JP2010502600A - 感染症に対する候補薬 - Google Patents
感染症に対する候補薬 Download PDFInfo
- Publication number
- JP2010502600A JP2010502600A JP2009526572A JP2009526572A JP2010502600A JP 2010502600 A JP2010502600 A JP 2010502600A JP 2009526572 A JP2009526572 A JP 2009526572A JP 2009526572 A JP2009526572 A JP 2009526572A JP 2010502600 A JP2010502600 A JP 2010502600A
- Authority
- JP
- Japan
- Prior art keywords
- plasminogen
- plg
- mice
- bacterial
- infection
- 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.)
- Granted
Links
- 208000035473 Communicable disease Diseases 0.000 title claims abstract description 46
- 239000003814 drug Substances 0.000 title description 14
- 229940079593 drug Drugs 0.000 title description 10
- 108010051456 Plasminogen Proteins 0.000 claims abstract description 152
- 102000013566 Plasminogen Human genes 0.000 claims abstract description 151
- 208000015181 infectious disease Diseases 0.000 claims abstract description 149
- 238000000034 method Methods 0.000 claims abstract description 77
- 208000004575 Infectious Arthritis Diseases 0.000 claims abstract description 74
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 208000025255 bacterial arthritis Diseases 0.000 claims abstract description 67
- 229940012957 plasmin Drugs 0.000 claims abstract description 59
- 230000007123 defense Effects 0.000 claims abstract description 47
- 206010033078 Otitis media Diseases 0.000 claims abstract description 35
- 238000002347 injection Methods 0.000 claims description 66
- 239000007924 injection Substances 0.000 claims description 66
- 108010088842 Fibrinolysin Proteins 0.000 claims description 59
- 230000006378 damage Effects 0.000 claims description 49
- 238000011282 treatment Methods 0.000 claims description 49
- 230000001338 necrotic effect Effects 0.000 claims description 43
- 206010052428 Wound Diseases 0.000 claims description 42
- 230000033885 plasminogen activation Effects 0.000 claims description 42
- 241001465754 Metazoa Species 0.000 claims description 40
- 206010028851 Necrosis Diseases 0.000 claims description 40
- 208000027418 Wounds and injury Diseases 0.000 claims description 40
- 230000017074 necrotic cell death Effects 0.000 claims description 40
- 230000037361 pathway Effects 0.000 claims description 40
- 244000052769 pathogen Species 0.000 claims description 39
- 230000000694 effects Effects 0.000 claims description 35
- 210000004969 inflammatory cell Anatomy 0.000 claims description 34
- 230000002265 prevention Effects 0.000 claims description 29
- 230000003115 biocidal effect Effects 0.000 claims description 23
- 239000000126 substance Substances 0.000 claims description 23
- 238000012360 testing method Methods 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 21
- 239000003242 anti bacterial agent Substances 0.000 claims description 17
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 16
- 229940088710 antibiotic agent Drugs 0.000 claims description 15
- 230000001717 pathogenic effect Effects 0.000 claims description 15
- 230000007812 deficiency Effects 0.000 claims description 14
- 230000002458 infectious effect Effects 0.000 claims description 13
- 102000004127 Cytokines Human genes 0.000 claims description 12
- 108090000695 Cytokines Proteins 0.000 claims description 12
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 9
- 206010048038 Wound infection Diseases 0.000 claims description 9
- 230000000844 anti-bacterial effect Effects 0.000 claims description 9
- 230000001737 promoting effect Effects 0.000 claims description 9
- 230000009772 tissue formation Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 201000001223 septic arthritis Diseases 0.000 claims description 7
- 230000003612 virological effect Effects 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 108010087750 lysyl-plasminogen Proteins 0.000 claims description 6
- -1 salplase Proteins 0.000 claims description 6
- 206010010356 Congenital anomaly Diseases 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 5
- 230000028993 immune response Effects 0.000 claims description 5
- 229920001184 polypeptide Polymers 0.000 claims description 5
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 5
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 206010040943 Skin Ulcer Diseases 0.000 claims description 4
- 208000031650 Surgical Wound Infection Diseases 0.000 claims description 4
- 239000012190 activator Substances 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 208000007565 gingivitis Diseases 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 108010015052 miniplasmin Proteins 0.000 claims description 4
- 201000001245 periodontitis Diseases 0.000 claims description 4
- 229960005322 streptomycin Drugs 0.000 claims description 4
- 108010058207 Anistreplase Proteins 0.000 claims description 3
- 206010010741 Conjunctivitis Diseases 0.000 claims description 3
- 229930182555 Penicillin Natural products 0.000 claims description 3
- 206010036410 Postoperative wound infection Diseases 0.000 claims description 3
- 101710145796 Staphylokinase Proteins 0.000 claims description 3
- 108010023197 Streptokinase Proteins 0.000 claims description 3
- 108010039185 Tenecteplase Proteins 0.000 claims description 3
- 239000004098 Tetracycline Substances 0.000 claims description 3
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 3
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 3
- 229960003318 alteplase Drugs 0.000 claims description 3
- 229960000983 anistreplase Drugs 0.000 claims description 3
- 239000003429 antifungal agent Substances 0.000 claims description 3
- 229940121375 antifungal agent Drugs 0.000 claims description 3
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 claims description 3
- 229960000282 metronidazole Drugs 0.000 claims description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 3
- 108010049112 miniplasminogen Proteins 0.000 claims description 3
- 108010075698 monteplase Proteins 0.000 claims description 3
- 229950005805 monteplase Drugs 0.000 claims description 3
- 108010085108 pamiteplase Proteins 0.000 claims description 3
- 229950003603 pamiteplase Drugs 0.000 claims description 3
- 229940049954 penicillin Drugs 0.000 claims description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 3
- 230000000241 respiratory effect Effects 0.000 claims description 3
- 229960002917 reteplase Drugs 0.000 claims description 3
- 108010051412 reteplase Proteins 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 229960005202 streptokinase Drugs 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- 229960000216 tenecteplase Drugs 0.000 claims description 3
- 229960002180 tetracycline Drugs 0.000 claims description 3
- 229930101283 tetracycline Natural products 0.000 claims description 3
- 235000019364 tetracycline Nutrition 0.000 claims description 3
- 150000003522 tetracyclines Chemical class 0.000 claims description 3
- 230000000451 tissue damage Effects 0.000 claims description 3
- 231100000827 tissue damage Toxicity 0.000 claims description 3
- 230000009261 transgenic effect Effects 0.000 claims description 3
- 150000003952 β-lactams Chemical class 0.000 claims description 3
- 210000005067 joint tissue Anatomy 0.000 claims description 2
- 108010051044 lanoteplase Proteins 0.000 claims 1
- 229950010645 lanoteplase Drugs 0.000 claims 1
- 201000002282 venous insufficiency Diseases 0.000 claims 1
- 230000002269 spontaneous effect Effects 0.000 abstract description 12
- 238000010171 animal model Methods 0.000 abstract description 8
- 230000002708 enhancing effect Effects 0.000 abstract description 6
- 238000012216 screening Methods 0.000 abstract description 3
- 241000699670 Mus sp. Species 0.000 description 253
- 230000001580 bacterial effect Effects 0.000 description 98
- 210000000629 knee joint Anatomy 0.000 description 89
- 210000001519 tissue Anatomy 0.000 description 84
- 241000894006 Bacteria Species 0.000 description 65
- 210000004027 cell Anatomy 0.000 description 47
- 230000002950 deficient Effects 0.000 description 45
- 108090000623 proteins and genes Proteins 0.000 description 38
- 239000000306 component Substances 0.000 description 33
- 210000000959 ear middle Anatomy 0.000 description 33
- 206010003246 arthritis Diseases 0.000 description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 31
- 201000010099 disease Diseases 0.000 description 30
- 102000009816 urokinase plasminogen activator receptor activity proteins Human genes 0.000 description 29
- 108040001269 urokinase plasminogen activator receptor activity proteins Proteins 0.000 description 29
- 238000011081 inoculation Methods 0.000 description 28
- 210000002540 macrophage Anatomy 0.000 description 28
- 108090000790 Enzymes Proteins 0.000 description 27
- 102000004190 Enzymes Human genes 0.000 description 27
- 229940088598 enzyme Drugs 0.000 description 27
- 230000004054 inflammatory process Effects 0.000 description 27
- 102000004169 proteins and genes Human genes 0.000 description 27
- 206010061218 Inflammation Diseases 0.000 description 26
- 230000002917 arthritic effect Effects 0.000 description 26
- 235000018102 proteins Nutrition 0.000 description 26
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 25
- 238000002474 experimental method Methods 0.000 description 25
- 208000014674 injury Diseases 0.000 description 23
- 108010073385 Fibrin Proteins 0.000 description 22
- 102000009123 Fibrin Human genes 0.000 description 22
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 22
- 229950003499 fibrin Drugs 0.000 description 22
- 210000000440 neutrophil Anatomy 0.000 description 22
- 108010001014 Plasminogen Activators Proteins 0.000 description 20
- 102000001938 Plasminogen Activators Human genes 0.000 description 19
- 229940127126 plasminogen activator Drugs 0.000 description 19
- 210000003454 tympanic membrane Anatomy 0.000 description 18
- 102000003814 Interleukin-10 Human genes 0.000 description 17
- 108090000174 Interleukin-10 Proteins 0.000 description 17
- 230000001965 increasing effect Effects 0.000 description 17
- 229940076144 interleukin-10 Drugs 0.000 description 17
- 210000001503 joint Anatomy 0.000 description 17
- 241000700605 Viruses Species 0.000 description 16
- 102000004889 Interleukin-6 Human genes 0.000 description 14
- 108090001005 Interleukin-6 Proteins 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 230000035876 healing Effects 0.000 description 13
- 241000283973 Oryctolagus cuniculus Species 0.000 description 12
- 150000001413 amino acids Chemical group 0.000 description 12
- 210000000988 bone and bone Anatomy 0.000 description 12
- 210000001258 synovial membrane Anatomy 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 11
- 102000040430 polynucleotide Human genes 0.000 description 11
- 108091033319 polynucleotide Proteins 0.000 description 11
- 239000002157 polynucleotide Substances 0.000 description 11
- 208000035143 Bacterial infection Diseases 0.000 description 10
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 10
- 230000003213 activating effect Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000011532 immunohistochemical staining Methods 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 208000036142 Viral infection Diseases 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 210000000845 cartilage Anatomy 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 230000003247 decreasing effect Effects 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 230000028709 inflammatory response Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 244000005700 microbiome Species 0.000 description 9
- 244000045947 parasite Species 0.000 description 9
- 230000009469 supplementation Effects 0.000 description 9
- 230000009885 systemic effect Effects 0.000 description 9
- 230000009385 viral infection Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 230000002147 killing effect Effects 0.000 description 8
- 230000002797 proteolythic effect Effects 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000000699 topical effect Effects 0.000 description 8
- 206010015150 Erythema Diseases 0.000 description 7
- 241000233866 Fungi Species 0.000 description 7
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 7
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 7
- 210000003719 b-lymphocyte Anatomy 0.000 description 7
- 231100000321 erythema Toxicity 0.000 description 7
- 230000008595 infiltration Effects 0.000 description 7
- 238000001764 infiltration Methods 0.000 description 7
- 239000012188 paraffin wax Substances 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 238000010186 staining Methods 0.000 description 7
- 230000008961 swelling Effects 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 241000283707 Capra Species 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 108010076876 Keratins Proteins 0.000 description 6
- 102000011782 Keratins Human genes 0.000 description 6
- 241000191967 Staphylococcus aureus Species 0.000 description 6
- 241000193996 Streptococcus pyogenes Species 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 210000005006 adaptive immune system Anatomy 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- LQOLIRLGBULYKD-JKIFEVAISA-N cloxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl LQOLIRLGBULYKD-JKIFEVAISA-N 0.000 description 6
- 229960003326 cloxacillin Drugs 0.000 description 6
- 210000005069 ears Anatomy 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 230000006698 induction Effects 0.000 description 6
- 208000022760 infectious otitis media Diseases 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 210000001539 phagocyte Anatomy 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000013207 serial dilution Methods 0.000 description 6
- 230000007838 tissue remodeling Effects 0.000 description 6
- 206010059866 Drug resistance Diseases 0.000 description 5
- 239000006142 Luria-Bertani Agar Substances 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 210000003423 ankle Anatomy 0.000 description 5
- 210000000544 articulatio talocruralis Anatomy 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 210000001124 body fluid Anatomy 0.000 description 5
- 239000010839 body fluid Substances 0.000 description 5
- 208000024035 chronic otitis media Diseases 0.000 description 5
- 230000008021 deposition Effects 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 210000000613 ear canal Anatomy 0.000 description 5
- 210000000416 exudates and transudate Anatomy 0.000 description 5
- 230000020764 fibrinolysis Effects 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 238000002991 immunohistochemical analysis Methods 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 239000006166 lysate Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000004877 mucosa Anatomy 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 206010053555 Arthritis bacterial Diseases 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 4
- 108010049003 Fibrinogen Proteins 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 208000005141 Otitis Diseases 0.000 description 4
- 208000025865 Ulcer Diseases 0.000 description 4
- 230000033289 adaptive immune response Effects 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 208000019258 ear infection Diseases 0.000 description 4
- 229940012952 fibrinogen Drugs 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 210000003127 knee Anatomy 0.000 description 4
- 208000005923 otitis media with effusion Diseases 0.000 description 4
- 230000000242 pagocytic effect Effects 0.000 description 4
- 102000013415 peroxidase activity proteins Human genes 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 210000002345 respiratory system Anatomy 0.000 description 4
- OARRHUQTFTUEOS-UHFFFAOYSA-N safranin Chemical compound [Cl-].C=12C=C(N)C(C)=CC2=NC2=CC(C)=C(N)C=C2[N+]=1C1=CC=CC=C1 OARRHUQTFTUEOS-UHFFFAOYSA-N 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 231100000397 ulcer Toxicity 0.000 description 4
- 208000006400 Arbovirus Encephalitis Diseases 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241000206602 Eukaryota Species 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 206010061216 Infarction Diseases 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- 239000006137 Luria-Bertani broth Substances 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 241000607768 Shigella Species 0.000 description 3
- 108010067390 Viral Proteins Proteins 0.000 description 3
- 230000002924 anti-infective effect Effects 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000004154 complement system Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 206010014599 encephalitis Diseases 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000003527 fibrinolytic agent Substances 0.000 description 3
- 230000003480 fibrinolytic effect Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000009215 host defense mechanism Effects 0.000 description 3
- 230000007574 infarction Effects 0.000 description 3
- 239000012678 infectious agent Substances 0.000 description 3
- 210000005007 innate immune system Anatomy 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 201000009240 nasopharyngitis Diseases 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 229940056360 penicillin g Drugs 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000001732 thrombotic effect Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 208000004639 AIDS-Related Opportunistic Infections Diseases 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 208000003918 Acute Kidney Tubular Necrosis Diseases 0.000 description 2
- 244000105975 Antidesma platyphyllum Species 0.000 description 2
- 108700042778 Antimicrobial Peptides Proteins 0.000 description 2
- 102000044503 Antimicrobial Peptides Human genes 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 241000193403 Clostridium Species 0.000 description 2
- 241000186216 Corynebacterium Species 0.000 description 2
- 241000938605 Crocodylia Species 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 206010056340 Diabetic ulcer Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- RZSYLLSAWYUBPE-UHFFFAOYSA-L Fast green FCF Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC(O)=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 RZSYLLSAWYUBPE-UHFFFAOYSA-L 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 206010018612 Gonorrhoea Diseases 0.000 description 2
- 208000009889 Herpes Simplex Diseases 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- 206010023232 Joint swelling Diseases 0.000 description 2
- 102000007547 Laminin Human genes 0.000 description 2
- 108010085895 Laminin Proteins 0.000 description 2
- 241000589902 Leptospira Species 0.000 description 2
- 208000016604 Lyme disease Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 241000186359 Mycobacterium Species 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 206010031252 Osteomyelitis Diseases 0.000 description 2
- 208000009608 Papillomavirus Infections Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 208000037581 Persistent Infection Diseases 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 2
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010038540 Renal tubular necrosis Diseases 0.000 description 2
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 241000193998 Streptococcus pneumoniae Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000008952 bacterial invasion Effects 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000000721 bacterilogical effect Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000004579 body weight change Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 238000002316 cosmetic surgery Methods 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 230000008260 defense mechanism Effects 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 230000001066 destructive effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 210000003094 ear ossicle Anatomy 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 210000005081 epithelial layer Anatomy 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 244000053095 fungal pathogen Species 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 208000001786 gonorrhea Diseases 0.000 description 2
- 235000009424 haa Nutrition 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 206010023332 keratitis Diseases 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000016087 ovulation Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000013610 patient sample Substances 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 108010036385 plasmin-plasmin inhibitor complex Proteins 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 2
- 238000011477 surgical intervention Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000008409 synovial inflammation Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 229950003937 tolonium Drugs 0.000 description 2
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- XYGVIBXOJOOCFR-BTJKTKAUSA-N (z)-but-2-enedioic acid;8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepine Chemical compound OC(=O)\C=C/C(O)=O.C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F XYGVIBXOJOOCFR-BTJKTKAUSA-N 0.000 description 1
- UGBLISDIHDMHJX-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]butan-1-one;hydrochloride Chemical compound [Cl-].COC1=CC=CC=C1N1CC[NH+](CCCC(=O)C=2C=CC(F)=CC=2)CC1 UGBLISDIHDMHJX-UHFFFAOYSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010063746 Accidental death Diseases 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 102400000069 Activation peptide Human genes 0.000 description 1
- 101800001401 Activation peptide Proteins 0.000 description 1
- 208000009663 Acute Necrotizing Pancreatitis Diseases 0.000 description 1
- 208000004142 Acute Retinal Necrosis Syndrome Diseases 0.000 description 1
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 208000007407 African swine fever Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 208000009828 Arbovirus Infections Diseases 0.000 description 1
- 208000005989 Arenaviridae Infections Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010060968 Arthritis infective Diseases 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241001112741 Bacillaceae Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- 208000015898 Bacterial Skin disease Diseases 0.000 description 1
- 208000004926 Bacterial Vaginosis Diseases 0.000 description 1
- 201000004538 Bacteriuria Diseases 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 206010005098 Blastomycosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010051728 Bone erosion Diseases 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 208000008371 Bunyaviridae Infections Diseases 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- 208000006339 Caliciviridae Infections Diseases 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000321538 Candidia Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000004672 Cardiovascular Infections Diseases 0.000 description 1
- 208000000135 Cardiovascular Syphilis Diseases 0.000 description 1
- 208000000431 Cardiovascular Tuberculosis Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 208000001619 Central Nervous System Bacterial Infections Diseases 0.000 description 1
- 208000018663 Central Nervous System Viral disease Diseases 0.000 description 1
- 206010057854 Cerebral Toxoplasmosis Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 208000007190 Chlamydia Infections Diseases 0.000 description 1
- 208000005753 Circoviridae Infections Diseases 0.000 description 1
- 241000193155 Clostridium botulinum Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- 241000223203 Coccidioides Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010009895 Colitis ischaemic Diseases 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010010755 Conjunctivitis viral Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 208000001528 Coronaviridae Infections Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 201000007336 Cryptococcosis Diseases 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- 241000221204 Cryptococcus neoformans Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- 208000004449 DNA Virus Infections Diseases 0.000 description 1
- 102000000541 Defensins Human genes 0.000 description 1
- 108010002069 Defensins Proteins 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 208000007163 Dermatomycoses Diseases 0.000 description 1
- 229920001605 Dextranomer Polymers 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010014612 Encephalitis viral Diseases 0.000 description 1
- 206010014666 Endocarditis bacterial Diseases 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 206010014909 Enterovirus infection Diseases 0.000 description 1
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 201000000297 Erysipelas Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 208000035874 Excoriation Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010054261 Flavivirus infection Diseases 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000701047 Gallid alphaherpesvirus 2 Species 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 241001064231 Goat enterovirus Species 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 208000008913 Hantavirus Infections Diseases 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000000903 Herpes simplex encephalitis Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 206010074248 Herpes zoster meningoencephalitis Diseases 0.000 description 1
- 208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
- 208000005100 Herpetic Keratitis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 208000029534 Infectious Bone disease Diseases 0.000 description 1
- 208000002900 Infectious Pregnancy Complications Diseases 0.000 description 1
- 208000022535 Infectious Skin disease Diseases 0.000 description 1
- 201000003129 Kidney Papillary Necrosis Diseases 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 241000588915 Klebsiella aerogenes Species 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 241000589242 Legionella pneumophila Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 208000008551 Lyme Neuroborreliosis Diseases 0.000 description 1
- 102000014944 Lysosome-Associated Membrane Glycoproteins Human genes 0.000 description 1
- 108010064171 Lysosome-Associated Membrane Glycoproteins Proteins 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 208000006758 Marek Disease Diseases 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 244000062730 Melissa officinalis Species 0.000 description 1
- 235000010654 Melissa officinalis Nutrition 0.000 description 1
- 206010027202 Meningitis bacterial Diseases 0.000 description 1
- 206010027260 Meningitis viral Diseases 0.000 description 1
- 241000191938 Micrococcus luteus Species 0.000 description 1
- 208000004068 Morbillivirus Infections Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000186362 Mycobacterium leprae Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 208000001572 Mycoplasma Pneumonia Diseases 0.000 description 1
- 201000008235 Mycoplasma pneumoniae pneumonia Diseases 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 206010028885 Necrotising fasciitis Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 241000588656 Neisseriaceae Species 0.000 description 1
- 241000187654 Nocardia Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010073938 Ophthalmic herpes simplex Diseases 0.000 description 1
- 206010030865 Ophthalmic herpes zoster Diseases 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 208000009620 Orthomyxoviridae Infections Diseases 0.000 description 1
- 208000009360 Osteoarticular Tuberculosis Diseases 0.000 description 1
- 206010058096 Pancreatic necrosis Diseases 0.000 description 1
- 208000008071 Parvoviridae Infections Diseases 0.000 description 1
- 206010057343 Parvovirus infection Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010058674 Pelvic Infection Diseases 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- 208000006735 Periostitis Diseases 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 208000005155 Picornaviridae Infections Diseases 0.000 description 1
- 102000004179 Plasminogen Activator Inhibitor 2 Human genes 0.000 description 1
- 108090000614 Plasminogen Activator Inhibitor 2 Proteins 0.000 description 1
- 206010035734 Pneumonia staphylococcal Diseases 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- 208000004692 Pneumovirus Infections Diseases 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 208000005585 Poxviridae Infections Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038422 Renal cortical necrosis Diseases 0.000 description 1
- 208000008104 Reoviridae Infections Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 241000606683 Rickettsiaceae Species 0.000 description 1
- 208000000705 Rift Valley Fever Diseases 0.000 description 1
- 206010067470 Rotavirus infection Diseases 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 1
- 101150043341 Socs3 gene Proteins 0.000 description 1
- 241000589970 Spirochaetales Species 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 206010066409 Staphylococcal skin infection Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000194019 Streptococcus mutans Species 0.000 description 1
- 241000194023 Streptococcus sanguinis Species 0.000 description 1
- 241000193987 Streptococcus sobrinus Species 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000058015 Suppressor of Cytokine Signaling 3 Human genes 0.000 description 1
- 108700027337 Suppressor of Cytokine Signaling 3 Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010043647 Thrombotic Stroke Diseases 0.000 description 1
- 208000035056 Tick-Borne disease Diseases 0.000 description 1
- 208000000255 Togaviridae Infections Diseases 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 208000004062 Tumor Virus Infections Diseases 0.000 description 1
- 206010045210 Tympanic Membrane Perforation Diseases 0.000 description 1
- 241000202898 Ureaplasma Species 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 208000037009 Vaginitis bacterial Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000000394 Varicella Zoster Encephalitis Diseases 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- 206010058874 Viraemia Diseases 0.000 description 1
- 208000002365 Viral Bronchiolitis Diseases 0.000 description 1
- 208000005914 Viral Conjunctivitis Diseases 0.000 description 1
- 208000000222 Viral Eye Infections Diseases 0.000 description 1
- 208000012544 Viral Skin disease Diseases 0.000 description 1
- 208000028227 Viral hemorrhagic fever Diseases 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- 206010071212 Vulvovaginal injury Diseases 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 229920000392 Zymosan Polymers 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 206010000269 abscess Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 201000007691 actinomycosis Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 244000309743 astrovirus Species 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 201000007032 bacterial conjunctivitis Diseases 0.000 description 1
- 208000009361 bacterial endocarditis Diseases 0.000 description 1
- 201000009904 bacterial meningitis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 208000003836 bluetongue Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 201000004827 cardiac tuberculosis Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008355 cartilage degradation Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 208000007085 cutaneous syphilis Diseases 0.000 description 1
- 208000001763 cytomegalovirus retinitis Diseases 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 201000003929 dermatomycosis Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000000883 ear external Anatomy 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940092559 enterobacter aerogenes Drugs 0.000 description 1
- 230000000688 enterotoxigenic effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 210000003495 flagella Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 102000054767 gene variant Human genes 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 208000029629 hantavirus infectious disease Diseases 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000013210 hematogenous Diseases 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 201000010284 hepatitis E Diseases 0.000 description 1
- 201000010884 herpes simplex virus keratitis Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000002169 hydrotherapy Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000013115 immunohistochemical detection Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000012750 in vivo screening Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000002864 infectious keratoconjunctivitis Diseases 0.000 description 1
- 201000007119 infective endocarditis Diseases 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 201000008222 ischemic colitis Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 208000005430 kidney cortex necrosis Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000012633 leachable Substances 0.000 description 1
- 229940115932 legionella pneumophila Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000007970 necrotizing fasciitis Diseases 0.000 description 1
- 208000002040 neurosyphilis Diseases 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 208000008940 ocular tuberculosis Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 206010033072 otitis externa Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007110 pathogen host interaction Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 210000000680 phagosome Anatomy 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 208000009305 pseudorabies Diseases 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000017702 response to host Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940115037 santyl Drugs 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 201000003196 skeletal tuberculosis Diseases 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 244000005714 skin microbiome Species 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 208000004048 staphylococcal pneumonia Diseases 0.000 description 1
- 238000000551 statistical hypothesis test Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000031068 symbiosis, encompassing mutualism through parasitism Effects 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000003685 thermal hair damage Effects 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- QQJLHRRUATVHED-UHFFFAOYSA-N tramazoline Chemical compound N1CCN=C1NC1=CC=CC2=C1CCCC2 QQJLHRRUATVHED-UHFFFAOYSA-N 0.000 description 1
- 229960001262 tramazoline Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000013042 tunel staining Methods 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229940118696 vibrio cholerae Drugs 0.000 description 1
- 201000002498 viral encephalitis Diseases 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 201000010044 viral meningitis Diseases 0.000 description 1
- 208000009421 viral pneumonia Diseases 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
- 210000003857 wrist joint Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/484—Plasmin (3.4.21.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
- G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21007—Plasmin (3.4.21.7), i.e. fibrinolysin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/195—Assays involving biological materials from specific organisms or of a specific nature from bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Mycology (AREA)
- Zoology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Toxicology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Obesity (AREA)
Abstract
Description
本発明は、プラスミノーゲン活性化経路の成分、およびプラスミノーゲンの活性化能を有する化合物を感染性疾患と組織壊死のための新規改良戦略に用いることができるという驚くべき発見に関する。本発明の局面は、炎症細胞を活性化し、細菌を殺し、壊死組織を除去し、サイトカインの発現を促進することにより、例えば、S. aureus誘発関節炎および開放創傷感染に対する防御の役割を果たすプラスミノーゲン、またはプラスミノーゲン活性化経路の他のメンバーもしくはプラスミノーゲン活性化能を有する化合物に関する。そのような感染状態には、さらに、感染性疾患、ならびに組織感染が例えば組織特異的感染防御、全体的身体感染防御、急性感染症、慢性感染症、慢性潰瘍、開放創傷感染、および糖尿病性潰瘍時に一般に観察される他の疾患が含まれる。
(a)被検物質を細菌性関節炎を有する動物に投与し、
(b)少なくとも1のパラメーター:(i)殺菌度(細菌の殺滅度)、(ii)壊死組織形成、(iii)炎症細胞の活性化、(iv)感染症、例えば細菌性関節炎のサイトカインの発現、を評価し、
(c)工程(b)の選択したパラメーターをコントロール値と比較し、
(d)選択したパラメーターがコントロール値と比較して、感染症に対する宿主の防御を促進するのに有用な薬剤としてより有益なあらゆる被検物質を選択する、ことを含む方法に関する。
(発明の説明)
本明細書で用いた用語は、一般的には、本発明の文脈内および各用語が用いられている特定の文脈において当該分野における通常の意味を有する。ある用語は、本発明の組成物および方法ならびにその製造および使用方法を説明するのに当業者にさらなる手引きを与えるために以下または本明細書の他の箇所で論じている。
分子生物学的定義
プラスミノーゲン活性化系
感染を試験するための細菌性関節炎モデル
本実施例は、プラスミノーゲン欠乏マウスが野生型コントロール同胞種に比べて持続的炎症および組織破壊を有することを示す。S. aureus性細菌性関節炎ではplg+/+マウスよりplg-/-マウスで有意により重度の組織病理学的変化がみられる。
方法
結果
方 法
結 果
方 法
本実験は、細菌をカウントする以外は実施例1と同様に行った。
細菌のカウント:細菌注射後第2、3、4、5、7、14、および28日に、膝関節を得、1mlの無菌PBS中でホモゲナイズした。連続希釈後、ホモジネートの溶液をLB寒天プレート上に塗布し、37℃で一夜培養した。次に、生細菌コロニーをカウントし、各ホモジネート中の細菌数を評価した。
結 果
表1.1x106 CFUのS. aureus Philipsの関節内注射後のplg+/+およびplg-/-マウスの膝関節中の細菌の回収
方 法
結 果
方 法
plg -/- マウスへのヒトプラスミノーゲンの補給。
結 果
方 法
結 果
方 法
結 果
方 法
結 果
方 法
本実験は、ウエスタンブロット分析を除き、実施例1と同様に行った。
ウエスタンブロット分析
結 果
方 法
結 果
方 法
plg+/+およびplg-/-マウスに、200μl無菌PBS中の1x106 CFUのS. aureus Phillipsを静脈内(i.v.)注射して細菌性関節炎を誘発した。接種後毎日個々にマウスを追跡した。足(paw)を24時間毎に検査し、接種後第21日にすべてのマウスを屠殺した。関節炎は、可視的な関節の腫脹および/または掌(palm)、手関節(wrist)および足関節(ankle)の紅斑で定義した。関節炎の強さを評価するため、肉眼検査により各足につき0〜5ポイントのスコアを生じる系を用いて、臨床スコア付け(関節炎指数)を行った(0 = 正常、1 = わずかな腫脹または紅斑;2 = 軽度の腫脹および紅斑;3 = 中等度の腫脹および紅斑;4 = 顕著な腫脹および紅斑;5 = 顕著な腫脹および変形)。各試験動物について4つ全ての足からのスコアを加えることにより総スコアを計算し、各個々のマウスについて0〜20の範囲の関節炎スコアを得た。マウスの体重を第0日から第21日まで毎日測定した。
結 果
方 法
200μlの無菌PBS中の1x106 CFUのS. aureus Phillipsの静脈内(i.v.)注射によりplg+/+およびplg-/-マウスに細菌性関節炎を誘発した。
結 果
方 法
結 果
方 法
結 果
方 法
実験方法:18週間中、マウスを種々の時間間隔で25μl Dormicum(登録商標)(Roche AB、Stockholm、Sweden)、25μl Hypnorm(登録商標)(Janssen Pharmaceutica、Beerse、Belgium)および50μl無菌水の混合物100μlの腹腔内注射により麻酔した。鼓膜(TM)の肉眼所見(詳しく説明)を注意深く試験し、耳顕微鏡(otomicroscope)下で記録した。18週間の終了時に、すべての動物を屠殺し、18匹の動物(野生型、n=7;plg欠乏、n=11)の耳を、それぞれ、細菌の同定(野生型、n=6;plg欠乏、n=6)、樹脂包埋(野生型、n=4;plg欠乏、n=6)、およびパラフィン包埋(野生型、n=4;plg欠乏、n=10)用に無作為に3群に分けた。
結 果
b 形態学的に分析すると、耳顕微鏡下で正常を示したplg欠乏マウスの中耳は、鼓膜に付着している中耳腔中の薄層の不定形の組織塊のみを伴う、それほど顕著ではない炎症性変化を有することがわかった。
方 法
この実験は、細菌学的同定を除き、実施例8と同様に行った。
細菌学的同定:野生型およびplg欠乏群からの鼓室胞を解剖して軟部組織を除去し、該胞の骨床(bony floor)の小片をナイフで除去した。無菌スワブを中耳腔(MEC)内に浸漬し、スワブを使って材料をさらにLuriaブロス(LB)プレート上に塗布し、速やかに37℃で48時間培養した。得られたコロニーをCowan & Steelに従って同定した(16)。
結 果
方 法
この実験は、免疫組織化学染色以外は実施例8と同様に行った。
免疫組織化学染色:パラフィン包埋切片をエタノール濃度が減少する系列中で再水和し、次いで蒸留水ですすいだ。内因性パーオキシダーゼ活性を3% H2O2で10分間ブロックし、スライドをさらにPBSで洗浄した。次に、連続切片を下記の抗体で処理した。すべての免疫組織化学染色において、一次抗体の代わりに非免疫動物の血清でインキュベーションした隣り合ったスライドを陰性コントロールに用いた。
結 果
(参考文献リスト)
2. Hauschildt,S., and Kleine,B. 1995. Bacterial stimulators of macrophages. Int. Rev. Cytol. 161:263-331.
3. Chertov,O., Yang,D., Howard,O.M., and Oppenheim,J.J. 2000. Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol. Rev. 177:68-78.
4. Ny,A., Leonardsson,G., Hagglund,A.C, Hagglof,P., Ploplis,V.A., Carmeliet,P., and Ny,T. 1999. Ovulation in plasminogen-deficient mice. Endocrinology 140:5030-5035.
5. Teele,D.W., Klein, J.O., and Rosner,B. 1989. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. J. Infect. Dis. 160:83-94.
6. Alexander CM, and Werb,Z. 1991. Extracellular matrix degradation. Cell Biology of Extracellular Matrix. Hay ED編, Plenum Press. New York. 255-302.
7. Travis, J., and Salvesen,G. 1983. Control of coagulation and fibrinolysis by plasma proteinase inhibitors. Behring Inst. Mitt.56-65.
8. Wiman,B., and Wallen,P. 1975. Structural relationship between "glutamic acid" and "lysine" forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography. Eur. J. Biochem. 50:489-494.
9. Saksela,O., and Rifkin,D.B. 1988. Cell-associated plasminogen activation: regulation and physiological functions. Annu. Rev. Cell Biol. 4:93-126.
10. Collen,D., and Lijnen,H.R. 1991. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 78:3114-3124.
11. Liu,Z.Q., Deng,G.M., Foster,S., and Tarkowski,A. 2001. Staphylococcal peptidoglycans induce arthritis. Arthritis Res. 3:375-380.
12. Qasimi,P., Ming-Lum,A., Ghanipour,A., Ong,C.J., Cox,M.E., Ihle,J., Cacalano,N., Yoshimura,A., and Mui,A.L. 2006. Divergent mechanisms utilized by SOCS3 to mediate interleukin-10 inhibition of tumor necrosis factor alpha and nitric oxide production by macrophages. J. Biol. Chem. 281:6316-6324.
13. Gjertsson,L, Hultgren,O.H., and Tarkowski,A. 2002. Interleukin-10 ameliorates the outcome of Staphylococcus aureus arthritis by promoting bacterial clearance. Clin. Exp. Immunol. 130:409-414.
14. Carmeliet,P., Schoonjans,L., Kieckens,L., Ream,B., Degen,J., Bronson,R., De,V.R., van den Oord,J.J., Collen,D., and Mulligan,R.C. 1994. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 368:419-424.
15. Eriksson,P.O., Mattsson,C, and Hellstrom,S. 2003. First forty-eight hours of developing otitis media: an experimental study. Ann. Otol. Rhinol. Laryngol. 112:558-566.
16. COWAN,S. T., and STEEL,K.J. 1961. Diagnostic tables for the common medical bacteria. J Hyg.(Lond) 59:357-372.
Claims (22)
- 感染性疾患の防御、予防、および/または治療用の医薬組成物を製造するための、プラスミノーゲンを直接またはプラスミノーゲン活性化経路を介して活性化する能力を有するかまたはプラスミノーゲン活性化経路の成分である化合物の使用。
- プラスミノーゲン活性化経路の成分が、プラスミノーゲン、Lys-プラスミノーゲン、Glu-プラスミノーゲン、プラスミン、プラスミノーゲンおよびプラスミンのクリングルドメイン、ミニ-プラスミノーゲン、ミニ-プラスミン、プラスミノーゲン活性化因子、tPA、およびuPAから選ばれる請求項1記載の使用。
- プラスミノーゲンを直接またはプラスミノーゲン活性化経路を介して活性化する能力を有する化合物が、ストレプトキナーゼ、サルプラーゼ、アルテプラーゼ、レテプラーゼ、テネクテプラーゼ、アニストレプラーゼ、モンテプラーゼ、ラノテプラーゼ、パミテプラーゼ、スタフィロキナーゼ、およびプラスミノーゲン活性化経路の成分の組換え型および変異体から選ばれる請求項1記載の使用。
- 感染性疾患が細菌感染性疾患またはウイルス感染性疾患である請求項1〜3のいずれかに記載の使用。
- 細菌感染性疾患が、中耳炎、細菌性関節炎、歯肉炎、歯周炎、結膜炎、創傷感染、外科的創傷感染、壊死、肺炎、火傷および/または感染症により生じる呼吸器官の損傷および糖尿病、静脈不全または静脈/動脈複合不全、または感染性関節炎などに罹患した患者の感染性慢性脚潰瘍、感染により生じた関節組織の損傷、好ましくは中耳炎または細菌性関節炎から選ばれる請求項4記載の使用。
- 該組成物が請求項1〜3に記載の2またはそれ以上の化合物の組み合わせを含む先の請求項のいずれかに記載の使用。
- 該組成物がさらに少なくとも1の抗生剤を含む先の請求項のいずれかに記載の使用。
- 抗生剤が、テトラサイクリン、アンフェニコール、ベータ・ラクタム、ペニシリン、スルホンアミド、マクロライド、リンコサミド、ストレプトガミン、ストレプトマイシン、キノロン、およびメトロニダゾールからなる群から選ばれる請求項7記載の使用。
- 対象が哺乳動物、特にヒトである先の請求項のいずれかに記載の使用。
- 対象がプラスミンまたはプラスミノーゲン欠乏(欠損)症である先の請求項のいずれかに記載の使用。
- 欠乏が先天性、後天性、および/または局所性である請求項10記載の使用。
- 該化合物が全身的、局所的(locally、topically)、静脈内、筋肉内、皮下、髄腔内、または経直腸的に、または吸入、局所注射、関節内注射で投与される先の請求項のいずれかに記載の使用。
- 該化合物が適切なポリペプチド担体または安定化剤と組み合わせて投与される先の請求項のいずれかに記載の使用。
- 該化合物が、0.05mg〜約10mg、好ましくは約0.5〜約5mgの用量で投与される先の請求項のいずれかに記載の使用。
- 該化合物の投与が少なくとも1回、好ましくは少なくとも毎日反復される先の請求項のいずれかに記載の使用。
- 該投与が、請求項1〜15に記載の化合物を含む創傷被覆材を感染領域に適用することにより行われる先の請求項のいずれかに記載の使用。
- 感染性疾患の防御、予防、および/または治療が感染性病原体に対する免疫反応を誘導することを含む先の請求項のいずれかに記載の使用。
- 感染性疾患の防御、予防、および/または治療方法であって、そのような治療を必要とする対象に、有効量の請求項1〜17に記載の化合物を含む医薬組成物を投与することを含む方法。
- 有効量の請求項1〜17に記載の化合物を含む感染性疾患の防御、予防、および/または治療用の医薬組成物。
- 有効量の請求項1〜17に記載の化合物および少なくとも1の抗生剤もしくは抗真菌剤を別のバイアルに含む感染性疾患の防御、予防、および/または治療に用いる部分のキット。
- 感染症に対する宿主の防御を促進するのに有用な物質の同定方法であって、
(a)被検物質を細菌性関節炎を有する動物に投与し、
(b)少なくとも1のパラメーター:(i)殺菌度、(ii)壊死組織形成、(iii)炎症細胞の活性化、(iv)感染症、例えば細菌性関節炎のサイトカインの発現、を評価し、
(c)工程(b)の選択したパラメーターをコントロール値と比較し、
(d)選択したパラメーターがコントロール値と比較して、感染症に対する宿主の防御を促進するのに有用な物質としてより有益なあらゆる被検物質を選択することを含む方法。 - 該動物が野生型動物およびプラスミノーゲンの内因性発現を欠くトランスジェニック動物からなる群のメンバーから選ばれる請求項21に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US82366506P | 2006-08-28 | 2006-08-28 | |
US60/823,665 | 2006-08-28 | ||
PCT/SE2007/050585 WO2008026999A2 (en) | 2006-08-28 | 2007-08-28 | Candidates against infection |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2010502600A true JP2010502600A (ja) | 2010-01-28 |
JP2010502600A5 JP2010502600A5 (ja) | 2010-09-09 |
JP5566105B2 JP5566105B2 (ja) | 2014-08-06 |
Family
ID=39136397
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009526572A Expired - Fee Related JP5566105B2 (ja) | 2006-08-28 | 2007-08-28 | 感染症に対する候補薬 |
Country Status (12)
Country | Link |
---|---|
US (3) | US8318661B2 (ja) |
EP (1) | EP2056864B1 (ja) |
JP (1) | JP5566105B2 (ja) |
KR (1) | KR101517626B1 (ja) |
CN (2) | CN101573134B (ja) |
AU (1) | AU2007290881B2 (ja) |
CA (1) | CA2662101C (ja) |
DK (1) | DK2056864T3 (ja) |
EA (1) | EA016250B1 (ja) |
ES (1) | ES2451015T3 (ja) |
MX (1) | MX2009002226A (ja) |
WO (1) | WO2008026999A2 (ja) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108289935A (zh) * | 2015-11-03 | 2018-07-17 | 普罗米蒂克生物治疗有限公司 | 纤溶酶原缺乏症的纤溶酶原替代疗法 |
JP2019500427A (ja) * | 2015-12-18 | 2019-01-10 | タレンゲン インターナショナル リミテッドTalengen International Limited | 子宮膣部びらんを予防及び治療するための方法 |
JP2019500425A (ja) * | 2015-12-18 | 2019-01-10 | タレンゲン インターナショナル リミテッドTalengen International Limited | 肝組織損傷及びその関連疾患を予防及び治療するための方法 |
JP2020502135A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 薬物性腎損傷を予防及び治療するための方法 |
JP2020502132A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 皮膚の繊維化を予防及び治療するための方法 |
JP2020502151A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | インスリン分泌を促進する方法 |
JP2020524689A (ja) * | 2017-06-23 | 2020-08-20 | プロメティック・バイオセラピューティクス・インコーポレイテッドProMetic BioTherapeutics,Inc. | Pai−1過剰発現に関連する状態のプラスミノーゲン処置 |
US11007253B2 (en) | 2015-12-18 | 2021-05-18 | Talengen International Limited | Method for preventing or treating radiation and chemical damage |
US11207387B2 (en) | 2016-12-15 | 2021-12-28 | Talengen International Limited | Method and drug for preventing and treating obesity |
US11389515B2 (en) | 2016-12-15 | 2022-07-19 | Talengen International Limited | Method for mitigating heart disease |
US11478535B2 (en) | 2016-12-15 | 2022-10-25 | Talengen International Limited | Method for preventing and treating fatty liver |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9107864B2 (en) | 2004-06-07 | 2015-08-18 | Qu Biologics Inc. | Tissue targeted antigenic activation of the immune response to treat cancers |
US8501198B2 (en) | 2004-06-07 | 2013-08-06 | Qu Biologics Inc. | Tissue targeted antigenic activation of the immune response to treat cancers |
EP2056865B1 (en) | 2006-08-28 | 2013-12-25 | Omnio Healer AB | Novel drug target of preventing and treating periodontal disease, improving healing of periodontal wounds and promoting oral health |
JP5819293B2 (ja) | 2009-07-10 | 2015-11-24 | スロンボジェニックス・ナムローゼ・フェンノートシャップThromboGenics NV | プラスミノーゲンおよびプラスミンの変異体 |
US20120189609A1 (en) * | 2009-08-28 | 2012-07-26 | Thrombogenics Nv | Improvement to trabeculectomy |
NZ702796A (en) * | 2010-07-26 | 2017-03-31 | Qu Biologics Inc | Immunogenic anti-inflammatory compositions |
WO2012093132A1 (en) | 2011-01-05 | 2012-07-12 | Thrombogenics Nv | Plasminogen and plasmin variants |
AU2012296884B2 (en) | 2011-08-12 | 2015-02-05 | Thrombogenics N.V. | Plasminogen and plasmin variants |
CN102507707B (zh) * | 2011-10-12 | 2015-10-21 | 山东大学 | 一种检测龈沟液中蛋白裂解酶含量的方法 |
CA2947631A1 (en) | 2014-05-02 | 2015-11-05 | Qu Biologics Inc. | Anti-microbial immunomodulation |
WO2017101867A1 (zh) | 2015-12-18 | 2017-06-22 | 深圳瑞健生命科学研究院有限公司 | 一种预防或治疗糖尿病性神经损伤及其相关病症的方法 |
US11090372B2 (en) | 2015-12-18 | 2021-08-17 | Talengen International Limited | Method of treating diabetic nephropathy comprising administering plasminogen |
TWI624268B (zh) | 2015-12-18 | 2018-05-21 | Talengen Institute Of Life Sciences Co Ltd | 纖溶酶原在製備藥劑上的用途及包括纖溶酶原之藥劑 |
CA3008691A1 (en) | 2015-12-18 | 2017-06-22 | Talengen International Limited | Method for preventing or treating diabetic retinopathy |
CN106890321A (zh) * | 2015-12-18 | 2017-06-27 | 深圳瑞健生命科学研究院有限公司 | 一种用于预防和治疗宫颈糜烂的方法 |
TWI746581B (zh) * | 2016-12-15 | 2021-11-21 | 大陸商深圳瑞健生命科學硏究院有限公司 | 纖溶酶原在製備預防和治療脂質腎損傷之藥劑上的用途 |
CN108210906A (zh) * | 2016-12-15 | 2018-06-29 | 深圳瑞健生命科学研究院有限公司 | 治疗冠状动脉粥样硬化及其并发症的药物及其用途 |
US11938172B2 (en) | 2017-06-19 | 2024-03-26 | Talengen International Limited | Method for regulating and controlling GLP-1/GLP-1R and drug |
CN107496911A (zh) * | 2017-10-20 | 2017-12-22 | 滕敏子 | 一种外科手术后用于防肿胀、抗感染的愈合剂 |
EP3883598A1 (en) * | 2018-11-19 | 2021-09-29 | Nordmark IP GmbH | Ancrod for the treatment or prophylaxis of endocarditis |
CN111742887A (zh) * | 2019-12-19 | 2020-10-09 | 广西医科大学第一附属医院 | 放疗后分泌性中耳炎树鼩模型的建立方法 |
WO2021160092A1 (zh) * | 2020-02-11 | 2021-08-19 | 泰伦基国际有限公司 | 一种治疗病毒性肺炎的方法和药物 |
WO2021180068A1 (zh) * | 2020-03-09 | 2021-09-16 | 泰伦基国际有限公司 | 一种治疗2019新型冠状病毒引发疾病的方法和药物 |
US10973908B1 (en) | 2020-05-14 | 2021-04-13 | David Gordon Bermudes | Expression of SARS-CoV-2 spike protein receptor binding domain in attenuated salmonella as a vaccine |
CN115845036B (zh) * | 2023-02-20 | 2023-05-09 | 滨州益洁口腔有限公司 | 用于口腔种植体牙龈组织的蛋白酶及制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003020297A2 (en) * | 2001-09-06 | 2003-03-13 | Omnio Ab | Method of improving wound healing |
JP2005510302A (ja) * | 2001-11-26 | 2005-04-21 | ジェネンテック・インコーポレーテッド | カテーテル組成物とその用途 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3023143A (en) * | 1959-10-14 | 1962-02-27 | American Cyanamid Co | Process for preparing a veterinary composition |
AT402367B (de) * | 1990-10-11 | 1997-04-25 | Immuno Ag | Pharmazeutische zubereitung auf basis von lys-plasminogen |
US6054122A (en) * | 1990-11-27 | 2000-04-25 | The American National Red Cross | Supplemented and unsupplemented tissue sealants, methods of their production and use |
US5792835A (en) | 1991-09-05 | 1998-08-11 | Baxter International Inc. | Method of preparing a topical fibrinogen complex |
US5397578A (en) * | 1994-03-29 | 1995-03-14 | Tovarischestvo S Ogranichennoi Otvetstvennostiju "Taurus" | Method of treatment of chronic purulent inflammations of ear in children |
US6372473B1 (en) | 1997-05-28 | 2002-04-16 | Human Genome Sciences, Inc. | Tissue plasminogen activator-like protease |
US6420622B1 (en) * | 1997-08-01 | 2002-07-16 | 3M Innovative Properties Company | Medical article having fluid control film |
WO2000004941A1 (en) | 1998-07-24 | 2000-02-03 | Pharmacal Biotechnologies, Inc. | Osseous tissue reconstruction system and method |
US6656496B1 (en) | 1999-03-01 | 2003-12-02 | The Uab Research Foundation | Porous tissue scaffolding materials and uses thereof |
US20030026794A1 (en) * | 2001-07-31 | 2003-02-06 | Howard Fein | Selective enzyme treatment of skin conditions |
WO2003066842A2 (de) * | 2002-02-06 | 2003-08-14 | Trommsdorff Gmbh & Co. Kg Arzneimittel | Verfahren zur herstellung von rekombinanten proteinen in mikroorganismen |
CN1420126A (zh) | 2002-07-10 | 2003-05-28 | 牛勃 | 一种重组人纤溶酶原Kringle5突变体蛋白rhPK-5的制备方法 |
EP2056865B1 (en) | 2006-08-28 | 2013-12-25 | Omnio Healer AB | Novel drug target of preventing and treating periodontal disease, improving healing of periodontal wounds and promoting oral health |
-
2007
- 2007-08-28 KR KR1020097005738A patent/KR101517626B1/ko active IP Right Grant
- 2007-08-28 US US12/439,517 patent/US8318661B2/en active Active
- 2007-08-28 ES ES07794195.3T patent/ES2451015T3/es active Active
- 2007-08-28 EA EA200970233A patent/EA016250B1/ru not_active IP Right Cessation
- 2007-08-28 CA CA2662101A patent/CA2662101C/en not_active Expired - Fee Related
- 2007-08-28 CN CN2007800324051A patent/CN101573134B/zh active Active
- 2007-08-28 MX MX2009002226A patent/MX2009002226A/es active IP Right Grant
- 2007-08-28 WO PCT/SE2007/050585 patent/WO2008026999A2/en active Application Filing
- 2007-08-28 DK DK07794195.3T patent/DK2056864T3/en active
- 2007-08-28 EP EP07794195.3A patent/EP2056864B1/en not_active Not-in-force
- 2007-08-28 CN CN200780032092XA patent/CN101563100B/zh active Active
- 2007-08-28 JP JP2009526572A patent/JP5566105B2/ja not_active Expired - Fee Related
- 2007-08-28 AU AU2007290881A patent/AU2007290881B2/en not_active Ceased
-
2012
- 2012-11-26 US US13/685,466 patent/US20130149321A1/en not_active Abandoned
-
2015
- 2015-12-09 US US14/964,481 patent/US10729750B2/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003020297A2 (en) * | 2001-09-06 | 2003-03-13 | Omnio Ab | Method of improving wound healing |
JP2005510302A (ja) * | 2001-11-26 | 2005-04-21 | ジェネンテック・インコーポレーテッド | カテーテル組成物とその用途 |
Non-Patent Citations (6)
Title |
---|
JPN6012046117; Circulation, 1995, Vol.92 p.2585-2593 * |
JPN6012046118; 新薬と治療, 2000, Vol.50 No.5 p.19-21 * |
JPN6012046120; NEJM., 1998, Vol.339 No.23 p.1679-1686 * |
JPN6012046123; Surgery, 1954, Vol.98 No.6 p.667-674 * |
JPN6013038717; Blood. Vol.91 No.5 p.1616-24. (1998) * |
JPN6013038718; 日本臨床, Vol.62 Suppl.12 p.697-9 (2004) * |
Cited By (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018533589A (ja) * | 2015-11-03 | 2018-11-15 | プロメティック・バイオセラピューティクス・インコーポレイテッドProMetic BioTherapeutics,Inc. | プラスミノーゲン欠損症のためのプラスミノーゲン補充療法 |
CN108289935A (zh) * | 2015-11-03 | 2018-07-17 | 普罗米蒂克生物治疗有限公司 | 纤溶酶原缺乏症的纤溶酶原替代疗法 |
US10874721B2 (en) | 2015-12-18 | 2020-12-29 | Talengen International Limited | Method for preventing and treating cervical erosion |
JP2019500427A (ja) * | 2015-12-18 | 2019-01-10 | タレンゲン インターナショナル リミテッドTalengen International Limited | 子宮膣部びらんを予防及び治療するための方法 |
JP2019500425A (ja) * | 2015-12-18 | 2019-01-10 | タレンゲン インターナショナル リミテッドTalengen International Limited | 肝組織損傷及びその関連疾患を予防及び治療するための方法 |
US11007253B2 (en) | 2015-12-18 | 2021-05-18 | Talengen International Limited | Method for preventing or treating radiation and chemical damage |
JP7171572B2 (ja) | 2016-12-15 | 2022-11-15 | タレンゲン インターナショナル リミテッド | 糖尿病を治療するための新しい方法 |
US11207387B2 (en) | 2016-12-15 | 2021-12-28 | Talengen International Limited | Method and drug for preventing and treating obesity |
JP2020502140A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 糖尿病を治療するための新しい方法 |
JP2020502133A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 肺の繊維化を予防及び治療するための方法 |
JP2020511413A (ja) * | 2016-12-15 | 2020-04-16 | タレンゲン インターナショナル リミテッドTalengen International Limited | 肝の繊維化を予防及び治療するための方法 |
JP2020512288A (ja) * | 2016-12-15 | 2020-04-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 組織器官の繊維化を予防及び治療するための方法 |
JP7313058B2 (ja) | 2016-12-15 | 2023-07-24 | タレンゲン インターナショナル リミテッド | 組織器官の繊維化を予防及び治療するための方法 |
JP2020502151A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | インスリン分泌を促進する方法 |
JP2020502132A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 皮膚の繊維化を予防及び治療するための方法 |
JP2020502134A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 病理学的腎組織損傷を予防及び治療するための方法 |
US11389515B2 (en) | 2016-12-15 | 2022-07-19 | Talengen International Limited | Method for mitigating heart disease |
US11478535B2 (en) | 2016-12-15 | 2022-10-25 | Talengen International Limited | Method for preventing and treating fatty liver |
JP2020502135A (ja) * | 2016-12-15 | 2020-01-23 | タレンゲン インターナショナル リミテッドTalengen International Limited | 薬物性腎損傷を予防及び治療するための方法 |
JP7182793B2 (ja) | 2016-12-15 | 2022-12-05 | タレンゲン インターナショナル リミテッド | 病理学的腎組織損傷を予防及び治療するための方法 |
US11547746B2 (en) | 2016-12-15 | 2023-01-10 | Talengen International Limited | Method for treating coronary atherosclerosis and complications thereof |
JP7213552B2 (ja) | 2016-12-15 | 2023-01-27 | タレンゲン インターナショナル リミテッド | 肝の繊維化を予防及び治療するための方法 |
JP7213553B2 (ja) | 2016-12-15 | 2023-01-27 | タレンゲン インターナショナル リミテッド | 肺の繊維化を予防及び治療するための方法 |
JP7242057B2 (ja) | 2016-12-15 | 2023-03-20 | タレンゲン インターナショナル リミテッド | 薬物性腎損傷を予防及び治療するための方法 |
JP2020524689A (ja) * | 2017-06-23 | 2020-08-20 | プロメティック・バイオセラピューティクス・インコーポレイテッドProMetic BioTherapeutics,Inc. | Pai−1過剰発現に関連する状態のプラスミノーゲン処置 |
Also Published As
Publication number | Publication date |
---|---|
JP5566105B2 (ja) | 2014-08-06 |
WO2008026999A3 (en) | 2008-05-22 |
EA200970233A1 (ru) | 2009-08-28 |
CA2662101A1 (en) | 2008-03-06 |
EP2056864A2 (en) | 2009-05-13 |
KR101517626B1 (ko) | 2015-05-07 |
EP2056864A4 (en) | 2012-01-25 |
KR20090059122A (ko) | 2009-06-10 |
CA2662101C (en) | 2015-07-07 |
DK2056864T3 (en) | 2014-03-10 |
CN101563100B (zh) | 2013-08-07 |
MX2009002226A (es) | 2009-09-07 |
US20160243204A1 (en) | 2016-08-25 |
CN101573134B (zh) | 2013-03-06 |
EA016250B1 (ru) | 2012-03-30 |
EP2056864B1 (en) | 2013-12-11 |
WO2008026999A2 (en) | 2008-03-06 |
US10729750B2 (en) | 2020-08-04 |
ES2451015T3 (es) | 2014-03-26 |
US20130149321A1 (en) | 2013-06-13 |
AU2007290881A1 (en) | 2008-03-06 |
US20100099600A1 (en) | 2010-04-22 |
US8318661B2 (en) | 2012-11-27 |
AU2007290881B2 (en) | 2013-03-07 |
CN101573134A (zh) | 2009-11-04 |
CN101563100A (zh) | 2009-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5566105B2 (ja) | 感染症に対する候補薬 | |
Glasser et al. | Mechanisms of lung fibrosis resolution | |
Majchrzak-Gorecka et al. | Secretory leukocyte protease inhibitor (SLPI), a multifunctional protein in the host defense response | |
Zhu et al. | Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation | |
US20180092961A1 (en) | Extracellular histones as biomarkers for prognosis and molecular targets for therapy | |
Vega-Carrascal et al. | Dysregulation of TIM-3–galectin-9 pathway in the cystic fibrosis airways | |
Yang et al. | Reduction of arthritis severity in protease‐activated receptor–deficient mice | |
Gabre et al. | Activated protein C accelerates venous thrombus resolution through heme oxygenase‐1 induction | |
JP2023052764A (ja) | 急性虚血性脳卒中の処置のための方法及び医薬組成物 | |
Homma et al. | Potential involvement of the epidermal growth factor receptor ligand epiregulin and matrix metalloproteinase-1 in pathogenesis of chronic rhinosinusitis | |
JP2020023519A (ja) | 異常な皮膚瘢痕化の治療 | |
JP2017532365A (ja) | コラーゲンivの置き換え | |
JP2009528339A (ja) | ペプチド及びその使用 | |
JP6793748B2 (ja) | 放射性および化学的損傷を予防及び治療するための方法 | |
Van Veen et al. | Anticoagulant and anti‐inflammatory effects after peritoneal lavage with antithrombin in experimental polymicrobial peritonitis | |
JP5576657B2 (ja) | カスパーゼ−8ならびに炎症、感染および創傷治癒 | |
JP2013532649A (ja) | 初期免疫防御において新規な機能を発揮する先祖セリンプロテアーゼ凝固カスケード | |
Sacitharan | Linking ageing and arthritis: The role of the longevityrelated SIRT1 molecule in age-related cartilage degeneration and osteoarthritis | |
Dale | Genetic Predisposition and M1 Macrophage Polarization Created by Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation | |
Gyorke | The Role of Interleukin-1a and the Noncanonical Inflammasome in Murine Chlamydial Oviduct Disease | |
Portou | The role of Toll-like Receptor 4 in diabetic foot ulceration | |
Liu | Role of Fibulin1 in the Pathogenesis of Chronic Pulmonary Diseases | |
Wernersson | Mast Cell Proteases | |
Hendel | Granzyme B in vascular remodeling and pathological angiogenesis | |
Verma et al. | The Role of Anticoagulation in IPF |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100716 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100716 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120904 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121114 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121121 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130226 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130806 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20131011 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20131021 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140204 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140527 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140617 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5566105 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |