CN101066478B - Biodegradable slow released medicated rack for myocardial blood transport reconstruction and its preparation process - Google Patents
Biodegradable slow released medicated rack for myocardial blood transport reconstruction and its preparation process Download PDFInfo
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- CN101066478B CN101066478B CN 200710057459 CN200710057459A CN101066478B CN 101066478 B CN101066478 B CN 101066478B CN 200710057459 CN200710057459 CN 200710057459 CN 200710057459 A CN200710057459 A CN 200710057459A CN 101066478 B CN101066478 B CN 101066478B
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Abstract
The present invention discloses one kind of biodegradable slow released medicated rack for myocardial revascularization and its preparation process. The rack includes one inner tube made of biodegradable polymer, and one medicine carrying film layer of biodegradable polymer in the outer surface of the inner tube. The inner tube and the film layer have through holes of 0.2-1 mm diameter, and the carried medicine is cell growth factor and/or heparin. The rack of the present invention can release cell growth factor and/or heparin slowly to prevent the self closure of cardiac muscle, prevent thrombosis and promote blood vessel endoderm growth in the hole wall, and is used in the optimized reconstruction of myocardial blood vessel.
Description
Technical field
The wood invention relates to a kind of biodegradable support and preparation method, particularly relates to a kind of Biodegradable slow released medicated rack and preparation method that is used for myocardial blood transport reconstruction.
Background technology
Saturating locular wall myocardial revascularization (TMR) is a new surgical technology that grew up in recent years, myocardial blood transport reconstruction there is better action, this method utilizes laser or mechanical means to carry out the locular wall transmyocardial revascularization, it is mainly used in the patient with angina pectoris in late period of treatment CABG (coronary artery bypass grafting) or PTCA (percutaneous arterial cannulation arteria coronaria urethroptasty) inadaptation, and the effect that it alleviates angina pectoris, improve the ischemic myocardium perfusion, improve cardiac function has obtained extensive concern.But in the TMR postoperative short time, myocardium pipeline is just inaccessible because of blood coagulation, and therefore, the perforation of the myocardium pipeline in punching back needs emphasis to solve, and its direct relation the quality of myocardial revascularization effect.
Transmyocardial revascularization revascularization art and support method for posting combined to alleviate this problem, this is because three kinds of fine structures that have any other muscular tissue not possess in the cardiac muscular tissue: all straight-through chambers of the heart of tremulous pulse chambers of the heart blood vessel, myocardial sinuses and smallest cardiac veins, its medium-sized artery chambers of the heart blood vessel and smallest cardiac veins.These three kinds of fine structures make and have played the little vasoganglion that extends in all direction in the cardiac muscular tissue.When myocardial ischemia, this little vasoganglion is to producing side Zhi Xunhuan, protecting ischemic myocardium to play important function.By carry out array punching in the ischemic myocardium zone, produce the tunnel of a plurality of straight-through chambers of the heart, insert that the method by " tunnel " stops its closure voluntarily behind the support.U.S. Myocardial stents company and Kensey Nash company have reported such myocardium metal rack and method for implantation thereof respectively in patent US5878757 and US6514271.
Metal rack implants and has certain shortcoming, compares with metal rack, and the biodegradable polymer support has more advantage.The biodegradable polymer support can keep the support performance of support within a certain period of time, be degraded to then innocuous substance (Biomaterials, 2002,23:3575-3582, Biomaterials, 2006,27:1573-1578).After they finish its supporting role, can be organized absorption fully, side effect is less.Its mechanical property and degradation time can be controlled by the degree of polymerization and preparation process simultaneously, so they have bigger potentiality in clinical practice.The Biodegradable scaffold good biocompatibility can carry more multiple medicines thing, reaches longer release time.By the degradation rate of control material, support is disappeared after finishing the treatment function, avoid forever being detained and bring adverse effect in the body.Wherein Yan Jiu more timbering material comprises polycaprolactone, polylactic acid, polylactic acid-polyglycolic acid copolymer etc.Taminh etc. have reported six months experimental result (Circulation of polylactic acid bracket implant into body, 102 (4): 399-404, JUL25,2000), DattaA etc. have reported a kind of medicine slow release stent in patent EP1110561-A2, two-layer inside and outside being divided into, can carry different pharmaceutical, to regulate the slow release speed of medicine.
By cell growth factor, as blood vessel endothelial cell growth factor VEGF, basic fibroblast growth factor bFGF, transforming growth factors,type beta TGF-β etc., all can stimulate revascularization, improve the tissue blood perfusion.A large amount of clinical trials also show (Circulation, 2000,101 (2): 118-121), such somatomedin to the vascularization of bringing out ischemic myocardium, to set up effects such as collateral circulation and treatment ischemic disease of limb good.Research worker (J Thorac Cardiovasc Surg1999; 118:849-56) International Journal of Cardiology, 2004,95 (1): S70-72, InteractiveCardiovascular and Thoracic Surgery, 2004,3:138-144; ) effect of saturating locular wall myocardial revascularization and cell growth factor is combined, the result shows that the gene therapy of transmyocardial revascularization reconstructive vascular operation binding growth factor is more effective than simple myocardial revascularization, it can improve the local myocardial perfusion effect, promote arteries to generate, help the reparation of local myocardial function.But the half-life of somatomedin in blood circulation is very short, is tens of minutes only, is difficult to bring into play short angiogenesis function permanent, that continue, and general is widely applied adverse side effects such as can causing blood pressure drops again.Therefore, need a kind of somatomedin that can make badly and slowly discharge, help the support of blood coagulation again.
Summary of the invention
The objective of the invention is to overcome deficiency of the prior art, a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction is provided.
Second purpose of the present invention provides a kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction.
Technical scheme of the present invention is summarized as follows:
A kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction, comprise the hollow interior pipe made from biodegradable polymers, described hollow in the outer surface of pipe be provided with medicine carrying biodegradable polymers thin layer, run through and be provided with the hole that diameter is 0.2mm-1mm on pipe and the medicine carrying biodegradable polymers thin layer in hollow described, described medicine is that cell growth factor is or/and heparin.
Described medicine carrying biodegradable polymers thin layer can be to make with following method: in the ratio of 5-30g:100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, transfer in the mould, form thin film in the back fully in solvent evaporates, be cut into bar shaped, or/and heparin is arranged in the double-layer films, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg with described cell growth factor.
Described medicine carrying biodegradable polymers thin layer can also be to make with following method: in the ratio of 5-30g:100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, make biodegradable polymers solution, with described cell growth factor or/and heparin be dispersed in the described biodegradable polymers solution, transfer in the mould, form thin film in the back fully in solvent evaporates, be cut into bar shaped, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg.
Described cell growth factor can be a basic fibroblast growth factor, also can be VEGF or transforming growth factors,type beta.
Described biodegradable polymers can be polycaprolactone or polylactic acid or polyglycolic acid or polylactic acid-polyglycolic acid copolymer or polycaprolactone-copolymer of poly lactic acid or poly-dioxane.
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with the biodegradable polymer, by melt extruding into external diameter is 1-5mm, and wall thickness is 0.1-0.5mm, and being cut into length is the hollow interior pipe of 0.5-1cm; (2) described hollow in the outer surface of pipe with dichloromethane, chloroform, oxolane or acetone bonding on medicine carrying biodegradable polymers thin layer, run through the hole that diameter is 0.2mm-1mm is set on pipe and the medicine carrying biodegradable polymers thin layer in hollow described, described medicine is that cell growth factor is or/and heparin.
Described medicine carrying biodegradable polymers thin layer can be to make with following method: in the ratio of 5-30g:100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, transfer in the mould, form thin film in the back fully in solvent evaporates, be cut into bar shaped, or/and heparin is arranged in the double-layer films, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg with described cell growth factor.
Described medicine carrying biodegradable polymers thin layer can also be to make with following method: in the ratio of 5-30g:100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, make biodegradable polymers solution, with described cell growth factor or/and heparin be dispersed in the described biodegradable polymers solution, transfer in the mould, form thin film in the back fully in solvent evaporates, be cut into bar shaped, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg.
Described cell growth factor can be basic fibroblast growth factor, VEGF or transforming growth factors,type beta.
Described biodegradable polymers is polycaprolactone or polylactic acid or polyglycolic acid or polylactic acid-polyglycolic acid copolymer or polycaprolactone-copolymer of poly lactic acid or poly-dioxane.
A kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction of the present invention, can slowly discharge somatomedin or/and heparin, can not only stop cardiac muscle closed voluntarily, can prevent thrombosis again, also can promote hole wall to generate blood vessel endothelium, be the optimization to saturating locular wall myocardial revascularization.
Description of drawings
Fig. 1 is a support external morphology sem photograph of the present invention.
Fig. 2 is support cross-sectional scans Electronic Speculum figure of the present invention.
Fig. 3 is that support of the present invention is implanted 6 week of pig myocardium back picture.
Fig. 4 is a support combination of the present invention wall type cardiac muscle boring promotion revascularization effect (vascular smooth muscle cell dyeing picture) (the arrow place is the support of not degrading fully as yet) thoroughly.
Fig. 5 promotes revascularization effect (vascular endothelial cell dyeing picture) (the arrow place is the support of not degrading fully as yet) for the boring of the saturating wall type cardiac muscle of support combination of the present invention.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment.
Embodiment 1
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is that 30,000 polycaprolactone is a raw material with molecular weight, by fusion, it is 3mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.2mm, and being cut into length is the hollow interior pipe of 1cm; (2) dichloromethane is joined in the polylactic acid-polyglycolic acid copolymer (mol ratio is 50/50), be made into the polymer solution that concentration is 15% (g/ml), fully stir, dissolving; After solution was poured the mould of politef into, at room temperature natural drying was treated to form thin film after the solvent evaporates, and by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 2cm, and length is the strip form film of 3cm; Getting basic fibroblast growth factor and heparin evenly is layered on the thin film, folding then, be prepared into the pharmaceutical film that width is 1cm, make every pharmaceutical film contain basic fibroblast growth factor 10ug and heparin 10mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several dichloromethane then to hollow interior pipe,, treat that solvent evaporates is complete so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 1mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.(rack surface pattern such as Fig. 1 are shown in 2)
Embodiment 2
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with the polylactic acid, by fusion, it is 5mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.5mm, and being cut into length is the hollow interior pipe of 1cm; (2) chloroform is joined in polycaprolactone-copolymer of poly lactic acid (mol ratio is 60/40), be made into the polymer solution that concentration is 30% (g/ml), fully stir, dissolving; After solution was poured the mould of politef into, at room temperature natural drying was treated to form thin film after the solvent evaporates, and by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 2cm, and length is the strip form film of 3cm; Getting VEGF and heparin evenly is layered on the thin film, folding then, be prepared into the pharmaceutical film that width is 1cm, make every pharmaceutical film contain VEGF 50ug and heparin 50mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several chloroform then to hollow interior pipe,, treat that solvent evaporates is complete so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.5mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with the polyglycolic acid, by fusion, it is 1mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.1mm, and being cut into length is the hollow interior pipe of 0.5cm; (2) oxolane is joined in the poly-dioxane, be made into the polymer solution that concentration is 5% (g/ml), fully stir, dissolving; After solution was poured the mould of politef into, at room temperature natural drying was treated to form thin film after the solvent evaporates, and by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 1cm, and length is the strip form film of 1cm; Getting VEGF and heparin evenly is layered on the thin film, folding then, be prepared into the pharmaceutical film that width is 0.5cm, make every pharmaceutical film contain VEGF 1ug and heparin 1mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several oxolanes then to hollow interior pipe,, treat that solvent evaporates is complete so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.2mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 4
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with polylactic acid-polyglycolic acid copolymer (mol ratio is 85/15), by fusion, it is 3mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.2mm, and being cut into length is the hollow interior pipe of 1cm; (2) acetone is joined in the polycaprolactone, be made into the polymer solution that concentration is 15% (g/ml), fully stir, dissolving; After solution was poured the mould of politef into, at room temperature natural drying was treated to form thin film after the solvent evaporates, and by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 2cm, and length is the strip form film of 2cm; Getting transforming growth factors,type beta is layered on the thin film, folding then, be prepared into the pharmaceutical film that width is 1cm, make every pharmaceutical film contain transforming growth factors,type beta 20ug, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several acetone then to hollow interior pipe,, treat that solvent evaporates is complete so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.5mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 5
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with poly-dioxane, by fusion, it is 3mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.2mm, and being cut into length is the hollow interior pipe of 1cm; (2) acetone is joined in the polycaprolactone, be made into the polymer solution that concentration is 15% (g/ml), fully stir, dissolving; After solution was poured the mould of politef into, at room temperature natural drying was treated to form thin film after the solvent evaporates, and by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 2cm, and length is the strip form film of 2cm; Taking heparin is layered on the thin film, folding then, be prepared into the pharmaceutical film that width is 1cm, make every pharmaceutical film contain heparin 30mg, folding then, be prepared into the pharmaceutical film that width is 1cm, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several acetone then to hollow interior pipe,, treat that solvent evaporates is complete so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.5mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 6
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is that 30,000 polycaprolactone is a raw material with molecular weight, by fusion, it is 3mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.2mm, and being cut into length is the hollow interior pipe of 1cm; (2) dichloromethane is joined in the polylactic acid-polyglycolic acid copolymer (mol ratio is 50/50), be made into the polymer solution that concentration is 15% (g/ml), fully stir, dissolving; Add basic fibroblast growth factor and heparin in the solution, fully stir, mix homogeneously, after pouring the mould of politef into, natural drying at room temperature, treat to form thin film after the solvent evaporates, by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 1cm, length is the strip form film of 3cm, make every pharmaceutical film contain basic fibroblast growth factor 10ug and heparin 10mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several dichloromethane then to hollow interior pipe, so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow, treat that solvent evaporates is complete; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 1mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 7
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with the polylactic acid, by fusion, it is 5mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.5mm, and being cut into length is the hollow interior pipe of 1cm; (2) chloroform is joined in polycaprolactone-copolymer of poly lactic acid (mol ratio is 60/40), be made into the polymer solution that concentration is 30% (g/ml), fully stir, dissolving; Add VEGF and heparin in the solution, fully stir, mix homogeneously, after pouring the mould of politef into, natural drying at room temperature, treat to form thin film after the solvent evaporates, by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 1cm, length is the strip form film of 1cm, make every pharmaceutical film contain VEGF 50ug and heparin 50mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several chloroform then to hollow interior pipe, so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow, treat that solvent evaporates is complete; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.5mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 8
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with the polyglycolic acid, by fusion, it is 1mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.1mm, and being cut into length is the hollow interior pipe of 0.5cm; (2) oxolane is joined in the poly-dioxane, be made into the polymer solution that concentration is 5% (g/ml), fully stir, dissolving; Add VEGF and heparin in the solution, fully stir, mix homogeneously, after pouring the mould of politef into, natural drying at room temperature, treat to form thin film after the solvent evaporates, by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 0.5cm, length is the strip form film of 1cm, make every pharmaceutical film contain VEGF 50ug and heparin 50mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several oxolanes then to hollow interior pipe, so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow, treat that solvent evaporates is complete; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.2mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 9
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with polylactic acid-polyglycolic acid copolymer (mol ratio is 85/15), by fusion, it is 3mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.2mm, and being cut into length is the hollow interior pipe of 1cm; (2) acetone is joined in the polycaprolactone, be made into the polymer solution that concentration is 15% (g/ml), fully stir, dissolving; Add transforming growth factors,type beta in the solution, fully stir, mix homogeneously, after pouring the mould of politef into, natural drying at room temperature, treat to form thin film after the solvent evaporates, by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 1cm, length is the strip form film of 1cm, make every pharmaceutical film contain transforming growth factors,type beta 20ug, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several acetone then to hollow interior pipe, so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow, treat that solvent evaporates is complete; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.5mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 10
A kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, comprise the steps: that (1) is raw material with poly-dioxane, by fusion, it is 3mm that screw rod is extruded into external diameter, wall thickness is the hollow interior pipe of 0.2mm, and being cut into length is the hollow interior pipe of 1cm; (2) acetone is joined in the polycaprolactone, be made into the polymer solution that concentration is 15% (g/ml), fully stir, dissolving; Add heparin in the solution, fully stir, mix homogeneously, after pouring the mould of politef into, natural drying at room temperature, treat to form thin film after the solvent evaporates, by controlling the thickness of the amount controlling diaphragm of pouring into a mould solution, becoming mould thickness is 0.2mm, and being prepared into width is 1cm, length is the strip form film of 1cm, make every pharmaceutical film contain heparin 30mg, the said medicine thin film is wrapped in a hollow interior pipe outside, drip several acetone then to hollow interior pipe, so that pipe is combined closely with medicine carrying biodegradable polymers thin layer in hollow, treat that solvent evaporates is complete; It with diameter evenly punching around the sidewall of motor machine drill bit pipe in being covered with medicine carrying biodegradable polymers thin layer hollow of 0.5mm, little hole number is 4 of weeks, 16 apertures of totally 4 rows are made a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction.
Embodiment 11
Zoopery is passed through the pentobarbital sodium injecting anesthetic with experiment pig, along mid-sternal incision, open thoracic cavity and pericardium, expose heart, direct-view is carried out transmyocardial revascularization at left chamber antetheca down, blood penetrates from the chambers of the heart after penetrating heart wall, and the support with the present invention's preparation is placed in the myocardium duct rapidly, and fixes in the place's ligation of pipeline collar extension.Animal is all put to death in 6 weeks of postoperative. and cardiac muscle is drawn materials through formalin fixed. the paraffin serial section, dyeing, light microscopic is observed morphological change such as revascularization and reconstruction down.(Fig. 3,4, Fig. 5 is experimental result)
A kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction of the present invention is embedded in the purpose that support can play slow release with somatomedin.Add the inhibition that heparin helps the blood coagulation phenomenon in the support of the present invention.Simultaneously because heparin and somatomedin have very high affinity, it can improve its biological activity, its half-life can also be prolonged widely, of the present invention is placed in the myocardium hole, can not only stop it closed voluntarily, can prevent thrombosis again, also can promote hole wall to generate blood vessel endothelium, make it finally to become and wall between " blood vessel " of fine structure Communicating.This support can obtain more excellent myocardial revascularization effect with saturating combining of locular wall myocardial revascularization.
The biodegradable polymer polycaprolactone that the present invention selects for use, polylactic acid, polyglycolic acid, the polylactic acid-polyglycolic acid copolymer, polycaprolactone-copolymer of poly lactic acid or poly-dioxane, such material all is proved to be the medical material that can be used for human body, can control intensity, degradation time and the sustained drug release effect of support by the composition of regulating timbering material.With the Biodegradable polymer material is timbering material, it gives the stent support performance on the one hand, carry medicine on the other hand, as drug release carrier, by improving the support preparation method or rack surface being carried out modification, optimize the medicament slow release technology, biodegradability composite slow release support in the preparation cardiac muscle, this support can the sustained release heparin, medicines such as somatomedin, can not only play anticoagulant effect, genomic medicine can promote revascularization simultaneously, by support transmission blood flow and support side opening ishemic part is directly poured in addition, this method can improve the myocardial revascularization effect, solves the myocardial ischemia disease better.
Claims (6)
1. Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction, comprise the hollow interior pipe made from biodegradable polymers, described hollow in the outer surface of pipe be provided with medicine carrying biodegradable polymers thin layer, run through and be provided with the hole that diameter is 0.2mm-1mm on pipe and the medicine carrying biodegradable polymers thin layer in hollow described, described medicine is that cell growth factor is or/and heparin, described medicine carrying biodegradable polymers thin layer is to make with a kind of of following two kinds of methods, first kind: in the ratio of 5-30g: 100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, transfer in the mould, form thin film in the back fully in solvent evaporates, be cut into bar shaped, or/and heparin is arranged in the double-layer films, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg with described cell growth factor; Second kind: in the ratio of 5-30g: 100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, make biodegradable polymers solution, with described cell growth factor or/and heparin be dispersed in the described biodegradable polymers solution, transfer in the mould, fully form thin film in the back in solvent evaporates, be cut into bar shaped, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg.
2. a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction according to claim 1 is characterized in that described cell growth factor is basic fibroblast growth factor, VEGF or transforming growth factors,type beta.
3. a kind of Biodegradable slow released medicated rack that is used for myocardial blood transport reconstruction according to claim 1 is characterized in that described biodegradable polymers is polycaprolactone or polylactic acid or polyglycolic acid or polylactic acid-polyglycolic acid copolymer or polycaprolactone-copolymer of poly lactic acid or poly-dioxane.
4. preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction, it is characterized in that comprising the steps: that (1) is raw material with the biodegradable polymer, by melt extruding into external diameter is 1-5mm, wall thickness is 0.1-0.5mm, and being cut into length is the hollow interior pipe of 0.5-1cm; (2) described hollow in the outer surface dichloromethane of pipe, chloroform, the bonding medicine carrying biodegradable polymers thin layer of going up of oxolane or acetone, run through the hole that diameter is 0.2mm-1mm is set on pipe and the medicine carrying biodegradable polymers thin layer in hollow described, described medicine is that cell growth factor is or/and heparin, described medicine carrying biodegradable polymers thin layer is to make with a kind of of following two kinds of methods, first kind: in the ratio of 5-30g: 100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, transfer in the mould, form thin film in the back fully in solvent evaporates, be cut into bar shaped, or/and heparin is arranged in the double-layer films, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg with described cell growth factor; Second kind: in the ratio of 5-30g: 100ml, biodegradable polymers is dissolved in dichloromethane or chloroform or oxolane or the acetone, make biodegradable polymers solution, with described cell growth factor or/and heparin be dispersed in the described biodegradable polymers solution, transfer in the mould, fully form thin film in the back in solvent evaporates, be cut into bar shaped, to make amount that each support contains cell growth factor be 1ug-50ug or/and to contain the amount of heparin be 1mg-50mg.
5. a kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction according to claim 4 is characterized in that described cell growth factor is basic fibroblast growth factor, VEGF or transforming growth factors,type beta.
6. a kind of preparation method that is used for the Biodegradable slow released medicated rack of myocardial blood transport reconstruction according to claim 4 is characterized in that described biodegradable polymers is polycaprolactone or polylactic acid or polyglycolic acid or polylactic acid-polyglycolic acid copolymer or polycaprolactone-copolymer of poly lactic acid or poly-dioxane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710057459 CN101066478B (en) | 2007-05-24 | 2007-05-24 | Biodegradable slow released medicated rack for myocardial blood transport reconstruction and its preparation process |
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| CN 200710057459 CN101066478B (en) | 2007-05-24 | 2007-05-24 | Biodegradable slow released medicated rack for myocardial blood transport reconstruction and its preparation process |
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| CN101066478A CN101066478A (en) | 2007-11-07 |
| CN101066478B true CN101066478B (en) | 2011-05-04 |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101347642B (en) * | 2008-07-03 | 2013-10-02 | 泰达国际心血管病医院 | Biodegradable sustained-release medicament stent for TMR and preparation method |
| CN101361988B (en) * | 2008-09-12 | 2011-12-21 | 西南交通大学 | Preparation method of blood vessel support or cardiac valve surface coating with good biocompatibility |
| CN102210616B (en) * | 2010-04-09 | 2014-04-30 | 乐普（北京）医疗器械股份有限公司 | Completely degradable polymer medicine elution stent and preparation method thereof |
| CN101999952A (en) * | 2010-12-17 | 2011-04-06 | 东华大学 | Polycaprolactone (PCL) and polylactic acid (PLA) human body absorbable vascular stent and preparation method thereof |
| CN102294076A (en) * | 2011-06-02 | 2011-12-28 | 中国医学科学院生物医学工程研究所 | Biodegradable traditional Chinese medicine slow release implant for revascularization of ischemic lower limbs and preparation thereof |
| CN102784418B (en) * | 2012-08-10 | 2014-04-16 | 中国医学科学院生物医学工程研究所 | Procedurally-released biological drug nanoporous intravascular stent, preparation method and application thereof |
| CN104888282B (en) * | 2015-05-05 | 2017-11-24 | 乐普（北京）医疗器械股份有限公司 | A kind of degradable zinc-base micropore carried stent and preparation method thereof |
| CN109394399A (en) * | 2018-10-22 | 2019-03-01 | 乐畅医疗器械(上海)有限公司 | A kind of medicine slow release stent |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1110561A2 (en) * | 1999-12-22 | 2001-06-27 | Ethicon, Inc. | Biodegradable stent |
| CN1475193A (en) * | 2003-07-04 | 2004-02-18 | 中国人民解放军总医院 | Double layer hollow blood vessel internal support used for vascular anastomosis and its preparation method |
| CN1513567A (en) * | 2002-12-31 | 2004-07-21 | 中国科学院金属研究所 | Cardiovascular support having control releasing therapeutic medicine |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1110561A2 (en) * | 1999-12-22 | 2001-06-27 | Ethicon, Inc. | Biodegradable stent |
| CN1513567A (en) * | 2002-12-31 | 2004-07-21 | 中国科学院金属研究所 | Cardiovascular support having control releasing therapeutic medicine |
| CN1475193A (en) * | 2003-07-04 | 2004-02-18 | 中国人民解放军总医院 | Double layer hollow blood vessel internal support used for vascular anastomosis and its preparation method |
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