CN116747360A - Coating material for surface modification of magnesium-based vascular stent material, modification method, modified magnesium-based vascular stent material and application - Google Patents

Coating material for surface modification of magnesium-based vascular stent material, modification method, modified magnesium-based vascular stent material and application Download PDF

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CN116747360A
CN116747360A CN202310810737.9A CN202310810737A CN116747360A CN 116747360 A CN116747360 A CN 116747360A CN 202310810737 A CN202310810737 A CN 202310810737A CN 116747360 A CN116747360 A CN 116747360A
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magnesium
stent material
vascular stent
surface modification
compound
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张皓
申孝龙
王海波
苏佳
杨晓凤
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Panzhihua University
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Panzhihua University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02Inorganic materials
    • A61L31/022Metals or alloys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42Anti-thrombotic agents, anticoagulants, anti-platelet agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings

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Abstract

The invention provides a coating material for surface modification of a magnesium-based vascular stent material, a modification method, a modified magnesium-based vascular stent material and application thereof, and belongs to the field of biomedical materials. The modification method comprises the following steps: (1) Polishing, cleaning and drying the magnesium-based vascular stent material; (2) Dissolving a degradable high polymer material, a compound with an o-phenolic hydroxyl structure and a selenium-containing compound in an organic solvent to prepare a coating solution; (3) And (3) placing the magnesium-based intravascular stent material treated in the step (1) into the coating solution in the step (2), volatilizing, immersing with water, ultrasonically cleaning, and drying under a protective atmosphere to obtain the target material. The method utilizes the capability of complexing metal ions of the ortho-phenol structure to realize the self-repairing function of the coating, and simultaneously, the ortho-phenol structure compound plays a role in slowly releasing the loaded selenium-containing compound to realize controllable release, and finally, the bionic endothelial function of the material surface is realized.

Description

Coating material for surface modification of magnesium-based vascular stent material, modification method, modified magnesium-based vascular stent material and application
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a coating material for surface modification of a magnesium-based vascular stent material, a modification method, a modified magnesium-based vascular stent material and application.
Background
The magnesium alloy is used for preparing vascular stents, has the advantage of degradability compared with the traditional biomedical stainless steel, nickel-titanium alloy or cobalt-chromium alloy and other metal materials, but has high chemical and electrochemical activities, and long-term difficult problems of over-fast degradation in physiological environments. The surface with excellent corrosion resistance and biological functionalization is always the investigation means and purpose of realizing the function of the magnesium-based vascular stent.
Coating magnesium-based vascular stents with degradable polymeric coatings is an effective method to improve their corrosion resistance and can be loaded with drugs simultaneously to confer specific biological functions. The degradable polymer coating commonly used at present comprises polylactic acid (PLA), polylactic acid-polyglycolic acid (PLGA), polycaprolactone (PCL), poly trimethylene carbonate (PTMC) coating and the like. However, once the coatings are destroyed, the coatings cannot be repaired by themselves and have adverse effects on the sustained release of the drug, so that improvements on the degradability and drug carrying capacity of the coatings are still needed.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide a coating material for surface modification of a magnesium-based vascular stent material, a surface modification method of the magnesium-based vascular stent material, the modified magnesium-based vascular stent material and application.
The invention is realized in the following way:
in a first aspect, the invention provides a coating material for surface modification of a magnesium-based intravascular stent material, which comprises a degradable high polymer material, a compound with an o-phenolic hydroxyl structure and a selenium-containing compound.
In some specific embodiments, the mass ratio of the degradable high molecular material, the compound with the ortho-phenolic hydroxyl structure and the selenium-containing compound is (15-750): 1-5.
In some embodiments, the magnesium-based vascular stent material is preferably a medical metal magnesium-based material.
In some embodiments, the degradable polymeric material is at least one of polylactic acid, polylactic acid-polyglycolic acid, polycaprolactone, polytrimethylene carbonate.
In some embodiments, the compound having an ortho-phenolic hydroxyl structure is at least one of catechol, epicatechin, epigallocatechin gallate, epicatechin gallate, gallic acid, tannic acid.
In some embodiments, the selenium-containing compound is at least one of selenocysteine, ibutene, sodium selenite, sodium selenate.
