WO2009082876A1

WO2009082876A1 - A controlled degradation magnesium metal coating scaffold and its preparation method

Info

Publication number: WO2009082876A1
Application number: PCT/CN2008/001313
Authority: WO
Inventors: Saying Dong; Zhengcai Zhang; Xiaogang Liu; Lixiao Zhao; Zhongjie Pu
Original assignee: Lepu Medical Technology (Beijing) Co., Ltd.
Priority date: 2008-01-03
Filing date: 2008-07-14
Publication date: 2009-07-09
Also published as: CN101214396A

Abstract

A controlled degradation magnesium metal coating scaffold includes a backbone made of medical high pure magnesium or Mg-alloy. The surface of the scaffold backbone has an anticorrosive coating. The surface of the anticorrosive coating has a degradable polymer film drug-loading coating which loads a curative drug. The preparation method of the scaffold includes: anticorrosive treating on the surface of the backbone to form anticorrosive coating, coating the degradable polymer film drug-loading coating on the surface of the anticorrosive coating, and coating the curative drug on the surface of the drug-loading coating and so on.

Description

Controllable degradation magnesium metal coated stent and preparation method thereof

The invention belongs to the field of medical instruments, and particularly relates to a magnesium metal coated stent capable of controlled degradation and a preparation method thereof. Background technique

In 1976, the German scholar Andrea 'Glonzgo first proposed the idea of installing stents in the arteries. By the 1990s, coronary stents have been widely used in clinical treatment. At present, the coronary stent technique has been developed to a drug-eluting stent based on stainless steel and cobalt-chromium alloy, but it still cannot fundamentally solve the problem of stent thrombosis and restenosis. There is a high rate of restenosis after surgery and a strong thrombus source. And the stent remains permanently in the body and other defects, the long-term effect is not ideal.

Magnesium is one of the most abundant elements on the earth. It is also the fourth most abundant cation in the human body and the second most abundant cation in the human body. It is an indispensable nutrient element in the human body. It is about 20 grams in the human body. Magnesium promotes the formation of bones and cells during life, catalyzes or activates more than 300 enzyme systems in the body, participates in energy metabolism in the body, and plays a key role in the transport, storage and utilization of energy. Magnesium affects protein synthesis by regulating the structure of ribosomal DNA and RNA in the three major metabolisms of the body. The chemical reaction of magnesium in the aqueous medium is converted into magnesium ions, and the magnesium ions are adjusted by the absorption in the body and the metabolism of the kidney, so that the magnesium alloy material is gradually degraded and absorbed in the body. Magnesium alloys have become the material of choice for stents due to their good mechanical properties, controlled corrosion properties and minimal side effects of degradation products. Magnesium has good medical safety as a biomedical material, and is especially suitable for the treatment of cardiovascular diseases. Although magnesium alloy stents have good magnetic resonance imaging (MRI) compatibility, they cannot be displayed under "X-ray". Intravascular ultrasound guidance must be used when implanting; another disadvantage of magnesium alloy stents is that the degradation rate is too fast. It has completely degraded in about 2 months.

The degradable polymer material has the advantages of non-toxicity, non-irritation, easy processing and molding, and large drug loading. However, as a scaffold material, its strength is low, hardness and rigidity are difficult to meet the needs of use. At the same time, the degradable polymer scaffold has a series of shortcomings such as poor degradation controllability, poor processing stability, poor storage stability, accumulation of local acidic degradation products, and affecting healing.

Patent CN1857742A discloses a scaffold material used in combination with a degradable polymer material, which can delay the corrosion of the magnesium alloy, prolong the service life of the stent, and increase the drug loading and the mechanical strength of the stent. However, since there is no surface anti-corrosion treatment process of the magnesium alloy, in the blood, the polymer material may start to degrade at the same time as the magnesium alloy, and there is a disadvantage that the degradation rate of the magnesium alloy material is fast. Summary of the invention

The object of the present invention is to provide a controllable and degradable magnesium metal coated stent and a preparation method thereof. The stent is provided with a coating composed of a magnesium alloy anticorrosive layer and a degradable polymer material, which can reduce the corrosion of the magnesium alloy stent. Rate and control the release of the drug; in this method, the surface of the magnesium alloy stent is treated with anti-corrosion treatment to delay the degradation of the magnesium alloy stent.

