CN101185779B - A kind of preparation method of drug sustained-release stent - Google Patents
A kind of preparation method of drug sustained-release stent Download PDFInfo
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- CN101185779B CN101185779B CN2007103024031A CN200710302403A CN101185779B CN 101185779 B CN101185779 B CN 101185779B CN 2007103024031 A CN2007103024031 A CN 2007103024031A CN 200710302403 A CN200710302403 A CN 200710302403A CN 101185779 B CN101185779 B CN 101185779B
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- drug
- lactate
- slow
- release
- coating
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Abstract
一种药物缓释支架的制备方法，包括准备支架和在支架上经过药物涂敷构成药物缓释支架，支架的药物涂敷由下列步骤依次组成：(1)、缓释药物涂层的制备；(2)、缓释药物涂层的涂敷；(3)、干燥。本发明的缓释药物支架在in vitro试验中，支架上所覆载的药物组份剂量与设计剂量相符合，并能够完全按照设计要求在规定的时段按照规定的剂量释放。本发明具有良好的生物相容性，喷涂工艺成本低，成品率高，涂层厚度可控，药物释放速率平缓。A method for preparing a drug sustained-release stent, comprising preparing a stent and coating the stent with a drug to form a drug sustained-release stent, wherein the drug coating of the stent consists of the following steps in sequence: (1), preparation of a sustained-release drug coating; (2), coating of slow-release drug coating; (3), drying. In the in vitro test of the sustained-release drug stent of the present invention, the dose of the drug component covered on the stent conforms to the designed dose, and can be released at the prescribed dose within a prescribed period of time in full accordance with the design requirements. The invention has good biocompatibility, low cost of spraying process, high yield, controllable coating thickness and gentle drug release rate.
Description
Technical field
The invention belongs to medicine and medical apparatus and instruments (getting involved the class medical apparatus and instruments) field, relate to the bracket for eluting medicament that can reduce neointimal proliferation, treatment vascular restenosis, be specifically related to a kind of medicine slow release stent and preparation method thereof with non-oxidizability.
Background technology
Along with growth in the living standard, patients with coronary heart disease is increasing, and (Percutaneous Coronary Intervention PCI) has become one of coronary heart disease conventional treatments to the percutaneous coronary interventional procedure, and success rate can reach more than 95% at present.But the operation back had the patient of 25-50% that restenosis can take place in 3-6 month, had limited the late result of PCI.
The mechanism of support postoperative restenosis is: human vas causes the endotheliocyte and the smooth muscle cell damage of blood vessel wall after support or the expansion of other implantation instruments, can cause thrombosis and inflammatory reaction.Follow the release of hematoblastic cell growth factor, the propagation of stimulated vascular smooth muscle cell and migration.The smooth muscle cell that is activated is synthetic phenotype by shrinking phenotypic transformation, and in impaired back 3 days, about 40% middle film smooth muscle cell enters cell generation cycle.New synthetic cell migration is secreted a large amount of extracellular matrixs to the smooth muscle theca interna.Simultaneously, inflammatory cell can be attacked damage location, the more deep layer of intravasation wall.The endotheliocyte of dysfunction is also contributed to some extent to the propagation and the migration of smooth muscle cell.Endothelium up to damaged part grows up to again, and intimal proliferation just slows down gradually, yet extracellular matrix increases and further causes intimal thickening.This multiple bioprocess acts on the generation of the restenosis that has caused the postoperative blood vessel simultaneously.
In order to solve this difficult problem of PCI postoperative restenosis, laser, radiosiotope, multiple therapy methods such as ultrasonic were once used in explorations of constantly bringing forth new ideas in the past 20 years of medical circle both at home and abroad, did not still all solve this difficult problem well.The nineties in 20th century, research worker is selected the polymer of those good biocompatibilities as medium, with medicament mixed therein, be coated in rack surface, make rack surface with medicine can slowly discharge and keep effective treatment concentration of long period in the pathological changes part in the support back that implants, successfully develop bracket for eluting medicament (Drug Eluting Stent, DES) control PCI postoperative restenosis.The medicament selection of bracket for eluting medicament is turned to the medicine that suppresses smooth muscle cell proliferation and obtains promising result.It is the patent of invention of CN1647776A that China's invention also discloses publication number, it is an effective ingredient with Oleum Curcumae liquid, with the stainless steel material is support, controlled releasing coating is polybutyl methacrylate/nanometer silicon dioxide composite material, and this invention has cell growth inhibiting and cell death inducing, antiinflammatory, antithrombotic form, inhibition collagen is synthetic and safety is good.So far, the effect of bracket for eluting medicament in the control in-stent restenosis obtains establishing.Bracket for eluting medicament can make medicine be confined to the part to reach effective treatment concentration and keep the long period, and the whole body toxic and side effects almost can be ignored.Bracket for eluting medicament is to reduce or eliminate restenosis to have brought huge hope, and support has social and economic significance widely as the topical therapeutic of band drug carrier.
Present normally rapamycin (can be described as sirolimus, Sirolimus, Rapamycin again) and paclitaxel (Paclitaxe) or their pharmacy acceptable derivates of the entrained medicine of bracket for eluting medicament, rapamycin (U.S. Patent No. 4,885,171) be the anti-rejection drugs of the novel macrolide of streptomyces hygroscopicus generation, be present up-to-date in the world potent immunosuppressant, be used for the anti-rejection of organ transplantation and the treatment of autoimmune disease clinically.But sirolimus (Sirolimus) and paclitaxel (Paclitaxe) class some characteristics structurally are as sirolimus, it is that structure is the macrolide of 36 yuan of ring conjugated trienes, molecule contains the lactone of unsaturated polyenoid key, character instability, easily oxidation and hydrolysis.Therefore, with these drug stents after preparation and making, if there is not special protection, then can be oxidized and slow release decomposition, until complete actual effect.Particularly in some water miscible solvents, accelerated the speed that oxidation of drug is decomposed especially.At present the most common way is to dry processing the high molecular polymer that carries medicine sprays on the support after, perhaps the aluminium-foil paper that use can lucifuge in packing.But these methods all can not well be stopped the release of entrained medicine on the support and decompose from the source.And in making the bracket for eluting medicament process, how can guarantee medicine components not oxidized decomposition in manufacturing process, guarantee that its according to the rules dosage in official hour discharges the quality good or not that has determined bracket for eluting medicament.
Summary of the invention
The present invention makes drug stent have non-oxidizability to suppress medicine and decompose to discharge exactly, thereby improves the effectiveness of entrained medicine on the drug stent.
For achieving the above object, the technical solution used in the present invention is: a kind of preparation method of medicine slow release stent, and be included on the support and apply the formation medicine slow release stent through medicine, the medicine coating of support is made of successively the following step:
(1), the preparation of slow releasing pharmaceutical coating
A, preparation slow releasing pharmaceutical coating material, described slow releasing pharmaceutical coating material is made up of slow-release material, drug material and antioxidant;
1., slow-release material is selected one or both and two or more mixture of following material for use: the hexenoic acid polymer, acrylate copolymer, fluorine-based polymer, polyurethane, polyolefin, Acetic acid, hydroxy-, bimol. cyclic ester, lactide, Acetic acid, hydroxy-, bimol. cyclic ester/lactide copolymer, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polylactide, methyl lactate, ethyl lactate, isopropyl lactate, propyl lactate, butyl lactate, the lactic acid monooctyl ester, lactose, the lactose mixture, aluctyl., ferric lactate, magnesium lactate, manganese lactate, zinc lactate, polyamino acid, poly phosphate, biological species apatite, the heparinization polymer, heparin and polylactic acid (PLA);
2., drug material is selected one or both and two or more mixture of following material for use: heparin sodium, the acceptable extract of reptilase pharmacy, Ahylysantinfarctase, aspirin (Acenterine), trihydroxy-isoflavone, hirudin (Hirudin), colchicine (Colchicine), rapamycin, Everolimus, Biolimus, Zotarolimus, Tracrolimus, Pimecrolimus, simvastatin (Simvastatin), lovastatin (Lovastatin), atorvastatin (Atorvastatin), pravastatin (Pravastatin), ciclosporin (Ciclosporin), Anti-CD34, dexamethasone (Dexamethasone), bleomycin (Bleomycin), plicamycin (Plicamycin), rubidomycin (Daunorubicin), ametycin (Mitomycin), actinomycin D (Dactinomycin), paclitaxel (Paclitaxel), tripterine (Celastrol), methotrexate, 5-fluorouracil (5-FU), cytosine arabinoside (Cytarabine), Ismipur (6-MP);
3., antioxidant is selected one or both and two or more mixture of following material for use: Butylated hydroxyanisole (BHA), dibenzylatiooluene (BHT), propyl gallate (PG), D-arabo-ascorbic acid and sodium salt thereof, tea polyphenols, phytic acid, tertiarybutylhydroquinone (TBHQ), Radix Glycyrrhizae antioxygen thing, calcium ascorbate, phospholipid, ascorbyl palmitate, the thio-2 acid dilaurate, the 4-hexyl resorcin, ascorbic acid (vitamin C), sodium ascorbate, vitamin E, Herba Rosmarini Officinalis extract and AOB;
B, preparation solvent, described solvent is selected one of following material for use: glycerol, isopropyl alcohol, acetone, butanone, Ketohexamethylene, ethyl acetate, butyl acetate, oxolane, dichloromethane and normal hexane;
C, the slow releasing pharmaceutical coating material is added in the solvent, stir after the mixing, wherein, slow-release material, drug material and antioxidant are 0.01～0.1,0.002～0.02 and 0.0005～0.01 with the mass ratio of solvent respectively;
(2), the coating of slow releasing pharmaceutical coating
The method that the slow releasing pharmaceutical coating that is dissolved with slow-release material, drug material and antioxidant is soaked into by ultrasonic atomizatio spraying or support is coated to the surfaces externally and internally of support, and the rack surface medicament contg is 35～300 μ g/cm
2
(3), drying
With the support that is coated with the slow releasing pharmaceutical coating move into temperature be less than or equal to 90 ℃, more than or equal to carrying out drying in 15 ℃ the vacuum drying oven.
Because the technique scheme utilization, the present invention compared with prior art has following advantage and effect:
1, slow releasing pharmaceutical support of the present invention is in vitro test, covering the medicine components dosage that carries on the support is consistent with design dosage, and can discharge at the period of regulation dosage according to the rules according to designing requirement fully, this proves that fully medicine components does not have oxidized decomposition in preparation process.
2, the present invention has excellent biological compatibility, and the spraying coating process cost is low, and the yield rate height has repeatability, coating layer thickness is controlled, its reasonable disposition coating process, and coating is stable, firm with rack surface absorption, coating is even, and drug release rate is milder.
3, slow releasing pharmaceutical stent drug coating performance of the present invention is stable, and preparation technology is simple.
The specific embodiment
Below in conjunction with embodiment the present invention is further described:
Embodiment one
0.5 gram hexenoic acid polymer and acrylate copolymer, 0.1 gram Sirolimus (rapamycin) and 0.01 gram BHT are joined in the 10ml oxolane, mix to stir forming uniform solution.To off-the-shelf rack surface, the number of times of control spraying makes the drug loading of support reach 40ug/cm2, support is inserted in the vacuum drying oven again, carries out 24 hours dried under 35 ℃ of conditions with solution spraying.
Polymer can also be selected fluorine-based polymer, polyurethane, polyolefin, Acetic acid, hydroxy-, bimol. cyclic ester, lactide, Acetic acid, hydroxy-, bimol. cyclic ester/lactide copolymer, poly-Acetic acid, hydroxy-, bimol. cyclic ester, polylactide, methyl lactate, ethyl lactate, isopropyl lactate, propyl lactate, butyl lactate, the lactic acid monooctyl ester, lactose, the lactose mixture, aluctyl., ferric lactate, magnesium lactate, manganese lactate, zinc lactate, polyamino acid, poly phosphate, biological species apatite, the heparinization polymer, in heparin and the polylactic acid (PLA) one or both and above mixture thereof.
Medicine can also be selected heparin sodium, the acceptable extract of reptilase pharmacy, Ahylysantinfarctase, aspirin (Acenterine), trihydroxy-isoflavone, hirudin (Hirudin), colchicine (Colchicine), Everolimus, Biolimus, Zotarolimus, Tracrolimus, Pimecrolimus, simvastatin (Simvastatin), lovastatin (Lovastatin), atorvastatin (Atorvastatin), pravastatin (Pravastatin), ciclosporin (Ciclosporin), Anti-CD34, dexamethasone (Dexamethasone), bleomycin (Bleomycin), plicamycin (Plicamycin), rubidomycin (Daunorubicin), ametycin (Mitomycin), actinomycin D (Dactinomycin), paclitaxel (Paclitaxel), tripterine (Celastrol), methotrexate, 5-fluorouracil (5-FU), cytosine arabinoside (Cytarabine), in the Ismipur (6-MP) one or both and above mixture thereof.
Antioxidant can also be selected Butylated hydroxyanisole (BHA), propyl gallate (PG), D-arabo-ascorbic acid and sodium salt thereof, tea polyphenols, phytic acid, tertiarybutylhydroquinone (TBHQ), Radix Glycyrrhizae antioxygen thing, calcium ascorbate, phospholipid, ascorbyl palmitate, the thio-2 acid dilaurate, four-hexyl resorcin, ascorbic acid (vitamin C), sodium ascorbate, vitamin E, in Herba Rosmarini Officinalis extract and the AOB one or both and above mixture thereof.
Solvent can also be selected glycerol, isopropyl alcohol, acetone, butanone, Ketohexamethylene, ethyl acetate, butyl acetate; Oxolane, dichloromethane, normal hexane.
The drug stent of this patent invention is carried out the release in vitro test:
Be placed on the particular manufacturing craft of drug release test machine propping up, in the slow release pipe, put into the bovine serum albumin phosphoric acid sustained-release liquid of 20ml.The running temperature that configures equipment is set and was respectively 6 hours, 1 day, 2 days, 7 days, 14 days, 28 days 1 hour running time at 37.5 ℃.
Take out the stent drug sustained-release liquid of corresponding time period respectively, measure the content of sirolimus with HPLC.
The parameter setting of HPLC is as follows:
Mobile phase: methanol: water=75: 25,
Flow velocity: 1.0ml/min
Column temperature: 50 ℃
Detect wavelength: 276nm
Chromatographic column: Supelcosil LC-18DB (4.6mm * 250mm, 5 μ m)
Embodiment two
A kind of preparation method of medicine slow release stent joins 0.4 gram polylactic acid (PLA), 0.07 gram paclitaxel (Paclitaxel) and 0.01 gram ascorbic acid (vitamin C) in the 7ml glycerol, mixes to stir forming uniform solution.To off-the-shelf rack surface, the number of times of control spraying makes the drug loading of support reach 100ug/cm2, support is inserted in the vacuum drying oven again, under 60 ℃ of conditions, carries out 24 hours dried with solution spraying.
The drug stent of this patent invention is carried out the release in vitro test:
Be placed on the particular manufacturing craft of drug release test machine propping up, in the slow release pipe, put into the bovine serum albumin phosphoric acid sustained-release liquid of 20ml.The running temperature that configures equipment is set and was respectively 6 hours, 1 day, 2 days, 7 days, 14 days, 28 days 1 hour running time at 37.5 ℃.
Take out the stent drug sustained-release liquid of corresponding time period respectively, measure the content of paclitaxel with HPLC.
The parameter setting of HPLC is as follows:
Mobile phase: acetonitrile and water
Chromatographic column: Venusil XBP C18 (4.6mm * 250mm)
Flow velocity: V=1.5ml/min
Column temperature: 40 ℃
Detector: UV/VIS 227nm
Sample size: 20 μ L
Paclitaxel: chromatographic column is kromasil C18 (5 μ m, 0.46 * 25cm)
Acetonitrile/water binary gradient chromatographic condition is:
0-15min 40% acetonitrile (isocratic elution);
15-45min 40% acetonitrile-51% acetonitrile (linear elution);
45-55min 51% acetonitrile-70% acetonitrile (linear elution);
55-70min 70% acetonitrile (isocratic elution);
The detection wavelength is 227nm.
Embodiment three
0.01～0.1,0.002～0.02 and 0.0005～0.01;
A kind of preparation method of medicine slow release stent joins 0.6 gram Acetic acid, hydroxy-, bimol. cyclic ester/lactide copolymer, 0.13 gram paclitaxel (Paclitaxel) and 0.06 gram vitamin E in the 13ml isopropyl alcohol, mixes to stir forming uniform solution.To off-the-shelf rack surface, the number of times of control spraying makes the drug loading of support reach 280ug/cm with solution spraying
2, again support is inserted in the vacuum drying oven, under 80 ℃ of conditions, carry out 24 hours dried.
Embodiment four
0.65 gram methyl lactate, ethyl lactate, isopropyl lactate and propyl lactate mixture, 0.1 gram paclitaxel and 0.07 gram AOB are joined in the 9ml ethyl acetate, mix to stir forming uniform solution.To off-the-shelf rack surface, the number of times of control spraying makes the drug loading of support reach 120ug/cm2, support is inserted in the vacuum drying oven again, under 65 ℃ of conditions, carries out dried with solution spraying.
Embodiment five
With 0.5 gram polylactic acid (PLA), 0.1 gram ciclosporin (Ciclosporin), dexamethasone (Dexamethasone), bleomycin (Bleomycin) and plicamycin (Plicamycin) mixture, 0.08 gram tea polyphenols and phytic acid mixture join in the 11ml normal hexane, mix to stir to form uniform solution.To off-the-shelf rack surface, the number of times of control spraying makes the drug loading of support reach 240ug/cm2, support is inserted in the vacuum drying oven again, under 25 ℃ of conditions, carries out dried with solution spraying.
Embodiment six
0.6 gram heparinization polymer, 0.08 gram paclitaxel (Paclitaxel) and 0.02 gram ascorbic acid (vitamin C) are joined in the 11ml isopropyl alcohol, mix to stir forming uniform solution.To off-the-shelf rack surface, the number of times of control spraying makes the drug loading of support reach 80ug/cm2, support is inserted in the vacuum drying oven again, under 45 ℃ of conditions, carries out dried with solution spraying.
The foregoing description only is explanation technical conceive of the present invention and characteristics, and its purpose is to allow the personage who is familiar with this technology can understand content of the present invention and enforcement according to this, can not limit protection scope of the present invention with this.All equivalences that spirit is done according to the present invention change or modify, and all should be encompassed within protection scope of the present invention.
Claims (1)
1. the preparation method of a medicine slow release stent is included on the support and applies the formation medicine slow release stent through medicine, it is characterized in that: the medicine coating of support is made of successively the following step:
(1), the preparation of slow releasing pharmaceutical coating
A, preparation slow releasing pharmaceutical coating material, described slow releasing pharmaceutical coating material is made up of slow-release material, drug material and antioxidant;
1., slow-release material is selected one or both and two or more mixture of following material for use: the hexenoic acid polymer, acrylate copolymer, fluorine-based polymer, polyurethane, polyolefin, Acetic acid, hydroxy-, bimol. cyclic ester, lactide, Acetic acid, hydroxy-, bimol. cyclic ester/lactide copolymer, poly-Acetic acid, hydroxy-, bimol. cyclic ester, methyl lactate, ethyl lactate, isopropyl lactate, propyl lactate, butyl lactate, the lactic acid monooctyl ester, lactose, aluctyl., ferric lactate, magnesium lactate, manganese lactate, zinc lactate, polyamino acid, poly phosphate, the heparinization polymer, heparin and polylactic acid;
2., drug material is selected one or both and two or more mixture of following material for use: heparin sodium, Ahylysantinfarctase, aspirin, trihydroxy-isoflavone, hirudin, colchicine, rapamycin, Everolimus, Biolimus, Zotarolimus, Tracrolimus, Pimecrolimus, simvastatin, lovastatin, atorvastatin, pravastatin, ciclosporin, Anti-CD34, dexamethasone, bleomycin, plicamycin, rubidomycin, ametycin, actinomycin D, paclitaxel, tripterine, methotrexate, 5-fluorouracil, cytosine arabinoside, Ismipur;
3., antioxidant is selected one or both and two or more mixture of following material for use: Butylated hydroxyanisole, dibenzylatiooluene, propyl gallate, D-arabo-ascorbic acid and sodium salt thereof, tea polyphenols, phytic acid, tertiarybutylhydroquinone, Radix Glycyrrhizae antioxygen thing, calcium ascorbate, phospholipid, ascorbyl palmitate, the thio-2 acid dilaurate, the 4-hexyl resorcin, ascorbic acid, sodium ascorbate, vitamin E, Herba Rosmarini Officinalis extract and AOB;
B, preparation solvent, described solvent is selected one of following material for use: glycerol, isopropyl alcohol, acetone, butanone, Ketohexamethylene, ethyl acetate, butyl acetate, oxolane, dichloromethane and normal hexane;
C, the slow releasing pharmaceutical coating material is added in the solvent, stir after the mixing, wherein, slow-release material, drug material and antioxidant are 0.01～0.1,0.002～0.02 and 0.0005～0.01 with the mass ratio of solvent respectively;
(2), the coating of slow releasing pharmaceutical coating
The method that the slow releasing pharmaceutical coating that is dissolved with slow-release material, drug material and antioxidant is soaked into by ultrasonic atomizatio spraying or support is coated to the surfaces externally and internally of support, and the rack surface medicament contg is 35～300 μ g/cm
2
(3), drying
With the support that is coated with the slow releasing pharmaceutical coating move into temperature be less than or equal to 90 ℃, more than or equal to carrying out drying in 15 ℃ the vacuum drying oven.
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Families Citing this family (25)
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| CN106924812B (en) * | 2017-03-14 | 2019-11-22 | 浙江巴泰医疗科技有限公司 | A kind of medicine slow release stent and its preparation method and application |
| CN109966563B (en) * | 2017-12-28 | 2021-08-03 | 元心科技(深圳)有限公司 | Implanted medicine carrying device |
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| CN119280490B (en) * | 2024-12-12 | 2025-03-21 | 四川省医学科学院·四川省人民医院 | A coating with anesthetic and antibacterial functions and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513567A (en) * | 2002-12-31 | 2004-07-21 | 中国科学院金属研究所 | A cardiovascular stent with controlled release of therapeutic drugs |
| CN1557507A (en) * | 2004-01-16 | 2004-12-29 | 东南大学 | Anti-restenosis drug slow-release vascular stent and preparation method thereof |
-
2007
- 2007-12-19 CN CN2007103024031A patent/CN101185779B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1513567A (en) * | 2002-12-31 | 2004-07-21 | 中国科学院金属研究所 | A cardiovascular stent with controlled release of therapeutic drugs |
| CN1557507A (en) * | 2004-01-16 | 2004-12-29 | 东南大学 | Anti-restenosis drug slow-release vascular stent and preparation method thereof |
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