DE60313982T2 - Dimere von thrombinpeptidderivaten - Google Patents
Dimere von thrombinpeptidderivaten Download PDFInfo
- Publication number
- DE60313982T2 DE60313982T2 DE60313982T DE60313982T DE60313982T2 DE 60313982 T2 DE60313982 T2 DE 60313982T2 DE 60313982 T DE60313982 T DE 60313982T DE 60313982 T DE60313982 T DE 60313982T DE 60313982 T2 DE60313982 T2 DE 60313982T2
- Authority
- DE
- Germany
- Prior art keywords
- gly
- asp
- dimer
- pro
- thrombin peptide
- 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
- 239000000539 dimer Substances 0.000 title claims abstract description 76
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 148
- 229960004072 thrombin Drugs 0.000 claims abstract description 118
- 108090000190 Thrombin Proteins 0.000 claims abstract description 117
- 150000001413 amino acids Chemical group 0.000 claims abstract description 82
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 239000012634 fragment Substances 0.000 claims abstract description 23
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 23
- 210000004899 c-terminal region Anatomy 0.000 claims abstract description 20
- 229920001184 polypeptide Polymers 0.000 claims abstract description 20
- 229940117028 Thrombin receptor agonist Drugs 0.000 claims abstract description 7
- OXHYRVSBKWIFES-WWSDOYNLSA-N trap-14 peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=CC=C1 OXHYRVSBKWIFES-WWSDOYNLSA-N 0.000 claims abstract description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 20
- 239000000178 monomer Substances 0.000 claims description 20
- 210000000988 bone and bone Anatomy 0.000 claims description 13
- 230000008468 bone growth Effects 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 102000003790 Thrombin receptors Human genes 0.000 claims description 10
- 108090000166 Thrombin receptors Proteins 0.000 claims description 10
- 150000001408 amides Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 230000008439 repair process Effects 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 7
- 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 claims description 6
- 208000037803 restenosis Diseases 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 230000029663 wound healing Effects 0.000 claims description 5
- 210000000845 cartilage Anatomy 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 208000010392 Bone Fractures Diseases 0.000 claims description 3
- 208000002607 Pseudarthrosis Diseases 0.000 claims description 3
- 206010017076 Fracture Diseases 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 12
- 239000003869 thrombin derivative Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 15
- 235000001014 amino acid Nutrition 0.000 description 42
- 229940024606 amino acid Drugs 0.000 description 42
- AHMIRVCNZZUANP-LPBAWZRYSA-N chrysalin Chemical compound CC(O)=O.CC(O)=O.C([C@@H](C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)N)C1=CC=CC=C1.C([C@@H](C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)N)C1=CC=CC=C1.C([C@@H](C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)N)C1=CC=CC=C1 AHMIRVCNZZUANP-LPBAWZRYSA-N 0.000 description 39
- 208000027418 Wounds and injury Diseases 0.000 description 38
- 206010052428 Wound Diseases 0.000 description 37
- 108010018091 rusalatide acetate Proteins 0.000 description 30
- 239000003981 vehicle Substances 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 15
- 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 description 14
- 239000000203 mixture Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 229920000642 polymer Polymers 0.000 description 11
- 230000000694 effects Effects 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 235000010355 mannitol Nutrition 0.000 description 7
- 229920002627 poly(phosphazenes) Polymers 0.000 description 7
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 229920000954 Polyglycolide Polymers 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000035876 healing Effects 0.000 description 5
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 5
- 239000011859 microparticle Substances 0.000 description 5
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 5
- 239000004633 polyglycolic acid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 229920002732 Polyanhydride Polymers 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229920000747 poly(lactic acid) Polymers 0.000 description 4
- 239000004626 polylactic acid Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000012224 working solution Substances 0.000 description 4
- ZLUFYQVHJAVDHU-NSCUHMNNSA-N (6e)-2-methyl-2,3-dihydro-1,4-dioxocine-5,8-dione Chemical class CC1COC(=O)\C=C\C(=O)O1 ZLUFYQVHJAVDHU-NSCUHMNNSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 3
- 239000002250 absorbent Substances 0.000 description 3