In order to achieve the above object, the present invention uses the following technical solutions:

A controllable degradation magnesium metal coated stent, wherein the stent body is made of medical high-purity magnesium or magnesium alloy, the surface of the stent body has an anti-corrosion coating, and the surface of the anti-corrosion coating is coated with a degradable polymer film for drug loading a coating that carries a therapeutic drug.

Wherein, the anticorrosive coating may be a medically acceptable metal oxide coating, preferably a magnesium oxide coating.

The degradable polymer film-coated coating comprises one or more of the following substances: polylactic acid, poly-L-lactic acid, polyglycolide, polyglycolic acid, polycyanoacrylate, polycaprolactone , polyanhydrides, polylactic acid copolymers, polyhydroxybutyrate, polyacetylglutamic acid, polyorthoester, polyethylene oxide, polybutene copolymer, polyorthoester, polycaprolactone, polyglycolic acid , polyethylene oxide, polybutylene terephthalate copolymer, methacrylate or ester, methacrylate or ester, polyurethane, silicone, polyvinyl alcohol, vinyl alcohol, polyglycolic acid, poly Phospholipase, and a copolymer between the above polymers, collagen, gelatin, and chitin.

Wherein, the therapeutic drug comprises one or more of the following: anti-proliferative agent, anti-drug Biotin, antimetabolites, hormonal drugs, anticoagulant drugs, antisecretory drugs, etc. Wherein, the magnesium alloy may be a magnesium-aluminum alloy, a magnesium-manganese alloy, a magnesium-zinc alloy, a magnesium-zirconium alloy, a magnesium rare earth alloy, a magnesium-lithium alloy, a magnesium-calcium alloy or a magnesium-silver alloy. Or a binary, ternary or multi-component magnesium alloy composed of these systems, wherein any of the above magnesium alloys has a magnesium content of more than 50%.

The medical device made of the magnesium alloy includes but is not limited to: a blood vessel stent, a bone suture, a bone nail, a bone connector, a spinal bone plate, a suture anchor, a hemostatic forceps, a hemostatic screw, a hemostatic plate, and a hemostasis. Clips and so on.

The invention also provides a preparation method of a controlled degradation magnesium metal coated stent, wherein the stent body material is medical high-purity magnesium or magnesium alloy, the method comprises the following steps: preserving the stent body, after anti-corrosion treatment The surface of the stent body is formed with an anti-corrosion coating; a surface of the anti-corrosion coating is coated with a degradable polymer film-loaded coating; and a therapeutic drug is coated on the surface of the drug-loading coating.

In the method, the stent body is made by laser engraving or machining before the stent body is subjected to an anticorrosive treatment.

The body of the bracket should be clean and the surface of the bracket body should be cleaned before the anti-corrosion treatment, including mechanical cleaning and chemical cleaning. The mechanical cleaning can be carried out according to the following steps: grinding the surface of the bracket body through a belt, mechanically removing the surface oxide, adjusting the surface roughness; cleaning the surface of the bracket body with ultrasonic waves, and removing impurities on the surface of the bracket body; Chemical cleaning can be carried out according to the following steps: cleaning with medical ethanol solvent; cleaning with medical ethanol solvent and cleaning with acetone analytical pure solution; acetone analysis for pure solution cleaning and washing with deionized water. The chemical cleaning may further comprise the steps of: immersing the stent body in a sodium hydroxide solution for removing grease and scale; then washing with deionized water and drying under vacuum.

In this method, the anticorrosive treatment can be carried out by a chemical oxidation or anodization method. The chemical oxidation preservative treatment can be realized by the following method: immersing the stent body in a chemical oxidation bath at a temperature of 343 ~ 353K, and an oxidation time of 0.5 ~ 2.0 minutes, the tank The liquid contains: potassium dichromate 15~20g/L, nitric acid 15~25g/L, sodium chloride 0.75 ~ 1.25g/L. The anodizing treatment can be performed by alternating current oxidation. The specific method is to install the same bracket body on the two electrodes, and immerse the bracket in the bath at a temperature of 293 333K, an oxidation time of 10 to 50 minutes, and a current density of 0.1 to 10 A/ Dm ² , using an AC voltage of 50 ~ 90 V, the bath contains: potassium permanganate 15 ~ 20g / L, trisodium phosphate 15 ~ 55 gL, potassium fluoride 25 ~ 55g / L, potassium hydroxide 65 ~165g / L, aluminum hydroxide 15 ~ 65 g / L; in this method, dip coating, spray coating, thermal spraying, electrostatic coating, sol-gel, supercritical liquid coating, etc., in the anti-corrosion The surface of the coating is coated with a degradable polymer film-loaded coating. For example, the preservative-treated stent can be immersed in a degradable polymer material solution, properly soaked, and vacuum dried. The concentration of the degradable polymer material solution is usually about 1.0 mg/mL, and the soaking time is usually 5 to 20 minutes. Of course, the soaking time of the stent in different solutions can be adjusted accordingly, for example, immersing in a polylactic acid solution for 5 to 15 minutes, and using a polyglycolic acid solution for 20 minutes, which is mainly related to degradable polymer polymerization. The type of material and the thickness of the film required. The excess surface solution can be removed by low-speed centrifugation, for example, at 1000 rpm for 3 minutes. The temperature can be set at 30~40 °C during vacuum drying, and it can be dried for 30~60min.

In this method, the therapeutic drug can also be applied to the surface of the drug-loaded coating by dip coating or spraying. Taking rapamycin as an example, the spraying method may be: using methanol as a solvent, using a rapamycin solution having a concentration of l~15 g/ml for directional ultrasonic spraying on the surface of the stent body, rotating the stent body at a constant speed, according to the stent The surface of the body should be sprayed 1~15 times. The dip coating method can be: using tetrahydrofuran as an organic solvent to prepare a rapamycin solution with a concentration of 1~15 g/ml, soak the stent body in the above solution. - 10 minutes, repeat dip coating four times.

In the method, the coating process of coating the degradable polymer film-loading coating or coating the therapeutic drug, using any one of the following or a combination thereof: dip coating, spray coating, thermal spraying, electrostatic coating , sol-gel, supercritical liquid coating.

In the method, the anti-corrosion treatment may also adopt any one or more of the following anti-corrosion methods: Ion implantation, laser surface treatment, thermal diffusion, metal plating, vapor deposition, organic coating. The positive beneficial effects of the present invention include:

1. Excellent mechanical and pharmaceutical properties: The surface-coated controlled degradable pure magnesium and magnesium alloy stents still maintain the excellent mechanical properties of the metal materials, improve the mechanical strength of the stent, and enable the implantation of magnesium materials. The device can effectively maintain good mechanical properties during service; at the same time, the use of the surface degradable polymer layer greatly improves the type and quantity of drugs required for the stent, and improves the stability of the drug fixation; the magnesium alloy anti-corrosion layer The coating composed of the degradable polymer material can fix different drugs and dosages by adjusting the molecular weight and the thickness of the polymer layer, and can carry a plurality of therapeutic drugs, and the drug loading amount is more than 30%;

2. The degradation rate of magnesium material is reduced, and the service life of the stent is prolonged. Due to the intimacy of the polymer material, no matter how thick the polymer is, it is difficult for the polymer material to prevent the water molecules from reaching the surface of the magnesium alloy. Therefore, the magnesium alloy will start simultaneously with the polymer material. Degradation; preparation of anti-corrosion coating on magnesium alloy surface can delay the corrosion of magnesium alloy, prolong the service life of the stent, greatly reduce the degradation rate of magnesium alloy and control the release of the drug, and avoid the problem of reduced function due to degradation of the stent;

3, safe use, meet clinical needs: As we all know, magnesium and magnesium alloys can be gradually degraded by the body in the physiological environment and absorbed or metabolized by the body. The degradation products are mainly magnesium ions required by the human body, and other magnesium alloy materials. The content of alloying elements is within the range of biomedicine. Therefore, it is safe to prepare controlled degradable medical implanted devices with pure magnesium and magnesium alloys. At the same time, biodegradable polymer materials are gradually degraded by hydrolysis reaction in organisms. For C0 ₂ and H ₂ 0, the degradation products are safe to the human body; the accumulation of local acidic degradation products of the existing degradable polymer scaffolds is improved, and the healing condition is affected to meet the clinical needs. DRAWINGS

1 is a schematic structural view of a metal-coated stent with controlled degradation according to the present invention;

Figure 2 is an enlarged cross-sectional view taken along line AA of Figure 1; 3 is a flow chart of a method for preparing a metal-coated stent with controlled degradation according to the present invention.

In the figure: 1, stent; 101, stent body; 102, anti-corrosion coating; 103, drug-coated coating; 104, therapeutic drugs;

Figure 4 is a comparison of corrosion resistance of a magnesium alloy stent before and after application of a degradable polymer film. Curve 1 is a linear polarization curve of a stent surface coated with a degradable polymer film, and curve 2 is a linearity of a magnesium alloy bare stent. Polarization curve. detailed description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

As shown in FIG. 1 , the controllable degradable magnesium metal coated stent provided by the invention can be made of medical high-purity magnesium or magnesium alloy. The magnesium alloy is a binary, ternary or multi-component magnesium alloy with a magnesium content of more than 50%. The content of alloying elements in the magnesium alloy should basically meet the requirements of biomedicine, so that the degradation amount in the degradation process should not be Within the dose range that causes tissue toxicity. The magnesium alloy includes magnesium alloy series alloy, magnesium manganese series alloy, magnesium zinc series alloy, magnesium zirconium series alloy, magnesium rare earth series alloy, magnesium lithium series alloy, magnesium calcium series alloy or magnesium silver series alloy and other different alloy systems. One or a binary, ternary or multi-component magnesium alloy in which these systems are combined, but is not limited thereto.

The stent 1 is formed by laser engraving or machining, and can be made into a blood vessel stent, and can also be made into a bone suture, a bone nail, a bone connector, a spinal push bone plate, a suture anchor, a hemostatic forceps. , hemostatic screws, hemostatic plates, hemostatic clips, and medical equipment such as tissue adhesives, sealants, artificial bones.

As shown in FIG. 2, the stent 1 includes a stent body 101, an anti-corrosion coating 102, a drug-loaded coating 103, a therapeutic drug 104, and the like; a surface of the stent body 101 is provided with an anti-corrosion coating 102, and the surface of the anti-corrosion coating 102 A degradable polymer film-loaded drug coating 103 is disposed, and the drug-loaded coating 103 carries a therapeutic drug 104 thereon.

The anti-corrosion coating 102 may be magnesium oxide, but is not limited thereto.

The degradable polymer film-coated coating 103 comprises one or more of the following substances: polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolide or polyhydroxyl Acetic acid (PGA), polycyanoacrylate (PACA), polycaprolactone (PCL), polyanhydrides: including aliphatic polyanhydrides, aromatic polyanhydrides, heterocyclic polyanhydrides, polyacid anhydrides and cross-linkable Polylactic acid copolymer, etc., polylactic acid copolymer (PLGA), polyhydroxybutyrate (PHBV), polyacetylglutamic acid (PAGA), polyorthoester (POE), polyethylene oxide / polybutene copolymer (PEO) /PBTP), polyorthoester, polycaprolactone, polyglycolic acid, polyoxyethylene/polybutylene terephthalate copolymer, methacrylate or ester, methacrylate or ester, polyurethane , silicone resin, polyvinyl alcohol, vinyl alcohol, polyglycolic acid, polyphosphatase, etc., and copolymers between the above polymers, in addition to natural degradable polymer materials such as collagen, gelatin, and chitin. , but not limited to this.

The therapeutic drug 104 includes one or more of the following: an anti-proliferative agent, an antibiotic, an antimetabolite, a hormonal drug, an anticoagulant drug, a secretory drug, and the like, but is not limited thereto.

FIG. 3 is a flow chart showing a method for preparing a controllable degradable magnesium metal coated stent according to the present invention. The method mainly comprises the steps of: 1 forming a stent body by laser engraving or machining; 2 surface cleaning; 3 surface antiseptic treatment; 4 coating a degradable polymer film-loaded drug coating; 5 coating a therapeutic drug process step, wherein:

2 surface cleaning: including mechanical cleaning and chemical cleaning;

Specific mechanical cleaning and chemical cleaning methods are:

a. The surface of the bracket body 101 is ground by a belt, mechanically removing oxides on the surface, and adjusting the surface roughness;

b. Ultrasonic cleaning of the surface of the stent to remove impurities on the surface of the stent body 101, the ultrasonic frequency is 28~100khz, the cleaning time is 5-15 minutes; the cleaning step includes 1) cleaning with a concentration of 75% medical ethanol solvent; ) using a solution of 99.5% acetone to clean the solution; 3) using deionized water for cleaning;

c The stent body 101 is immersed in a sodium hydroxide solution having a concentration of 15 to 60 g/L and a temperature of 343 to 373 K for 5 to 10 minutes to remove grease and scale; and then washed with deionized water; The cleaned stent body 101 is placed in a vacuum dryer to be dried, the temperature is set at 30 to 40 ° C, and dried for 30 to 60 minutes, and then taken out.

3 Surface anti-corrosion treatment: including chemical oxidation treatment, anodizing treatment, or any one of them;

The specific method is:

a. The composition of the bath for chemical oxidation treatment is: potassium dichromate 15~20g/L, nitric acid 15~25g/L, sodium chloride 0.75~ 1.25g/L; the stent body 101 is immersed in the above solution, the temperature is selected 343 ~ 353K, oxidation time is 0.5 ~ 2.0 minutes, the surface can form an oxide film; b. Anodizing treatment 交流 is oxidized by alternating current, the same magnesium alloy support 1 is installed on both electrodes, and the bath composition for anodizing treatment is: Potassium permanganate 15~20g/L, trisodium phosphate 15 ~ 55g/L, potassium fluoride 25 ~ 55g / L, potassium hydroxide 65 ~ 165 g / L, aluminum hydroxide 15 65 g / L; temperature Select 293-333K, oxidation time is 10 ~ 50 minutes, current density is 0.1 ~ 10A / dm ² , the AC voltage is 50~90V, the surface can form an oxide film;

In addition to the above chemical oxidation treatment and anodizing treatment, any one of various anticorrosive processes such as ion implantation, laser surface treatment, thermal diffusion, metal plating, vapor deposition, organic coating, or the like may be used to form the surface. Anti-corrosion coatings, these anti-corrosion treatment technologies are all prior art and will not be described in detail here.

4 preparing a degradable polymer film carrying drug coating;

Prepared by any of the following methods:

a. The preservative-treated stent 1 is immersed in a degradable polymer material polylactic acid (PLA) solution at a concentration of 1.0 mg/mL for 5 to 15 minutes, on a flying pigeon TGL-16G centrifuge at 1000 rpm. Centrifuge at a speed of 3 minutes for 3 minutes, then dry the holder 1 in a vacuum oven, set the temperature at 30~40 °C, and remove it after drying for 30~60 minutes;

b. Soak the preservative-treated stent 1 in a polyglycolic acid (PGA) solution at a concentration of 1.0 mg/mL for 20 minutes, on a flying pigeon TGL-16G centrifuge, to 1000 Centrifuge at a speed of rpm for 3 minutes, then dry the holder 1 in a vacuum oven, set the temperature at 30 ~ 40 ° C, and remove it after drying for 30 - 60 minutes;

5 coating a therapeutic drug;

After the degradable polymer film-coated coating 103 on the surface of the stent 1 is fixed, a therapeutic drug is applied by any one of the following methods:

a. Using methanol as a solvent, adding rapamycin or paclitaxel at a concentration of 1 ~ 15μ^π1 to the surface of the stent 1 for directional ultrasonic spraying, rotating the stent 1 at a constant speed, spraying 1 to 15 times according to the surface drug content of the stent 1 ;

b. Using tetrahydrofuran as an organic solvent, add rapamycin at a concentration of l ~ 15 g/ml, soak the stent 1 in the above solution for 5 - 10 minutes, and repeat dip coating four times.

In the method, the surface coating process except 4 coating the degradable polymer polymer film-loading coating; 5 coating the therapeutic drug process step, in addition to dip coating, spraying, thermal spraying, electrostatic coating Any one of sol gel, supercritical liquid coating process or a combination thereof.

The preferred embodiment is given below.

Example 1

After high-purity magnesium is polished, it is laser-engraved into a blood vessel stent;

1 Surface cleaning: 1) Using a 75% concentration of medical ethanol solvent, the surface of the stent body 101 is cleaned by ultrasonic waves for 10 minutes; 2) cleaning with a solution of 99.5% acetone; 3) Ionized water is washed, and the cleaned stent body 101 is placed in a vacuum dryer to be dried;

2 surface anti-corrosion treatment: The stent body 101 is immersed in a solution of potassium dichromate 15g / L, 15g / L of nitric acid, 1.0 g / L of sodium chloride, and oxidized at 80 ° C for 1 minute, the surface can form an oxide film;

3 Preparation of degradable polymer film-loaded coating: The anti-corrosion-treated stent 1 was immersed in a polylactic acid (PLA) solution at a concentration of 1.0 mg/mL for 15 minutes on a flying pigeon TGL-16G centrifuge. Centrifuge at 1000 rpm for 3 minutes, then place the holder 1 in a vacuum oven to dry, set the temperature at 30 ° C, and dry for 60 minutes. take out;

4 Coating therapeutic drug: Using methanol as a solvent, adding rapamycin at a concentration of 10 _μβ / ηη1, spraying on the surface of the stent 1 and repeating spraying 10 times.

Example 2

After the AZ31B magnesium alloy is polished, it is laser-engraved into a blood vessel stent;

2 Surface anti-corrosion treatment: The stent body 101 is anodized, and the same stent body 101 is mounted on the two electrodes. The bath composition of the anodizing treatment is: potassium permanganate 15 g/L, trisodium phosphate 15 g/L, Potassium fluoride 25 g / L, potassium hydroxide 65 g / L, aluminum hydroxide 15 g / L, oxidation at 30 ° C for 15 minutes, current density of 3A / dm ² , AC voltage is 60V, the surface is An oxide film can be formed;

3 Preparation of degradable polymer film drug-loaded coating: The preservative-treated stent 1 was immersed in a 1.0 mg/mL polyglycolic acid (PMA) solution for 20 minutes on a flying pigeon TGL-16G centrifuge to 1000 Centrifugal treatment for 3 minutes at rpm, then the stent 1 was placed in a vacuum oven to dry, the temperature was set at 40 ° C, and dried for 40 minutes and then taken out;

4 Coating therapeutic drug: tetrahydrofuran was used as an organic solvent, and rapamycin having a concentration of 10 g/ml was added, and the stent body 1 was immersed in the above solution for 5 minutes, and dip coating was repeated four times.

Experimental example 1

This example was used to investigate the degradation of the stent after preservative treatment.

Materials and Methods

The stent prepared in Example 2 was used as an experimental object, and the change in corrosion resistance before and after the stent was coated with the degradable polymer film was compared. Using the linear scanning function of the M2273 potentiostat, the stent was placed in a phosphate buffer solution of pH 7.4, and the linear polarization curves of the bare stent and the coated polymer membrane stent were tested at room temperature. The results are shown in FIG. Curve 2 in Figure 4 is a linear polarization curve of a magnesium alloy stent in pH 7.4 PBS, and curve 1 is a linear polarization curve after coating the surface of the stent with a degradable polymer film. Can be seen from Figure 4:

1. After the magnesium alloy stent is coated with the degradable polymer film, the potential is obviously positively shifted, and the corrosion resistance is improved; at the same time, the corrosion current is also significantly reduced.

2. The linear polarization resistance of curve 2 is 656.3 ohms, the linear polarization resistance of curve 1 is 9574.6 ohms, and the reciprocal of the polarization resistance represents the corrosion rate of the metal material. Therefore, the corrosion resistance of the stent surface is significantly improved after coating the degradable polymer film, and the service life of the magnesium alloy stent is prolonged.

Although the present invention has been described in detail with reference to the preferred embodiments of the present invention, it will be apparent to those skilled in the art. Therefore, such modifications or improvements made without departing from the spirit of the invention are intended to be within the scope of the invention. Industrial applicability

After the surface anti-corrosion treatment, the pure magnesium or magnesium alloy stent of the invention can delay the corrosion of the magnesium alloy, prolong the service life of the stent, greatly reduce the degradation rate of the magnesium alloy and control the release of the drug, and avoid the use function caused by the degradation of the stent. The problem of reduction, by modifying the degradable polymer material, improving the controllability of degradation, processing stability, easy processing, and its strength, hardness and rigidity can meet the requirements of medical use. The use of pure magnesium and magnesium alloys for the preparation of controlled degradation medical implants is safe and practical.

Claims

Claim

A controllable degradation magnesium metal coated stent, wherein the stent body is made of medical high-purity magnesium or magnesium alloy, wherein the surface of the stent body is coated with an anti-corrosion coating, and the surface of the anti-corrosion coating is coated with The polymeric polymer film-loaded coating is degraded, and the drug-loaded coating carries a therapeutic drug.

2. The controlled degradation magnesium metal coated stent according to claim 1, wherein the anticorrosive coating is magnesium oxide.

3. The controlled degradation magnesium metal coated stent according to claim 1, wherein the degradable polymer film-loaded coating comprises one or more of the following: polylactic acid, poly-L-lactic acid , polyglycolide, polyglycolic acid, polycyanoacrylate, polycaprolactone, polyanhydride, polylactic acid copolymer, amyl hydroxybutyrate, polyacetyl glutamic acid, polyorthoester, polyoxidation Ethylene, polybutene copolymer, polyorthoester, polycaprolactone, polyglycolic acid, polyethylene oxide, polybutylene terephthalate copolymer, methacrylate or ester, methacrylate or ester, Polyurethane, silicone, polyvinyl alcohol, vinyl alcohol, polyglycolic acid, polyphosphatase, and copolymers between the above polymers, collagen, gelatin, chitin.

4. The controlled degradation magnesium metal coated stent according to claim 1, wherein the therapeutic drug comprises one or more of the following: an anti-proliferative agent, an antibiotic, an antimetabolite, a hormone. Drugs, anticoagulants, and secreted drugs.

The controllable degradable magnesium metal coated stent according to any one of claims 1 to 4, wherein the magnesium alloy is a magnesium-aluminum alloy, a magnesium-manganese alloy, a magnesium-zinc alloy, and magnesium. a zirconium series alloy, a magnesium rare earth series alloy, a magnesium lithium series alloy, a magnesium calcium series alloy or a magnesium silver series alloy, or a binary system, a ternary system or a multicomponent magnesium alloy formed by combining these systems, any of the above The magnesium content of the magnesium alloy is greater than 50%.

The controlled degradation magnesium metal coated stent according to any one of claims 1 to 4, wherein the magnesium alloy is formed by a stent comprising: a blood vessel stent, a bone suture, a bone nail, and a bone. Connector, ridge push plate, suture anchor, hemostat, hemostatic screw, hemostatic plate, Hemostatic clips, as well as medical scaffolds for tissue adhesives, sealants, and artificial bones.

A method of preparing the stent according to any one of claims 1 to 6, comprising the steps of:

And preserving the stent body to form an anticorrosive coating on the surface thereof; coating a surface of the anticorrosive coating with a degradable polymer film-loading coating; and coating the surface of the drug-loading coating with therapeuticity drug.

8. The method of claim 7, wherein the stent body is made by laser engraving or machining.

9. The method of claim 7 further comprising the step of mechanically cleaning and chemically cleaning the surface of the stent body prior to the preservative treatment.

10. The method according to claim 7, wherein the preservative treatment is a chemical oxidation treatment or an anodization treatment.

The method according to claim 10, wherein the chemical oxidation treatment tank used in the chemical oxidation preservative treatment comprises: potassium dichromate 15-20 g/L, nitric acid 15-25 g/L, chlorine Sodium hydride 0.75 1.25 g/L; The stent body is immersed in the bath for chemical oxidation treatment at a temperature of 343 - 353 K and an oxidation time of 0.5 - 2.0 minutes.

12. The method according to claim 10, wherein the anodizing treatment is performed by alternating current oxidation, and the same stent body is mounted on the two electrodes, and the bath for anodizing treatment comprises: potassium permanganate 15-20 g/ L, trisodium phosphate 15 ~ 55 g / L, potassium fluoride 25 ~ 55 g / L, potassium hydroxide 65 ~ 165 g / L, aluminum hydroxide 15 ~ 65 g / L; temperature 293 ~ 333K, oxidation time For 10 50 minutes, the current density is 0.1 ~ 10A/dm ² , and the AC voltage used is 50 ~ 90V.

13. The method according to claim 9, wherein the mechanical cleaning step is: grinding the surface of the bracket body through a belt, removing oxides on the surface, adjusting surface roughness; and using ultrasonic waves on the surface of the bracket body Cleaning is performed to remove impurities from the surface of the stent body.

14. The method of claim 9 wherein said chemical cleaning step For: Wash with medical ethanol solvent; clean with acetone to analyze pure solution; finally rinse with deionized water.

15. The method according to claim 14, further comprising the following steps after chemically cleaning the surface of the support body:

The stent body is immersed in an alkaline solution for removing grease and scale; then washed with deionized water and dried under vacuum.

The method according to claim 7, wherein the method for coating the surface of the anti-corrosion coating with a degradable polymer film coating is selected from any one of the following: Soak in a degradable polymer material polylactic acid solution with a concentration of 1.0 mg/mL for 5 15 minutes, centrifuge at 1000 rpm for 3 minutes, and place the holder body in a vacuum drying oven to dry. The temperature is set at 30 ~ Remove at 40 °C for 30 to 60 minutes;

The stent body was immersed in a polyglycolic acid solution having a concentration of 1.0 mg/mL for 20 minutes, centrifuged at 1000 rpm for 3 minutes, and the stent body was placed in a vacuum drying oven to be dried. The temperature was set at 30 ~ 40 ° C, dry for 30 ~ 60min and remove.

The method according to claim 7, wherein the method for applying a therapeutic drug to the surface of the degradable polymer film coating layer is any one of the following: using methanol as a solvent The rapamycin solution having a concentration of l ~ 15 g/ml is subjected to directional ultrasonic spraying on the surface of the stent body, and the stent body is rotated at a constant speed, and spraying is performed 1 to 15 times according to the drug content of the stent body surface;

Using tetrahydrofuran as an organic solvent, a rapamycin solution having a concentration of l ~ 15 g/ml was prepared, and the stent body was immersed in the above solution for 5-10 minutes, and dip coating was repeated four times.

18. The method according to claim 7, wherein the coating process of coating the degradable polymer film-coated coating or coating the therapeutic drug is selected from any one of the following or a combination thereof: Dip coating, spray coating, thermal spraying, electrostatic coating, sol-gel, supercritical liquid

19. The method according to claim 7, wherein the anticorrosive treatment is as follows Any one or more of the anti-corrosion methods: ion implantation, laser surface treatment, thermal diffusion, metal plating, vapor deposition, organic coating.