CN104857570B - A kind of degradable zinc-containing alloy support and preparation method thereof - Google Patents

Abstract

The invention relates to a degradable zinc-based alloy stent and a preparation method thereof. The stent includes a stent matrix of a degradable zinc-based material, and the surface of the stent matrix is provided with a degradable polymer eluting coating containing therapeutic drugs. The stent The matrix is a cylindrical mesh structure. The preparation method includes: 1) processing the degradable zinc-based material into a stent matrix; 2) performing surface pretreatment on the stent matrix; 3) performing electrolytic polishing on the stent matrix; 4) coating the surface of the stent after treatment Degradable polymer materials for sexual drugs. The stent provided by the present invention maintains good support of the stent after being implanted for more than 4 months due to the superior corrosion resistance of the base material zinc alloy, and the surface of the base is coated with a polymer coating with good biocompatibility to improve the zinc-based The compatibility of the alloy is conducive to the coverage of endothelial cells on the surface of the stent, and can control the drug release, reducing the sudden release of the drug and allowing the drug to be released slowly and continuously at a certain concentration, so as to reduce the risk of local inflammation, restenosis and stent thrombosis after stent implantation .

Description

A kind of degradable zinc-based alloy stent and its preparation method

technical field

The invention relates to a biodegradable metal bracket and a preparation method thereof, belonging to the technical field of implantable medical devices.

Background technique

In 1977, Gruentzing successfully performed the first case of percutaneous transluminal coronary angioplasty, which opened the era of simple balloon dilatation for cardiovascular treatment. This new technology without thoracotomy ended the dominance of coronary blood supply in cardiac surgery History of reconstruction. In 1987, Sigwart successfully implemented coronary artery stent surgery for the first time. A large number of clinical experiments confirmed that coronary artery stent implantation can effectively avoid the medical disadvantages of simple balloon expansion, and it was widely accepted as the second milestone in the history of interventional treatment of coronary heart disease. . After the coronary artery stent is implanted, it can maintain a support state for a long time at the lesion position, which can effectively solve the risk of acute vascular occlusion after surgery, improve the safety of PTCA, and improve the negative remodeling of diseased blood vessels, so that the postoperative The incidence of long-term restenosis is reduced to less than 15%, and the implantation of coronary stents has greatly broadened the indications for stent interventional treatment of cardiovascular diseases. Since 2003, with the advent of drug-eluting stents represented by CYPHER and TAXUS, and achieved gratifying results in clinical applications, the era of drug-eluting stents that inhibit smooth muscle cell proliferation and reduce intravascular restenosis has come. , has become a new focus of stent interventional therapy for cardiovascular diseases as soon as it is launched on the market. Drug-eluting stents can not only prevent early vascular elastic recoil after stent implantation like bare stents, but also can be inhibited by the pharmacological effects of anti-proliferative drugs. It has become a new landmark breakthrough to reduce postoperative smooth muscle cell proliferation and prevent restenosis caused by neointimal thickening.

However, the development in the past 10 years has also exposed the shortcomings of drug-eluting stents. For example, although drug-eluting stents can effectively reduce the occurrence of restenosis, they delay the healing of the vascular endothelium, making it difficult to repair and reconstruct the blood vessels to complete endothelialization, making the stents exposed for a long time. In blood vessels, the occurrence of medium and long-term thrombosis in the stent is increased. The currently clinically used stents cannot be completely degraded and remain in the vessel wall for a long time, affecting the vasomotor function and increasing the risk of local inflammation, restenosis and stent thrombosis. However, an ideal stent system should be compatible with the physiological structure and function of the coronary artery. After implantation, it can not only improve the local blood supply of the coronary artery, but also restore and maintain the original function of the blood vessel. The degradable stent can theoretically Restoring the structure and function of blood vessels to their natural state is considered to be the "fourth technological innovation" in coronary interventional therapy following PTCA, BMS, and DES. In recent years, Abbott of the United States and Biotronik of Germany have made major breakthroughs in the field of fully degradable stents. Degradable coronary stents represented by BVS and AMS stents are expected to lead the fourth revolution in interventional treatment of coronary heart disease. The technological revolution has brought about a new era of coronary heart disease treatment. On the one hand, stent intervention technology replaces traditional surgery to treat diseases and provides a less invasive treatment method. On the other hand, it completely solves some diseases that are difficult to treat with traditional surgery. , Stent interventional technology has become an effective means of treatment of coronary heart disease, bringing good news to the majority of patients.

The fully degradable coronary stent plays the role of a "temporary stent" in interventional therapy, and the stent material has good biocompatibility, and can maintain effective vascular support in the early stage of implantation in the lesion site. It can be completely degraded after a period of time, thus fundamentally overcoming many shortcomings and complications of permanent metal stents, and can better load drugs and cells, and realize the controlled release and sustained release of the carried substances through the gradual degradation of biomaterials. Efficacy has become a frontier hotspot in the research of interventional therapy for coronary heart disease at home and abroad. The current research on biodegradable stents focuses on two aspects: degradable polymer stents and degradable metal stents.

In terms of polymer stents, early studies tended to use stents with a slower degradation rate, which can complete the formation of the vascular intima and avoid thrombosis, but too slow degradation rate will affect the growth of the blood vessel itself and prolong the inflammatory response of the vessel wall. At the same time, due to the low strength of the polymer, the stent will cause elastic retraction due to insufficient supporting force, which limits its use in small blood vessel lumens; biodegradable metal stents have the mechanical support properties of bare metal stents, and can effectively prevent Early retraction, X-ray impenetrability, and the degradable properties of polymer stents have attracted extensive attention from researchers. The current research on degradable metal stents mainly includes iron alloy stents and magnesium alloy stents. For example, patents CN101496910 A and CN 102228721 A disclose an iron-based degradable stent, and patents CN 101708140 A, CN101468216 A and CN102488932 A disclose a magnesium-based degradable stent.

However, the degradable scaffolds currently studied still have some disadvantages, which limit their wide application. For degradable polymer stents, there is still a problem of poor imaging effect that needs to be overcome. In addition to REVA, the stent is made of tyrosine polycarbonate and can be visualized by itself, which is convenient for the visualization of the implantation process and postoperative follow-up. Most of the other degradable stents have a specially made heavy metal tantalum imaging mark at one end and do not develop themselves. This will inevitably bring difficulties to the operation of aligning and connecting the two stents, which limits its application in longer vascular lesions. At the same time, the stent After degradation, tantalum as a sign will also remain in the body and exist as a foreign body for a long time; for degradable metal stents, magnesium alloy stents show a faster degradation rate, while iron alloy stents degrade slower, which is not conducive to the blood vessel itself. Reconstruction requires controlling the degradation rate and providing more appropriate supporting force to adapt to the process of positive vascular remodeling.

Zinc is one of the essential trace elements in the human body. It participates in all physiological metabolic processes in the body. In addition to playing a catalytic or structural role in various metalloenzymes, transcription factors and other proteins, zinc also acts as a neurotransmitter or modulator. Form fulfills its function. Compared with polymers, zinc metal has excellent mechanical properties and developability. At the same time, studies have found that it has better biocompatibility and better degradation performance than magnesium-based alloys. It has potential research value as a biomedical metal material. However, zinc-based alloys are rarely reported as degradable metal materials. After searching the literature of the prior art, D Vojtěch et al. reported the mechanical properties and corrosion properties of Zn-Mg alloys, and discussed its application in orthopedic implants. Feasibility of application (Actabiomaterialia,2011,7(9):3515-3522); PK Bowen et al. reported the implantation experiment of pure zinc in the abdominal aorta of mice, revealed its corrosion characteristics in vivo, and discussed pure Zn as a scaffold The feasibility of using metallic materials (Advanced Materials, 2013, 25(18): 2577-2582), however, the design of scaffolds that can degrade zinc and its alloys has not been reported.

Contents of the invention

The purpose of the present invention is to provide a new type of degradable metal-based stent made of zinc and zinc alloy, to overcome the non-degradable traditional metal-based stent in the body, and to avoid inflammatory irritation caused by long-term foreign matter in the body. Degradable polymer stents have medical limitations caused by poor mechanical support performance and no imaging effect, as well as the disadvantages of degradable iron-based stents and magnesium-based stents that do not match the degradation speed and lumen reconstruction. Drugs that inhibit the proliferation of smooth muscle cells inhibit intimal hyperplasia and thickening through the pharmacological effects of drugs, thereby reducing or even eliminating the occurrence of in-stent restenosis.

The purpose of the present invention is achieved like this:

A novel degradable zinc-based alloy stent, comprising: a degradable zinc-based material stent base; the surface of the stent base is provided with a degradable polymer eluting coating containing therapeutic drugs; the stent base is a cylindrical mesh shape structure.

The stent matrix is preferably a cylindrical mesh structure, which exhibits good flexibility, is convenient for intervention and placement, and has good radial support performance, and the stent has good development performance due to the metal zinc of the matrix material, which is convenient Surgical operation stent intervention and postoperative follow-up.

The degradable zinc-based material is pure zinc or zinc-based alloy; the zinc-based alloy is preferably Zn-Mg alloy, Zn-Ca alloy, Zn-Sr alloy, Zn-Sn alloy, Zn-Mg-Mn alloy, Zn -Mg-Ca alloy, Zn-Mg-Sr alloy, Zn-Mg-Sn alloy, Zn-Mg-Mn-Ca alloy, Zn-Mg-Ca-Sr alloy, etc.; further preferably the degradable zinc The base material is Zn-(0～1.5)%Ca alloy, Zn-(0～1.5)%Sn alloy, Zn-(0～1.5)%Mg-(0～1)%Mn alloy, Zn-(0～1.5% )%Mg-(0~1)%Sn alloy, Zn-(0~1.5)%Mg-(0~1)%Ca-(0~0.5)%Mn alloy, Zn-(0~1.5)%Mg Alloy or Zn-(0~1.5)%Mg-(0~1)%Ca alloy.

In the present invention, the meaning of the term "Zn-1%Mg alloy" means "the Mg content in the alloy is 1%, and the balance is Zn"; the meaning of the term "Zn-1%Mg-0.5%Ca alloy" means "the Mg content in the alloy is The content is 1%, the Ca content is 0.5%, and the balance is Zn". Others are similar.

The degradable polymer eluting coating containing therapeutic drugs provided on the surface of the stent matrix, wherein the degradable polymer includes polylactic acid, polyglycolide, polyanhydride, polylactic acid copolymer, polyglycolic acid, poly A copolymer of one or more of artificially synthesized degradable polymer materials such as pentyl hydroxybutyrate and polycyanoacrylate, and one of natural degradable polymer materials such as collagen, gelatin, and chitin , it can even be a blend of artificially synthesized polymer materials and natural degradable polymer materials; the therapeutic drugs can be drugs with anti-cell proliferation effects such as rapamycin, paclitaxel, emodin, curcumin, etc. One or more of them are compounded; the preferred therapeutic drug is rapamycin, the preferred degradable polymer is polylactic acid, and the preferred thickness of the eluting coating is 10-50 μm.

The surface of the stent matrix is provided with a degradable polymer eluting coating containing therapeutic drugs, which can improve the biocompatibility of the bare metal stent, facilitate the coverage of endothelial cells on the surface of the stent, and control the release of drugs, reducing drug breakthrough. Release the drug slowly and continuously at a certain concentration to reduce the incidence of acute and subacute thrombosis after stent implantation.

The degradable zinc-based material of the stent matrix of the present invention is designed from the perspective of the biological effects of alloy elements, and is selected to alloy with beneficial elements for the human body. After processing, the comprehensive mechanical properties are improved, drawn into tubes, and laser engraved. The bare stent has better degradation performance than the magnesium-based stent; the stent matrix is a cylindrical mesh structure, and the design of the stent shows good flexibility, which is convenient for intervention and placement, and has better radial support performance, and due to the matrix The material metal zinc endows the stent with better imaging performance, which is convenient for stent intervention and postoperative tracking; at the same time, one or more layers of degradable polymer coatings containing therapeutic drugs are coated on the surface of the degradable zinc-based alloy stent , the designed degradable polymer coating can improve the biocompatibility of the bare metal stent, facilitate the coverage of endothelial cells on the surface of the stent, and control the drug release, reducing the sudden release of the drug so that the drug can be released slowly and continuously at a certain concentration. To reduce the incidence of acute and subacute thrombosis after stent implantation.

The present invention also includes:

The preparation method of the above-mentioned degradable zinc-based alloy stent includes: 1) processing the degradable zinc-based material into a stent matrix; 2) pretreating the stent matrix to remove processing residues and surface appendages; 3) electrolyzing the stent matrix Polishing treatment; 4) Coating a degradable polymer eluting coating containing therapeutic drugs on the surface of the stent matrix after the polishing treatment.

The step 2) pretreating the stent matrix to remove processing residues and surface appendages, including: a) performing mechanical treatment on the stent matrix; b) performing pickling or alkali cleaning on the mechanically treated stent matrix; c) Ultrasonic cleaning is performed on the stent matrix after pickling or alkali cleaning. Wherein, said a) mechanically treating the stent matrix means using physical methods to remove residual burrs and the like after hollowing out. b) pickling or alkali cleaning the mechanically treated stent matrix, that is, placing the stent in pickling solution or alkaline solution for cleaning (at room temperature) to remove impurities such as oil stains or oxides on the surface of the stent. The pickling solution is a mixed solution of acetic acid and neutral sodium salt, which can be a blend solution of acetic acid and neutral sodium salts such as sodium chloride or sodium nitrate, and can be cleaned at room temperature for 3-5 minutes; the alkali The washing liquid is a mixed solution of sodium hydroxide and alkaline sodium salt, which can be a blended solution of sodium hydroxide and alkaline sodium salt such as sodium carbonate or sodium bicarbonate, and can be cleaned at room temperature for 5-10 minutes. In c) ultrasonic cleaning of the acid-washed or alkaline-washed stent matrix is to use clean water, generally pure water, to clean the treated stent to remove acid or lye attached to the surface of the stent.

Step 3) Perform electropolishing treatment on the bracket base, that is, put the bracket base into (suspend) the electrolytic tank containing the electrolyte to perform electrolytic polishing treatment. The specific process is: the DC voltage is 2.5-30V, and the current is 0.2-10A. The electropolishing time is 0.5-20 minutes, and the electrolysis temperature is 10-40°C; the electrolyte is an alcoholic acid solution, and the acid can be phosphoric acid or perchloric acid or a mixture thereof; the electrolyte component can be phosphoric acid The volume ratio with dehydrated ethanol is 2～5:5～2, also can be that the volume ratio of perchloric acid and dehydrated alcohol is 1～4:20, or can also be perchloric acid: phosphoric acid: dehydrated alcohol The volume ratio is 1-5:5-15:24-40. The electrolytic polishing process also includes the step of cleaning the polished bracket with purified water.

The step 4) coating the degradable polymer eluting coating containing therapeutic drug on the surface of the stent matrix after polishing treatment, that is, the degradable polymer containing therapeutic drug is prepared by spraying, dipping or electrostatic coating. The solution is coated on the surface of the zinc and zinc alloy stent substrate, preferably by spraying, preferably with a thickness of 10-50 μm for degradable polymer elution coating; more preferably, the thickness of the coating is 20-40 μm;

The degradable polymer solution containing the therapeutic drug is the above-mentioned high molecular material polymer-organic solvent solution carrying the above-mentioned therapeutic drug, wherein the high molecular material polymer is preferably polylactic acid; the organic solvent is preferably chloroform, bis Chloromethane, tetrafluorohydrofuran and other volatile organic solvents; the preferred organic solvent is chloroform; the mass ratio of the preferred drug (such as rapamycin) and high molecular material polymer (such as polylactic acid) is 1～3:9～ 27. The volume ratio of high molecular material polymer (such as polylactic acid) to organic solvent (such as chloroform) is 1-5: 20-50; the preferred drug is rapamycin; the more preferred solution is that the therapeutic drug The degradable polymer solution is a polylactic acid-chloroform homogeneous solution carrying rapamycin, the mass ratio of rapamycin to polylactic acid is 1:10, and the volume ratio of polylactic acid to chloroform is 1:20.

The stent made of biodegradable materials has the characteristics of temporary persistence, and its metabolites are harmless to the body. It can not only provide the necessary support for the lumen in the short term, but also avoid the damage caused by the long-term storage of metal stents. Complications can also carry various drugs and exogenous genes to act on the diseased lumen, which has become a new research direction for the prevention and treatment of in-stent restenosis and in-stent thrombosis. The advantages of the novel degradable zinc-based alloy stent proposed by the present invention are:

1. From the perspective of the composition design of the matrix material, the biological effects of the alloying elements are given priority, and the elements beneficial to the human body are selected for alloying, avoiding the introduction of alloying elements with cytotoxicity and genotoxicity, and the prepared zinc-based alloy Low toxicity, good biocompatibility.

From the perspective of the biological effect of magnesium, magnesium ion (Mg ²⁺ ) is the second most important cation in human cells and is harmless to human body. In addition, magnesium also has a variety of special physiological functions. It can activate various enzymes in the body, inhibit abnormal nerve excitability, maintain the stability of nucleic acid structure, participate in protein synthesis, muscle contraction and temperature regulation in the body.

From the perspective of the biological effects of manganese, manganese is an element beneficial to the cardiovascular system, especially important for maintaining the function of mitochondria in cells. It can also maintain normal brain function, maintain normal sugar and fat metabolism, and improve the body's hematopoietic function. Manganese can also enhance endocrine function, maintain normal thyroid function, promote the synthesis of sex hormones, and regulate nerve response.

From the perspective of the biological effects of calcium, calcium can maintain the normal physiological state of cells. Calcium ions in cells are the medium for cells to respond to stimuli. Calcium and receptor calcium jointly regulate many important physiological functions of the body, including contraction of skeletal muscle and cardiac muscle, smooth muscle and non-muscle cell activity and maintenance of nerve excitation. Calcium is also involved in the blood clotting process. At present, at least four vitamin K-dependent calcium-binding proteins are known to participate in the blood coagulation process, that is, the cascade reaction can only be completed in the presence of calcium ions, and finally the soluble fibrinogen is converted into fibrin to form blood coagulation.

From the perspective of the biological effects of strontium, strontium is an indispensable trace element for the human body and a normal component of human bones and teeth. Its function on the human body is mainly related to the formation of bones; The structure is also related, and its mechanism of action may be that strontium competes with sodium for absorption in the intestine, thereby reducing the body's absorption of sodium, increasing sodium excretion, and preventing cardiovascular diseases.

2. The biomedical degradable zinc-based alloy stent has controllable bioabsorption and degradation characteristics. It will not be like traditional metal stents such as stainless steel, cobalt chromium, and nickel titanium. Strong inflammatory response, and persists in the lumen wall for a long time, affects the diastolic function of the lumen, increases the risk of local inflammation, restenosis and thrombosis in the stent; the corrosion characteristic of the zinc-based alloy in the physiological environment is uniform corrosion, and the stent It can maintain a support state for a long time in the blood vessel, and the effective support can reach more than 4 months. It can effectively solve the risk of acute lumen occlusion after surgery, and avoid the mismatch between the degradation speed of degradable iron-based stents and magnesium-based stents and lumen reconstruction. Disadvantages, which are beneficial to the reconstruction of the lumen itself; compared with degradable polymer stents, the zinc-based stent has better imaging performance, which is convenient for surgical operation stent intervention and postoperative tracking, and the supporting force provided is more appropriate and can adapt to The process of positive luminal remodeling.

3. The surface of the zinc-based alloy stent provided by the present invention is one or more layers of degradable polymer coatings containing therapeutic drugs, which has good biocompatibility, can significantly improve the compatibility of the zinc-based alloy stent, and can resist Coagulation and anti-proliferation, reduce acute thrombosis and vascular inflammation, and facilitate the coverage of endothelial cells on the surface of the stent; at the same time, the therapeutic drug is uniformly blended in the polymer, which can realize the controlled release of the drug, reducing the sudden release of the drug and slowing down the drug Keep releasing at a certain concentration to reduce the incidence of acute and subacute thrombosis after stent implantation.

A method for preparing a degradable zinc-based alloy stent provided by the present invention is simple and convenient, and the electrolytic polishing process is safe. The degradable zinc-based alloy stent that can be prepared by using this method can be a vascular stent, a tracheal stent, an esophageal stent, and an intestinal stent , biliary stent or urethral stent, etc.

Description of drawings

Specific embodiments of the present invention will be described in detail in conjunction with the accompanying drawings.

Fig. 1 is a flowchart of a preparation method of a degradable zinc-based alloy stent provided by the present invention.

detailed description

The following examples of the present invention are given to further illustrate the present invention, but not to limit the scope of the present invention.

A novel degradable zinc-based alloy stent in the present invention comprises: a degradable zinc-based material stent matrix; the surface of the stent matrix is provided with a degradable polymer eluting coating containing therapeutic drugs; the stent matrix is Cylindrical mesh structure. Among them, the base material of the stent is designed from the perspective of the biological effects of alloying elements, and the elements beneficial to the human body are selected for alloying. Superior to magnesium-based stents; the degradable zinc-based material is pure zinc or zinc-based alloy; the zinc-based alloy is preferably Zn-Mg alloy, Zn-Ca alloy, Zn-Sr alloy, Zn-Sn alloy, Zn- One of Mg-Mn alloy, Zn-Mg-Ca alloy, Zn-Mg-Sr alloy, Zn-Mg-Sn alloy, Zn-Mg-Mn-Ca alloy, Zn-Mg-Ca-Sr alloy, etc.; further Preferably, the degradable zinc-based material is Zn-(0-1.5)% Ca alloy, Zn-(0-1.5)% Sn alloy, Zn-(0-1.5)% Mg-(0-1)% Mn alloy, Zn-(0～1.5)%Mg-(0～1)%Sn alloy, Zn-(0～1.5)%Mg-(0～1)%Ca-(0～0.5)%Mn alloy, Zn-( One of 0-1.5)% Mg alloy or Zn-(0-1.5)% Mg-(0-1)% Ca alloy.

The stent matrix is preferably a cylindrical mesh structure. The design of the stent shows better flexibility, which is convenient for intervention and placement, and has better radial support performance, and the stent has better development due to the metal zinc of the matrix material. performance, which is convenient for stent intervention and postoperative tracking; at the same time, one or more layers of degradable polymer eluting coatings containing therapeutic drugs are coated on the surface of the degradable zinc-based material stent matrix, and the degradable polymer Polylactic acid, polyglycolide, polyanhydride, polylactic acid copolymer, polyglycolic acid, polyhydroxybutyrate, polycyanoacrylate and other artificially synthesized degradable polymer materials It can also include one of natural degradable polymer materials such as collagen, gelatin or chitin, or even a blend of artificially synthesized degradable polymer materials and natural degradable polymer materials; the designed The biodegradable polymer coating can improve the biocompatibility of the bare metal stent, facilitate the coverage of endothelial cells on the surface of the stent, and control the release of drugs, reducing the sudden release of drugs and allowing the drug to be released slowly and continuously at a certain concentration to reduce the risk of stent implantation. The incidence of acute and subacute thrombosis after entry.

The flow chart of the preparation method of a degradable zinc-based alloy stent according to an embodiment of the present invention is shown in Figure 1, including the following steps:

1) Process the degradable zinc-based material into a stent matrix; the zinc-based material is composed of pure zinc or zinc-based alloy material, and can be processed into a vascular stent, a tracheal stent, an esophageal stent, an intestinal stent, a biliary stent or a urethral stent matrix etc.

2) The stent matrix is pretreated to remove processing residues and surface appendages; including a) performing mechanical treatment on the stent matrix; b) pickling or alkali cleaning the mechanically treated stent matrix; c) acid-washing or alkali-washing The stent matrix after cleaning is ultrasonically cleaned.

The step of mechanically treating the bracket base body is to use physical methods to remove residual burrs and the like after hollowing out.

The step of acid-washing or alkali-washing the mechanically treated stent matrix is to put the stent into pickling solution or alkaline solution for cleaning treatment (at room temperature) to remove impurities such as oil stains or oxides on the surface of the stent.

The pickling solution is a mixed solution of acetic acid and neutral sodium salt, which can be a blend solution of acetic acid and neutral sodium salts such as sodium chloride or sodium nitrate, and can be cleaned at room temperature for 3-5 minutes; the alkali The washing liquid is a mixed solution of sodium hydroxide and alkaline sodium salt, which can be a blended solution of sodium hydroxide and alkaline sodium salt such as sodium carbonate or sodium bicarbonate, and can be cleaned at room temperature for 5-10 minutes.

The step of ultrasonically cleaning the stent matrix after pickling or alkali cleaning involves cleaning the treated stent with clean water, generally pure water, to remove the acid or lye attached to the surface of the stent.

3) Electrolytic polishing is performed on the support base, that is, the support base is suspended in an electrolytic tank containing an electrolyte solution for electrolytic polishing.

The specific process is as follows: the DC voltage is 2.5-30V, the current is 0.2-10A, the electrolytic polishing time is 0.5-20 minutes, and the electrolytic temperature is 10-40°C.

Described electrolytic solution is the alcoholic solution of acid, and described acid can be phosphoric acid or perchloric acid or its mixture; The volume ratio of perchloric acid to absolute ethanol may be 1-4:20, or the volume ratio of perchloric acid: phosphoric acid: absolute ethanol may be 1-5:5-15:24-40.

The step 3) performing electropolishing treatment on the stent matrix also includes the step of cleaning the polished stent with purified water, that is, cleaning the treated stent with clean water, generally pure water, to remove ions attached to the surface of the stent.

4) Coating the degradable polymer eluting coating containing therapeutic drugs on the surface of the stent matrix after polishing, that is, the degradable polymer containing therapeutic drugs that will be prepared by spraying, dipping, electrostatic coating, etc. The solution is coated on the surface of the zinc-based material stent matrix. Spraying process is preferred, and the thickness of the degradable polymer elution coating is preferably 10-50 μm;

The degradable polymer includes one of artificially synthesized degradable polymer materials such as polylactic acid, polyglycolide, polyanhydride, polylactic acid copolymer, polyglycolic acid, polyhydroxypentyl butyrate, polycyanoacrylate, etc. or several kinds of copolymers; it can also include one or more of natural degradable polymer materials such as collagen, gelatin, and chitin, and even include artificially synthesized degradable polymer materials and natural degradable polymer materials. Blend; the therapeutic drug may be compounded with one or more drugs with anti-cell proliferation effects, such as rapamycin, paclitaxel, emodin, curcumin, etc., preferably rapamycin.

The degradable polymer solution containing the therapeutic drug is the above-mentioned high molecular material polymer-organic solvent solution carrying the above-mentioned therapeutic drug, wherein the high molecular material polymer is preferably polylactic acid; the organic solvent is preferably chloroform, bis Volatile organic solvents such as methyl chloride and tetrafluorohydrofuran; the preferred solvent is chloroform; the preferred drug is rapamycin;

Preferably, the mass ratio of rapamycin to polylactic acid is 1-3:9-27, and the volume ratio of polylactic acid to chloroform is 1-5:20-50.

A more preferred scheme is that the degradable polymer solution containing therapeutic drugs is a polylactic acid-chloroform homogeneous solution carrying rapamycin, the mass ratio of rapamycin to polylactic acid is 1:10, polylactic acid and chloroform The volume ratio is 1:20.

The present invention unexpectedly finds that when the degradable zinc-based material is selected as Zn-1%Mg alloy or Zn-1%Mg-0.5%Ca alloy, the high molecular material polymer is polylactic acid, and the therapeutic drug is rapamycin, When the organic solvent for preparing the degradable polymer solution is chloroform and the thickness of the drug coating is 20-40 μm, the stent of the present invention has particularly excellent performance in terms of degradation speed, biocompatibility and drug sustained release.

A preferred embodiment of a degradable zinc-based alloy stent and its preparation method according to the present invention is given below.

Example 1

A novel degradable zinc-based alloy stent in the present invention comprises a degradable zinc-based material stent base and a degradable polymer elution coating containing therapeutic drugs on the surface of the stent base; wherein the degradable zinc-based material is Zn -1% Mg alloy, the therapeutic drug is rapamycin, the degradable polymer is polylactic acid, the organic solvent for preparing the degradable polymer solution is chloroform, and the thickness of the elution coating is 30 μm.

Example 2

A novel degradable zinc-based alloy stent in the present invention comprises a stent matrix of degradable zinc-based material and a degradable polymer eluting coating containing therapeutic drugs on the surface of the stent matrix. Among them, the degradable zinc-based material is Zn-1%Mg-0.5%Ca alloy, the therapeutic drug is rapamycin, the degradable polymer is polylactic acid, the organic solvent for preparing the degradable polymer solution is chloroform, and the coating is eluted The thickness is 30 μm.

Example 3

The preparation method of the novel degradable zinc-based alloy stent described in embodiment 1 comprises the following steps:

1) Process the degradable zinc-based material into a stent matrix; that is, select a Zn-1%Mg alloy as the matrix material, draw it into capillary microtubes, and use laser engraving to make the stent matrix.

2) The stent matrix is pretreated to remove processing residues and surface appendages;

That is, it specifically includes a) removing the processing residues and obvious burrs from the above-mentioned bracket base under an optical magnifying glass; b) then immersing it in a mixed pickling solution of acetic acid and sodium nitrate, and pickling at room temperature for 5 minutes, wherein the components of the pickling solution are 40ml/L acetic acid and 10g/L sodium nitrate, and the balance is pure water; c) Place the stent base in clean water and clean it with an ultrasonic cleaner for 10 minutes.

3) Perform electrolytic polishing on the stent substrate

After drying the pretreated stent matrix, put it into an electrolytic tank filled with electrolyte for electrolytic polishing. The specific electrolytic polishing process is as follows: DC voltage is 10V, current is 1A, electrolytic polishing time is 3min, electrolytic temperature is 40°C and Use a constant temperature water bath to control the temperature; the electrolyte is a mixed acid-alcohol solution, and the specific formula is perchloric acid: phosphoric acid: absolute ethanol volume ratio of 1:13:26; then use pure water to ultrasonically clean the treated bracket to remove Acid ions attached to the surface of the scaffold.

4) Coating a degradable polymer eluting coating containing therapeutic drugs on the surface of the stent matrix after polishing;

After drying the polished stent matrix, fix it on a stent ultrasonic atomization spraying machine for spraying treatment, wherein, the propeller is filled with a polylactic acid-chloroform homogeneous solution carrying rapamycin, rapamycin and polylactic acid The mass ratio of polylactic acid to chloroform was 1:10, and the volume ratio of polylactic acid to chloroform was 1:20; after spraying, the stent was placed in a vacuum drying oven and dried at a constant temperature of 37°C for 24 hours to remove residual organic solvents.

Example 4

The preparation method of the novel degradable zinc-based alloy stent described in embodiment 2 comprises the following steps:

1) Process the degradable zinc-based material into a scaffold matrix;

That is, an alloy with a composition of Zn-1%Mg-0.5%Ca is selected as a matrix material, drawn into capillary microtubes, and laser-engraved to form a vascular stent matrix.

2) The stent matrix is pretreated to remove processing residues and surface appendages;

The specific steps include: a) first remove the processing residues and obvious burrs under the optical magnifying glass; b) then immerse in the mixed alkali washing solution of sodium hydroxide and sodium carbonate, and perform alkaline washing treatment at room temperature for 5 minutes, wherein the composition of the alkaline washing solution is 10g/L sodium hydroxide and 10g/L sodium carbonate, and the balance is pure water; c) place the stent base in clean water and clean it with an ultrasonic cleaner for 10 minutes.

3) Perform electrolytic polishing on the stent substrate

After drying the pretreated stent matrix, put it into an electrolytic tank filled with electrolyte for electrolytic polishing. The specific electrolytic polishing process is as follows: DC voltage is 15V, current is 2A, electrolytic polishing time is 5min, electrolytic temperature is 40°C and Use a constant temperature water bath to control the temperature, and the electrolyte formula is 350ml:650ml phosphoric acid alcohol solution; then use pure water to ultrasonically clean the treated stent to remove the ions attached to the surface of the stent.

4) Coating a degradable polymer eluting coating containing therapeutic drugs on the surface of the stent matrix after polishing;

After drying the polished stent matrix, fix it on a stent ultrasonic atomization spraying machine for spraying treatment, wherein, the propeller is filled with a polylactic acid-chloroform homogeneous solution carrying rapamycin, rapamycin and polylactic acid The mass ratio of polylactic acid to chloroform was 1:10, and the volume ratio of polylactic acid to chloroform was 1:20; after spraying, the stent was placed in a vacuum drying oven and dried at a constant temperature of 37°C for 24 hours to remove residual organic solvents.

Examples 5-10 The preparation methods of the degradable zinc-based alloy stents in these 6 examples are the same as in Example 3, and the specific parameters of each are shown in Table 1.

Comparative Experiment

1*The radial stress when the specified deformation is 10% in the experiment.

2*Data quoted from Journal of Materials Science: Materials in Medicine, 2013,24(3):713-724.

3*Quoted from The Lancet, 2013, 381(9869):836-844.

4*Quoted from International journal of cardiology, 2013, 167(1): 11-21.

Although the present invention has been described in detail with general descriptions and specific embodiments above, it is obvious to those skilled in the art that some modifications or improvements can be made on the basis of the present invention. Therefore, the modifications or improvements made on the basis of not departing from the spirit of the present invention all belong to the protection scope of the present invention.

Claims (5)

1. a kind of degradable zinc-containing alloy support, it is characterised in that include：Degradable Zr-based materials rest body；The support base Body surface face is provided with the degradable polymer eluting coatings containing curative drug；The rest body is drum type brake network structure； The degradable Zr-based materials are Zn- (0～1.5) %Ca alloys, Zn- (0～1.5) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Mn alloys, Zn- (0～1.5) %Mg- (0～1) %Sn alloys, Zn- (0～1.5) %Mg- (0～1) %Ca- (0～ 0.5) one kind in %Mn alloys, Zn- (0～1.5) %Mg alloys or Zn- (0～1.5) %Mg- (0～1) %Ca alloys；It is described Degradable polymer is polylactic acid；The curative drug is rapamycin；The thickness of the eluting coatings is 10～50 μm；With Chloroform prepares PLA solution for solvent, and polylactic acid is 1～5: 20～50 with the mass volume ratio of chloroform；Rapamycin and poly- breast The mass ratio of acid is 1～3: 9～27.

2. degradable zinc-containing alloy support according to claim 1, it is characterised in that the degradable Zr-based materials are Zn- 1%Mg alloys or Zn-1%Mg-0.5%Ca alloys；The thickness of the eluting coatings is 30 μm；The mass body of polylactic acid and chloroform Product is than being 1: 20；Rapamycin is 1: 10 with the mass ratio of polylactic acid.

3. degradable zinc-containing alloy support according to claim 1, it is characterised in that the degradable Zr-based materials are Zn- 1%Ca alloys, Zn-1%Sn alloys, Zn-1%Mg-0.5%Mn alloys, Zn-1%Mg-0.5%Sn alloys or Zn-1%Mg- 0.5%Ca-0.1%Mn；The thickness of the eluting coatings is 30 μm；Polylactic acid is 1: 20 with the mass volume ratio of chloroform；Thunder handkerchief Mycin is 1: 10 with the mass ratio of polylactic acid.

4. the preparation method of the arbitrary degradable zinc-containing alloy support of claim 1-3, including：1) by degradable Zr-based materials It is processed into rest body；2) pretreatment is carried out to rest body, processing residual and surface appurtenance is rejected；3) rest body is entered The process of row electrobrightening；4) polishing after-poppet matrix surface degradable polymer eluting of the coating containing curative drug is applied Layer；

The step 2) include：Pickling or alkali cleaning process step are carried out to the rest body after mechanical treatment；The pickle is Acetic acid and Sodium Chloride or the blend solution of sodium nitrate；Described alkali wash water is that sodium hydroxide is molten with sodium carbonate or sodium bicarbonate blending Liquid；

The step 3) it is that rest body is put into electrolyte to carry out electrobrightening process：DC voltage be 2.5～30V, electric current For 0.2～10A, the electrobrightening time is 0.5～20 minute, and electrolysis temperature is 10～40 DEG C；The electrolyte is the anhydrous of acid Ethanol solution, the acid are phosphoric acid or perchloric acid or its mixed liquor；The electrolyte is phosphoric acid and the volume ratio of dehydrated alcohol is 2 ～5: 5～2, or the volume ratio of perchloric acid and dehydrated alcohol is 1～4: 20, or perchloric acid: phosphoric acid: dehydrated alcohol Volume ratio is 1～5: 5～15: 24～40.

5. the preparation method of degradable zinc-containing alloy support according to claim 4, it is characterised in that step 4) it is to configure The degradable polymer solution containing curative drug rest body table is coated in by spraying, dip-coating or electrostatic coating method Face.