CN1524590A - Medicament elution interventional medical apparatus and preparing method thereof - Google Patents
Medicament elution interventional medical apparatus and preparing method thereof Download PDFInfo
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- CN1524590A CN1524590A CNA031155960A CN03115596A CN1524590A CN 1524590 A CN1524590 A CN 1524590A CN A031155960 A CNA031155960 A CN A031155960A CN 03115596 A CN03115596 A CN 03115596A CN 1524590 A CN1524590 A CN 1524590A
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- medicament elution
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Abstract
The invention discloses a medicament elution intervene medical appliance and method for making same, wherein a speed control layer is arranged on the medicament elution intervene medical appliance to realize the control of release rate for the medicament from the support bracket, the coating layer is made of dimethylbenzene through vacuum vapor deposition at indoor temperature needing no dissolvent and catalyst, the coating thickness is generally 0.01-10 micrometer. The novel coating can effectively control the release for medicament in particular for medicament with small molecular weight, thus achieving the effect of long-term slow release treatment.
Description
Technical field
The present invention relates to a kind of medical apparatus and instruments, be specifically related to a kind of interventional medical device of pastille.
Technical background
Along with the raising of medical procedure, implanted medical device is introduced places such as esophagus, air flue, colon, biliary tract urethra, vascular system and become more and more usual.For example, many vascular lesions need be introduced support, conduit, sacculus silk-guiding etc.But these medical apparatus and instruments cause blood vessel injury through regular meeting when passing lesion region, and the blood coagulation of injury region and thrombosis may cause the narrow or inaccessible of blood vessel.More be worth the thing of putting forward, surpass certain hour if apparatus is detained in blood vessel, the apparatus surface forms thrombosis through regular meeting, thereby can cause narrowly or inaccessible once more, and the patient is placed in the dangerous edge of multiple complications as a result.Remove these risks, medical apparatus and instruments must carry out some improvement.
Another approach that causes angiostenosis is a disease, and modal is coronary atherosclerosis.Atherosclerosis causes that luminal stenosis or obstruction are the main causes that causes ischemic heart desease (coronary heart disease), causes 500 every year, 000-600,000 people's death.Percutaneous transluminal coronary angioplasty (PTCA) adopts full inaccessible or narrow blood vessel is expanded of sacculus to open, and makes blood supply recover normal, is accepted and be applied to treat coronary heart disease widely at present.Though PTCA treatment coronary heart disease clinical effectiveness is satisfactory, its acute vascular obturation and postoperative vascular restenosis have limited the development of PTCA to a certain extent.It is reported 10% patient when PTCA, acute or subacute coronary occlusion can take place; Behind the PTCA by the probability of the coronary artery generation restenosis expanded then up to 30-50% (referring to Popma, J.J.et al., Circulation, 84,1426-1436 (1991); And Gruentzig, A.R.et al., N Engl J Med, 316,1127-1132 (1987)).Acute or subacute coronary occlusion is mainly because elasticity of blood vessels bounces back and/or platelet causes in lesion deposition and then formation thrombosis.Restenosis is caused by multiple factor behind the PTCA, comprises the elasticity of blood vessels retraction, platelet deposition and artery thrombosis, neointimal hyperplasia etc.
For PTCA, intravascular stent is very useful adnexa, is especially running into the acute obturation of postangioplasty.Support is implanted to the expansion artery place, prevents unexpected obturation or restenosis by mechanical support.Unfortunately, although in the implant frame process, carry out antiplatelet, anticoagulant therapy by systemic administration, the incidence rate of thrombotic vascular occlusion and complication thereof is still very serious.And also get nowhere-producing in-stent restenosis aspect the pre-preventing restenosis of blood vessel.Rising because PTCA and discharge the damage that the support process causes for the local vascular inner membrance of in-stent restenosis, thus tunica intima hamartoplasia stimulated.In addition, support is inserted the directly long-term contact of heel blood can cause thrombosis (probability is 20-25%), and stimulates the hypertrophy of smooth muscle cell, causes that blood vessel is narrow once more.How solving in-stent restenosis becomes the focus and the difficult problem of coronary heart disease interventional therapy, is perplexing patient and doctor for a long time.
