The surface is provided with rustless steel angiocarpy bracket of medication coat and preparation method thereof
Technical field
The present invention relates to a kind of insertion type medical apparatus, particularly a kind of surface that is used for human body coronary heart disease interventional therapy is provided with stainless steel stent of medication coat and preparation method thereof.
Background technology
Percutaneous coronary angioplasty (Percutaneous transluminal coronaryangioplasty, PTCA) art owing to have need not open breast, success rate height, wound little, need not general anesthesia, convenient advantage such as quick, thereby become and treat one of common method of coronary heart disease at present clinically.But a large amount of clinical practice results shows that behind the balloon expandable, because the acute locking and the factors such as elastical retraction, improper reconstructing blood vessel and hamartoplasia of blood vessel wall cause PTCA postoperative restenosis rate up to 30%~50%, especially postoperative is 3~6 months.
1987, Sigwart etc. were used for coronary artery with metal rack in the blood vessel first, had received beyond thought effect, for treatment blood vessel blockage disease provides good approach.Coronary stent is an eyelid retractor in a kind of blood vessel of being made by the metal stainless steel material, it has good plasticity and geometrical stability, can under closure state, deliver to diseased region, with methods such as air bag expansions it be launched then, play the effect of interim support blood vessels through conduit.Coronary artery stent implantation is because the acute locking of blood vessel wall after having avoided balloon expandable effectively, elastical retraction and improper blood vessel are reinvented, and it is more obvious that initial tube chamber is enlarged, and restenosis rate obviously reduces.But because support can't avoid hamartoplasia, the thrombus source of metal itself in addition still has 13%~20% restenosis generation after making support implant.This shows that although coronary stent has reduced the generation of vascular restenosis after PTCA to a certain extent, its clinical practice also is faced with following problem: 1) subacute stent thrombosis (in the postoperative 10 days); 2) tardy property thrombosis; 3) inner membrance, middle film hypertrophy (14 days peaks continue about 1 month) that cause of smooth muscle cell hyper-proliferative, migration.
In order to address the above problem, people attempt to adopt physics, chemistry etc. method rack surface carried out suitable modification handle to improve its biocompatibility.Wherein, pharmaceutical pack is exactly wherein to be expected to most one of method of modifying that obtains clinical practice.The medicine coating stent is that medicine (as antithrombotic agents, antiproliferative) is applied to rack surface by methods such as ionic bond, covalent bond or physical absorptions, and medicine is transported to the pathological changes target area along with support, discharges into blood in the target area.Thereby the side effect of avoiding systemic administration to cause effectively improves the target area drug concentrations.
US 4,613, and 665. at rack surface elder generation load coupling agent, by ionic bond heparin is carried on rack surface then.US 5,112, and 457. using plasma technology are at rack surface deposition one deck N-hexyl pyrrolidone film, then by surperficial carbonyl grafting heparin.EP0,879,595A2. is at the two-layer different material of stent surface coated, and skin is heparin and Alamine 304 class surfactant, and internal layer is made up of heparin and silicones, and heparin slowly discharges with certain speed.More than the antithrombotic property of coating stent of medicine of three Patent publish all be greatly improved, but the anti-hamartoplasia performance of support remains further to be improved.
USP 6,153, and 252. reports are material with 6-caprolactone-glycolide copolymer, preparation rapamycin bracket for eluting medicament.Result of study shows, the support that contains rapamycin film in inner membrance has good anti-narrow performance than the support that obviously is better than not containing medicine aspect (intima area/media area).
Chen etc.
[18]Studies show that the support that EVAL coats vincaleucoblastine can reach local slow and discharge medicine, suppresses the hypertrophy of smooth muscle cell and the effect of translation effectively.
Xu Zhongying
[19]Be drug model with the dexamethasone then, polylactic acid is a carrier, has studied endovascular stent to the outgrowth influence of inner membrance.The result shows, it is about 33% that drug stent reduces new intima thickness, and incidence of thrombus is higher than bare bracket.
US6,231, designed a kind of overbrushing layer support technology that can prevent that hamartoplasia and thrombosis from taking place in 600: ground floor is made up of polymer, antiproliferative pharmaceutical (paclitaxel) and cross-linking agent (aziridine), and the second layer is anticoagulant medicine heparin, and heparin is bonded in rack surface by cross-linking agent.But this preparation technology is complicated, and has introduced noxious substance (aziridine), is unfavorable for the clinical practice popularization.
By dicyclohexyl carbon imido crosslinked the going up in poly-(lactic-co-glycolic acid-aspartic acid) of antithrombotic agents heparin formed heparinization poly-(lactic-co-glycolic acid-aspartic acid) earlier among the CN 01142641.1, then support be impregnated in the chloroformic solution of heparinization poly-(lactic-co-glycolic acid-aspartic acid) and anti-proliferative agent (rapamycin), becoming to after the drying has the support of anti-hypertrophy and thrombosis.Although the not anti-body fluid of this technology overcomes traditional physical blending washes away and the chemical bond process in introduce the defective of noxious substance, but the preparation process of heparinization poly-(lactic-co-glycolic acid-aspartic acid) is comparatively complicated, the acidic materials that generate behind the material degradation can stimulate the hyperplasia of smooth muscle cell, and the anti-proliferative agent that discloses in the patent (rapamycin) is coated on the support outermost layer, the difficult control of the rate of release of rapamycin is difficult to satisfy clinical demand.
Summary of the invention:
The technical issues that need to address of the present invention are to disclose a kind of surface that can prevent simultaneously that hamartoplasia and thrombosis from taking place to be provided with rustless steel angiocarpy bracket of medication coat and preparation method thereof.
Design of the present invention is such:
The non-biodegradation elastomer that utilization has good biocompatibility and mechanical property coats anti-proliferative drug at stainless steel surfaces, simultaneously at rack outer surface grafting antithrombotic agents.After this support was implanted, anti-proliferative drug slowly discharged, thereby suppresses hyper-proliferative, migration and the inner membrance of smooth muscle cell, the hypertrophy of middle film effectively.The grafted heparin difficult drop-off of support surfaces externally and internally can prevent the generation of subacute and long-range thrombosis, and the heparin immobilization helps improving the hydrophilic and the biocompatibility of material surface; Promote adhesion and the growth of endotheliocyte, quicken rack surface and blood vessel wall endothelialization process, quicken the healing of injury blood vessel wall at material surface; Simultaneously, the material surface of heparinization has certain antiinflammatory action.
High molecular polymer as the coating surface use, should have the favorable tissue compatibility, again as the carrier of medicine and control release rate of drugs, simultaneously also must with matrix bond firmly and have enough intensity and elasticity and wash away various stress in the process to bear support transportation, support expansion and body fluid.The block copolymer of ethylene-vinyl acetate, propylene-vinylacetate, ethylene-methyl methacrylate methyl ester, ethylene-methyl methacrylate butyl ester, polyurethane etc. or random copolymer and methyl methacrylate, butyl methacrylate etc. have bigger fracture strength and elongation at break, excellent drug permeability and biocompatibility.Therefore, the present invention adopts the block copolymer of ethylene-vinyl acetate, propylene-vinylacetate, ethylene-methyl methacrylate methyl ester, ethylene-methyl methacrylate butyl ester, polyurethane etc. or random copolymer and methyl methacrylate, the butyl methacrylate coating material as stainless steel surfaces.
Medicines such as paclitaxel, rapamycin, dactinomycin, cyclosporin, vincaleucoblastine, emodin or dexamethasone have anti-preferably hamartoplasia effect, therefore, the present invention adopts medicines such as paclitaxel, rapamycin, dactinomycin, cyclosporin, vincaleucoblastine, emodin or dexamethasone to suppress the hyper-proliferative and the migration of smooth muscle cell, solves inner membrance and middle film hypertrophy problem after support is implanted.
Low temperature plasma belongs to gas-solid phase dry type reaction system to the modification of high polymer, and free from environmental pollution and reaction only relates to the shallow surface of material, and (π 10
-8M), can when keeping the material self-characteristic, give its surface new function.For this reason, the present invention adopts low temperature plasma that Polymer Surface is handled, and produces oxygen, nitrogen free radical with reactivity, improves the reactivity of material surface.
Heparin not only has good antithrombotic, and the polymer surfaces of surface grafting heparin can promote cell adhesion and growth, has excellent biological compatibility (Wang Xiufen etc., plasma causes polyethylene surface heparinization and biocompatibility thereof); In addition, heparin can obviously suppress the release of pro-inflammatory cytokine such as interleukin-6, interleukin 8 etc., increases the level of anti-inflammatory cytokines such as interleukin 10, thereby improves the antiinflammatory performance of material effectively.(Grossi?EA,Kallenbach?K,Chau?S,et?al.Impact?of?heparin?bonding?on?pediatriccardiopulmonary?bypass:a?prospectiverandomized?study.Ann?ThoracSurg,2000,70:191~196)。Therefore, this research is at rack outer surface grafting heparin.
Should consider following 3 points at implantation material surface grafting heparin: the heparin amount that 1) increases implant surface as far as possible; 2) structure of guaranteeing heparin can not change, so that its biological activity can effectively be brought into play; 3) improve grafted firmness, avoid coming off of heparin.For this reason, the present invention adopts the outer surface that low temperature plasma causes, vapor phase method evenly grafts on heparin support.
Technical scheme of the present invention:
Surface of the present invention is provided with the rustless steel angiocarpy bracket of medication coat, comprise support, be coated in rack surface the non-biodegradation elastomer medication coat that contains the anti-proliferative drug for the treatment of effective dose, be coated in rack surface non-biodegradation elastomer coating and be grafted on the heparin on non-biodegradation elastomer coating surface.Preferred medication coat thickness is 0.2~1000um, and wherein, anti-proliferative drug content counts 0.01~20% with the non-biodegradation flexible weight.
According to the present invention, also can the non-biodegradation elastomer coating that one layer thickness is 0.2~2000um be set again at rack surface.
Said rustless steel angiocarpy bracket comprises the support of present routine, as 316L stainless steel stent, Ti-Ni alloy support, polymer support etc., preferably adopts the 316L rustless steel.
Said medicine comprises a kind of in paclitaxel, rapamycin, dactinomycin, cyclosporin, vincaleucoblastine, emodin or the dexamethasone etc.;
The polymer of block copolymers such as said non-biodegradation elastomer optimal ethylene-vinylacetate, propylene-vinylacetate, ethylene-methyl methacrylate methyl ester, ethylene-methyl methacrylate butyl ester, polyurethane or random copolymer or methyl methacrylate, butyl methacrylate.
. what need stress is, heparin is grafted on coating surface, has therefore only improved the character of coating surface, and has kept the original performance of coating, and the grafting amount is 0.1ug~20ug/cm
2
Preparation method of the present invention comprises the steps:
(1) will contain antiproliferative medicine, the conventional method of the elastomeric organic solution employing of non-biodegradation, dipping or spraying method as the US2001/0014717A1 patent disclosure are coated in rack surface, said toluene, chloroform, the N of comprising, N-dimethyl acetylamide, N, a kind of in dinethylformamide or the dichloromethane;
Said impregnation technology above-mentionedly comprises anti-proliferative drug and non-biodegradation elastomer solution (wherein for support is immersed in, the elastomeric concentration of non-biodegradation is 1~10%, drug level is 0.01~10%, is weight percentage) in, dip time is 30~100s.Said spraying coating process will be for comprising anti-proliferative drug and the elastomeric solution of non-biodegradation (wherein, the elastomeric concentration of non-biodegradation is 0.5~10%, drug level is 0.01~10%, is weight percentage) place nebulizer to make its atomizing, be sprayed at rack surface then.The support that dipping or spraying are comprised behind anti-proliferative drug and the elastomeric solution of non-biodegradation moves in the vacuum desiccator dry.
(2) adopt dipping or spraying coating process that the non-biodegradation elastomer solution is coated on rack surface again.
(3) propping up of step (2) is placed in the low-temperature plasma device, being evacuated to back of the body end vacuum is 5Pa, and aerating oxygen, nitrogen or argon are opened radio frequency source and discharged.Wherein treatment conditions are: radio-frequency power 20~500w, vacuum 10~100Pa, time 20~600s.Turn off radio frequency source and gas after handling well, open valve and feed heparin solution steam, the time is 5~120 minutes, preferred 30~80 minutes, heparin can be grafted on non-biodegradation elastomer coating surface.
According to optimized technical scheme of the present invention, cleaned support can be impregnated in earlier in the mixed aqueous solution of mineral acid and hexamethylenetetramine, wherein, the concentration expressed in percentage by weight of mineral acid is 1~10%, the concentration expressed in percentage by weight of hexamethylenetetramine is 0.1~10%, and dip time is 0.5~30 minute, takes out, deionized water rinsing number minute, 70~120 ℃ of dryings to remove residual deionized water;
In the preferred hydrochloric acid of said mineral acid, sulphuric acid, phosphoric acid or the nitric acid one or more;
And then support be impregnated in the aqueous solution that concentration expressed in percentage by weight is 0.5~10% silane coupler, dip time is 2~100s, takes out natural aging 5~24h, 70~120 ℃ of dryings 10~120 minutes;
Said silane coupler is the chemical compound with following general structure:
XR′SiR
3
Wherein, X=amino, sulfydryl, vinyl, epoxy radicals etc.; R '=C
1~C
6Alkyl; R=C
1~C
6Alkoxyl.
Silane coupler adopts the commercially available prod.
At first adopt acid solution to handle support, wash remained on surface organic pollution and abluent, and roughening and activation rack surface.And at rack surface introducing silane coupler, utilize active groups a large amount of in the silane coupled agent molecule between metal and organic polymer, to form " molecule bridge ", thereby polymer firmly is fixed on rack surface, avoid coating shedding.
The non-biodegradation elastomer that utilization of the present invention has good biocompatibility and mechanical property coats anti-proliferative drug at stainless steel surfaces, utilizes lower temperature plasma technology to cause antithrombotic agents simultaneously and is grafted on the support surfaces externally and internally.After this support was implanted, anti-proliferative drug slowly discharged, thereby suppresses hyper-proliferative, migration and the inner membrance of smooth muscle cell, the hypertrophy of middle film effectively; The grafted heparin difficult drop-off of support surfaces externally and internally, can prevent the generation of subacute and long-range thrombosis, and the heparin immobilization helps improving the hydrophilic and the biocompatibility of material surface, promote adhesion and the growth of endotheliocyte, quicken rack surface and blood vessel wall endothelialization process at material surface.
Effect assessment of the present invention
(1) evaluation of anchoring strength of coating
The coating stent of medicine for preparing is expanded to a certain size, under 37 ℃ of temperature, liquid flow rate 50mL/min, washed away 24 hours then.Take out, vacuum drying is removed remained on surface water.The JSM-6360LV type scanning electron microscope (SEM) of producing in NEC company (JEOL) is observed the micro structure of rack surface coating then.
(2) the vitro drug release measurement device is adopted in the rate of release evaluation of anti-proliferative drug
Put into the slow release bottle that fills the 4mL pure water with preparing coating stent of medicine, the slow release bottle is put in 37 ℃ of constant incubators carries out slow release then.The release initial stage, change the slow release medium every day, then every 3-7 days of later stage was changed a slow release medium.With the drug level in the efficient liquid phase chromatographic analysis sustained-release liquid.Calculate the cumulative release percentage rate of medicine.
High performance liquid chromatograph is angilent serials, C
18Post, mobile phase: acetonitrile-water (50: 50), flow velocity are 1.0mL/min, and the detection wavelength is 227nm, and each sample size is 20 μ L, operates under the room temperature.
Drug level calculates by following standard curve:
(c is drug level ug/mL to c=0.20247x-0.02759, and x is a peak height, R=0.99988)
(3) evaluation of surface grafting heparin amount:
The toluidines blue laws is adopted in the quantitative analysis of heparin.The support for preparing is put into the solution of 2mL normal saline and 2mL toluidine blue, vibration, after treating fully reaction, add the vibration of 2mL normal hexane and extract the complex that generates, remaining toluidine blue adopts ultraviolet spectrophotometer to measure absorbance at the 631nm place in the aqueous layer, calculates the concentration of heparin according to the standard curve of demarcating.React away the amount of the total amount-residual toluene amine indigo plant of the amount=adding toluidine blue of toluidine blue, the amount that reacts away toluidine blue is the grafting amount of rack surface heparin.Again in conjunction with the surface area of support, the grafting amount of heparin on the unit of account area.
The demarcation of the standard curve of heparin sodium, compound concentration is the heparin sodium normal saline solution of 1.50~7.50ug/mL respectively, get 2mL and add certain density toluidine blue solution 2mL, after treating fully reaction, add the 2mL normal hexane, vibration is taken off layer aqueous solution and is surveyed its absorbance at 631nm wavelength place after mixing, and demarcates standard curve.
Description of drawings
Fig. 1 is the crown arterial bracket structural representation of the 316L rustless steel support of this structure (but be not limited to)
Fig. 2 expands, washes away the structural representation after 24 hours for 316L rustless steel hybrid medicine support.
Fig. 3 be anti-proliferative drug release rate over time
The specific embodiment
Detailed description below by the specific embodiment of the inventive method is further set forth the present invention, but embodiment is not a limitation of the present invention.
Embodiment 1
Get the 316L stainless steel stent, cleaning, drying.Above-mentioned support be impregnated in 30s in the solution that contains 0.00004 gram paclitaxel, 0.40 gram ethylene-vinyl acetate, 7.59 gram toluene, take out, 60 ℃ of following vacuum dryings 20 hours.Again support be impregnated in 30s in the solution that contains 0.2 gram ethylene-vinyl acetate, 9.8 gram toluene, taking-up, drying.Adopt nitrogen gas plasma to cause the heparin grafting.Plasma process conditions is: radio-frequency power 20w, vacuum 50Pa, time 10min.The heparin solution of feeding 4% 30 minutes gets final product to such an extent that surperficial heparin grafting amount is 5.3ug/cm after the drying
2Drug stent, this support is designated as TH-1.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3, and after drug release finished, the amount of rack surface heparin was 4.5ug/cm
2
Embodiment 2
Get the 316L stainless steel stent, clean drying.Above-mentioned support be impregnated in 100s in the solution that contains 0.02 gram paclitaxel, 0.18 gram ethylene-vinyl acetate, 7.8 gram toluene, take out drying.Again support be impregnated in 30s in the solution that contains 0.1 gram ethylene-vinyl acetate, 9.9 gram toluene, take out drying.Adopt nitrogen gas plasma to cause the heparin grafting, plasma process conditions is: radio-frequency power 100w, vacuum 10Pa, time 2min.The heparin solution of feeding 4% 10 minutes, can get heparin grafting amount after the drying is 5.1ug/cm
2Drug stent, this support is designated as TH-2.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 4.2ug/cm
2
Embodiment 3
Get the 316L stainless steel stent, cleaning, drying.Toluene solution 20 grams that will contain 0.002 gram paclitaxel, 0.198 gram propylene-vinylacetate are sprayed at rack surface, drying.Again support be impregnated in the solution that contains 0.2 gram ethylene-methyl methacrylate methyl ester, 9.8 gram toluene, take out drying.Adopt oxygen gas plasma to cause the heparin grafting.Plasma process conditions is: radio-frequency power 500w, vacuum 100Pa, time 10min.Fed 4% heparin solution 15 minutes, can get content after the drying is 3.2ug/cm
2The heparin drug stent, this support is designated as TH-3.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 2.8ug/cm
2
Embodiment 4
Get the 316L stainless steel stent, cleaning, drying.Toluene solution 20 grams that will contain 0.01 gram paclitaxel, 0.19 gram propylene-vinylacetate are sprayed at rack surface, drying.Again at the ethylene-methyl methacrylate butyl acetate solution of support spraying 1%, drying.Adopt argon plasma to cause the heparin grafting.Radio-frequency power 20w, vacuum 50Pa, time 10min.Fed 4% heparin solution 120 minutes, dry 20 hours can get content is 19.5ug/cm
2The heparin drug stent, this support is designated as TH-4.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 17.3ug/cm
2
Embodiment 5
Get the 316L stainless steel stent, clean drying.At the polyurethane solutions of rack surface spraying 1%, take out 60 ℃ of following vacuum dryings 15 hours.Toluene solution 20 grams that will contain 0.01 gram paclitaxel, 0.19 gram EVA again are sprayed at rack surface, take out drying.And then, take out drying at the ethylene-vinyl acetate solution of rack surface spraying 1%.Adopt oxygen gas plasma to cause the heparin grafting.Radio-frequency power 200w, vacuum 20Pa, time 5min.Fed 4% heparin solution 30 minutes, got final product to such an extent that content is 8.9ug/cm in dry 20 hours
2The heparin drug stent, this support is designated as TH-5.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 8.0ug/cm
2
Embodiment 6
Get the 316L stainless steel stent, cleaning, drying.Above-mentioned support be impregnated in the solution 30s that contains 0.004 gram paclitaxel, 0.40 gram ethylene-vinyl acetate, 7.596 gram toluene, take out, 60 ℃ of following vacuum dryings 20 hours.Again support be impregnated in 30s in the solution that contains 0.2 gram ethylene-vinyl acetate, 9.8 gram toluene, drying.Adopt nitrogen gas plasma to cause the heparin grafting, plasma process conditions is: radio-frequency power 100w, vacuum 100Pa, time 10min.Fed 4% heparin solution 30 minutes, can get content after the drying is 7.9ug/cm
2The heparin drug stent, this support is designated as TH-6.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 6.9ug/cm
2
Embodiment 7
Get the 316L stainless steel stent, cleaning, drying.Above-mentioned support be impregnated in the solution that contains 0.40 gram paclitaxel, 0.08 gram ethylene-vinyl acetate, 7.52 gram toluene, drying.Again support be impregnated in 60s in the solution that contains 0.2 gram butyl methacrylate, 9.8 gram toluene, take out, 60 ℃ of following vacuum dryings 20 hours.Adopt nitrogen gas plasma to cause the heparin grafting, plasma process conditions is: radio-frequency power 100w, vacuum 50Pa, time 10min.Fed 4% heparin solution 30 minutes, can get content after the drying is 6.2ug/cm
2The heparin drug stent, this support is designated as TH-7.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3, and after drug release finished, the residual heparin amount of rack surface was 4.5ug/cm
2
Embodiment 8
Get the 316L stainless steel stent, clean drying.Toluene solution 20 grams that will contain 0.3 gram paclitaxel, 2 gram methyl methacrylates are sprayed at rack surface, take out drying.In the propylene-vinyl acetate solution of support spraying 0.5%, take out drying again.Adopt argon plasma to cause the heparin grafting, plasma process conditions is: radio-frequency power 500w, vacuum 10Pa, time 10min.Feed 4% heparin solution 120min, got final product in dry 20 hours surperficial heparin grafting amount 20ug/cm
2Drug stent, this support is designated as TH-8.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 18.2ug/cm
2
Embodiment 9
Get the 316L stainless steel stent, clean drying.Toluene solution 20 grams that will contain 0.4 gram paclitaxel, 2 gram propylene-vinylacetates are sprayed at rack surface, take out drying.The propylene-vinyl acetate solution of rack surface spraying 1% 5 minutes, take out drying again.Adopt argon plasma to cause the heparin grafting.Plasma process conditions is: radio-frequency power 200w, vacuum 100Pa, time 20s.Fed 4% heparin solution 5 minutes, drying gets final product to such an extent that the grafting amount is 0.1g/cm
2The heparin drug stent, this support is designated as TH-9.This polymer-coated surface is smooth, transparent and firm with matrix bond.Wherein, the rate of release of anti-proliferative drug is seen accompanying drawing 3.After drug release finished, the residual heparin amount of rack surface was 0.06ug/cm
2
By the result of the foregoing description as seen, test the release that designed hybrid medicament smear layer can suppress the anti-proliferative drug paclitaxel significantly, and along with the increase of medicament contg and outermost layer coating layer thickness, release rate of drugs descends obviously.
Embodiment 10
Get the 316L stainless steel stent, clean 10min, dry.Support be impregnated in contain in the hydrochloric acid solution that 5mL concentrated hydrochloric acid (36wt%), 0.42g hexamethylenetetramine, 15.34g water be made into, flood after 5 minutes and take out drying.And then support be impregnated in the solution that contains 2.0gKH550,52.0g dehydrated alcohol and 12.67g water, take out behind the 10s, dry 15h, 110 ℃ aging 20 minutes, take out.The support that above-mentioned pretreatment is good adopts the method for embodiment 1 to carry out coating, after the support expansion, washes away the support after 24 hours, and the SEM microscopically shows that as shown in Figure 2 the drug prepared coating surface is smooth, smooth, does not see obviously to come off.