- 230000002745 absorbent Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 238000002399 angioplasty Methods 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 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 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000001612 chondrocyte Anatomy 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000003349 gelling agent Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 229920001519 homopolymer Polymers 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 230000000278 osteoconductive effect Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010056340 Diabetic ulcer Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 238000013222 sprague-dawley male rat Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960002898 threonine Drugs 0.000 description 2
- 229940078499 tricalcium phosphate Drugs 0.000 description 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
- 235000019731 tricalcium phosphate Nutrition 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- BVLVGYXYGXOSOG-UHFFFAOYSA-N 2-hexoxybenzoic acid Chemical compound CCCCCCOC1=CC=CC=C1C(O)=O BVLVGYXYGXOSOG-UHFFFAOYSA-N 0.000 description 1
- VBISQLWPGDULSX-UHFFFAOYSA-N 4-[3-(4-carboxyphenoxy)propoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCCCOC1=CC=C(C(O)=O)C=C1 VBISQLWPGDULSX-UHFFFAOYSA-N 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- 241000242757 Anthozoa Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 206010007710 Cartilage injury Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010066259 Collagraft Proteins 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000651439 Homo sapiens Prothrombin Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 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 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
- ODYCAZSSUVCHNU-XLAORIBOSA-N Laurencin Natural products CC[C@H]1C[C@H](CC=CC[C@@H]1Br)[C@@H](CC=CC#C)OC(=O)C ODYCAZSSUVCHNU-XLAORIBOSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000006833 Multifunctional Enzymes Human genes 0.000 description 1
- 108010047290 Multifunctional Enzymes Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 229920001963 Synthetic biodegradable polymer Polymers 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940031955 anhydrous lanolin Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000004068 calcium phosphate ceramic Substances 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010252 digital analysis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000001839 endoscopy Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012527 feed solution Substances 0.000 description 1
- 108060002894 fibrillar collagen Proteins 0.000 description 1
- 102000013373 fibrillar collagen Human genes 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 210000001564 haversian system Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940039715 human prothrombin Drugs 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000008384 inner phase Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000002357 laparoscopic surgery Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000004820 osteoconduction Effects 0.000 description 1
- 210000005009 osteogenic cell Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001299 polypropylene fumarate Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100001055 skeletal defect Toxicity 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 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
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 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
- -1 vaseline Substances 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6429—Thrombin (3.4.21.5)
-
- 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
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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)
- C12Y304/21005—Thrombin (3.4.21.5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39357902P | 2002-07-02 | 2002-07-02 | |
| US393579P | 2002-07-02 | ||
| PCT/US2003/020626 WO2004005317A2 (en) | 2002-07-02 | 2003-07-01 | Thrombin peptide derivative dimers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60313982D1 DE60313982D1 (de) | 2007-07-05 |
| DE60313982T2 true DE60313982T2 (de) | 2008-01-17 |
Family
ID=30115603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60313982T Expired - Lifetime DE60313982T2 (de) | 2002-07-02 | 2003-07-01 | Dimere von thrombinpeptidderivaten |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7456250B2 (https=) |
| EP (1) | EP1539800B1 (https=) |
| JP (1) | JP4668612B2 (https=) |
| AT (1) | ATE362939T1 (https=) |
| AU (1) | AU2003247848B2 (https=) |
| CA (1) | CA2491135A1 (https=) |
| DE (1) | DE60313982T2 (https=) |
| WO (1) | WO2004005317A2 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1913917B (zh) * | 2003-12-31 | 2012-02-01 | 正统逻辑公司 | 凝血酶肽衍生物的药物组合物 |
| JP2010504336A (ja) * | 2006-09-22 | 2010-02-12 | オーソロジック コーポレイション | 血管内皮機能不全を治療する方法 |
| WO2008100567A2 (en) * | 2007-02-15 | 2008-08-21 | Orthologic Corp. | Thrombin peptide derivatives for treating fractures in osteopenic patients |
| EP2155234A1 (en) * | 2007-04-10 | 2010-02-24 | The Board of Regents,The University of Texas System | Combination therapy for chronic dermal ulcers |
| WO2008124173A1 (en) * | 2007-04-10 | 2008-10-16 | The Board Of Regents, The University Of Texas System | Combination therapy for cardiac revascularization and cardiac repair |
| CA2722621A1 (en) * | 2008-03-26 | 2009-10-01 | Orthologic Corp. | Thrombin derived peptides for smooth muscle relaxation |
| EP2280722A2 (en) * | 2008-03-26 | 2011-02-09 | Orthologic Corp. | Method of treating degenerative diseases |
| US20110105400A1 (en) * | 2008-03-26 | 2011-05-05 | Orthologic Corp. | Methods for treating acute myocardial infarction |
| WO2009120307A2 (en) * | 2008-03-26 | 2009-10-01 | Orthologic Corp. | Method of treating peripheral arterial disease |
| CU23716A1 (es) * | 2008-09-30 | 2011-10-05 | Ct Ingenieria Genetica Biotech | Péptido antagonista de la actividad de la interleucina-15 |
| JP2013529600A (ja) | 2010-06-11 | 2013-07-22 | ザ ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム | 放射の影響を軽減し、及び全身性感染症のリスクを減少させる方法 |
| US10220078B2 (en) | 2014-06-11 | 2019-03-05 | The Board Of Regents Of The University Of Texas System | Methods of using thrombin derivatives to treat medulloblastoma |
| EP3952991A4 (en) * | 2019-04-12 | 2023-08-09 | Affirmed Pharma, LLC | RUSALATIDE ACETATE COMPOSITIONS |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5352664A (en) | 1986-10-31 | 1994-10-04 | Board Of Regents, The University Of Texas System | Thrombin derived polypeptides; compositions and methods for use |
| US6500934B1 (en) * | 1996-07-24 | 2002-12-31 | Michael Rush Lerner | Bivalent agonists for G-protein coupled receptors |
| TWI257307B (en) | 2000-07-12 | 2006-07-01 | Orthologic Corp | Pharmaceutical composition for cardiac tissue repair |
| ATE254925T1 (de) | 2000-07-19 | 2003-12-15 | Univ Texas | Stimulierung des knochenwachstums mit peptidderivaten von thrombin |
| AU7356101A (en) | 2000-07-20 | 2002-02-05 | Univ Texas | Stimulation of cartilage growth with agonists of the non-proteolytically activated thrombin receptor |
| ES2271216T3 (es) | 2001-07-27 | 2007-04-16 | Orthologic Corp. | Uso de los peptidos derivados de la trombina para la terapia de las ulceras dermicas cronicas. |
| TW200407905A (en) * | 2002-11-06 | 2004-05-16 | Leadtek Research Inc | Data write-in and read-out method of flash memory and circuit thereof |
| CN1913917B (zh) | 2003-12-31 | 2012-02-01 | 正统逻辑公司 | 凝血酶肽衍生物的药物组合物 |
-
2003
- 2003-07-01 DE DE60313982T patent/DE60313982T2/de not_active Expired - Lifetime
- 2003-07-01 AT AT03763062T patent/ATE362939T1/de not_active IP Right Cessation
- 2003-07-01 JP JP2004519705A patent/JP4668612B2/ja not_active Expired - Fee Related
- 2003-07-01 WO PCT/US2003/020626 patent/WO2004005317A2/en not_active Ceased
- 2003-07-01 CA CA002491135A patent/CA2491135A1/en not_active Abandoned
- 2003-07-01 AU AU2003247848A patent/AU2003247848B2/en not_active Ceased
- 2003-07-01 EP EP03763062A patent/EP1539800B1/en not_active Expired - Lifetime
-
2004
- 2004-12-30 US US11/027,795 patent/US7456250B2/en not_active Expired - Lifetime
-
2008
- 2008-10-10 US US12/287,703 patent/US7919457B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1539800B1 (en) | 2007-05-23 |
| JP2006507229A (ja) | 2006-03-02 |
| JP4668612B2 (ja) | 2011-04-13 |
| AU2003247848C1 (en) | 2004-01-23 |
| US7919457B2 (en) | 2011-04-05 |
| ATE362939T1 (de) | 2007-06-15 |
| US20050153893A1 (en) | 2005-07-14 |
| DE60313982D1 (de) | 2007-07-05 |
| WO2004005317A2 (en) | 2004-01-15 |
| EP1539800A2 (en) | 2005-06-15 |
| AU2003247848B2 (en) | 2006-12-21 |
| US20090124550A1 (en) | 2009-05-14 |
| US7456250B2 (en) | 2008-11-25 |
| CA2491135A1 (en) | 2004-01-15 |
| EP1539800A4 (en) | 2005-11-16 |
| WO2004005317A3 (en) | 2004-09-30 |
| AU2003247848A1 (en) | 2004-01-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE602004005564T2 (de) | Pharmazeutische Zusammensetzung für Thrombinpeptidderivaten | |
| DE60101339T2 (de) | Stimulierung des knochenwachstums mit peptidderivaten von thrombin | |
| DE60225185T2 (de) | Wachstumsfaktor-modifizierte proteinmatrizes zur geweberekonstruktion (tissue engineering) | |
| US7919457B2 (en) | Thrombin peptide derivative dimers | |
| DE60100740T2 (de) | Verwendung von thrombin-derivierten peptiden zur therapie von kardiovaskuläre krankheiten | |
| KR910005886B1 (ko) | 연골조직의 치료약제 | |
| DE60105772T2 (de) | Stimulation des knorpelwachstums mit agonisten des nicht-proteolytisch aktivierten thrombin rezeptors | |
| CA2835369C (en) | Peptide fragments for inducing synthesis of extracellular matrix proteins | |
| DE69202332T2 (de) | Wachstumsfaktor enthaltende matrix zur behandlung von knorpelschäden. | |
| DE69928472T2 (de) | Stabilisierte pharmazeutische Zusammensetzungen von Hedgehog-Proteinen und deren Verwendung | |
| DE69736487T2 (de) | Peptidzusammensetzung mit wachstumsfaktor-ähnlicher aktivität | |
| CH665356A5 (de) | Pharmazeutische formulierung. | |
| DE68911061T2 (de) | Mittel zur Kontrolle von Thrombenbildungen. | |
| EP0047647A2 (en) | Pharmaceutical compositions for promoting the healing of wounds | |
| US7713934B2 (en) | Thrombin peptide derivatives | |
| JPH09500897A (ja) | 銅と細胞接着タンパク質との錯体 | |
| DE102007051059B4 (de) | Bioverbundmaterial für die kontrollierte Freisetzung von Wirkstoffen | |
| JPH101439A (ja) | 神経変性疾患治療剤 | |
| DE69814133T2 (de) | Zusammensetzung um die löslichkeit von igf-i zu erhöhen | |
| WO2007031329A2 (de) | Verwendung eines kollagens xenogenen ursprungs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |