CN111420129B - Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material - Google Patents

Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material Download PDF

Info

Publication number
CN111420129B
CN111420129B CN202010381096.6A CN202010381096A CN111420129B CN 111420129 B CN111420129 B CN 111420129B CN 202010381096 A CN202010381096 A CN 202010381096A CN 111420129 B CN111420129 B CN 111420129B
Authority
CN
China
Prior art keywords
coating
degradable
polycarbonate
corrosion
magnesium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202010381096.6A
Other languages
Chinese (zh)
Other versions
CN111420129A (en
Inventor
李小杰
潘凯
魏玮
刘仁
刘晓亚
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiangnan University
Original Assignee
Jiangnan University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jiangnan University filed Critical Jiangnan University
Priority to CN202010381096.6A priority Critical patent/CN111420129B/en
Publication of CN111420129A publication Critical patent/CN111420129A/en
Application granted granted Critical
Publication of CN111420129B publication Critical patent/CN111420129B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L31/00—Materials 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
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L31/00—Materials 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
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L31/00—Materials 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
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
    • B05D5/08—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures to obtain an anti-friction or anti-adhesive surface
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D7/00—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials
    • B05D7/14—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials to metal, e.g. car bodies
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D7/00—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials
    • B05D7/24—Processes, other than flocking, specially adapted for applying liquids or other fluent materials to particular surfaces or for applying particular liquids or other fluent materials for applying particular liquids or other fluent materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G64/00—Macromolecular compounds obtained by reactions forming a carbonic ester link in the main chain of the macromolecule
    • C08G64/20—General preparatory processes
    • C08G64/30—General preparatory processes using carbonates
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/24—Crosslinking, e.g. vulcanising, of macromolecules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D2202/00—Metallic substrate
    • B05D2202/20—Metallic substrate based on light metals
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2369/00—Characterised by the use of polycarbonates; Derivatives of polycarbonates

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The invention discloses a preparation method of a degradable polycarbonate coating for reducing the corrosion rate of a medical magnesium-based material. The modified polycarbonate resin is used as matrix resin of a coating, a multi-arm thiol cross-linking agent and other additives are added, the cross-linking and curing of the coating are realized through rapid thiol-ene addition reaction, and the degradable polycarbonate coating is prepared on the surface of medical magnesium metal. The coating has unique surface corrosion degradation behavior, fundamentally avoids the problems of the traditional commercialized polyester that the protective performance is reduced and the corrosion of the magnesium base material is even accelerated due to the body degradation mode and the acidic degradation product, has excellent long-acting corrosion resistance, and can effectively delay the degradation rate of the magnesium base material. In addition, the prepared polycarbonate coating has excellent surface hardness, good mechanical property, firm adhesion and good biocompatibility.

Description

Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material
Technical Field
The invention relates to a functional material, in particular to the technical field of surface anticorrosion treatment of medical magnesium-based materials, and specifically relates to a preparation method of a degradable polycarbonate coating for reducing the corrosion rate of the medical magnesium-based materials.
Background
In recent years, magnesium alloys have a wide application prospect in the field of medical implants due to good biocompatibility and biodegradability, and are receiving wide attention of researchers. However, magnesium alloys are very susceptible to degradation due to their reactive chemical properties, which can cause local cytotoxicity, hydrogen bubble enrichment, and premature failure of mechanical properties of the material. These problems limit the clinical application of magnesium-based implants. In order to solve the problems, a polymer coating, especially a degradable polymer coating, is prepared on the surface of the magnesium alloy, and is an effective method for controlling the corrosion rate of the magnesium alloy in both research and clinical application.
Most of the carriers of the currently common drug eluting stents are commercialized degradable polyesters such as polylactic acid CN109161882A and copolymers thereof. The degradation mode is a body dissolution type, the degradation mode is first-order kinetics, the degradation speed is uncontrollable, the polymer continuously decreases from inside to outside of the molecular weight in the corrosion process, the mechanical property and the integrity of the coating are rapidly damaged, the coating is easily corroded to penetrate through the exposed matrix, the protection effect is lost in the service period of the device, and the corrosion rate of the magnesium substrate is too high. In addition, the degradation products of the polyester are acidic, can react with alkaline magnesium alloy base materials and corrosion products thereof to further accelerate corrosion of magnesium alloy devices, and can easily cause over-high local acidity in vivo, generate toxic and side effects such as inflammatory reaction, thrombus and the like, thereby threatening human health.
CN102327862A discloses a method for preparing a surface erosion type polymer coating such as polycarbonate, polyanhydride, polyorthoester, etc. on a magnesium alloy device, wherein the degradation behavior is surface erosion type degradation, i.e. the surface of the material is gradually degraded inwards, the whole degradation process is a linear process, the degradation rate is linearly controllable, and the degradation is zero order kinetic degradation. The literature reports also prove that compared with bulk corrosion type polyester commercialized degradable polymers represented by PCL, the surface corrosion aliphatic carbonate PTMC always provides good protection effect on the surface of the magnesium alloy before the degradation is complete due to the surface corrosion degradation action of the PTMC; and degradation products of the polymer are near-neutral carbon dioxide and water, magnesium-based accelerated corrosion caused by degradation is fundamentally avoided, and inflammatory reaction caused by stimulation of the degradation products is avoided (Juan Wang, et al, Acta biomaterials, 9(2013), 8678-.
However, in many of the above conventional methods, a surface-eroding polymer having a simple structure and a single function is applied to the surface of a magnesium alloy material or an instrument. The polymer structure lacks structural design and the basic properties of these polymer coatings, such as hardness and mechanical properties, are not fully satisfactory due to their own physicochemical properties, such as glass transition temperature, limitations of mechanical properties. Aliphatic carbonate PTMC due to its lower glass transition temperature (T)gAbout 17 ℃), the prepared coating has poor dimensional stability and mechanical properties in the environment of high temperature of human body, and the surface hardness of the coating is also low. The polyanhydride is brittle, and meanwhile, the degradation intermediate product is organic acid, and the problem of acidic degradation products existing in the polyester polymer also exists. Meanwhile, the main chains of the polymers lack functional groups, and in order to improve the bioactivity of the coating surface, the surface of the polymer is often required to be further coated or modified (CN 205379387U; CN 102327862A). The above problems limit practical applications of surface-eroding polymers.
Therefore, a surface-etching-type degradable coating material with good mechanical properties, excellent surface hardness, scratch resistance and convenient functionalization is needed. Crosslinking of the coating is an effective means to solve the above problems, but crosslinking may affect the degradation behavior of the coating or even render the coating undegradable, and therefore the design of the polymer structure as well as the coating formulation and preparation method is required.
The invention provides a preparation method of a rapid-curing degradable polycarbonate coating for reducing the corrosion rate of a medical magnesium-based material, which not only has the surface-corrosion-type degradation behavior and the formation of a neutral degradation product and a curing network, but also effectively delays the degradation rate of the coating and further prolongs the protective performance of the coating. And the biological coating has pencil hardness and adhesion comparable to industrial coatings, as well as excellent mechanical properties. In addition, the coating preparation method can be used for simply and rapidly introducing the functional molecules with biological activity into the coating cross-linked network through chemical bonding in the coating curing process. Can be applied to magnesium-based medical instruments such as magnesium-based vascular stents, magnesium-based bone fixation instruments (bone screws and bone splints), anastomats and the like. For the sake of clarity, the magnesium-based material and its medical implant device are hereinafter referred to as medical magnesium-based materials.
Disclosure of Invention
In view of the deficiencies of the prior art solutions set forth above, the present invention aims to provide a method for preparing a degradable polycarbonate coating having surface erosion degradation behavior that reduces the corrosion rate of medical magnesium-based materials. Compared with polycarbonate without crosslinking, the coating prepared by the invention has the advantages of obviously reduced degradation rate, obviously improved corrosion resistance, excellent scratch resistance, firm adhesion, good mechanical property and excellent biocompatibility. In the preparation process of the coating, functional molecules represented by functional drugs can be chemically bonded in a coating curing network through convenient chemical modification, so that the coating has different medical functions.
The object of the present invention is achieved by the following means.
