated Mycobacterium africanum lysate 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL PPD 0.004 ng/mL Inactivated Neisseria gonorrhoeae lysate 6.94 mg/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Tetanus toxoid 50 units of Lf/mL Inactivated Shigella flexneri and Shigella sonnei lysate in equal parts 6.94 g/mL Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated surface antigen of the hepatitis B (HBs AG) virus lysate 200 g/mL Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 25:
(38) TABLE-US-00026 Component Concentration PPD 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Diphtheria toxoid 67 units of Lf/mL Tetanus toxoid 50 units of Lf/mL Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Acinetobacter baumannii lysate. 6.94 g/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated lysate of antigens of the mumps virus (Urabe AM19 strain) 50,000 TDCI50/mL Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 26:
(39) TABLE-US-00027 Component Concentration Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Chlamydia trachomatis, Chlamydia psittaci, and Chamydia 6.94 g/mL pneumoniae lysate in equal parts. Bordetella pertussis toxoid 75 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Neisseria gonorrhoeae lysate 6.94 mg/mL Tetanus toxoid 50 units of Lf/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Polio virus lysate 40 UD of type I antigens; 1.8 UD of type 2 antigens; 32 UD of type 3 antigens Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated YF-17D lysate 3,000,000 PFU/mL
Composition 27:
(40) TABLE-US-00028 Component Concentration Inactivated YF-17D lysate 3,000,000 PFU/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated BCG lysate 50 mg/mL PPD 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Klebsiella oxytoca and Klebsiella pneumonia lysate in 6.94 g/mL equal parts Inactivated Neisseria meningitides lysate 6.94 g/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Shigella flexneri and Shigella sonnei lysate in equal parts 6.94 g/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Bordetella pertussis toxoid 75 g/mL Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 28:
(41) TABLE-US-00029 Component Concentration Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium avium lysate 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Neisseria meningitides lysate 6.94 g/mL Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.444 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.111 g/mL purification. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Enterobacter aerogenes, Enterobacter cloacae, and 6.94 g/mL Enterobacter agglomerans group lysate. Inactivated Helicobacter pylori lysate. 6.94 g/mL Tetanus toxoid 50 units of Lf/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 29:
(42) TABLE-US-00030 Component Concentration Inactivated lysate of antigens of the mumps virus (Urabe AM9 strain) 50,000 TDCI50/mL Inactivated BCG lysate 50 mg/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium leprae lysate 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Serratia marcencens and Serratia liquefaciens lysate 6.94 g/mL Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Tetanus toxoid 50 units of Lf/mL Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 30:
(43) TABLE-US-00031 Component Concentration Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Mycobacterium africanum lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Salmonella typhi, Salmonella paratyphiand Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Acinetobacter baumannii lysate. 6.94 g/mL Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated YF-17D lysate 3,000,000 PFU/mL Inactivated lysate of antigens of the mumps virus (Urabe AM9 strain) 50,000 TDCI50/mL Inactivated Polio virus lysate 40 UD of type I antigens; 1.8 UD of type 2 antigens; 32 UD of type 3 antigens Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 31:
(44) TABLE-US-00032 Component Concentration Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Mycobacterium leprae lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL PPD 0.004 ng/mL Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Diphtheria toxoid 67 units of Lf/mL Inactivated Neisseria gonorrhoeae lysate 6.94 mg/mL Inactivated Streptococcus agalactiae lysate, inactivated Streptococcus 6.94 g/mL mix (Streptococcus pyogenes, Streptococcus pneumoniae and Enterococcus faecalis) lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Neisseria meningitides lysate 6.94 g/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Haemophilus influenza lysate. 6.94 g/mL Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated Serratia marcencens e Serratia liquefaciens lysate 6.94 g/mL Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Antigens of the rubella virus (Wistar RA 27/3M strain) 10,000 TDCI50/mL Inactivate antigen of the Varicella zoster virus lysate 149231 PFU/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 32:
(45) TABLE-US-00033 Component Concentration Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Mycobacterium avium lysate 0.004 ng/mL Inactivated Mycobacterium kansasii lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Neisseria gonorrhoeae lysate 6.94 mg/mL Tetanus toxoid 50 units of Lf/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated Chlamydia trachomatis, Chlamydia psittaci, and Chamydia 6.94 g/mL pneumoniae lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Klebsiella oxytoca and Klebsiella pneumonia lysate in 6.94 g/mL equal parts Antigens of the rubella virus (Wistar RA 27/3M strain) 10,000 TDCI50/mL Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 33:
(46) TABLE-US-00034 Component Concentration Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Mycobacterium leprae lysate 0.004 ng/mL Inactivated Mycobacterium avium lysate 0.004 ng/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Tetanus toxoid 50 units of Lf/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Shigella flexneri and Shigella sonnei lysate in equal parts 6.94 g/mL Inactivated Helicobacter pylori lysate. 6.94 g/mL Inactivated Serratia marcencens e Serratia liquefaciens lysate 6.94 g/mL Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated antigen of HSV-I and HSV-II lysate 149231 PFU/mL Inactivated lysate of antigens of the measles virus (Schwarz strain). 10,000 TDCI50/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 34:
(47) TABLE-US-00035 Component Concentration Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Mycobacterium africanum lysate 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL PPD 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Tetanus toxoid 50 units of Lf/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Neisseria meningitides lysate 6.94 g/mL Diphtheria toxoid 67 units of Lf/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated Shigella flexneri and Shigella sonnei lysate in equal parts 6.94 g/mL Inactivated Proteus mirabilis, Proteus vulgaris, and Proteus penerii 6.94 g/mL lysate in equal parts. Inactivated surface antigen of the hepatitis B (HBs AG) virus lysate 200 g/mL Inactivated lysate of antigens of the measles virus (Schwarz strain). 110,000 TDCI50/mL Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 35:
(48) TABLE-US-00036 Component Concentration Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. PPD 0.004 ng/mL Inactivated BCG lysate 50 mg/mL Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Staphylococcus aureus lysate, inactivated Staphylococcus 6.94 g/mL epidermidis lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Inactivated Neisseria meningitides lysate 6.94 g/mL Tetanus toxoid 50 units of Lf/mL Diphtheria toxoid 67 units of Lf/mL Inactivated Streptococcus equinus, Streptococcus bovis, and 6.94 g/mL Streptococcus of the viridans group lysate in equal parts. Inactivated Serratia marcencens e Serratia liquefaciens lysate 6.94 g/mL Inactivated Acinetobacter baumannii lysate. 6.94 g/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Inactivated YF-17D lysate 3,000,000 PFU/mL Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Inactivated lysate of antigens of the mumps virus (Urabe AM9 strain) 50,000 TDCI50/mL Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
Composition 36:
(49) TABLE-US-00037 Component Concentration Inactivated Apergillus fumigatus, Apergillus flavus, and Apergillus 6.94 g/mL terreus lysate in equal parts. Koch's Turberculin (inactivated Mycobacterium bovis lysate). 0.004 ng/mL Inactivated Mycobacterium tuberculosis lysate 0.004 ng/mL Inactivated BCG lysate 50 mg/mL PPD (purified protein derivative) 0.004 ng/mL Inactivated Streptococcus pyogenes lysate, inactivated Streptococcus 6.94 g/mL pneumonie lysate, Enterococcus faecalis lysate in equal parts. Inactivated Chlamydia trachomatis, Chlamydia psittaci, and Chamydia 6.94 g/mL pneumoniae lysate in equal parts. Inactivated Epidermophyton floccosum, Microsporum cannis, 6.94 g/mL Trichophyton mentagrophytes of the interdigitale variety lysate in equal parts). Bordetella pertussis toxoid 75 g/mL Inactivated Haemophilus influenza lysate. 6.94 g/mL Streptokinase derived from inactivated beta-hemolytic Streptococcus 0.444 g/mL lysate purification. Dornase derived from inactivated beta-hemolytic Streptococcus lysate 0.111 g/mL purification. Inactivated Salmonella typhi, Salmonella paratyphi and Salmonella 6.94 g/mL enterica lysate in equal parts. Tetanus toxoid 50 units of Lf/mL Inactivated surface antigen of the hepatitis B (HBs AG) virus lysate 200 g/mL Inactivated enteropathogenic (EPEC), shiga-like toxin producer 6.94 g/mL (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and extraintestinal (ExPEC) Escherichia coli lysate in equal parts. Inactivated Candida albicans lysate, inactivated Candida parapsilosis 6.94 g/mL lysate, inactivated Candida glabrata lysate in equal parts. Inactivated Polio virus lysate 40 UD of type I antigens; 1.8 UD of type 2 antigens; 32 UD of type 3 antigens Inactivated antigen of the Vaccinia (smallpox) virus lysate 1 to 10 10.sup.9 PFU/mL Inactivated YF-17D lysate 3,000,000 PFU/mL Glycerol 500 mg/mL Phenol 2.5 mg/mL Water q.s.
(50) When there are parasitic diseases, associated or to be fought, the formulations will preferentially contain antigenic agens of parasitic origin. In this case, according to the concept described in the present invention, the formulations should comprise antigenic agents originating from the most prevalent parasites for which the individuals have more memory cells, according to the geographic distribution and the local and regional human development (developed or non-developed countries). Such parameters are determinant for the occurrence of these parasites and the existence of corresponding memory cells in the immune system of the population of a given region.
(51) Composition 37: Association of Composition 2 with:
(52) TABLE-US-00038 Component Concentration Inactivated Toxoplasma gondii lysate 400 g/mL
Composition 38: Association of Composition 3 with:
(53) TABLE-US-00039 Component Concentration Inactivated Giardi lamblia lysate 400 g/mL
Composition 39: Association of Composition 4 with:
(54) TABLE-US-00040 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL
Composition 40: Association of Composition 5 with:
(55) TABLE-US-00041 Component Concentration Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 41: Association of Composition 6 with:
(56) TABLE-US-00042 Component Concentration Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 42: Association of Composition 7 with:
(57) TABLE-US-00043 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 43: Association of Composition 8 with:
(58) TABLE-US-00044 Component Concentration Inactivated Giardi lamblia lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 44: Association of Composition 9 with:
(59) TABLE-US-00045 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL
Composition 45: Association of Composition 10 with:
(60) TABLE-US-00046 Component Concentration Inactivated Giardia lamblia lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 46: Association of Composition 11 with:
(61) TABLE-US-00047 Component Concentration Inactivated Toxoplasma gondii lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL
Composition 47: Association of Composition 12 with
(62) TABLE-US-00048 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Cryptosporidium spp. lysate 400 g/mL
Composition 48: Association of Composition 13 with:
(63) TABLE-US-00049 Component Concentration Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Toxoplasma gondii lysate 400 g/mL
Composition 49: Association of Composition 14 with:
(64) TABLE-US-00050 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL
Composition 50: Association of Composition 15 with:
(65) TABLE-US-00051 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 51: Association of Composition 16 with:
(66) TABLE-US-00052 Component Concentration Inactivated Trichomonas vaginalis lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 52: Association of Composition 17 with:
(67) TABLE-US-00053 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 53: Association of Composition 18 with:
(68) TABLE-US-00054 Component Concentration Inactivated Giardia lamblia lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL Inactivated Toxoplasma gondii lysate 400 g/mL
Composition 54: Association of Composition 19 with:
(69) TABLE-US-00055 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL
Composition 55: Association of Composition 20 with:
(70) TABLE-US-00056 Component Concentration Inactivated Giardia lamblia lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Strongyloides stercoralis lysate 400 g/mL
Composition 56: Association of Composition 21 with:
(71) TABLE-US-00057 Component Concentration Inactivated Toxoplasma gondii lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL
Composition 57: Association of Composition 22 with:
(72) TABLE-US-00058 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Cryptosporidium spp. lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL
Composition 58: Association of Composition 23 with:
(73) TABLE-US-00059 Component Concentration Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Toxoplasma gondii lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 59: Association of Composition 24 with:
(74) TABLE-US-00060 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 60: Association of Composition 25 with:
(75) TABLE-US-00061 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL
Composition 61: Association of Composition 26 with:
(76) TABLE-US-00062 Component Concentration Inactivated Trichomonas vaginalis lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL
Composition 62: Association of Composition 27 with:
(77) TABLE-US-00063 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL Inactivated Cryptosporidium spp. lysate 400 g/mL
Composition 63: Association of Composition 28 with:
(78) TABLE-US-00064 Component Concentration Inactivated Giardia lamblia lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL Inactivated Toxoplasma gondii lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 64: Association of Composition 29 with:
(79) TABLE-US-00065 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 65: Association of Composition 30 with:
(80) TABLE-US-00066 Component Concentration Inactivated Giardia lamblia lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL
Composition 66: Association of Composition 31 with:
(81) TABLE-US-00067 Component Concentration Inactivated Toxoplasma gondii lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL
Composition 67: Association of Composition 32 with:
(82) TABLE-US-00068 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Cryptosporidium spp. lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL
Composition 68: Association of Composition 33 with:
(83) TABLE-US-00069 Component Concentration Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Toxoplasma gondii lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL Inactivated Cryptosporidium spp. lysate 400 g/mL
Composition 69: Association of Composition 34 with:
(84) TABLE-US-00070 Component Concentration Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Trichomonas vaginalis lysate 400 g/mL
Composition 70: Association of Composition 35 with:
(85) TABLE-US-00071 Component Concentration Inactivated Strongyloides stercoralis lysate 400 g/mL Inactivated Enterobius vermicularis lysate 400 g/mL Inactivated Entamoeba histolytica lysate 400 g/mL Inactivated Cryptosporidium spp. lysate 400 g/mL
Composition 71: Association of Composition 36 with:
(86) TABLE-US-00072 Component Concentration Inactivated Trichomonas vaginalis lysate 400 g/mL Inactivated Ascaris lumbricoides lysate 400 g/mL Inactivated Giardia lamblia lysate 400 g/mL
Example 2: Treating Septicemia
(87) Patient Data
(88) Patient J-P, 58 years old, male.
(89) Principal Diagnosis
(90) Septicemia.
(91) Secondary Diagnoses
(92) Polytrauma with:
(93) Complex infected wounds with major loss of tissue of approximately 40 cm. extensive infected tissue necrosis with indication for amputation of the left lower limb.
infected grade IIIB open fracture with osteomyelitis of the left femur with lateral exposure. open wounds, infected cut-contusion without possibility of suture on the left arm, back of the left foot and on the right lateral malleolus region.
Identification and Summary of the Clinical History
(94) On Jan. 12, 2011 the patient was admitted to the Intensive Care Unit of the Octavian Constantine Hospital das Clinicas of Teresopolis, victim of a landslide with a grade III b open fracture of the left femur with the exposure of the lateral cut and medial cut-contusion with an extension of 40 cm in depth that communicated with the exposure of the side. Lacerations, contusion on the left arm, back of the left foot and right lateral malleolus region. Evolved to a sepsis scenario in 24 hours, with microbiological identification of Pseudomonas aeruginosa.
(95) Conventional Proposed and Realized Treatment
(96) External fixation of the femur in the emergency room, administration of clindamycin, vancomycin and cefepime, associated to a daily surgical debridement.
(97) Results of the Performed Conventional Treatment
(98) Initially, it improved the septic scenario, followed by the evolution of the infection of the left lower limb with extensive areas of muscle necrosis with a high risk of amputation. 15 days after the admission the sepsis got worse, with febrile episodes of 39 C., profound anemia (receiving transfusions) and exchange of the antimicrobial medication to Tazocim. The patient was transferred with an aerial mobile ICU to Sao Paulo under medical supervision.
(99) The completion of conventional treatment showed a relapse in sepsis and increased necrosis of the left leg with an indication for amputation.
(100) Proposed DECA Treatment Associated with Conventional Surgical Treatment
(101) The patient was admitted to the ICU of Hospital Alemo Oswaldo Cruz for debridement and application of treatment with DECA which took the following form: Application of 1.8 cc of the DECA composition divided into 2 applications of 0.9 cc per composition along the 10 main lymphatic territories. 3-4 cm distance margin between applications to facilitate the reading of the evolution of the treatment at an interval of 41 days. These applications were made together with the surgical debridement (on average 1 to 2 times per week). Administration of 36 extra perilesional compositions of 1.8 cc of each DECA in two applications of 0.9 cc per set, skirting the following open injuries without possibility of suture: the left inguinal region, the lateral side of the left thigh, the anterior left thigh and medial aspect of the left thigh, instep region and left lateral malleolus of the right leg. Application of recombinant human interleukin-2 at low doses, at a receptor saturation level with a concentration of 1 to 2 million units per m.sup.2 of the patient's body surface located in the region of the extra DECA applications. 3 million daily units were subcutaneously injected in the left thigh or inguinal region for the patient. In the exposed regions 15 compositions DECA were applied, 1.8 cc each, for infiltration of exposed raw areas. This extensive immunotherapy was always applied in the operating days of cleansing and surgical debridement under general anesthesia.
(102) Thus, the first phase of immunotherapy began on 29 Jan. 2011 and ended on 19 Mar. 2011 totalling a total of nine DECA applications in periods ranging from one to two times per week, once the cleaning and debridement schedule was being followed, in the operating room (due to the severity of the pain and risk of infection by the broad extensive exposure of internal tissues in the raw areas).
(103) Results of the Treatment with DECA Associated with Surgical Debridement and Antibiotic Therapy
(104) Initial assessment of the patient's injuries in the operating room on 29 Jan. 2011 showed all wounds bleeding with many clots, with extensive areas of necrosis and foul-smelling pus. After surgical cleaning, tissue continued to perform poorly with a winy general appearance without any appearance of healthy granulation tissue (
(105) After 24 hours the first assessment of the surgical treatment associated with DECA immunotherapy was made and it demonstrated that: red lesions, with the appearance of healthy granulation tissue, with few necrotic areas with sparse secretion without foul odor and no active bleeding. The lesions were cleaned and the DECA immunotherapy was applied as noted above. On this occasion the antibiotic therapy was changed to Tazocim Meronem, Cubicin and Rifampicin pending culture results.
(106) On 1 Feb. 2011 the result of the cultures from the injury area, peripheral blood and central catheter showed: in the wound of the left thigh isolation of multidrug-resistant Pseudomonas aeruginosa, multiresistant Acinetobacter baunnamii sensitive only to polymyxin B and multiresistant Proteus mirabiles. in the peripheral blood and in the central catheter the isolation of multidrug-resistant Acinetobacter baunnamii sensitive only to polymyxin B.
Conclusion:
(107) These results demonstrated that the poor prognosis of injuries in the left leg led to a new sepsis episode with Acinetobacter baunnamii and because of its multidrug resistance and sensitivity only to polymyxin B, did not respond to treatment with intravenous Tazocim. On the other hand, it strongly supports a beneficial effect of the DECA composition in joint surgical treatment in the local and systemic protection against this infection, since there was improvement in systemic infection and injuries before the application of polymyxin B could neutralize this etiologic agent.
(108) That day, Meronem was exchanged for 20,000 IU/kg twice daily of Polymyxin B without changing the other medication.
(109) On 3 Feb. 2011, it was found that the combination antibiotic therapy, debridement and DECA immunotherapy caused the remission of the septic scenario, which allowed the transfer of the patient from the ICU to the ward thereafter (
(110) On 6 Feb. 2011, given the toxicity of Polymyxin B administration and other antimicrobials, the patient presented a picture of acute renal failure with oliguria. As a consequence, on the period between 6 Feb. 2011 and 15 Feb. 2011 (12 days) administration of these antibiotics was suspended, with Limezolida (Zyvox) being introduced for protection against a hospital staphylococcal contamination. On 15 Feb. 2011 the complete remission of renal failure in the patient was confirmed. In this 12-day period, with only the combination therapy of debridement, antibiotic prophylaxis and DECA immunotherapy, the patient showed excellent overall progress of the infectious and injuries being, after this period, able to withdraw the external fixator, have a surgical cleanup, and introduction of an internal rod for fixing the fracture on a surgery performed on 17 Feb. 2011. Thus, in this period, together with orthopedic surgery, there was a significant reduction in raw areas without skin with extensive tissue regeneration and no new infections.
(111) The patient was discharged on 15 Mar. 2011, with complete cure of the infection of all complex injuries and wounds, including osteomyelitis. The patient was discharged without antibiotic therapy.
(112) Conclusion of the Case
(113) The existence of a severe and widespread infection and of a complex wound infected with multidrug-resistant Acinetobacter baunnamii sensitive only to polymyxin B which was controlled without specific antibiotic therapy with broad progression to the healing of sepsis, of all exposed lesions, and of osteomyelitis, strongly suggest a decisive role of the DECA immunotherapy, associated with debridement and antibiotics, to cure the clinical scenario, in a relatively short time.
