CN1378865A - Medicine coated support frame of blood vessel - Google Patents
Medicine coated support frame of blood vessel Download PDFInfo
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- CN1378865A CN1378865A CN 02112955 CN02112955A CN1378865A CN 1378865 A CN1378865 A CN 1378865A CN 02112955 CN02112955 CN 02112955 CN 02112955 A CN02112955 A CN 02112955A CN 1378865 A CN1378865 A CN 1378865A
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Abstract
A medicine coated support frame for blood vessel is composed of netted tube as support frame, medicine, and carrier. The mentioned medicine may be sartan kind of medicine, including valsartan, losartan, irbesartan, candesartan, telmisartan, eprosartan, saprisartan, tasosartan and zolasartan. This invention adopts a medicine action path different from that in the post, it is to play the part from the receptor's blockade action, and the sartan kind of medicines is selected as the ATI receptor blocking agent. Its advantages are better control of the speed to release medicine and high effect on preventing the recurrence of angiostenosis.
Description
Technical field
The present invention relates to medical instruments field, relate to a kind of vasodilation support that adopts medicine to coat, be specifically related to a kind of intravascular stent that sartans coats that contains.This medicament intravascular stent can effectively prevent the generation of support postoperative restenosis.
Background technology
Since the main means of intravascular stent as interventional therapy cardiovascular and peripheral blood vessel obstruction pathological changes, this technical development is rapid, has accounted for more than 80% of this type of disease treatment at present.But the greatest drawback of this technology is the generation of vascular restenosis behind the stenting, and from present statistics, support postoperative restenosis incidence rate is about 15%-30%.The reason of vascular restenosis is behind the stenting: the support expansion has been brought out vascular smooth muscle cell generation transition propagation after causing the tunica intima damage, thereby causes the hypertrophy of tunica intima, and the result causes the restenosis behind the stenting.
Accompanying drawing 1 forms the mechanism sketch map for endothelium.Mechanism problem people at restenosis have carried out a large amount of experimentatioies, think that following mechanism may participate in the process of restenosis: (i) vessel endothelium and induced endothelial, the startup of inflammatory process, receptor (ii) smooth muscle cell (the smooth muscle cell that is activated, the secretion of propagation SMC), migration and extracellular matrix: the propagation of the SMC that somatomedin relies on, the SMC of protease dependence is to the migration of affected area, the deposition of the substrate that cytokine starts.
At present can be by the disinthibite generation of restenosis of following approach:
1, reduces blood vessel injury
This method is mainly relevant with support and stenting operation, can improve the biocompatibility of support by improving support Design.Can also in the support expansion, adopt the mode of low pressure expansion simultaneously, thereby reduce damage artificially blood vessel.
2, inflammation-inhibiting reaction
Mainly be to reach by improving biocompatibility.Rack surface is carried out modification handle, as carry out plated film (as SiC, plated films such as TiOx) 316L stainless steel stent surface is coated, improve the antiplatelet deposition capability on surface, suppress simultaneously that element such as nickel, chromium in the stainless steel material is separated out and the inflammatory reaction that causes.
The medicine that can select some inflammation-inhibitings to react in addition carries out support films, as selects for use dexamethasone (Dexamethasone), radiosone medicines such as (Methyl-prednisolone) to come the inflammation-inhibiting reaction, thereby reduces the generation of restenosis.
3, suppress cell migration
Because cell migration is an important step in vascular smooth muscle cell (SMC) growth.Hinder cell migration, also just meaned the propagation degree that has reduced cell, reduced the generation of restenosis.As select Ba Dimasitaite (Batimastat) for use; prolyl 3-hydroxylase inhibitors (Prolyl Hydroxylaseinhibitors); Solenognathus Fu Jinuo (halofuginone), c-protease inhibitor MMP inhibitor such as (C-Proteinaseinhibitors) can be used as the medicine that suppresses cell migration.
4, the medicine of cell proliferation
Multiplicative stage in the cell growth cycle is the reason that support causes vascellum endometrial hyperplasia.Can select the medicine that suppresses cell proliferation for use in this stage, thunderous handkerchief mycin (Rapamycin), actinomycin methotrexate (Actinomycin methothrexate), QP-2, paclitaxel (Taxol), Angiopeptin, BCP678, Paclitaxel, vincristine (Vincristine), mitomycin (Mitomycin) and A Bote ABT-578 medicines such as (Abbott ABT-578) carries out support films, and the restenosis behind the inhibition stenting, such medicine are the support coating medicines that suppresses restenosis that generally adopts at present.
5, promote the medicine of healing and endothelialization
As to select BCP671, estrogen (Estrogen) and VE somatomedin (VEGF) for use all be the support peplos medicine that can promote blood vessel endotheliumization.
In conjunction with the approach of above-mentioned various inhibition support postoperative restenosis, the support that can find to suppress restenosis is filmed medicine can be from a plurality of angle generation effects restenosis that disinthibites.However, the sickness rate of vascular restenosis is not effectively controlled yet behind the stenting.For this reason, the present invention is different from above-mentioned approach, is the angle that works from the receptor blocking level, selects suitable drug to make the medicine coating stent and comes prevention of restenosis, thereby realize slowing down even eliminating the generation of vascular restenosis.
Summary of the invention
For achieving the above object, the technical solution used in the present invention is: a kind of medicine coated support frame of blood vessel, mainly be made up of pipe network shape intravascular stent, medicine and carrier, medicine is coated on the intravascular stent surface by carrier, and described medicine comprises one or more the mixing in the sartans; Described sartans comprises valsartan (Valsartan), losartan (losartan), irbesartan (irbesartan), Candesartan (candesartan), telmisartan (telmisartan), eprosartan (eprosartan), saprisartan (saprisartan), tasosartan (tasosartan) and zolasartan (zolasartan).
The related content and the change interpretation of technique scheme are as follows:
Described " intravascular stent " is meant a kind of vasodilation support that is used for as interventional therapy cardiovascular and peripheral blood vessel obstruction pathological changes, comprises stainless steel stent, cobalt alloy support and nick-eltitanium alloy stent etc.Intravascular stent is that (wound is only about 2mm) interventional therapy method is hindered by a kind of novel Wicresoft, this method is to utilize the foley's tube in the PTCA operation that support is sent into the blood vessel place that narrows down, in balloon expandable, strut support, thereby reach the purpose of blood vessel dilating.Present most typical support is to be formed through cut by stainless steel tube, and integral body is the net form tubular structure.During use, under the monitoring of medical imaging device, utilize medical apparatus and instruments such as puncture needle, conduit, this support is delivered to diseased region through tremulous pulse, support is expanded, strut the pathological changes tremulous pulse, reach the purpose of treatment.
In the technique scheme, described " medicine comprises one or more the mixing in the sartans ", wherein " comprise " the open implication of expression, promptly husky smooth class is necessary in the medicine, can also comprise other medicines, only contain sartans in the medicine certainly and also allow.Wherein " one or more mixing " expression can be selected a kind of in 9 kinds of the sartans or more than one to mix to use on support.According to this explanation, a kind of scheme preferably of medicine of the present invention is: the mixing of one or more in the sartans.Another kind scheme preferably is: the hybrid medicine of one or more in the sartans and cell proliferation class.
Sartans comprises valsartan (Valsartan) at present, losartan (losartan), irbesartan (irbesartan), Candesartan (candesartan), telmisartan (telmisartan), eprosartan (eprosartan), saprisartan (saprisartan), nine kinds of tasosartan (tasosartan) and zolasartans (zolasartan), the Chinese of wherein preceding four kinds of sartans is by colleague's approval, then the Chinese of five kinds of sartans is transliteration, should be as the criterion with English name.In addition, additional disclosure: the translation of title in the patent application document of the present invention, if inaccurately all be as the criterion with English or expressed object.
The present invention is to be that carrier is coated on metal support surface with the polymer with sartans such as valsartan, and its structure mainly is made up of the coating of metal rack and polymer support and medicine.
After having selected suitable medicine, the release that reasonably realizes medicine is important.
The present invention adopts two kinds of delivery modes: a kind of coating of being discharges, and promptly discharges by polymer support; Another kind is that film discharges, and promptly discharges by polymeric film and biological material film etc.
Release rate of drugs be coated with that form membrane, film coated surface are long-pending, coating thickness, the factors such as diffusion coefficient of medicine in polymer support be relevant.Therefore select the suitable mode of filming, polymer support and control coating thickness just to determine the release of medicine.Described " carrier " is meant can be with a kind of medium of medicine efficient loading on support, and the effect of carrier has 2 points at least: the one, and drug loading, the 2nd, control release rate of drugs.Below also to introduce in detail.
The structure and the mode of the medicine coating stent that the present invention adopts comprise following three kinds: i.e. embedding mode, suction type and chuck mode, and wherein embedding and absorption dual mode belong to the coating delivery mode, and the chuck mode belongs to the film delivery mode.
1, embedding mode
Shown in accompanying drawing 2, described carrier is a polymer, intravascular stent surface-coated one layer of polymeric coating, the outer repaste of this polymer coating covers one deck medicine or hybrid medicament smear layer, the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating, constitutes the supporting structure of sandwich style embedding medicinal with this.Specifically can to increase the affinity of support and drug-carried coat, follow coating one deck drug-carrying polymer coating or one deck medicine earlier in support top layer coating one deck straight polymer coating, outermost layer is the polymer coating of band micropore.If the release that will slow down medicine can be adopted on the top that outermost layer adopts biodegradable simple polymer or contains porous non-degradation polymer and be coated with the release that (Top-coat) delays medicine.The release that in the past slowed down medicine is to realize by the thickness that increase is filmed, but the thickness of often filming makes the mechanical properties decrease of filming again after increasing easily.If will can be with medication coat as outermost layer with the medicine rapid release.
2, suction type
Shown in accompanying drawing 3, described carrier is a polymer, the polymer coating of intravascular stent surface-coated one deck band micropore, and medicine is adsorbed in the micropore of polymer coating through the dip-coating mode, constitutes the supporting structure that micropore discharges medicine with this.Can at first prepare the polymer coating of being with micropore during concrete operations, then medicine is adsorbed within the micropore, by capillary theory with drug release.
3, chuck mode
Shown in accompanying drawing 4, described carrier is polymeric film or biological material film, intravascular stent surface-coated medication coat, and support and medication coat integral body are clipped in the middle of two layers of polymers film or the biological material film.The difference of chuck mode and embedding mode is: the chuck mode embodies with the integral membrane clamp structure, all comprise medicine on the bar of pipe network support and in the space between the rod member, and the embedding mode only is coated with medicine on the backbone metal bar, does not have medicine in the space between the ordinary circumstance rod member.
Filming or applying described in the present invention can adopt dip-coating and two kinds of methods of spraying to carry out, to decide according to the concentration and the actual needs of medicine and carrier in concrete the enforcement, generally speaking, the most dip-coating modes that adopt of medicine, in order to avoid cause the waste of spraying, and most employing of polymer sprays, because dip-coating causes biofilm easily when concentration is high.
First spraying one deck straight polymer coating on support in the embedding mode, a certain amount of medicine dispersion liquid of dip-coating again after the film forming sprays one layer of polymeric coating (Top-coat) at last again, thereby forms the sandwich coating structure.So both saved medicine, and satisfied in the support use requirement to polymer coating again, this mode of filming has realized that also medicine discharges with comparatively ideal pattern simultaneously.
Polymer support is a biocompatibility better polymerization thing in the coating embedding delivery mode of the present invention.Described biodegradable polymer support has following several:
PLA (Polylactic acid-PLA), aliphatic polyester (aliphatic polyesters), polyamino acid poly (amino acids), copolymerization (ether-ester) copoly (ether-esters), polyolefin oxalates (polyalkylenes oxalates), polyamide (polyamides), poly-iminocarbonic acid salt poly (iminocarbonates), positive polyester (polyorthoesters), polyether ester (polyoxaesters), polyesteramide (polyamidoesters), the polyether ester (polyoxaesters containing amidogroups) that band is amino, polyanhydride poly (anhydrides), poly phosphate (polyphosphazenes) etc.
Polymer of the present invention requires to possess the favorable mechanical performance simultaneously, promptly has higher elongation at break, and has good adhesiveness with support, so the biodegradable polymer elastomer material of our many employings.
Nonbiodegradable polymer support mostly is biological stability better polymerization thing in the coating embedding delivery mode of the present invention.Described nonbiodegradable polymer support has following several:
Polyurethane (Polyurethanes-PU), silicones (silicones), polymethacrylates (poly (meth) acrylates), polyester (polyesters), poly(ethylene oxide) polyalkyl oxides (polyethylene oxide), polyvinyl alcohol (polyvinyl alcohols), polyethylene glycols (Polyethylene Glycol) and polyvinyl pyrrolidone (polyvinylpyrrolidone), glutin (gelatin), polysiloxanes (Polysiloxane) etc.
Polymer support is the polymeric material of micropore in the coating absorption delivery mode of the present invention.Comprise PLA (Polylactic acid-PLA) as above-mentioned polymer support, aliphatic polyester (aliphatic polyesters), polyamino acid poly (amino acids), copolymerization (ether-ester) copoly (ether-esters), polyolefin oxalates (polyalkylenes oxalates), polyamide (polyamides), poly-iminocarbonic acid salt poly (iminocarbonates), positive polyester (polyorthoesters), polyether ester (polyoxaesters), polyesteramide (polyamidoesters), the polyether ester (polyoxaesters containing amido groups) that band is amino, polyanhydride poly (anhydrides), poly phosphate (polyphosphazenes), polyurethane (Polyurethanes-PU), silicones (silicones), polymethacrylates (poly (meth) acrylates), polyesters (polyester), polyalkyl oxides (polyethylene oxide) poly(ethylene oxide), polyvinyl alcohol (polyvinylalcohols), polyethylene glycols (Polyethylene Glycol) and polyvinyl pyrrolidone (polyvinylpyrrolidone), glutin (gelatin), polysiloxanes (Polysiloxane) etc. and micropore ceramics.
Polymer support is the polymer of biocompatibility and better mechanical property in the film delivery mode of the present invention.Described polymer support has following several: polyurethane (PU), polytetrafluoroethylene (PTFE), Merlon (PC) etc.Described biomaterial has the collagen protein that extracts from caval vein of animal and chamber tremulous pulse.
Choice of Solvent is the dissolubility of viscosity, coherent condition and the medicament of polymer comprehensively, the wettability of support, and combined factors such as the evaporation rate of solvent are considered.First-selected solvent should be that medicament and polymer can both be dissolved in wherein.Then be that polymer can be dissolved in the solvent in some cases, medicament then is to be distributed in the mixed solution of polymer and solvent.In this case, should select little agent molecule to be suspended in wherein, but it is gathered or condense caked solvent, the pharmacy particle that gathers when preventing to use blocks the space of support.The main foundation that though solvent volatility is for we to be selected, preferably it can volatilize fully, the avirulence of solvent, and non-carcinogenesis and environment formedness also are the important indicators that we select.We also can use mixed solvent system to control viscosity and rate of volatilization.Under any circumstance selected solvent all should be relatively stable, not with medicament and polymer supported precursor reactant.
The solvent of first-selection of the present invention comprises:
Acetone (acetone), N-methylpyrrole (N-methylpyrrolidone) (NMP), dimethyl sulfoxide (DMSO), toluene (toluene), dichloromethane (methylene chloride), chloroform (chloroform), 1,1,2-trichloroethane (TCE), fluorine Lyons (freon), dioxane (dioxane), ethyl acetate (ethyl acetate), oxolane (THF), dimethyl formamide (DMF) and dimethyl acetylamide (DMAC) etc.
Because the technique scheme utilization, the present invention compared with prior art has the following advantages and good effect:
The angiotensin antagonist that the present invention adopts is as the AT1 receptor blocking agent, the antiproliferative medicine that influences cell cycle that acts on different from the past, as immunosuppressant rapamycin (Rapamycin), latter's pair cell has damaging action, influence the healing of endothelium, cause the formation of thrombosis.