A preparation method of a fast-curing degradable polycarbonate coating for reducing the corrosion rate of a medical magnesium-based material comprises the following steps of preparing a polymer functional coating for reducing the corrosion rate on the surface of the magnesium-based material:
s1, taking a functionalized six-membered cyclic carbonate monomer as a feeding monomer, and preparing a degradable polycarbonate copolymer with the molecular weight of 1000-100000 Da through polymerization of two or more monomers;
s2, dissolving a cross-linking agent with low biological toxicity (preferably a thiol cross-linking agent) and the polycarbonate copolymer prepared from S1 in an organic solvent, wherein the solid content is 1-20 wt%;
s3, coating the mixed solution prepared in the step S2 on the surface of a clean medical magnesium alloy base material; and carrying out rapid curing treatment after the coating is dried, and finally obtaining the functional coating.
Specifically, the functionalized six-membered cyclic carbonate monomer in the first step is: 1, 3-dioxan-2-one (TMC), 5-methyl-5-allyloxycarbonyl-1, 3-dioxan-2-one (MAC), 5-allyloxy-1, 3-dioxan-2-one (ATMC), 2- (methacrylamido) trimethylene carbonate (MATC), 5-methyl-5-acryloyloxy-1, 3-dioxan-2-one (AC) and 5-methyl-5-methacryloyloxy-1, 3-dioxan-2-one (MA). The specific structure is as follows:
Figure GDA0003210840390000031
specifically, the polycarbonate copolymer prepared in the first step has a double bond in a pendant group, as shown in the following structural formula.
Figure GDA0003210840390000032
Wherein:
R1independently selected from H, CH3；
R2Independently selected from H, -OC (O) -CH2＝CH2、-NH-C(O)-CH(CH3)＝CH2、-O-CH2-CH＝CH2、-COO-CH＝CH2and-OC (O) -C (CH)3)＝CH2；
R3Independently selected from H, CH3；
R4Independently selected from H, -OC (O) -CH2＝CH2、-NH-C(O)-CH(CH3)＝CH2、-O-CH2-CH＝CH2、-COO-CH＝CH2and-OC (O) -C (CH)3)＝CH2；
R2、R4Cannot be simultaneously H;
x and y are positive integers, and x + y is less than 400.
Specifically, the polymerization reaction in S1 is ring-opening copolymerization carried out under oxygen-free water conditions, and the initiator is a small molecule or a polymer containing a hydroxyl functional group, such as a small molecule monohydric alcohol containing a hydroxyl group represented by benzyl alcohol and isopropanol; the catalyst is one or more of stannous octoate, DBU (diazabicyclo), TBD (1,5, 7-triazabicyclo [4.4.0] dec-5-ene) and MTBD (1-methyl-1, 5, 7-triazabicyclo [4.4.0] dec-5-ene). The reaction temperature is 20-160 ℃.
Specifically, the thiol crosslinking agent of S2 is trimethylolpropane tris (3-mercaptopropionate) (TMPMP), trimethylolpropane tris (2-mercaptoacetate) (TTMA), pentaerythritol tetrakis (3-mercaptopropionate) (PETMP), and Dithiothreitol (DTT);
more specifically, the molar ratio of the mercaptan in the mercaptan crosslinking agent to the unsaturated bond in the polycarbonate copolymer is 9: 10-3: 2.
More specifically, an auxiliary agent is also added into the mixed solution, and the auxiliary agent is one or two of an initiator and a bioactive substance; wherein the initiator is one or more of Irgacure 2959, ethyl pyruvate and phenyl-2, 4, 6-trimethyl benzoyl lithium phosphonate (LAP); the bioactive substance is one or two of RGD peptide and 2-Methacryloyloxyethyl Phosphorylcholine (MPC); preferably, the content of the initiator is 0-0.1 wt%, and the content of the bioactive substance is 0-5 wt%.
Specifically, the organic solvent in the second step is dichloromethane, dimethyl sulfoxide, tetrahydrofuran or ethyl acetate.
Specifically, the rapid curing conditions described in the third step include radiation, heat, or a combination thereof. Radiation includes UV light, electron beams, and other forms of light such as visible light, infrared light, and other forms of electromagnetic radiation.
The invention prepares a degradable coating which is crosslinked and solidified through a thiol-ene chemical reaction. Firstly, a polycarbonate copolymer with alkenyl (or alkene) functional groups is prepared, then, a multifunctional thiol is added as a cross-linking agent, and a biomedical coating with excellent corrosion resistance, good mechanical property and adhesive force and excellent scratch resistance can be prepared through a rapid free radical reaction.
The beneficial technical effects of the invention are as follows:
the degradable polycarbonate coating prepared by the method can effectively reduce the corrosion rate of the medical magnesium-based material and improve the biocompatibility of the surface of the medical magnesium-based material. Due to the unique surface corrosion behavior, the magnesium base material is well protected until the magnesium base material is completely degraded, and corrosion caused by contact between a corrosion medium and the base material is prevented; fundamentally avoids the problems of the conventional commercialized polyester that the protective performance is reduced and the corrosion of the magnesium substrate is accelerated due to the body degradation mode and the acidic degradation product, and has excellent long-acting corrosion resistance. In addition, the coating of the present invention solves the problems of poor mechanical properties, surface hardness and abrasion resistance of surface erosion-degradable polymers represented by polytrimethylene carbonate through "thiol-ene" chemical crosslinking, while still achieving complete degradation of the coating. It is also convenient to impart different biological functions to the coating by chemically modifying functional molecules represented by functional drugs in the crosslinked network of the coating.
Drawings
FIG. 1 shows the NMR spectrum of polycarbonate copolymer 1 in example 1.
FIG. 2 is a total reflection IR spectrum of the polymer coating material of example 1 before and after photocuring.
FIG. 3 is a scanning electron microscope photograph of the surface of the bare magnesium alloy in test example 1, and six samples in examples 1 to 3 and comparative examples 1 to 2, after immersion in human body simulated fluid (SBF) at 37 ℃ for 0, 5, 15, and 30 days.
Fig. 4 is a graph showing the cell viability of different surfaces of the bare magnesium alloy, example 1, example 3, example 5, comparative example 1 and comparative example 2, in test example 3, after culturing the same on the surface for 24h and 48h using L929 cells.
Detailed Description
The invention is further illustrated below with reference to specific embodiments. It is to be understood that the present invention is not limited to the following embodiments, which are regarded as conventional methods unless otherwise specified. The materials are commercially available from the open literature unless otherwise specified. Example 1:
(1) synthesis of polycarbonate copolymer 1: using benzyl alcohol as initiator, Sn (Oct)2As a catalyst, polymerization was carried out in a toluene solution at 100 ℃. A mixture of monomer MAC (9.602g,48mmol) and TMC (3.267g,32mmol) was placed in a well dried Schlenk apparatus. The reaction vessel was sealed, evacuated and purged three times with nitrogen. Next, toluene (20mL) was rapidly injected into the Schlenk flask under magnetic stirring. After the monomers were thoroughly mixed, a toluene solution of benzyl alcohol (1.6mL,0.5M) and Sn (Oct) were added via syringe2Toluene solution (4.8mL, 0.1M). The reaction vessel was placed in an oil bath at 100 ℃ with magnetic stirring. Polymerization was carried out for 24 hours and toluene was removed by rotary evaporation. The polycarbonate copolymer was dissolved in methylene chloride, precipitated into a quantity of cold methanol, isolated by filtration, and dried under vacuum at room temperature. The results of the polycarbonate copolymer are characterized by nuclear magnetic hydrogen spectroscopy, and are shown in figure 1, so that the metal corrosion early warning polymer coating material is successfully synthesized.
(2) Preparation of degradable polycarbonate coating: polycarbonate copolymer 1 in CH2Cl2The mixture was adjusted to a concentration of 20% (w/v) and stirred for 2 hours. The polycarbonate copolymer 1 solution was then mixed with pentaerythritol tetrakis (3-mercaptopropionate) PETMP such that the molar ratio of mercaptans to olefins was 1: 1. and 0.1 wt% Irgacure I2959 was added and dissolved in the solution. The solution is dipped on the surface of medical magnesium alloy which is polished and cleaned, and then dried for 3h at room temperature. Then, a thiol-ene photocrosslinked coating was finally formed by UV illumination (365nm) for 30 s. FIG. 2 shows the total reflection infrared spectrum of the polymer film on the substrate surface before and after UV irradiation, and the infrared absorption peaks of thiol groups and double bonds are present on the substrate surface before UV irradiation. After illumination, the infrared absorption peaks of the two disappear, the successful implementation of the mercaptan-alkene reaction is proved, and the coating realizes photocuringAnd (4) transforming.
Example 2:
(1) synthesis of polycarbonate copolymer 2: using isopropanol as initiator, Sn (Oct)2As a catalyst, polymerization was carried out in a xylene solution at 80 ℃. A mixture of monomer MA (6.4g,32mmol) and TMC (4.9g,48mmol) was placed in a well-dried Schlenk flask. The reaction vessel was sealed, evacuated and purged three times with nitrogen. Next, toluene (20mL) was rapidly injected into the Schlenk flask under magnetic stirring. After the monomers were thoroughly mixed, a toluene solution of isopropanol (1.6mL,0.5M) and Sn (Oct) were added via syringe2Toluene solution (4.8mL, 0.1M). The reaction vessel was placed in an oil bath at 80 ℃ with magnetic stirring. Polymerization was carried out for 24 hours and toluene was removed by rotary evaporation. Polycarbonate copolymer 2 was dissolved in methylene chloride, precipitated into a quantity of cold methanol, isolated by filtration, and dried under vacuum at room temperature.
(2) Preparation of degradable polycarbonate coating: polycarbonate copolymer 2 in CH2Cl2The mixture was adjusted to a concentration of 20% (w/v) and stirred for 2 hours. Then, the polycarbonate copolymer 2 solution was mixed with trimethylolpropane tris (3-mercaptopropionate) (TMPMP) so that the molar ratio of mercaptan to olefin was 1: 1. the solution is dipped on the surface of medical magnesium alloy which is polished and cleaned, and then dried for 3h at room temperature. Then, the thiol-ene electron beam cured coating was finally formed by curing for 60s by an electron beam curing machine (200 kV).
Example 3:
(1) synthesis of polycarbonate copolymer 3: polymerization was carried out in anhydrous dichloromethane at 25 ℃ using benzyl alcohol as initiator and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) as catalyst. A mixture of monomer AC (9.4g,48mmol) and TMC (3.267g,32mmol) was placed in a well dried Schlenk flask. The reaction vessel was sealed, evacuated and purged three times with nitrogen. After the monomers were thoroughly mixed, a solution of benzyl alcohol in dichloromethane (1.6mL,0.5M) and DBU in dichloromethane (5mL,0.1M) were added via syringe. The polymerization was carried out for 24 hours, the polycarbonate copolymer 3 solution was precipitated in cold methanol, isolated by filtration and dried under vacuum at room temperature.
(2) Preparation of degradable polycarbonate coating: polycarbonate copolymer 3 in CH2Cl2Was prepared at a concentration of 20% (w/v) and stirred at room temperature for 2 hours or less, then polycarbonate copolymer 3 solution was mixed with trimethylolpropane tris (2-mercaptoacetate) (TTMA) so that the molar ratio of mercaptan to olefin was 3: 2, and 0.1 wt% Irgacure I2959 was added. The solution is dipped on the surface of medical magnesium alloy which is polished and cleaned, and then dried for 3h at room temperature. Then, a photo-crosslinked coating was finally formed by UV irradiation (365nm) for 60 s.
Example 4:
(1) synthesis of polycarbonate copolymer 4: the polymerization was carried out in anhydrous dichloromethane at 25 ℃ using benzyl alcohol as initiator and TBD (1,5, 7-triazabicyclo [4.4.0] dec-5-ene) as catalyst. A mixture of monomers MATC (2.9g,16mmol) and TMC (6.27g,64mmol) was placed in a well-dried Schlenk flask. The reaction vessel was sealed, evacuated and purged three times with nitrogen. After the monomers were thoroughly mixed, a solution of benzyl alcohol in dichloromethane (1.6mL,0.5M) and TBD in dichloromethane (5mL,0.1M) were added via syringe. After 24 hours of polymerization, the polycarbonate copolymer 4 solution was precipitated in a mixed solution of cold methanol and water, separated by filtration, and dried under vacuum at room temperature.
(2) Preparation of degradable polycarbonate coating: polycarbonate copolymer 4 in CH2Cl2Was prepared at a concentration of 5% (w/v) and stirred at room temperature for 2 hours or less, and then the polycarbonate copolymer 4 solution was mixed with Dithiothreitol (DTT) so that the molar ratio of thiol to olefin was 1: 1. The solution is dipped on the surface of medical magnesium alloy which is polished and cleaned, and then dried for 3h at room temperature. Then, the coating was cured for 60 seconds by an electron beam curing machine (200kV) to finally form an electron beam cured coating.
Example 5:
(1) synthesis of polycarbonate copolymer 5: using benzyl alcohol as initiator, Sn (Oct)2As a catalyst, polymerization was carried out in a toluene solution at 90 ℃. Monomers ATMC (7.2g,48mmol), MA (6.4g,32mmol) were placed in a well-dried Schlenk's packAnd (4) neutralizing. The reaction vessel was sealed, evacuated and purged three times with nitrogen. Next, toluene (15mL) was rapidly injected into the Schlenk flask under magnetic stirring. After the monomers were thoroughly mixed, a toluene solution of benzyl alcohol (1.6mL,0.5M) and Sn (Oct) were added via syringe2Toluene solution (4.8mL, 0.1M). The reaction vessel was placed in an oil bath at 90 ℃ with magnetic stirring. Polymerization was carried out for 24 hours and toluene was removed by rotary evaporation. Polycarbonate copolymer 5 was dissolved in methylene chloride, precipitated into a quantity of cold methanol, isolated by filtration, and dried under vacuum at room temperature.
(2) Preparation of degradable polycarbonate coating: polycarbonate copolymer 5 was dissolved in THF to prepare a solution having a concentration of 10% (w/v), and the solution was stirred for 2 hours. The polycarbonate polymer 5 solution was then mixed with Dithiothreitol (DTT) so that the molar ratio of thiol to olefin was 9: 10. and 0.1 wt% of Irgacure I2959, and 5 wt% of bioactive substance RGD peptide were added and dissolved in the solution. The solution is dipped on the surface of medical magnesium alloy which is polished and cleaned, and then dried for 3h at room temperature. Then, the thiol-ene photocrosslinking bioactive coating is finally formed by UV illumination (365nm) for 30 s.
Comparative example 1:
commercial PTMC polymer, prepared as a 10 wt% dichloromethane solution, was dip-coated on the polished cleaned medical magnesium alloy surface, and then dried at room temperature for 24 h. Comparative example 1 is a commonly used surface erodible degradable polymer and is used in chinese patent CN 102327862B.
Comparative example 2:
commercial PLLA polymer, formulated as a 10 wt% THF solution, was dip coated on the polished cleaned medical magnesium alloy surface and then dried at room temperature for 24 h. Comparative example 2 is a degradable polymer coating (chinese patent CN109161882 a) that can be applied to medical magnesium alloy anticorrosion, as a degradable polyester, PLLA degradation behavior is bulk erosion degradation.
Test example 1
The corrosion resistance of the magnesium alloy surface treated by the examples and the comparative examples is tested.
The test method comprises the following steps: untreated bare magnesium alloys, samples prepared in examples 1-5 and comparative examples 1-2 (thickness was kept consistent about 10 μm), were immersed in SBF (human body simulant) and then immersed in a water bath at 37 ± 0.5 ℃ for 30 days. During the soaking period, SBF was changed every 2 days. The corrosion resistance of the samples was judged by measuring the weight loss of the samples before and after soaking, as shown in table 1.
TABLE 1 weight loss of samples before and after soaking
Figure GDA0003210840390000071
Figure GDA0003210840390000081
From the results of examples 1-5, the degradable coatings obtained from examples 1-5 were able to have a mass loss rate of less than 6% after 30 days of soaking, relative to the bare magnesium alloy, indicating that their degradable coatings have very excellent corrosion protection properties, allowing the substrate to remain highly intact after soaking. While comparative example 2 had a mass loss of nearly 50% after 30 days of immersion, even higher than the bare magnesium sample without coating, due to its acidic degradation products further accelerating the corrosion and degradation of the substrate. The mass loss of comparative example 1 is significantly less than that of the bare magnesium alloy, but also significantly greater than the results obtained in examples 1-5, indicating that the corrosion protection performance of examples 1-5 is significantly better than that of comparative examples 1 and 2, because the crosslinked network formed by curing can reduce the degradation rate of the coating and more effectively isolate the corrosion medium from corroding the magnesium substrate.
Test example 2:
the corrosion resistance of the magnesium alloy surface treated by the examples and the comparative examples is tested.
The test method comprises the following steps: untreated bare magnesium alloys, samples prepared in examples 1-3 and comparative examples 1-2 (thickness was kept consistent about 10 μm), were immersed in SBF (human body simulant) and then immersed in a water bath at 37 ± 0.5 ℃ for 30 days. During the soaking period, SBF was changed every 2 days. The surface morphology of the samples was observed by FE-SEM at 5 days, 15 days and 20 days, as shown in fig. 3.
From the results of examples 1 to 3, compared with the bare magnesium alloy, the degradable coatings obtained in examples 1 to 3 can maintain complete morphology within 30 days (before the coatings are completely degraded), so that the base material and the corrosive medium can be isolated all the time, and long-term protection of the base material is realized. In contrast, in comparative example 1, cracks generated by corrosion already appear on the surface of the sample after soaking for 15 days, which shows that although comparative example 1 and examples 1-3 are both degradation behaviors of surface corrosion, the corrosion prevention effect is obviously inferior to that of examples 1-3. Comparative example 2 micropores appeared on the surface of the coating layer after 5 days of immersion, the micropores became large and spread over the entire surface at 15 days, and were completely degraded after 30 days and large cracks appeared on the surface of the base material. Thus, the test results show that the corrosion prevention performance of examples 1-3 is significantly better than that of comparative examples 1-2.
Test example 3:
the basic performance of the coating prepared on the surface of the magnesium alloy in the test example and the comparative example is tested.
The test method comprises the following steps: the adhesion of the coatings was tested for examples 1-5 and comparative examples 1-2 using the national standard GB/T9286-; the pencil hardness of the coating was tested using the national standard GB/T6739-. The thickness of the coating was tested using a film thickness gauge. As shown in table 2:
table 2 basic performance test results for coatings
Figure GDA0003210840390000082
Figure GDA0003210840390000091
From the test results, the examples 1 to 3 have higher pencil hardness and excellent adhesion, and the performance is obviously better than that of the two comparative examples. Illustrating the significant advantages of the present invention in the basic performance of the coating.
Test example 4:
the method is used for testing the cell activity of the magnesium alloy surface after the treatment of the examples and the comparative examples.
The test method comprises the following steps: the bare magnesium alloy samples, examples 1,3,5 and comparative examples 1-2 were first subjected to ultraviolet light sterilization. L929 cells were plated at 6.0X 10 per well4Individual cells were seeded at a concentration on their surface. After inoculation, L929 cells were cultured in medium containing 10% fetal bovine serum and 1% antibiotics (37 ℃, 5% CO)2In a humid atmosphere of concentration). After 24 and 48 hours of culture, different samples were tested for cell activity by MTT. As shown in fig. 4:
from the test results, the coating samples in examples and comparative examples have similar cell activities after 24h of cell culture, however, after 48h of continuous culture, the cell activities of the samples in examples 1,3 and 5 are far better than those of comparative examples 1-2 due to the good preservation performance and the non-toxic carbon dioxide and water as degradation products. The biological functional coating prepared by the invention has more excellent cell compatibility.
The above is only a preferred embodiment of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.

