ES2241124T3 - Actividad inhibidora de serin-proteinasa mediante tetraciclina hidrofoba. - Google Patents
Actividad inhibidora de serin-proteinasa mediante tetraciclina hidrofoba.Info
- Publication number
- ES2241124T3 ES2241124T3 ES98908747T ES98908747T ES2241124T3 ES 2241124 T3 ES2241124 T3 ES 2241124T3 ES 98908747 T ES98908747 T ES 98908747T ES 98908747 T ES98908747 T ES 98908747T ES 2241124 T3 ES2241124 T3 ES 2241124T3
- Authority
- ES
- Spain
- Prior art keywords
- tetracycline
- cmt
- use according
- activity
- elastase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000002401 inhibitory effect Effects 0.000 title abstract description 15
- 239000004098 Tetracycline Substances 0.000 claims abstract description 79
- 235000019364 tetracycline Nutrition 0.000 claims abstract description 76
- 150000003522 tetracyclines Chemical class 0.000 claims abstract description 76
- 229960002180 tetracycline Drugs 0.000 claims abstract description 48
- 230000000694 effects Effects 0.000 claims abstract description 47
- 229930101283 tetracycline Natural products 0.000 claims abstract description 45
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 20
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 17
- 239000002537 cosmetic Substances 0.000 claims abstract description 13
- 108010028275 Leukocyte Elastase Proteins 0.000 claims description 28
- 102000016799 Leukocyte elastase Human genes 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 6
- 230000006866 deterioration Effects 0.000 claims description 6
- 206010014561 Emphysema Diseases 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 231100000331 toxic Toxicity 0.000 claims description 5
- 230000002588 toxic effect Effects 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000019693 Lung disease Diseases 0.000 claims description 4
- 208000004221 Multiple Trauma Diseases 0.000 claims description 4
- 208000023637 Multiple injury Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 208000017169 kidney disease Diseases 0.000 claims description 4
- 231100000614 poison Toxicity 0.000 claims description 4
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
- 208000033626 Renal failure acute Diseases 0.000 claims description 3
- 201000011040 acute kidney failure Diseases 0.000 claims description 3
- 208000012998 acute renal failure Diseases 0.000 claims description 3
- 239000002574 poison Substances 0.000 claims description 3
- 206010069351 acute lung injury Diseases 0.000 claims description 2
- 238000002485 combustion reaction Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000779 smoke Substances 0.000 claims description 2
- 230000035882 stress Effects 0.000 claims description 2
- 239000003440 toxic substance Substances 0.000 claims description 2
- 206010038687 Respiratory distress Diseases 0.000 claims 1
- 102000012479 Serine Proteases Human genes 0.000 abstract description 18
- 108010022999 Serine Proteases Proteins 0.000 abstract description 18
- 102000016387 Pancreatic elastase Human genes 0.000 abstract description 16
- 108010067372 Pancreatic elastase Proteins 0.000 abstract description 16
- 230000006378 damage Effects 0.000 abstract description 16
- 238000000034 method Methods 0.000 abstract description 12
- 210000000265 leukocyte Anatomy 0.000 abstract description 7
- 206010061218 Inflammation Diseases 0.000 abstract description 3
- 230000004054 inflammatory process Effects 0.000 abstract description 3
- 239000003001 serine protease inhibitor Substances 0.000 abstract description 2
- 101710187074 Serine proteinase inhibitor Proteins 0.000 abstract 1
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 48
- 102100033174 Neutrophil elastase Human genes 0.000 description 46
- 229940040944 tetracyclines Drugs 0.000 description 31
- 239000000758 substrate Substances 0.000 description 27
- 230000005764 inhibitory process Effects 0.000 description 26
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 23
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 23
- 210000002744 extracellular matrix Anatomy 0.000 description 23
- 239000003112 inhibitor Substances 0.000 description 23
- 210000000440 neutrophil Anatomy 0.000 description 18
- 230000015556 catabolic process Effects 0.000 description 17
- 241000700159 Rattus Species 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 16
- 238000006731 degradation reaction Methods 0.000 description 15
- 230000001404 mediated effect Effects 0.000 description 15
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 14
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 14
- 210000001519 tissue Anatomy 0.000 description 13
- 230000003024 amidolytic effect Effects 0.000 description 12
- 238000003556 assay Methods 0.000 description 10
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 102000035195 Peptidases Human genes 0.000 description 9
- 108091005804 Peptidases Proteins 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 230000003115 biocidal effect Effects 0.000 description 8
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 8
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 7
- -1 4- (methylsulfinyl) phenyl Chemical group 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 229960003722 doxycycline Drugs 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000000099 in vitro assay Methods 0.000 description 6
- 230000008595 infiltration Effects 0.000 description 6
- 238000001764 infiltration Methods 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 208000037816 tissue injury Diseases 0.000 description 6
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 5
- 102000015636 Oligopeptides Human genes 0.000 description 5
- 108010038807 Oligopeptides Proteins 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000000845 anti-microbial effect Effects 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 229960004023 minocycline Drugs 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 4
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003602 elastase inhibitor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- 239000004100 Oxytetracycline Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- BVFDLIAWTKFZQD-JXVDNWKRSA-N cmt-8 Chemical compound O=C1C2=C(O)C=CC=C2C(C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)C[C@@H]1C2O BVFDLIAWTKFZQD-JXVDNWKRSA-N 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 210000002808 connective tissue Anatomy 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000004195 gingiva Anatomy 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000003448 neutrophilic effect Effects 0.000 description 3
- 229960000625 oxytetracycline Drugs 0.000 description 3
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 3
- 235000019366 oxytetracycline Nutrition 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 208000028169 periodontal disease Diseases 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229940096998 ursolic acid Drugs 0.000 description 3
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 3
- XCCHQGIGHCRZOS-KBKZQPOHSA-N (4as,5as,6s,12ar)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@@](C)(O)[C@@H](C[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)C3)(O)C3=O)C3=C(O)C2=C1O XCCHQGIGHCRZOS-KBKZQPOHSA-N 0.000 description 2
- OWFJMIVZYSDULZ-DVJPNYBFSA-N (4r,4ar,5s,5ar,6s,12ar)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O OWFJMIVZYSDULZ-DVJPNYBFSA-N 0.000 description 2
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 2
- 101100221122 Caenorhabditis elegans cmt-1 gene Proteins 0.000 description 2
- 102000004173 Cathepsin G Human genes 0.000 description 2
- 108090000617 Cathepsin G Proteins 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 102000016942 Elastin Human genes 0.000 description 2
- 108010014258 Elastin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102100030635 Leukocyte elastase inhibitor Human genes 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102100030411 Neutrophil collagenase Human genes 0.000 description 2
- 101710118230 Neutrophil collagenase Proteins 0.000 description 2
- 206010053159 Organ failure Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000038016 acute inflammation Diseases 0.000 description 2
- 230000006022 acute inflammation Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229960004050 aminobenzoic acid Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000008614 cellular interaction Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002849 elastaseinhibitory effect Effects 0.000 description 2
- 229920002549 elastin Polymers 0.000 description 2
- 102000036444 extracellular matrix enzymes Human genes 0.000 description 2
- 108091007167 extracellular matrix enzymes Proteins 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000000224 granular leucocyte Anatomy 0.000 description 2
- 102000052502 human ELANE Human genes 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000003591 leukocyte elastase inhibitor Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000006225 natural substrate Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 201000001245 periodontitis Diseases 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229940072172 tetracycline antibiotic Drugs 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 150000003648 triterpenes Chemical class 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- MWUTTXATIMURBN-VSAOOKSHSA-N (4aS,5aS,6S,12aR)-3,6,10,11-tetrahydroxy-6-methyl-1,12-dioxo-4a,5,5a,12a-tetrahydro-4H-tetracene-2-carboxamide Chemical compound C[C@]1(O)[C@H]2C[C@H]3CC(O)=C(C(N)=O)C(=O)[C@H]3C(=O)C2=C(O)c2c(O)cccc12 MWUTTXATIMURBN-VSAOOKSHSA-N 0.000 description 1
- XIYOPDCBBDCGOE-IWVLMIASSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O XIYOPDCBBDCGOE-IWVLMIASSA-N 0.000 description 1
- 125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 description 1
- GVUGADOWXGKRAE-SRVKXCTJSA-N 4-[[(2s)-1-[[(2s)-1-[[(2s)-1-(4-nitroanilino)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 GVUGADOWXGKRAE-SRVKXCTJSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000001187 Collagen Type III Human genes 0.000 description 1
- 108010069502 Collagen Type III Proteins 0.000 description 1
- 102000004266 Collagen Type IV Human genes 0.000 description 1
- 108010042086 Collagen Type IV Proteins 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 229920005682 EO-PO block copolymer Polymers 0.000 description 1
- 229940122858 Elastase inhibitor Drugs 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000013382 Gelatinases Human genes 0.000 description 1
- 108010026132 Gelatinases Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 1
- 101001010513 Homo sapiens Leukocyte elastase inhibitor Proteins 0.000 description 1
- 101710091916 Leukocyte elastase inhibitor Proteins 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 206010072574 Periodontal inflammation Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241001522306 Serinus serinus Species 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical class [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- WYWZRNAHINYAEF-AWEZNQCLSA-N [(2s)-2-ethylhexyl] 4-(dimethylamino)benzoate Chemical compound CCCC[C@H](CC)COC(=O)C1=CC=C(N(C)C)C=C1 WYWZRNAHINYAEF-AWEZNQCLSA-N 0.000 description 1
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000003255 anti-acne Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004475 chlortetracycline Drugs 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- HISOCSRUFLPKDE-KLXQUTNESA-N cmt-2 Chemical compound C1=CC=C2[C@](O)(C)C3CC4C(N(C)C)C(O)=C(C#N)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O HISOCSRUFLPKDE-KLXQUTNESA-N 0.000 description 1
- 230000007691 collagen metabolic process Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000004177 elastic tissue Anatomy 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000516 lung damage Toxicity 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940042016 methacycline Drugs 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 230000006959 non-competitive inhibition Effects 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229960002638 padimate o Drugs 0.000 description 1
- IJTNSXPMYKJZPR-UHFFFAOYSA-N parinaric acid Chemical compound CCC=CC=CC=CC=CCCCCCCCC(O)=O IJTNSXPMYKJZPR-UHFFFAOYSA-N 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 150000002966 pentacyclic triterpenoids Chemical class 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 210000002379 periodontal ligament Anatomy 0.000 description 1
- 210000004261 periodontium Anatomy 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- AJENTGJUWPNAEZ-UHFFFAOYSA-N propane-1,2-diol;propan-2-ol Chemical compound CC(C)O.CC(O)CO AJENTGJUWPNAEZ-UHFFFAOYSA-N 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- ORUDTFXLZCCWNY-UHFFFAOYSA-N pyrene-1,2,3-trisulfonic acid Chemical compound C1=CC=C2C=CC3=C(S(O)(=O)=O)C(S(=O)(=O)O)=C(S(O)(=O)=O)C4=CC=C1C2=C43 ORUDTFXLZCCWNY-UHFFFAOYSA-N 0.000 description 1
- HAPZIXGMIWJCJF-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid;sodium Chemical compound [Na].OC(=O)N1CCCC1 HAPZIXGMIWJCJF-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960003600 silver sulfadiazine Drugs 0.000 description 1
- UEJSSZHHYBHCEL-UHFFFAOYSA-N silver(1+) sulfadiazinate Chemical compound [Ag+].C1=CC(N)=CC=C1S(=O)(=O)[N-]C1=NC=CC=N1 UEJSSZHHYBHCEL-UHFFFAOYSA-N 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940063650 terramycin Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 229940126702 topical medication Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US816551 | 1986-01-06 | ||
| US08/816,551 US5773430A (en) | 1997-03-13 | 1997-03-13 | Serine proteinase inhibitory activity by hydrophobic tetracycline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2241124T3 true ES2241124T3 (es) | 2005-10-16 |
Family
ID=25220936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98908747T Expired - Lifetime ES2241124T3 (es) | 1997-03-13 | 1998-02-26 | Actividad inhibidora de serin-proteinasa mediante tetraciclina hidrofoba. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5773430A (enExample) |
| EP (1) | EP0975349B1 (enExample) |
| JP (1) | JP4339411B2 (enExample) |
| KR (1) | KR100530683B1 (enExample) |
| AT (1) | ATE292972T1 (enExample) |
| AU (1) | AU733308B2 (enExample) |
| CA (1) | CA2283071C (enExample) |
| DE (1) | DE69829748T2 (enExample) |
| DK (1) | DK0975349T3 (enExample) |
| ES (1) | ES2241124T3 (enExample) |
| NZ (1) | NZ337578A (enExample) |
| PT (1) | PT975349E (enExample) |
| WO (1) | WO1998040079A1 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6608112B1 (en) * | 1997-05-20 | 2003-08-19 | The Trustees Of Columbia University In The City Of New York | Use of metalloproteinase inhibitors in the treatment and prevention of pulmonary emphysema |
| US5977091A (en) * | 1998-09-21 | 1999-11-02 | The Research Foundation Of State University Of New York | Method of preventing acute lung injury |
| US5998390A (en) * | 1998-09-28 | 1999-12-07 | The Research Foundation Of State University Of New York | Combination of bisphosphonate and tetracycline |
| US6946453B2 (en) | 1998-11-18 | 2005-09-20 | Collagenex Pharmaceuticals, Inc. | 4-dedimethylaminotracycline derivatives |
| US6506740B1 (en) | 1998-11-18 | 2003-01-14 | Robert A. Ashley | 4-dedimethylaminotetracycline derivatives |
| US6887678B2 (en) * | 1998-12-02 | 2005-05-03 | Cindy L. Bristow | Method for the quantitative determination of proteinase inhibitors |
| WO2000066107A2 (en) * | 1999-04-30 | 2000-11-09 | Apt Pharmaceuticals, L.L.C. | Antimalarian agents for the treatment of asthma |
| GB0004531D0 (en) * | 2000-02-25 | 2000-04-19 | Richards Andrew J M | The treatment of respiratory diseases |
| US6627785B1 (en) * | 2000-02-29 | 2003-09-30 | Virginia Commwealth University | Wound dressings with protease-lowering activity |
| US6503892B2 (en) | 2000-04-26 | 2003-01-07 | New England Medical Center Hospitals Inc. | Method of using matrix metalloproteinase inhibitors in filtering blebs following glaucoma filtering surgery and in the treatment of ischemic damage to the retina and optic nerve |
| US20020132798A1 (en) * | 2000-06-16 | 2002-09-19 | Nelson Mark L. | 7-phenyl-substituted tetracycline compounds |
| US7247704B2 (en) * | 2000-12-18 | 2007-07-24 | Arriva Pharmaceuticals, Inc. | Multifunctional protease inhibitors and their use in treatment of disease |
| AU2002256092C1 (en) * | 2001-04-05 | 2009-10-15 | Collagenex Pharmaceuticals, Inc. | Controlled delivery of tetracycline compounds and tetracycline derivatives |
| EP1801240A1 (en) * | 2001-06-05 | 2007-06-27 | Auckland Uniservices Limited | Methods and compositions for assessment of pulmonary function and disorders |
| US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
| EP2332546A1 (en) | 2001-07-13 | 2011-06-15 | Paratek Pharmaceuticals, Inc. | Tetracyclines for the treatment of stroke |
| US20030181371A1 (en) * | 2001-12-28 | 2003-09-25 | Angiotech Pharmaceuticals, Inc. | Compositions and methods of using collajolie |
| EP2311797A1 (en) | 2002-01-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | 4-dedimethylamino tetracycline compounds |
| EA201000491A1 (ru) | 2002-03-08 | 2010-08-30 | Паратек Фармасьютикалс, Инк. | Аминометилзамещенные тетрациклиновые соединения |
| WO2003079984A2 (en) | 2002-03-21 | 2003-10-02 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| EA012136B1 (ru) | 2002-07-12 | 2009-08-28 | Пэрэтек Фамэсьютикэлс, Инк. | Замещенные соединения тетрациклина, фармацевтическая композиция и способ лечения чувствительного к тетрациклину состояния у субъекта |
| US20040092491A1 (en) * | 2002-11-09 | 2004-05-13 | The Research Foundation Of State University Of New York | Method of treating sepsis-induced ARDS |
| JP5586123B2 (ja) * | 2003-04-07 | 2014-09-10 | スパーナス ファーマシューティカルズ インコーポレイテッド | テトラサイクリンの1日1回製剤 |
| CA2526222A1 (en) * | 2003-05-16 | 2004-12-02 | Arriva Pharmaceuticals, Inc. | Treatment of respiratory disease associated with matrix metalloprotease inhibitors |
| EP1648859B1 (en) | 2003-07-09 | 2013-02-27 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| JP4738333B2 (ja) | 2003-07-09 | 2011-08-03 | パラテック ファーマシューティカルズ インコーポレイテッド | 9−アミノメチルテトラサイクリン化合物のプロドラッグ |
| EP2332904A3 (en) | 2004-01-15 | 2012-04-11 | Paratek Pharmaceuticals, Inc. | Derivatives of tetracycline compounds |
| EP2284152A3 (en) | 2004-10-25 | 2011-10-05 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| CA2585418A1 (en) | 2004-10-25 | 2006-05-04 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| CA2608142A1 (en) * | 2005-05-10 | 2006-11-16 | Synergenz Bioscience Limited | Methods and compositions for assessment of pulmonary function and disorders |
| JP2008545390A (ja) * | 2005-05-19 | 2008-12-18 | シナージェンズ バイオサイエンス リミティド | 遺伝的多型を用いた肺癌を発達させるリスクの評価方法 |
| AU2006248189A1 (en) * | 2005-05-20 | 2006-11-23 | Synergenz Bioscience Limited | Methods of analysis of polymorphisms and uses thereof |
| AU2006272698B2 (en) * | 2005-07-21 | 2012-11-01 | Paratek Pharmaceuticals, Inc. | 10-substituted tetracyclines and methods of use thereof |
| US8795730B2 (en) * | 2006-01-31 | 2014-08-05 | David John Vachon | Compositions and methods for promoting the healing of tissue of multicellular organisms |
| ES2548261T3 (es) | 2006-12-21 | 2015-10-15 | Paratek Pharmaceuticals, Inc. | Derivados de tetraciclina para el tratamiento de infecciones bacterianas, virales y parasitarias |
| AU2007338681B2 (en) | 2006-12-21 | 2013-09-26 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of inflammatory skin disorders |
| WO2008134048A2 (en) * | 2007-04-27 | 2008-11-06 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing and purifying aminoalkyl tetracycline compounds |
| CN101784517A (zh) * | 2007-07-06 | 2010-07-21 | 帕拉特克药品公司 | 合成取代的四环素化合物的方法 |
| TW202021946A (zh) * | 2008-05-19 | 2020-06-16 | 美商派洛泰克藥物股份有限公司 | 四環素化合物之甲苯磺酸鹽及同素異形體 |
| ES2655911T3 (es) | 2008-08-08 | 2018-02-22 | Tetraphase Pharmaceuticals, Inc. | Compuestos de tetraciclina sustituidos con C7-fluoro |
| NZ610356A (en) | 2008-08-28 | 2015-03-27 | Astute Medical Inc | Methods and compositions for diagnosis and prognosis of renal injury and renal failure |
| ES2627772T3 (es) | 2009-05-08 | 2017-07-31 | Tetraphase Pharmaceuticals, Inc. | Compuestos de tetraciclina |
| JP5944825B2 (ja) | 2009-08-28 | 2016-07-05 | テトラフェース ファーマシューティカルズ,インコーポレイテッド | テトラサイクリン化合物 |
| JP5820462B2 (ja) | 2010-03-31 | 2015-11-24 | テトラフェース ファーマシューティカルズ,インコーポレイテッド | 多環式テトラサイクリン化合物 |
| BR112015004523B1 (pt) | 2012-08-31 | 2020-08-04 | Tetraphase Pharmaceuticals, Inc | Compostos de tetraciclina, composições farmacêuticas e seus usos |
| ES2978198T3 (es) | 2016-10-19 | 2024-09-06 | Tetraphase Pharmaceuticals Inc | Formas cristalinas de eravaciclina |
| WO2020097450A1 (en) | 2018-11-09 | 2020-05-14 | Tetraphase Pharmaceuticals, Inc. | Polymorphic forms of a compound and uses thereof |
| WO2023133096A1 (en) * | 2022-01-04 | 2023-07-13 | The Research Foundation For The State University Of New York | Cmt-3 formulations and methods of using the same |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4704383A (en) * | 1983-12-29 | 1987-11-03 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| US4925833A (en) * | 1983-12-29 | 1990-05-15 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of osteoporosis |
| USRE34656E (en) * | 1983-12-29 | 1994-07-05 | The Research Foundation Of State University Of New York | Use of tetracycline to enhance bone protein synthesis and/or treatment of bone deficiency |
| US4666897A (en) * | 1983-12-29 | 1987-05-19 | Research Foundation Of State University | Inhibition of mammalian collagenolytic enzymes by tetracyclines |
| US4935412A (en) * | 1983-12-29 | 1990-06-19 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same |
| US5308839A (en) * | 1989-12-04 | 1994-05-03 | The Research Foundation Of State University Of New York | Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline |
| JP3016587B2 (ja) * | 1989-12-04 | 2000-03-06 | ザ・リサーチ・ファンデーション・オブ・ステート・ユニバーシティ・オブ・ニューヨーク | 非ステロイド抗炎症剤及びテトラサイクリンの配合 |
| US5045538A (en) * | 1990-06-28 | 1991-09-03 | The Research Foundation Of State University Of New York | Inhibition of wasting and protein degradation of mammalian muscle by tetracyclines |
| US5223248A (en) * | 1991-02-11 | 1993-06-29 | The Research Foundation Of State University Of New York | Non-antibacterial tetracycline compositions possessing antiplaque properties |
| US5258371A (en) * | 1992-05-29 | 1993-11-02 | Kuraray Co., Ltd. | Method to reduce connective tissue destruction |
| CA2103189C (en) * | 1992-11-17 | 2005-05-03 | Lorne M. Golub | Tetracyclines including non-antimicrobial chemically-modified tetracyclines inhibit excessive collagen crosslinking during diabetes |
| US5523297A (en) * | 1993-03-02 | 1996-06-04 | The Research Foundation Of State University Of New York | Inhibition of excessive phospholipase A2 activity and/or production by non-antimicrobial tetracyclines |
| JP3929484B2 (ja) * | 1993-09-14 | 2007-06-13 | ジェネンテック・インコーポレーテッド | エコチンおよびその同族体を含む医薬的組成物 |
| US5618792A (en) * | 1994-11-21 | 1997-04-08 | Cortech, Inc. | Substituted heterocyclic compounds useful as inhibitors of (serine proteases) human neutrophil elastase |
| GB9502152D0 (en) * | 1995-02-03 | 1995-03-29 | Zeneca Ltd | Proline derivatives |
| US5789395A (en) * | 1996-08-30 | 1998-08-04 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds for inhibition of endogenous nitric oxide production |
-
1997
- 1997-03-13 US US08/816,551 patent/US5773430A/en not_active Expired - Lifetime
-
1998
- 1998-02-26 AU AU66698/98A patent/AU733308B2/en not_active Ceased
- 1998-02-26 DE DE69829748T patent/DE69829748T2/de not_active Expired - Lifetime
- 1998-02-26 NZ NZ337578A patent/NZ337578A/en not_active IP Right Cessation
- 1998-02-26 KR KR10-1999-7008325A patent/KR100530683B1/ko not_active Expired - Fee Related
- 1998-02-26 EP EP98908747A patent/EP0975349B1/en not_active Expired - Lifetime
- 1998-02-26 DK DK98908747T patent/DK0975349T3/da active
- 1998-02-26 WO PCT/US1998/003782 patent/WO1998040079A1/en not_active Ceased
- 1998-02-26 JP JP53959398A patent/JP4339411B2/ja not_active Expired - Fee Related
- 1998-02-26 ES ES98908747T patent/ES2241124T3/es not_active Expired - Lifetime
- 1998-02-26 CA CA002283071A patent/CA2283071C/en not_active Expired - Fee Related
- 1998-02-26 AT AT98908747T patent/ATE292972T1/de active
- 1998-02-26 PT PT98908747T patent/PT975349E/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK0975349T3 (da) | 2005-08-01 |
| JP4339411B2 (ja) | 2009-10-07 |
| EP0975349B1 (en) | 2005-04-13 |
| ATE292972T1 (de) | 2005-04-15 |
| EP0975349A4 (en) | 2002-10-30 |
| CA2283071A1 (en) | 1998-09-17 |
| KR20000076231A (ko) | 2000-12-26 |
| PT975349E (pt) | 2005-08-31 |
| AU6669898A (en) | 1998-09-29 |
| WO1998040079A1 (en) | 1998-09-17 |
| DE69829748T2 (de) | 2006-03-09 |
| AU733308B2 (en) | 2001-05-10 |
| NZ337578A (en) | 2001-08-31 |
| JP2001524948A (ja) | 2001-12-04 |
| CA2283071C (en) | 2009-01-27 |
| EP0975349A1 (en) | 2000-02-02 |
| US5773430A (en) | 1998-06-30 |
| KR100530683B1 (ko) | 2005-11-24 |
| DE69829748D1 (de) | 2005-05-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2241124T3 (es) | Actividad inhibidora de serin-proteinasa mediante tetraciclina hidrofoba. | |
| US6277061B1 (en) | Method of inhibiting membrane-type matrix metalloproteinase | |
| Golub et al. | Low‐dose doxycycline therapy: Effect on gingival and crevicular fluid collagenase activity in humans | |
| ES2320579T3 (es) | Uso de tetraciclinas sub-antimicrobianas para tratar rosacea ocular. | |
| US6379667B1 (en) | Medical use of matrix metalloproteinase inhibitors for inhibiting tissue contraction | |
| US5532227A (en) | Tetracyclines including non-antimicrobial chemically-modified tetracyclines inhibit excessive glycosylation of different types of collagen and other proteins during diabetes | |
| ES2237945T3 (es) | Combinacion de bisfosfonato y tetraciclina. | |
| EP0848951B1 (en) | Use of acetylcysteine for the manufacture of a medicament for the treatment of chronic ulcers | |
| JP2006508971A (ja) | プロテアーゼ阻害剤を使用して炎症性疾患を治療する組成物及び方法 | |
| Hurewitz et al. | Tetracycline and doxycycline inhibit pleural fluid metalloproteinases: a possible mechanism for chemical pleurodesis | |
| Lang et al. | Tyrothricin–an underrated agent for the treatment of bacterial skin infections and superficial wounds? | |
| US6949509B2 (en) | Pharmaceutical composition containing a small or medium size peptide | |
| AU7816400A (en) | Pharmaceutical composition for treatment of mucosal epithelial ulceration and/or erosion | |
| KR0163563B1 (ko) | 피부질환 치료용 의약조성물 | |
| Rees et al. | Effects of cystic fibrosis airway secretions on rat lung: role of neutrophil elastase | |
| BRPI0615588A2 (pt) | uso de um inibidor de aureolisina para o tratamento de condições inflamatórias da pele caracterizadas por colonização com staphylococcus aureus | |
| Valenta et al. | Lysozyme-caffeic acid conjugates: possible novel preservatives for dermal formulations | |
| US7288622B1 (en) | Composition for treatment of burns and wounds | |
| AU2003242647B2 (en) | Use of amide derivative of GE 2270 factor A3 for the treatment of acne | |
| EP1121935A1 (en) | Pharmaceutical composition containing a small or medium size peptide |