COMPOSITION FOR TREATING A PATIENT WITH A RESPIRATORY DISEASE CAUSED BY CHRONIC INFLAMMATION, PRODUCTION METHOD, AND USE OF SAID COMPOSITION
20210161939 · 2021-06-03
Assignee
Inventors
Cpc classification
A61P29/00
HUMAN NECESSITIES
C12N2320/35
CHEMISTRY; METALLURGY
A61K31/7088
HUMAN NECESSITIES
A61K45/06
HUMAN NECESSITIES
A61K31/711
HUMAN NECESSITIES
A61K9/0073
HUMAN NECESSITIES
C12N15/113
CHEMISTRY; METALLURGY
International classification
A61K31/711
HUMAN NECESSITIES
A61K45/06
HUMAN NECESSITIES
Abstract
The invention relates to a composition for treating a patient suffering from a respiratory tract disease associated with chronic inflammations, the composition comprising at least one DNAzyme which specifically downregulates the expression of GATA-3 and/or comprising at least one DNAzyme which specifically downregulates the expression of Tbet. The composition is characterized in that the concentration of the DNAzyme in the composition is lower than 75 mg/ml. The invention also relates to a method for producing the composition according to the invention and to the use of the composition drug for treating a patient suffering from a respiratory tract disease associated with chronic inflammations.
Claims
1. A composition for treating a patient suffering from a respiratory tract disease associated with chronic inflammations, the composition comprising at least one DNAzyme which specifically downregulates the expression of GATA-3 and/or comprising at least one DNAzyme which specifically downregulates the expression of Tbet, characterized in that the concentration of the DNAzyme in the composition is lower than 75 mg/ml.
2. The composition as claimed in claim 1, characterized in that the concentration of the DNAzyme in the composition is between 20 mg/ml and 50 mg/ml.
3. The composition as claimed in claim 1, characterized in that the composition has a viscosity lower than 3.5 mPa.Math.s.
4. The composition as claimed in claim 1, characterized in that the DNAzyme is selected from a group comprising the DNAzymes hgd1 to hgd70 (SEQ ID No. 1 to SEQ ID No. 70) and/or from a group comprising the DNAzymes td1 to td78 (SEQ ID No. 71 to SEQ ID No. 148).
5. The composition as claimed in claim 4, characterized in that the DNAzyme has the sequence hgd40 GTGGATGGAggctagctacaacgaGTCTTGGAG (SEQ ID No. 40).
6. The composition as claimed in claim 1, characterized in that the composition comprises at least one nuclease inhibitor.
7. The composition as claimed in claim 6, characterized in that the nuclease inhibitor specifically inactivates deoxyribonucleases.
8. The composition as claimed in claim 1, characterized in that the composition comprises at least one salt and/or at least one cation.
9. The composition as claimed in claim 1, characterized in that the composition comprises at least one inorganic and/or organic additive and/or a solubilizer and/or a preservative.
10. A method for producing the composition as claimed in claim 1, characterized in that the method comprises at least the following steps: a) preparing a DNAzyme-containing solution, the DNAzyme concentration in the solution not exceeding 80 mg/ml; b) filtering the solution from step a) until the solution has a DNAzyme concentration of under 75 mg/ml.
11. The method as claimed in claim 10, characterized in that the method also comprises at least one of the following steps: adding the at least one nuclease inhibitor to the solution from step b); adding the at least one salt and/or the at least one cation to the solution from step b); adding the at least one inorganic and/or organic additive to the solution from step b); adding the solubilizer and/or the preservative to the solution from step b).
12. A method for treating a patient suffering from a respiratory tract disease associated with chronic inflammations, the method comprising administering a therapeutically effective amount of the composition of claim 1.
