EA030384B1 - Терапия легочной формы высотной болезни - Google Patents
Терапия легочной формы высотной болезни Download PDFInfo
- Publication number
- EA030384B1 EA030384B1 EA201500061A EA201500061A EA030384B1 EA 030384 B1 EA030384 B1 EA 030384B1 EA 201500061 A EA201500061 A EA 201500061A EA 201500061 A EA201500061 A EA 201500061A EA 030384 B1 EA030384 B1 EA 030384B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- peptide
- present
- pulmonary
- use according
- altitude sickness
- Prior art date
Links
- 208000008445 altitude sickness Diseases 0.000 title claims abstract description 63
- 230000002685 pulmonary effect Effects 0.000 title claims abstract description 59
- 238000002560 therapeutic procedure Methods 0.000 title abstract description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 212
- 150000001413 amino acids Chemical group 0.000 claims abstract description 70
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 239000003937 drug carrier Substances 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 45
- 239000004471 Glycine Substances 0.000 claims description 25
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000004472 Lysine Substances 0.000 claims description 12
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- 102000004169 proteins and genes Human genes 0.000 claims description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 11
- 239000011780 sodium chloride Substances 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 6
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 3
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 3
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 3
- 229930091371 Fructose Natural products 0.000 claims description 3
- 239000005715 Fructose Substances 0.000 claims description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 3
- 108010008488 Glycylglycine Proteins 0.000 claims description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 claims description 3
- 241000282412 Homo Species 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 229920000954 Polyglycolide Polymers 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 3
- 239000007983 Tris buffer Substances 0.000 claims description 3
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 3
- 229920001577 copolymer Polymers 0.000 claims description 3
- 239000008121 dextrose Substances 0.000 claims description 3
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 3
- 229940093471 ethyl oleate Drugs 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 150000004676 glycans Chemical class 0.000 claims description 3
- 229940043257 glycylglycine Drugs 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000000346 nonvolatile oil Substances 0.000 claims description 3
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 3
- 229920001282 polysaccharide Polymers 0.000 claims description 3
- 239000005017 polysaccharide Substances 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 239000001509 sodium citrate Substances 0.000 claims description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 239000008215 water for injection Substances 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 34
- 229910052760 oxygen Inorganic materials 0.000 abstract description 34
- 239000001301 oxygen Substances 0.000 abstract description 34
- 230000027455 binding Effects 0.000 abstract description 8
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 abstract 1
- 238000012961 medicinal therapy Methods 0.000 abstract 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 abstract 1
- 235000001014 amino acid Nutrition 0.000 description 62
- 229940024606 amino acid Drugs 0.000 description 62
- 210000004027 cell Anatomy 0.000 description 60
- 102000004196 processed proteins & peptides Human genes 0.000 description 58
- 210000004072 lung Anatomy 0.000 description 38
- 241000700159 Rattus Species 0.000 description 35
- 239000012530 fluid Substances 0.000 description 31
- 108010069514 Cyclic Peptides Proteins 0.000 description 28
- 102000001189 Cyclic Peptides Human genes 0.000 description 28
- 230000000694 effects Effects 0.000 description 28
- 238000012360 testing method Methods 0.000 description 27
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 24
- 229960002576 amiloride Drugs 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 201000010099 disease Diseases 0.000 description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 16
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 15
- 125000003277 amino group Chemical group 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 13
- 235000013922 glutamic acid Nutrition 0.000 description 13
- 239000004220 glutamic acid Substances 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 238000007363 ring formation reaction Methods 0.000 description 13
- 210000004899 c-terminal region Anatomy 0.000 description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 10
- 206010021143 Hypoxia Diseases 0.000 description 9
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 9
- 230000001154 acute effect Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 229940000635 beta-alanine Drugs 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 7
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 7
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 7
- 206010037423 Pulmonary oedema Diseases 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 235000003704 aspartic acid Nutrition 0.000 description 7
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 7
- 229960003104 ornithine Drugs 0.000 description 7
- 208000005333 pulmonary edema Diseases 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 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 6
- 241000700157 Rattus norvegicus Species 0.000 description 6
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 102000003837 Epithelial Sodium Channels Human genes 0.000 description 5
- 108090000140 Epithelial Sodium Channels Proteins 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 238000009640 blood culture Methods 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 229940100601 interleukin-6 Drugs 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 229910001415 sodium ion Inorganic materials 0.000 description 5
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 4
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- 108010052164 Sodium Channels Proteins 0.000 description 4
- 102000018674 Sodium Channels Human genes 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- 238000002651 drug therapy Methods 0.000 description 4
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 4
- 235000003642 hunger Nutrition 0.000 description 4
- 230000007954 hypoxia Effects 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 230000037351 starvation Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 206010047139 Vasoconstriction Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000013160 medical therapy Methods 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000037081 physical activity Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000025033 vasoconstriction Effects 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000024188 Andala Species 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 241001503987 Clematis vitalba Species 0.000 description 2
- 206010013647 Drowning Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010020952 Hypocapnia Diseases 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 208000004221 Multiple Trauma Diseases 0.000 description 2
- 208000023637 Multiple injury Diseases 0.000 description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000007123 Pulmonary Atelectasis Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 206010069351 acute lung injury Diseases 0.000 description 2
- 206010001053 acute respiratory failure Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000019504 cigarettes Nutrition 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000008706 hypoxic vasoconstriction Effects 0.000 description 2
- 230000037427 ion transport Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000008741 proinflammatory signaling process Effects 0.000 description 2
- 210000001147 pulmonary artery Anatomy 0.000 description 2
- 208000002815 pulmonary hypertension Diseases 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 201000004193 respiratory failure Diseases 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- LKVFMOMQYXIFRK-KSVAIKAXSA-N (3S,6S,9S,12S,18S,21S,27S,30S,33S,36S,42R,47R,50S,53S,56S)-42-amino-3-(4-aminobutyl)-36-(3-amino-3-oxopropyl)-33-(3-carbamimidamidopropyl)-9,18,30-tris(2-carboxyethyl)-27-[(1R)-1-hydroxyethyl]-50-[(4-hydroxyphenyl)methyl]-53-(1H-indol-3-ylmethyl)-6,12-dimethyl-2,5,8,11,14,17,20,26,29,32,35,38,41,49,52,55-hexadecaoxo-44,45-dithia-1,4,7,10,13,16,19,25,28,31,34,37,40,48,51,54-hexadecazatricyclo[54.3.0.021,25]nonapentacontane-47-carboxylic acid Chemical compound C[C@@H](O)[C@@H]1NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]2CCCN2C1=O)C(O)=O LKVFMOMQYXIFRK-KSVAIKAXSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- DIOSHTLNZVXJOF-UHFFFAOYSA-N 2,5-bis(3-oxobutanoylamino)benzenesulfonic acid Chemical group CC(=O)CC(=O)NC1=CC=C(NC(=O)CC(C)=O)C(S(O)(=O)=O)=C1 DIOSHTLNZVXJOF-UHFFFAOYSA-N 0.000 description 1
- 108010049501 AP301 peptide Proteins 0.000 description 1
- WPWUFUBLGADILS-WDSKDSINSA-N Ala-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O WPWUFUBLGADILS-WDSKDSINSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 240000006890 Erythroxylum coca Species 0.000 description 1
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 1
- 208000003241 Fat Embolism Diseases 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 206010020591 Hypercapnia Diseases 0.000 description 1
- 206010021133 Hypoventilation Diseases 0.000 description 1
- 206010022773 Intracranial pressure increased Diseases 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000034388 Mountain sickness acute Diseases 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108700023707 TUG1 Proteins 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical group [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- YSLMFVXKNNRMIG-UHFFFAOYSA-N [C].NCC(O)=O Chemical compound [C].NCC(O)=O YSLMFVXKNNRMIG-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 230000008382 alveolar damage Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000000233 bronchiolar non-ciliated Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003683 cardiac damage Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000008957 cocaer Nutrition 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry 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
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940000673 orphan drug Drugs 0.000 description 1
- 239000002859 orphan drug Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000037074 physically active Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- XWIJIXWOZCRYEL-UHFFFAOYSA-M potassium;methanesulfonate Chemical compound [K+].CS([O-])(=O)=O XWIJIXWOZCRYEL-UHFFFAOYSA-M 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 201000008312 primary pulmonary hypertension Diseases 0.000 description 1
- 230000007112 pro inflammatory response Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000007114 proinflammatory cascade Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000020874 response to hypoxia Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 208000037812 secondary pulmonary hypertension Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- KKVTYAVXTDIPAP-UHFFFAOYSA-M sodium;methanesulfonate Chemical compound [Na+].CS([O-])(=O)=O KKVTYAVXTDIPAP-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000009421 viral pneumonia Diseases 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12173983.3A EP2679239A1 (de) | 2012-06-28 | 2012-06-28 | Pharmazeutische Zusammensetzung zur Behandlung der durch Sauerstoffarmut und verringerten Luftdruck vermittelten pulmonalen Form der Höhenkrankheit |
| PCT/EP2013/062777 WO2014001177A1 (de) | 2012-06-28 | 2013-06-19 | Pharmazeutische zusammensetzung zur behandlung der durch sauerstoffarmut und verringerten luftdruck vermittelten pulmonalen form der höhenkrankheit |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201500061A1 EA201500061A1 (ru) | 2015-06-30 |
| EA030384B1 true EA030384B1 (ru) | 2018-07-31 |
Family
ID=48672620
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201500061A EA030384B1 (ru) | 2012-06-28 | 2013-06-19 | Терапия легочной формы высотной болезни |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US9802985B2 (OSRAM) |
| EP (2) | EP2679239A1 (OSRAM) |
| JP (1) | JP6113277B2 (OSRAM) |
| KR (1) | KR102010793B1 (OSRAM) |
| CN (1) | CN104427993B (OSRAM) |
| AP (1) | AP2014008162A0 (OSRAM) |
| AU (1) | AU2013283563B2 (OSRAM) |
| CA (1) | CA2875749C (OSRAM) |
| EA (1) | EA030384B1 (OSRAM) |
| ES (1) | ES2602197T3 (OSRAM) |
| IN (1) | IN2015DN00585A (OSRAM) |
| MX (1) | MX354302B (OSRAM) |
| PE (1) | PE20150198A1 (OSRAM) |
| WO (1) | WO2014001177A1 (OSRAM) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015132294A1 (en) * | 2014-03-04 | 2015-09-11 | Apeptico Forschung Und Entwicklung Gmbh | Attenuation of intrapulmonary inflammation |
| JP6397984B2 (ja) * | 2014-03-18 | 2018-09-26 | アペプティコ・フォルシュング・ウント・エントヴィックルング・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＡｐｅｐｔｉｃｏ Ｆｏｒｓｃｈｕｎｇ Ｕｎｄ Ｅｎｔｗｉｃｋｌｕｎｇ Ｇｍｂｈ | 乾燥粉末ペプチド医薬 |
| KR20180041749A (ko) | 2015-08-25 | 2018-04-24 | 바-일란 유니버시티 | 비대칭형 전기 화학 전지 장치 및 그 작동 방법 |
| EP3624885A4 (en) | 2017-05-19 | 2021-03-10 | Trudell Medical International | EXPIRATORY OVERPRESSURE DEVICE |
| USD903097S1 (en) | 2018-05-18 | 2020-11-24 | Trudell Medical International | Mask |
| USD874064S1 (en) | 2018-05-18 | 2020-01-28 | Trudell Medical International | Mask |
| USD893806S1 (en) | 2018-11-09 | 2020-08-18 | Trudell Medical Internationl | Mask and shroud |
| WO2021087037A1 (en) * | 2019-10-29 | 2021-05-06 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Lung-specific targeting-peptide (ltp), compositions, and uses thereof |
| EP4051307B1 (en) | 2020-05-08 | 2023-02-01 | APEPTICO Forschung und Entwicklung GmbH | Peptide for prevention or treatment of covid-19 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000009149A1 (en) * | 1998-08-14 | 2000-02-24 | Innogenetics N.V. | Tnf-derived peptides for use in treating oedema |
| WO2006013183A1 (en) * | 2004-08-06 | 2006-02-09 | Altana Pharma Ag | Composition comprising a pulmonary surfactant and a tnf-derived peptide |
| EP2009023A1 (en) * | 2007-06-04 | 2008-12-31 | Rentschler Beteiligungs GmbH | Novel peptides and their use for the treatment of edema |
| WO2009073909A1 (de) * | 2007-12-12 | 2009-06-18 | Apeptico Forschung Und Entwicklung Gmbh | Zyklisches, cystein-freies protein |
| WO2011085423A1 (de) * | 2010-01-14 | 2011-07-21 | Apeptico Forschung Und Entwicklung Gmbh | Zyklische peptide zur regulierung von vektoriellen ionenkanälen |
| WO2012065201A1 (de) * | 2010-11-18 | 2012-05-24 | Apeptico Forschung Und Entwicklung Gmbh | Zusammensetzung umfassend ein peptid und ein hemmstoff der viralen neuraminidase |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4069819A (en) | 1973-04-13 | 1978-01-24 | Societa Farmaceutici S.P.A. | Inhalation device |
| IT1228459B (it) | 1989-02-23 | 1991-06-19 | Phidea S R L | Inalatore con svuotamento regolare e completo della capsula. |
| CA2155103A1 (en) | 1993-02-03 | 1994-08-18 | Rudolph Lucas | Tnf-alpha muteins and a process for preparing them |
| CA2791847C (en) * | 2009-03-04 | 2017-05-02 | Mannkind Corporation | An improved dry powder drug delivery system |
| AT507953B1 (de) * | 2009-03-05 | 2011-02-15 | Apeptico Forschung & Entwicklung Gmbh | Verfahren zur vermeidung und zur behandlung einer hyperpermeabilität |
-
2012
- 2012-06-28 EP EP12173983.3A patent/EP2679239A1/de not_active Withdrawn
-
2013
- 2013-06-19 WO PCT/EP2013/062777 patent/WO2014001177A1/de not_active Ceased
- 2013-06-19 JP JP2015518983A patent/JP6113277B2/ja active Active
- 2013-06-19 US US14/410,642 patent/US9802985B2/en active Active
- 2013-06-19 PE PE2014002486A patent/PE20150198A1/es not_active Application Discontinuation
- 2013-06-19 CA CA2875749A patent/CA2875749C/en active Active
- 2013-06-19 EP EP13730877.1A patent/EP2866824B1/de active Active
- 2013-06-19 KR KR1020157000350A patent/KR102010793B1/ko active Active
- 2013-06-19 AU AU2013283563A patent/AU2013283563B2/en not_active Ceased
- 2013-06-19 EA EA201500061A patent/EA030384B1/ru unknown
- 2013-06-19 MX MX2014015048A patent/MX354302B/es active IP Right Grant
- 2013-06-19 IN IN585DEN2015 patent/IN2015DN00585A/en unknown
- 2013-06-19 AP AP2014008162A patent/AP2014008162A0/xx unknown
- 2013-06-19 ES ES13730877.1T patent/ES2602197T3/es active Active
- 2013-06-19 CN CN201380033379.XA patent/CN104427993B/zh active Active
-
2017
- 2017-09-25 US US15/714,111 patent/US20190211061A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000009149A1 (en) * | 1998-08-14 | 2000-02-24 | Innogenetics N.V. | Tnf-derived peptides for use in treating oedema |
| WO2006013183A1 (en) * | 2004-08-06 | 2006-02-09 | Altana Pharma Ag | Composition comprising a pulmonary surfactant and a tnf-derived peptide |
| EP2009023A1 (en) * | 2007-06-04 | 2008-12-31 | Rentschler Beteiligungs GmbH | Novel peptides and their use for the treatment of edema |
| WO2009073909A1 (de) * | 2007-12-12 | 2009-06-18 | Apeptico Forschung Und Entwicklung Gmbh | Zyklisches, cystein-freies protein |
| WO2011085423A1 (de) * | 2010-01-14 | 2011-07-21 | Apeptico Forschung Und Entwicklung Gmbh | Zyklische peptide zur regulierung von vektoriellen ionenkanälen |
| WO2012065201A1 (de) * | 2010-11-18 | 2012-05-24 | Apeptico Forschung Und Entwicklung Gmbh | Zusammensetzung umfassend ein peptid und ein hemmstoff der viralen neuraminidase |
Non-Patent Citations (1)
| Title |
|---|
| MAGGIORINI, M.: "High altitude-induced pulmonary oedema", CARDIOVASCULAR RESEARCH, OXFORD UNIVERSITY PRESS, GB, vol. 72, no. 1, 1 October 2006 (2006-10-01), GB, pages 41 - 50, XP025011558, ISSN: 0008-6363, DOI: 10.1016/j.cardiores.2006.07.004 * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2866824A1 (de) | 2015-05-06 |
| ES2602197T3 (es) | 2017-02-20 |
| AU2013283563A1 (en) | 2015-01-15 |
| EP2679239A1 (de) | 2014-01-01 |
| CA2875749A1 (en) | 2014-01-03 |
| KR102010793B1 (ko) | 2019-08-14 |
| CA2875749C (en) | 2019-02-26 |
| KR20150037815A (ko) | 2015-04-08 |
| PE20150198A1 (es) | 2015-02-19 |
| AP2014008162A0 (en) | 2014-12-31 |
| JP2015526399A (ja) | 2015-09-10 |
| CN104427993A (zh) | 2015-03-18 |
| CN104427993B (zh) | 2017-03-08 |
| AU2013283563B2 (en) | 2017-06-08 |
| EA201500061A1 (ru) | 2015-06-30 |
| WO2014001177A1 (de) | 2014-01-03 |
| MX2014015048A (es) | 2015-06-05 |
| US20150225460A1 (en) | 2015-08-13 |
| EP2866824B1 (de) | 2016-08-10 |
| JP6113277B2 (ja) | 2017-04-12 |
| IN2015DN00585A (OSRAM) | 2015-06-26 |
| MX354302B (es) | 2018-02-23 |
| US9802985B2 (en) | 2017-10-31 |
| US20190211061A1 (en) | 2019-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EA030384B1 (ru) | Терапия легочной формы высотной болезни | |
| Yamada et al. | Serum interleukin-6, interleukin-8, hepatocyte growth factor, and nitric oxide changes during thoracic surgery | |
| US11639368B2 (en) | Method for preventing and treating hyperpermeability | |
| Chohan et al. | Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide | |
| Khafagy et al. | Systemic and brain delivery of leptin via intranasal coadministration with cell-penetrating peptides and its therapeutic potential for obesity | |
| Zhang et al. | Activation of CXCR7 alleviates cardiac insufficiency after myocardial infarction by promoting angiogenesis and reducing apoptosis | |
| Itoh et al. | Secretion of N-terminal fragment of gamma-human atrial natriuretic polypeptide. | |
| KR20220166809A (ko) | 급성 호흡곤란 증후군 및 바이러스 감염 치료를 위한 cxcr4 억제제 | |
| US20020128203A1 (en) | Methods of identifying inhibitory compounds and uses thereof | |
| Salo et al. | Urinary excretion of urodilatin in patients with cirrhosis | |
| EP4545971A2 (en) | Peptide with neutralizing activity against severe acute respiratory syndrome coronavirus 2 | |
| US20240325496A1 (en) | Cxc chemokine agonists and antagonists in covid-19 disease and diagnostic assays | |
| Moriarty et al. | Effect of peptide histidine isoleucine on water and electrolyte transport in the human jejunum. | |
| Wang et al. | orexin B alleviates sepsis‐associated lung injury through the attenuation of pulmonary endothelial barrier dysfunction by regulating the rho‐associated coiled‐coil containing protein kinase 2/zonula occludens‐1 (ROCK2/ZO‐1) axis | |
| US20240002437A1 (en) | Compositions and methods of treating inflammatory lung diseases | |
| US20070207162A1 (en) | Ubiquitin and ubiquitin related molecules for treatment and prevention of harmful activation of the immune system | |
| CN112368014A (zh) | 抗分泌因子在治疗和/或预防急性呼吸衰竭中的用途 | |
| US8372799B2 (en) | Reverse protein | |
| CN120965818A (zh) | 抑制TNFa蛋白活性的舒缓抗炎多肽 | |
| KR20240001620A (ko) | hsa-miR-4517 발현 촉진제를 포함하는 천식 예방, 치료, 또는 개선용 조성물 및 마이크로코커스 루테우스 유래 소포를 이용한 천식 진단방법 | |
| HK40065839A (zh) | 使用补体抑制剂治疗神经疾病 | |
| CN117441105A (zh) | 用于危重病患者中皮质类固醇疗法分层的成熟肾上腺髓质素 | |
| Amano et al. | Filter leukapheresis—The new promising therapeutic approach for inflammatory bowel disease | |
| Kitamura et al. | Biochemistry of adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP) | |
| PITTET | in Patients with Sepsis |