CN108619578A - 药物洗脱支架及其制备和应用 - Google Patents
药物洗脱支架及其制备和应用 Download PDFInfo
- Publication number
- CN108619578A CN108619578A CN201710172227.8A CN201710172227A CN108619578A CN 108619578 A CN108619578 A CN 108619578A CN 201710172227 A CN201710172227 A CN 201710172227A CN 108619578 A CN108619578 A CN 108619578A
- Authority
- CN
- China
- Prior art keywords
- bracket
- ginsenoside
- drug
- eluting medicament
- holder
- 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.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 78
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 229940079593 drug Drugs 0.000 claims abstract description 40
- UFNDONGOJKNAES-UHFFFAOYSA-N Ginsenoside Rb1 Natural products CC(=CCCC(C)(OC1OC(COC2OC(CO)C(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CC(O)C45C)C UFNDONGOJKNAES-UHFFFAOYSA-N 0.000 claims abstract description 29
- GZYPWOGIYAIIPV-JBDTYSNRSA-N ginsenoside Rb1 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GZYPWOGIYAIIPV-JBDTYSNRSA-N 0.000 claims abstract description 29
- TXEWRVNOAJOINC-UHFFFAOYSA-N ginsenoside Rb2 Natural products CC(=CCCC(OC1OC(COC2OCC(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CCC45C)C TXEWRVNOAJOINC-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910000684 Cobalt-chrome Inorganic materials 0.000 claims description 28
- 239000010952 cobalt-chrome Substances 0.000 claims description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 23
- WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical compound [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 claims description 20
- 229910052751 metal Inorganic materials 0.000 claims description 20
- 239000002184 metal Substances 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- 239000008367 deionised water Substances 0.000 claims description 18
- 229910021641 deionized water Inorganic materials 0.000 claims description 18
- 238000004140 cleaning Methods 0.000 claims description 11
- 238000003618 dip coating Methods 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- 239000008151 electrolyte solution Substances 0.000 claims description 11
- 239000005416 organic matter Substances 0.000 claims description 11
- 229920000642 polymer Polymers 0.000 claims description 11
- 238000005507 spraying Methods 0.000 claims description 11
- 229920000058 polyacrylate Polymers 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 230000000694 effects Effects 0.000 abstract description 9
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 7
- 230000004224 protection Effects 0.000 abstract description 7
- 239000010410 layer Substances 0.000 description 28
- 208000037803 restenosis Diseases 0.000 description 10
- 238000007711 solidification Methods 0.000 description 8
- 230000008023 solidification Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 241000208340 Araliaceae Species 0.000 description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 6
- 235000003140 Panax quinquefolius Nutrition 0.000 description 6
- 235000008434 ginseng Nutrition 0.000 description 6
- KWDWBAISZWOAHD-MHOSXIPRSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-2-[[(3s,5r,8r,9r,10r,12r,13r,14r,17s)-12-hydroxy-4,4,8,10,14-pentamethyl-17-(6-methylhepta-1,5-dien-2-yl)-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]o Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4C(=C)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O KWDWBAISZWOAHD-MHOSXIPRSA-N 0.000 description 5
- NJUXRKMKOFXMRX-RNCAKNGISA-N Ginsenoside Rg5 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1CC[C@]2(C)[C@H]3C[C@@H](O)[C@H]4[C@@]([C@@]3(CC[C@H]2C1(C)C)C)(C)CC[C@@H]4C(/C)=C/CC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O NJUXRKMKOFXMRX-RNCAKNGISA-N 0.000 description 5
- KWDWBAISZWOAHD-UHFFFAOYSA-N Ginsenoside Rk1 Natural products CC(C)=CCCC(=C)C1CCC(C2(CCC3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O KWDWBAISZWOAHD-UHFFFAOYSA-N 0.000 description 5
- NJUXRKMKOFXMRX-AXUZFSSLSA-N ginsenoside Rg5 Natural products CC(=CCC=C(C)[C@H]1CC[C@]2(C)[C@@H]1[C@H](O)C[C@@H]3[C@@]4(C)CC[C@@H](O[C@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O[C@H]6O[C@H](CO)[C@@H](O)[C@H](O)[C@H]6O)C(C)(C)[C@@H]4CC[C@@]23C)C NJUXRKMKOFXMRX-AXUZFSSLSA-N 0.000 description 5
- NJUXRKMKOFXMRX-UHFFFAOYSA-N ginsenoside Rz1 Natural products CC(C)=CCC=C(C)C1CCC(C2(CCC3C4(C)C)C)(C)C1C(O)CC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O NJUXRKMKOFXMRX-UHFFFAOYSA-N 0.000 description 5
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 4
- PWAOOJDMFUQOKB-WCZZMFLVSA-N ginsenoside Re Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@](C)(CCC=C(C)C)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O PWAOOJDMFUQOKB-WCZZMFLVSA-N 0.000 description 4
- AOGZLQUEBLOQCI-UHFFFAOYSA-N ginsenoside-Re Natural products CC1OC(OCC2OC(OC3CC4(C)C(CC(O)C5C(CCC45C)C(C)(CCC=C(C)C)OC6OC(CO)C(O)C(O)C6O)C7(C)CCC(O)C(C)(C)C37)C(O)C(O)C2O)C(O)C(O)C1O AOGZLQUEBLOQCI-UHFFFAOYSA-N 0.000 description 4
- 230000002980 postoperative effect Effects 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
- 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 4
- 230000002792 vascular Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 229940089161 ginsenoside Drugs 0.000 description 2
- 229930182494 ginsenoside Natural products 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 244000309715 mini pig Species 0.000 description 2
- 239000002344 surface layer Substances 0.000 description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 235000016408 Podocarpus macrophyllus Nutrition 0.000 description 1
- 244000162450 Taxus cuspidata Species 0.000 description 1
- 235000009065 Taxus cuspidata Nutrition 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 201000006828 endometrial hyperplasia Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000027849 smooth muscle hyperplasia Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 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
- 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
- A61L31/10—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
- 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
- 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
- A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
本发明提供一种药物洗脱支架,其药物涂层中,人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.07‑0.3μg/mm2。本发明还涉及上述药物洗脱支架的制备和应用。本发明通过动物实验发现,本发明实施例可以实现很好的抗ISR及保护心脑血管效果。
Description
技术领域
本发明涉及一种药物洗脱支架及其制备和应用。
背景技术
心脑血管病每年导致全球1750万人死亡。脑卒中是美国第三大导致死亡的原因,每年大约有795000美国人遭受新的或复发性脑卒中,其中超过三分之二为首发病。自从2009年以来,脑卒中造成的直接和间接经济损失估计达到68.9亿美元。同样,中国也是脑卒中高发的国家,脑卒中发病率居世界第2位。
随着血管支架的技术及材料的不断发展,到目前心脑血管支架已成为治疗心脑血管性疾病的一个重要手段,且疗效确切,安全性好,受到广泛认同。然而,尽管支架成形术降低了术后血管的再狭窄率,但是病变血管仍然可能出现支架内再狭窄(ISR),支架内再狭窄导致卒中成为影响其疗效的一个重要因素,有研究显示金属裸支架再狭窄率高达50%。
支架植入后出现的再狭窄现象,严重影响了其作为一种介入治疗技术的临床应用价值。人们发现ISR的危害以来,一直在研究和寻找预防和治疗ISR的方法,提出了多种新技术,包括系统的药物治疗,机械治疗,局部放射治疗,以及药物洗脱支架等等,其中药物洗脱支架(DES)技术得到最成功的运用。常用的药物洗脱支架涂层药物有:肝素、地塞米松、紫杉醇、雷帕霉素、基因药物、纳米药物、抗血小板受体拮抗剂。
发明内容
本发明提供一种药物洗脱支架,其药物涂层中,人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.07-0.3μg/mm2。
具体来讲,其药物涂层中,人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.15μg/mm2。
在一具体实施例中,所述药物洗脱支架为L605钴铬支架,所述药物洗脱支架的载药层为聚乳酸-羟基乙酸共聚物载药层。
本发明实施例还涉及制备上述药物洗脱支架的方法,包括如下步骤:
将支架清洗,除去金属表面的有机物;
清洗后的支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍,取出用去离子水冲洗后,干燥备用;
聚丙烯酸酯溶解于四氢呋喃中并配制成30%浓度的溶液;
将人参皂苷Rb1、Rg1、Rg5、Re、Rd混合入聚合物溶液中;
用浸涂或喷涂的方式将载药层涂覆于支架,60℃固化,反复5次。
本发明还涉及上述药物洗脱支架在介入治疗中的应用。
本发明将人参皂苷涂覆于血管药物洗脱支架的表层。本发明通过动物实验发现,本发明实施例可以实现很好的抗ISR及保护心脑血管效果。人参皂苷作为涂覆于心脑血管支架表层的药物,不仅能预防支架植入术后血管的再狭窄(抑制平滑肌增生),还能起到抗氧化、抗炎症、保护神经及治疗心脑血管疾病等作用。
本发明的其它特征和优点将在随后的说明书中阐述,并且,部分地从说明书中变得显而易见,或者通过实施本发明而了解。本发明的目的和其他优点可通过在所写的说明书、权利要求书中所特别指出的结构来实现和获得。
具体实施方式
下面更详细地描述本公开的示例性实施例。虽然本部分显示了本公开的示例性实施例,然而应当理解,可以以各种形式实现本公开而不应被这里阐述的实施例所限制。相反,提供这些实施例是为了能够更透彻地理解本公开,并且能够将本公开的范围完整的传达给本领域的技术人员。
为了说明本发明所述的技术方案,下面通过具体实施例来进行说明。
对照例采用L605钴铬裸支架。
实施例1
本实施例提供的血管支架,在金属支架的外侧涂覆有人参皂苷Rg3和聚乳酸-羟基乙酸共聚物(PLGA)载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3PLGA溶解于氯仿中并配制成浓度为40%的溶液;然后将人参皂苷Rg3混合入聚合物溶液中,人参皂苷Rg3的浓度为50%。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rg3的药物含量为1μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rg3在30天内规律稳定释放80%,在40天内全部释放完毕。
实施例2
本实施例提供的血管支架,在金属支架的外侧涂覆有人参皂苷Rk1和聚乳酸-羟基乙酸共聚物(PLGA)载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3PLGA溶解于四氢呋喃中并配制成浓度为30%的溶液;然后将人参皂苷Rk1混合入聚合物溶液中,人参皂苷Rk1浓度为60%。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rk1的药物含量为1μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rk1在30天内规律稳定释放70%,在50天内全部释放完毕。
实施例3
本实施例提供的血管支架,在金属支架的外侧涂覆有人参皂苷Rg5和聚乳酸-羟基乙酸共聚物(PLGA)载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3PLGA溶解于四氢呋喃中并配制成浓度为30%的溶液;然后将人参皂苷Rg5混合入聚合物溶液中,人参皂苷Rg5浓度为60%。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rg5的药物含量为1μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rg5在30天内规律稳定释放70%,在50天内全部释放完毕。
实施例4
本实施例提供的血管支架,在金属支架的外侧涂覆有人参皂苷Re、雷帕霉素组合物和聚乳酸-羟基乙酸共聚物(PLGA)载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3PLGA溶解于二甲亚砜中并配制成浓度为30%的溶液;然后将人参皂苷Re、雷帕霉素组合物混合入聚合物溶液中,人参皂苷Re浓度为45%、雷帕霉素浓度为5%。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Re、雷帕霉素组合物的药物含量分别为0.9μg/mm2和0.1μg/mm2
本实施例的药物释放结果表明,人参皂苷Rg3、Rg1组合物在30天内规律稳定释放75%和80%,在40天内全部释放完毕。
实施例5
本实施例提供的血管支架,在金属支架的外侧涂覆有多组分人参皂苷Rb1、Rg1、Re组合物和聚乳酸-羟基乙酸共聚物(PLGA)载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3PLGA溶解于四氢呋喃中并配制成浓度为30%的溶液;然后将人参皂苷Rb1、Rg1、Re混合入聚合物溶液中,人参皂苷Rb1、Rg1、Re浓度分别为40%、20%、10%,即Rb1:Rg1:Re=4:2:1。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rb1、Rg1、Re的药物含量分别为0.6μg/mm2、0.3μg/mm2、0.15μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rb1、Rg1、Re在30天内规律稳定释放70%、80%、80%,在50天内全部释放完毕。
实施例6
本实施例提供的血管支架,在金属支架的外侧涂覆有多组分人参皂苷Rb1、Rg1、Rg5、Re、Rd组合物和聚丙烯酸酯载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3聚丙烯酸酯溶解于四氢呋喃中并配制成30%浓度的溶液;然后将人参皂苷Rb1、Rg1、Rg5、Re、Rd混合入聚合物溶液中,人参皂苷Rb1、Rg1、Rg5、Re、Rd浓度分别为20%、20%、10%、10%、10%,即Rb1:Rg1:Rg5:Re:Rd=2:2:1:1:1。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.15μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rb1、Rg1、Rg5、Re、Rd在30天内规律稳定释放70%、70%、80%、70%、70%,在50天内全部释放完毕,可有效防止再狭窄并起到保护和治疗血管疾病的作用。
实施例7
本实施例提供的血管支架,在金属支架的外侧涂覆有多组分人参皂苷Rb1、Rg1、Rg5、Re、Rd组合物和聚丙烯酸酯载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3聚丙烯酸酯溶解于四氢呋喃中并配制成30%浓度的溶液;然后将人参皂苷Rb1、Rg1、Rg5、Re、Rd混合入聚合物溶液中,人参皂苷Rb1、Rg1、Rg5、Re、Rd浓度分别为20%、20%、10%、10%、5%。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.07μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rb1、Rg1、Rg5、Re、Rd在30天内规律稳定释放70%、70%、70%、70%、70%,在50天内全部释放完毕,可有效防止再狭窄并起到保护和治疗血管疾病的作用。
实施例8
本实施例提供的血管支架,在金属支架的外侧涂覆有多组分人参皂苷Rb1、Rg1、Rg5、Re、Rd组合物和聚丙烯酸酯载药层。具体制备如下:
步骤1将L605钴铬支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物。
步骤2清洗后的L605钴铬支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍。取出用去离子水冲洗后,干燥备用。
步骤3聚丙烯酸酯溶解于四氢呋喃中并配制成30%浓度的溶液;然后将人参皂苷Rb1、Rg1、Rg5、Re、Rd混合入聚合物溶液中,人参皂苷Rb1、Rg1、Rg5、Re、Rd浓度分别为20%、20%、10%、10%、20%。
步骤4用浸涂或喷涂的方式将载药层涂覆于L605钴铬金属支架,60℃固化,反复5次。人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.3μg/mm2。
本实施例的药物释放结果表明,人参皂苷Rb1、Rg1、Rg5、Re、Rd在30天内释放率分别为70%、70%、70%、70%、70%,在50天内全部释放完毕,可有效防止再狭窄并起到保护和治疗血管疾病的作用。
实施例9
动物植入实验
按上述对照例及实施例1-8方法制备的药物洗脱支架分别植入45只小型猪过度扩张血管模型中,观察术后28天内膜增生及炎症反应情况。结果如下。
表2对照例及实施例支架植入术后血管组织形态学分析结果(±s)
从表2可以看出,在小型猪过度扩张血管模型中术后28天组织形态学复查,实施例6组较对照组及其它实施例组,剩余管腔面积大,新生内膜厚度小,新生内膜面积小,炎症积分小,因此,以多组分人参皂苷Rb1、Rg1、Rg5、Re、Rd为主要成分,以Rb1:Rg1:Rg5:Re:Rd=2:2:1:1:1的质量比进行混合制备的药物洗脱支架,可以达到最佳的抑制血管平滑肌增生的效果,从而起到防止再狭窄以及保护和治疗心脑血管疾病的作用。
显然,本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样,倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内,则本发明也意图包含这些改动和变型在内。
Claims (8)
1.一种药物洗脱支架,其特征在于,药物涂层中,人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.07-0.3μg/mm2。
2.权利要求1所述药物洗脱支架,其特征在于,药物涂层中,人参皂苷Rb1、Rg1、Rg5、Re、Rd的药物含量分别为0.3μg/mm2、0.3μg/mm2、0.15μg/mm2、0.15μg/mm2、0.15μg/mm2。
3.权利要求1或2任一所述药物洗脱支架,其特征在于,所述药物洗脱支架为L605钴铬支架。
4.权利要求3所述药物洗脱支架,其特征在于,所述药物洗脱支架的载药层为聚乳酸-羟基乙酸共聚物载药层。
5.制备权利要求1-4任一项所述药物洗脱支架的方法,其特征在于,包括如下步骤:
将支架清洗,除去金属表面的有机物;
清洗后的支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍,取出用去离子水冲洗后,干燥备用;
聚丙烯酸酯溶解于四氢呋喃中并配制成30%浓度的溶液;
将人参皂苷Rb1、Rg1、Rg5、Re、Rd混合入聚合物溶液中;
用浸涂或喷涂的方式将载药层涂覆于支架,60℃固化,反复5次。
6.制备权利要求5所述药物洗脱支架的方法,其特征在于,包括如下步骤:
将支架在丙酮、去离子水及甲醇混合液中超声清洗,除去金属表面的有机物;
清洗后的支架置于电解质溶液中进行电解抛光以除去氧化层及表面污渍,取出用去离子水冲洗后,干燥备用;
聚丙烯酸酯溶解于四氢呋喃中并配制成30%浓度的溶液;
将人参皂苷Rb1、Rg1、Rg5、Re、Rd混合入聚合物溶液中;
用浸涂或喷涂的方式将载药层涂覆于支架,60℃固化,反复5次。
7.权利要求5或6任一所述方法,其特征在于,所述支架为L605钴铬支架。
8.权利要求1-4任一所述药物洗脱支架在介入治疗中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710172227.8A CN108619578A (zh) | 2017-03-22 | 2017-03-22 | 药物洗脱支架及其制备和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710172227.8A CN108619578A (zh) | 2017-03-22 | 2017-03-22 | 药物洗脱支架及其制备和应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN108619578A true CN108619578A (zh) | 2018-10-09 |
Family
ID=63706390
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710172227.8A Pending CN108619578A (zh) | 2017-03-22 | 2017-03-22 | 药物洗脱支架及其制备和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108619578A (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102159257A (zh) * | 2008-07-17 | 2011-08-17 | 米歇尔技术公司 | 药物递送医疗设备 |
CN203436435U (zh) * | 2013-07-01 | 2014-02-19 | 雅伦生物科技(北京)有限公司 | 一种脑血管药物洗脱支架 |
-
2017
- 2017-03-22 CN CN201710172227.8A patent/CN108619578A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102159257A (zh) * | 2008-07-17 | 2011-08-17 | 米歇尔技术公司 | 药物递送医疗设备 |
CN203436435U (zh) * | 2013-07-01 | 2014-02-19 | 雅伦生物科技(北京)有限公司 | 一种脑血管药物洗脱支架 |
Non-Patent Citations (2)
Title |
---|
ZULAIKA MISWAN等: "Drug-eluting coating of ginsenoside Rg1 and Re incorporated poly(lactic-co-glycolic acid) on stainless steel 316L: Physicochemical and drug release analyses", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
杨世海: "《中药资源学》", 31 August 2006, 北京:中国农业出版社 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Park et al. | In vivo evaluation and characterization of a bio-absorbable drug-coated stent fabricated using a 3D-printing system | |
JP6114274B2 (ja) | マグネシウム合金を含む吸収性ステント | |
US20060085062A1 (en) | Implantable stent with endothelialization factor | |
CN110139681A (zh) | 具有氟化镁涂层和有机涂层的由可生物降解的镁合金制成的支架 | |
Grube et al. | Rapamycin analogs for stent-based local drug delivery | |
EP2111818B1 (en) | Intracoronary stent with asymmetric drug releasing controlled coating | |
EP2380528A1 (en) | Medicament eluting apparatus with micro-hole structure capable of storing and releasing multiple medicines and preparation method | |
Lange et al. | Second-generation drug-eluting coronary stents | |
JPWO2009031295A1 (ja) | 薬剤徐放性ステント | |
US9433709B2 (en) | Interventional medical device and manufacturing method thereof | |
JP7074747B2 (ja) | ポリマーフリー薬剤溶出型血管ステント | |
Jeong et al. | Augmented re-endothelialization and anti-inflammation of coronary drug-eluting stent by abluminal coating with magnesium hydroxide | |
MX2015001673A (es) | Dispositivo medico implantable de elucion direccional. | |
Ali et al. | A novel CX3CR1 antagonist eluting stent reduces stenosis by targeting inflammation | |
Qi et al. | Current status of research and application in vascular stents | |
US9968717B2 (en) | Scaffold with drug coating for treating restenosis and preparation method thereof | |
CN107913119A (zh) | 一种介入医疗器械及其制备方法 | |
Steffel et al. | Biological effects of drug-eluting stents in the coronary circulation | |
US8591571B2 (en) | Drug-eluting stent | |
CN108619578A (zh) | 药物洗脱支架及其制备和应用 | |
KR101595267B1 (ko) | 재협착과 염증 조절을 위한 순차적 약물 방출 스텐트의 제조방법 | |
US20200384161A1 (en) | Composite anti-restenosis drug for coronary drug-eluting stent and controlled release system thereof | |
US20160008518A1 (en) | Pharmaceutical compositions and devices for treatment of proliferative diseases | |
EP3213721B1 (en) | Drug-eluting stent | |
JP2009521961A (ja) | 再狭窄予防治療のために薬物組成を放出する冠状動脈ステントとその組み立て工程 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181009 |
|
RJ01 | Rejection of invention patent application after publication |