13. The method as claimed in claim 12, characterized in that the composition is administered in the form of an aerosol.
Description
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EXEMPLARY EMBODIMENTS
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TABLE-US-00003 TABLE 1 GATA-3-specific DNAzymes SEQ ID Name Sequence SEQ ID No: 1 hgd1 5′-TCGGTCAGAggctagctacaacgaTGC GTTGCT-3′ SEQ ID No: 2 hgd2 5′-GGCGTACGAggctagctacaacgaCTG CTCGGT-3′ SEQ ID No: 3 hgd3 5′-GGCGGCGTAggctagctacaacgaGAC CTGCTC-3′ SEQ ID No: 4 hgd4 5′-CTCGGGTCAggctagctacaacgaCTG GGTAGC-3′ SEQ ID No: 5 hgd5 5′-TCCTCTGCAggctagctacaacgaCGG GGTCCT-3′ SEQ ID No: 6 hgd6 5′-ACTCTGCAAggctagctacaacgaTCT GCGAGC-3′ SEQ ID No: 7 hgd7 5′-GGGCGACGAggctagctacaacgaTCT GCAATT-3′ SEQ ID No: 8 hgd8 5′-AAGGGGCGAggctagctacaacgaGAC TCTGCA-3′ SEQ ID No: 9 hgd9 5′-AAAACGGGAggctagctacaacgaCAG GTTGTA-3′ SEQ ID No: 10 hgd10 5′-AGAATAAAAggctagctacaacgaGGG ACCAGG-3′ SEQ ID No: 11 hgd11 5′-ATGGCAGAAggctagctacaacgaAAA ACGGGA-3′ SEQ ID No: 12 hgd12 5′-AACTGGGTAggctagctacaacgaGGC AGAATA-3′ SEQ ID No: 13 hgd13 5′-ATCCAAAAAggctagctacaacgaTGG GTATGG-3′ SEQ ID No: 14 hgd14 5′-AGGGGAAGAggctagctacaacgaAAA AATCCA-3′ SEQ ID No: 15 hgd15 5′-TTTTAAAAAggctagctacaacgaTAT CTTGGA-3′ SEQ ID No: 16 hgd16 5′-GTGGGGGGAggctagctacaacgaGGG AAGGCT-3′ SEQ ID No: 17 hgd17 5′-GTTGAATGAggctagctacaacgaTTG CTTTCG-3′ SEQ ID No: 18 hgd18 5′-GTCGTTGAAggctagctacaacgaGAT TTGCTT-3′ SEQ ID No: 19 hgd19 5′-GGCCCGGAAggctagctacaacgaCCG CGCGCG-3′ SEQ ID No: 20 hgd20 5′-TCACCTCCAggctagctacaacgaGGC CTCGGC-3′ SEQ ID No: 21 hgd21 5′-CCGCCGTCAggctagctacaacgaCTC CATGGC-3′ SEQ ID No: 22 hgd22 5′-GGTGGCTCAggctagctacaacgaCCA GCGCGG-3′ SEQ ID No: 23 hgd23 5′-CGTTGAGCAggctagctacaacgaGGC GGGGTG-3′ SEQ ID No: 24 hgd24 5′-CCGCGTCCAggctagctacaacgaGTA GGAGTG-3′ SEQ ID No: 25 hgd25 5′-CAGCGGGTAggctagctacaacgaTGC GCCGCG-3′ SEQ ID No: 26 hgd26 5′-GCACATCCAggctagctacaacgaCTC CTCCGG-3′ SEQ ID No: 27 hgd27 5′-AAAAGCACAggctagctacaacgaCCA CCTCCT-3′ SEQ ID No: 28 hgd28 5′-TAAAAAGCAggctagctacaacgaATC CACCTC-3′ SEQ ID No: 29 hgd29 5′-GACCGTCGAggctagctacaacgaGTT AAAAAG-3′ SEQ ID No: 30 hgd30 5′-TTGCCTTGAggctagctacaacgaCGT CGATGT-3′ SEQ ID No: 31 hgd31 5′-AGGGCGGGAggctagctacaacgaGTG GTTGCC-3′ SEQ ID No: 32 hgd32 5′-TGGCCCTGAggctagctacaacgaCGA GTTTCC-3′ SEQ ID No: 33 hgd33 5′-ACCTCTGCAggctagctacaacgaCGT GGCCCT-3′ SEQ ID No: 34 hgd34 5′-CGGAGGGTAggctagctacaacgaCTC TGCACC-3′ SEQ ID No: 35 hgd35 5′-GGCGGCACAggctagctacaacgaCTG GCTCCC-3′ SEQ ID No: 36 hgd36 5′-CGGGCGGCAggctagctacaacgaACC TGGCTC-3′ SEQ ID No: 37 hgd37 5′-AGGGATCCAggctagctacaacgaGAA GCAGAG-3′ SEQ ID No: 38 hgd38 5′-GGGTAGGGAggctagctacaacgaCCA TGAAGC-3′ SEQ ID No: 39 hgd39 5′-GGGCTGAGAggctagctacaacgaTCC AGGGGG-3′ SEQ ID No: 40 hgd40 5′-GTGGATGGAggctagctacaacgaGTC TTGGAG-3′ SEQ ID No: 41 hgd41 5′-CGTGGTGGAggctagctacaacgaGGA CGTCTT-3′ SEQ ID No: 42 hgd42 5′-GGGGGTAGAggctagctacaacgaGGA GAGGGG-3′ SEQ ID No: 43 hgd43 5′-GGAGGAGGAggctagctacaacgaGAG GCCGGG-3′ SEQ ID No: 44 hgd44 5′-GCCCCCCGAggctagctacaacgaAAG GAGGAG-3′ SEQ ID No: 45 hgd45 5′-CCGGGGAGAggctagctacaacgaGTC CTTCGG-3′ SEQ ID No: 46 hgd46 5′-GGACAGCGAggctagctacaacgaGGG TCCGGG-3′ SEQ ID No: 47 hgd47 5′-TGGGGTGGAggctagctacaacgaAGC GATGGG-3′ SEQ ID No: 48 hgd48 5′-CTTGAGGCAggctagctacaacgaTCT TTCTCG-3′ SEQ ID No: 49 hgd49 5′-CACCTGGTAggctagctacaacgaTTG AGGCAC-3′ SEQ ID No: 50 hgd50 5′-GCAGGGGCAggctagctacaacgaCTG GTACTT-3′ SEQ ID No: 51 hgd51 5′-CCAGCTTCAggctagctacaacgaGCT GTCGGG-3′ SEQ ID No: 52 hgd52 5′-GTGGGACGAggctagctacaacgaTCC AGCTTC-3′ SEQ ID No: 53 hgd53 5′-GGAGTGGGAggctagctacaacgaGAC TCCAGC-3′ SEQ ID No: 54 hgd54 5′-ATGCTGCCAggctagctacaacgaGGG AGTGGG-3′ SEQ ID No: 55 hgd55 5′-GGGCGGTCAggctagctacaacgaGCT GCCACG-3′ SEQ ID No: 56 hgd56 5′-GAGGCTCCAggctagctacaacgaCCA GGGCGG-3′ SEQ ID No: 57 hgd57 5′-GTGGGTCGAggctagctacaacgaGAG GAGGCT-3′ SEQ ID No: 58 hgd58 5′-AGGTGGTGAggctagctacaacgaGGG GTGGTG-3′ SEQ ID No: 59 hgd59 5′-ACTCGGGCAggctagctacaacgaGTA GGGCGG-3′ SEQ ID No: 60 hgd60 5′-GGAGCTGTAggctagctacaacgaTCG GGCACG-3′ SEQ ID No: 61 hgd61 5′-GGACTTGCAggctagctacaacgaCCG AAGCCG-3′ SEQ ID No: 62 hgd62 5′-GGGCCTGGAggctagctacaacgaTTG CATCCG-3′ SEQ ID No: 63 hgd63 5′-TGTGCTGGAggctagctacaacgaCGG GCCTTG-3′ SEQ ID No: 64 hgd64 5′-GTTCACACAggctagctacaacgaTCC CTGCCT-3′ SEQ ID No: 65 hgd65 5′-CAGTTCACAggctagctacaacgaACT CCCTGC-3′ SEQ ID No: 66 hgd66 5′-CACAGTTCAggctagctacaacgaACA CTCCCT-3′ SEQ ID No: 67 hgd67 5′-GTTGCCCCAggctagctacaacgaAGT TCACAC-3′ SEQ ID No: 68 hgd68 5′-TCGCCGCCAggctagctacaacgaAGT GGGGTC-3′ SEQ ID No: 69 hgd69 5′-CCCGTGCCAggctagctacaacgaCTC GCCGCC-3′ SEQ ID No: 70 hgd70 5′-GGCGTTGCAggctagctacaacgaAGG TAGTGT-3′
TABLE-US-00004 TABLE 2 Tbet-specific DNAzymes SEQ ID Name Sequence SEQ ID No: 71 td1 5′-TGGCTTCTAggctagctacaacgaGCC CTCGTC-3′ SEQ ID No: 72 td2 5′-GGGCTCTGAggctagctacaacgaGCC TGGCTT-3′ SEQ ID No: 73 td3 5′-GGGACCCCAggctagctacaacgaCGG AGCCCG-3′ SEQ ID No: 74 td4 5′-GGTGGGGGAggctagctacaacgaCCC ACCGGA-3′ SEQ ID No: 75 td5 5′-GGCGGGGGAggctagctacaacgaCCG AGGGCC-3′ SEQ ID No: 76 td6 5′-GGGCTGGGAggctagctacaacgaGGG CAGGGA-3′ SEQ ID No: 77 td7 5′-CGTCGAGGAggctagctacaacgaCCG CCCCTC-3′ SEQ ID No: 78 td8 5′-GGGCTGGCAggctagctacaacgaCTT CCCGTA-3′ SEQ ID No: 79 td9 5′-CGATGCCCAggctagctacaacgaCCG GGGCGG-3′ SEQ ID No: 80 td10 5′-GCTCCACGAggctagctacaacgaGCC CATCCG-3′ SEQ ID No: 81 td11 5′-CCGGCTCCAggctagctacaacgaGAT GCCCAT-3′ SEQ ID No: 82 td12 5′-TCTCCGCAAggctagctacaacgaCCG GCTCCA-3′ SEQ ID No: 83 td13 5′-CCGTCAGCAggctagctacaacgaGTC TCCGCA-3′ SEQ ID No: 84 td14 5′-TCCCCGGCAggctagctacaacgaCGG CTCGGT-3′ SEQ ID No: 85 td15 5′-CCCCCGCGAggctagctacaacgaGCT CGTCCG-3′ SEQ ID No: 86 td16 5′-GTAGGGAGAggctagctacaacgaCCC AGGCTG-3′ SEQ ID No: 87 td17 5′-GGGCGGGCAggctagctacaacgaCAA GGCGCC-3′ SEQ ID No: 88 td18 5′-CGGGAAGGAggctagctacaacgaTCG CCCGCG-3′ SEQ ID No: 89 td19 5′-TAGTCCTCAggctagctacaacgaGCG GCCCCG-3′ SEQ ID No: 90 td20 5′-TCCCCGACAggctagctacaacgaCTC CAGTCC-3′ SEQ ID No: 91 td21 5′-TTTCCCCGAggctagctacaacgaACC TCCAGT-3′ SEQ ID No: 92 td22 5′-TGAGCGCGAggctagctacaacgaCCT CAGTTT-3′ SEQ ID No: 93 td23 5′-GGACCACAAggctagctacaacgaAGG TGGTTG-3′ SEQ ID No: 94 td24 5′-CTTGGACCAggctagctacaacgaAAC AGGTGG-3′ SEQ ID No: 95 td25 5′-AAACTTGGAggctagctacaacgaCAC AACAGG-3′ SEQ ID No: 96 td26 5′-CTGATTAAAggctagctacaacgaTTG GACCAC-3′ SEQ ID No: 97 td27 5′-TGGTGCTGAggctagctacaacgaTAA ACTTGG-3′ SEQ ID No: 98 td28 5′-TGATGATCAggctagctacaacgaCTC TGTCTG-3′ SEQ ID No: 99 td29 5′-TGGTGATGAggctagctacaacgaCAT CTCTGT-3′ SEQ ID No: 100 td30 5′-GCTTGGTGAggctagctacaacgaGAT CATCTC-3′ SEQ ID No: 101 td31 5′-ATGGGAACAggctagctacaacgaCCG CCGTCC-3′ SEQ ID No: 102 td32 5′-GAATGGGAAggctagctacaacgaATC CGCCGT-3′ SEQ ID No: 103 td33 5′-TGACAGGAAggctagctacaacgaGGG AACATC-3′ SEQ ID No: 104 td34 5′-AGTAAATGAggctagctacaacgaAGG AATGGG-3′ SEQ ID No: 105 td35 5′-CACAGTAAAggctagctacaacgaGAC AGGAAT-3′ SEQ ID No: 106 td36 5′-GCCCGGCCAggctagctacaacgaAGT AAATGA-3′ SEQ ID No: 107 td37 5′-CCACAAACAggctagctacaacgaCCT GTAGTG-3′ SEQ ID No: 108 td38 5′-GTCCACAAAggctagctacaacgaATC CTGTAG-3′ SEQ ID No: 109 td39 5′-CCACGTCCAggctagctacaacgaAAA CATCCT-3′ SEQ ID No: 110 td40 5′-CCAAGACCAggctagctacaacgaGTC CACAAA-3′ SEQ ID No: 111 td41 5′-CCACCAAGAggctagctacaacgaCAC GTCCAC-3′ SEQ ID No: 112 td42 5′-GCTGGTCCAggctagctacaacgaCAA GACCAC-3′ SEQ ID No: 113 td43 5′-GCTCTGGTAggctagctacaacgaCGC CAGTGG-3′ SEQ ID No: 114 td44 5′-CTGCACCCAggctagctacaacgaTTG CCGCTC-3′ SEQ ID No: 115 td45 5′-CACACTGCAggctagctacaacgaCCA CTTGCC-3′ SEQ ID No: 116 td46 5′-CTTTCCACAggctagctacaacgaTGC ACCCAC-3′ SEQ ID No: 117 td47 5′-GCCTTTCCAggctagctacaacgaACT GCACCC-3′ SEQ ID No: 118 td48 5′-TTCCTGGCAggctagctacaacgaGCT GCCCTC-3′ SEQ ID No: 119 td49 5′-GTGGACGTAggctagctacaacgaAGG CGGTTT-3′ SEQ ID No: 120 td50 5′-CCGGGTGGAggctagctacaacgaGTA CAGGCG-3′ SEQ ID No: 121 td51 5′-CCTGGCGCAggctagctacaacgaCCA GTGCGC-3′ SEQ ID No: 122 td52 5′-CAAATGAAAggctagctacaacgaTTC CTGGCG-3′ SEQ ID No: 123 td53 5′-TTTCCCAAAggctagctacaacgaGAA ACTTCC-3′ SEQ ID No: 124 td54 5′-ATTGTTGGAggctagctacaacgaGCC CCCTTG-3′ SEQ ID No: 125 td55 5′-TGGGTCACAggctagctacaacgaTGT TGGACG-3′ SEQ ID No: 126 td56 5′-TCTGGGTCAggctagctacaacgaATT GTTGGA-3′ SEQ ID No: 127 td57 5′-GCACAATCAggctagctacaacgaCTG GGTCAC-3′ SEQ ID No: 128 td58 5′-GGAGCACAAggctagctacaacgaCAT CTGGGT-3′ SEQ ID No: 129 td59 5′-ACTGGAGCAggctagctacaacgaAAT CATCTG-3′ SEQ ID No: 130 td60 5′-ATGGAGGGAggctagctacaacgaTGG AGCACA-3′ SEQ ID No: 131 td61 5′-TGGTACTTAggctagctacaacgaGGA GGGACT-3′ SEQ ID No: 132 td62 5′-GGGCTGGTAggctagctacaacgaTTA TGGAGG-3′ SEQ ID No: 133 td63 5′-TCAACGATAggctagctacaacgaGCA GCCGGG-3′ SEQ ID No: 134 td64 5′-CCTCAACGAggctagctacaacgaATG CAGCCG-3′ SEQ ID No: 135 td65 5′-TCACCTCAAggctagctacaacgaGAT ATGCAG-3′ SEQ ID No: 136 td66 5′-CGTCGTTCAggctagctacaacgaCTC AACGAT-3′ SEQ ID No: 137 td67 5′-GTAAAGATAggctagctacaacgaGCG TGTTGG-3′ SEQ ID No: 138 td68 5′-AAGTAAAGAggctagctacaacgaATG CGTGTT-3′ SEQ ID No: 139 td69 5′-GGCAATGAAggctagctacaacgaTGG GTTTCT-3′ SEQ ID No: 140 td70 5′-TCACGGCAAggctagctacaacgaGAA CTGGGT-3′ SEQ ID No: 141 td71 5′-AGGCAGTCAggctagctacaacgaGGC AATGAA-3′ SEQ ID No: 142 td72 5′-ATCTCGGCAggctagctacaacgaTCT GGTAGG-3′ SEQ ID No: 143 td73 5′-GCTGAGTAAggctagctacaacgaCTC GGCATT-3′ SEQ ID No: 144 td74 5′-TATTATCAAggctagctacaacgaTTT CAGCTG-3′ SEQ ID No: 145 td75 5′-GGGTTATTAggctagctacaacgaCAA TTTTCA-3′ SEQ ID No: 146 td76 5′-AAGGGGTTAggctagctacaacgaTAT CAATTT-3′ SEQ ID No: 147 td77 5′-CTCCCGGAAggctagctacaacgaCCT TTGGCA-3′ SEQ ID No: 148 td78 5′-GTACATGGAggctagctacaacgaTCA AAGTTC-3′
TABLE-US-00005 TABLE 3 Example of a composition according to the invention Substance [% w/w] DNAzyme 0.01-0.75 Nuclease inhibitor variable Example: DNase inhibitor
TABLE-US-00006 TABLE 4 Possible additional components of the composition from Table 3 Substance [% w/w] Salt and/or cation variable Example: Na, Mg, K, Li, Ca, Fe, Cu, Ag, HPO.sub.4.sup.2−, H.sub.2PO.sub.4.sup.−, EDTA variable TRIS variable Solubilizer variable Example: glycerol derivatives, polyethylene glycols, lecithins Preservative variable Example: paraben
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[0059] The graph from
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[0061] In the case of a viscosity of over 3.5 mPa.Math.s, the pressure which a common inhaler would have to exert for atomization of the composition is too high. This can lead to the inhalers usually used for the treatment of corresponding patients blocking up or clogging up after just a short. This risk is significantly minimized by a composition, the DNAzyme concentration of which is lower than 75 mg/ml.
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[0064] The measurement results from
[0065] It is consequently apparent that the invention relates to a composition for treating a patient suffering from a respiratory tract disease associated with chronic inflammations, the composition comprising at least one DNAzyme which specifically downregulates the expression of GATA-3 and/or comprising at least one DNAzyme which specifically downregulates the expression of Tbet. The composition is characterized in that the concentration of the DNAzyme in the composition is lower than 75 mg/ml, the concentration of the DNAzyme in the composition being preferably between 20 mg/ml and 50 mg/ml.
[0066] The invention also relates to a method for producing the composition according to the invention, which composition comprises at least one DNAzyme which specifically downregulates the expression of GATA-3 and/or comprises at least one DNAzyme which specifically downregulates the expression of Tbet. Here too, what is provided is that the concentration of the DNAzyme in the composition is lower than 75 mg/ml, and is preferably lower than 3.5 mPa.Math.s.
[0067] The use of the composition is directed to a drug which is used for treating a patient suffering from a respiratory tract disease associated with chronic inflammations.