CN1911459A - Blood ressel stent medicinal conting layer capable of relieving free radical harmful to cell after blood deficiency refilling - Google Patents
Blood ressel stent medicinal conting layer capable of relieving free radical harmful to cell after blood deficiency refilling Download PDFInfo
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- CN1911459A CN1911459A CN 200610015368 CN200610015368A CN1911459A CN 1911459 A CN1911459 A CN 1911459A CN 200610015368 CN200610015368 CN 200610015368 CN 200610015368 A CN200610015368 A CN 200610015368A CN 1911459 A CN1911459 A CN 1911459A
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Abstract
A coated medical layer of vascular scaffold for relaxing the damage of free radicals to cells after ischemia-refilling is composed of the medicine (1-90%) chosen from antioxidizing medicine, the mixture of more antioxidizing medicines, and the mixture of antioxidizing medicine(s) and the medicine preventing re-angiostenosis.
Description
Technical field
The present invention relates to medical instruments field, particularly a kind of blood vessel stent drug coating that adopts radical pair cell injury behind the ischemia-reperfusion alleviated that anti-oxidation medicine coats.
Technical background
Atherosclerosis is the important diseases that influences health, and the pathological changes that wherein feeds through to heart coronary artery is called coronary heart disease.Coronary heart disease often causes deficiency myocardial blood supply, and gently then angina pectoris is heavy then cause myocardial infarction, even dead.The U.S. in 2000 ischemic heart desease death accounts for 21.4% of dead sum, and wherein acute myocardial infarction death accounts for 8%.
It is clinical medical in recent years impressive progress that patients of acute myocardial infarction adopts the treatment of revascularization art, because dredging vascellum or reproduce blood vessel and make cardiac muscular tissue obtain the perfusion again of blood behind the ischemia really can be received excellent curative as a rule.Yet, recover again sometimes to increase the weight of myocardial structural damages and dysfunction on the contrary behind the blood flow, even cause severe arrhythmia.The damage that how can reduce ischemia-reperfusion effectively is the problem that domestic and international medical circle is paid close attention to always.
In recent years, along with the coronary artery balloon expandable forms applying of art, with the intravascular stent that contains radioactive substance is that patients with coronary heart disease brings glad tidings, but, preparation and use to carry out protection to lonizing radiation because containing the radioactive substance intravascular stent, it is very complicated that operation is implemented, simultaneously because therefore the problem that also exists the Excreta that must prevent to contain radioactive substance that environment is polluted makes it be restricted in clinical use.
Produced afterwards into preventing vascular restenosis drug-carried coat support, this type of medicine is at platelet GBIIb/IIIa receptor antagonist or influences cell division, quicken the cancer therapy drug of natural death of cerebral cells, but there is in controlled-release coating processing technology instability or the operation process damage to the rack surface controlled release layer, and be created in the too fast too high possibility of local blood drug level that causes of rate of release in the human body, bring the further risk of damage of myocardial cell.
Method by intravenous injection antioxidant (coenzyme Q10) also once was applied to clinical, because the time is short, can not keep local drug concentration, and curative effect is also undesirable.Therefore how local application and use which kind of ingredient collocation to become the another development trend of research medicine slow release stent with the cooperative effect that reaches treatment and protection.
The theoretical basis that the present invention is based on is carried out following analysis:
The basic theories of 1 free radical
Free radical is the group that has one or more unpaired electronics in out orbit, and this is the material that a class has greater activity.Free radical is the interior intermediate product [list of references 1] about catalytic aerobic metabolism process of enzyme system and electron transport chain electron transport of organism, also is the intermediate product that bio-tissue or cell form in some chemical damage process.It brings into play the effect of strong oxidizer in vivo directly or indirectly, thereby damage organism macromole and various kinds of cell composition, also can react with other materials (as nucleic acid, protein, lipid etc.), generate the oxide or the peroxide of this class material, to body cause damage [list of references 2].Free radical comprises ultra-oxygen anion free radical (O2-), hydroxy radical (OH), hydrogen peroxide (H2O2), singlet oxygen (O2-), hydroperoxyl radical (HOO), peroxy radical (ROO), nitric oxide free radical (NO), semiquinone free radical (QH), peroxynitrite base (ONOO-); Alkane free radical (R), alkoxy free group (RO), alkane peroxy radical (ROO); Fat oxygen-derived free radicals (LO), fat peroxy radical (LOO) isoreactivity oxygen (ROS).With the intermediate product malonaldehyde (malondialdehyde MDA) of lipid peroxidation representative product [list of references 3] as lipid peroxidation, it is used as the sensitive indicator of weighing the body Radical Metabolism, and its content can reflect objectively that body produces the level of free radical.
2 lipid peroxidations
It is that the main diseases of coronary atherosclerosis is because of [list of references 4] that serum oxidized low-density lipoprotein (OxLDL) raises.Diagnosis and treatment for coronary atherosclerosis, intervention property heart radiology is by means of the development of image apparatus and conduit technology, conduit can be positioned over aortic sinus and near-end coronarius through femoral artery, use balloon tamponade, the atherosis narrow blood vessel of expansion or placement stainless steel stent and strut blood vessel, to improve the blood supply of heart muscle tissue.This technology and surgery's coronary bypass has formed the method that complements one another.The several years patient vessel is narrow once more behind the transluminal coronary angioplasty still has higher probability, warn people when the expansion of seeking narrow blood vessel, should strengthen monitoring, and more need strengthen control [list of references 5] the OxLDL level in the blood circulation to coronary restenosis.
The control of coronary heart disease is atherosclerosis to a great extent, and its key link is to reduce OxLDL, thereby avoids macrophage phagocytic, forms foam cell, and the triggering speckle forms, fibrosis causes tremulous pulse medicated porridge sample to change [list of references 6].So removing OxLDL in blood becomes prevention and treats arteriosclerotic key, also becomes an important ring of coronary heart disease control simultaneously.
OxLDL is intravital free radical source, and macrophage is not attacked natural low density lipoprotein, LDL (LDL), thereby does not cause arteriosclerotic lesion.Therefore antioxidant becomes the target that the research of resisting coronary heart disease pharmaceutics is paid close attention to.Water miscible antioxidant is by preventing lipophilic vitamin E loss, and the LDL in the protection blood avoids oxidation [list of references 2]; The LDL of blood vessel endothelium lower floor then relies on remaining fat antioxidant action.These chemical compounds will be the important sources that exploitation prevents and treats arteriosclerosis and medicaments for coronary disease.
The intravital antioxidant system of 3 machines
Enzyme antioxidant superoxide dismutase (SOD) is a main enzyme of eliminating body O2-, be distributed in the endochylema and mitochondrion of cell, there are two kinds of isozyme Cu in it, Zn-SOD (endochylema) and Mn-SOD (mitochondrion), and its activity high definition is more removed the ability strong more [list of references 7] of free radical.Catalase (CAT) is an important enzyme of eliminating hydrogen peroxide (H2O2) in the body, is present in microgranule and the mitochondrion.Reduced glutathion (GSH) is as the intravital important protection factor; can protect the activity of sulfydryl enzyme; it can also make superoxide anion (O2-), hydrogen peroxide (H2O2) and fat hydroperoxides (LOOH) become the hypotoxicity material under the catalysis of GSH-PX, plays an important role to protecting biomembrane and biomacromolecule to avoid radical damage.The important enzyme that a kind of catalyzing hydrogen peroxide that extensively exists in the glutathion peroxidase (GSH-PX), body decomposes, catalysis GSH plays the effect of protection membrane structure and functional completeness to the reduction reaction of hydrogen peroxide specifically.Glutathione transferase (CST) extensively is present in mammiferous each tissue, content is particularly abundant in the hepatocyte, participate in the important function of detoxification of liver, and can combine with the electrophilic group of chemical substance by catalysis GSH, finally form mercapturic acid and excrete [list of references 8].
The non-enzyme antioxidant is with its cancellation free radical, prevention or interrupt lipid peroxidation, stabilate film and bring into play the antioxidative effect.Mainly comprise: liposoluble substance, as lycopene, vitamin E, beta-carotene, coenzyme Q10 and flavone compound etc.; Water-soluble substances is as vitamin C, CSH etc.In addition, trace element (zinc (Zn), selenium (Se), chromium (Cr), manganese (Mn)) participates in the biosynthesis of enzyme antioxidant, and plays antioxidative effect [list of references 9] with the character of self electron transport.
Ideal pharmaceutical carrier should have " zero level " (i.e. " constant speed ") release behavior, i.e. drug releasing rate time to time change not, thus can make blood drug level continue to maintain the level of optimum curative effect.With biodegradable macromolecular material during as pharmaceutical carrier, though carrier also will slow down along with the degraded of medicament contg to the rate of release of medicine, but owing to progressively degraded along with pharmaceutical carrier, the structure of carrier becomes loose, drug molecule is accelerated to body dissolving and diffusance from carrier, and release amount of medicine increases.Therefore, in the biodegradation rate that is adjusted to carrier is a timing, just can make the minimizing that reduces the release amount of medicine cause owing to medicament contg with offseting the constant release of realization medicine because drug molecule dissolving diffusion velocity is accelerated the increase of the release amount of medicine that causes.In addition, because the Biodegradable high molecular pharmaceutical carrier is degraded into micromolecule or monomer under the physiological environment in vivo, so that finally absorbed or metabolism by body, therefore also having not to need the advantage of taking out again in body after drug release is finished, be optimal pharmaceutical carrier.
The present invention is by above-mentioned rationale and cause damage problem to carry out sufficient research and analysis to easy pair cell of myocardial ischemia-reperfusion and tissue, show after deliberation, myocardial ischemia reperfusion injury can further strengthen myocardial infarction area, the cardiac dysfunction degree is heavier than acute myocardial infarction, and case fatality rate is higher.During reperfusion injury, because free radical effect and Ca2+ overload have damaged cell membrane and mitochondrion, permeability of cell membrane is increased, tissue necrosis causes the various enzymes of myocardial cell to leak outside, and is released into blood, causes that a series of serum zymetologys change [list of references 10].Serum creatine kinase isozyme (CK-MB), the determination of activity of lactate dehydrogenase L DH and glutamic oxaloacetic transaminase, GOT AST can be used as observe myocardial ischemia reperfusion injury degree and medicine resist myocardial ischemia the reperfusion injury curative effect and more after one of index.
During myocardial ischemia reperfusion injury, arterial endothelium is impaired, the prostacyclin (PGI) that mainly results from the coronary blood endothelial cell is synthesized disturbed, subcutaneous collagen tissue in platelet is killed and invested further discharges the vaso-excitor material based on thromboxane A (TXA).TXA can be used as carrier and directly promotes stream and dense tubular system Ca2+ release in the Ca2+, thereby promotes platelet aggregation and local vasoconstriction, increases the weight of endothelial injury [list of references 10].
Therefore oxygen-derived free radicals is one of key factor that causes reperfusion injury to histiocytic infringement.In myocardial ischemia and the refilling process; the superoxide dismutase (SOD) of cardiac muscle; the content of catalase (CAT) and glutathion peroxidase (GSH-Px) etc. reduces; malonaldehyde (MDA) content increases, so exogenous antioxidant or the free radical scavenger of giving is to ischemia and pour into cardiac muscle again and have significant protective effect [list of references 11].And, improve the endogenous activities of antioxidant enzymes and further alleviate oxygen-derived free radicals induced myocardial injury by suppressing the lipid peroxidation process.
Summary of the invention
In sum; anti-oxidation medicine should become treatment and protect the main medicine that human body cell and tissue is caused damage because of ischemia-reperfusion; it is a carrier with enzyme and non-enzyme antioxidant with the Biodegradable polymer; be coated on the intravascular stent surface; and the analysis by pharmacological action; it can singly be planted and prepare; again can multiple mixed preparing; can also with anti-angiogenic restenosis medicaments mixed preparing; by local application, can alleviate effectively and reduce because of the final realization treatment of the damage of radical pair human body cell and tissue behind myocardial ischemia-reperfusion cardiac dysfunction.
The blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion provided by the invention, the blood vessel stent drug coating by the anti-oxidation medicine of 1%-90% (weight ratio) or 1%-99% (weight ratio) anti-oxidation medicine and anti-angiogenic restenosis medicaments mix and the pharmaceutical carrier of 10%-99% (weight ratio) is formed.
Anti-oxidation medicine of the present invention comprises superoxide dismutase (SOD), catalase (CAT), coenzyme Q10, glutathion peroxidase (GSH-PX), lycopene, reduced glutathion (GSH), vitamin E, beta-carotene, vitamin C and trace element (zinc (Zn), selenium (Se), chromium (Cr), manganese (Mn)) and through the product behind the molecular modification, in the said medicine any one or any several drugs all can be prepared with pharmaceutical carrier, wherein, any one content of medicines during several drugs mixes should account for the 1%-99% (weight ratio) of the total proportion of medicine;
Described anti-angiogenic restenosis class medicine is anticoagulation class medicine, anticancer class medicine, inhibition vascular smooth muscle cell curing class activity inhibitor, anti-inflammatory drug and immunosuppressant, wherein:
Anticoagulation class medicine comprises aspirin, heparin, hirudin, antiplatelet GPIIb/IIIa receptor antagonist, clopidogrel;
Anticancer class medicine comprises colchicine, paclitaxel;
Suppress vascular smooth muscle cell curing class activity inhibitor and comprise angiogenic peptide, 17-hydroxy-11-dehydrocorticosterone, calcium ion antagonist;
Anti-inflammatory drug comprises dactinomycin, depsidomycin, KanglemycinC, spergualin, cammunomicin, demethomycin, tetranactin, stevastelins, myriocin, gllooxin;
Immunosuppressant comprises rapamycin, the plain A of ring spore enzyme, the plain C of ring spore enzyme, brefeldin A;
Medication coat of the present invention can be made up of the pharmaceutical carrier of any one and 10%-99% (weight ratio) in anti-oxidation medicine superoxide dismutase, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and the zinc of 1%-90%, selenium, chromium, the manganese microelement.
Medication coat of the present invention can be made up of mixing several arbitrarily in anti-oxidation medicine superoxide dismutase, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and the zinc of 1%-90% (weight ratio), selenium, chromium, the manganese microelement and the pharmaceutical carrier of 10%-99% (weight ratio); Wherein, the content of any one anti-oxidation medicine in the medicament mixed should account for the 1%-99% (weight ratio) of the total proportion of medicine.
Medication coat of the present invention can be by the anti-oxidation medicine superoxide dismutase of 1%-90%, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and zinc, selenium, chromium, in the manganese microelement any one and aspirin, heparin, hirudin, antiplatelet GPIIb/IIIa receptor antagonist, clopidogrel, tazettine, paclitaxel, angiogenic peptide, 17-hydroxy-11-dehydrocorticosterone, calcium ion antagonist, the plain A of ring spore enzyme, dactinomycin, rapamycin, the plain C of ring spore enzyme, brefeldin A, depsidomycin, KanglemycinC, spergualin, cammunomicin, demethomycin, tetranactin, stevastelins, myriocin, the pharmaceutical carrier of the mixing of any one among the gllooxin and 10%-99% (weight ratio) is formed; Wherein, the content of any one anti-oxidation medicine in the medicament mixed should account for the 1%-99% (weight ratio) of the total proportion of medicine.
Medication coat of the present invention can be by the anti-oxidation medicine superoxide dismutase of 1%-90%, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and zinc, selenium, chromium, any several and aspirin in the manganese microelement, heparin, hirudin, antiplatelet GPIIb/IIIa receptor antagonist, clopidogrel, tazettine, paclitaxel, angiogenic peptide, 17-hydroxy-11-dehydrocorticosterone, calcium ion antagonist, the plain A of ring spore enzyme, dactinomycin, rapamycin, the plain C of ring spore enzyme, brefeldin A, depsidomycin, KanglemycinC, spergualin, cammunomicin, demethomycin, tetranactin, stevastelins, myriocin, the pharmaceutical carrier of the mixing of any one among the gllooxin and 10%-99% (weight ratio) is formed; Wherein, the content of any one anti-oxidation medicine in the medicament mixed should account for the 1%-99% (weight ratio) of the total proportion of medicine.
Pharmaceutical carrier of the present invention is Biodegradable material and non-degradable material.Biodegradable material comprises copolymer or the blend between PTMC and PLA, glutin, polyurethane, poly phosphate or the polyglycolic acid ester, its copolymerization or blend ratio are 1%: 99%-99%: in 1% (weight ratio) scope, and its molecular weight 5000-500000kd.
The non-degradable material comprises copolymer or the blend between plastic of poly vinyl acetate and polymethyl methacrylate, sodium alginate, gelatin, arabic gum or the polybutyl methacrylate, its copolymerization or blend ratio are 1%: 99%-99%: in 1% (weight ratio) scope, and its molecular weight 5000-500000kd.
The material of the intravascular stent that the present invention adopts is a rustless steel, Ultimum Ti ， Gu Chrome alloy or with the macromolecular material of bio-compatible.
Preparation method provided by the invention comprises two kinds (mainly being the preparations at multicomponent pharmaceutical), and a kind of is with the medicament mixed coating, and another kind is the layering coating.Layering coating should be with anti-angiogenic restenosis class medicine as the intermediate layer, and anti-oxidation medicine is coated in the top layer of intravascular stent, no matter be any, the bottom of every pair of support all has one deck Parylene (Parylene) polymeric film.Coating method can adopt the spraying process of medicine coating method or infusion process any one, no matter take any method, all should reach coating evenly and its medication coat thickness should be between the 1-100 micron, the drug loading of every pair of support is between the 10-1000 microgram.
What the preparation method of the embodiment of the invention adopted is spraying process and infusion process, the rotatable support frame angle repeats spraying several times in spraying process, it is reached evenly, and the medication coat content on the support can be controlled by the concentration of drug solution and the number of times of coating.Its preparation method is as follows:
1. mix coating: at first xylol is heated to 950 ℃, generate the xylol dimer, then 680 ℃ of following cracking, form monomer vapours, support is placed on the indoor back of room temperature deposition feeds monomer vapours, standby behind the polymeric film of rack surface formation one deck even compact, then pharmaceutical carrier is dissolved in the solvent, adding medicine stirs, after treating fully dissolving and filtering, evenly be coated on the intravascular stent surface that is covered with the parylene polymer film, and in noble gas solvent flashing, descended dry 12 hours in vacuum condition afterwards, again the ethane via epoxyethane sterilization.
2. layering coating: at first xylol is heated to 950 ℃, generate the xylol dimer, then 680 ℃ of following cracking, form monomer vapours, support is placed on the indoor back of room temperature deposition feeds monomer vapours, standby behind the polymeric film of rack surface formation one deck even compact, then pharmaceutical carrier is dissolved in the solvent, adding anti-angiogenic restenosis class medicine stirs, after treating fully dissolving and filtration, evenly be coated on the intravascular stent surface that is covered with the parylene polymer film, and in noble gas solvent flashing; Pharmaceutical carrier is dissolved in the solvent, adding the polyphenoils medicine then stirs, after treating fully dissolving and filtration, evenly be coated on the intravascular stent surface that is covered with anti-angiogenic restenosis class medication coat, and in noble gas solvent flashing, descended dry 12 hours in vacuum condition afterwards, again the ethane via epoxyethane sterilization.
The advantage of layering coating is, both can discharge the anti-oxidation medicine skin earlier to reach the purpose of alleviating and reducing because of the damage of radical pair human body cell and tissue behind the myocardial ischemia-reperfusion, the anti-angiogenic restenosis class medicine that can control the intermediate layer again in human body because the too fast danger that causes of release.
The solvent that compounding pharmaceutical coating solution of the present invention uses is heterocyclic arene class, pure ketone, esters, alkanes, aromatic hydrocarbons and water; Comprise any one of methanol, ethanol, sodium lactate, acetonitrile, isopropyl alcohol, oxolane, acetone, dichloromethane, chloroform or purified water.The noble gas that uses in the medication coat preparation process can be any one of other noble gas in nitrogen, helium and the periodic table of chemical element.
The release cycle of anti-oxidation medicine of the present invention is one thoughtful 6 months.
The specific embodiment
Embodiment one: after the copolymer of 0.3g PTMC and polylactic acid (10/90 (mol/mol)) is dissolved in 10ml acetone, adding 0.2g superoxide dismutase (SOD) stirs, after dissolving all even filtration, be sprayed on the 316L stainless steel stent surface of the middle medication coat of copolymer (10/90 (mol/mol)) that is covered with 0.1g ciclosporin A and 0.3g PTMC and polylactic acid on Parylene (Parylene) the polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment two: after the copolymer of 0.2g PTMC and polyurethane (5/95 (mol/mol)) is dissolved in the 10ml acetonitrile, add the 0.5g lycopene, 0.01g coenzyme Q10 and 0.01g vitamin E, stir, after dissolving all even filtration, be sprayed on the 316L stainless steel stent surface of the middle medication coat of copolymer (10/90 (mol/mol)) that is covered with 0.1g dactinomycin and 0.3g PTMC and polylactic acid on Parylene (Parylene) the polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment three: after the copolymer of 0.3g PTMC and polylactic acid (15/85 (mol/mol)) is dissolved in 10ml ethanol, adding 0.3g coenzyme Q10 and 0.01g rapamycin stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment four: after the copolymer of 0.5g PTMC and polylactic acid (25/75 (mol/mol)) is dissolved in the 10ml acetonitrile, adding 0.1g coenzyme Q10 and 0.2g paclitaxel stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment five: after the copolymer of 0.2g PTMC and polyurethane (30/70 (mol/mol)) is dissolved in 10ml ethanol, add the 0.1g coenzyme Q10, stir, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment six: after the 0.4g plastic of poly vinyl acetate is dissolved in 10ml acetone, adding 0.3g coenzyme Q10 and 0.1g ciclosporin A stirs, after dissolving all even filtration, be sprayed on Parylene (Parylene) the polymeric film bottom and be covered with 316L stainless steel stent surface, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, makes it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment seven: after the copolymer of 0.3g PTMC and polyglycolic acid ester (10/90 (mol/mol)) is dissolved in the 10ml oxolane, add 0.2g superoxide dismutase (SOD) and 0.1g vitamin E, stir, after dissolving all even filtration, be sprayed on the 316L stainless steel stent surface of the middle medication coat of copolymer (10/90 (mol/mol)) that is covered with 0.1g ciclosporin A and 0.3g PTMC and polylactic acid on Parylene (Parylene) the polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment eight: after the copolymer of 0.1g PTMC and polylactic acid (5/95 (mol/mol)) is dissolved in 10ml acetone, adding the 0.2g lycopene stirs, after dissolving all even filtration, be sprayed on the 316L stainless steel stent surface of the middle medication coat of copolymer (10/90 (mol/mol)) that is covered with 0.1g dactinomycin and 0.3g PTMC and polylactic acid on Parylene (Parylene) the polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment nine: after the copolymer of 0.3g PTMC and polylactic acid (10/90 (mol/mol)) is dissolved in the 10ml oxolane, add 0.2g superoxide dismutase (SOD) and 0.1g vitamin E, stir, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment ten: after the copolymer of 0.5g PTMC and polyglycolic acid ester (25/75 (mol/mol)) is dissolved in 10ml ethanol, adding 0.1g beta-carotene and 0.2g paclitaxel stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 11: after the copolymer of 0.3g PTMC and polyurethane (10/90 (mol/mol)) is dissolved in the 10ml isopropyl alcohol, adding the 0.2g vitamin C stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 12: after the copolymer of 0.2g PTMC and poly phosphate (5/95 (mol/mol)) is dissolved in 10ml ethanol, add the 0.01g vitamin C, 0.01g coenzyme Q10 and 0.3g vitamin E, stir, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 13: after the copolymer of 0.5g PTMC and polylactic acid (15/85 (mol/mol)) is dissolved in the 10ml acetonitrile, adding 0.02g vitamin C and 0.03g rapamycin stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 14: after the copolymer of 0.3g PTMC and polyglycolic acid ester (25/75 (mol/mol)) is dissolved in the 10ml isopropyl alcohol, adding 0.1g vitamin C and 0.2g paclitaxel stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 15: after the copolymer of 0.4g PTMC and polyurethane (30/70 (mol/mol)) is dissolved in 10ml acetone, adding the plain A of 0.01g vitamin C and 0.01g ring spore enzyme stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 16: after the copolymer of 0.3g PTMC and polyurethane (10/90 (mol/mol)) is dissolved in the 10ml acetonitrile, adding the 0.2g catalase stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 17: after the copolymer of 0.2g PTMC and poly phosphate (5/95 (mol/mol)) is dissolved in 10ml acetone, add 0.1g catalase and 0.1g vitamin E, stir, after dissolving all even filtration, dip-coating is to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 18: after the copolymer of 0.5g PTMC and polylactic acid (15/85 (mol/mol)) is dissolved in the 10ml acetonitrile, adding 0.1g catalase and 0.2g rapamycin stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 19: after the copolymer of 0.3g PTMC and polyglycolic acid ester (25/75 (mol/mol)) is dissolved in the 10ml oxolane, adding 0.1g catalase and 0.2g paclitaxel stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Embodiment 20: after the copolymer of 0.4g PTMC and polyurethane (30/70 (mol/mol)) is dissolved in the 10ml acetonitrile, adding the plain A of 0.01g catalase and 0.1g ring spore enzyme stirs, after dissolving all even filtration, spray to the 316L stainless steel stent surface that is covered with Parylene (Parylene) polymeric film bottom, solvent flashing in nitrogen, and the runing rest angle repeats spraying several times, make it evenly be coated on rack surface, in nitrogen behind the solvent flashing again under vacuum condition in drying at room temperature 12 hours. the ethane via epoxyethane sterilization.
Obviously, the above embodiment of the present invention only is for example clearly is described, and is not to be qualification to embodiment of the present invention.Can also make other changes in different forms on the basis of the above description.Here need not also can't give exhaustive to all embodiments.And these belong to conspicuous variation or the change that spirit of the present invention amplified out and still belong among protection scope of the present invention.
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Claims (10)
1. the blood vessel stent drug coating that can alleviate radical pair cell injury behind the ischemia-reperfusion, it is characterized in that, the blood vessel stent drug coating by the anti-oxidation medicine of 1%-90% or 1%-99% anti-oxidation medicine and anti-angiogenic restenosis medicaments mix and the pharmaceutical carrier of 10%-99% is formed.
2. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1, it is characterized in that described medication coat can be made up of the pharmaceutical carrier of any one and 10%-99% in anti-oxidation medicine superoxide dismutase, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and the zinc of 1%-90%, selenium, chromium, the manganese microelement.
3. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1, it is characterized in that described medication coat can be made up of mixing several arbitrarily in anti-oxidation medicine superoxide dismutase, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and the zinc of 1%-90%, selenium, chromium, the manganese microelement and the pharmaceutical carrier of 10%-99%; Wherein, the content of any one anti-oxidation medicine in the medicament mixed should account for the 1%-99% of the total proportion of medicine.
4. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1, it is characterized in that described medication coat can be by the anti-oxidation medicine superoxide dismutase of 1%-90%, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and zinc, selenium, chromium, in the manganese microelement any one and aspirin, heparin, hirudin, antiplatelet GPIIb/IIIa receptor antagonist, clopidogrel, tazettine, paclitaxel, angiogenic peptide, 17-hydroxy-11-dehydrocorticosterone, calcium ion antagonist, the plain A of ring spore enzyme, dactinomycin, rapamycin, the plain C of ring spore enzyme, brefeldin A, depsidomycin, KanglemycinC, spergualin, cammunomicin, demethomycin, tetranactin, stevastelins, myriocin, the mixing of any one among the gllooxin and the pharmaceutical carrier of 10%-99% are formed; Wherein, the content of any one anti-oxidation medicine in the medicament mixed should account for the 1%-99% of the total proportion of medicine.
5. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1, described medication coat can be by the anti-oxidation medicine superoxide dismutase of 1%-90%, catalase, coenzyme Q10, glutathion peroxidase, lycopene, reduced glutathion, vitamin E, beta-carotene, vitamin C and zinc, selenium, chromium, any several and aspirin in the manganese microelement, heparin, hirudin, antiplatelet GPIIb/IIIa receptor antagonist, clopidogrel, tazettine, paclitaxel, angiogenic peptide, 17-hydroxy-11-dehydrocorticosterone, calcium ion antagonist, the plain A of ring spore enzyme, dactinomycin, rapamycin, the plain C of ring spore enzyme, brefeldin A, depsidomycin, KanglemycinC, spergualin, cammunomicin, demethomycin, tetranactin, stevastelins, myriocin, the mixing of any one among the gllooxin and the pharmaceutical carrier of 10%-99% are formed; Wherein, the content of any one anti-oxidation medicine in the medicament mixed should account for the 1%-99% of the total proportion of medicine.
6. as claim 1,2,3,4, the 5 described blood vessel stent drug coatings of alleviating radical pair cell injury behind the ischemia-reperfusion, it is characterized in that described pharmaceutical carrier can be copolymer or in the blend any one between PTMC and PLA, glutin, polyurethane, poly phosphate or the polyglycolic acid ester; Perhaps can be copolymer or in the blend any one between plastic of poly vinyl acetate and polymethyl methacrylate, sodium alginate, gelatin, arabic gum or the polybutyl methacrylate, its copolymerization or blend ratio be all 1%: 99%-99%: in 1% scope.
7. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1, its preparation method is as follows: at first xylol is heated to 950 ℃, generate the xylol dimer, then 680 ℃ of following cracking, form monomer vapours, support is placed on the indoor back of room temperature deposition feeds monomer vapours, standby behind the polymeric film of rack surface formation one deck even compact, then pharmaceutical carrier is dissolved in the solvent, adding medicine stirs, after treating fully dissolving and filtration, evenly be coated on the intravascular stent surface that is covered with the parylene polymer film, and in noble gas solvent flashing, afterwards in vacuum condition dry 12 hours down, ethane via epoxyethane sterilization again.
8. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1, another kind of preparation method is as follows: at first xylol is heated to 950 ℃, generate the xylol dimer, then 680 ℃ of following cracking, form monomer vapours, support is placed on the indoor back of room temperature deposition feeds monomer vapours, standby behind the polymeric film of rack surface formation one deck even compact, then pharmaceutical carrier is dissolved in the solvent, adding anti-angiogenic restenosis class medicine stirs, after treating fully dissolving and filtering, evenly be coated on the intravascular stent surface that is covered with the parylene polymer film, and in noble gas solvent flashing; Pharmaceutical carrier is dissolved in the solvent, adding the polyphenoils medicine then stirs, after treating fully dissolving and filtration, evenly be coated on the intravascular stent surface that is covered with anti-angiogenic restenosis class medication coat, and in noble gas solvent flashing, descended dry 12 hours in vacuum condition afterwards, again the ethane via epoxyethane sterilization.
9. as claim 7 or the 8 described preparation methoies of alleviating the blood vessel stent drug coating of radical pair cell injury behind the ischemia-reperfusion, it is characterized in that described solvent adopts any one in methanol, ethanol, sodium lactate, acetonitrile, isopropyl alcohol, oxolane, acetone, dichloromethane, chloroform or the purified water; Described noble gas can use any one of other noble gas in nitrogen, helium or the periodic table of chemical element; Described intravascular stent material be rustless steel, Ultimum Ti, Gu Chrome alloy or with the high molecule plastic of bio-compatible.
10. the blood vessel stent drug coating of alleviating radical pair cell injury behind the ischemia-reperfusion as claimed in claim 1 is characterized in that described medication coat thickness is between the 1-100 micron, and the drug loading of every pair of support is between the 10-1000 microgram; The release cycle of described anti-oxidation medicine is one thoughtful 6 months.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101703813B (en) * | 2009-11-25 | 2012-11-28 | 南开大学 | Method for constructing anti-blood coagulation blood vessel scaffold by utilizing endogenous NO donor |
| CN111407930A (en) * | 2020-03-19 | 2020-07-14 | 中国科学院长春应用化学研究所 | Polymer bionic coating and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1209105C (en) * | 2002-01-04 | 2005-07-06 | 中国科学院化学研究所 | Coronary artery skeleton medicinal coating for preventing restenosis of blood vessel |
| KR100511618B1 (en) * | 2005-01-17 | 2005-08-31 | 이경범 | Multi-layer coating of drug release controllable coronary stent and method for manufacturing the same |
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2006
- 2006-08-18 CN CNB2006100153680A patent/CN100431627C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101703813B (en) * | 2009-11-25 | 2012-11-28 | 南开大学 | Method for constructing anti-blood coagulation blood vessel scaffold by utilizing endogenous NO donor |
| CN111407930A (en) * | 2020-03-19 | 2020-07-14 | 中国科学院长春应用化学研究所 | Polymer bionic coating and preparation method thereof |
| CN111407930B (en) * | 2020-03-19 | 2021-01-08 | 中国科学院长春应用化学研究所 | Polymer bionic coating and preparation method thereof |
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