Their a kind of Angiotensin IIs (AngII) as the treatment hypertension were used in the past, because Angiotensin II (AngII) is one of most important factor that participates in vascular endothelial function and neointimal hyperplasia, now with sartans as the AT1 receptor blocking agent.The AT1 receptor blocking agent has high degree of protection to endothelial function, can prevent neointima proliferation.At present, very not clear and definite for the mechanism of action of AT1 receptor blocking agent, think that mainly its mechanism may be: thus the oxidation prevention of arterial that suppresses low density lipoprotein, LDL is atherosis; Reduce the release of free radical and the contraction of blood vessel; Blocking platelet derivative growth factor-BB (PDGF-BB) and epidermal growth factor (EGF) are to the synergism of smooth muscle cell proliferation; Antiinflammatory action.The Val-PREST result of the test of up-to-date announcement show valsartan the B2 type of complexity and C type pathological changes are inserted support after neointima proliferation preventive effect is arranged, make valsartan reduce to 20% from nearly 40% to the restenosis rate that height restenosis risk patient is arranged.
The Val-PREST result of the test shows that the administration of valsartan whole body can reduce restenosis rate behind PTCA and the stenting.Whether adopt the valsartan coating stent can more effective prevention of restenosis, find bibliographical information in this respect at present as yet.
Intravascular stent with anti-restenosis angiotensin antagonist coating of the present invention can reduce the incidence rate of angiemphraxis patient restenosis after interventional therapy effectively, and the complication that lowers patient significantly takes place, and improves patient's survival rate and quality of life; From economic angle,, reduced the medical expense of patient's restenosis owing to the reduction of restenosis incidence rate.
Description of drawings
Accompanying drawing 1 forms the mechanism sketch map for this endothelium;
Accompanying drawing 2 is the drug stent coating structure sketch map of embedding mode of the present invention;
Accompanying drawing 3 is the drug stent coating structure sketch map of suction type of the present invention;
Accompanying drawing 4 is the drug stent structural representation of chuck mode of the present invention.
In the above accompanying drawing: 1, straight polymer coating; 2, medicine or hybrid medicament smear layer; 3, biological degradation polyalcohol or microporous polymer coating; 4, metal rack; 5, micropore; 6, polymer coating; 7, polymeric film or biological material film.
The specific embodiment
Below in conjunction with drawings and Examples the present invention is further described:
Embodiment 1: sees shown in the accompanying drawing 3, and a kind of porous absorption coating stent of medicine, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1g HCL again, after mixing is uniformly dispersed under 40 ℃ of conditions, formed colloidal sol in 2 hours, be sprayed at rack surface then, will prop up again and be placed on 80 ℃ of baking ovens, solidified 24 hours, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.Again this support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) alcoholic solution.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the valsartan or the losartan coating stent of medicine of porous silicon gel pottery absorption.
Embodiment 2: sees shown in the accompanying drawing 3, and a kind of porous absorption coating stent of medicine, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1g HCL again, after mixing is uniformly dispersed under 40 ℃ of conditions, formed colloidal sol in 2 hours, be sprayed at rack surface then, will prop up again and be placed on 80 ℃ of baking ovens, solidified 24 hours, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.Again this support is dipped in 1min-60min in Irbesartan (irbesartan) dichloromethane solution of concentration 1%-60%.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the irbesartan coating stent of medicine of porous silicon gel pottery absorption.
Embodiment 3: sees shown in the accompanying drawing 3, and a kind of porous absorption coating stent of medicine, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1gHCL again, after mixing is uniformly dispersed under 40 ℃ of conditions, formed colloidal sol in 2 hours, be sprayed at rack surface then, will prop up again and be placed on 80 ℃ of baking ovens, solidified 24 hours, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.Again this support is dipped in 1min-60min in Candesartan (Candesartan) methanol solution of concentration 1%-60%.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the Candesartan coating stent of medicine of porous silicon gel pottery absorption.
Embodiment 4: sees shown in the accompanying drawing 3, and a kind of porous absorption coating stent of medicine, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1gNaOH again, 70 ℃ are disperseed to form in 1 hour colloidal sol, be sprayed at rack surface then, again support was solidified 24 hours under 150 ℃ of conditions, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.Again this support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) alcoholic solution.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the valsartan or the losartan coating stent of medicine of porous silicon gel pottery absorption.
Embodiment 5: sees shown in the accompanying drawing 3, and a kind of porous absorption coating stent of medicine, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1gNaOH again, 70 ℃ are disperseed to form in 1 hour colloidal sol, be sprayed at rack surface then, again support was solidified 24 hours under 150 ℃ of conditions, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.Again this support is dipped in 1min-60min in Irbesartan (irbesartan) dichloromethane solution of concentration 1%-60%.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the irbesartan coating stent of medicine of porous silicon gel pottery absorption.
Embodiment 6: sees shown in the accompanying drawing 3, and a kind of porous absorption coating stent of medicine, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1gNaOH again, 70 ℃ are disperseed to form in 1 hour colloidal sol, be sprayed at rack surface then, again support was solidified 24 hours under 150 ℃ of conditions, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.Again this support is dipped in 1min-60min in Candesartan (Candesartan) methanol solution of concentration 1%-60%.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the Candesartan coating stent of medicine of porous silicon gel pottery absorption.
Embodiment 7: sees shown in the accompanying drawing 3, and a kind of porous absorption hybrid medicament smear layer support, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1g HCL again, after mixing is uniformly dispersed under 40 ℃ of conditions, formed colloidal sol in 2 hours, be sprayed at rack surface then, will prop up again and be placed on 80 ℃ of baking ovens, solidified 24 hours, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.This support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0 again.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the hybrid medicament smear layer support of porous silicon gel pottery absorption.
Embodiment 8: sees shown in the accompanying drawing 3, and a kind of porous absorption hybrid medicament smear layer support, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1g HCL again, after mixing is uniformly dispersed under 40 ℃ of conditions, formed colloidal sol in 2 hours, be sprayed at rack surface then, will prop up again and be placed on 80 ℃ of baking ovens, solidified 24 hours, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.1min-60min in the Candesartan (Candesartan) that again this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the hybrid medicament smear layer support of porous silicon gel pottery absorption.
Embodiment 9: sees shown in the accompanying drawing 3, and a kind of porous absorption hybrid medicament smear layer support, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1gNaOH again, 70 ℃ are disperseed to form in 1 hour colloidal sol, be sprayed at rack surface then, again support was solidified 24 hours under 150 ℃ of conditions, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.This support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0 again.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the hybrid medicament smear layer support of porous silicon gel pottery absorption.
Embodiment 10: sees shown in the accompanying drawing 3, and a kind of porous absorption hybrid medicament smear layer support, the polymer coating 6 of support 4 surface-coated one deck band micropores 5, medicine is adsorbed in the micropore 5 of polymer coating 6 through the dip-coating mode.Be specially: 10g ethyl orthosilicate (TEOS) adds 10g water, add 0.1gNaOH again, 70 ℃ are disperseed to form in 1 hour colloidal sol, be sprayed at rack surface then, again support was solidified 24 hours under 150 ℃ of conditions, then its drying between 250-800 ℃ is made its densification, form porous silicon gel ceramic coating support.1min-60min in the Candesartan (Candesartan) that again this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.40 ℃ of following vacuum dryings remove solvent after taking out support, promptly are prepared into the hybrid medicament smear layer support of porous silicon gel pottery absorption.
Embodiment 11: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.Valsartan (valsartan) that is 1-80% with this support immersion concentration or Losartan (losartan) ethanol drug solution are 30 minutes again, take out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, multilamellar Valsartan of the structure that promptly sandwiches (valsartan) or Losartan (losartan) coating stent of medicine.
Embodiment 12: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.This support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0 again.Took out behind the support 40 ℃ of following vacuum drying treatment 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, the hybrid medicament smear layer support of the structure that promptly sandwiches.
Embodiment 13: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.Valsartan (valsartan) that is 1-80% with this support immersion concentration or Losartan (losartan) ethanol drug solution are 30 minutes again, take out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, add the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed, in 2 hours film-formings of 60 ℃ of curing, promptly generate the multilamellar Valsartan (valsartan) or Losartan (losartan) coating stent of medicine of sandwich structure again.
Embodiment 14: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.This support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0 again.Took out behind the support 40 ℃ of following vacuum drying treatment 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, adds the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed, solidify 2 hours film-formings, the hybrid medicament smear layer support of the structure that promptly sandwiches in 60 ℃ again.
Embodiment 15: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.Irbesartan (irbesartan) the dichloromethane drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate multilamellar Irbesartan (irbesartan) coating stent of medicine of sandwich structure.
Embodiment 16: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.Irbesartan (irbesartan) the dichloromethane drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, add the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed,, promptly generate multilamellar Irbesartan (irbesartan) coating stent of medicine of sandwich structure again in 2 hours film-formings of 60 ℃ of curing.
Embodiment 17: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.Candesartan (Candesartan) the methanol drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate multi-layer C andesartan (Candesartan) coating stent of medicine of sandwich structure.
Embodiment 18: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.1min-60min in the Candesartan (Candesartan) that again this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.Took out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate the hybrid medicament smear layer support of sandwich structure.
Embodiment 19: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.Candesartan (Candesartan) the methanol drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, add the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed,, promptly generate multi-layer C andesartan (Candesartan) coating stent of medicine of sandwich structure again in 2 hours film-formings of 60 ℃ of curing.
Embodiment 20: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get the new distilled methyl methacrylate monomer of 10g and put into clean dry conical flask, add initiator benzoyl peroxide (be monomer heavy 0.1%).Steam enters in the conical flask when preventing pre-polymerization, can wrap one deck cellophane at bottleneck, and the reuse elastic tape is tightened.With 80-90 ℃ of heating in water bath conical flask, when extremely prepolymer viscosity is close with glycerol viscosity in the bottle, stops heating immediately and make prepolymer be chilled to room temperature with cold water.With this solution spraying to support.The above-mentioned support that coats film is put into 40 ℃ of baking ovens, continue to make monomer polymerization more than 24 hours, and then 100 ℃ were handled 1 hour.1min-60min in the Candesartan (Candesartan) that again this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.Took out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, adds the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed,, promptly generate the hybrid medicament smear layer support of sandwich structure again in 2 hours film-formings of 60 ℃ of curing.
Embodiment 21: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Valsartan (valsartan) that is 1-80% with this support immersion concentration or Losartan (losartan) ethanol drug solution are 30 minutes again, take out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate the multilamellar Valsartan (valsartan) or Losartan (losartan) coating stent of medicine of sandwich structure.
Embodiment 22: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Valsartan (valsartan) that is 1-80% with this support immersion concentration or Losartan (losartan) ethanol drug solution are 30 minutes again, take out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, add the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed, in 3 hours film-formings of 40 ℃ of curing, promptly generate the multilamellar Valsartan (valsartan) or Losartan (losartan) coating stent of medicine of sandwich structure again.
Embodiment 23: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Irbesartan (irbesartan) the dichloromethane drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate multilamellar Irbesartan (irbesartan) coating stent of medicine of sandwich structure.
Embodiment 24: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Irbesartan (irbesartan) the dichloromethane drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, add the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed,, promptly generate multilamellar Irbesartan (irbesartan) coating stent of medicine of sandwich structure again in 3 hours film-formings of 40 ℃ of curing.
Embodiment 25: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.This support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0 again.Took out behind the support 40 ℃ of following vacuum drying treatment 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, the hybrid medicament smear layer support of the structure that promptly sandwiches.
Embodiment 26: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.This support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0 again.Took out behind the support 40 ℃ of following vacuum drying treatment 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, adds the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed, solidify 3 hours film-formings, the hybrid medicament smear layer support of the structure that promptly sandwiches in 40 ℃ again.
Embodiment 27: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Candesartan (Candesartan) the methanol drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate multi-layer C andesartan (Candesartan) coating stent of medicine of sandwich structure.
Embodiment 28: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.1min-60min in the Candesartan (Candesartan) that again this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.Took out back 40 ℃ of dried 10 hours.At last the 10g glutin is dissolved in and forms 10% aqueous gelatin solution in the 90g water, add the 1g glycerol again, after being uniformly dispersed, add 0.5g firming agent (triazine: formaldehyde=1: 3), after being uniformly dispersed, dispersion liquid is sprayed on the support, takes out back cold curing 24 hours, promptly generate the hybrid medicament smear layer support of sandwich structure.
Embodiment 29: see shown in the accompanying drawing 2, a kind of sandwich style embedding medicinal coating bracket, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck medication coat 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Candesartan (Candesartan) the methanol drug solution that is 1-60% with this support immersion concentration is 30 minutes again, takes out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, add the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed,, promptly generate multi-layer C andesartan (Candesartan) coating stent of medicine of sandwich structure again in 3 hours film-formings of 40 ℃ of curing.
Embodiment 30: see shown in the accompanying drawing 2, a kind of sandwich style embedding hybrid medicament smear layer support, stent surface coated one deck straight polymer coating 1, this polymer coating 1 outer repaste covers one deck hybrid medicament smear layer 2, and the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating 3.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.This solution spraying behind rack surface, is placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.1min-60min in the Candesartan (Candesartan) that again this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.Took out back 40 ℃ of dried 10 hours.At last 20g polylactic acid (PLA) is dissolved in the 20g chloroformic solution, adds the 0.5g tween 80, be coated on the support surfaces externally and internally after being uniformly dispersed, in 3 hours film-formings of 40 ℃ of curing, promptly generate sandwich structure hybrid medicament smear layer support again.
Embodiment 31: sees shown in the accompanying drawing 4, and a kind of chuck drug stent, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.After support is dipped in this solution 30s-30min, be placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Valsartan (valsartan) that is 1-80% with this support immersion concentration or Losartan (losartan) alcoholic solution are 30 minutes then, take out back 40 ℃ of dried 10 hours.Again support is dipped at last in the polyurethane solutions behind the 30s-30min, in dry 24 hours of 40 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)].Promptly make the coating bracket of polyurethane chuck Valsartan (valsartan) or Losartan (losartan) medicine.
Embodiment 32: sees shown in the accompanying drawing 4, and a kind of chuck drug stent, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.After support is dipped in this solution 30s-30min, be placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Then this support was immersed in Irbesartan (irbesartan) dichloromethane solution that concentration is 1-60% 30 minutes, took out back 40 ℃ of dried 10 hours.Again support is dipped at last in the polyurethane solutions behind the 30s-30min, in dry 24 hours of 40 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)].Promptly make the coating bracket of polyurethane chuck Irbesartan (irbesartan) medicine.
Embodiment 33: sees shown in the accompanying drawing 4, and a kind of chuck hybrid medicine support, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.After support is dipped in this solution 30s-30min, be placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Then this support is dipped in 1min-60min in the Valsartan (valsartan) of concentration 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) and the blended alcoholic solution of Rapamycin, mixed proportion is 1: 0.5-1.0.Took out behind the support 40 ℃ of following vacuum drying treatment 10 hours.Again support is dipped at last in the polyurethane solutions behind the 30s-30min, in dry 24 hours of 40 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)].Promptly make the coating bracket of polyurethane chuck hybrid medicine.
Embodiment 34: sees shown in the accompanying drawing 4, and a kind of chuck drug stent, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.After support is dipped in this solution 30s-30min, be placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.Then this support was immersed in Candesartan (Candesartan) methanol solution that concentration is 1-60% 30 minutes, took out back 40 ℃ of dried 10 hours.Again support is dipped at last in the polyurethane solutions behind the 30s-30min, in dry 24 hours of 40 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)].Promptly make the coating bracket of polyurethane chuck Candesartan (Candesartan) medicine.
Embodiment 35: sees shown in the accompanying drawing 4, and a kind of chuck hybrid medicine support, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: get 1g polyurethane (graininess) and be dissolved in the 8ml dimethyl formamide, make solution.After support is dipped in this solution 30s-30min, be placed on ventilated chamber dry 10-12h under infrared lamp, with after most of solvent evaporates in 60 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)] dry 8-10 hour.1min-60min in the Candesartan (Candesartan) that then this support is dipped in concentration 1%-80% and the blended methanol solution of Rapamycin, mixed proportion is 1: 0.5-1.0.Took out behind the support 40 ℃ of following vacuum drying treatment 10 hours.Again support is dipped at last in the polyurethane solutions behind the 30s-30min, in dry 24 hours of 40 ℃ of vacuum drying ovens [vacuum＜1.33KPa (10mmHg)].Promptly make the coating bracket of polyurethane chuck hybrid medicine.
Embodiment 36: sees shown in the accompanying drawing 4, and a kind of chuck drug stent, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: the PTFE film of getting suitable dimension is sewn in internal stent.The Valsartan (valsartan) or Losartan (losartan) alcoholic solution that with concentration are 1%-80% then are sprayed at rack outer surface, 40 ℃ of vacuum drying treatment 10 hours.Again one deck PTFE film is sewn in rack outer surface at last.Promptly make the support of PTFE film chuck Valsartan (valsartan) or Losartan (losartan) medicine.
Embodiment 37: sees shown in the accompanying drawing 4, and a kind of chuck drug stent, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: the PTFE film of getting suitable dimension is sewn in internal stent.Irbesartan (irbesartan) dichloromethane solution that with concentration is 1%-60% then is sprayed at rack outer surface, 40 ℃ of vacuum drying treatment 10 hours.Again one deck PTFE film is sewn in rack outer surface at last.Promptly make the support of PTFE film chuck Irbesartan (irbesartan) medicine.
Embodiment 38: sees shown in the accompanying drawing 4, and a kind of chuck drug stent, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: the PTFE film of getting suitable dimension is sewn in internal stent.Candesartan (Candesartan) methanol solution that with concentration is 1%-80% then is sprayed at rack outer surface, 40 ℃ of vacuum drying treatment 10 hours.Again one deck PTFE film is sewn in rack outer surface at last.Promptly make the support of PTFE film chuck Candesartan (Candesartan) medicine.
Embodiment 39: sees shown in the accompanying drawing 4, and a kind of chuck hybrid medicine support, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: the PTFE film of getting suitable dimension is sewn in internal stent.Be that the Valsartan (valsartan) of 1%-80% or Losartan (losartan) or Irbesartan (irbesartan) are sprayed at rack outer surface with the blended alcoholic solution of Rapamycin then with concentration, 40 ℃ of vacuum drying treatment 10 hours.The medicament mixed ratio is 1: 0.5-1.0.Again one deck PTFE film is sewn in rack outer surface at last.Promptly make the support of PTFE film chuck Valsartan (valsartan) or Losartan (losartan) medicine.
Embodiment 40: sees shown in the accompanying drawing 4, and a kind of chuck hybrid medicine support, support 4 surface-coated medication coats 2, support 4 and medication coat 2 integral body are clipped in the middle of two layers of polymers film or the biological material film 7.Be specially: the PTFE film of getting suitable dimension is sewn in internal stent.The Candesartan (Candesartan) and the blended methanol solution of Rapamycin that with concentration are 1%-80% then are sprayed at rack outer surface, 40 ℃ of following vacuum drying treatment 10 hours.The medicament mixed ratio is 1: 0.5-1.0.Again one deck PTFE film is sewn in rack outer surface at last.Promptly make the support of PTFE film chuck hybrid medicine.
Claims (6)
1, a kind of medicine coated support frame of blood vessel mainly is made up of pipe network shape intravascular stent, medicine and carrier, and medicine is coated on the intravascular stent surface by carrier, it is characterized in that: described medicine comprises one or more the mixing in the sartans; Described sartans comprises valsartan (Valsartan), losartan (losartan), irbesartan (irbesartan), Candesartan (candesartan), telmisartan (telmisartan), eprosartan (eprosartan), saprisartan (saprisartan), tasosartan (tasosartan) and zolasartan (zolasartan).
2, intravascular stent according to claim 1 is characterized in that: described medicine is one or more the mixing in the sartans.
3, intravascular stent according to claim 1 is characterized in that: described medicine is the hybrid medicine of one or more and cell proliferation class in the sartans.
4, intravascular stent according to claim 1, it is characterized in that: described carrier is a polymer, intravascular stent surface-coated one layer of polymeric coating, the outer repaste of this polymer coating covers one deck medicine or hybrid medicament smear layer, the outer repaste of this layer covers one deck biodegradable polymers or microporous polymer coating, constitutes the supporting structure of sandwich style embedding medicinal with this.
5, intravascular stent according to claim 1, it is characterized in that: described carrier is a polymer, the polymer coating of intravascular stent surface-coated one deck band micropore, medicine is adsorbed in the micropore of polymer coating through the dip-coating mode, constitutes the supporting structure that micropore discharges medicine with this.
6, intravascular stent according to claim 1 is characterized in that: described carrier is polymeric film or biological material film, intravascular stent surface-coated medication coat, and support and medication coat integral body are clipped in the middle of two layers of polymers film or the biological material film.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 02112955 CN1191099C (en) | 2002-04-26 | 2002-04-26 | Medicine coated support frame of blood vessel |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02112955 CN1191099C (en) | 2002-04-26 | 2002-04-26 | Medicine coated support frame of blood vessel |
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| CN1378865A true CN1378865A (en) | 2002-11-13 |
| CN1191099C CN1191099C (en) | 2005-03-02 |
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| CN 02112955 Expired - Fee Related CN1191099C (en) | 2002-04-26 | 2002-04-26 | Medicine coated support frame of blood vessel |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1306917C (en) * | 2002-12-17 | 2007-03-28 | 微创医疗器械(上海)有限公司 | Scaffold for preventing/treating intravascular re-stricture by compound action mechanism |
| CN100371032C (en) * | 2004-01-16 | 2008-02-27 | 东南大学 | Re-stricture preventing medicinal sustained releasing bracket and its preparation |
| CN100450557C (en) * | 2004-08-13 | 2009-01-14 | 重庆大学 | Medication eluting type blood vessel bracket |
| US7695731B2 (en) | 2004-03-22 | 2010-04-13 | Cordis Corporation | Local vascular delivery of etoposide in combination with rapamycin to prevent restenosis following vascular injury |
| US7875282B2 (en) | 2004-03-22 | 2011-01-25 | Cordis Corporation | Coated medical device for local vascular delivery of Panzem® in combination with rapamycin to prevent restenosis following vascular injury |
| CN1891298B (en) * | 2005-07-04 | 2012-04-25 | 比奥特罗尼克血管干预专利股份公司 | Drug depot for parenteral drug release, in particular intravascular drug release |
| CN101703812B (en) * | 2009-11-20 | 2013-01-02 | 东华大学 | Polyamide 66 membrane covered nickel-titanium alloy intravascular scaffold and preparation method thereof |
| CN103445895A (en) * | 2013-09-12 | 2013-12-18 | 徐贵丽 | Medical cavity support capable of slowly releasing medicine |
| CN104127266A (en) * | 2014-06-16 | 2014-11-05 | 苏州固基电子科技有限公司 | Drug-loading vascular stent |
| CN113648013A (en) * | 2021-08-25 | 2021-11-16 | 心凯诺医疗科技(上海)有限公司 | Close net support of blood flow direction |
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2002
- 2002-04-26 CN CN 02112955 patent/CN1191099C/en not_active Expired - Fee Related
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1306917C (en) * | 2002-12-17 | 2007-03-28 | 微创医疗器械(上海)有限公司 | Scaffold for preventing/treating intravascular re-stricture by compound action mechanism |
| CN100371032C (en) * | 2004-01-16 | 2008-02-27 | 东南大学 | Re-stricture preventing medicinal sustained releasing bracket and its preparation |
| CN103170012A (en) * | 2004-03-22 | 2013-06-26 | 科迪斯公司 | Local vascular delivery of 2-methoxyestradiol in combination with rapamycin to prevent restenosis following vascular injury |
| US7695731B2 (en) | 2004-03-22 | 2010-04-13 | Cordis Corporation | Local vascular delivery of etoposide in combination with rapamycin to prevent restenosis following vascular injury |
| CN1672745B (en) * | 2004-03-22 | 2010-08-11 | 科迪斯公司 | Local vascular delivery of etoposide in combination with rapamycin to prevent restenosis following vascular injury |
| US7875282B2 (en) | 2004-03-22 | 2011-01-25 | Cordis Corporation | Coated medical device for local vascular delivery of Panzem® in combination with rapamycin to prevent restenosis following vascular injury |
| CN103170012B (en) * | 2004-03-22 | 2016-12-21 | 科迪斯公司 | The combination of local vascular delivery 2 methoxyestradiol and rapamycin is in case restenosis after hemostatic tube damage |
| CN100450557C (en) * | 2004-08-13 | 2009-01-14 | 重庆大学 | Medication eluting type blood vessel bracket |
| CN1891298B (en) * | 2005-07-04 | 2012-04-25 | 比奥特罗尼克血管干预专利股份公司 | Drug depot for parenteral drug release, in particular intravascular drug release |
| CN101703812B (en) * | 2009-11-20 | 2013-01-02 | 东华大学 | Polyamide 66 membrane covered nickel-titanium alloy intravascular scaffold and preparation method thereof |
| CN103445895A (en) * | 2013-09-12 | 2013-12-18 | 徐贵丽 | Medical cavity support capable of slowly releasing medicine |
| CN103445895B (en) * | 2013-09-12 | 2015-11-11 | 徐贵丽 | A kind of can the Medical cavity duct stent of slow releasing medicine |
| CN104127266A (en) * | 2014-06-16 | 2014-11-05 | 苏州固基电子科技有限公司 | Drug-loading vascular stent |
| CN113648013A (en) * | 2021-08-25 | 2021-11-16 | 心凯诺医疗科技(上海)有限公司 | Close net support of blood flow direction |
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| CN1191099C (en) | 2005-03-02 |
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Assignee: Promed Medical Tech (Suzhou) Co., Ltd. Assignor: Weike Medical Apparatus Co Ltd (Suzhou) Contract record no.: 2010320000491 Denomination of invention: Medicine coated support frame of blood vessel Granted publication date: 20050302 License type: Exclusive License Open date: 20021113 Record date: 20100429 |
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