Claims (9)

1. A preparation method of a degradable polycarbonate coating for reducing the corrosion rate of a medical magnesium-based material is characterized by comprising the following steps:
s1, preparing a polycarbonate copolymer with a molecular weight of 1000-100000 Da through ring-opening copolymerization of at least two six-membered cyclic carbonate monomers, wherein the polycarbonate copolymer is degradable polycarbonate with alkenyl on a side group; the six-membered cyclic carbonate monomer comprises: 1, 3-dioxan-2-one TMC, 5-methyl-5-allyloxycarbonyl-1, 3-dioxan-2-one MAC, 5-allyloxy-1, 3-dioxan-2-one ATMC, 2- (methacrylamido) trimethylene carbonate MATC, 5-methyl-5-acryloyloxy-1, 3-dioxan-2-one AC and 5-methyl-5-methacryloyloxy-1, 3-dioxan-2-one MA;
s2, dissolving a thiol crosslinking agent and the polycarbonate copolymer prepared in the step (S1) in an organic solvent to prepare a mixed solution with the solid content of 1-20 wt%, and performing thiol-ene addition reaction for crosslinking and curing;
s3, coating the mixed solution obtained in the step (S2) on the surface of a clean medical magnesium alloy base material; and carrying out rapid curing treatment after the coating is dried to obtain a degradable polycarbonate coating; the rapid cure includes radiation including electron beam, UV light, visible light, infrared light, and other forms of electromagnetic radiation.
2. The method for preparing the degradable polycarbonate coating for reducing the corrosion rate of the medical magnesium-based material according to claim 1, wherein an initiator and a catalyst are added in the ring-opening copolymerization reaction process in the step of S1, the initiator is a small molecule or a high molecule containing one hydroxyl functional group, and the catalyst is one or more of stannous octoate, diazabicyclo, 1,5, 7-triazabicyclo [4.4.0] dec-5-ene and 1-methyl-1, 5, 7-triazabicyclo [4.4.0] dec-5-ene.
3. The method for preparing the degradable polycarbonate coating for reducing the corrosion rate of the medical magnesium-based material according to claim 2, wherein the initiator comprises benzyl alcohol and isopropanol.
4. The method of claim 1, wherein the thiol crosslinking agent in step S2 comprises one or more of trimethylolpropane tris (3-mercaptopropionate), trimethylolpropane tris (2-mercaptoacetate), pentaerythritol tetrakis (3-mercaptopropionate), and dithiothreitol, and the molar ratio of thiol in the thiol crosslinking agent to unsaturated bonds in the polycarbonate copolymer is 9: 10 to 3: 2.
5. The method of claim 1, wherein the organic solvent in step S2 is one of dichloromethane, dimethyl sulfoxide, tetrahydrofuran and ethyl acetate.
6. The method for preparing the degradable polycarbonate coating for reducing the corrosion rate of the medical magnesium-based material as claimed in claim 1, wherein an auxiliary agent is added during the step of S2, the auxiliary agent is one or two of an initiator and a bioactive substance, the initiator is one or more of Irgacure 2959, ethyl pyruvate and phenyl-2, 4, 6-trimethylbenzoyllithium phosphonate, and the bioactive substance is one or two of RGD peptide and 2-methacryloyloxyethyl choline phosphate (MPC); in the mixed solution, the content of the initiator is 0-0.1 wt%, and the content of the bioactive substance is 0-10 wt%.
7. The method of claim 1, wherein the rapid solidification conditions of step S3 further comprise heat.
8. A degradable polycarbonate coating for reducing the corrosion rate of medical magnesium-based materials prepared according to the method of claim 1.
9. Use of the degradable polycarbonate coating of claim 8 to reduce the corrosion rate of medical magnesium based materials for corrosion control and/or to improve the bioactivity of device surfaces on medical devices made from magnesium and its alloys.
CN202010381096.6A 2020-05-08 2020-05-08 Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material Active CN111420129B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010381096.6A CN111420129B (en) 2020-05-08 2020-05-08 Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010381096.6A CN111420129B (en) 2020-05-08 2020-05-08 Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material

Publications (2)

Publication Number Publication Date
CN111420129A CN111420129A (en) 2020-07-17
CN111420129B true CN111420129B (en) 2021-11-02

Family

ID=71550785

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010381096.6A Active CN111420129B (en) 2020-05-08 2020-05-08 Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material

Country Status (1)

Country Link
CN (1) CN111420129B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114058294B (en) * 2021-11-25 2023-04-14 江苏兴达文具集团有限公司 Preparation process of degradable gold powder glue
CN115708896B (en) * 2022-11-16 2024-03-19 南京友德邦医疗科技有限公司 Degradable magnesium alloy composite material and preparation method thereof
CN115779142B (en) * 2022-11-18 2024-01-12 江南大学 Degradable drug-carrying coating for zinc alloy implant surface, and preparation method and application thereof
CN117045872B (en) * 2023-10-13 2023-12-15 四川大学 Corrosion-resistant composite coating, magnesium-based bracket containing corrosion-resistant composite coating and preparation method of magnesium-based bracket

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1680362A (en) * 2005-02-02 2005-10-12 武汉大学 5-acrylic oxo-trimethylene carbonate and its preparation and use
CN101914085A (en) * 2010-08-03 2010-12-15 武汉大学 2-methacrylamiotrimethylene carbonate, preparation method and application thereof
CN102712616A (en) * 2009-07-23 2012-10-03 Ssens有限责任公司 A method of making a polymer preferably an (alkyl) acryloyl polycarbonate, the polymer and (alkyl)acryloyl polycarbonate obtained, and a biodevice comprising same
US20130172482A1 (en) * 2010-08-27 2013-07-04 Novomer, Inc. Polymer compositions and methods
CN103930412A (en) * 2011-07-04 2014-07-16 Ssens有限责任公司 Method for making polymer, polymer article, biodevice, and cyclic carbonate
CN109912790A (en) * 2019-03-04 2019-06-21 西南交通大学 A kind of modified polycarbonate with highly blood coagulation resistant
CN110478526A (en) * 2011-10-03 2019-11-22 新特斯有限责任公司 It is reacted using the thiol-ene polymerization of vinyl esters and vinylcarbonates

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1680362A (en) * 2005-02-02 2005-10-12 武汉大学 5-acrylic oxo-trimethylene carbonate and its preparation and use
CN102712616A (en) * 2009-07-23 2012-10-03 Ssens有限责任公司 A method of making a polymer preferably an (alkyl) acryloyl polycarbonate, the polymer and (alkyl)acryloyl polycarbonate obtained, and a biodevice comprising same
CN101914085A (en) * 2010-08-03 2010-12-15 武汉大学 2-methacrylamiotrimethylene carbonate, preparation method and application thereof
US20130172482A1 (en) * 2010-08-27 2013-07-04 Novomer, Inc. Polymer compositions and methods
CN103930412A (en) * 2011-07-04 2014-07-16 Ssens有限责任公司 Method for making polymer, polymer article, biodevice, and cyclic carbonate
CN110478526A (en) * 2011-10-03 2019-11-22 新特斯有限责任公司 It is reacted using the thiol-ene polymerization of vinyl esters and vinylcarbonates
CN109912790A (en) * 2019-03-04 2019-06-21 西南交通大学 A kind of modified polycarbonate with highly blood coagulation resistant

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A surface-eroding poly(1,3-trimethylene carbonate) coating for fully biodegradable magnesium-based stent applications: Toward better biofunction, biodegradation and biocompatibility;Juan Wang,et al.;《Acta Biomaterialia》;20130301;第9卷(第10期);第8679页左栏倒数第二段、第8687段右栏最后一段 *
High performance thiol-ene thermosets based on fully bio-based poly(limonene carbonate)s;Chunliang Li，et al.;《EUROPEAN POLYMER JOURNAL》;20170922;第9卷;第339页倒数第二段、第347页倒数第二段 *

Also Published As

Publication number Publication date
CN111420129A (en) 2020-07-17

Similar Documents

Publication Publication Date Title
CN111420129B (en) Preparation method of degradable polycarbonate coating for reducing corrosion rate of medical magnesium-based material
Skarja et al. Synthesis and characterization of degradable polyurethane elastomers containing an amino acid-based chain extender
CA2701186C (en) Oligofluorinated cross-linked polymers and uses thereof
JP5671024B2 (en) Process for making polymers, preferably (alkyl) acryloyl polycarbonates, resulting polymers and (alkyl) acryloyl polycarbonates, and biodevices comprising the same
Bat et al. Resorbable elastomeric networks prepared by photocrosslinking of high-molecular-weight poly (trimethylene carbonate) with photoinitiators and poly (trimethylene carbonate) macromers as crosslinking aids
CN1418116A (en) Polyphosphazene derivatives
EP2729457B1 (en) Method for making a polymer, a polymer article, a biodevice, and cyclic carbonate
WO2013155173A2 (en) Methods and compositions relating to biodegradable epoxy elastomers
KR102208921B1 (en) Shape memory polymer, preparation method thereof, and the use of the same
CA2891048A1 (en) Method for grafting polymers on metallic substrates
EP2576646A1 (en) Method for preparing a degradable polymer network
Lv et al. Synthesis, evaluation of phospholipid biomimetic polycarbonate for potential cardiovascular stents coating
CN110075369A (en) Metal-macromolecule compound rest and its preparation method and application of degradation rate is adjusted with Multi-layer design
CN111437442B (en) Preparation method of degradable electrophoretic coating for magnesium-based medical implant surface
Kessler et al. Wettability and cell spreading enhancement in poly (sulfone) and polyurethane surfaces by UV-assisted treatment for tissue engineering purposes
Kayaman-Apohan et al. Poly (dl-lactic acid)/triblock PCL–PDMS–PCL copolymers: synthesis, characterization and demonstration of their cell growth effects in vitro
Natarajan et al. Maltitol-based biodegradable polyesters with tailored degradation and controlled release for bone regeneration
CN110124115B (en) Hydrophobic coating, preparation method and application thereof, and absorbable implantable device
Condat et al. Design of cytocompatible bacteria-repellent bio-based polyester films via an aqueous photoactivated process
Jung et al. Surface Graft Polymerization of Poly (Ethylene Glycol) Methacrylate onto Polyurethane via Thiol–Ene Reaction: Preparation and Characterizations
CN115779142B (en) Degradable drug-carrying coating for zinc alloy implant surface, and preparation method and application thereof
Madalosso et al. Collagen-decorated electrospun scaffolds of unsaturated copolyesters for bone tissue regeneration
KR102721932B1 (en) Composition, kit and method for treating surface of biomaterials
Yan et al. Synthesis and RGD peptide modification of poly {(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]}
Delmar-Greenberg et al. Non cell adhesive photopolymerized cross-linked layers (I): synthesis and characterization

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant