WO2018219035A1 - 一种抗菌硅橡胶、制备方法及其应用 - Google Patents

一种抗菌硅橡胶、制备方法及其应用 Download PDF

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Publication number
WO2018219035A1
WO2018219035A1 PCT/CN2018/081292 CN2018081292W WO2018219035A1 WO 2018219035 A1 WO2018219035 A1 WO 2018219035A1 CN 2018081292 W CN2018081292 W CN 2018081292W WO 2018219035 A1 WO2018219035 A1 WO 2018219035A1
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Prior art keywords
silicone rubber
antibacterial
acid
polyamino acid
macromolecule
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PCT/CN2018/081292
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English (en)
French (fr)
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牛之猛
张善勇
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苏州度博迈医疗科技有限公司
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Application filed by 苏州度博迈医疗科技有限公司 filed Critical 苏州度博迈医疗科技有限公司
Priority to US16/497,321 priority Critical patent/US11001688B2/en
Priority to EP18810066.3A priority patent/EP3584277B1/en
Publication of WO2018219035A1 publication Critical patent/WO2018219035A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L83/00—Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers
    • C08L83/10—Block- or graft-copolymers containing polysiloxane sequences
    • 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
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12—Chemical modification
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/89—Polysiloxanes
    • A61K8/896—Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate
    • A61K8/898—Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate containing nitrogen, e.g. amodimethicone, trimethyl silyl amodimethicone or dimethicone propyl PG-betaine
    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • 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
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04—Macromolecular materials
    • A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • 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
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12—Chemical modification
    • C08J7/16—Chemical modification with polymerisable compounds
    • 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
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12—Chemical modification
    • C08J7/16—Chemical modification with polymerisable compounds
    • C08J7/18—Chemical modification with polymerisable compounds using wave energy or particle radiation
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0043—Catheters; Hollow probes characterised by structural features
    • A61M2025/0056—Catheters; Hollow probes characterised by structural features provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
    • 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
    • C08G77/00—Macromolecular compounds obtained by reactions forming a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon in the main chain of the macromolecule
    • C08G77/42—Block-or graft-polymers containing polysiloxane sequences
    • C08G77/452—Block-or graft-polymers containing polysiloxane sequences containing nitrogen-containing sequences
    • C08G77/455—Block-or graft-polymers containing polysiloxane sequences containing nitrogen-containing sequences containing polyamide, polyesteramide or polyimide sequences
    • 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
    • C08J2383/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen, or carbon only; Derivatives of such polymers
    • C08J2383/04—Polysiloxanes

Definitions

  • the invention relates to a silicone rubber, a preparation method and application thereof, in particular to an antibacterial silicone rubber, a preparation method and application thereof.
  • Silicone rubber has excellent bio-safety and mechanical properties. It has been widely used in medical, health care, cosmetics and other fields for its products such as catheters, drainage tubes, respiratory catheters, cervical occlusion devices, and wound dressings. However, silicone rubber needs to be in contact with human tissues such as the urethra and skin for a long time during use. As an exogenous artificial material, the surface of the silicone rubber is prone to bacterial adhesion and proliferation, and even forms a biofilm on its surface, and With the increase in the retention time of silicone rubber, the probability of bacterial infection is also greater.
  • Antibiotics or organic antibacterial agents are combined with silicone rubber by bulk addition or surface coating to inhibit bacterial proliferation by specific antibacterial groups of antibiotics.
  • silicone rubber for example: Chinese patent CN201558397U "sustained release amikacin silicone rubber", the polylactic acid-polyglycolic acid carrying amikacin is applied to the surface of silicone rubber, and the antibacterial effect is obtained by slow release of amikacin. .
  • a large amount of antibiotics need to be added, and the use of a large amount of antibiotics may cause bacterial resistance, resulting in failure of antibiotics.
  • a chitin or chitosan derivative is applied to the surface of a silicone rubber to prepare an antibacterial silicone rubber.
  • the chitin or chitosan derivative has a weak antibacterial effect, and it has no covalent bonding with the surface of the silicone rubber, and has weak binding force and is easy to fall off.
  • the inorganic silver-loaded, copper or zinc-based antibacterial agent is compounded with silicone rubber to achieve antibacterial activity by releasing antibacterial metal ions (Ag+, Cu 2+ or Zn 2+ ) or by the action of nanoparticles on the surface of the silicone rubber.
  • antibacterial metal ions Ag+, Cu 2+ or Zn 2+
  • nanoparticles Ag+, Cu 2+ or Zn 2+
  • Chinese patent application CN2778285Y antibacterial silicone rubber
  • nano silver is coated on the surface layer of silicone rubber to prepare antibacterial silicone rubber
  • Chinese patent application CN101912638A nano silver-silica catheter and its production method
  • the nano-silver-loaded silica is incorporated into the silica gel, and then the antibacterial silicone rubber catheter is prepared by a vulcanization process.
  • the first technical problem to be solved by the present invention is to provide an antibacterial silicone rubber.
  • the antibacterial silicone rubber has long-lasting antibacterial property, and the bacteria are not easy to produce drug resistance; the antibacterial active substance does not precipitate and enter the cell to cause cytotoxicity problem, and the antibacterial silicone rubber has good biocompatibility with cells.
  • a second technical problem to be solved by the present invention is to provide a method for preparing the above-mentioned antibacterial silicone rubber.
  • a third technical problem to be solved by the present invention is to provide an application of the above-mentioned antibacterial silicone rubber.
  • the molecular structure is as follows:
  • R 1 is any one of the structures shown below:
  • R 2 is any one of the structures shown below:
  • R 3 is any one of the structures shown below:
  • R 4 is any one of the structures shown below:
  • polyamino acid macromolecules can be purchased directly from the market, or can be synthesized by those skilled in the art according to well-known methods.
  • the polyamino acid macromolecule is a polyamino acid homopolymer obtained by ring-opening polymerization of an amino acid-N-internal carboxylic anhydride by a primary or secondary amine molecule containing a vinyl or alkynyl group.
  • Amino acid block copolymer the specific preparation method is as follows:
  • the initiator and the amino acid-N-internal carboxylic anhydride A are dissolved in N,N-dimethylformamide or tetrahydrofuran, wherein the mass ratio of the initiator to the amino acid-N-internal carboxylic anhydride A is 1:10-1: 1000, the mass ratio of amino acid-N-internal carboxylic anhydride A to N,N-dimethylformamide or tetrahydrofuran is 1:5-1:100, protected by nitrogen, and stirred at 10-40 ° C.
  • the structural formula of the initiator is as follows:
  • R 3 is any one of the following structures:
  • R 4 is any one of the following structures:
  • a is an integer from 0 to 2000, and "*" is a chemical bonding point of R 3 , R 4 and its adjacent groups;
  • the polyamino acid with a protecting group is dissolved in trifluoroacetic acid, and a 33% hydrogen bromide/glacial acetic acid mixed solution is added under nitrogen protection and protection from light, and reacted at 20-40 ° C for 1-3 hours for product use.
  • the diethyl ether is precipitated, filtered, washed, and dried to obtain a polyamino acid macromolecule.
  • the amino acid-N-internal carboxylic anhydride A is selected from the group consisting of N( ⁇ )-benzyloxycarbonyl-L-lysine-N-carboxy anhydride, N'-benzyloxycarbonyl-L-ornithine, L-histidine One or more of -N-carboxy anhydride, L-arginine-N-carboxy anhydride;
  • the amino acid-N-internal carboxylic anhydride B is selected from the group consisting of N( ⁇ )-benzyloxycarbonyl-L-lysine-N-carboxy anhydride, N'-benzyloxycarbonyl-L-ornithine-N-carboxy anhydride, L-histidine-N-carboxy anhydride, L-arginine-N-carboxy anhydride, L-alanine-N-carboxy anhydride, L-leucine-N-carboxy anhydride, L-isoleucine Acid-N-carboxy anhydride, L-valine-N-carboxy anhydride, L-phenylalanine-N-carboxy anhydride, one of L-methionine-N-carboxy anhydride, ⁇ -benzyl-L- One or more of glutamic acid-carboxy anhydride and ⁇ -benzyl-L-aspartic acid-carboxylic anhydride.
  • the functional macromolecule may further comprise a hydrophilic molecule selected from the group consisting of N-vinyl pyrrolidone and its derivatives, acrylic acid and its derivatives, vinyl phosphate, One of the integers;
  • the N-vinylpyrrolidone derivative includes, but is not limited to, 5-vinyl-2-pyrrolidone;
  • the acrylic acid derivative includes, but is not limited to, acrylamide, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxybutyl acrylate Ester, hydroxyethyl methacrylate, hydroxypropyl methacrylate or hydroxybutyl methacrylate.
  • the present invention provides a method for preparing the above-mentioned antibacterial silicone rubber, comprising the following steps:
  • Another method for preparing the above-mentioned antibacterial silicone rubber provided by the present invention comprises the following steps:
  • the silicone rubber is taken out and subjected to conventional post-treatment to obtain an antibacterial silicone rubber.
  • the conventional aftertreatment includes ultrasonic cleaning, drying, packaging, and sterilization steps.
  • the certain initiation measure adopts one of ultraviolet light irradiation to initiate grafting, ⁇ -ray radiation initiation grafting, microwave initiation grafting, and heating initiation grafting.
  • the initiator is one or more of an azo-based radical initiator and a peroxide-based radical initiator; more preferably, the initiator includes, but is not limited to, ammonium persulfate, persulfate One or more of potassium, hydrogen peroxide, azobisisobutylphosphonium hydrochloride, and benzoyl peroxide.
  • the surface of the silicone rubber is subjected to an activation treatment to construct a chemical reaction site on the surface thereof, wherein the chemical reaction site is chemically bonded to the surface with free radicals, unsaturated carbon-carbon bonds, and stacks.
  • an activation treatment to construct a chemical reaction site on the surface thereof, wherein the chemical reaction site is chemically bonded to the surface with free radicals, unsaturated carbon-carbon bonds, and stacks.
  • nitrogen groups One or more of nitrogen groups
  • the method of performing the activation treatment on the surface of the silicone rubber includes, but is not limited to, one or more of the following methods:
  • Method A using a argon, helium, carbon, nitrogen, oxygen, hydrogen or H 2 O plasma to activate the surface of the silicone rubber, bonding carbon radicals, oxygen radicals or nitrogen radicals on the surface of the silicone rubber;
  • Method B Soaking the silicone rubber in an oxidizing agent such as sulfuric acid, hydrogen peroxide, potassium permanganate, periodic acid or hypochlorous acid or a blend thereof for 0-120 minutes, soaking in a vinyl silane coupling agent after ultrasonic washing Or after mixing the solution of one or more methacryloxysilane coupling agents in 0.01 to 24 hours, ultrasonically washing, bonding unsaturated carbon-carbon bonds on the surface of the silicone rubber;
  • an oxidizing agent such as sulfuric acid, hydrogen peroxide, potassium permanganate, periodic acid or hypochlorous acid or a blend thereof for 0-120 minutes
  • a vinyl silane coupling agent after ultrasonic washing Or after mixing the solution of one or more methacryloxysilane coupling agents in 0.01 to 24 hours, ultrasonically washing, bonding unsaturated carbon-carbon bonds on the surface of the silicone rubber
  • Method C Soaking the silicone rubber in an oxidizing agent such as sulfuric acid, hydrogen peroxide, potassium permanganate, periodic acid, hypochlorous acid or a mixture thereof for 0-120 minutes, ultrasonically washing and soaking in chloropropyltrimethoxysilane After 0.01-24 hours, the silicone rubber is immersed in a solution containing sodium azide in N,N-dimethylformamide, treated for 0.1-6 hours, then ultrasonically washed to bond the azide on the surface of the silicone rubber. Group.
  • an oxidizing agent such as sulfuric acid, hydrogen peroxide, potassium permanganate, periodic acid, hypochlorous acid or a mixture thereof for 0-120 minutes
  • the invention also provides the application of the antibacterial silicone rubber on an antibacterial catheter, an antibacterial wound dressing, an antibacterial breathing tube, an antibacterial drainage tube, an antibacterial gel, an antibacterial cervical occlusion device or an antibacterial mask.
  • the present invention has the following beneficial effects:
  • the polyamino acid macromolecule is combined with the surface of the silicone rubber by chemical bonding, and the macromolecule does not precipitate and enters the cell to produce cytotoxicity, and has good biocompatibility.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • the polyamino acid macromolecule and potassium persulfate are sequentially dissolved in water, and a functional reaction solution is disposed, wherein the mass ratio of the polyamino acid macromolecule, potassium persulfate and water is 1:0.0001:99;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 1 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Escherichia coli and Staphylococcus aureus; according to the standard GB/T 16886.5- Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test. Cytotoxicity test.
  • the antibacterial rate of the antibacterial silicone rubber obtained in Example 1 against Escherichia coli and Staphylococcus aureus was 99.92% and 99.65%, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • polyamino acid macromolecule, hydroxyethyl acrylate and ammonium persulfate are sequentially dissolved in water, and a functional reaction solution is disposed, wherein the mass ratio of polyamino acid macromolecule, hydroxyethyl acrylate, ammonium persulfate and water is 1:94. :3.8:5;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 2 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans; According to the standard GB/T 16886.5-2003 medical device biological evaluation part 5: in vitro cytotoxicity test for cytotoxicity test, the test cells are L929 mouse fibroblasts.
  • the antibacterial rate of the antibacterial silicone rubber obtained in Example 2 against S. aureus, Pseudomonas aeruginosa and Candida albicans was 99.21%, 99.78%, 98.86%, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • the polyamino acid macromolecule, acrylamide, and azobisisobutylphosphonium hydrochloride are sequentially dissolved in water, and a functional reaction solution is disposed, wherein the polyamino acid macromolecule, acrylamide, azobisisobutylphosphonium hydrochloride,
  • the water mass ratio is 0.5:50:0.05:49.5;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 3 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa; GB/T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • Example 3 The antibacterial silicone rubber obtained in Example 3 was tested against Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa by 96.81%, 95.94%, and 98.89%, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • polyamino acid macromolecule, hydroxypropyl acrylate and benzoyl peroxide are sequentially dissolved in water, and a functional reaction solution is arranged, wherein the mass ratio of polyamino acid macromolecule, hydroxypropyl acrylate, benzoyl peroxide and water is Is 1:1:0.04:98;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 4 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa; Standard GB/T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test is carried out, and the test cells are L929 mouse fibroblasts.
  • the antibacterial silicone rubber obtained in Example 4 was tested to be 99.81%, 99.94%, and 99.89%, respectively, against S. aureus, Escherichia coli, and Pseudomonas aeruginosa, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • polyamino acid macromolecule, hydroxybutyl acrylate and benzoyl peroxide are sequentially dissolved in water, and a functional reaction solution is arranged, wherein the mass ratio of polyamino acid macromolecule, hydroxybutyl acrylate, benzoyl peroxide and water is Is 1:5:0.02:94;
  • the silicone rubber is taken out, ultrasonically washed twice with deionized water, dried, packaged and sterilized to obtain an antibacterial silicone rubber which can be used for an antibacterial silicone rubber wound dressing.
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 5 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa; Standard GB/T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test is carried out, and the test cells are L929 mouse fibroblasts.
  • Example 5 The antibacterial silicone rubber obtained in Example 5 was tested against S. aureus, Escherichia coli and Pseudomonas aeruginosa by 99.21%, 99.97%, and 99.16%, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • the silicone rubber is taken out, ultrasonically washed twice with deionized water, dried, packaged and sterilized to obtain an antibacterial silicone rubber which can be used for an antibacterial hydrophilic silicone rubber mask.
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 6 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus and Pseudomonas aeruginosa; according to the standard GB/ T16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • the antibacterial silicone rubber obtained in Example 6 was tested to be 99.88% and 99.75% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • polyamino acid macromolecule, hydroxybutyl methacrylate and benzoyl peroxide are sequentially dissolved in water, and a functional reaction solution is arranged, wherein polyamino acid macromolecule, hydroxybutyl methacrylate, benzoyl peroxide,
  • the water mass ratio is 2: 30:0.2:68;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 7 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus epidermidis and Pseudomonas aeruginosa; according to the standard GB/T16886 .5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • Example 7 The antibacterial silicone rubber obtained in Example 7 was tested for S. epidermidis and Pseudomonas aeruginosa at 99.28% and 99.58%, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial silicone rubber obtained in Example 8 was tested for antibacterial properties according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus epidermidis and Candida albicans; according to the standard GB/T16886.5 -2003 Medical Device Biology Evaluation Part 5: In Vitro Cytotoxicity Test A cytotoxicity test was performed, and the test cells were L929 mouse fibroblasts.
  • Example 8 The antibacterial silicone rubber obtained in Example 8 was tested for S. epidermidis and Candida albicans at 99.18% and 94.58%, respectively, and the cytotoxicity was 0.
  • the preparation method of the antibacterial silicone rubber comprises the following steps: (1) dissolving the polyamino acid macromolecule, 5-vinyl-2-pyrrolidone and azobisisobutylphosphonium hydrochloride in water, and disposing the functional reaction solution.
  • the mass ratio of polyamino acid macromolecule, 5-vinyl-2-pyrrolidone, azobisisobutylphosphonium hydrochloride and water is 8:12:0.2:80;
  • (2) using argon plasma injection to silica gel silicone rubber The surface is treated. Immediately after the treatment, the silicone rubber is immersed in the functional reaction solution and treated by ultraviolet irradiation for 4 hours. (3) The silicone rubber is taken out, ultrasonically washed twice with deionized water, dried, packaged and sterilized.
  • Antibacterial silicone rubber which is used in antibacterial silicone rubber breathing tubes.
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial silicone rubber obtained in Example 9 was tested for antibacterial properties according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus and Pseudomonas aeruginosa; according to the standard GB/ T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • the antibacterial silicone rubber obtained in Example 9 was tested to be 99.74% and 99.92% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • polyamino acid macromolecule, 5-vinyl-2-pyrrolidone, and azobisisobutylphosphonium hydrochloride are sequentially dissolved in water, and a functional reaction solution is disposed, wherein the polyamino acid macromolecule, 5-vinyl-2-
  • the mass ratio of pyrrolidone, azobisisobutylphosphonium hydrochloride, and water is 8:40:0.2:52;
  • the silicone rubber is taken out, ultrasonically washed twice with deionized water, dried, packaged and sterilized to obtain an antibacterial silicone rubber which can be used for an antibacterial super-slip silicone rubber catheter.
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial silicone rubber obtained in Example 10 was tested for antibacterial properties according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus and Candida albicans; according to the standard GB/T 16886.5 -2003 Medical Device Biology Evaluation Part 5: In Vitro Cytotoxicity Test A cytotoxicity test was performed, and the test cells were L929 mouse fibroblasts.
  • the antibacterial silicone rubber obtained in Example 10 was tested to be 99.74%, 97.92% for Staphylococcus aureus and Candida albicans, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • the polyamino acid macromolecule, N-vinylpyrrolidone, potassium persulfate, and azobisisobutylphosphonium hydrochloride are sequentially dissolved in water, and a functional reaction solution is disposed, wherein the polyamino acid macromolecule, N-vinylpyrrolidone,
  • the mass ratio of potassium persulfate and azobisisobutylphosphonium hydrochloride is 8:12:0.1:0.1:80;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial silicone rubber obtained in Example 11 was tested for antibacterial properties according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus and Candida albicans; according to the standard GB/T 16886.5 -2003 Medical Device Biology Evaluation Part 5: In Vitro Cytotoxicity Test A cytotoxicity test was performed, and the test cells were L929 mouse fibroblasts.
  • the antibacterial silicone rubber obtained in Example 11 was tested to be 99.74%, 97.92% for Staphylococcus aureus and Candida albicans, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • polyamino acid macromolecule, vinyl phosphoric acid, and potassium persulfate are sequentially dissolved in water, and a functional reaction solution is disposed, wherein the mass ratio of the polyamino acid macromolecule, the vinyl phosphoric acid, the potassium persulfate, and the water is 5:25:0.6. :70;
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 12 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus and Pseudomonas aeruginosa; according to the standard GB/ T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • Example 12 The antibacterial silicone rubber obtained in Example 12 was tested to be 96.74% and 92.92% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the cytotoxicity was 0.
  • a method for preparing an antibacterial silicone rubber comprising the following steps:
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 13 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus aureus, Escherichia coli and Candida albicans; /T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • the antibacterial silicone rubber obtained in Example 13 was 99.84%, 99.92%, and 97.65%, respectively, against Staphylococcus aureus, Escherichia coli, and Candida albicans, and the cytotoxicity was 0.
  • An antibacterial silicone rubber and a preparation method thereof comprising the following steps:
  • the structural formula of the polyamino acid macromolecule is as follows:
  • the antibacterial property of the antibacterial silicone rubber obtained in Example 14 was tested according to the antibacterial property of the standard ISO 22196-2011 plastic and other non-porous surfaces, and the test bacteria were Staphylococcus epidermidis, Escherichia coli and Candida albicans; according to the standard GB/ T 16886.5-2003 Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test The cytotoxicity test was carried out, and the test cells were L929 mouse fibroblasts.
  • Example 14 The antibacterial silicone rubber obtained in Example 14 was tested against Staphylococcus epidermidis, Escherichia coli and Candida albicans by 99.44%, 99.88%, and 96.65%, respectively, and the cytotoxicity was 0.

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Abstract

本发明公开一种抗菌硅橡胶，在硅橡胶表面化学键合有功能大分子，所述功能大分子含乙烯基或乙炔基，功能大分子通过乙烯基或乙炔基与硅橡胶表面化学键合；所述功能大分子包括聚氨基酸大分子，其分子结构如（I）（II）所示：本发明的抗菌硅橡胶在硅橡胶表面化学键合聚氨基酸大分子，通过聚氨基酸大分子与细菌中带负电的细胞膜相互作用而抗菌，抗菌持久，且细菌不易产生耐药性；同时聚氨基酸大分子通过化学键合的方式与硅橡胶表面相结合，大分子不会析出而进入细胞内，具有良好的生物相容性。

Description

一种抗菌硅橡胶、制备方法及其应用 技术领域
本发明涉及一种硅橡胶、制备方法及其应用，尤其是涉及一种抗菌硅橡胶、制备方法及其应用。
背景技术
硅橡胶具有优异的生物安全性和机械性能，将它制作成导尿管、引流管、呼吸导管、宫颈封堵器、伤口敷料等产品已广泛应用到医疗、保健、化妆品等领域中。然而，硅橡胶在使用过程中需要与尿道、皮肤等人体组织长时间接触，作为外源性人工材料，硅橡胶表面易发生细菌粘附和增殖现象，甚至在其表面形成生物菌膜，而且随着硅橡胶留置时间的增加，其发生细菌感染的概率也越大。生物菌膜作为微生物的“保护伞”可以抵御抗生素对微生物的影响，甚至进入人体血液引发败血症，甚至危及患者生命。据统计，每年因使用硅橡胶而引起的细菌感染占院内感染总数的40％，且硅橡胶的细菌感染率还在逐年增加。因此，硅橡胶表面抗菌性能至关重要，开发抗菌硅橡胶及其产品对于提高硅橡胶的留置周期、增加使用舒适度、减少医护工作量、保障患者生命安全具有重要意义。
目前研究和开发抗菌硅橡胶主要有以下两种方式：
1)将抗生素或者有机抗菌剂通过本体添加或者表面涂覆的方式与硅橡胶结合，通过抗生素的特定抗菌基团抑制细菌的增殖。例如：中国专利CN201558397U“载缓释阿米卡星硅橡胶”中，将载有阿米卡星的聚乳酸-聚羟基乙酸涂覆到硅橡胶表面，通过缓释阿米卡星来获得抗菌效果。然而，由于硅橡胶留置时间较长，为确保抗菌效果，需添加大量抗生素，且大量使用抗生素的会导致细菌产生耐药性，导致抗生素失效。中国专利申请CN201431691Y“一种抗菌亲水涂层硅橡胶”中，将甲壳素或壳聚糖的衍生物涂覆到硅橡胶表面，制备抗菌硅橡胶。然而，甲壳素或壳聚糖衍生物的抗菌效果较弱，且其与硅橡胶表面无共价键合，结合力弱，易于脱落。
2)将无机载银、铜或锌类抗菌剂与硅硅橡胶复合，通过释放抗菌金属离子(Ag+、Cu 2+或Zn 2+)或者其纳米粒子与硅橡胶表面细菌作用而实现抗菌。例如：中国专利申请CN2778285Y“抗菌硅橡胶”中，将纳米银包覆在硅橡胶表层，制备抗菌硅橡胶；中国专利申请CN101912638A“纳米载银-二氧化硅导尿管及其生产方法”中，将纳米载银的二氧化硅掺入硅胶中，再经硫化等工艺制备抗菌硅橡胶导尿管。然而，抗菌金属离子或者纳米颗 粒的不断析出和累积，破坏周围组织的微环境平衡，干扰周围细胞的正常生长，促使细胞内活性氧(ROS)的含量升高，产生细胞毒性，导致硅橡胶的生物相容性差。
由此可见，现有的技术方案均存在无法避免细菌耐药性或抗菌活性物质析出引起的细胞毒性问题。
发明内容
本发明要解决的第一个技术问题是提供一种抗菌硅橡胶。该抗菌硅橡胶抗菌持久，细菌不易产生耐药性；抗菌活性物质不会析出而进入细胞内引起细胞毒性问题，抗菌硅橡胶与细胞具有良好的生物相容性。
本发明要解决的第二个技术问题是提供一种上述抗菌硅橡胶的制备方法。
本发明要解决的第三个技术问题是提供一种上述抗菌硅橡胶的应用。
为解决上述第一个技术问题，发明采用如下的技术方案：
一种抗菌硅橡胶，在硅橡胶表面化学键合有功能大分子，所述功能大分子含乙烯基或乙炔基，功能大分子通过乙烯基或乙炔基与硅橡胶表面化学键合；所述功能大分子包括聚氨基酸大分子，其分子结构如下所示：
Figure PCTCN2018081292-appb-000001
式中R 1为以下所示结构中的任意一种：
Figure PCTCN2018081292-appb-000002
式中R 2为以下所示结构中的任意一种：
Figure PCTCN2018081292-appb-000003
式中R 3为以下所示结构中的任意一种：
Figure PCTCN2018081292-appb-000004
式中R 4为以下所示结构中的任意一种：
H，CH 3，CH 2CH 3，
Figure PCTCN2018081292-appb-000005
式中m、n、z、a均为整数，m＝5-10000，n＝0-5000，z＝1-200，a＝0-2000；“*”为R 1、R 2、R 3、R 4与其相邻基团的化学键合点。
所述聚氨基酸大分子可由市场上直接购买，也可由本领域的专业技术人员根据熟知的方法合成。
在本申请中，优选地，所述聚氨基酸大分子通过含乙烯基或炔基的伯胺或仲胺类分子引发氨基酸-N-内羧酸酐开环聚合而得到的聚氨基酸均聚物或者聚氨基酸嵌段共聚物，具体制备方法如下：
S1、将引发剂和氨基酸-N-内羧酸酐A溶于N,N-二甲基甲酰胺或四氢呋喃中，其中引发剂与氨基酸-N-内羧酸酐A的质量比1:10-1:1000，氨基酸-N-内羧酸酐A与N,N-二甲基甲酰胺或四氢呋喃的质量比为1:5-1:100，通入氮气保护，在10-40℃下搅拌反应12-96小时；然后再加入氨基酸-N-内羧酸酐B，氨基酸-N-内羧酸酐B与氨基酸-N-内羧酸酐A的质量比为0:1-1:1，在10-40℃下搅拌反应12-96小时；反应结束后，将溶液减压浓缩除去溶剂，将浓缩后的溶液在乙醚中沉淀，烘干得到聚氨基酸或带有保护基的聚氨基酸；
所述引发剂的结构式如下：
Figure PCTCN2018081292-appb-000006
式中，R 3为以下所示结构中的任意一种：
Figure PCTCN2018081292-appb-000007
式中，R 4为以下所示结构中的任意一种：
H，CH 3，CH 2CH 3，
Figure PCTCN2018081292-appb-000008
式中，a为0-2000的整数，“*”为R 3、R 4与其相邻基团的化学键合点；
S2、将带有保护基的聚氨基酸用三氟乙酸溶解，在氮气保护和避光条件下加入33％溴化氢/冰醋酸混合溶液，在20-40℃下反应1-3小时，产物用乙醚沉降，过滤，洗涤，干燥，即得聚氨基酸大分子。
所述氨基酸-N-内羧酸酐A选自N(ε)-苄氧羰基-L-赖氨酸-N-羧酸酐、N'-苄氧羰基-L-鸟氨酸、L-组氨酸-N-羧酸酐、L-精氨酸-N-羧酸酐中的一种或几种；
所述氨基酸-N-内羧酸酐B选自N(ε)-苄氧羰基-L-赖氨酸-N-羧酸酐、N'-苄氧羰基-L-鸟氨酸-N-羧酸酐、L-组氨酸-N-羧酸酐、L-精氨酸-N-羧酸酐、L-丙氨酸-N-羧酸酐中、L-亮氨酸-N-羧酸酐、L-异亮氨酸-N-羧酸酐、L-缬氨酸-N-羧酸酐、L-苯丙氨酸-N-羧酸酐、L-蛋氨酸-N-羧酸酐中的一种、γ-苄基-L-谷氨酸-羧酸酐、β-苄基-L-天冬氨酸-羧酸酐中的一种或几种。
优选地，所述功能大分子还可以包括亲水性分子，所述亲水性分子选自N-乙烯基吡咯烷酮及其衍生物、丙烯酸及其衍生物、乙烯基磷酸、
Figure PCTCN2018081292-appb-000009
整数中的一种；
优选地，所述N-乙烯基吡咯烷酮衍生物包含但不限于5-乙烯基-2-吡咯烷酮；所述丙烯酸衍生物包含但不限于丙烯酰胺、丙烯酸羟乙酯、丙烯酸羟丙酯、丙烯酸羟丁酯、甲基丙烯酸羟乙酯、甲基丙烯酸羟丙酯或甲基丙烯酸羟丁酯。
为解决上述第二个技术问题，本发明提供一种上述抗菌硅橡胶的制备方法，包括如下步骤：
S01、配置含聚氨基酸大分子和引发剂的功能反应水溶液，所述聚氨基酸大分子在反应水溶液中的质量浓度为0.1％-95％，引发剂的质量为聚氨基酸大分子质量的0.01％-4％；
S02、将硅橡胶浸泡在功能反应水溶液中，并施加一定的引发措施反应0.05-12小时；
S03、取出硅橡胶，常规后处理，获得抗菌硅橡胶。
本发明提供的另一种上述抗菌硅橡胶的制备方法，包括如下步骤：
S11、配置含聚氨基酸大分子、亲水性分子和引发剂的功能反应水溶液，聚氨基酸大分子和亲水性分子在水溶液中总质量浓度为0.1％-95％，聚氨基酸大分子与亲水性分子的质量比为1:0-1:100，引发剂的质量为聚氨基酸大分子和亲水性分子总质量的0.01％-4％；
S12、将硅橡胶浸泡在功能反应溶液中，并施加一定的引发措施反应0.05-12小时；
S13、取出硅橡胶，常规后处理，获得抗菌硅橡胶。
优选地，所述常规后处理包括超声清洗、干燥、包装和灭菌步骤。
优选地，所述一定的引发措施采用紫外光辐照引发接枝、γ射线辐射引发接枝、微波引发接枝、加热引发接枝中的一种。
优选地，所述引发剂为偶氮类自由基引发剂、过氧化物类自由基引发剂中的一种或多种；更优选地，所述引发剂包括但不限于过硫酸铵、过硫酸钾、过氧化氢、偶氮二异丁脒盐酸盐、过氧化苯甲酰中的一种或多种。
优选地，在进行步骤S02和S12之前，先对硅橡胶表面进行活化处理，在其表面构建 化学反应位点，所述化学反应位点为表面化学键合有自由基、不饱和碳碳键、叠氮基团中的一种或多种；
所述对硅橡胶表面进行活化处理的方法包括但不限定于如下方法中的一种或多种：
方法A：使用氩、氦、碳、氮、氧、氢或H 2O等离子体对硅橡胶表面进行活化，在硅橡胶表面键合碳自由基、氧自由基或氮自由基；
方法B：将硅橡胶浸泡在硫酸、双氧水、高锰酸钾、高碘酸、次氯酸等氧化剂或它们的共混液中0-120分钟后，超声洗涤后浸泡在乙烯基硅烷类偶联剂或甲基丙烯酰氧基硅烷类偶联剂的一种或多种混合溶液中0.01-24小时后，超声洗涤，在硅橡胶表面键合不饱和碳碳键；
方法C：将硅橡胶浸泡在硫酸、双氧水、高锰酸钾、高碘酸、次氯酸等氧化剂或它们的共混液中0-120分钟后，超声洗涤后浸泡在氯丙基三甲氧基硅烷中0.01-24小时后，再将硅橡胶浸泡至含叠氮化钠的N，N-二甲基甲酰胺的溶液中，处理0.1-6小时后，超声洗涤，在硅橡胶表面键合叠氮基团。
本发明还提供所述抗菌硅橡胶在抗菌导尿管、抗菌伤口敷料、抗菌呼吸导管、抗菌引流管、抗菌凝胶、抗菌宫颈封堵器或抗菌面膜上的应用。
与现有技术相比，本发明具有如下有益效果：
(1)在硅橡胶表面化学键合聚氨基酸大分子，通过聚氨基酸大分子与细菌中带负电的细胞膜相互作用而抗菌，抗菌持久，且细菌不易产生耐药性。
(2)聚氨基酸大分子通过化学键合的方式与硅橡胶表面相结合，大分子不会析出而进入细胞内产生细胞毒性，具有良好的生物相容性。
具体实施方式
为了更清楚地说明本发明，下面结合优选实施例对本发明做进一步的说明。本领域技术人员应当理解，下面所具体描述的内容是说明性的而非限制性的，不应以此限制本发明的保护范围。
实施例1
一种抗菌硅橡胶制备方法，包括如下步骤：
(1)将聚氨基酸大分子、过硫酸钾依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、过硫酸钾、水的质量比为1：0.0001：99；
(2)将硅橡胶浸泡在功能反应溶液中，微波加热至120℃，处理0.05小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌呼吸导管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000010
对实施例1中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为大肠杆菌和金黄色葡萄菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试。
经测试，实施例1中得到的抗菌硅橡胶对大肠杆菌和金黄色葡萄球菌的抗菌率分别为99.92％、99.65％，细胞毒性为0级。
实施例2
一种抗菌硅橡胶制备方法，包括如下步骤：
(1)将聚氨基酸大分子、丙烯酸羟乙酯、过硫酸胺依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、丙烯酸羟乙酯、过硫酸胺、水的质量比为1：94：3.8：5；
(2)将硅胶硅橡胶浸泡在功能反应溶液中，微波加热至80℃，处理0.5小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌超滑导尿管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000011
对实施例2中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄菌、铜绿假单胞菌和白色念珠菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例2中得到的抗菌硅橡胶对金黄色葡萄菌、铜绿假单胞菌和白色念珠菌抗菌率分别为99.21％、99.78％、98.86％，细胞毒性为0级。
实施例3
一种抗菌硅橡胶制备方法，包括如下步骤：
(1)将聚氨基酸大分子、丙烯酰胺、偶氮二异丁脒盐酸盐依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、丙烯酰胺、偶氮二异丁脒盐酸盐、水的质量比为0.5：50：0.05：49.5；
(2)使用氧等离子体注入对硅胶硅橡胶表面进行处理，处理完成后立即将硅橡胶浸泡在功能反应溶液中，紫外辐照处理0.2小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌引流管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000012
对实施例3中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为表皮葡萄球菌、大肠杆菌和铜绿假单胞菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例3中得到的抗菌硅橡胶对表皮葡萄球菌、大肠杆菌和铜绿假单胞菌分别为96.81％、95.94％、98.89％，细胞毒性为0级。
实施例4
一种抗菌硅橡胶制备方法，包括如下步骤：
(1)将聚氨基酸大分子、丙烯酸羟丙酯、过氧化苯甲酰依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、丙烯酸羟丙酯、过氧化苯甲酰、水的质量比为1：1：0.04：98；
(2)使用氧等离子体注入对硅橡胶表面进行处理，处理完成后立即将硅橡胶浸泡在功能反应溶液中，γ射线辐照处理12小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌硅橡胶凝胶。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000013
对实施例4中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例4中得到的抗菌硅橡胶对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌分别为99.81％、99.94％、99.89％，细胞毒性为0级。
实施例5
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、丙烯酸羟丁酯、过氧化苯甲酰依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、丙烯酸羟丁酯、过氧化苯甲酰、水的质量比为1：5：0.02：94；
(2)使用硫酸和双氧水的混合溶液对硅胶硅橡胶表面进行处理1分钟，超声洗涤后再将其浸泡在乙烯基三乙氧基硅烷中0.01小时后，超声洗涤，在硅橡胶表面键合不饱和碳碳键；
(3)将步骤(2)处理完的硅橡胶浸泡在功能反应溶液中，加热至60℃，反应1小时；
(4)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌硅橡胶伤口敷料。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000014
对实施例5中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌； 依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例5中得到的抗菌硅橡胶对金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌分别为99.21％、99.97％、99.16％，细胞毒性为0级。
实施例6
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、甲基丙烯酸羟丙酯、过氧化氢依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、甲基丙烯酸羟丙酯、过氧化氢、水的质量比为1：20：0.1：79；
(2)将硅胶硅橡胶浸泡在γ-甲基丙烯酰氧基三乙氧基硅烷中24小时后，超声洗涤，在硅橡胶表面键合不饱和碳碳键；
(3)将步骤(2)处理完的硅橡胶浸泡在功能反应溶液中，加热至80℃，反应1小时；
(4)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌亲水硅橡胶面膜。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000015
对实施例6中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌和铜绿假单胞菌；依据标准GB/T16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例6中得到的抗菌硅橡胶对金黄色葡萄球菌和铜绿假单胞菌分别为99.88％、99.75％，细胞毒性为0级。
实施例7
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、甲基丙烯酸羟丁酯、过氧化苯甲酰依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、甲基丙烯酸羟丁酯、过氧化苯甲酰、水的质量比为2： 30：0.2：68；
(2)将硅胶硅橡胶浸泡在氯丙基三甲氧基硅烷中2小时后，再将硅橡胶浸泡至含叠氮化钠的N，N-二甲基甲酰胺的溶液中，处理0.1小时后，超声洗涤，在硅橡胶表面键合叠氮基团；
(3)将步骤(2)处理完的硅橡胶浸泡在功能反应溶液中，紫外辐射处理1小时；
(4)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌硅橡胶宫颈封堵器。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000016
对实施例7中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为表皮葡萄球菌和铜绿假单胞菌；依据标准GB/T16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例7中得到的抗菌硅橡胶对表皮葡萄球菌和铜绿假单胞菌分别为99.28％、99.58％，细胞毒性为0级。
实施例8
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、甲基丙烯酸羟乙酯、偶氮二异丁脒盐酸盐依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、甲基丙烯酸羟乙酯、偶氮二异丁脒盐酸盐、水的质量比为10：10：0.25：80；
(2)使用氮等离子体注入对硅胶硅橡胶表面进行处理，处理完成后立即将硅橡胶浸泡在功能反应溶液中，紫外辐照处理2小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌硅橡胶导尿管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000017
对实施例8中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为表皮葡萄球菌和白色念珠菌；依据标准GB/T16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例8中得到的抗菌硅橡胶对表皮葡萄球菌和白色念珠菌分别为99.18％、94.58％，细胞毒性为0级。
实施例9
一种抗菌硅橡胶的制备方法，包括如下步骤：(1)将聚氨基酸大分子、5-乙烯基-2-吡咯烷酮、偶氮二异丁脒盐酸盐依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、5-乙烯基-2-吡咯烷酮、偶氮二异丁脒盐酸盐、水的质量比为8：12：0.2：80；(2)使用氩等离子体注入对硅胶硅橡胶表面进行处理，处理完成后立即将硅橡胶浸泡在功能反应溶液中，紫外辐照处理4小时；(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌硅橡胶呼吸导管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000018
对实施例9中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌和铜绿假单胞菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例9中得到的抗菌硅橡胶对金黄色葡萄球菌和铜绿假单胞菌分别为99.74％、99.92％，细胞毒性为0级。
实施例10
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、5-乙烯基-2-吡咯烷酮、偶氮二异丁脒盐酸盐依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、5-乙烯基-2-吡咯烷酮、偶氮二异丁脒盐酸盐、水的质量比为8：40：0.2：52；
(2)使用高锰酸钾溶液对硅胶硅橡胶表面进行处理120分钟，超声洗涤后再将其浸泡在乙烯基三甲氧基硅烷中0.1小时后，超声洗涤，在硅橡胶表面键合不饱和碳碳键；
(3)将步骤(2)处理完的硅橡胶浸泡在功能反应溶液中，加热至80℃，反应1小时；
(4)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌超滑硅橡胶导尿管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000019
对实施例10中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌和白色念珠菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例10中得到的抗菌硅橡胶对金黄色葡萄球菌和白色念珠菌分别为99.74％、97.92％，细胞毒性为0级。
实施例11
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、N-乙烯基吡咯烷酮、过硫酸钾、偶氮二异丁脒盐酸盐依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、N-乙烯基吡咯烷酮、过硫酸钾、偶氮二异丁脒盐酸盐水的质量比为8：12：0.1：0.1：80；
(2)使用氩等离子体注入对硅胶硅橡胶表面进行处理，处理完成后立即将硅橡胶浸泡在功能反应溶液中，γ射线辐照处理8小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌超滑硅橡胶导尿管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000020
对实施例11中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌和白色念珠菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例11中得到的抗菌硅橡胶对金黄色葡萄球菌和白色念珠菌分别为99.74％、97.92％，细胞毒性为0级。
实施例12
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、乙烯基磷酸、过硫酸钾依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、乙烯基磷酸、过硫酸钾、水的质量比为5：25：0.6：70；
(2)将硅胶硅橡胶浸泡在功能反应溶液中，微波加热至80℃，处理0.5小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌呼吸导管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000021
对实施例12中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌和铜绿假单胞菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例12中得到的抗菌硅橡胶对金黄色葡萄球菌和铜绿假单胞菌分别为96.74％、92.92％，细胞毒性为0级。
实施例13
一种抗菌硅橡胶的制备方法，包括如下步骤：
(1)将聚氨基酸大分子、
Figure PCTCN2018081292-appb-000022
过氧化氢依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、
Figure PCTCN2018081292-appb-000023
过氧化氢、水的质量比为5：35：1：60；
(2)将硅橡胶浸泡在功能反应溶液中，加热至80℃，处理3小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌硅橡胶伤口敷料。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000024
对实施例13中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为金黄色葡萄球菌、大肠杆菌和白色念珠菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例13中得到的抗菌硅橡胶对金黄色葡萄球菌、大肠杆菌和白色念珠菌分别为99.84％、99.92％、97.65％，细胞毒性为0级。
实施例14
一种抗菌硅橡胶及其制备方法，包括如下步骤：
(1)将聚氨基酸大分子、
Figure PCTCN2018081292-appb-000025
过硫酸钾依次溶于水中，配置功能反应溶液，其中聚氨基酸大分子、
Figure PCTCN2018081292-appb-000026
过硫酸钾、水的质量比为10：40：1：50；
(2)将硅胶硅橡胶浸泡在功能反应溶液中，微波加热至120℃，处理5小时；
(3)取出硅橡胶，用去离子水超声清洗2次，晾干，包装并灭菌，获得抗菌硅橡胶，该抗菌硅橡胶可用于抗菌超滑硅橡胶导尿管。
所述聚氨基酸大分子的结构式如下：
Figure PCTCN2018081292-appb-000027
对实施例14中得到的抗菌硅橡胶依据标准ISO 22196-2011塑料与其他无孔表面的抗菌性测定进行抗菌性能测试，测试用菌为表皮葡萄球菌、大肠杆菌和白色念珠菌；依据标准GB/T 16886.5-2003医疗器械生物学评价第5部分：体外细胞毒性试验进行细胞毒性测试，测试用细胞为L929小鼠成纤维细胞。
经测试，实施例14中得到的抗菌硅橡胶对表皮葡萄球菌、大肠杆菌和白色念珠菌分别为99.44％、99.88％、96.65％，细胞毒性为0级。
显然，本发明的上述实施例仅仅是为清楚地说明本发明所作的举例，而并非是对本发明的实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无法对所有的实施方式予以穷举。凡是属于本发明的技术方案所引伸出的显而易见的变化或变动仍处于本发明的保护范围之列。

Claims (10)

  1. 一种抗菌硅橡胶，其特征在于：在硅橡胶表面化学键合有功能大分子，所述功能大分子含乙烯基或乙炔基，功能大分子通过乙烯基或乙炔基与硅橡胶表面化学键合；所述功能大分子包括聚氨基酸大分子，其分子结构如下所示：
    Figure PCTCN2018081292-appb-100001
    式中R 1为以下所示结构中的任意一种：
    Figure PCTCN2018081292-appb-100002
    式中R 2为以下所示结构中的任意一种：
    Figure PCTCN2018081292-appb-100003
    式中R 3为以下所示结构中的任意一种：
    Figure PCTCN2018081292-appb-100004
    式中R 4为以下所示结构中的任意一种：
    H，CH 3，CH 2CH 3，
    Figure PCTCN2018081292-appb-100005
    式中m、n、z、a均为整数，且m＝5-10000，n＝0-5000，z＝1-200，a＝0-2000；“*”为R 1、R 2、R 3、R 4与其相邻基团的化学键合点。
  2. 根据权利要求1所述抗菌硅橡胶，其特征在于：所述聚氨基酸大分子通过含乙烯基或炔基的伯胺或仲胺类分子引发氨基酸-N-内羧酸酐开环聚合而得到的聚氨基酸均聚物或者聚氨基酸嵌段共聚物，具体制备方法如下：
    S1、将引发剂和氨基酸-N-内羧酸酐A溶于N,N-二甲基甲酰胺或四氢呋喃中，其中引发剂与氨基酸-N-内羧酸酐A的质量比1:10-1:1000，氨基酸-N-内羧酸酐与N,N-二甲基甲 酰胺或四氢呋喃的质量比为1:5-1:100，通入氮气保护，在10-40℃下搅拌反应12-96小时；然后再加入氨基酸N-内羧酸酐B，氨基酸N-内羧酸酐B与氨基酸N-内羧酸酐A的质量比为0:1-1:1，在10-40℃下搅拌反应12-96小时；反应结束后，将溶液减压浓缩除去溶剂，将浓缩后的溶液在乙醚中沉淀，烘干得到聚氨基酸或带有保护基的聚氨基酸；
    所述引发剂的结构式如下：
    Figure PCTCN2018081292-appb-100006
    式中，R 3为以下所示结构中的任意一种：
    Figure PCTCN2018081292-appb-100007
    式中，R 4为以下所示结构中的任意一种：
    H，CH 3，CH 2CH 3，
    Figure PCTCN2018081292-appb-100008
    式中，a为0-2000的整数，“*”为R 3、R 4与其相邻基团的化学键合点；
    S2、将带有保护基的聚氨基酸用三氟乙酸溶解，在氮气保护和避光条件下加入33％溴化氢/冰醋酸混合溶液，在20-40℃下反应1-3小时，产物用乙醚沉降，过滤，洗涤，干燥，即得聚氨基酸大分子。
  3. 根据权利要求2所述抗菌硅橡胶，其特征在于：
    所述氨基酸-N-内羧酸酐A选自N(ε)-苄氧羰基-L-赖氨酸-N-羧酸酐、N'-苄氧羰基-L-鸟氨酸、L-组氨酸-N-羧酸酐、L-精氨酸-N-羧酸酐中的一种或几种；
    所述氨基酸-N-内羧酸酐B选自N(ε)-苄氧羰基-L-赖氨酸-N-羧酸酐、N'-苄氧羰基-L-鸟氨酸-N-羧酸酐、L-组氨酸-N-羧酸酐、L-精氨酸-N-羧酸酐、L-丙氨酸-N-羧酸酐中、L-亮氨酸-N-羧酸酐、L-异亮氨酸-N-羧酸酐、L-缬氨酸-N-羧酸酐、L-苯丙氨酸-N-羧酸酐、L-蛋氨酸-N-羧酸酐中的一种、γ-苄基-L-谷氨酸-羧酸酐、β-苄基-L-天冬氨酸-羧酸酐中的一种或几种。
  4. 根据权利要求1所述抗菌硅橡胶，其特征在于：
    所述功能大分子还包括亲水性分子，所述亲水性分子选自N-乙烯基吡咯烷酮及其衍生物、丙烯酸及其衍生物、乙烯基磷酸、
    Figure PCTCN2018081292-appb-100009
    b＝5-500整数中的一种；
  5. 根据权利要求4所述抗菌硅橡胶，其特征在于：
    所述N-乙烯基吡咯烷酮衍生物包括但不限于5-乙烯基-2-吡咯烷酮；所述丙烯酸衍生 物包括但不限于丙烯酰胺、丙烯酸羟乙酯、丙烯酸羟丙酯、丙烯酸羟丁酯、甲基丙烯酸羟乙酯、甲基丙烯酸羟丙酯或甲基丙烯酸羟丁酯。
  6. 如权利要求1-5中任一所述抗菌硅橡胶的制备方法，其特征在于，包括如下步骤：
    S01、配置含聚氨基酸大分子和引发剂的功能反应水溶液，所述聚氨基酸大分子在反应水溶液中的质量浓度为0.1％-95％，引发剂的质量为聚氨基酸大分子质量的0.01％-4％；
    S02、将硅橡胶浸泡在功能反应水溶液中，并施加一定的引发措施反应0.05-12小时；
    S03、取出硅橡胶，常规后处理，获得抗菌硅橡胶。
  7. 如权利要求1-5中任一所述抗菌硅橡胶的制备方法，其特征在于，包括如下步骤：
    S11、配置含聚氨基酸大分子、亲水性分子和引发剂的功能反应水溶液，聚氨基酸大分子和亲水性分子在水溶液中总质量浓度为0.1％-95％，聚氨基酸大分子与亲水性分子的质量比为1:0-1:100，引发剂的质量为聚氨基酸大分子和亲水性分子总质量的0.01％-4％；
    S12、将硅橡胶浸泡在功能反应溶液中，并施加一定的引发措施反应0.05-12小时；
    S13、取出硅橡胶，常规后处理，获得抗菌硅橡胶。
  8. 根据权利要求6或7所述的制备方法，其特征在于：
    优选地，所述常规后处理包括超声清洗、干燥、包装和灭菌步骤；
    优选地，所述一定的引发措施采用紫外光辐照引发接枝、γ射线辐射引发接枝、微波引发接枝、加热引发接枝中的一种；
    优选地，所述引发剂为偶氮类自由基引发剂、过氧化物类自由基引发剂中的一种或多种；更优选地，所述引发剂包括但不限于过硫酸铵、过硫酸钾、过氧化氢、偶氮二异丁脒盐酸盐、过氧化苯甲酰中的一种或多种。
  9. 根据权利要求6或7所述的制备方法，其特征在于：
    在进行步骤S02和S12之前，先对硅橡胶表面进行活化处理；
    所述对硅橡胶表面进行活化处理的方法包括但不限定于如下方法中的一种或多种：
    方法A：使用氩、氦、碳、氮、氧、氢或H 2O等离子体对硅橡胶表面进行活化，在硅橡胶表面键合碳自由基、氧自由基或氮自由基；
    方法B：将硅橡胶浸泡在硫酸、双氧水、高锰酸钾、高碘酸、次氯酸等氧化剂或它们的共混液中0-120分钟后，超声洗涤后浸泡在乙烯基硅烷类偶联剂或甲基丙烯酰氧基硅烷类偶联剂的一种或多种混合溶液中0.01-24小时后，超声洗涤，在硅橡胶表面键合不饱和碳碳键；
    方法C：将硅橡胶浸泡在硫酸、双氧水、高锰酸钾、高碘酸、次氯酸等氧化剂或它们的共混液中0-120分钟后，超声洗涤后浸泡在氯丙基三甲氧基硅烷中0.01-24小时后，再 将硅橡胶浸泡至含叠氮化钠的N，N-二甲基甲酰胺的溶液中，处理0.1-6小时后，超声洗涤，在硅橡胶表面键合叠氮基团。
  10. 如权利要求1-5中任一所述抗菌硅橡胶在抗菌导尿管、抗菌伤口敷料、抗菌呼吸导管、抗菌引流管、抗菌凝胶、抗菌宫颈封堵器或抗菌面膜上的应用。
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