TWI257307B - Pharmaceutical composition for cardiac tissue repair - Google Patents
Pharmaceutical composition for cardiac tissue repair Download PDFInfo
- Publication number
- TWI257307B TWI257307B TW090116938A TW90116938A TWI257307B TW I257307 B TWI257307 B TW I257307B TW 090116938 A TW090116938 A TW 090116938A TW 90116938 A TW90116938 A TW 90116938A TW I257307 B TWI257307 B TW I257307B
- Authority
- TW
- Taiwan
- Prior art keywords
- glycine
- proline
- aspartate
- alanine
- peptide
- Prior art date
Links
- 210000005003 heart tissue Anatomy 0.000 title claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 230000017423 tissue regeneration Effects 0.000 title abstract description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 57
- 230000002491 angiogenic effect Effects 0.000 claims abstract description 15
- 208000037803 restenosis Diseases 0.000 claims abstract description 15
- 230000000250 revascularization Effects 0.000 claims abstract description 9
- 230000001737 promoting effect Effects 0.000 claims abstract description 8
- 239000003869 thrombin derivative Substances 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 108090000190 Thrombin Proteins 0.000 claims description 30
- 229960004072 thrombin Drugs 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 25
- 150000001413 amino acids Chemical group 0.000 claims description 23
- 230000002792 vascular Effects 0.000 claims description 16
- 230000008439 repair process Effects 0.000 claims description 10
- 239000004005 microsphere Substances 0.000 claims description 8
- 239000004471 Glycine Substances 0.000 claims description 7
- 229940009098 aspartate Drugs 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 210000004899 c-terminal region Anatomy 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 235000004279 alanine Nutrition 0.000 claims description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 6
- 229920000747 poly(lactic acid) Polymers 0.000 claims 3
- 239000004626 polylactic acid Substances 0.000 claims 3
- 238000013268 sustained release Methods 0.000 claims 3
- 239000012730 sustained-release form Substances 0.000 claims 3
- PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 17
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 11
- 230000004936 stimulating effect Effects 0.000 abstract description 6
- 206010053648 Vascular occlusion Diseases 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 208000021331 vascular occlusion disease Diseases 0.000 abstract 1
- 210000004204 blood vessel Anatomy 0.000 description 24
- 108090000166 Thrombin receptors Proteins 0.000 description 17
- 102000003790 Thrombin receptors Human genes 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- 210000002889 endothelial cell Anatomy 0.000 description 14
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 208000027418 Wounds and injury Diseases 0.000 description 9
- 230000033115 angiogenesis Effects 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 206010052428 Wound Diseases 0.000 description 7
- 230000010102 embolization Effects 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 108091036078 conserved sequence Proteins 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 108020002447 serine esterase Proteins 0.000 description 6
- 102000005428 serine esterase Human genes 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000002583 angiography Methods 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 5
- 208000005189 Embolism Diseases 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000012266 salt solution Substances 0.000 description 4
- 108010013043 Acetylesterase Proteins 0.000 description 3
- 150000008575 L-amino acids Chemical class 0.000 description 3
- 229920011250 Polypropylene Block Copolymer Polymers 0.000 description 3
- 206010036790 Productive cough Diseases 0.000 description 3
- 208000002847 Surgical Wound Diseases 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- -1 aspartate-alanine-cysteine-glutamic acid-glycine-aspartate-serine-glycine-glycine- Proline-phenylalanine-proline Chemical compound 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 208000031225 myocardial ischemia Diseases 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 210000003802 sputum Anatomy 0.000 description 3
- 208000024794 sputum Diseases 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 210000003090 iliac artery Anatomy 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 2
- 210000004925 microvascular endothelial cell Anatomy 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 238000011555 rabbit model Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000029663 wound healing Effects 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
- 229920001817 Agar Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 1
- 108010022355 Fibroins Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- LCGISIDBXHGCDW-VKHMYHEASA-N L-glutamine amide Chemical compound NC(=O)[C@@H](N)CCC(N)=O LCGISIDBXHGCDW-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 229940122985 Peptide agonist Drugs 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002607 contrast-enhanced ultrasound Methods 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010252 digital analysis Methods 0.000 description 1
- 229960001089 dobutamine Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 230000010595 endothelial cell migration Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000002431 foraging effect Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000000260 hypercholesteremic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 244000309715 mini pig Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 230000008692 neointimal formation Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 230000007180 physiological regulation Effects 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003354 serine derivatives Chemical class 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 238000006177 thiolation reaction Methods 0.000 description 1
- 230000002345 thrombinlike Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000006492 vascular dysfunction Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4833—Thrombin (3.4.21.5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Transplantation (AREA)
- Immunology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
- Prostheses (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21758300P | 2000-07-12 | 2000-07-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI257307B true TWI257307B (en) | 2006-07-01 |
Family
ID=22811661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW090116938A TWI257307B (en) | 2000-07-12 | 2001-07-11 | Pharmaceutical composition for cardiac tissue repair |
Country Status (10)
| Country | Link |
|---|---|
| US (5) | US6867190B2 (enExample) |
| EP (1) | EP1253937B1 (enExample) |
| JP (2) | JP3618736B2 (enExample) |
| CN (1) | CN100500211C (enExample) |
| AT (1) | ATE249238T1 (enExample) |
| AU (2) | AU2001278907B2 (enExample) |
| CA (1) | CA2415778A1 (enExample) |
| DE (2) | DE60100740T4 (enExample) |
| TW (1) | TWI257307B (enExample) |
| WO (1) | WO2002004008A2 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6774278B1 (en) * | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
| US6346510B1 (en) * | 1995-10-23 | 2002-02-12 | The Children's Medical Center Corporation | Therapeutic antiangiogenic endostatin compositions |
| AU2002241917B2 (en) * | 2000-07-12 | 2006-06-15 | The Board Of Regents, The University Of Texas System | Thrombin derived peptides for promoting cardiac tissue repair |
| TWI257307B (en) | 2000-07-12 | 2006-07-01 | Orthologic Corp | Pharmaceutical composition for cardiac tissue repair |
| US7803149B2 (en) * | 2002-07-12 | 2010-09-28 | Cook Incorporated | Coated medical device |
| DE10115740A1 (de) * | 2001-03-26 | 2002-10-02 | Ulrich Speck | Zubereitung für die Restenoseprophylaxe |
| CA2511223A1 (en) * | 2002-01-16 | 2003-07-31 | The Board Of Regents, The University Of Texas System | Thrombin derived peptides for promoting cardiac tissue repair |
| AU2003256343B2 (en) * | 2002-07-02 | 2006-12-21 | Orthologic Corp. | Thrombin peptide derivatives |
| EP1539800B1 (en) * | 2002-07-02 | 2007-05-23 | Orthologic Corp. | Thrombin peptide derivative dimers |
