CN104174074B - A kind of medication coat composition that is applicable to be coated in implantation or interventional medical device surface - Google Patents

A kind of medication coat composition that is applicable to be coated in implantation or interventional medical device surface Download PDF

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Publication number
CN104174074B
CN104174074B CN201410456663.4A CN201410456663A CN104174074B CN 104174074 B CN104174074 B CN 104174074B CN 201410456663 A CN201410456663 A CN 201410456663A CN 104174074 B CN104174074 B CN 104174074B
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China
Prior art keywords
component
taxol
solution
medication coat
medicine
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CN104174074A (en
Inventor
赵中
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Hangzhou success Medical Technology Co., Ltd.
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Zhejiang Gui Chuan Medical Devices Co Ltd
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Priority to CN201410456663.4A priority Critical patent/CN104174074B/en
Priority to PCT/CN2014/091205 priority patent/WO2016037413A1/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1027—Making of balloon catheters
    • A61M25/1029—Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M25/1027—Making of balloon catheters
    • A61M25/1029—Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
    • A61M2025/1031—Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes

Abstract

The invention belongs to technical field of medical instruments, particularly a kind of medication coat composition, its preparation method and utilize its implantation of making or interventional medical device. A medication coat composition that is applicable to be coated in implantation or interventional medical device surface, comprises following component: the first component is hydrophily high polymer; Second component is the treatment blood vessel medicine of hyperplasia again; The 3rd component is inorganic matter, is selected from one or more the composition in inorganic simple substance, water-soluble inorganic salt or amphipathic small molecules compound; The 4th component is dicyandiamide solution, and dicyandiamide solution comprises the solvent that the first component, second component and the 3rd component are dissolved separately. The medicinal balloon coating that medication coat composition of the present invention is made, good with the compatibility of sacculus, when folding, coating shedding is little, can quick disintegration after immersing in blood or distilled water, do not form large medicine crystal particle, avoid the situation of thrombosis and blood vessel blockage simultaneously.

Description

A kind of medication coat composition that is applicable to be coated in implantation or interventional medical device surface
Technical field
The invention belongs to technical field of medical instruments, particularly a kind of medication coat composition, its systemPreparation Method and utilize its implantation of making or interventional medical device.
Background technology
Medicine-coated balloon and bracket for eluting medicament (DES) all come from essence taking conduit as basic partThis concept of delivery device, suppresses endometrial hyperplasia by carrying medicine, the mode of just carrying medicine withAnd topical remedy's action time difference; Think traditionally, pharmaceutically-active the maintaining of local vascular is to bring into play it to resistThe basis of proliferative effect, but along with the carrying out of isolated cells, zoopery and human research, Ren MenfaExisting true really not so. Initial people carry medicine by contrast preparation to be made it to contact with vascular wall is of short duration, visitsBeg for this method and suppress the possibility of ISR, research finds, by add the contrast preparation of lipophilicity taxol-The VSMC of-Ultravist and cultivation is hatched altogether, gets final product completely even if of short duration 3min cultivatesSuppress vascular smooth muscle hyperplasia, and the time can reach 2 weeks; Cultivate after 15min, fat-soluble taxol entersThe dosage of local intra-arterial wall can DALT 20 times. Zoopery subsequently is also found, in art, uses and adds purpleThe Ultravist of China fir alcohol and taxol are coated with sacculus (expansion 1min), can make the dense of taxol in vascular wallDegree reaches the concentration (entering blood flow even if exceed 90% medicine) of suppressing cell reproduction, thereby significantly reduces narrow againNarrow generation, this effect is even better than DES, and this may be because the struts of support itself can causeInjury of blood vessel reaction, and the smooth damage of both having avoided operation itself to bring of balloon surface has ensured again medicineThing steadily evenly discharges and contacts. The appearance of medicine-coated balloon is just based on two theories: (1) is fat-solubleTaxol or sirolimus can be absorbed by vascular tissue rapidly, and the sustained release of anti-proliferative drugs is to suppressing narrow againNarrow inflammatory reaction process is also inessential; (2) medicine short-term exposes and can obviously block early stage hyperplasia and openReason.
Drug stent, through development for many years, has obtained extraordinary effect in coronary artery vascular diseasesReally, there is certain limitation in the application in periphery lower limb vascular support still. This be mainly due to, noBe same as coronary artery blood vessel, the arterial blood pipe range of shank and straight, is not the position of persistent movement. When blood vessel blockage is dredgedAfter logical, the ISR probability of periphery lower limb vascular is high more a lot of than coronary artery blood vessel. The advantage of medicament elution sacculus existsCan adapt in it the blood vessel that diameter range is very large, owing to there is no in vivo residual of metal, also just not existThe fragmentation that support may exist, the risk of hyperblastosis or even artery-clogging. In Europe, in intervene operationAdopt DEB treatment periphery lower limb vascular to be blocked in and external be proved to be a kind of effectively hand in clinicalSection, but there is launch in Europe You Shuo company not yet enters Chinese market, the domestic Zheng Chu of producerIn development, temporarily there is no Related product listing yet. Domestic market sales only have a not periphery ball of medicine carryingDuctus bursae, relevant enterprise mainly contains: Johnson & Johnson's medical treatment, happy general medical treatment, Boston science and technology, Cook, Ahmedabad stateBorder etc. Medicine-coated balloon conduit exists excellent greatly in late result with respect to medicine carrying foley's tube notGesture.
External main periphery medicinal balloon company is as following table:
Key prepared by medicinal balloon is the coating of medicine, and the product of different company has different establishingMeter theory, if the medicine of the SequentPlease balloon system of B.Braun company is taxol, adopts iodine generalSieve amine is carrier, by the water-soluble quick release that reaches taxol of Iopromide. DiorI is for sacculusSystem is used the technology of nanoporous directly taxol to be incorporated into balloon surface, by pressurizeing medicine from holeIn gap, discharge intravasation tissue. At clinical effectiveness, in hole absorption Hou Zai vascular tissueUptake is less, and therefore DiorII has changed technique, and employing shellac is carrier, and shellac absorbs water swollen in bloodAfter swollen, arrive lesion locations, after extruding, energy rapid delivery of pharmaceuticals, shows from public data, technique after changeDiseased region drug absorption be greatly improved.
The technological difficulties of medication coat are:
1. the selection of formula, under different formula conditions, the release profiles of medicine is different. For medicineSacculus, needs medicine to discharge fast, reduces the size of release particles when release as far as possible, withIn time, can reduce the loss in course of conveying as far as possible. And because medicinal balloon belongs to cardiovascular Interventional material,Just more limit the selection of material.
2. the selection of coating processes, chooses after formula, needs suitable technique that medicine carrying solution is coated toBalloon surface, the technique of this coating can directly have influence on the distribution uniformity of medicine in balloon surface, medicineIn the form of balloon surface, finally can have influence on the release of medicine, therefore the particle that medicine discharges, even if havingRipe formula in the case of not having suitable coating processes, also cannot obtain the medication coat of expecting.
3. the selection of folding technology, after the coating of sacculus is dried completely, need to roll over sacculusFolded, now, the medicinal balloon that look ahead can pass through smoothly in blood vessel, by process Chinese traditional medicine notCan lose in a large number, coating can not come off by sheet in transmitting procedure, the folding release song that can not have influence on medicineLine. Sometimes use three foldings, sometimes use five foldings.
Existing medicinal balloon and technology of preparing mainly contain following several:
The formula of the CVIngenuity of u s company (US Patent No. 8491925B2,US8257722B2, US8128951B2, US8114429B2) employing betadin(polynylpyrrolidone or PVP-I) is assistant agent, and the medication coat effect obtaining is pretty good, and coating is even,After water breakthrough, rate of release is fast, also can not form large taxol drug crystal. But the shortcoming of this formula is poly-Ethene pyrrolones iodine is by chemical synthesis (United States Patent (USP) 2,739,922, European patent EP 19790100966)And the stable complex of the polyvinyl pyrrolidone obtaining and iodine (stablecomplex, see http://en.wikipedia.org/wiki/Povidone-iodine). Betadin contains the very unit of high-load conventionallyThe iodine (brown or peony, 9-12%, the dry weight ratio of PVP) of element shape. It is killing as spectrum normallyBacterium, sterilization corrosion-resistant medicament. In the environment that the iodine of element state can discharge gradually, go. Cause like this and stimulate and mistakeQuick patient's ratio also can improve.
The Sequentplease medicine carrying sacculus of German company B.Braun is taking taxol as function medicament, iodineGeneral sieve amine is carrier material (US Patent No. 8439868B2; US8389043B2; US8257305B2;US7750041B2). By the fast feature of Iopromide rate of dissolution in water, reach the fast quick-release of taxolPut. This is the representative of first generation medicament elution sacculus, occupies no small market on market. But widelyIn use, the coating compatibility of issuing this class sacculus is very poor, and strength of coating is bad, before arrival discharges placeIn way, lose serious. After discharging, the taxol drug insoluble matter of bulk produces, easily artery-clogging.
It is pharmaceutical carrier that the product I n.Pact of u s company's Medtronic (Medtronic/Invatec) has used urea(US Patent No. 20110295200A1; US20100233228A1). But due to urea and taxol, propertyMatter is widely different, and solubility and Crystallization Characteristics in same solvent are different, so coating phase-splitting is brightAobvious, homogeneity is undesirable. Urea can not increase the compatibility between taxol and balloon surface yet. In addition itIn water dissolution velocity widely different, cause the formation compared with large medicament particles, increase the stifled of thrombus or blood vesselPlug. What similarly, the Passeo-18Lux of German company Biotronik used is butyryl citric acid tri-n-hexyl ester(n-Butyryltri-n-hexyl-citrate). This assistant agent fat-soluble than urea height a bit, with the phase of taxolSeparator well a bit, but is little molecule assistant agent after all, and the compatibility of coating formula and sacculus is poor, and coating stripping is tightHeavy, discharge in the future of place and lose seriously in arrival.
Formula (the US Patent No. 8425459B2 of LutonixMoxy; US8414526B2;US8241249B2) used surfactant, taxol is pretty good at the coating uniformity of balloon surface, with sacculusCohesive also good, but due to the use of surfactant, it is obvious that balloon surface absorbs moisture, medicine is coated withLayer easily comes off. Medicine is too even in addition, slowly-releasing well after intravasation wall. Drug effect is not good enough.
The sacculus coating of German company Aachen-Resonance and the COOKMedical of u s company is adoptedUse pure taxol, rely on the crystallization of medicine self to form single coating. The machinery producing in the time of balloon expandableIntravasation wall under pressure, has certain slow-release period. But owing to there is no carrier, cohesive is bad, sacculus foldingFolded be lose not little. Form oarse-grained chance a lot. Security is under suspicion.
German company EurocorFreeway (US Patent No. 20120143132A1;US20100076542A1; European patent EP 2125060B1;
EP2421572A2; EP2243501A1) used shellac, cohesive is good, and coating is transparent, allEven. But it is very crisp that shortcoming is shellac, after being combined with water-fast taxol, the stability of whole medication coatBad. Simultaneously because shellac is natural products, still unavoidable through purifying rear impurity. Biocompatibility and heatThe danger in source increases many.
In sum, medicament elution sacculus be get involved medical profession new effective treatment blood vessel andIn other bodies, the method for official jargon, has obtained doctor's generally accreditation in clinical use. On market, sell now andThe product of researching and developing has certain curative effect, also all has shortcoming in varying degrees.
Summary of the invention
The present invention aims to provide a kind of medication coat that is applicable to be coated in implantation or interventional medical device surfaceComposition, this medication coat composition after using, can make to implant or interventional medical device as medicine-coated balloon andBracket for eluting medicament (DES) etc. immerse disintegration fast in blood or distilled water, can not form large medicine crystalline substance simultaneouslyBody particle, avoids the situation of thrombosis and blood vessel blockage.
The present invention also provides a kind of preparation method of described medication coat composition.
The present invention also provides a kind of and utilizes the implantation of making of described medication coat composition or get involved medical treatmentApparatus, described implantation or interventional medical device comprise medicament elution sacculus, bracket for eluting medicament etc.
The technical solution adopted for the present invention to solve the technical problems is:
Be applicable to be coated in and implant or the medication coat composition on interventional medical device surface, comprise asLower component:
The first component is hydrophily high polymer;
Second component is the treatment blood vessel medicine of hyperplasia again;
The 3rd component is inorganic matter, is selected from inorganic simple substance, water-soluble inorganic salt or amphipathic small moleculesThe composition of one or more in compound;
In each component, hydrophily high polymer and treatment the blood vessel again weight ratio of the medicine of hyperplasia are 0.3-3: 1, the 3rd component accounted for the 0.005-5.0% of the first component, second component and the 3rd component gross weight;
The 4th component is dicyandiamide solution, and dicyandiamide solution comprises the first component, second component and the 3rd groupDivide the solvent dissolving separately. The therapentic part of this implantation or interventional medical device comprises: blood vessel and human body otherPipeline is as tracheae, esophagus, urethra, vagina and fallopian tubal.
Further, hydrophily high polymer and the treatment blood vessel medicine of hyperplasia again, i.e. the first componentWith the weight ratio of second component be 1.8-2.2: 1, the three component accounts for the first component, second component and the 3rd componentThe 0.005-2.0% of gross weight.
As preferably, described hydrophily high polymer is selected from polyvinyl pyrrolidone (PVP), contains coupling iodinePolyvinyl pyrrolidone, polyvinyl alcohol (PVA), polyethylene glycol oxide (PEO) or polyethylene glycol (PEG); DescribedTreatment blood vessel again the medicine of hyperplasia be selected from taxol or derivatives thereof, rapamycin or derivatives thereof,Anticoagulant medicine; Described inorganic simple substance is selected from iodine, bromine or niacinamide; Water-soluble inorganic salt is selected from sodium iodide,Calcium iodide, sodium chloride or calcium chloride, amphipathic small molecules compound is D-ALPHA-tocopheryl polyethylene glycol 1000 succinate. Here needBe pointed out that, due to polyvinyl pyrrolidone (PVP), the polyvinyl pyrrolidone that contains the iodine that is coupled, polyvinyl alcohol(PVA), polyethylene glycol oxide (PEO) or these several high polymers of polyethylene glycol (PEG) are at water or ethanol, in methyl alcoholSolubility basic identical, therefore can replace mutually, in use, make the medicine finally obtainingCoating hydrophilic is good, and disintegration rate is fast; And inorganic salts separate medicine in whole component, therefore can shapeBecome bulky grain medicine crystal.
As preferably, the derivative of described taxol comprises that the derivative of described taxol comprises that many west are purpleChina fir alcohol (docetaxel); Rapamycin derivative comprises everolimus (everolimus), if he coughs up Li Mosi(Zotarolimus), Baeyer Li Mosi (Biolimus); Anticoagulant cartridge bag is drawn together Cilostazol (Cilostazol), liverElement (heparin).
As preferably, described implantation or interventional medical device comprise: coronary blood pipe holder, coronary bloodPipe sacculus, peripheral vascular support, peripheral vascular sacculus, intracranial vessel support, intracranial vessel sacculus, urethraSupport, urethra sacculus, esophageal stents appear or esophagus sacculus.
As preferably, in described dicyandiamide solution, the solvent of the first components dissolved is selected to water, secondAlcohol, the composition of one or more in methyl alcohol or oxolane; The solvent that second component is dissolved isEthanol, methyl alcohol, the composition of one or more in oxolane or acetone; By the 3rd components dissolvedSolvent be water, the composition of one or more in ethanol or methyl alcohol. The first component and second groupIt is very important dividing dissolving and mixed process in different solvents. Different solvents can preferentially dissolve need notComponent, as medicine or high polymer, also have inorganic component etc., to obtain evenly firmly coating.
As preferably, with ethanol by obtaining the first component solution after the first components dissolved, to the first componentIn solution, add the 3rd component and suitable quantity of water to be fully mixed to get the 3rd component solution, with ethanol by second componentAfter dissolving, obtain second component solution, the volume between second component solution, the 3rd component solution and water threeThan being 1-2: 1-2: 0.1-1. Further, between second component solution, the 3rd component solution and water threeVolume ratio for being preferably 1: 1-2: 0.25-0.28.
A preparation method for described medication coat composition, comprises the steps: that a, the 3rd component are moltenThe preparation of liquid: the first component is fully mixed with solvent, and the first component that configuration concentration is 0.1-1g/ml is moltenLiquid, and preserve the first component is all dissolved at 40-50 DEG C of temperature, then to adding the in the first component solutionThree components are fully mixed, and obtain the 3rd component solution, make the concentration of the 3rd component in the 3rd component solution be0.001-0.1g/ml; The preparation of b, second component solution: second component is fully mixed with solvent, configure denseThe second component solution that degree is 0.05-0.5g/ml, and be incubated until second component is complete at 40-50 DEG C of temperatureDissolve; The preparation of c, medication coat composition: add described the 3rd component molten in described second component solutionLiquid and water, the volume ratio between second component solution, the 3rd component solution and water three is 1-2: 1-2: 0.1-1, sealing, stirs, and obtains the medication coat combination for being coated in implantation or interventional medical device surfaceThing.
Further, the preparation method of said medicine coating composition comprises a kind of following method, a, iodineThe preparation of solution: polyvinylpyrrolidone (PVP) is fully mixed with ethanol, and configuration concentration is 0.1-0.3g/mlPolyvinylpyrrolidone (PVP) ethanolic solution, and at 40-50 DEG C of temperature preserve PVP is all dissolved,In PVP ethanolic solution, add I fully to mix again, obtain iodine solution, concentration is 0.001-0.01g/ml;The preparation of b, taxol ethanolic solution: taxol is fully mixed with ethanol, and configuration concentration is 0.1-0.3g/mlTaxol ethanolic solution, and at 40-50 DEG C of temperature insulation until taxol dissolve completely; C, medicine are coated withThe preparation of layer composition: add described iodine solution and distilled water, taxol in described taxol ethanolic solutionVolume ratio between ethanolic solution, iodine solution and water three is 1: 1-2: 0.25-0.28, sealing, stirs allEven, obtain medication coat composition.
Further, the preparation method of said medicine coating composition comprises a kind of following method, a, iodineChange the preparation of sodium solution: polyvinylpyrrolidone (PVP) is fully mixed with ethanol, and configuration concentration is 0.1-Polyvinylpyrrolidone (PVP) ethanolic solution of 0.3g/ml, and preserve and make PVP complete at 40-50 DEG C of temperaturePortion dissolves, then adds NaI fully to mix in PVP ethanolic solution, obtains IodineSodium Solution, makes sodium iodideIn solution, NaI concentration is 0.05-0.5g/ml; The preparation of b, taxol ethanolic solution: by taxol and ethanolFully mix, the taxol ethanolic solution that configuration concentration is 0.1-0.3g/ml, and protect at 40-50 DEG C of temperatureTemperature until taxol dissolve completely; The preparation of c, medication coat composition: in described taxol ethanolic solutionAdd described IodineSodium Solution and distilled water, between taxol ethanolic solution, IodineSodium Solution and water threeVolume ratio is 1: 1-2: 0.25-0.28, sealing, stirs, and obtains medication coat composition.
Further, the preparation method of said medicine coating composition comprises a kind of following method, a, cigaretteThe preparation of amide solution: polyvinylpyrrolidone (PVP) is fully mixed with ethanol, and configuration concentration is 0.1-Polyvinylpyrrolidone (PVP) ethanolic solution of 0.3g/ml, and preserve and make PVP complete at 40-50 DEG C of temperaturePortion dissolves, then adds niacinamide fully to mix in PVP ethanolic solution, obtains nicotinamide soln, makes nicotinoylIn amine aqueous solution, concentration for nicotinamide is 0.02-0.2g/ml; The preparation of b, taxol ethanolic solution: by taxol withEthanol fully mixes, the taxol ethanolic solution that configuration concentration is 0.1-0.3g/ml, and 40-50 DEG C of temperatureLower insulation until taxol dissolve completely; The preparation of c, medication coat composition: molten at described taxol ethanolIn liquid, add described nicotinamide soln and distilled water, taxol ethanolic solution, nicotinamide soln and water three itBetween volume ratio be 1: 1-2: 0.25-0.28, sealing, stir, obtain medication coat composition.
Further, the preparation method of said medicine coating composition comprises a kind of following method, a, cigaretteThe preparation of acid amides calcium chloride solution: polyvinylpyrrolidone (PVP) is fully mixed with ethanol, and configuration concentration isPolyvinylpyrrolidone (PVP) ethanolic solution of 0.1-0.3g/ml, and preserve and make PVP at 40-50 DEG C of temperatureAll dissolve, then add niacinamide and calcium chloride fully to mix in PVP ethanolic solution, obtain niacinamide chlorineChange calcium solution, making concentration for nicotinamide in niacinamide calcium chloride solution is that 0.01-0.05g/ml, calcium chloride concentration are0.002-0.0lg/ml; The preparation of b, taxol ethanolic solution: taxol is fully mixed with ethanol, configure denseThe taxol ethanolic solution that degree is 0.1-0.3g/ml, and be incubated until taxol is complete at 40-50 DEG C of temperatureDissolve; The preparation of c, medication coat composition: add described niacinamide chlorine in described taxol ethanolic solutionChange calcium solution and distilled water, the volume between taxol ethanolic solution, niacinamide calcium chloride solution and water threeThan being 1: 1-2: 0.25-0.28, sealing, stirs, and obtains medication coat composition.
Further, the preparation method of said medicine coating composition comprises a kind of following method, a,The preparation of BHT solution: polyvinylpyrrolidone (PVP) is fully mixed with ethanol, and configuration concentration is 0.1-Polyvinylpyrrolidone (PVP) ethanolic solution of 0.3g/ml, and preserve and make PVP complete at 40-50 DEG C of temperaturePortion dissolves, then adds BHT fully to mix in PVP ethanolic solution, obtains BHT solution, and concentration is0.00025-0.01g/ml; The preparation of b, taxol ethanolic solution: taxol is fully mixed with ethanol, joinPutting concentration is the taxol ethanolic solution of 0.1-0.3g/ml, and is incubated until taxol at 40-50 DEG C of temperatureDissolve completely; The preparation of c, medication coat composition: described in adding in described taxol ethanolic solutionBHT solution and distilled water, the volume ratio between taxol ethanolic solution, BHT solution and water three is1: 1-2: 0.25-0.28, sealing, stirs, and obtains medication coat composition.
In the preparation method of the above-mentioned various preferred medication coat composition providing, the medicine purple of employingChina fir alcohol can be replaced by medicines such as taxol or derivatives thereof, rapamycin or derivatives thereof, anticoagulant medicines, whenWhen medicine is rapamycin, the compound method of rapamycin ethanolic solution and concentration control are molten with taxol ethanolLiquid. Further, in the time that medicine is rapamycin, system solvent can make rapamycin taking methyl alcohol as masterDissolubility is better.
The implantation or the interventional medical device that utilize described medication coat composition to prepare, its processBe: the implantation or the interventional medical device semi-finished product that do not apply through medicine are immersed in to medicine of the present inventionIn coating composition, maintenance 5-60 took out after second; Dry under room temperature, folding, sterilizing, obtains product.
As preferably, implantation or interventional medical device prepared by described medication coat composition, its surfaceThe density of coating is 0.5-10 μ g/mm2, medicine net content is 0.2-in the density on medicament eluting instrument surface8μg/mm2。
Specifically, the present invention adopts water soluble polymer if polyvinyl pyrrolidone is as medication coatCarrier. Due to the hydrophily high polymer having as polyvinyl pyrrolidone, medication coat meeting after contact blood vesselRapidly disintegration (within 60-120 second), allows the complete intravasation wall of medicine in coating. Simultaneously due to polyethylenePyrrolones is amphipathic compound (polarity and non-polar solven and compound are had to affinity), so with Japanese yewAlcohol can not form and be separated. Using after this class high polymer, medication coat is very even, with balloon surfaceBonding also very good. But be immersed in the water, coating disintegration, forms gr water-fast thickBulky grain. May artery-clogging.
Another key component of the present invention is the additive that has the mineral-type of special efficacy, as iodine, and iodineChange calcium, sodium iodide, calcium chloride or other water miscible little molecules, as niacinamide etc. These water miscible saltClass or inorganic elements (not being the iodide ion etc. of stablizing coupling or coordination with high polymer) exist with medication coat in,Medicine (as taxol and rapamycin) and hydrophilic high polymer (as polyvinyl pyrrolidone) are cut off. Form againEvenly, after the good sacculus coating of cohesive, immerse after water or blood, play the work of regulating drug granularityWith. Through evidence, the formula that ratio is suitable and coating, after sacculus coating is immersed in the water, reached fastSpeed disintegration and drug particles degree little (naked eyes range estimation is emulsion form, instead of bulky grain). These inorganic moleculesThe ratio of additive is very crucial, and consumption is too high, can affect coating and become thin performance (too crisp or too sticky), mistakeLow, can not play again the effect that forms small drug particles.
The 3rd key point of the present invention is the formula of solvent, and simple solvent does not have medicine (Japanese yewAlcohol or rapamycin) there is similar dissolubility with high polymer. So double solvents effect can be better, such as secondAlcohol, methyl alcohol, acetone, water, oxolane philosophy dissolved substance, high polymer, then mix two moltenLiquid, forms homogeneous phase masking liquid. The dicyandiamide solution of using in the present invention, the preferred solvent of the first component be ethanol,Water, or the mixed system of two kinds; The preferred solvent of second component is ethanol, acetone, oxolane,Or the mixed system of two kinds wherein; The preferred solvent of the 3rd component is ethanol, methyl alcohol, or two kindsMixed system.
Formula of the present invention and coating process have certain scope of application, such as well several inorganic salts and inProperty little molecule can both play adjusting coating uniformity, compatibility, and the speed of disintegration in (blood) in waterResidual with medication coat, also have the formation of medicine crystal particle.
By formula of the present invention and coating process, the medicinal balloon coating finally forming, evenly, withThe compatibility of sacculus is good, and when folding, coating shedding is little, can quick disintegration after immersing in blood or distilled water,In very short time, (being shorter than 1 minute) most medication coat all can depart from balloon surface, does not form large simultaneouslyMedicine crystal particle, avoid the situation of thrombosis and blood vessel blockage.
Detailed description of the invention
Below by specific embodiment, technical scheme of the present invention is described in further detail. ShouldWork as understanding, enforcement of the present invention is not limited to the following examples, and what the present invention was done is any formalFlexible and/or change and all will fall into protection domain of the present invention.
In the present invention, if not refer in particular to, all part, percentages are unit of weight, adoptEquipment and raw material etc. all can be buied from market or this area is conventional. Method in following embodiment, as nothingSpecify, be the conventional method of this area.
Embodiment 1A: containing the preparation method of inorganic salts medicinal balloon
The configuration of polyvinylpyrrolidone (PVP) ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle, and the ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol ethanolic solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
Preparation IodineSodium Solution: about 0.4gNaI is added in 25ml sample bottle; Draw with liquid-transfering gunPVP ethanolic solution 8ml joins in sample bottle;
Compounding pharmaceutical coating composition: the IodineSodium Solution that adds about 1-2ml in taxol ethanolic solutionWith the distilled water of a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition (solution); Keep 5-60Second, rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 1. Result: exceed 80% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is not observed bulky grain (without 10 microns of above particles of diameter).
Table 1
Embodiment 1B: containing the preparation method of inorganic salts medicinal balloon
The configuration of polyvinylpyrrolidone (PVP) methanol solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle, and the methyl alcohol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol methanol solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the methyl alcohol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
Preparation IodineSodium Solution: about 0.4gNaI is added in 25ml sample bottle; Draw with liquid-transfering gunPVP methanol solution 8ml joins in sample bottle;
Compounding pharmaceutical coating composition: the IodineSodium Solution that adds about 1-2ml in taxol methanol solutionWith the distilled water of a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 2. Result: exceed 72% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is not observed bulky grain (without 10 microns of above particles of diameter, lower same).
Table 2
Embodiment 2: the medicinal balloon preparation method containing little molecule assistant agent:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol ethanolic solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
Preparation nicotinamide soln: about 0.2g niacinamide is added in 25ml sample bottle; Draw with liquid-transfering gunPVP ethanolic solution 8ml joins in sample bottle;
Compounding pharmaceutical coating composition: the nicotinamide soln that adds about 1-2ml in taxol ethanolic solutionWith the distilled water of a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 3. Result: exceed 73% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is observed the bulky grain (10 microns of above particles of diameter) of minute quantity.
Table 3
Embodiment 3: the medicinal balloon preparation method containing two kinds of little molecule assistant agents:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol ethanolic solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
Preparation niacinamide calcium chloride solution: about 0.1g niacinamide and about 0.02g calcium chloride are added to 25mlIn sample bottle; Drawing PVP ethanolic solution 8ml with liquid-transfering gun joins in sample bottle;
Compounding pharmaceutical coating composition: the niacinamide chlorination that adds about 1-2ml in taxol ethanolic solutionThe distilled water of calcium solution and a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 4. Result: exceed 76% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is observed a certain amount of bulky grain (10 microns of above particles of diameter).
Table 4
Embodiment 4A: containing the medicinal balloon preparation method 1 (PTX: PVP: I=of inorganic iodine1.0: 1.33: 0.007, gram/gram/gram):
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol ethanolic solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation iodine: about 0.008g iodine is added in 25ml sample bottle; Draw with liquid-transfering gunPVP ethanolic solution 8ml joins in sample bottle;
Compounding pharmaceutical coating composition: add the element state iodine of about 1ml molten in taxol ethanolic solutionThe distilled water of liquid and a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 5. Result: exceed 90% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is not observed bulky grain medicine (10 microns of above particles of diameter).
Table 5
Embodiment 4B: containing the medicinal balloon preparation method 2 (PTX: PVP: I=of inorganic iodine1.5: 1: 0.005, gram/gram/gram)
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol (PTX) ethanolic solution: weigh about 0.30g taxol, add 25ml glassBottle; In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation iodine: about 0.008g iodine is added in 25ml sample bottle; Draw with liquid-transfering gunPVP ethanolic solution 8ml joins in sample bottle;
Compounding pharmaceutical coating composition: add the element state iodine of about 1ml molten in taxol ethanolic solutionThe distilled water of liquid and a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 6. Result: exceed 90% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is not observed bulky grain medicine (10 microns of above particles of diameter).
Table 6
Embodiment 5A contains the medicinal balloon preparation method of little molecule assistant agent D-ALPHA-tocopheryl polyethylene glycol 1000 succinate:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol ethanolic solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation D-ALPHA-tocopheryl polyethylene glycol 1000 succinate: about 0.002g D-ALPHA-tocopheryl polyethylene glycol 1000 succinate is addedIn 25ml sample bottle; Drawing PVP ethanolic solution 8ml with liquid-transfering gun joins in sample bottle;
Compounding pharmaceutical coating composition: in taxol ethanolic solution, add the vitamin E of about 1-2ml-The distilled water of TPGS solution and a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 7. Result: exceed 75% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle observe some bulky grain medicine crystal (10 microns of diameters aboveGrain).
Table 7
Embodiment 5B contains the medicinal balloon preparation method of little molecule assistant agent D-ALPHA-tocopheryl polyethylene glycol 1000 succinate:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol acetone soln: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the acetone of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation D-ALPHA-tocopheryl polyethylene glycol 1000 succinate: about 0.002g D-ALPHA-tocopheryl polyethylene glycol 1000 succinate is addedIn 25ml sample bottle; Drawing PVP ethanolic solution 8ml with liquid-transfering gun joins in sample bottle;
Compounding pharmaceutical coating composition: in taxol acetone soln, add the vitamin E of about 1-2ml-The distilled water of TPGS solution and a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 8. Result: exceed 60% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle observe some bulky grain medicine crystal (10 microns of diameters aboveGrain).
Table 8
Embodiment 5C contains the medicinal balloon preparation method of little molecule assistant agent D-ALPHA-tocopheryl polyethylene glycol 1000 succinate:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol tetrahydrofuran solution: weigh about 0.15g taxol, add 25ml glassBottle; In vial, add the oxolane of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation D-ALPHA-tocopheryl polyethylene glycol 1000 succinate: about 0.002g D-ALPHA-tocopheryl polyethylene glycol 1000 succinate is addedIn 25ml sample bottle; Drawing PVP ethanolic solution 8ml with liquid-transfering gun joins in sample bottle;
Compounding pharmaceutical coating composition: the vitamin that adds about 1-2ml in taxol tetrahydrofuran solutionThe distilled water of E-TPGS solution and a small amount of (0.262ml), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 9. Result: exceed 80% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle observe some bulky grain medicine crystal (10 microns of diameters aboveGrain).
Table 9
Embodiment 6A is containing small molecule antioxidant BHT (3,5-di-tert-butyl-4-hydroxytoluene, BHT) medicinal balloon preparation method:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of taxol ethanolic solution: weigh about 0.15g taxol, add 25ml vial; ?In vial, add the ethanol of 1ml; Be incubated until taxol dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation BHT: about 0.002gBHT is added in 25ml sample bottle; With moving liquidRifle is drawn PVP ethanolic solution 8ml and is joined in sample bottle;
Compounding pharmaceutical coating composition: in taxol ethanolic solution, add the vitamin E of about 1-2ml-The distilled water of TPGS solution and a small amount of (0.262m1), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 10. Result: exceed 80% medication coat and be successfully discharged into bufferingIn liquid, simultaneous buffering liquid bottle is observed the bulky grain medicine crystal of minute quantity.
Table 10
Embodiment 6B is containing small molecule antioxidant BHT (3,5-di-tert-butyl-4-Hydroxytoluene, BHT) medicinal balloon preparation method:
The configuration of PVP ethanolic solution: with the balance weighing of 0.0001g precision4gPVP (PovidoneK30), adds in 25ml sample bottle; The ethanol of drawing 20ml with liquid-transfering gun addsIn sample bottle. Screw bottle stopper, after vibration is stirred, be put into 45 DEG C of baking ovens and preserve until PVP all dissolves.
The preparation of rapamycin ethanolic solution: weigh about 0.15g rapamycin, add 25ml glassBottle; In vial, add the ethanol of 1ml; Be incubated until rapamycin dissolves completely at 45 DEG C of baking ovens.
The ethanolic solution of preparation BHT: about 0.002gBHT is added in 25ml sample bottle; With moving liquidRifle is drawn PVP ethanolic solution 8ml and is joined in sample bottle;
Compounding pharmaceutical coating composition: the vitamin that adds about 1-2ml in rapamycin ethanolic solutionThe distilled water of E-TPGS solution and a small amount of (0.262m1), sealing, stirs.
Sacculus coating: sacculus is immersed in above-mentioned medication coat composition; Keep 5-60 second,Rear taking-up; Drying at room temperature 6 hours; Folding, sterilizing, packaging.
Drug releasing rate and granularity test: the inflated to 2 that said method an is made atmospherePress, be then put in the phosphate buffer bottle of 0.1M of 20ml, static 1 minute, then take out ballCapsule, dry, weigh. Observe the medicine in residual condition and the buffer solution bottle of balloon surface medication coat simultaneouslyThe state of crystal, result of the test is in table 11. Result: 58% medication coat is successfully discharged into buffer solutionIn, simultaneous buffering liquid bottle is observed the bulky grain medicine crystal of minute quantity.
Table 11
In above each embodiment of the present invention, the first component solution of employing---PVP ethanolic solution is denseDegree be 0.2g/ml, the 0.2g/ml is here optium concentration, from integrated artistic angle, its concentration withThe medication coat density finally obtaining is relevant, can suitably increase under a proportional relationship or reduce, thereby regulateThe density of coating.
Above-described embodiment is preferably scheme more of the present invention, not the present invention is appointedWhat pro forma restriction also has other change under the prerequisite that does not exceed the technical scheme that claim recordsBody and remodeling.

Claims (5)

1. a medication coat composition that is applicable to be coated in implantation or interventional medical device surface, is characterized in that comprising as followsComponent:
The first component is hydrophily high polymer;
Second component is the treatment blood vessel medicine of hyperplasia again;
The 3rd component is calcium chloride;
In each component, hydrophily high polymer and treatment the blood vessel again weight ratio of the medicine of hyperplasia are 0.3-3:1, the 3rd componentAccount for the 0.005-5.0% of the first component, second component and the 3rd component gross weight;
The 4th component is dicyandiamide solution, and dicyandiamide solution comprises the solvent that the first component, second component and the 3rd component are dissolved separately;Described hydrophily high polymer is selected from polyvinyl pyrrolidone (PVP), the polyvinyl pyrrolidone that contains the iodine that is coupled, polyethyleneAlcohol (PVA), polyethylene glycol oxide (PEO) or polyethylene glycol (PEG); Described treatment blood vessel hyperplasia againMedicine is selected from taxol or derivatives thereof, rapamycin or derivatives thereof, anticoagulant medicine.
2. medication coat composition according to claim 1, is characterized in that: the derivative of described taxol comprises manyWestern taxol (docetaxel); Rapamycin derivative comprises everolimus (everolimus), if he coughs up Li Mosi(Zotarolimus), Baeyer Li Mosi (Biolimus); Anticoagulant cartridge bag is drawn together Cilostazol (Cilostazol), heparin(heparin)。
3. medication coat composition according to claim 1, is characterized in that: described implantation or interventional medical deviceComprise: coronary blood pipe holder, coronary artery blood saccule, peripheral vascular support, peripheral vascular sacculus, intracranial vessel support,Intracranial vessel sacculus, urethra rack, urethra sacculus, esophageal stents appear or esophagus sacculus.
4. medication coat composition according to claim 1, is characterized in that: in described dicyandiamide solution, by firstThe solvent of components dissolved is selected from water, ethanol, the composition of one or more in methyl alcohol or oxolane; By secondThe solvent of components dissolved is ethanol, methyl alcohol, the composition of one or more in oxolane or acetone; By the 3rdThe solvent of components dissolved is water, the composition of one or more in ethanol or methyl alcohol.
5. medication coat composition according to claim 4, is characterized in that: with ethanol will be after the first components dissolvedTo the first component solution, molten to adding the 3rd component and suitable quantity of water to be fully mixed to get the 3rd component in the first component solutionLiquid, obtains second component solution, second component solution, the 3rd component solution and water three after with ethanol, second component being dissolvedVolume ratio between person is 1-2:1-2:0.1-1.
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