CN101049518A - Surface modified coat of bracket of blood vessel, and preparation method - Google Patents
Surface modified coat of bracket of blood vessel, and preparation method Download PDFInfo
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- CN101049518A CN101049518A CN 200710021454 CN200710021454A CN101049518A CN 101049518 A CN101049518 A CN 101049518A CN 200710021454 CN200710021454 CN 200710021454 CN 200710021454 A CN200710021454 A CN 200710021454A CN 101049518 A CN101049518 A CN 101049518A
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Abstract
A coated layer for modifying the surface of vascular scaffold by controlling the content of polyoxyethene in the coated layer to regulate its medicine-carrying performance and the release of medicinal is a polysulfone-polyoxyethene block copolymer with 10000-300000 for its number average molecular weight. Its preparing process features that said block copolymer is coated on the surface of said vascular scaffold directly or after the medicine is added to its solution.
Description
Technical field
The present invention is specifically related to a kind of surface modified coat of intravascular stent of may command drug release.Belong to the technical field that medical apparatus and instruments is made,
Background technology
Technology with the method treatment angiostenosis that gets involved is called angioplasty, english abbreviation PTCA (Percutaneous Transluminal Coronary Angioplasty).The whole surgery process approximately continues 1～2 hour, and generally speaking, the symptom of postoperative patient can disappear immediately, and patient just can go home to live normally after surgery next day.Compare advantage such as it is little that intervention property angioplasty has risk, and Wicresoft hinders, and it is fast that postoperative patient recovers, and curative effect is reliable, and relapse rate is low, and it is simple to perform the operation, and surgery cost is relatively low with traditional method of opening breast treatment vascular lesion.This technology worldwide is subjected to doctor and patient's welcome after occurring immediately, progressively substitutes traditional Therapeutic Method.In developed country, it has become treatment because the main Therapeutic Method of the myocardial infarction that the disease, particularly coronary stricture that Cardiovascular abnormality causes causes.
The secondary stricture again that takes place after the angioplasty is called restenosis, and successful PTCA postoperative still has 30%～50% restenosis generation in 3～6 months.Prevention of restenosis become Wicresoft's noticeable focus in interventional therapy cardiovascular disease field.Along with people deepen continuously to the mechanism research that restenosis takes place, find that it is 3 main causes that cause restenosis that Wicresoft's interventional therapy causes smooth muscle cell proliferation, thrombosis and the blood vessel wall of vascular damaged initiation to reinvent, and proposed series of solutions:
At first, the implant frame art plays a supportive role to the blood vessel that is damaged, and can reduce the influence that blood vessel wall is reinvented, thereby becomes the main method that the solution blood vessel wall is reinvented.Intravascular stent is temporarily fixed on the foley's tube that microballoon is arranged endways, enter human body from femoral artery or carotid artery then, under the guiding of seal wire, observe moving of seal wire and conduit by DSA (Digital Subtraction X ray real-time imaging system), driving in the wrong direction along tremulous pulse arrives narrow positions coronarius.After sacculus and intravascular stent arrival appointed part, sacculus is expanded gradually, open the blood vessel of stenosis or occlusion with the pressure of sacculus.Meanwhile, intravascular stent is opened by sacculus, supports blood vessel, and can't bounce back, and keeps the open state of blood vessel.
Secondly, medical research shows that the vascular restenosis rate successively decreases along with the increase of used drug dose, and therefore keeping local high drug level and secular medicine controlled releasing is treatment smooth muscle cell proliferation, thrombotic main method that vascular damaged caused.So corresponding medication coat or bracket for eluting medicament (drugeluting stent) of having produced.
The coating stent of medicine product of a success should have 3 key elements: support, suppress restenosis medicine, serve as medicine and adhere to carrier coating (being generally high molecular polymer) on the support.Ideal medicine controlled releasing be unable to do without the suitable coating compounds material selection.
Coating material at first must possess excellent biological compatibility; Secondly can in the sufficiently long time, carry out controlled delivery of pharmaceutical agents with the speed of setting and discharge; The 3rd will have the good mechanical performance can not cause coming off of coating or break to ensure apparatus because of deformation takes place in implantation process or in the use after implanting; After finishing, the 4th drug release do not produce inflammatory reaction or thrombosis.The used material of bracket for eluting medicament can't possess above all advantages simultaneously at present, though therefore existing bracket for eluting medicament successfully is used for human body, but still there are some problems, especially advanced thrombus vascular occlusion, this fatal late complication is closely related with used nondegradable macromolecular material.Have some scholars to place hope on the application of degradable material, but also there is problems such as causing the local inflammation reaction easily in catabolite.
Summary of the invention
Technical problem: the objective of the invention is surface modified coat that proposes a kind of intravascular stent and preparation method thereof, this surface modified coat block copolymer has the advantage of the mechanical performance excellence of molecular weight height, narrow molecular weight distribution, good film-forming property, film.
Technical scheme: the polysulfone-polyethylene epoxide block copolymer that utilizes different polyethylene glycol oxide content is as the stent drug coated carrier.Contain inflexible polysulfones segment and flexible polyoxyethylene segments in the structure of polysulfone-polyethylene epoxide block copolymer simultaneously.Polyethylene glycol oxide is a kind of water-soluble polymer, has fabulous biocompatibility.Polyethylene glycol oxide and hydrophobicity polysulfones are formed block copolymer and are had hydrophilic segment and hydrophobic part simultaneously, therefore have amphipathicly, can form micelle in water.
The test of the biocompatibility of polysulfone-polyethylene epoxide block copolymer having been carried out according to the relevant criterion of medical implant, mainly comprise many indexs such as acute general toxicity test, Intradermal stimulation, sensitization, cytotoxicity, Implantation Test, haemolysis, pyrogen testing, the result shows its good biocompatibility.Preliminary animal experiment has also shown the blood compatibility that it is good.This material can be used as the coating of intravascular stent and other medical implants, improves material or apparatus surfaces for biocompatibility.
Can form hydrophilicity and hydrophobicity and the medicine of regulating material significantly by the change copolymer and melt erosion speed, the content of polyethylene glycol oxide directly has influence on the character of copolymer in the block copolymer, both can regulate its medicine carrying performance by the content that changes polyethylene glycol oxide in the polysulfone-polyethylene epoxide block copolymer, also be used for controlling the rate of release of contained drug behind its medicine carrying.
The present invention is dissolved in polysulfone-polyethylene epoxide block copolymer in the organic solvent, obtains polysulfone-polyethylene epoxide block copolymer solution, and used organic solvent is oxolane, chloroform, isopropyl alcohol, 1, a kind of in the 4-dioxane; Perhaps add medicine, obtain containing drug solns at above-mentioned polysulfone-polyethylene epoxide block copolymer solution.Adopt rotary spraying, dipping, ultrasonic spraying or other spraying method to form modified coating then at rack surface.
The surface modified coat of intravascular stent of the present invention is polysulfones-polyethylene oxide block copolymer, the quality percentage composition of the polyethylene glycol oxide in described polysulfones-polyethylene oxide block copolymer is 1%-70%, and the number-average molecular weight of polysulfones-polyethylene oxide block copolymer is 10000～300000; This modified coating is coated on the intravascular stent surface and makes the not coating of pastille; Perhaps in the aforementioned solution that contains polysulfones-polyethylene oxide block copolymer, add medicine with pre-preventing restenosis of blood vessel, be coated on the intravascular stent surface then and make drug-carried coat, the quality percentage composition of medicine in polysulfones-polyethylene oxide block copolymer is 0.1%-40%.
The surface modified coat of the intravascular stent of making is the single coating structure, and so-called single coating structure is meant that in one or more layers coating the polyethylene glycol oxide content in polysulfones-polyethylene oxide block copolymer is identical, and the gross thickness of each coating is the 1-200 micron.The surface modified coat of the intravascular stent of making is a composite coating structure, and described composite coating structure is meant coating branch multilamellar, every layer of composition difference that coating is contained, and every layer thickness is the 1-180 micron, the gross thickness of coating is the 1-200 micron; The contained composition different manifestations of coating is:
1) add or do not add medicine in each coating, adding medicine is one or more;
2) polyethylene glycol oxide content difference in each coating body polysulfones-polyethylene oxide block copolymer;
3) medicine that adds in each coating is identical, but the drug level difference;
4) the medicine difference of adding in each coating,
Described composite coating structure is meant alternately coats the accurate controlled release that the intravascular stent surface is beneficial to medicine with the aforementioned coating solution that contains heterogeneity or various combination.
Added medicine is: divide a word with a hyphen at the end of a line medicine, short endothelium healing medicine and other of antithrombotic reagent, anti-inflammatory medicaments, anti-VSMC propagation medicine, anti-VSMC have a kind of in the medicine of prevention of restenosis effect or several mixture.Described intravascular stent comprises arterial bracket, vein support, filter, stopper, cardiac valve, other implanted medical device.
Polysulfones-polyethylene oxide block copolymer is dissolved in the organic solvent, obtains polysulfone-polyethylene epoxide block copolymer solution; In this copolymer solution, the quality percentage composition of polysulfones-polyethylene oxide block copolymer is 0.1%-40%, this copolymer solution is coated on the intravascular stent surface makes the not coating of pastille; Perhaps add the medicine with pre-preventing restenosis of blood vessel in the aforementioned solution that contains polysulfones-polyethylene oxide block copolymer, be coated on the intravascular stent surface then and make drug-carried coat, concrete making step is:
1) ultrasonic surface of support cleans and oven dry: keep the support clean dried,
2) configuration of coating solution: polysulfones-polyethylene oxide block copolymer is dissolved in the organic solvent, and the quality percentage composition of polysulfones-polyethylene oxide block copolymer is 0.1-40w%; Add medicine in the coating solution of preparation, the quality percentage composition of medicine in polysulfones-polyethylene oxide block copolymer is 0.1%-40w%,
3) face coat: adopt the ultrasonic atomizatio method, in the spraying of rack surface ultrasonic atomization repeatedly, coating layer thickness 1-200 micron,
4) vacuum drying: coating bracket is inserted vacuum drying oven, and room temperature oven dry is down adorned box or standby after 48 hours.
Described organic solvent is oxolane, chloroform, isopropyl alcohol, 1, a kind of in the 4-dioxane.Described surface coating method is the infusion process coating, is specially support was soaked in coating solution 1-10 minute, takes out normal temperature drying, repeatedly soaks drying again, until satisfying required thickness.
The medication coat that the present invention uses goes for the various medicines that may be dissolved in the above-mentioned organic solvent, for example antithrombotic reagent heparin, hirudin, prostacyclin, abciximab etc.; Anti-inflammatory medicaments is as dexamethasone (DXM), methyl meticortelone, Diphosphonate liposome etc.; Anti-VSMC propagation medicine comprises rapamycin (RAPM) and paclitaxel (PTX), angiopeptin, Mycophenolic Acid, Tracolimus, Everolimus, ciclosporin A, methyl-RAPM etc.; The anti-VSMC medicine of dividing a word with a hyphen at the end of a line is as batimastat etc.; Short endothelium healing medicine is as 17 β estradiol, VEGF etc.; Other drug is as ligustrazine and with the compatibility of Chinese medicine astragalus, ginseng arteries and veins, emodin etc. etc.
The surface modified coat that the present invention uses goes for the surface modification of arterial brackets such as coronary stent, carotid stents, cerebral arteries support, aortic stents, also is applicable to the surface modification of implanted medical devices such as vein support, filter, stopper, cardiac valve.
Surface modified coat of the present invention is not limited only to the surface modification of intravascular stent, the surface modification that also is used for non-vessel stent, comprise alimentary stents such as esophageal stents appear, biliary tract rack, intestinal support, with trachea bracket, urethra rack etc., also be used for the face coat of the implant of the long-term or short term contact of other and human body.
Beneficial effect: the present invention is at first according to the requirement of implanting has been carried out evaluation of its biocompatibility to the polysulfone-polyethylene epoxide block copolymer of different polyethylene glycol oxide content, mainly comprise many indexs such as acute general toxicity test, Intradermal stimulation, sensitization, cytotoxicity, Implantation Test, haemolysis, pyrogen testing, the result shows that it has excellent biological compatibility.Adopt ultrasonic atomizatio spraying coating process cost low, the yield rate height has repeatability, and coating layer thickness is controlled.By the reasonable disposition coating process, coating is stable, has elasticity, with metal support surface absorption firmly, coating evenly, surfacing, no adhesion, do not have twine, no clogging.Coating bracket expansion back coating structure is complete, does not have defectives such as ftractureing, peel off.Drug release behind the coating medicine carrying meets the release rule (accompanying drawing 3) of the existing commercial drug stent that uses, and drug release rate is relatively milder, even.The drug stent that uses this coating has been carried out the animal experiment that the pig arteria coronaria is implanted, and one month result shows that blood vessel does not have restenosis, and this coating of clinical use is feasible, has very big using value, and market prospect is wide.
Description of drawings
Fig. 1 is a kind of single coating structure chart, and wherein 1 is rack body, and 2 is the polysulfone-polyethylene epoxide block copolymer inert coatings of not pastille.
Fig. 2 is a kind of composite coating structure figure, wherein 1 is rack body, 2 is the polysulfone-polyethylene epoxide block copolymer inert coatings of not pastille, and 3 is the polysulfone-polyethylene epoxide block copolymer coating of first kind medicine, and 4 for carrying the polysulfone-polyethylene epoxide block copolymer coating of second kind medicine.
Fig. 3 is medicine carrying (paclitaxel, 10wt% drug loading), 30% polyethylene glycol oxide content polysulfone-polyethylene epoxide block copolymer bracket coating at 37 ℃, volume ratio is drug release curve chart in ethanol/buffer solution of 10: 90.
The specific embodiment
The following examples are to further specify of the present invention, rather than limit the scope of the invention.
The surface modified coat of intravascular stent of the present invention is polysulfones-polyethylene oxide block copolymer, the quality percentage composition of the polyethylene glycol oxide in described polysulfones-polyethylene oxide block copolymer is 1%-70%, and the number-average molecular weight of polysulfones-polyethylene oxide block copolymer is 10000～300000; This modified coating is coated on the intravascular stent surface and makes the not coating of pastille; Perhaps in the aforementioned solution that contains polysulfones-polyethylene oxide block copolymer, add medicine with pre-preventing restenosis of blood vessel, be coated on the intravascular stent surface then and make drug-carried coat, the quality percentage composition of medicine in polysulfones-polyethylene oxide block copolymer is 0.1%-40%.
The surface modified coat of the intravascular stent of making is the single coating structure, and so-called single coating structure is meant that in one or more layers coating the polyethylene glycol oxide content in polysulfones-polyethylene oxide block copolymer is identical, and the gross thickness of each coating is the 1-200 micron.The surface modified coat of the intravascular stent of making is a composite coating structure, and described composite coating structure is meant coating branch multilamellar, every layer of composition difference that coating is contained, and every layer thickness is the 1-180 micron, the gross thickness of coating is the 1-200 micron; The contained composition different manifestations of coating is:
1) add or do not add medicine in each coating, adding medicine is one or more;
2) polyethylene glycol oxide content difference in each coating body polysulfones-polyethylene oxide block copolymer;
3) medicine that adds in each coating is identical, but the drug level difference;
4) the medicine difference of adding in each coating,
Described composite coating structure is meant alternately coats the accurate controlled release that the intravascular stent surface is beneficial to medicine with the aforementioned coating solution that contains heterogeneity or various combination.Added medicine is: divide a word with a hyphen at the end of a line medicine, short endothelium healing medicine and other of antithrombotic reagent, anti-inflammatory medicaments, anti-VSMC propagation medicine, anti-VSMC have a kind of in the medicine of prevention of restenosis effect or several mixture.Described intravascular stent comprises arterial bracket, vein support, filter, stopper, cardiac valve, other implanted medical device.
1) cleaning of support: support was put into the acetone ultrasonic waves for cleaning 20 minutes, then put into 60-100 degree centigrade hot water ultrasonic waves for cleaning 20 minutes, put into medical disinfecting ethanol ultrasonic waves for cleaning then 10 minutes, took out dry for standby at last.
2) preparation of coating solution: measure 15 milliliters of oxolanes and insert in the tool plug flask, weighing polyethylene glycol oxide content is 560 milligrams of polysulfones-polyethylene oxide block copolymer of 35% then, the jam-pack bottle stopper is fixed on to shake on the shaking table and dissolved fully until copolymer in 20-60 minute.
3) end with cleaned support is fixed in the rotating shaft of the motor that can be rotated motion and move forward and backward.
4) the syringe pump extraction step 2) solution of being joined, utilize ultrasonic nozzle, with its atomizing, be applied to rack surface then.Utilize moving back and forth of support to finish its 10 times sprayings.
5) take off support from rotating shaft, retighten the support other end, repeating step 4) spraying process, finishing for the first time, stiff end is not coated with part.
6) take out support, put under the vacuum drying oven room temperature and dried 48 hours, do not contained the polymeric coating layer intravascular stent of medicine.
1) cleaning of support: support was put into the acetone ultrasonic waves for cleaning 20 minutes, then put into 60-100 degree centigrade hot water ultrasonic waves for cleaning 20 minutes, put into medical disinfecting ethanol ultrasonic waves for cleaning then 10 minutes, took out dry for standby at last.
2) preparation of coating solution: measure 15 milliliters of oxolanes and insert in the tool plug flask, weighing polyethylene glycol oxide content is 600 milligrams of polysulfones-polyethylene oxide block copolymer of 35% then, the jam-pack bottle stopper is fixed on to shake on the shaking table and dissolved fully until copolymer in 20-60 minute; Place shaking table to shake again after in this solution, adding 200 milligrams of drug rapamycin to dissolving.
3) end with cleaned support is fixed in the rotating shaft of the motor that can be rotated motion and move forward and backward.
4) the syringe pump extraction step 2) solution of being joined, utilize ultrasonic nozzle, with its atomizing, be applied to rack surface then.Utilize moving back and forth of support to finish 10 sprayings.
5) take off support from rotating shaft, retighten the support other end, repeating step 4) spraying process, finish support for the first time stiff end be not coated with the spraying of part.
6) take out support, put under the vacuum drying oven room temperature and dried 48 hours, obtain containing the coating blood vessel support of medicine rapamycin.
1) cleaning of support: support was put into the acetone ultrasonic waves for cleaning 20 minutes, then put into 60-100 degree centigrade hot water ultrasonic waves for cleaning 20 minutes, put into medical disinfecting ethanol ultrasonic waves for cleaning then 10 minutes, took out dry for standby at last.
2) preparation of coating solution: measure 15 milliliters of oxolanes and insert in the tool plug flask, weighing polyethylene glycol oxide content is 500 milligrams of polysulfones-polyethylene oxide block copolymer of 45% then, the jam-pack bottle stopper is fixed on to shake on the shaking table and dissolved fully until copolymer in 20-60 minute; Place shaking table to shake again after in this solution, adding 150 milligrams of medicine ligustrazine to dissolving.
3) end with cleaned support is fixed in the rotating shaft of the motor that can be rotated motion and move forward and backward.
4) the syringe pump extraction step 2) solution of being joined, utilize ultrasonic nozzle, with its atomizing, be applied to rack surface then.Utilize moving back and forth of support to finish 10 sprayings.
5) take off support from rotating shaft, retighten the support other end, repeating step 4) spraying process, finish support for the first time stiff end be not coated with the spraying of part.
6) take out support, put under the vacuum drying oven room temperature and dried 48 hours, obtain containing the polymeric coating layer intravascular stent of medicine.
1) cleaning of support: support was put into the acetone ultrasonic waves for cleaning 20 minutes, then put into 60-100 degree centigrade hot water ultrasonic waves for cleaning 20 minutes, put into medical disinfecting ethanol ultrasonic waves for cleaning then 10 minutes, took out dry for standby at last.
2) coating solution A preparation: measure 20 milliliters of oxolanes and insert in the tool plug flask, weighing polyethylene glycol oxide content is 600 milligrams of polysulfones-polyethylene oxide block copolymer of 45% then, the jam-pack bottle stopper is fixed on to shake on the shaking table and dissolved fully until copolymer in 20-60 minute; Place shaking table to shake again after in this solution, adding 250 milligrams of drug rapamycin to dissolving, solution A.
3) coating solution B preparation: measure 10 milliliters of oxolanes and insert in the tool plug flask, weighing polyethylene glycol oxide content is 300 milligrams of polysulfones-polyethylene oxide block copolymer of 30% then, the jam-pack bottle stopper is fixed on to shake on the shaking table and dissolved fully until copolymer in 20-60 minute; Place shaking table to shake again after in this solution, adding 50 milligrams of medicine heparin to dissolving, solution B.
4) end with cleaned support is fixed in the rotating shaft of the motor that can be rotated motion and move forward and backward.
5) syringe pump extracts solution A, utilizes ultrasonic nozzle, with its atomizing, is applied to rack surface then.Utilize moving back and forth of support to finish 10 sprayings.
6) take off support from rotating shaft, retighten the support other end, repeating step 5) spraying process, finish support for the first time stiff end be not coated with the spraying of part.
7) syringe pump is extracted thing and changes solution B into, repeating step 4), 5), 6), but utilize moving back and forth of support to finish 5 sprayings.
8) take out support, put under the vacuum drying oven room temperature and dried 24 hours, obtain containing the polymeric coating layer intravascular stent of two kinds of medicines.
Embodiment 5
1) cleaning of support: support was put into the acetone ultrasonic waves for cleaning 20 minutes, then put into 60-100 degree centigrade hot water ultrasonic waves for cleaning 20 minutes, put into medical disinfecting ethanol ultrasonic waves for cleaning then 10 minutes, took out dry for standby at last.
2) preparation of coating solution A: measure 30 milliliters of oxolanes and insert in the tool plug flask, weighing polyethylene glycol oxide content is 1000 milligrams of polysulfones-polyethylene oxide block copolymer of 35% then, the jam-pack bottle stopper, be fixed on to shake on the shaking table and dissolved fully until copolymer in 20-60 minute, obtain solution A.
3) preparation of coating solution B: take out 1/3rd solution A, place shaking table to shake again after adding 100 milligrams of drug taxol therein to dissolving, solution B.
4) preparation of coating solution C: take out 1/3rd solution A, add 50 milligrams of medicine heparin therein and place shaking table to shake again, get solution C to dissolving.
5) end with cleaned support is fixed in the rotating shaft of the motor that can be rotated motion and move forward and backward.
6) syringe pump extracts solution B, utilizes ultrasonic nozzle, with its atomizing, is applied to rack surface then.Utilize moving back and forth of support to finish 10 sprayings.
7) take off support from rotating shaft, retighten the support other end, repeating step 6) spraying process, finish support for the first time stiff end be not coated with the spraying of part.
8) syringe pump is extracted thing and changes solution C into, repeating step 4), 5), 6), but utilize moving back and forth of support to finish 5 sprayings.
9) syringe pump is extracted thing and changes solution A into, repeating step 4), 5), 6), but utilize moving back and forth of support to finish 3 sprayings.
10) take out support, put under the vacuum drying oven room temperature and dried 48 hours, obtain containing polymeric coating layer intravascular stent two kinds of medicines and that inert layer is arranged.
Make not 4 pieces of pastille coating blood vessel supports by the manufacture method of embodiment 1, implant the coronary artery of 2 health pig respectively; Press the manufacture method of embodiment 2 in addition and make 8 pieces of rapamycins coating intravascular stents, implant the coronary artery of 4 health pig respectively; Simultaneously 6 pieces of naked metal racks are implanted the coronary artery of 3 health pig respectively.It is good that the digital at once radiography of postoperative shows that support discharges, and has no adverse reaction.Line number word radiography and intravascular ultrasound check are checked to show that vascular flow is unobstructed after 4 weeks, and no thrombosis takes place, and the support portions caliber changes very little, and coating bracket all is better than bare bracket, and drug-carried coat support result is better than not pastille coating bracket.
Claims (8)
1. the surface modified coat of an intravascular stent, it is characterized in that this modified coating is polysulfones-polyethylene oxide block copolymer, the quality percentage composition of the polyethylene glycol oxide in described polysulfones-polyethylene oxide block copolymer is 1%-70%, and the number-average molecular weight of polysulfones-polyethylene oxide block copolymer is 10000～300000; This modified coating is coated on the intravascular stent surface and makes the not coating of pastille; Perhaps in the aforementioned solution that contains polysulfones-polyethylene oxide block copolymer, add medicine with pre-preventing restenosis of blood vessel, be coated on the intravascular stent surface then and make drug-carried coat, the quality percentage composition of medicine in polysulfones-polyethylene oxide block copolymer is 0.1%-40%.
2. the surface modified coat of intravascular stent according to claim 1, the surface modified coat that it is characterized in that the intravascular stent made is the single coating structure, so-called single coating structure is meant in one or more layers coating, polyethylene glycol oxide content in polysulfones-polyethylene oxide block copolymer is identical, and the gross thickness of each coating is the 1-200 micron.
3. the surface modified coat of intravascular stent according to claim 1, the surface modified coat that it is characterized in that the intravascular stent made is a composite coating structure, described composite coating structure is meant coating branch multilamellar, every layer of composition difference that coating is contained, every layer thickness is the 1-180 micron, and the gross thickness of coating is the 1-200 micron; The contained composition different manifestations of coating is:
1) add or do not add medicine in each coating, adding medicine is one or more;
2) polyethylene glycol oxide content difference in each coating body polysulfones-polyethylene oxide block copolymer;
3) medicine that adds in each coating is identical, but the drug level difference;
4) the medicine difference of adding in each coating,
Described composite coating structure is meant alternately coats the accurate controlled release that the intravascular stent surface is beneficial to medicine with the aforementioned coating solution that contains heterogeneity or various combination.
4. according to the surface modified coat of claim 1 or 3 described intravascular stents, it is characterized in that added medicine is: divide a word with a hyphen at the end of a line medicine, short endothelium healing medicine and other of antithrombotic reagent, anti-inflammatory medicaments, anti-VSMC propagation medicine, anti-VSMC have a kind of in the medicine of prevention of restenosis effect or several mixture.
5. the surface modified coat of intravascular stent according to claim 1 is characterized in that described intravascular stent comprises arterial bracket, vein support, filter, stopper, cardiac valve, other implanted medical device.
6. the preparation method of the surface modified coat of an intravascular stent as claimed in claim 1 is characterized in that polysulfones-polyethylene oxide block copolymer is dissolved in the organic solvent, obtains polysulfones-polyethylene oxide block copolymer solution; In this copolymer solution, the quality percentage composition of polysulfones-polyethylene oxide block copolymer is 0.1%-40%, this copolymer solution is coated on the intravascular stent surface makes the not coating of pastille; Perhaps add the medicine with pre-preventing restenosis of blood vessel in the aforementioned solution that contains polysulfones-polyethylene oxide block copolymer, be coated on the intravascular stent surface then and make drug-carried coat, concrete making step is:
1) ultrasonic surface of support cleans and oven dry: keep the support clean dried,
2) configuration of coating solution: polysulfones-polyethylene oxide block copolymer is dissolved in the organic solvent, and the quality percentage composition of polysulfones-polyethylene oxide block copolymer is 0.1-40w%; Add medicine in the coating solution of preparation, the quality percentage composition of medicine in polysulfones-polyethylene oxide block copolymer is 0.1%-40w%,
3) face coat: adopt the ultrasonic atomizatio method, in the spraying of rack surface ultrasonic atomization repeatedly, coating layer thickness 1-200 micron,
4) vacuum drying: coating bracket is inserted vacuum drying oven, and room temperature oven dry is down adorned box or standby after 48 hours.
7. the preparation method of the surface modified coat of intravascular stent as claimed in claim 6 is characterized in that described organic solvent is oxolane, chloroform, isopropyl alcohol, 1, a kind of in the 4-dioxane.
8. the preparation method of the surface modified coat of intravascular stent as claimed in claim 6, it is characterized in that described surface coating method is the infusion process coating, be specially support was soaked in coating solution 1-10 minute, take out normal temperature drying, repeatedly soak drying again, until satisfying required thickness.
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| CN101279111B (en) * | 2008-05-15 | 2011-06-22 | 哈尔滨工程大学 | Method for preparing blood vessel stent with polyester medicament eluting coating |
| CN103566418A (en) * | 2013-08-13 | 2014-02-12 | 重庆大学 | Preparation method of multi-coating drug eluting intravascular stent |
| CN105833360A (en) * | 2016-03-25 | 2016-08-10 | 西南交通大学 | Preparation method of anti-vascular calcification degradable drug-carrying coated scaffold |
| CN106390211A (en) * | 2016-08-30 | 2017-02-15 | 南京永明医疗器械有限公司 | Surface coating composition of implantable medical apparatus, medical apparatus and manufacturing method of medical apparatus |
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| CN111035485A (en) * | 2019-12-16 | 2020-04-21 | 西南交通大学 | Intravascular stent and preparation method and application thereof |
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- 2007-04-13 CN CN200710021454A patent/CN100577221C/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101279111B (en) * | 2008-05-15 | 2011-06-22 | 哈尔滨工程大学 | Method for preparing blood vessel stent with polyester medicament eluting coating |
| CN103566418A (en) * | 2013-08-13 | 2014-02-12 | 重庆大学 | Preparation method of multi-coating drug eluting intravascular stent |
| CN103566418B (en) * | 2013-08-13 | 2016-01-20 | 重庆大学 | A kind of preparation method of laminated coating drug eluting vascular support |
| CN105833360A (en) * | 2016-03-25 | 2016-08-10 | 西南交通大学 | Preparation method of anti-vascular calcification degradable drug-carrying coated scaffold |
| CN106390211A (en) * | 2016-08-30 | 2017-02-15 | 南京永明医疗器械有限公司 | Surface coating composition of implantable medical apparatus, medical apparatus and manufacturing method of medical apparatus |
| CN106623220A (en) * | 2016-12-28 | 2017-05-10 | 苏州华碧微科检测技术有限公司 | Method for cleaning fracture of medical metal bone plate |
| CN107308506A (en) * | 2017-07-23 | 2017-11-03 | 北京化工大学 | A kind of anti-inflammatory method of modifying based on the medical terylene set of haemodialysis |
| CN111035485A (en) * | 2019-12-16 | 2020-04-21 | 西南交通大学 | Intravascular stent and preparation method and application thereof |
| CN113144376A (en) * | 2021-04-16 | 2021-07-23 | 上海市胸科医院 | Nano double-resistance deep venous catheter |
| CN113144376B (en) * | 2021-04-16 | 2024-03-29 | 上海市胸科医院 | Nanometer double-resistance deep vein catheter |
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