| DE10244847A1 (de) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medizinische Vorrichtung zur Arzneimittelabgabe |
| AU2004211592B2 (en) | 2003-02-12 | 2008-04-10 | Monsanto Technology Llc | Cotton event MON 88913 and compositions and methods for detection thereof |
| US8383158B2 (en) * | 2003-04-15 | 2013-02-26 | Abbott Cardiovascular Systems Inc. | Methods and compositions to treat myocardial conditions |
| DE602004005564T2 (de) * | 2003-12-31 | 2007-12-13 | Orthologic Corp., Tempe | Pharmazeutische Zusammensetzung für Thrombinpeptidderivaten |
| CA2576971A1 (en) * | 2004-08-20 | 2006-03-02 | Entremed, Inc. | Compositions and methods comprising proteinase activated receptor antagonists |
| US9539410B2 (en) | 2005-04-19 | 2017-01-10 | Abbott Cardiovascular Systems Inc. | Methods and compositions for treating post-cardial infarction damage |
| US20080125745A1 (en) | 2005-04-19 | 2008-05-29 | Shubhayu Basu | Methods and compositions for treating post-cardial infarction damage |
| JP2006321740A (ja) * | 2005-05-18 | 2006-11-30 | Kanazawa Univ | 虚血後血管新生促進剤 |
| US9242005B1 (en) | 2006-08-21 | 2016-01-26 | Abbott Cardiovascular Systems Inc. | Pro-healing agent formulation compositions, methods and treatments |
| CA2663547C (en) * | 2006-09-22 | 2020-08-25 | Orthologic Corp. | Method of treating endothelial dysfunction |
| US9005672B2 (en) | 2006-11-17 | 2015-04-14 | Abbott Cardiovascular Systems Inc. | Methods of modifying myocardial infarction expansion |
| US8227412B2 (en) * | 2007-03-29 | 2012-07-24 | Tsopanoglou Nikos E | Bioactive parstatin peptides and methods of use |
| EP2155236A1 (en) * | 2007-04-10 | 2010-02-24 | The Board of Regents,The University of Texas System | Combination therapy for cardiac revascularization and cardiac repair |
| US8202528B2 (en) * | 2007-06-05 | 2012-06-19 | Abbott Cardiovascular Systems Inc. | Implantable medical devices with elastomeric block copolymer coatings |
| GB2450747A (en) * | 2007-07-06 | 2009-01-07 | Univ Sheffield | Treatment of sensorineural hearing loss |
| US8586398B2 (en) * | 2008-01-18 | 2013-11-19 | Miasole | Sodium-incorporation in solar cell substrates and contacts |
| AU2009229395A1 (en) * | 2008-03-26 | 2009-10-01 | The Board Of Regents, The University Of Texas System | Method of treating degenerative diseases |
| US20110117075A1 (en) * | 2008-03-26 | 2011-05-19 | Orthologic Corp. | Thrombin derived peptides for smooth muscle relaxation |
| EP2268304A2 (en) * | 2008-03-26 | 2011-01-05 | Orthologic Corp. | Methods for treating acute myocardial infarction |
| WO2009120307A2 (en) * | 2008-03-26 | 2009-10-01 | Orthologic Corp. | Method of treating peripheral arterial disease |
| US20110319340A1 (en) * | 2008-09-19 | 2011-12-29 | The Board Of Regents, The University Of Texas System | Methods for treating cancer |
| US20130101574A1 (en) * | 2010-06-11 | 2013-04-25 | Darrell H. Carney | Methods of using thrombin peptide derivatives |
| GB201314312D0 (en) * | 2013-08-09 | 2013-09-25 | Regentec Ltd | Composition and delivery system |
| US20160039876A1 (en) | 2014-03-28 | 2016-02-11 | Claresa Levetan | Insulin independence among patients with diabetes utilizing an optimized hamster reg3 gamma peptide |
| 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 |
| WO2020210087A1 (en) * | 2019-04-12 | 2020-10-15 | Affirmed Pharma, Llc | Rusalatide acetate compositions |
Family Cites Families (11)
| 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 |
| US5244460A (en) * | 1991-11-27 | 1993-09-14 | The United States Of America As Represented By The Department Of Health And Human Services | Method to foster myocardial blood vessel growth and improve blood flow to the heart |
| EP0697883A1 (en) | 1993-04-29 | 1996-02-28 | Washington University | Use of platelet-derived growth factor to improve collateral circulation |
| ATE273322T1 (de) * | 1995-10-24 | 2004-08-15 | Chemo Sero Therapeut Res Inst | Tfpi-verwandte peptide die das wachstums von glatten muskelzellen inhibieren |
| US5912229A (en) * | 1996-03-01 | 1999-06-15 | Novo Nordisk Als | Use of a pharmaceutical composition comprising an appetite-suppressing peptide |