People thought that a lot of methods handled neointimal hyperplasia and reduce restenosis.Although all these methods have success in various degree more, there is not a kind of method fundamentally thoroughly to avoid the generation of restenosis.The scheme of PTCA postoperative Drug therapy restenosis is relatively success in zoopery, but poor effect clinically.
People are interested in the support carrying medicaments at present.It controls medicine in endovascular release by degradable or non-degradation polymer.With regard to this approach, also do not accomplish complete success.The medicine of finding that can suppress neointimal hyperplasia is a lot of at present, mainly concentrates on several aspects such as immunosuppressant, cancer therapy drug, anti-inflammatory drug, antiplatelet drug.But various medicines widely different on molecular weight (little of two or three hundred, as to arrive tens thousand of greatly) are even cause same carrier completely identical to the sustained release ability of different pharmaceutical.Therefore medicine is even inadequately, effective from the process that support discharges, and healing potion discharges when really needing in the time of most.In addition, before endothelialization, the release of medicine may cause more serious consequence, especially when drug toxicity is bigger.In addition, initial burst release meeting causes the delay of endothelialization process.Based on above reason, the urgent hope of people can provide some restenosiss that reduce postangioplasty or hypertrophy and don't stop the medical apparatus and instruments of blood vessel endothelium process.
Summary of the invention
The technical issues that need to address of the present invention provide a kind of medicament elution interventional medical device and preparation method thereof, to overcome the above-mentioned defective that prior art exists, satisfy people's demand.
Technical conceive of the present invention is such:
The inventor is provided with one deck rate controlled layer (compacted zone) on the medicine layer of medicament elution interventional medical device, thereby reaches the speed that the control medicine discharges from support.
Technical scheme of the present invention:
A kind of medicament elution interventional medical device, comprise the apparatus body, be coated in the apparatus surface the medicine that has the different molecular weight that contains therapeutical effect in one deck coating at least coating and at least one deck be coated in rate controlled layer on the medicine layer.
Said rate controlled layer by must degraded or erosion material make, preferably comprise polytetrafluoroethylene (PTFE), Parylene (Parylene, Parylene) and derivant.
According to the present invention, rate controlled layer thickness 0.01-10 micron.
According to the present invention, have at least one deck rate controlled layer to form by the Parylene or derivatives thereof.
Said Parylene (Parylene) is the trade name of Parylene; Parylene is a kind of novel coating material of middle nineteen sixties U.S. Union Carbide Co. Application and Development.
The apparatus of being addressed comprises sacculus, conduit, seal wire or support, and support especially is as the coronary artery bracket and the 02266010.0 disclosed intracranial stent of ZL00217528.2 or ZL01246774 patent disclosure.
The molecular weight of rate controlled strata compound is 300,000～600,000, by regulating sedimentation time and pressure etc., can form the rate controlled layer of different-thickness, different aperture.
The medicine of said different molecular weight comprises a kind of in immunosuppressant, cancer therapy drug, anti-inflammatory drug, the antiplatelet drug etc., as a kind of or and the compositions in Rapamycin, Radix Tripterygii Wilfordii monomer and derivant thereof, FTY720, Epo-D, 10-hydroxycamptothecine, dexamethasone, the cilostazol (Cilostazol).
The system method of apparatus of the present invention comprises the steps:
(1) adopt conventional method on the apparatus of being addressed, to apply the medicine of different molecular weight;
(2) adopt method method cracking xylol dimer well known in the art, obtain monomer whose steam, the apparatus that step (1) is coated with medicine places room temperature deposition indoor, feed monomer vapor, form the polymer of one deck even compact on the apparatus surface, be the rate controlled layer, thereby obtain medicament eluting instrument of the present invention;
Observation Parylene coating shows the slow release effect of different molecular weight: under the identical situation of Parylene coating layer thickness, and its rate of release difference of the medicine of different molecular weight, molecular weight is big more, discharges slow more.And along with the increase of coating layer thickness, its rate of release is slack-off.By above-mentioned disclosed technical scheme as seen, rate controlled layer on the apparatus disclosed by the invention is prepared from by xylol dimer room temperature vacuum vapor deposition, solvent-free, catalyst-free, coating procedure does not influence the activity of medicine, and the thickness of coating is generally the 0.01-10 micron, can control the release of medicine effectively, especially the release of small-molecular weight medicine reaches the effect of long-term slow release treatment.
Description of drawings
Fig. 1 is the release in vitro curve of Parylene coating control different molecular weight medicine of the present invention.
Fig. 2 is the release in vitro curve of Parylene coating control small-molecular weight medicine of the present invention.
The specific embodiment
Embodiment 1
The preparation method of Parylene coating.
At first xylol is heated to 950 ℃, generate the xylol dimer, then 680 ℃ of following cracking, form monomer vapours, it is indoor that stainless steel stent is placed on room temperature deposition, feeds monomer vapor, forms the polymer of one deck even compact on the stainless steel stent surface, the molecular weight of polymer is estimated about 500,000.
Embodiment 2
4 parts of polylactic acid, 1 part of polycaprolactone are dissolved in 100 parts of chloroforms, add 2 parts of small-molecular weight medicine Cilostazol and 2 parts of macromolecule medicine Rapamycin again, be uniformly dispersed under the room temperature condition, be sprayed at rack surface, vacuum drying, 30 ℃ of temperature.Then, the method for employing embodiment 1 is coated with and is covered with the Parylene coating, observes the slow release effect of Parylene coating to different molecular weight, sees Fig. 1.The result shows: under the identical situation of Parylene coating layer thickness, and its rate of release difference of the medicine of different molecular weight, molecular weight is big more, discharges slow more.And along with the increase of coating layer thickness, its rate of release is slack-off.
1 part of polybutyl methacrylate, 1 part of ethylene-acetate ethylene copolymer are dissolved in 100 parts of oxolanes, add 1 part of small-molecular weight medicine 10-hydroxycamptothecine again, be uniformly dispersed under the room temperature condition, be sprayed at the stainless steel stent surface, in 40 ℃ of vacuum drying ovens, dry.Then, handle, observe different coating layer thickness (as 0.05 micron, 0.4 micron, 1 micron) and, see Fig. 2 the release of small-molecular weight controlled delivery of pharmaceutical agents with the Parylene coating.The result shows: the Parylene coating can be controlled the slow release of small-molecular weight medicine effectively.Coating is thick more, and the space is few more, and drug releasing rate is slow more, promptly can reach the purpose of expected drug rate of release by the thickness of control Parylene coating.
Embodiment 4
4 parts of lactide caprolactone copolymers are dissolved in 100 parts of chloroformic solutions, add 2 parts of small-molecular weight medicine FTY720 again, be sprayed at the surface of support, behind 50 ℃ of vacuum dryings, handle with the Parylene vapor deposition polymerization.Extracorporeal releasing experiment shows, compares with matched group support (support that Parylene of no use is handled) with the drug stent that Parylene is handled, and rate of release obtains good control, can reach the purpose of the long-term slow release treatment of medicine.
2 parts of polybutyl methacrylates are dissolved in 100 parts of n-butyl acetates, add 1 part of small-molecular weight medicine (Epo-D) again, be uniformly dispersed under the room temperature condition, be sprayed at the stainless steel stent surface, in 30 ℃ of vacuum drying ovens, dry.Then, handle with the Parylene coating.The result shows: the Parylene coating can be controlled the slow release of small-molecular weight medicine effectively.Release time can be from 1 day to 90 days.
Embodiment 6
2 parts of lactide caprolactone copolymers are dissolved in 100 parts of chloroformic solutions, add 2 parts of small-molecular weight medicine Radix Tripterygii Wilfordiis again, be sprayed at the surface of rustless steel intracranial stent, behind 40 ℃ of vacuum dryings, handle with the Parylene vapor deposition polymerization.Extracorporeal releasing experiment shows, compares with matched group support (support that Parylene of no use is handled) with the drug stent that Parylene is handled, and rate of release obtains good control, can reach the purpose of the long-term slow release treatment of medicine.
After this support suffers from the entocranial artery of glioma animal model in implantation, can effectively suppress to wither away until glioma.
Embodiment 7
The protective action example of Parylene coating.
In surperficial vapour deposition one deck Parylene coating of drug stent, medicine layer that can the protective cradle surface.When doing the PTCA operation, support is transported to diseased region by sacculus.Support contacts for a long time with sacculus, and the medicine layer of rack surface is easy to be bonded together with sacculus, thus the damage medicine layer.Parylene coating of the present invention is a kind of inertia barrier layer, and experiment finds, on the surface of drug stent or after handle with Parylene on the surface of sacculus, all can prevent bonding between bracket coating and the sacculus effectively.
Embodiment 8
Drug stent extracorporeal releasing experiment assay method of the present invention.
Support is placed extracorporeal circulation apparatus respectively, add 10% alcoholic solution of 200ml, keeping temperature is 37 ± 0.5 ℃, changes release medium weekly one time.
At 1h, 1 day, 7 days, 28 days, 30 days taking-up drug stents,, calculate release rate respectively with the amount that HPLC analyzes the medicine that discharges.
Claims (10)
1. medicament elution interventional medical device, comprise the apparatus body and be coated in the coating of the medicine that has the different molecular weight that contains therapeutical effect in one deck coating at least of apparatus surface, it is characterized in that also comprising that one deck at least is coated in the rate controlled layer on the medication coat.
2. medicament elution interventional medical device according to claim 1 is characterized in that, said rate controlled layer by must degraded or erosion material make.
3. medicament elution interventional medical device according to claim 2 is characterized in that, said rate controlled layer comprises polytetrafluoroethylene (PTFE) or Parylene (Parylene) and derivant thereof.
4. medicament elution interventional medical device according to claim 3 is characterized in that, has at least one deck rate controlled layer to be made up of the Parylene or derivatives thereof.
5. medicament elution interventional medical device according to claim 1 is characterized in that, rate controlled layer thickness 0.01-10 micron.
6. medicament elution interventional medical device according to claim 1 is characterized in that, the molecular weight of the polymer of rate controlled layer is 300,000～600,000.
7. medicament elution interventional medical device according to claim 1 is characterized in that, the medicine of said different molecular weight comprises a kind of in immunosuppressant, cancer therapy drug, anti-inflammatory drug, the antiplatelet drug.
8. medicament elution interventional medical device according to claim 7, it is characterized in that the medicine of being addressed comprises a kind of or and the compositions in Rapamycin, Radix Tripterygii Wilfordii monomer and derivant thereof, FTY720, Epo-D, 10-hydroxycamptothecine, dexamethasone, the cilostazol (Cilostazol).
9. according to each described medicament elution interventional medical device of claim 1～8, it is characterized in that the apparatus of being addressed comprises foley's tube, seal wire or support.
10. according to the preparation method of each described medicament elution interventional medical device of claim 1～9, it is characterized in that comprising the steps:
(1) adopt conventional method on the apparatus of being addressed, to apply the medicine of different molecular weight;
(2) adopt method method cracking xylol dimer well known in the art, obtain monomer whose steam, the apparatus that step (1) is coated with medicine places room temperature deposition indoor, feed monomer vapor, form the polymer of one deck even compact on the apparatus surface, be the rate controlled layer, promptly obtain medicament eluting instrument of the present invention.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031155960A CN100435880C (en) | 2003-02-28 | 2003-02-28 | Medicament elution interventional medical apparatus and preparing method thereof |
| JP2004548875A JP2005531391A (en) | 2002-06-27 | 2003-06-25 | Drug release stent |
| PCT/CN2003/000489 WO2004002367A1 (en) | 2002-06-27 | 2003-06-25 | Drug eluting stent |
| EP03739968A EP1516597A4 (en) | 2002-06-27 | 2003-06-25 | Drug eluting stent |
| AU2003280437A AU2003280437A1 (en) | 2002-06-27 | 2003-06-25 | Drug eluting stent |
| US10/943,636 US20050043788A1 (en) | 2002-06-27 | 2004-09-17 | Drug-eluting stent |
| US10/943,633 US20050033414A1 (en) | 2002-06-27 | 2004-09-17 | Drug-eluting stent with multi-layer coatings |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031155960A CN100435880C (en) | 2003-02-28 | 2003-02-28 | Medicament elution interventional medical apparatus and preparing method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN1524590A true CN1524590A (en) | 2004-09-01 |
| CN100435880C CN100435880C (en) | 2008-11-26 |
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| CNB031155960A Expired - Lifetime CN100435880C (en) | 2002-06-27 | 2003-02-28 | Medicament elution interventional medical apparatus and preparing method thereof |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721753B (en) * | 2009-12-23 | 2014-04-09 | 天津大学 | Absorbable magnesium alloy bracket of inorganic and organic antiseptic biocompatible composite coating and preparation method thereof |
| CN105030390A (en) * | 2005-04-05 | 2015-11-11 | 万能医药公司 | Degradable implantable medical devices |
| CN105828805A (en) * | 2013-08-07 | 2016-08-03 | 学校法人近畿大学 | Nanoparticles and nanoparticle composition, and method for producing nanoparticles and nonparticle composition |
| CN106512188A (en) * | 2016-12-13 | 2017-03-22 | 天津飞捷科技有限公司 | Mechanical and electrical integrated targeted drug release intervention medical instrument and preparation method thereof |
| CN110547897A (en) * | 2019-09-04 | 2019-12-10 | 中国人民解放军总医院 | blood vessel support device |
| CN111035485A (en) * | 2019-12-16 | 2020-04-21 | 西南交通大学 | Intravascular stent and preparation method and application thereof |
| CN112137757A (en) * | 2019-09-08 | 2020-12-29 | 上海宏派医疗科技有限公司 | Novel coated blood vessel covered stent |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4792448A (en) * | 1987-06-11 | 1988-12-20 | Pfizer Inc. | Generic zero order controlled drug delivery system |
| US5378475A (en) * | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
| KR100576583B1 (en) * | 1997-12-22 | 2006-05-04 | 알자 코포레이션 | Rate controlling membranes for controlled drug delivery devices |
| US6375972B1 (en) * | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
| CN1223385C (en) * | 2002-12-31 | 2005-10-19 | 中国科学院金属研究所 | Cardiovascular support having control releasing therapeutic medicine |
-
2003
- 2003-02-28 CN CNB031155960A patent/CN100435880C/en not_active Expired - Lifetime
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105030390A (en) * | 2005-04-05 | 2015-11-11 | 万能医药公司 | Degradable implantable medical devices |
| US10350093B2 (en) | 2005-04-05 | 2019-07-16 | Elixir Medical Corporation | Degradable implantable medical devices |
| CN101721753B (en) * | 2009-12-23 | 2014-04-09 | 天津大学 | Absorbable magnesium alloy bracket of inorganic and organic antiseptic biocompatible composite coating and preparation method thereof |
| CN105828805A (en) * | 2013-08-07 | 2016-08-03 | 学校法人近畿大学 | Nanoparticles and nanoparticle composition, and method for producing nanoparticles and nonparticle composition |
| CN105828805B (en) * | 2013-08-07 | 2020-06-23 | 学校法人近畿大学 | Nanoparticles and nanoparticle compositions and methods for producing nanoparticles and nanoparticle compositions |
| CN106512188A (en) * | 2016-12-13 | 2017-03-22 | 天津飞捷科技有限公司 | Mechanical and electrical integrated targeted drug release intervention medical instrument and preparation method thereof |
| CN110547897A (en) * | 2019-09-04 | 2019-12-10 | 中国人民解放军总医院 | blood vessel support device |
| CN110547897B (en) * | 2019-09-04 | 2021-04-23 | 中国人民解放军总医院 | Blood vessel support device |
| CN112137757A (en) * | 2019-09-08 | 2020-12-29 | 上海宏派医疗科技有限公司 | Novel coated blood vessel covered stent |
| 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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| CN100435880C (en) | 2008-11-26 |
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