(114) TABLE-US-00073 TABLE 1 Result of the association of DECA immunotherapy, antibiotics and surgical debridement for sepsis and severe infection of complex injuries. Result of the association of immunotherapy, antibiotic therapy, and surgical Infected Pre-immunotherapy cultures debridement (15 Mar. regions (29 Jan. 2011) 2011) Injury in the Multiresistant Pseudomonas No signs of infection left thigh aeroginosa, multiresistent Acinetobacter baumannii only sensitive to Aztreonam and polymyxin B Peripheric multiresistent Acinetobacter No signs of infection blood baumannii only sensitive to Aztreonam and polymyxin B Central multiresistent Acinetobacter No signs of infection catheter baumannii only sensitive to Aztreonam and polymyxin B
Example 3: Treating Sepsis Associated with Urinary Infections and Concomitant Oropharynx with Terminal Gastric Carcinoma
(115) Patient Information
(116) Patient CMSFemale, 38 Years Old.
(117) Diagnosis
(118) Terminal gastric carcinoma with comorbidity of aspirative pneumonia with chemical and infection pneumonia, urinary tract and oropharyngeal infections associated with sepsis on 3 Oct. 2011. The central catheter and tracheal fluid culture was positive for Pseudomonas aeruginosa (Serratia marecescens was isolated only in tracheal aspirates) while the urine culture had isolation of multiresistant Klebsiella pneumoniae sensitive only to IMIPENEM and derivatives. At ICU the sepsis was characterized by hemodynamic changes and crash initially requiring the use of vasoactive drugs and respiratory support to control the episode. The patient also presented platelet blockade with major bleeding associated with an acute anemic condition (hemoglobin 8.6 g/dL) also had hypokalaemic, hyponatremic and lymphopenic (lymphocyte count of 3,000/microliter) condition.
(119) Prior Conventional Treatment
(120) Antibiotic therapy, vasoactive drugs, respiratory support and parenteral nutrition.
(121) Treatment with VITER
(122) The immunotherapy treatment was performed during a single session on 4 Oct. 2011 with the informed consent of the patient. VITER immunotherapy was performed as follows: Application of 0.2 mL of each one of the VITER formulation (Example 1). Attenuated yellow fever virus strain 17 D204 20 g/mL near the main 10 lymphatic territories. Application of a low dose of recombinant human interleukin 2, at a receptor saturation level with a concentration of 1 to 2 million units per meter of body surface.
Result of Immunotherapy Treatment with VITER
(123) On Jul. 10, 2011, anemia and thrombocytopenia were reversed with a platelet count of 178,000/microliter and a platelet aggregation function compatible with normal parameters. We also noted the normalization of serum electrolytes.
(124) The immunostimulation caused immunocompetence recovery and activation of the effector T loop as the lymphocyte count increased from 3,000/microliter on 3 Oct. 2011 to 9,400/microliter on Jul. 10, 2011. C-reactive protein concentration was reduced to 61 mg/l indicating control the infection. It is necessary to mention that the patient remained unther immunological treatment at Home care regimen. On Jan. 11, 2011 was diagnosed an aspiration pneumonia confirmed by chest tomography with amazing recovery before the current state of the art in 03 days of immunotherapy associated with antimicrobial treatment according to CT scan of Apr. 11, 2011 (
(125) Case Conclusion
(126) Discharge from hospital to home care on Sep. 10, 2011. The evaluated data and the clinical course of the patient indicate that the innovative immunotherapy was responsible for the amazing recovery from the critical sepsis condition the patient was in. The continuity of immunostimulatory treatment also contributes to the improvement of the patient's life quality and an amazing improvement in life expectancy. According to the state of the art this widespread and terminal cancer condition leads to death in about 1 month, while the immunostimulation of the present invention allowed for an unexpected survival of 1 year and a half, enjoying the company of relatives.
Example 4: Treating Infection (Multiresistant Bacteria of SARS in Septic Shock)
(127) Patient Information
(128) Patient AMBfemale, 39 years old.
(129) Primary Diagnosis
(130) Severe sepsis and Septic shock
(131) Secondary Diagnosis
(132) Presented as comorbity:
(133) Severe Acute Respiratory Syndrome (SARS); Shock; Acute Renal Failure; Disseminated Intravascular Coagulation; Hepatic failure signs;
Identification and Summary of the Clinical History
(134) On 19 Apr. 2007 were hospitalized with diagnosis of community pneumonia, non-produced cough and high fever. After 10 hours of hospital admission, patient got worse requiring tranferece to Intense Care Unit (ICU) with respiratory infection and septic shock characterized by: hipotension, SARS; renal and hepatic failure; Disseminated Intravascular Coagulation; serum lactate increase, hemodynamic and eletrolytes colapse.
(135) Prior Conventional Treatment
(136) On 20 Apr. 2007 were treated with Ceftriaxone and Levofloxacin. However, after clinical complication and ICU admission when became essential: i) start respiratory and hemodynamic support; ii) antimicrobial regimen replace by Meropenem with Vancomicin; iii) association of plasma transfusion 08U and IV active protein C to reverse Disseminated Intravascular Coagulation and make opsonization process possible. Inspite of all efforts patient did not experince any clinical and laboratory improvement.
(137) Proposed IRS with DECA Treatment Associated with Conventional Treatment
(138) The immunotherapy treatment was performed nine sessions starting on Apr. 21, 2011 after informed consent of the patient. DECA immunotherapy was performed as follows: Application of 0.2 mL of each one of the 10 antigenic components (1. Koch's Tuberculin ((lysate inactivated Mycobacterium bovis 0.0036 ng/mL); 2. PPD (0.0036 g/mL); 3. Lysate inactivated Staphylococcus (Staphylococcus aureus and Staphylococcus epidermidis in equal parts 6.31 g/mL); 4 Lysate inactivated Streptococcus (Streptococcus pyogenes, Streptococcus pneumonie and Enterococcus faecalis in equal parts 6.31 g/mL).; 5. Streptokinase derived from lysate inactivated and purified Streptococcus beta-hemolytic 0.404 g/mL); 6. Dornase derived from lysate inactivated and purified Streptococcus beta-hemolytic 0.101 g/mL); 7. Oidiomycin (antigenic extract of Candida albicans 6.31 g/mL); 8. Trichophytin (antigenic extract of Tricophyton spp 6.31 g/mL); 9. Lysate inactivated Escherichia coli (EPEC 6.31 g/mL); 10. Lysate inactivated Salmonella (Salmonella bongori, Salmonella enterica and Salmonella subterranea in equal parts 6.31 g/mL).
Result of Immunotherapy with IRS-DECA Associated with Conventional Treatment
(139) On 26 May 2007 serum eletrolytes and lactate reached normal levels and thrombocytopenia were reversed with a platelet count of 167,000/mm.sup.3 and a platelet aggregation function compatible with normal parameters. ON Apr. 27, 2007 SARS still very severe and start to improve. On 29 May 2007 arterial blood gas analysis saturation and pO.sub.2 were reversed evidencing hemodynamic recover. The immunostimulation caused immunocompetence recovery and activation of the effector T loop with normalized complement fractions on 28 Apr. 2007, the lymphocyte count decreased from 21.100/mm.sup.3 on 20 Apr. 2007 (that got worse to 43.700/mm.sup.3 on 22 Apr. 2007) to 11.000/mm.sup.3 on 30 Apr. 2007 when CD3, CD4 and CD8 fractions presented proper levels. The respiratory condition improve drastically after Apr. 29, 2007 and respiratory support were removed. Patient was discharged from ICU on 6 May 2007 with complete recover of severe sepsis. On 19 Apr. 2007 was diagnosed an community pneumonia confirmed by chest X-Ray of 24 Apr. 2007 (
(140) Case Conclusion
(141) Discharge from hospital on 6 May 2007. The evaluated data and the clinical course of the patient indicate that the innovative immunotherapy was responsible for the amazing recovery from the critical severe sepsis and septic shock conditions that the patient was in. The continuity of immunostimulatory treatment also contributes to the complete extinguish the severe infection and an amazing improvement in life expectancy. According to the state of the art this multiresistant bacteria of SARS in septic shock associated with renal and hepatic failure conditions leads to death in hours, while the immunostimulation of the present invention allowed for an unexpected survival with no sequel.
(142) In short, the clinical cases presented hereinabove demonstrate that high complexity illnesses and diseases, with obscure to very poor prognosis, have been addressed more properly, with advantageous and more efficient approaches through the use of the IRS compositions the present invention.
REFERENCES
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