| US6197751B1 (en) * | 1997-11-10 | 2001-03-06 | The United States Of America As Represented By The Department Of Health And Human Services | Thymosin α1 promotes tissue repair, angiogenesis and cell migration |
| US6033436A (en) * | 1998-02-17 | 2000-03-07 | Md3, Inc. | Expandable stent |
| JP2002512200A (ja) | 1998-04-17 | 2002-04-23 | アンジオジェニックス, インコーポレイテッド | 治療的な脈管形成因子およびその使用方法 |
| CA2340593C (en) | 1998-10-26 | 2012-05-08 | Kari Alitalo | Use of vegf-c or vegf-d gene or protein to prevent restenosis |
| US6363938B2 (en) * | 1998-12-22 | 2002-04-02 | Angiotrax, Inc. | Methods and apparatus for perfusing tissue and/or stimulating revascularization and tissue growth |
| TWI257307B (en) * | 2000-07-12 | 2006-07-01 | Orthologic Corp | Pharmaceutical composition for cardiac tissue repair |
-
2001
- 2001-07-11 TW TW090116938A patent/TWI257307B/zh not_active IP Right Cessation
- 2001-07-12 AU AU2001278907A patent/AU2001278907B2/en not_active Ceased
- 2001-07-12 JP JP2002508462A patent/JP3618736B2/ja not_active Expired - Fee Related
- 2001-07-12 DE DE60100740T patent/DE60100740T4/de not_active Expired - Lifetime
- 2001-07-12 EP EP01957136A patent/EP1253937B1/en not_active Expired - Lifetime
- 2001-07-12 AU AU7890701A patent/AU7890701A/xx active Pending
- 2001-07-12 DE DE60100740A patent/DE60100740D1/de not_active Expired - Lifetime
- 2001-07-12 US US09/904,090 patent/US6867190B2/en not_active Expired - Lifetime
- 2001-07-12 AT AT01957136T patent/ATE249238T1/de active
- 2001-07-12 CN CNB018154581A patent/CN100500211C/zh not_active Expired - Fee Related
- 2001-07-12 CA CA002415778A patent/CA2415778A1/en not_active Abandoned
- 2001-07-12 WO PCT/US2001/021944 patent/WO2002004008A2/en not_active Ceased
-
2002
- 2002-01-16 US US10/050,611 patent/US6861407B2/en not_active Expired - Fee Related
-
2004
- 2004-08-09 JP JP2004232356A patent/JP2005036007A/ja not_active Withdrawn
- 2004-09-30 US US10/957,427 patent/US7034001B2/en not_active Expired - Fee Related
-
2005
- 2005-12-02 US US11/293,495 patent/US7214661B2/en not_active Expired - Fee Related
-
2007
- 2007-04-13 US US11/787,114 patent/US7732411B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60100740D1 (de) | 2003-10-16 |
| JP3618736B2 (ja) | 2005-02-09 |
| CN1455678A (zh) | 2003-11-12 |
| JP2004502739A (ja) | 2004-01-29 |
| CN100500211C (zh) | 2009-06-17 |
| EP1253937A2 (en) | 2002-11-06 |
| AU7890701A (en) | 2002-01-21 |
| HK1060302A1 (zh) | 2004-08-06 |
| WO2002004008A2 (en) | 2002-01-17 |
| US7034001B2 (en) | 2006-04-25 |
| AU2001278907B2 (en) | 2004-10-21 |
| US6867190B2 (en) | 2005-03-15 |
| US20060134167A1 (en) | 2006-06-22 |
| WO2002004008A3 (en) | 2002-08-22 |
| US6861407B2 (en) | 2005-03-01 |
| US20050153884A1 (en) | 2005-07-14 |
| US20080131474A1 (en) | 2008-06-05 |
| DE60100740T4 (de) | 2005-01-27 |
| DE60100740T2 (de) | 2004-07-01 |
| US7214661B2 (en) | 2007-05-08 |
| EP1253937B1 (en) | 2003-09-10 |
| US20020061852A1 (en) | 2002-05-23 |
| US20020187933A1 (en) | 2002-12-12 |
| JP2005036007A (ja) | 2005-02-10 |
| US7732411B2 (en) | 2010-06-08 |
| CA2415778A1 (en) | 2002-01-17 |
| ATE249238T1 (de) | 2003-09-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI257307B (en) | Pharmaceutical composition for cardiac tissue repair | |
| US20060062768A1 (en) | Biocompatible hydrogel compositions | |
| AU2001278907A1 (en) | Methods of therapy with thrombin derived peptides | |
| JP2013513657A (ja) | 新規ペプチドおよびその用途 | |
| JPH04211019A (ja) | 創傷治癒促進のためのトロンボスポンデインの使用 | |
| JP4668612B2 (ja) | トロンビンペプチド誘導体ダイマー | |
| JP4205592B2 (ja) | 心臓組織修復を促進するためのトロンビン由来ペプチド | |
| JP4925551B2 (ja) | 血管形成剤及びその使用 | |
| JP2001122799A (ja) | プレイオトロフィンを含む結合組織修復促進組成物および該組成物の調製におけるプレイオトロフィンの使用 | |
| EP3856249B1 (en) | Treatment of myocardial infarction | |
| JPH09502726A (ja) | 血管障害を防ぐポリペプチドを用いる治療的処置 | |
| AU2002241917B2 (en) | Thrombin derived peptides for promoting cardiac tissue repair | |
| JP2003500113A (ja) | アルファ平滑筋アクチン活性を調節する薬剤の治療的使用 | |
| HK1060302B (en) | Methods of therapy with thrombin derived peptides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |