CN110665072A - Targeted drug release interventional medical instrument and preparation method thereof - Google Patents
Targeted drug release interventional medical instrument and preparation method thereof Download PDFInfo
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- CN110665072A CN110665072A CN201911160349.0A CN201911160349A CN110665072A CN 110665072 A CN110665072 A CN 110665072A CN 201911160349 A CN201911160349 A CN 201911160349A CN 110665072 A CN110665072 A CN 110665072A
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- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- YHHSONZFOIEMCP-UHFFFAOYSA-O phosphocholine Chemical compound C[N+](C)(C)CCOP(O)(O)=O YHHSONZFOIEMCP-UHFFFAOYSA-O 0.000 claims description 3
- 229950004354 phosphorylcholine Drugs 0.000 claims description 3
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- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
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- 235000011176 polyphosphates Nutrition 0.000 claims description 3
- 229920002635 polyurethane Polymers 0.000 claims description 3
- 239000004814 polyurethane Substances 0.000 claims description 3
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 3
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- 239000011148 porous material Substances 0.000 claims description 3
- 229960002965 pravastatin Drugs 0.000 claims description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- YYSFXUWWPNHNAZ-PKJQJFMNSA-N umirolimus Chemical compound C1[C@@H](OC)[C@H](OCCOCC)CC[C@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 YYSFXUWWPNHNAZ-PKJQJFMNSA-N 0.000 claims description 3
- 229940045136 urea Drugs 0.000 claims description 3
- 235000019165 vitamin E Nutrition 0.000 claims description 3
- 229940046009 vitamin E Drugs 0.000 claims description 3
- 239000011709 vitamin E Substances 0.000 claims description 3
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 claims description 3
- 229950009819 zotarolimus Drugs 0.000 claims description 3
- 230000000968 intestinal effect Effects 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 4
- 210000003556 vascular endothelial cell Anatomy 0.000 abstract description 4
- 230000035876 healing Effects 0.000 abstract description 3
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- 208000007536 Thrombosis Diseases 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 1
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Classifications
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/082—Inorganic materials
- A61L31/086—Phosphorus-containing materials, e.g. apatite
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- A—HUMAN NECESSITIES
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
- A61L2300/608—Coatings having two or more layers
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- A61L2420/00—Materials or methods for coatings medical devices
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- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention relates to the technical field of medical instruments, in particular to a targeted drug release intervention type medical instrument and a preparation method thereof, wherein a slow-release drug coating on the targeted drug release intervention type medical instrument has high bonding strength with the surface of an intracavity intervention type medical instrument, no drug material is lost in the subsequent processing process, when a drug is slowly released, a slow-release drug coating B is firstly released, the slow-release drug coating B can accelerate the healing of vascular endothelial cells, when the slow-release drug coating B is released, the slow-release drug coating A starts to be slowly released, the slow-release drug coating A can effectively inhibit the hyperplasia of the vascular intima, reduce the probability of restenosis, has good drug treatment effect, and micropores capable of loading the drug are formed on the surface of the intervention type medical instrument by etching, so that no drug material loss caused by the sliding of the intervention type medical instrument during use can be avoided, further improving the treatment effect of the medicine.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to a targeted drug release interventional medical instrument and a preparation method thereof.
Background
With the wide application of the drug sustained-release stent system and the continuous development of new technologies, people have more intensive research on the drug sustained-release stent system. In operation, it is found that when a stent is implanted into a blood vessel, the inner wall of the blood vessel is inevitably scraped due to the expanded support of the stent of a metal or nonmetal structure, thereby causing damage. After surgery, patients need to take anticoagulant medication to avoid thrombosis. Compared with a naked stent without a drug coating, the vascular endothelial cells can automatically heal within 30 days, and a patient does not need to take anticoagulant drugs any more, but the probability of restenosis is 25-50%. While the slow-release stent of the drugs (including rapamycin and derivatives thereof, paclitaxel and derivatives thereof) effectively inhibits the vascular intimal hyperplasia, the healing of vascular endothelial cells is delayed due to the slow release of the drugs. Creating the potential risk of death from acute thrombosis in the late stage of stent implantation. According to the related data, the drug sustained-release stent still has the case of acute thrombosis after being implanted into the blood vessel for two years.
Disclosure of Invention
In order to solve the technical problem, the invention provides an unmanned rescue vehicle which is suitable for all-terrain rescue.
The technical problem to be solved by the invention is realized by adopting the following technical scheme:
the invention provides a preparation method of a targeted drug release interventional medical device, which comprises the following steps:
(1) preparation of sustained-release drug coating A
A. Preparing a slow-release drug coating A material, wherein the slow-release drug coating A material is composed of a drug material A, a drug carrier material A, an antioxidant and an adhesive;
①, the drug carrier A is selected from one or a mixture of at least two of polyphosphate, biological apatite, heparinized polymer, heparin, polylactic acid, iodixanol, iopromide, urea, polyvinyl alcohol, lac and chitin at any ratio;
②, the medicinal material A is selected from one or more of heparin sodium, batroxobin, antithrombotic enzyme, aspirin, hirudin, colchicine, rapamycin, Everolimus, Biolimus, Zotarolimus, Tracrolimus, atorvastatin, pravastatin, cyclosporin, Anti-CD34, dexamethasone, bleomycin, plicamycin, mitomycin C, actinomycin D, taxol, tripterine, and methotrexate;
B. preparing a solvent, wherein the solvent is a mixture of formic acid and acetone, and the volume ratio of the formic acid to the acetone is 1: 8;
C. adding the slow-release drug coating material into a solvent, mixing and uniformly stirring, wherein the mass ratio of the drug carrier material, the antioxidant, the drug material and the adhesive to the solvent is 0.001-0.35, 0.00002-0.0020, 0.0005-0.20 and 0.00002-0.20 respectively; obtaining a slow-release drug coating A;
(2) preparation of sustained-release drug coating B
A. Preparing a slow-release drug coating B material, wherein the slow-release drug coating B material consists of a drug material B, a drug carrier material B, an antioxidant and an adhesive;
①, the drug carrier B is selected from one or a mixture of at least two of the following materials in any proportion, polylactic acid, polyethylene glycol, styrene butylene copolymer, polycaprolactone, polybutylmethacrylate, polyethyl methacrylate, polyvinyl acetate, polyurethane, polyvinylpyrrolidone, poly choline phosphate, fibroin, gelatin and chitin;
②, the medicinal material B is selected from one or more of the following materials including borrelidin, heparin sodium, aspirin, captopril, batroxobin, betalake, external recombinant human epidermal growth factor, and chitosan;
B. preparing a solvent, wherein the solvent is a mixture of formic acid and acetone, and the volume ratio of the formic acid to the acetone is 1: 8;
C. adding the slow-release drug coating B material into a solvent, mixing and uniformly stirring, wherein the mass ratio of the drug carrier material B, the antioxidant B, the drug material B and the adhesive B to the solvent is 0.001-0.35, 0.00002-0.0020, 0.0005-0.20 and 0.00002-0.20 respectively; obtaining a slow-release drug coating B;
(3) application of sustained-release drug coating A
The solvent dissolved with the slow-release drug coating A is coated on the surface of the interventional medical appliance by utilizing the methods of ultrasonic atomization spraying, liquid absorption coating, injection coating, air-assisted spraying, electrostatic spraying, piezoelectric spraying, electrostatic spinning or dip coating, and the drug content on the surface of the interventional medical appliance is 4-10 mu g/mm2；
(4) Drying the mixture
Transferring the interventional medical device coated with the slow-release drug coating A into a vacuum drying oven at the temperature of 50-95 ℃ for drying;
(5) application of sustained-release drug coating B
The solvent dissolved with the slow-release drug coating B is coated on the surface of the interventional medical appliance finished in the step (4) by utilizing the methods of ultrasonic atomization spraying, liquid absorption coating, injection coating, air-assisted spraying, electrostatic spraying, piezoelectric spraying, electrostatic spinning or dip coating, and the drug content on the surface of the interventional medical appliance is 0.1-3 mu g/mm2；
(6) Drying the mixture
And (3) transferring the interventional medical device coated with the slow-release drug coating B into a vacuum drying oven at the temperature of 45-80 ℃ for drying.
Furthermore, the surface of the interventional medical instrument is formed with micropores by adopting an anodic oxidation, micro-arc oxidation or chemical corrosion method.
Furthermore, the depth of the micropores is 6-10 μm, and the pore diameter of the micropores is 0.3-1 μm.
Further, the antioxidant B is vitamin E; .
Further, the adhesive B is polymethyl methacrylate.
The invention also provides a targeted drug release interventional medical device which is formed by coating the interventional medical device with a drug, wherein the targeted drug release interventional medical device consists of the interventional medical device, a slow-release drug coating A and a slow-release drug coating B, and the slow-release drug coating A and the slow-release drug coating B are sequentially coated on the surface of the interventional medical device.
Furthermore, the interventional medical device is any one of a coronary artery stent, an intracranial vascular stent, a peripheral vascular stent, an intraoperative stent, a heart valve stent, a biliary tract stent, an esophagus stent, an intestinal tract stent, a pancreatic duct stent, a urethral stent or a tracheal stent.
Furthermore, the surface of the interventional medical device is provided with micropores, and a slow-release drug coating A and a slow-release drug coating B are coated in the micropores.
Compared with the prior art, the invention has the beneficial effects that: the slow-release drug coating on the targeted drug release interventional medical device has high bonding strength with the surface of the intraluminal interventional medical device, no loss of drug materials is generated in the subsequent processing process, when the drug is slowly released, the slow-release drug coating B is firstly released and can accelerate the healing of vascular endothelial cells, after the slow-release drug coating B is released, the slow-release drug coating A starts to be slowly released, the slow-release drug coating A can effectively inhibit the hyperplasia of the vascular intima, the probability of restenosis is reduced, the drug treatment effect is good, micropores capable of loading the drug are formed on the surface of the interventional medical device through etching, the loss of the drug materials caused by the sliding of the interventional medical device in use can be avoided, and the drug treatment effect is further improved.
Drawings
FIG. 1 is a flow chart of the preparation method of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides the following technical scheme:
referring to fig. 1, the present invention provides a method for preparing a targeted drug release interventional medical device, which comprises the following steps:
(1) preparation of sustained-release drug coating A
A. Preparing a slow-release drug coating A material, wherein the slow-release drug coating A material is composed of a drug material A, a drug carrier material A, an antioxidant and an adhesive;
①, the drug carrier A is selected from one or a mixture of at least two of polyphosphate, biological apatite, heparinized polymer, heparin, polylactic acid, iodixanol, iopromide, urea, polyvinyl alcohol, lac and chitin at any ratio;
②, the medicinal material A is selected from one or more of heparin sodium, batroxobin, antithrombotic enzyme, aspirin, hirudin, colchicine, rapamycin, Everolimus, Biolimus, Zotarolimus, Tracrolimus, atorvastatin, pravastatin, cyclosporin, Anti-CD34, dexamethasone, bleomycin, plicamycin, mitomycin C, actinomycin D, taxol, tripterine, and methotrexate;
B. preparing a solvent, wherein the solvent is a mixture of formic acid and acetone, and the volume ratio of the formic acid to the acetone is 1: 8;
C. adding the slow-release drug coating material into a solvent, mixing and uniformly stirring, wherein the mass ratio of the drug carrier material, the antioxidant, the drug material and the adhesive to the solvent is 0.001-0.35, 0.00002-0.0020, 0.0005-0.20 and 0.00002-0.20 respectively; obtaining a slow-release drug coating A;
(2) preparation of sustained-release drug coating B
A. Preparing a slow-release drug coating B material, wherein the slow-release drug coating B material consists of a drug material B, a drug carrier material B, an antioxidant and an adhesive;
①, the drug carrier B is selected from one or a mixture of at least two of the following materials in any proportion, polylactic acid, polyethylene glycol, styrene butylene copolymer, polycaprolactone, polybutylmethacrylate, polyethyl methacrylate, polyvinyl acetate, polyurethane, polyvinylpyrrolidone, poly choline phosphate, fibroin, gelatin and chitin;
②, the medicinal material B is selected from one or more of the following materials including borrelidin, heparin sodium, aspirin, captopril, batroxobin, betalake, external recombinant human epidermal growth factor, and chitosan;
B. preparing a solvent, wherein the solvent is a mixture of formic acid and acetone, and the volume ratio of the formic acid to the acetone is 1: 8;
C. adding the slow-release drug coating B material into a solvent, mixing and uniformly stirring, wherein the mass ratio of the drug carrier material B, the antioxidant B, the drug material B and the adhesive B to the solvent is 0.001-0.35, 0.00002-0.0020, 0.0005-0.20 and 0.00002-0.20 respectively; obtaining a slow-release drug coating B;
(3) application of sustained-release drug coating A
The solvent dissolved with the slow-release drug coating A is coated on the surface of the interventional medical appliance by utilizing the methods of ultrasonic atomization spraying, liquid absorption coating, injection coating, air-assisted spraying, electrostatic spraying, piezoelectric spraying, electrostatic spinning or dip coating, and the drug content on the surface of the interventional medical appliance is 4-10 mu g/mm2；
(4) Drying the mixture
Transferring the interventional medical device coated with the slow-release drug coating A into a vacuum drying oven at the temperature of 50-95 ℃ for drying;
(5) application of sustained-release drug coating B
The solvent dissolved with the slow-release drug coating B is coated on the surface of the interventional medical appliance finished in the step (4) by utilizing the methods of ultrasonic atomization spraying, liquid absorption coating, injection coating, air-assisted spraying, electrostatic spraying, piezoelectric spraying, electrostatic spinning or dip coating, and the drug content on the surface of the interventional medical appliance is 0.1-3 mu g/mm2；
(6) Drying the mixture
And (3) transferring the interventional medical device coated with the slow-release drug coating B into a vacuum drying oven at the temperature of 45-80 ℃ for drying.
The surface of the interventional medical instrument is subjected to anodic oxidation, micro-arc oxidation or chemical corrosion to form micropores on the surface of the interventional medical instrument.
The depth of the micropores is 6-10 μm, and the pore diameter of the micropores is 0.3-1 μm.
The antioxidant B is vitamin E; .
The adhesive B is polymethyl methacrylate.
The invention also provides a targeted drug release interventional medical device which is formed by coating the interventional medical device with a drug, wherein the targeted drug release interventional medical device consists of the interventional medical device, a slow-release drug coating A and a slow-release drug coating B, and the slow-release drug coating A and the slow-release drug coating B are sequentially coated on the surface of the interventional medical device.
The interventional medical device is any one of a coronary artery stent, an intracranial vascular stent, a peripheral vascular stent, an intraoperative stent, a heart valve stent, a biliary stent, an esophageal stent, an intestinal stent, a pancreatic duct stent, a urethral stent or a tracheal stent.
The surface of the interventional medical appliance is provided with micropores, and a slow-release drug coating A and a slow-release drug coating B are coated in the micropores.
While the invention has been described above with reference to an embodiment, various modifications may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In particular, the various features of the embodiments disclosed herein may be used in any combination, provided that there is no structural conflict, and the combinations are not exhaustively described in this specification merely for the sake of brevity and conservation of resources. Therefore, it is intended that the invention not be limited to the particular embodiments disclosed, but that the invention will include all embodiments falling within the scope of the appended claims.
Claims (8)
1. A preparation method of a targeted drug release interventional medical device is characterized by comprising the following steps: the preparation method comprises the following steps:
(1) preparation of sustained-release drug coating A
A. Preparing a slow-release drug coating A material, wherein the slow-release drug coating A material is composed of a drug material A, a drug carrier material A, an antioxidant and an adhesive;
①, the drug carrier A is selected from one or a mixture of at least two of polyphosphate, biological apatite, heparinized polymer, heparin, polylactic acid, iodixanol, iopromide, urea, polyvinyl alcohol, lac and chitin at any ratio;
②, the medicinal material A is selected from one or more of heparin sodium, batroxobin, antithrombotic enzyme, aspirin, hirudin, colchicine, rapamycin, Everolimus, Biolimus, Zotarolimus, Tracrolimus, atorvastatin, pravastatin, cyclosporin, Anti-CD34, dexamethasone, bleomycin, plicamycin, mitomycin C, actinomycin D, taxol, tripterine, and methotrexate;
B. preparing a solvent, wherein the solvent is a mixture of formic acid and acetone, and the volume ratio of the formic acid to the acetone is 1: 8;
C. adding the slow-release drug coating material into a solvent, mixing and uniformly stirring, wherein the mass ratio of the drug carrier material, the antioxidant, the drug material and the adhesive to the solvent is 0.001-0.35, 0.00002-0.0020, 0.0005-0.20 and 0.00002-0.20 respectively; obtaining a slow-release drug coating A;
(2) preparation of sustained-release drug coating B
A. Preparing a slow-release drug coating B material, wherein the slow-release drug coating B material consists of a drug material B, a drug carrier material B, an antioxidant and an adhesive;
①, the drug carrier B is selected from one or a mixture of at least two of the following materials in any proportion, polylactic acid, polyethylene glycol, styrene butylene copolymer, polycaprolactone, polybutylmethacrylate, polyethyl methacrylate, polyvinyl acetate, polyurethane, polyvinylpyrrolidone, poly choline phosphate, fibroin, gelatin and chitin;
②, the medicinal material B is selected from one or more of the following materials including borrelidin, heparin sodium, aspirin, captopril, batroxobin, betalake, external recombinant human epidermal growth factor, and chitosan;
B. preparing a solvent, wherein the solvent is a mixture of formic acid and acetone, and the volume ratio of the formic acid to the acetone is 1: 8;
C. adding the slow-release drug coating B material into a solvent, mixing and uniformly stirring, wherein the mass ratio of the drug carrier material B, the antioxidant B, the drug material B and the adhesive B to the solvent is 0.001-0.35, 0.00002-0.0020, 0.0005-0.20 and 0.00002-0.20 respectively; obtaining a slow-release drug coating B;
(3) application of sustained-release drug coating A
The solvent dissolved with the slow-release drug coating A is coated on the surface of the interventional medical appliance by utilizing the methods of ultrasonic atomization spraying, liquid absorption coating, injection coating, air-assisted spraying, electrostatic spraying, piezoelectric spraying, electrostatic spinning or dip coating, and the drug content on the surface of the interventional medical appliance is 4-10 mu g/mm2；
(4) Drying the mixture
Transferring the interventional medical device coated with the slow-release drug coating A into a vacuum drying oven at the temperature of 50-95 ℃ for drying;
(5) application of sustained-release drug coating B
The solvent dissolved with the slow-release drug coating B is coated on the surface of the interventional medical appliance finished in the step (4) by utilizing the methods of ultrasonic atomization spraying, liquid absorption coating, injection coating, air-assisted spraying, electrostatic spraying, piezoelectric spraying, electrostatic spinning or dip coating, and the drug content on the surface of the interventional medical appliance is 0.1-3 mu g/mm2；
(6) Drying the mixture
And (3) transferring the interventional medical device coated with the slow-release drug coating B into a vacuum drying oven at the temperature of 45-80 ℃ for drying.
2. The method for preparing a targeted drug release interventional medical device according to claim 1, wherein the method comprises the following steps: the surface of the interventional medical instrument is subjected to anodic oxidation, micro-arc oxidation or chemical corrosion to form micropores on the surface of the interventional medical instrument.
3. The method for preparing a targeted drug release interventional medical device according to claim 2, wherein the method comprises the following steps: the depth of the micropores is 6-10 μm, and the pore diameter of the micropores is 0.3-1 μm.
4. The method for preparing a targeted drug release interventional medical device according to claim 1, wherein the method comprises the following steps: the antioxidant B is vitamin E; .
5. The method for preparing a targeted drug release interventional medical device according to claim 1, wherein the method comprises the following steps: the adhesive B is polymethyl methacrylate.
6. A targeted drug release interventional medical device comprises a targeted drug release interventional medical device formed by coating drugs on the interventional medical device, and is characterized in that: the targeted drug release interventional medical device consists of an interventional medical device, a sustained-release drug coating A and a sustained-release drug coating B, wherein the sustained-release drug coating A and the sustained-release drug coating B are sequentially coated on the surface of the interventional medical device.
7. The targeted drug release interventional medical device as set forth in claim 6, wherein: the interventional medical device is any one of a coronary artery stent, an intracranial vascular stent, a peripheral vascular stent, an intraoperative stent, a heart valve stent, a biliary stent, an esophageal stent, an intestinal stent, a pancreatic duct stent, a urethral stent or a tracheal stent.
8. The targeted drug release interventional medical device of claim 7, wherein: the surface of the interventional medical appliance is provided with micropores, and a slow-release drug coating A and a slow-release drug coating B are coated in the micropores.
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