In a second aspect, the invention provides a surface modification method for a magnesium-based intravascular stent material, which specifically comprises the following steps:
(1) Polishing, cleaning and drying the magnesium-based vascular stent material;
(2) Dissolving a degradable high polymer material, a compound with an o-phenolic hydroxyl structure and a selenium-containing compound in an organic solvent to prepare a coating solution;
(3) And (3) placing the magnesium-based intravascular stent material treated in the step (1) into the coating solution in the step (2), volatilizing, immersing with water, ultrasonically cleaning, and drying under a protective atmosphere to obtain the target material.
According to the invention, the compound with the o-phenolic hydroxyl structure is introduced into the degradable high polymer material and coated on the surface of the magnesium-based vascular stent, so that the degradation speed of the magnesium-based vascular stent can be controlled on one hand; on the other hand, when the degradable polymer coating cracks or swells, the compound with the phenolic hydroxyl structure in the coating can be released freely to carry out complex reaction with metal ions released from the magnesium matrix to form stable complex to fill the defect, thereby realizing self-repairing of the coating. In addition, the selenium-containing compound introduced into the degradable high polymer material has the capability of in-situ inducing the catalytic decomposition of an endogenous Nitric Oxide (NO) donor to release NO signal factors, thereby playing a corresponding biological function. Meanwhile, the o-phenol structural compound in the coating also has excellent oxidation resistance and oxygen free radical scavenging capacity, and has a protective effect on cardiovascular and cerebrovascular diseases. In addition, the o-phenol structure compound is added into the coating loaded with the medicine, so that the stability of the coating can be effectively improved, the loading capacity of the medicine can be increased, and the effective sustained release of the medicine can be prolonged. This is mainly due to pi-pi stacking, weak intermolecular cross-linking and enriched hydrogen bonding brought about by polyphenols, which may exert a slow release effect on the loaded drug.
In some embodiments, the magnesium-based vascular stent material is preferably a medical metal magnesium-based material.
The medical metal magnesium-based material comprises: pure magnesium; commercial magnesium alloy systems including magnesium aluminum (Mg-Al), magnesium rare earth (Mg-RE) alloys such as AZ31 magnesium alloy, AZ91 magnesium alloy, WE43 magnesium alloy, and the like; novel biomedical magnesium alloys include AE21 magnesium alloys, mg-Mn-Zn alloys, mg-Si alloys, and the like.
In some embodiments, the degradable polymeric material is at least one of polylactic acid, polylactic acid-polyglycolic acid, polycaprolactone, polytrimethylene carbonate.
In some embodiments, the compound having an ortho-phenolic hydroxyl structure is at least one of catechol, epicatechin, epigallocatechin gallate, epicatechin gallate, gallic acid, tannic acid.
In some embodiments, the selenium-containing compound is at least one of selenocysteine, ibutene, sodium selenite, sodium selenate.
In some embodiments, the organic solvent is at least one of dichloromethane, chloroform, tetrahydrofuran.
In some embodiments, the water is preferably deionized water.
In some specific embodiments, the mass ratio of the degradable high molecular material, the compound with the ortho-phenolic hydroxyl structure and the selenium-containing compound in the coating solution is (15-750): 1-5.
In some embodiments, the volatilizing in step (3) is performed by: slowly volatilizing at 10-20deg.C for 24-72 hr.
In some embodiments, the specific steps of the ultrasonic cleaning are: ultrasonic cleaning for 3 times, each time for 2-5min.
In a third aspect, the present invention provides a modified magnesium-based vascular stent material prepared by the surface modification method of the magnesium-based vascular stent material.
In a fourth aspect, the invention provides the use of a modified magnesium-based vascular stent material in the preparation of a vascular repair product or vascular repair animal model.
Compared with the prior art, the invention has the following beneficial effects:
1. the traditional method for modifying the magnesium-based vascular stent on the surface of the degradable high polymer coating has the problems that the binding capacity with a metal substrate is weak and self-repairing cannot be realized.
2. The traditional degradable polymer coating for surface modification of the magnesium-based vascular stent mainly avoids adverse reactions such as thrombosis, intimal hyperplasia and the like by loading antithrombotic and antiproliferative medicaments, and the side effects (such as delayed functional endothelial coverage) and the controlled release of medicaments become application problems. The loaded seleno compound has the capability of in-situ inducing endogenous Nitric Oxide (NO) donor to catalyze and decompose and release NO signal factors, has the NO release function of bionic endothelial cells, and can effectively avoid the problems of the traditional drug-loaded polymer coating.
3. According to the invention, the polyphenol is added into the degradable high polymer coating loaded with the selenium-containing compound, pi-pi accumulation, weak intermolecular crosslinking and enriched hydrogen bonds can be formed between the polyphenol and the selenium-containing compound, so that the stability of the selenium-containing compound in the coating is effectively improved, and the effective sustained release of the selenium-containing compound is prolonged.
4) The coating to be prepared by the invention has less raw material investment, and can be modified on the surfaces of various magnesium-based materials. Compared with the traditional means, the method has the advantages of simple operation, lower cost and wide universality.
Drawings
FIG. 1 is a graph showing comparison of infrared absorption spectra of the materials prepared in comparative examples 1 to 3;
FIG. 2 is a graph showing the Tafel polarization profile obtained by immersing the materials prepared in comparative examples 1 to 3 in PBS buffer (pH 7.4, 37 ℃ C.) for 10 days and performing polarization detection for 1 day, 5 days, and 10 days, respectively;
FIG. 3 is a graph showing the results of in vivo whole blood evaluation of the material halves prepared in example 8, comparative example 1 and comparative example 2.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the pure magnesium material.
(2) Polylactic acid-polyglycolic acid (PLGA) is dissolved in dichloromethane organic solvent, and tannic acid TA and selenocysteine are added simultaneously, and are fully stirred until the polylactic acid-polyglycolic acid (PLGA), tannic acid TA and selenocysteine are completely dissolved, wherein the final concentration of polylactic acid-polyglycolic acid (PLGA), tannic acid TA and selenocysteine is 15mg/mL, 0.5mg/mL and 0.1mg/mL respectively.
(3) Placing the pure magnesium material treated in the step (1) into the solution system obtained in the step (2), slowly volatilizing for 36h at 25 ℃, immersing with deionized water, ultrasonically cleaning for 3 times each for 2min, and then placing in N 2 Drying under the condition to obtain the target material。
Example 2
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the AZ31 alloy material.
(2) Polylactic acid-polyglycolic acid (PLGA) is dissolved in tetrahydrofuran organic solvent, epicatechin gallate (ECG) and ebselen are added at the same time, and the mixture is fully stirred until the polylactic acid-polyglycolic acid (PLGA), epicatechin gallate (ECG) and ebselen are completely dissolved, and the final concentrations of the polylactic acid-polyglycolic acid (PLGA), epicatechin gallate (ECG) and ebselen are respectively 20mg/mL, 0.1mg/mL and 0.5mg/mL.
(3) Placing the AZ31 alloy material treated in the step (1) into the solution system obtained in the step (2), slowly volatilizing for 72 hours at 10 ℃, immersing the AZ31 alloy material in deionized water, ultrasonically cleaning the AZ31 alloy material for 3 times each for 3 minutes, and then placing the AZ31 alloy material in N 2 Drying under the condition to obtain the target material.
Example 3
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) And polishing, cleaning and drying the MgZnMn alloy.
(2) And dissolving Polycaprolactone (PCL) in a dichloromethane organic solvent, adding Gallic Acid (GA) and sodium selenate, and stirring thoroughly until the Polycaprolactone (PCL), the Gallic Acid (GA) and the sodium selenate are completely dissolved, wherein the final concentrations of the Polycaprolactone (PCL), the Gallic Acid (GA) and the sodium selenate are respectively 15mg/mL, 1mg/mL and 1mg/mL.
(3) Placing the MgZnMn alloy treated in the step (1) in the solution system obtained in the step (2), slowly volatilizing for 72 hours at 10 ℃, immersing with deionized water, ultrasonically cleaning for 3 times, each time for 5min, and then placing in N 2 Drying under the condition to obtain the target material.
Example 4
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) And polishing, cleaning and drying the WE43 magnesium alloy material.
(2) The Polycaprolactone (PCL) is dissolved in dichloromethane organic solvent, tannic acid and ebselen are added at the same time, and the mixture is fully stirred until the Polycaprolactone (PCL), tannic acid and ebselen are completely dissolved, and the final concentration of the Polycaprolactone (PCL), tannic acid and ebselen is 75mg/mL, 0.1mg/mL and 0.5mg/mL respectively.
(3) Placing the WE43 magnesium alloy material treated in the step (1) into the solution system obtained in the step (2), volatilizing for 24 hours at 20 ℃, immersing with deionized water, ultrasonically cleaning for 3 times, each time for 5min, and then placing in N 2 Drying under the condition to obtain the target material.
Example 5
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the pure magnesium material.
(2) And dissolving the polytrimethylene carbonate (PTMC) in tetrahydrofuran organic solvent, adding epigallocatechin and sodium selenite, and stirring fully until the polytrimethylene carbonate (PTMC), the epigallocatechin and the sodium selenite are completely dissolved, wherein the final concentrations of the polytrimethylene carbonate (PTMC), the epigallocatechin and the sodium selenite are 40mg/mL, 0.25mg/mL and 0.25mg/mL respectively.
(3) Placing the pure magnesium material treated in the step (1) into the solution system obtained in the step (2), volatilizing for 48 hours at 20 ℃, immersing with deionized water, ultrasonically cleaning for 3 times, each time for 5min, and then placing in N 2 Drying under the condition to obtain the target material.
Example 6
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the AZ31 magnesium alloy.
(2) Polylactic acid (PLA) is dissolved in tetrahydrofuran organic solvent, and gallic acid and ebselen are added at the same time, and are fully stirred until the polylactic acid (PLA), gallic acid and ebselen are completely dissolved, and the final concentration of the polylactic acid (PLA), gallic acid and ebselen is 8mg/mL, 0.25mg/mL and 0.1mg/mL respectively.
(3) Placing the AZ31 magnesium alloy treated in the step (1) in the solution system obtained in the step (2), slowly volatilizing for 72 hours at 10 ℃, immersing the magnesium alloy in deionized water, ultrasonically cleaning the magnesium alloy for 3 times, each for 4 minutes, and then placing the magnesium alloy in N 2 Drying under the condition to obtain the target material.
Example 7
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the magnesium-zinc-manganese alloy.
(2) The polytrimethylene carbonate (PTMC) was dissolved in methylene chloride organic solvent, tannic acid and selenocysteine were added at the same time, and stirred well until the complete dissolution was achieved, and the final concentrations of polytrimethylene carbonate (PTMC), tannic acid and selenocysteine were 15mg/mL, 1mg/mL and 1mg/mL, respectively.
(3) Placing the magnesium-zinc-manganese alloy treated in the step (1) in the solution system obtained in the step (2), volatilizing for 48 hours at 20 ℃, immersing the magnesium-zinc-manganese alloy in deionized water, ultrasonically cleaning the magnesium-zinc-manganese alloy for 3 times, each time for 5 minutes, and then placing the magnesium-zinc-manganese alloy in N 2 Drying under the condition to obtain the target material.
Example 8
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the pure magnesium material.
(2) Polytrimethylene carbonate (PTMC) was dissolved in tetrahydrofuran organic solvent while tannic acid and ebselen were added and stirred well to complete dissolution, with final concentrations of polytrimethylene carbonate (PTMC), tannic acid and ebselen of 40mg/mL, 1mg/mL and 1mg/mL, respectively.
(3) Placing the pure magnesium material treated in the step (1) into the solution system obtained in the step (2), volatilizing for 48 hours at 25 ℃, immersing with deionized water, ultrasonically cleaning for 3 times, each time for 5min, and then placing in N 2 Drying under the condition to obtain the target material.
Comparative example 1 (Mg)
Pure magnesium material was not modified.
Comparative example 2 (Mg-P)
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the pure magnesium material.
(2) The polytrimethylene carbonate (PTMC) was dissolved in tetrahydrofuran organic solvent and stirred well until it was completely dissolved, the final concentration of polytrimethylene carbonate (PTMC) was 40mg/mL.
(3) Placing the pure magnesium material treated in the step (1) into the solution system obtained in the step (2), volatilizing for 48 hours at 25 ℃, immersing with deionized water, ultrasonically cleaning for 3 times, each time for 5min, and then placing in N 2 Drying under the condition to obtain the Mg modified by the PTMC coating.
Comparative example 3 (Mg-P/TA)
The surface modification method of the magnesium-based intravascular stent material specifically comprises the following steps:
(1) Polishing, cleaning and drying the pure magnesium material.
(2) The poly (trimethylene carbonate) (PTMC) was dissolved in tetrahydrofuran organic solvent at the concentration, tannic acid was added, and stirred well until it was completely dissolved, and the final concentrations of poly (trimethylene carbonate) (PTMC) and tannic acid were 40mg/mL and 1mg/mL, respectively.
(3) Placing the pure magnesium material treated in the step (1) into the solution system obtained in the step (2), volatilizing for 48 hours at 25 ℃, immersing with deionized water, ultrasonically cleaning for 3 times, each time for 5min, and then placing in N 2 Drying under the condition to obtain the PTMC coating modified Mg loaded with tannic acid.
The infrared absorption spectra of the materials prepared in comparative examples 1 to 3 are shown in a graph a of FIG. 1, in which Mg represents the material prepared in comparative example 1, mg-P represents the material prepared in comparative example 2, and Mg-P/TA represents the material prepared in comparative example 3, and a graph b of FIG. 1 is a partial enlargement of the graph a.
As can be seen from FIG. 1, the coated sample showed-CH detected on both the Mg-P and Mg-P/TA surfaces as compared to pure magnesium 2 Stretching vibration peak (2977 and 2915 cm) -1 ) C=o stretching vibration peak of the, -COOR group (1740 cm -1 ) And C-O stretching vibration peak (1197 cm) -1 ) These groups are derived from the composition of the PTMC coating layer. In particular, compared with Mg-P, vibration peaks (1620, 1541, 1505 and 1470 cm) of the benzene ring skeleton were detected on the surface of PTMC coating (Mg-P/TA) loaded with tannic acid -1 ) And 3400cm -1 Broad peaks around (-OH stretching vibration). The infrared spectral results confirm that tannic acid was successfully loaded in the PTMC.
The materials prepared in comparative examples 1-3 were continuously soaked in PBS buffer (pH 7.4, 37 ℃) for 10 days, and polarization detection was performed for 1 day, 5 days, and 10 days respectively to obtain Tafel polarization curves, the results are shown in FIG. 2, wherein Mg represents the material prepared in comparative example 1, and the Tafel polarization curves are shown in FIG. 2, and the Tafel polarization curves are shown in FIG. a; mg-P represents the material prepared in comparative example 2, whose Tafel polarization graph is shown in graph b of fig. 2; mg-P/TA represents the material prepared in comparative example 3, and its Tafel polarization graph is shown in graph c of FIG. 2.
As can be seen from FIG. 2, mg exhibits the maximum corrosion current density i during the soaking process lasting 10 days corr (~2×10 -5 A/cm 2 ) I on day 1 of Mg-P and Mg-P/TA corr 1.23×10 respectively -7 A/cm 2 And 9.61×10 -8 A/cm 2 Is significantly lower than bare material. With increasing soaking time, i of Mg-P corr Significantly increased from 1.23×10 on day 1 -7 A/cm 2 6.71×10 increased to day 10 -6 A/cm 2 . In contrast, mg-P/TA maintained minimal self-corrosion current densities in both the 1,5 and 10 day test, with a corrosion inhibition of 99.97%. When the polymer coating is cracked or swelled, tannic acid in the coating can be released to carry out complexation reaction with metal ions released from the magnesium matrix to form stable complex to fill the defect, so that the self-repairing of the coating is realized. The polarization detection result shows that TA loaded in the PTMC layer can play a good self-repairing function in the service process of the PTMC layer.
The results of the in-vivo whole blood evaluation experiments performed on the materials prepared in example 8, comparative example 1 and comparative example 2 are shown in fig. 3, and fig. 3 a is an experimental diagram of the in-vitro circulating thrombosis of the New Zealand white rabbit arterial venous shunt model; panel b in FIG. 3 is an optical photograph of a lumen cross-section after 2 hours of cycling; panel c in FIG. 3 is a graph of thrombus condition on the surface of the sample after 2 hours of cycling; panel d in FIG. 3 is an SEM topography of the sample surface after 2 hours of cycling, wherein Mg represents the material prepared in comparative example 1, mg-P represents the material prepared in comparative example 2, and Mg-P/Ebs represents the material prepared in example 8.
From the optical photographs and SEM images in fig. 3, it is shown that the Mg surface exhibits a pronounced corrosion morphology, while the Mg-P surface slows down the too rapid corrosion of the magnesium substrate, the surface exhibits a severe thrombotic network, whereas the Mg-P/Ebs sample surface has only a small thrombotic network. The Ebuselenium loaded in the Mg-P/Ebs coating has the capability of in-situ inducing the catalytic decomposition of an endogenous Nitric Oxide (NO) donor to release NO signal factors, so that good blood compatibility is shown.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.

Claims (10)

1. The coating material for surface modification of the magnesium-based vascular stent material is characterized by comprising a degradable high polymer material, a compound with an ortho-phenolic hydroxyl structure and a selenium-containing compound.
2. The coating material for surface modification of a magnesium-based intravascular stent material according to claim 1, wherein the mass ratio of the degradable polymer material, the compound having an ortho-phenolic hydroxyl structure and the selenium-containing compound is (15-750): (1-5): (1-5).
3. The coating material for surface modification of a magnesium-based intravascular stent material according to claim 1, wherein,
the magnesium-based intravascular stent material is preferably a medical metal magnesium-based material;
the degradable high polymer material is at least one of polylactic acid, polylactic acid-polyglycolic acid, polycaprolactone and polytrimethylene carbonate;
the compound with the ortho-phenolic hydroxyl structure is at least one of catechol, epicatechin, epigallocatechin gallate, epicatechin gallate, gallic acid and tannic acid;
the selenium-containing compound is at least one of selenocyamine, ebselen, sodium selenite and sodium selenate.
4. The surface modification method of the magnesium-based vascular stent material is characterized by comprising the following steps of:
(1) Polishing, cleaning and drying the magnesium-based vascular stent material;
(2) Dissolving a degradable high polymer material, a compound with an o-phenolic hydroxyl structure and a selenium-containing compound in an organic solvent to prepare a coating solution;
(3) And (3) placing the magnesium-based intravascular stent material treated in the step (1) into the coating solution in the step (2), volatilizing, immersing with water, ultrasonically cleaning, and drying under a protective atmosphere to obtain the target material.
5. The method of claim 4, wherein the magnesium-based vascular stent material is preferably a medical metal magnesium-based material;
the degradable high polymer material is at least one of polylactic acid, polylactic acid-polyglycolic acid, polycaprolactone and polytrimethylene carbonate;
the compound with the ortho-phenolic hydroxyl structure is at least one of catechol, epicatechin, epigallocatechin gallate, epicatechin gallate, gallic acid and tannic acid;
the selenium-containing compound is at least one of selenocyamine, ibutene, sodium selenite and sodium selenate;
the organic solvent is at least one of dichloromethane, chloroform and tetrahydrofuran;
the water is preferably deionized water.
6. The method for surface modification of a magnesium-based intravascular stent material according to claim 4, wherein the mass ratio of the degradable polymer material, the compound having an ortho-phenolic hydroxyl structure and the selenium-containing compound in the coating solution is (15-750): 1-5.
7. The method for surface modification of a magnesium-based vascular stent material according to claim 4, wherein the volatilizing in the step (3) comprises the following specific steps: slowly volatilizing at 10-20deg.C for 24-72 hr.
8. The method for surface modification of a magnesium-based vascular stent material according to claim 4, wherein the specific steps of ultrasonic cleaning are as follows: ultrasonic cleaning for 3 times, each time for 2-5min.
9. The modified magnesium-based vascular stent material prepared by the surface modification method of the magnesium-based vascular stent material according to any one of claims 4 to 8.
10. Use of a modified magnesium-based vascular stent material according to claim 9 for the preparation of a vascular repair article or vascular repair animal model.
CN202310810737.9A 2023-07-04 2023-07-04 Coating material for surface modification of magnesium-based vascular stent material, modification method, modified magnesium-based vascular stent material and application Pending CN116747360A (en)

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