DE69937206T2 - TNF-Peptide und deren Verwendung zur Behandlung von Ödemen - Google Patents
TNF-Peptide und deren Verwendung zur Behandlung von Ödemen Download PDFInfo
- Publication number
- DE69937206T2 DE69937206T2 DE69937206T DE69937206T DE69937206T2 DE 69937206 T2 DE69937206 T2 DE 69937206T2 DE 69937206 T DE69937206 T DE 69937206T DE 69937206 T DE69937206 T DE 69937206T DE 69937206 T2 DE69937206 T2 DE 69937206T2
- Authority
- DE
- Germany
- Prior art keywords
- tnf
- peptide
- edema
- amino acids
- peptides
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 206010030113 Oedema Diseases 0.000 title claims abstract description 24
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 title claims abstract description 10
- 102100040247 Tumor necrosis factor Human genes 0.000 title description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims abstract description 93
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 93
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims abstract description 92
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 31
- 206010037423 Pulmonary oedema Diseases 0.000 claims abstract description 9
- 102000057041 human TNF Human genes 0.000 claims abstract description 7
- 150000001413 amino acids Chemical class 0.000 claims description 22
- 235000001014 amino acid Nutrition 0.000 claims description 20
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 14
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 9
- 208000005333 pulmonary edema Diseases 0.000 claims description 8
- GJLXVWOMRRWCIB-MERZOTPQSA-N (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanamide Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=C(O)C=C1 GJLXVWOMRRWCIB-MERZOTPQSA-N 0.000 claims description 5
- 230000027455 binding Effects 0.000 claims description 5
- 235000018417 cysteine Nutrition 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001945 cysteines Chemical class 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 abstract description 3
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- 210000004072 lung Anatomy 0.000 description 30
- 230000000694 effects Effects 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 23
- 239000012528 membrane Substances 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 150000002632 lipids Chemical class 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 101100046526 Mus musculus Tnf gene Proteins 0.000 description 9
- 210000002889 endothelial cell Anatomy 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000011533 pre-incubation Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000002502 liposome Substances 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- 241001529936 Murinae Species 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 230000000503 lectinlike effect Effects 0.000 description 6
- 108010021152 pepBs1-Ac peptide Proteins 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- ZVDGOJFPFMINBM-UHFFFAOYSA-N 3-(6-methoxyquinolin-1-ium-1-yl)propane-1-sulfonate Chemical compound [O-]S(=O)(=O)CCC[N+]1=CC=CC2=CC(OC)=CC=C21 ZVDGOJFPFMINBM-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 5
- 229960002576 amiloride Drugs 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 210000003024 peritoneal macrophage Anatomy 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 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 description 4
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 108090000862 Ion Channels Proteins 0.000 description 3
- 102000004310 Ion Channels Human genes 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- 239000000232 Lipid Bilayer Substances 0.000 description 3
- 101000648740 Mus musculus Tumor necrosis factor Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 101150009046 Tnfrsf1a gene Proteins 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 231100000057 systemic toxicity Toxicity 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000003384 trypanolytic effect Effects 0.000 description 3
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 2
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 101100425758 Mus musculus Tnfrsf1b gene Proteins 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 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 description 2
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007831 electrophysiology Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000010220 ion permeability Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000004983 pleiotropic effect Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 108010064171 Lysosome-Associated Membrane Glycoproteins Proteins 0.000 description 1
- 102000014944 Lysosome-Associated Membrane Glycoproteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CDOJPCSDOXYJJF-CBTAGEKQSA-N N,N'-diacetylchitobiose Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CDOJPCSDOXYJJF-CBTAGEKQSA-N 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 102000037602 Platelet Endothelial Cell Adhesion Molecule-1 Human genes 0.000 description 1
- 108010069381 Platelet Endothelial Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 208000009362 Pneumococcal Pneumonia Diseases 0.000 description 1
- 206010035728 Pneumonia pneumococcal Diseases 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 206010061924 Pulmonary toxicity Diseases 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 239000004231 Riboflavin-5-Sodium Phosphate Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010057179 Toxoplasma infections Diseases 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- DSNRWDQKZIEDDB-GCMPNPAFSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-[(z)-octadec-9-enoyl]oxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC DSNRWDQKZIEDDB-GCMPNPAFSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008846 dynamic interplay Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000002713 epithelial sodium channel blocking agent Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000001506 fluorescence spectroscopy Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- -1 non-natural AS) Chemical class 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 206010034674 peritonitis Diseases 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 231100000374 pneumotoxicity Toxicity 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000006432 protein unfolding Effects 0.000 description 1
- 230000008695 pulmonary vasoconstriction Effects 0.000 description 1
- 230000008704 pulmonary vasodilation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 208000021043 septic peritonitis Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 208000022218 streptococcal pneumonia Diseases 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction 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
- 108700012359 toxins Proteins 0.000 description 1
- 230000000654 trypanocidal effect Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
-
- 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
- A61P7/10—Antioedematous agents; Diuretics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/525—Tumour necrosis factor [TNF]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98870180 | 1998-08-14 | ||
| EP98870180 | 1998-08-14 | ||
| EP98870198 | 1998-09-18 | ||
| EP98870198 | 1998-09-18 | ||
| EP98870222 | 1998-10-21 | ||
| EP98870222 | 1998-10-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69937206D1 DE69937206D1 (de) | 2007-11-08 |
| DE69937206T2 true DE69937206T2 (de) | 2008-06-19 |
Family
ID=27239778
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69937206T Expired - Lifetime DE69937206T2 (de) | 1998-08-14 | 1999-08-10 | TNF-Peptide und deren Verwendung zur Behandlung von Ödemen |
| DE69938743T Expired - Lifetime DE69938743D1 (de) | 1998-08-14 | 1999-08-10 | TNF-Peptide zur Behandlung von Ödemen |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69938743T Expired - Lifetime DE69938743D1 (de) | 1998-08-14 | 1999-08-10 | TNF-Peptide zur Behandlung von Ödemen |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US20030105021A1 (enExample) |
| EP (3) | EP1105152A1 (enExample) |
| JP (1) | JP4542266B2 (enExample) |
| CN (1) | CN1181886C (enExample) |
| AT (2) | ATE395072T1 (enExample) |
| AU (1) | AU764992B2 (enExample) |
| BR (1) | BR9912899A (enExample) |
| CA (1) | CA2334941C (enExample) |
| CZ (1) | CZ302862B6 (enExample) |
| DE (2) | DE69937206T2 (enExample) |
| DK (1) | DK1264599T3 (enExample) |
| ES (1) | ES2296872T3 (enExample) |
| HU (1) | HU227661B1 (enExample) |
| IL (2) | IL141064A0 (enExample) |
| NZ (1) | NZ509604A (enExample) |
| PL (1) | PL203706B1 (enExample) |
| PT (1) | PT1264599E (enExample) |
| TR (1) | TR200100338T2 (enExample) |
| WO (1) | WO2000009149A1 (enExample) |
| ZA (1) | ZA200100656B (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ302862B6 (cs) | 1998-08-14 | 2011-12-21 | Lécivo na lécení otoku | |
| JP5108515B2 (ja) * | 2004-08-06 | 2012-12-26 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | 肺サーファクタント及びｔｎｆ由来ペプチドを含有する組成物 |
| EP2009023A1 (en) * | 2007-06-04 | 2008-12-31 | Rentschler Beteiligungs GmbH | Novel peptides and their use for the treatment of edema |
| AT506151B1 (de) | 2007-12-12 | 2010-01-15 | Apeptico Forschung Und Entwick | Fusionsprotein |
| AT506150B1 (de) * | 2007-12-12 | 2010-01-15 | Apeptico Forschung Und Entwick | Zyklisches und cystein-freies peptid |
| AT507953B1 (de) | 2009-03-05 | 2011-02-15 | Apeptico Forschung & Entwicklung Gmbh | Verfahren zur vermeidung und zur behandlung einer hyperpermeabilität |
| AT509267A1 (de) | 2010-01-14 | 2011-07-15 | Apeptico Forschung & Entwicklung Gmbh | Organische verbindungen zur regulierung von vektoriellen ionenkanälen |
| PL2397151T3 (pl) * | 2010-06-21 | 2015-10-30 | Apeptico Forschung & Entwicklung Gmbh | Leczenie powikłań naczyniowych cukrzycy |
| AT510585B1 (de) | 2010-11-18 | 2012-05-15 | Apeptico Forschung & Entwicklung Gmbh | Zusammensetzung umfassend ein peptid und ein hemmstoff der viralen neuraminidase |
| US11161881B2 (en) * | 2010-11-18 | 2021-11-02 | Apeptico Forschung Und Entwicklung Gmbh | Composition comprising a peptide and an inhibitor of viral neuraminidase |
| EP2679239A1 (de) * | 2012-06-28 | 2014-01-01 | Apeptico Forschung und Entwicklung GmbH | Pharmazeutische Zusammensetzung zur Behandlung der durch Sauerstoffarmut und verringerten Luftdruck vermittelten pulmonalen Form der Höhenkrankheit |
| US12004506B2 (en) | 2013-04-23 | 2024-06-11 | Apeptico Forschung Und Entwicklung Gmbh | Pharmaceutical composition comprising a cyclic peptide of formula X1-GQRETPEGAEAKPWY-X2 and use for extracorporeal lung treatment |
| ES2813379T3 (es) * | 2013-04-23 | 2021-03-23 | Apeptico Forschung & Entwicklung Gmbh | Tratamiento extracorporal del pulmón con un péptido cíclico de formula x1-gqretpegaeakpwy-x2 |
| ES2665180T3 (es) | 2014-03-18 | 2018-04-24 | Apeptico Forschung Und Entwicklung Gmbh | Medicamento de péptido en forma de polvo seco |
| CN110613838A (zh) * | 2018-06-19 | 2019-12-27 | 姜石松 | 增强细胞通透性的多肽及其应用 |
| CN120795059A (zh) | 2018-08-27 | 2025-10-17 | 瑞泽恩制药公司 | 拉曼光谱在下游纯化中的应用 |
| IL294894A (en) | 2020-05-08 | 2022-09-01 | Apeptico Forschung & Entwicklung Gmbh | A peptide for the prevention or treatment of covid-19 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE384179C (de) * | 1921-04-07 | 1923-10-27 | Ludwig Weil Dr | Laufrad fuer Kreiselpumpen und -geblaese |
| DE3841759A1 (de) | 1988-12-12 | 1990-06-13 | Basf Ag | Neue tnf-peptide |
| US5891679A (en) * | 1993-02-03 | 1999-04-06 | N.V. Innogenetics S.A. | TNF-alpha muteins and a process for preparing them |
| CZ302862B6 (cs) | 1998-08-14 | 2011-12-21 | Lécivo na lécení otoku |
-
1999
- 1999-08-10 CZ CZ20010538A patent/CZ302862B6/cs not_active IP Right Cessation
- 1999-08-10 DE DE69937206T patent/DE69937206T2/de not_active Expired - Lifetime
- 1999-08-10 EP EP99942835A patent/EP1105152A1/en not_active Withdrawn
- 1999-08-10 PT PT02077256T patent/PT1264599E/pt unknown
- 1999-08-10 BR BR9912899-3A patent/BR9912899A/pt active Search and Examination
- 1999-08-10 EP EP02077256A patent/EP1264599B1/en not_active Expired - Lifetime
- 1999-08-10 PL PL345997A patent/PL203706B1/pl unknown
- 1999-08-10 AU AU56209/99A patent/AU764992B2/en not_active Ceased
- 1999-08-10 JP JP2000564651A patent/JP4542266B2/ja not_active Expired - Lifetime
- 1999-08-10 IL IL14106499A patent/IL141064A0/xx unknown
- 1999-08-10 NZ NZ509604A patent/NZ509604A/en not_active IP Right Cessation
- 1999-08-10 DE DE69938743T patent/DE69938743D1/de not_active Expired - Lifetime
- 1999-08-10 WO PCT/EP1999/005806 patent/WO2000009149A1/en not_active Ceased
- 1999-08-10 TR TR2001/00338T patent/TR200100338T2/xx unknown
- 1999-08-10 HU HU0103117A patent/HU227661B1/hu not_active IP Right Cessation
- 1999-08-10 AT AT02077274T patent/ATE395072T1/de active
- 1999-08-10 AT AT02077256T patent/ATE374039T1/de active
- 1999-08-10 DK DK02077256T patent/DK1264599T3/da active
- 1999-08-10 EP EP02077274A patent/EP1247531B1/en not_active Expired - Lifetime
- 1999-08-10 ES ES02077256T patent/ES2296872T3/es not_active Expired - Lifetime
- 1999-08-10 CA CA2334941A patent/CA2334941C/en not_active Expired - Lifetime
- 1999-08-10 CN CNB998096555A patent/CN1181886C/zh not_active Expired - Lifetime
-
2001
- 2001-01-23 ZA ZA2001/00656A patent/ZA200100656B/en unknown
- 2001-01-24 IL IL141064A patent/IL141064A/en not_active IP Right Cessation
- 2001-02-09 US US09/779,703 patent/US20030105021A1/en not_active Abandoned
-
2002
- 2002-06-06 US US10/162,553 patent/US7258861B2/en not_active Expired - Lifetime
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69032600T3 (de) | Rekombinanter abkömmling des menschlichen faktors iii | |
| DE69230789T2 (de) | Methoden zur behandlung von durch den tumor nekrose faktor ausgelösten krankheiten | |
| DE60219611T2 (de) | Modifizierte annexin-proteine und verhinderung und behandlung von thrombose | |
| EP1247531B1 (en) | TNF-derived peptides for use in treating oedema | |
| US20110257601A1 (en) | Vegf antagonist formulations for intravitreal administration | |
| EP0705846B1 (de) | Hochmolekulare und niedermolekulare Fraktionen des von Willebrand-Faktors | |
| DE68929388T2 (de) | Aus Harn isolierte antikoagulierende Verbindung | |
| DE69830251T2 (de) | Langes pentraxin ptx3 enthaltende pharmazeutische zusammensetzungen | |
| DE69332654T2 (de) | Fragmente eines oberflächenaktiven lungenproteins | |
| EP2217619B1 (de) | Zyklisches, cystein-freies protein | |
| DE69637464T2 (de) | Therapeutische fragmente des "von willebrand" faktors | |
| DE69824358T2 (de) | Peptidfragment von LALF mit antiviraler Wirkung | |
| DE60011601T2 (de) | Rekombinantes sp-a zur behandlung und vorbeugung von pulmonaren infektionen und entzündungen | |
| EP2219663B9 (de) | Reverses protein | |
| HK1051805B (en) | Tnf-derived peptides for use in treating oedema | |
| HK1051802A (en) | Tnf-derived peptides for use in treating oedema | |
| WO1995007710A1 (en) | Remedy for wound | |
| MXPA01001527A (en) | Tnf-derived peptides for use in treating oedema | |
| LARSEN et al. | SOME PHYSIOLOGICAL EFFECTS OF FRACTIONATED JELLYFISH TOXIN | |
| DE69427546T2 (de) | Biologisch aktive peptide aus funktionellen domänen des baktericiden/die permeabilität erhöhenden proteins und ihre verwendung | |
| WO2004039978A2 (de) | Humanes chondroosteomodulin (tig2), herstellung und verwendung zur behandlung oder diagnose von knochen- und knorpelerkrankungen, fettsucht sowie entzündlichen erkrankungen und hauterkrankungen | |
| DE19948867A1 (de) | TNFalpha bindende Peptide und ihre Anwendung für Detektion, Inaktivierung und/oder Entfernung von TNFalpha aus biologischen Flüssigkeiten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |