JP5922674B2 - チタン酸化物薄膜コーティングを用いた遺伝子伝達ステントおよびその製造方法 - Google Patents
チタン酸化物薄膜コーティングを用いた遺伝子伝達ステントおよびその製造方法 Download PDFInfo
- Publication number
- JP5922674B2 JP5922674B2 JP2013544381A JP2013544381A JP5922674B2 JP 5922674 B2 JP5922674 B2 JP 5922674B2 JP 2013544381 A JP2013544381 A JP 2013544381A JP 2013544381 A JP2013544381 A JP 2013544381A JP 5922674 B2 JP5922674 B2 JP 5922674B2
- Authority
- JP
- Japan
- Prior art keywords
- titanium oxide
- drug
- stent
- titanium
- thin film
- 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.)
- Active
Links
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 title claims description 211
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 title claims description 111
- 239000010409 thin film Substances 0.000 title claims description 65
- 238000001476 gene delivery Methods 0.000 title claims description 32
- 238000009501 film coating Methods 0.000 title claims description 29
- 238000004519 manufacturing process Methods 0.000 title claims description 20
- 229940079593 drug Drugs 0.000 claims description 84
- 239000003814 drug Substances 0.000 claims description 84
- 239000002184 metal Substances 0.000 claims description 77
- 229910052751 metal Inorganic materials 0.000 claims description 76
- 108090000623 proteins and genes Proteins 0.000 claims description 64
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 52
- 239000004408 titanium dioxide Substances 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 30
- 108091034117 Oligonucleotide Proteins 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 239000010936 titanium Substances 0.000 claims description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 229910052719 titanium Inorganic materials 0.000 claims description 22
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 21
- 229910010413 TiO 2 Inorganic materials 0.000 claims description 20
- 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 claims description 19
- 125000000524 functional group Chemical group 0.000 claims description 19
- 229960002897 heparin Drugs 0.000 claims description 19
- 229920000669 heparin Polymers 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000012159 carrier gas Substances 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 16
- 239000002243 precursor Substances 0.000 claims description 16
- 238000000576 coating method Methods 0.000 claims description 15
- 239000007789 gas Substances 0.000 claims description 15
- 239000011248 coating agent Substances 0.000 claims description 14
- 238000012546 transfer Methods 0.000 claims description 13
- 229960000446 abciximab Drugs 0.000 claims description 11
- 230000004048 modification Effects 0.000 claims description 10
- 238000012986 modification Methods 0.000 claims description 10
- 239000012495 reaction gas Substances 0.000 claims description 9
- 229910052786 argon Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- -1 pDNA Proteins 0.000 claims description 8
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 108020004459 Small interfering RNA Proteins 0.000 claims description 5
- 239000002299 complementary DNA Substances 0.000 claims description 5
- 108020004999 messenger RNA Proteins 0.000 claims description 5
- 239000002679 microRNA Substances 0.000 claims description 5
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 4
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000010935 stainless steel Substances 0.000 claims description 4
- 229910001220 stainless steel Inorganic materials 0.000 claims description 4
- 239000001307 helium Substances 0.000 claims description 3
- 229910052734 helium Inorganic materials 0.000 claims description 3
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 3
- 108091070501 miRNA Proteins 0.000 claims description 3
- 239000002773 nucleotide Substances 0.000 claims description 3
- RXOOTVVRSACYPW-UHFFFAOYSA-N CC[Ti](CC)(CC)(CC)NC Chemical compound CC[Ti](CC)(CC)(CC)NC RXOOTVVRSACYPW-UHFFFAOYSA-N 0.000 claims description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 2
- WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical class [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 claims description 2
- YHWCPXVTRSHPNY-UHFFFAOYSA-N butan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCC[O-].CCCC[O-].CCCC[O-].CCCC[O-] YHWCPXVTRSHPNY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052804 chromium Inorganic materials 0.000 claims description 2
- 239000011651 chromium Substances 0.000 claims description 2
- 229910017052 cobalt Inorganic materials 0.000 claims description 2
- 239000010941 cobalt Substances 0.000 claims description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 2
- HLXZNVUGXRDIFK-UHFFFAOYSA-N nickel titanium Chemical compound [Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni] HLXZNVUGXRDIFK-UHFFFAOYSA-N 0.000 claims description 2
- 229910001000 nickel titanium Inorganic materials 0.000 claims description 2
- 125000003729 nucleotide group Chemical group 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229910052715 tantalum Inorganic materials 0.000 claims description 2
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 claims description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000000602 vitallium Substances 0.000 claims description 2
- 108091092584 GDNA Proteins 0.000 claims 2
- 239000002924 silencing RNA Substances 0.000 claims 2
- 230000005540 biological transmission Effects 0.000 claims 1
- 239000010410 layer Substances 0.000 description 55
- 239000013612 plasmid Substances 0.000 description 42
- 210000004027 cell Anatomy 0.000 description 26
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 10
- 208000007536 Thrombosis Diseases 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000005229 chemical vapour deposition Methods 0.000 description 8
- 239000002131 composite material Substances 0.000 description 8
- 208000037803 restenosis Diseases 0.000 description 8
- 229960002663 thioctic acid Drugs 0.000 description 8
- 230000002792 vascular Effects 0.000 description 8
- 210000003815 abdominal wall Anatomy 0.000 description 7
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 7
- 230000003110 anti-inflammatory effect Effects 0.000 description 7
- 108010005774 beta-Galactosidase Proteins 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 239000011247 coating layer Substances 0.000 description 7
- 210000004351 coronary vessel Anatomy 0.000 description 7
- 239000012153 distilled water Substances 0.000 description 7
- 235000019136 lipoic acid Nutrition 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 6
- 230000002785 anti-thrombosis Effects 0.000 description 6
- 230000009610 hypersensitivity Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 5
- 208000026935 allergic disease Diseases 0.000 description 5
- 239000003146 anticoagulant agent Substances 0.000 description 5
- 102000005936 beta-Galactosidase Human genes 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000004833 X-ray photoelectron spectroscopy Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 210000002808 connective tissue Anatomy 0.000 description 4
- 238000000151 deposition Methods 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 4
- 229960002930 sirolimus Drugs 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108020004635 Complementary DNA Proteins 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000010804 cDNA synthesis Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000007769 metal material Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 108020004418 ribosomal RNA Proteins 0.000 description 3
- 239000004055 small Interfering RNA Substances 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 230000003746 surface roughness Effects 0.000 description 3
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- OHJKXVLJWUPWQG-PNRHKHKDSA-N Heparinsodiumsalt Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](O)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H](C(O)=O)O1 OHJKXVLJWUPWQG-PNRHKHKDSA-N 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 239000007984 Tris EDTA buffer Substances 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 229930183665 actinomycin Natural products 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940127217 antithrombotic drug Drugs 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 101150066555 lacZ gene Proteins 0.000 description 2
- 229960002006 linsidomine Drugs 0.000 description 2
- FKDHHVKWGRFRTG-UHFFFAOYSA-N linsidomine Chemical compound [N-]1OC(=N)C=[N+]1N1CCOCC1 FKDHHVKWGRFRTG-UHFFFAOYSA-N 0.000 description 2
- 229910044991 metal oxide Inorganic materials 0.000 description 2
- 150000004706 metal oxides Chemical class 0.000 description 2
- 229960004027 molsidomine Drugs 0.000 description 2
- XLFWDASMENKTKL-UHFFFAOYSA-N molsidomine Chemical compound O1C(N=C([O-])OCC)=C[N+](N2CCOCC2)=N1 XLFWDASMENKTKL-UHFFFAOYSA-N 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 238000000623 plasma-assisted chemical vapour deposition Methods 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940107685 reopro Drugs 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000007447 staining method Methods 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- 102000007625 Hirudins Human genes 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 101150109636 Inos gene Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 108050000761 Serpin Proteins 0.000 description 1
- 102000008847 Serpin Human genes 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910003077 Ti−O Inorganic materials 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 108060005989 Tryptase Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 1
- 229950010817 alvocidib Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000011281 clinical therapy Methods 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 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
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- NZLHIVUUYZXTDR-OFSAWIQQSA-N iu18ho8u80 Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC(C)=O)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)C=3C=CC=CC=3)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OC(=O)CCCCC)C(=O)C1=CC=CC=C1 NZLHIVUUYZXTDR-OFSAWIQQSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000008692 neointimal formation Effects 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 230000009972 noncorrosive effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical class [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000000427 thin-film deposition Methods 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005342 tranilast Drugs 0.000 description 1
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- 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
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
- A61F2/07—Stent-grafts
-
- 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
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- 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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
-
- 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/082—Inorganic materials
- A61L31/088—Other specific inorganic materials not covered by A61L31/084 or A61L31/086
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2240/001—Designing or manufacturing processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00395—Coating or prosthesis-covering structure made of metals or of alloys
- A61F2310/00407—Coating made of titanium or of Ti-based alloys
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/23—Carbohydrates
- A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L2300/256—Antibodies, e.g. immunoglobulins, vaccines
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/258—Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/45—Mixtures of two or more drugs, e.g. synergistic mixtures
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/80—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special chemical form
- A61L2300/802—Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/08—Coatings comprising two or more layers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Surgery (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Materials For Medical Uses (AREA)
Description
1)金属ステントの表面に下記式1で表されるチタン酸化物をコーティングする酸化チタンコーティングステップと、
2)前記コーティングされた酸化チタン層の表面を改質してヒドロキシ基を導入させる表面改質ステップと、
3)薬物の官能基を前記酸化チタン層のヒドロキシ基と結合させ、前記表面が改質された酸化チタン層の上部に薬物を付着させて、薬物層を形成する薬物付着ステップ、および
4)オリゴヌクレオチドを前記薬物と結合させ、前記薬物層の上部にオリゴヌクレオチドを付着させて、オリゴヌクレオチド層を形成するオリゴヌクレオチド付着ステップ、
を含むことを特徴とするチタン酸化物薄膜コーティングを用いた遺伝子伝達ステントの製造方法を提供する。図1を参照する。
ステントとして用いられる材質のうち、ステンレス鋼を1cm×1cm大きさのディスク状の金属プレートに製作し、その金属プレートの表面に酸化チタン薄膜コーティングを実施した。
コーティングされた二酸化チタンの表面に薬物を化学的に付着するためには、薬物分子の官能基と化学的結合が可能な官能基が酸化チタンの表面に存在しなければならない。
用いられた試薬は次の通りである。
前記実施例(1)〜(3)の方法によって製造された金属プレートを12ウェルプレートに位置させ、フラスコ上に遺伝子を含む溶液(プラスミド総含量:20ug/200ul DW)を入れる。8〜12時間放置後、再び滅菌された3次蒸留水(脱イオン水:DW)200ulに30分間浸して非特異的こ付いている余分のDNAを除去した。洗浄液(洗浄DW)は、ナノドロップND−1000分光光度計(Thermo scientific、USA)を利用して洗浄液内のプラスミドの濃度を測定した。プレートは洗浄して滅菌ベンチにおいて乾燥させた後、以後の実験を行った。フラスコに付着しているDNAの量は、下記数学式1のように、初めの20ugのプラスミドから洗浄液内で測定されたDNA量を算術的に引いて予測した。
金属プレートの表面に二酸化チタン/薬物/遺伝子(プラスミド)複合体(以下、金属フラスコと称する)の形態で遺伝子が結合した後にもプラスミドが機能学的に変形がないかを確認するために、金属フラスコの生成後に人為的に遺伝子を分離させて活性有無を測定した。
前記実施例で製造された金属フラスコを実験用ラット(rat)の腹壁に各々移植した。移植7日後に腹壁の筋肉を採取し、前記実験例2で行ったX−gal染色方法と同様に実施し、染色後に腹壁の筋肉を切り、染色された部位を確認した。
前記実験例3で確認したように、遺伝子がコーティングされたプレートが結合組織および筋肉組織の他にもステントの主な移植部位となり得る血管平滑筋細胞に遺伝子が移入できるかを確認するために、金属プレートの表面に直接血管平滑筋細胞を培養して細胞内に遺伝子が移入されるかを確認した。
Claims (16)
- 1)金属ステントの表面に下記式1で表されるチタン酸化物をコーティングする酸化チタンコーティングステップと、
2)前記コーティングされた酸化チタン層の表面を改質してヒドロキシ基を導入させる表面改質ステップと、
3)薬物の官能基を前記酸化チタン層のヒドロキシ基と結合させ、前記表面が改質された酸化チタン層の上部に薬物を付着させて、薬物層を形成する薬物付着ステップ、および
4)オリゴヌクレオチドを前記薬物と結合させ、前記薬物層の上部にオリゴヌクレオチドを付着させて、オリゴヌクレオチド層を形成するオリゴヌクレオチド付着ステップ
を含むことを特徴とするチタン酸化物薄膜コーティングを用いた遺伝子伝達ステントの製造方法。
- 前記チタン酸化物は、TiO2、TiO 2−x N x (0.001≦x≦1)またはこれらの混合物であることを特徴とする、請求項1に記載の製造方法。
- 前記1)の酸化チタンコーティングステップは、プラズマ真空チャンバー内にチタン前駆体、搬送ガスおよび反応ガスを移送し、プラズマを発生させて、1時間〜6時間金属ステントの表面に酸化チタン薄膜をコーティングすることを特徴とする、請求項1または2に記載の製造方法。
- 前記金属ステントは、ステンレス鋼、ニチノール、タンタル、白金、チタニウム、コバルト、クロム、コバルト−クロム合金またはコバルト−クロム−モリブデン合金であることを特徴とする、請求項3に記載の製造方法。
- 前記2)の表面改質ステップは、プラズマ真空チャンバー内に水蒸気、または酸素および水素を移送し、低温プラズマを発生させて、10分〜2時間酸化チタン薄膜の表面を改質することを特徴とする、請求項1または2に記載の製造方法。
- 前記チタン前駆体は、チタニウムブトキシド、テトラエチルメチルアミノチタニウム、チタニウムエトキシド、チタニウム−イソプロポキシドおよびテトラ−メチル−ヘプタ−ジエン−チタニウムからなる群から選択される1種以上であることを特徴とする、請求項3に記載の製造方法。
- 前記搬送ガスは、窒素、アルゴン、ヘリウムからなる群から選択される1種以上であることを特徴とする、請求項3に記載の製造方法。
- 前記反応ガスは、水蒸気、オゾン、および酸素から選択される1種以上であることを特徴とする、請求項3に記載の製造方法。
- 前記反応ガスに窒素を添加することによって窒素がドープされた酸化チタンが形成されることを特徴とする、請求項8に記載の製造方法。
- 前記3)ステップの薬物は、アブシキシマブ、ALA、ヘパリンのうちいずれか一つ以上が選択されて付着していることを特徴とする、請求項1または2に記載の製造方法。
- 前記4)ステップのオリゴヌクレオチドは、gDNA、cDNA、pDNA、mRNA、tRNA、rRNA、siRNA、miRNA、およびアンチセンスオリゴヌクレオチドからなる群から選択されることを特徴とする、請求項1または2に記載の製造方法。
- 前記4)のオリゴヌクレオチド付着ステップは、オリゴヌクレオチドにある官能基が前記薬物にある官能基との間に水素結合、双極子−双極子結合、誘起双極子結合、およびジスルフィド結合(S−S結合)のうちいずれか一つ以上の結合によって付着していることを特徴とする、請求項1または2に記載の製造方法。
- 金属ステントの表面がTiO2、TiO 2−x N x (0.001≦x≦1)またはこれらの混合物でコーティングされ、前記コーティングされた表面を改質させてヒドロキシ基を導入した酸化チタン層と、
薬物の官能基が前記酸化チタン層のヒドロキシ基と結合して、薬物が前記酸化チタン層の上部に付着している薬物層、および
前記薬物層の上部にオリゴヌクレオチドが前記薬物と結合して付着しているオリゴヌクレオチド層
を含むことを特徴とするチタン酸化物薄膜コーティングを用いた遺伝子伝達ステント。 - 前記酸化チタン層は、二酸化チタン薄膜または窒素がドープされた酸化チタン(TiO 2−x N x (0.001≦x≦1))薄膜であることを特徴とする、請求項13に記載の遺伝子伝達ステント。
- 前記薬物は、アブシキシマブ、ALA、ヘパリンのうちいずれか一つ以上であることを特徴とする、請求項13に記載の遺伝子伝達ステント。
- 前記オリゴヌクレオチドは、gDNA、cDNA、pDNA、mRNA、tRNA、rRNA、siRNA、miRNA、およびアンチセンス−オリゴヌクレオチドからなる群から選択されることを特徴とする、請求項13に記載の遺伝子伝達ステント。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20100127251 | 2010-12-13 | ||
KR10-2010-0127251 | 2010-12-13 | ||
KR1020110121949A KR101116673B1 (ko) | 2010-12-13 | 2011-11-22 | 티타늄 산화물 박막코팅을 이용한 유전자 전달 스텐트 및 그 제조방법 |
KR10-2011-0121949 | 2011-11-22 | ||
PCT/KR2011/009298 WO2012081850A2 (ko) | 2010-12-13 | 2011-12-02 | 티타늄 산화물 박막코팅을 이용한 유전자 전달 스텐트 및 그 제조방법 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013545579A JP2013545579A (ja) | 2013-12-26 |
JP5922674B2 true JP5922674B2 (ja) | 2016-05-24 |
Family
ID=45840504
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013544381A Active JP5922674B2 (ja) | 2010-12-13 | 2011-12-02 | チタン酸化物薄膜コーティングを用いた遺伝子伝達ステントおよびその製造方法 |
Country Status (4)
Country | Link |
---|---|
US (2) | US9533074B2 (ja) |
JP (1) | JP5922674B2 (ja) |
KR (1) | KR101116673B1 (ja) |
WO (1) | WO2012081850A2 (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101423698B1 (ko) | 2012-09-14 | 2014-07-25 | 경북대학교 산학협력단 | 이산화티탄 나노튜브의 표면에 약물을 고정화하는 방법 및 이산화티탄 나노튜브의 표면에 고정화된 약물을 포함하는 복합체 |
KR101653535B1 (ko) * | 2016-05-31 | 2016-09-05 | 전남대학교병원 | 전기방사 기법을 이용한 폴리머 사용이 배제된 에베로리무스 혈관용 약물 용출 스텐트 |
KR102032752B1 (ko) * | 2017-08-29 | 2019-10-17 | (주)시지바이오 | 스텐트 및 이의 제조 방법 |
CN112891641B (zh) * | 2021-01-28 | 2021-10-26 | 四川大学 | 可抑制炎症反应的基因洗脱涂层材料及其制备方法 |
KR20240046348A (ko) | 2022-09-30 | 2024-04-09 | 신라대학교 산학협력단 | 의료용 튜브 |
KR20240046349A (ko) | 2022-09-30 | 2024-04-09 | 신라대학교 산학협력단 | 다층 구조를 갖는 의료용 튜브 |
KR20240046836A (ko) | 2022-09-30 | 2024-04-11 | 신라대학교 산학협력단 | 의료용 튜브 제조방법 |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0727424B2 (ja) | 1988-12-09 | 1995-03-29 | 富士通株式会社 | 定電流源回路 |
KR930008851B1 (ko) | 1990-08-29 | 1993-09-16 | 삼성전자 주식회사 | 플라즈마 화학 증착장치 |
CA2227754C (en) | 1995-07-25 | 2008-01-22 | Medstent, Inc. | Expandible stent |
AU734392B2 (en) | 1996-03-07 | 2001-06-14 | Med Institute, Inc. | An expandable stent |
US5868782A (en) | 1996-12-24 | 1999-02-09 | Global Therapeutics, Inc. | Radially expandable axially non-contracting surgical stent |
KR100351640B1 (ko) | 1999-08-27 | 2002-09-10 | 엘지정보통신주식회사 | 폴더형 이동 통신 단말기의 커버 개폐장치 |
JP2002047572A (ja) * | 2000-07-31 | 2002-02-15 | Dainippon Printing Co Ltd | 酸化チタン薄膜の製造方法 |
KR100426725B1 (ko) | 2000-11-22 | 2004-04-08 | 정종임 | 장식지의 광반사성 장식무늬 성형방법 |
KR100738837B1 (ko) | 2001-02-13 | 2007-07-12 | 엘지.필립스 엘시디 주식회사 | 플라즈마화학증착 장치 |
US7923055B2 (en) * | 2001-05-11 | 2011-04-12 | Exogenesis Corporation | Method of manufacturing a drug delivery system |
US6599314B2 (en) | 2001-06-08 | 2003-07-29 | Cordis Corporation | Apparatus and method for stenting a vessel using balloon-actuated stent with interlocking elements |
JP3605388B2 (ja) | 2001-10-16 | 2004-12-22 | 川澄化学工業株式会社 | ステント |
US7005137B1 (en) * | 2002-06-21 | 2006-02-28 | Advanceed Cardiovascular Systems, Inc. | Coating for implantable medical devices |
US20050119398A1 (en) * | 2003-09-11 | 2005-06-02 | Lu Zhang | Plasma synthesis of metal oxide nanoparticles |
JP2008521476A (ja) * | 2004-11-26 | 2008-06-26 | ステントミクス・インコーポレイテッド | 化学物質の医療インプラントへのキレート及び結合、作成された医療機器、及び治療への適用 |
KR101119780B1 (ko) | 2005-06-30 | 2012-03-23 | 엘지디스플레이 주식회사 | 플라즈마 화학증착장치 |
WO2007144383A1 (en) * | 2006-06-13 | 2007-12-21 | Alchimedics | Drug eluting stent with a biodegradable release layer attached with an electro-grafted primer coating |
DE102006038232A1 (de) * | 2006-08-07 | 2008-02-14 | Biotronik Vi Patent Ag | Endoprothese und Verfahren zur Herstellung einer solchen |
US20080057105A1 (en) * | 2006-09-06 | 2008-03-06 | Boston Scientific Scimed, Inc. | Medical devices having nanostructured coating for macromolecule delivery |
KR20080025870A (ko) * | 2006-09-19 | 2008-03-24 | 장양수 | 티타늄 옥사이드 코팅층을 갖는 알루미늄 옥사이드로코팅된 스텐트 및 그 제조방법 |
KR100752100B1 (ko) * | 2006-10-27 | 2007-08-27 | 한국과학기술연구원 | 설포베타인 폴리에틸렌글리콜 유도체로 표면개질된혈액적합성 금속재료 및 이의 제조방법 |
KR101023164B1 (ko) * | 2007-06-19 | 2011-03-18 | (주)바이오니아 | 화학물질로 코팅된 금도금 스텐트, 올리고뉴클레오타이드를 바인딩시킨 금도금 스텐트 및 이들의제조방법 |
KR100947094B1 (ko) * | 2008-01-02 | 2010-03-10 | 주식회사 디오 | 의료용 스텐트 및 그 제조방법 |
CN102365103A (zh) * | 2009-02-25 | 2012-02-29 | 奥索邦德公司 | 抗感染功能化的表面及其制备方法 |
US8574612B2 (en) * | 2009-03-04 | 2013-11-05 | Boston Scientific Scimed, Inc. | Medical devices having a coating of biologic macromolecules |
US8071156B2 (en) * | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
-
2011
- 2011-11-22 KR KR1020110121949A patent/KR101116673B1/ko active IP Right Grant
- 2011-12-02 US US13/993,896 patent/US9533074B2/en active Active
- 2011-12-02 JP JP2013544381A patent/JP5922674B2/ja active Active
- 2011-12-02 WO PCT/KR2011/009298 patent/WO2012081850A2/ko active Application Filing
-
2016
- 2016-12-05 US US15/368,825 patent/US9974889B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US9974889B2 (en) | 2018-05-22 |
WO2012081850A2 (ko) | 2012-06-21 |
US20170080131A1 (en) | 2017-03-23 |
US20140018908A1 (en) | 2014-01-16 |
US9533074B2 (en) | 2017-01-03 |
JP2013545579A (ja) | 2013-12-26 |
WO2012081850A3 (ko) | 2012-08-16 |
KR101116673B1 (ko) | 2012-02-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5922674B2 (ja) | チタン酸化物薄膜コーティングを用いた遺伝子伝達ステントおよびその製造方法 | |
Liu et al. | Enhanced in vitro and in vivo performance of Mg–Zn–Y–Nd alloy achieved with APTES pretreatment for drug-eluting vascular stent application | |
CN101309653B (zh) | 夺取祖内皮细胞的药物洗脱可移植的医疗设备 | |
Nazneen et al. | Surface chemical and physical modification in stent technology for the treatment of coronary artery disease | |
US7166464B2 (en) | Method of culturing cells to produce a tissue sheet | |
JP5117501B2 (ja) | 血管内皮細胞接着を促進するための被膜を有する医療器具およびそれを製造する方法 | |
CN1684641A (zh) | 用于递送丝裂霉素通过洗脱生物相容可移植医疗器件的装置和方法 | |
JP2007532187A (ja) | 生物活性物質のためのコーティング組成物 | |
CN101808677A (zh) | 具有陶瓷涂布表面的制品 | |
EP2205292B1 (en) | Therapeutic agent-eluting medical devices having textured polymeric surfaces | |
US20220218871A1 (en) | Medical device with a biocompatible coating | |
CN1950114A (zh) | 用于医疗物品的天然生物可降解的多糖涂层 | |
Ye et al. | Reduction-responsive nucleic acid delivery systems to prevent in-stent restenosis in rabbits | |
Yao et al. | Recent advances in cardiovascular stent for treatment of in-stent restenosis: Mechanisms and strategies | |
CN101195047A (zh) | 一种抗血栓、再狭窄的血管支架及其制备方法 | |
KR101668590B1 (ko) | 재협착 억제 및 재내피화 촉진을 위한 신규한 펩타이드 화합물 및 이의 제조방법 | |
Zhang et al. | Anti‐DNA antibody modified coronary stent for plasmid gene delivery: results obtained from a porcine coronary stent model | |
US20090263449A1 (en) | Delivery of nucleic acid complexes from materials including negatively charged groups | |
JP2002172159A (ja) | 体内埋め込み医療器具 | |
Ponce et al. | Controlled release on cardiovascular stents using plasma-enhanced adhesion of biodegradable nanoparticles | |
JP7041902B2 (ja) | 生体吸収性医療器具の表面処理方法 | |
US20110307054A1 (en) | Implant coating with nucleic acids | |
Lam et al. | The attachment, proliferation, and wound healing of endothelial and smooth muscle cells on nitinol thin film in vitro |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20141202 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150929 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151224 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160322 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160414 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5922674 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |