CN115607750B - In-situ anticoagulation modified medical PVC material, and preparation method and application thereof - Google Patents
In-situ anticoagulation modified medical PVC material, and preparation method and application thereof Download PDFInfo
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- CN115607750B CN115607750B CN202110805957.3A CN202110805957A CN115607750B CN 115607750 B CN115607750 B CN 115607750B CN 202110805957 A CN202110805957 A CN 202110805957A CN 115607750 B CN115607750 B CN 115607750B
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- 239000000463 material Substances 0.000 title claims abstract description 76
- 230000010100 anticoagulation Effects 0.000 title claims abstract description 52
- 238000011065 in-situ storage Methods 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- 239000000178 monomer Substances 0.000 claims abstract description 72
- 229920001577 copolymer Polymers 0.000 claims abstract description 43
- 238000002156 mixing Methods 0.000 claims abstract description 37
- 239000004014 plasticizer Substances 0.000 claims abstract description 32
- 125000000542 sulfonic acid group Chemical group 0.000 claims abstract description 30
- 239000011347 resin Substances 0.000 claims abstract description 29
- 229920005989 resin Polymers 0.000 claims abstract description 29
- 125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 27
- 238000004132 cross linking Methods 0.000 claims abstract description 24
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 19
- 239000003381 stabilizer Substances 0.000 claims abstract description 18
- 239000008280 blood Substances 0.000 claims abstract description 17
- 210000004369 blood Anatomy 0.000 claims abstract description 17
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- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
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- 238000010559 graft polymerization reaction Methods 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 38
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 16
- 239000008116 calcium stearate Substances 0.000 claims description 16
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- GPYYEEJOMCKTPR-UHFFFAOYSA-L zinc;dodecanoate Chemical compound [Zn+2].CCCCCCCCCCCC([O-])=O.CCCCCCCCCCCC([O-])=O GPYYEEJOMCKTPR-UHFFFAOYSA-L 0.000 claims description 16
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- APVVRLGIFCYZHJ-UHFFFAOYSA-N trioctyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCC)CC(=O)OCCCCCCCC APVVRLGIFCYZHJ-UHFFFAOYSA-N 0.000 claims description 9
- DZSVIVLGBJKQAP-UHFFFAOYSA-N 1-(2-methyl-5-propan-2-ylcyclohex-2-en-1-yl)propan-1-one Chemical group CCC(=O)C1CC(C(C)C)CC=C1C DZSVIVLGBJKQAP-UHFFFAOYSA-N 0.000 claims description 8
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 8
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- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 5
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- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 4
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- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 claims description 4
- GNSFRPWPOGYVLO-UHFFFAOYSA-N 3-hydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCO GNSFRPWPOGYVLO-UHFFFAOYSA-N 0.000 claims description 4
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- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 4
- CNCOEDDPFOAUMB-UHFFFAOYSA-N N-Methylolacrylamide Chemical compound OCNC(=O)C=C CNCOEDDPFOAUMB-UHFFFAOYSA-N 0.000 claims description 4
- 239000000944 linseed oil Substances 0.000 claims description 4
- 235000021388 linseed oil Nutrition 0.000 claims description 4
- OMNKZBIFPJNNIO-UHFFFAOYSA-N n-(2-methyl-4-oxopentan-2-yl)prop-2-enamide Chemical compound CC(=O)CC(C)(C)NC(=O)C=C OMNKZBIFPJNNIO-UHFFFAOYSA-N 0.000 claims description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 3
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 8
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- 238000004090 dissolution Methods 0.000 abstract description 16
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- 230000004048 modification Effects 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 4
- 229920000915 polyvinyl chloride Polymers 0.000 description 96
- 239000004800 polyvinyl chloride Substances 0.000 description 96
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- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 11
- 108010094028 Prothrombin Proteins 0.000 description 11
- 102100027378 Prothrombin Human genes 0.000 description 11
- 108090000190 Thrombin Proteins 0.000 description 11
- 108010000499 Thromboplastin Proteins 0.000 description 11
- 102000002262 Thromboplastin Human genes 0.000 description 11
- 229940039716 prothrombin Drugs 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 229960004072 thrombin Drugs 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 9
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 6
- 239000004711 α-olefin Substances 0.000 description 6
- 239000004971 Cross linker Substances 0.000 description 5
- 229920012485 Plasticized Polyvinyl chloride Polymers 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 4
- 239000002861 polymer material Substances 0.000 description 4
- 238000007792 addition Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010059598 Heparin resistance Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F259/00—Macromolecular compounds obtained by polymerising monomers on to polymers of halogen containing monomers as defined in group C08F14/00
- C08F259/02—Macromolecular compounds obtained by polymerising monomers on to polymers of halogen containing monomers as defined in group C08F14/00 on to polymers containing chlorine
- C08F259/04—Macromolecular compounds obtained by polymerising monomers on to polymers of halogen containing monomers as defined in group C08F14/00 on to polymers containing chlorine on to polymers of vinyl chloride
-
- 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
- A61L31/048—Macromolecular materials obtained 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
- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/0076—Chemical modification of the substrate
- A61L33/0082—Chemical modification of the substrate by reacting with an organic compound other than heparin
-
- 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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
- A61L33/064—Use of macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Surgery (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
The invention discloses an in-situ anticoagulation modified medical PVC material, a preparation method and application thereof. The preparation method comprises the following steps: blending PVC resin, a primary plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant in a banburying device, adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator, and performing free radical graft polymerization in an anaerobic environment to obtain a copolymer containing carboxylic acid groups and sulfonic acid groups, wherein the copolymer can form a reticular interpenetrating stable structure with cross-linking points with a PVC chain segment, and the obtained copolymer is subjected to cross-linking reaction in a vulcanizing device to obtain the in-situ anticoagulation modified medical PVC material. The preparation method is simple, does not use solvents, is environment-friendly, and can finish modification and preparation in one step, and the obtained anticoagulation medical PVC material has good biocompatibility, less dissolution, no teratogenesis and no anaphylactic reaction; also has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property.
Description
Technical Field
The invention belongs to the technical field of medical appliances, and particularly relates to an in-situ anticoagulation modified medical PVC material, a preparation method and application thereof.
Background
In the biomedical field, with the rapid development of modern medicine, medical polymer materials have been widely used in various medical means such as medical catheters, blood storage bags, surgical guide wires, and various extracorporeal circulation devices, etc. However, the existing devices still have problems of biocompatibility and blood compatibility in the use process, and often induce nonspecific adsorption of some biomolecules such as proteins, cells, bacteria and the like on the surface of the materials, so that coagulation is induced. As biomedical polymer materials, a material which is in direct contact with blood is required to have good biocompatibility, and a material which is in direct contact with blood is required to have good tissue compatibility and good anticoagulation property.
In the patent with publication number CN103965639A, CN105194742A, heparin is used as anticoagulant, and heparin is added into high molecular material to obtain medical high molecular material with excellent anticoagulation effect, and CN207384541U discloses a method for uniformly distributing heparin in anticoagulation hemodialysis management pipeline, and can stably release heparin in the use process to prevent coagulation and thrombosis. However, long-term use of heparin is easy to cause bleeding, thrombocytopenia, heparin resistance, osteoporosis and other diseases, and excessive heparin usage also causes spontaneous bleeding with great side effects; heparin micromolecules are easy to inactivate and dissolve in the using process, CN103524752A discloses a fluorosilicone-POSS acrylate segmented copolymer, a blood compatibility coating and a preparation method, the fluorosilicone-POSS acrylate segmented copolymer is sprayed on the surface of polymers such as PVC (polyvinyl chloride) to reduce surface platelet adhesion and improve blood compatibility, but the sprayed coating is easy to fall off along with blood flowing and long-time use, and has poor long-term stability.
Disclosure of Invention
Aiming at the problem of poor blood compatibility of medical polymer materials in the prior art, the main purpose of the invention is to provide an in-situ anticoagulation modified medical PVC material and a preparation method thereof, thereby overcoming the defects in the prior art.
The invention also aims at providing the application of the in-situ anticoagulation modified medical PVC material.
In order to achieve the purpose of the invention, the technical scheme adopted by the invention comprises the following steps:
the embodiment of the invention provides a preparation method of an in-situ anticoagulation modified medical PVC material, which comprises the following steps:
uniformly mixing PVC resin, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant to form a mixture;
putting the mixture into banburying equipment, plasticizing and mixing at 110-160 ℃ and 20-80 r/min, and fully and uniformly dispersing;
in an anaerobic environment, adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator into the banburying equipment, and carrying out free radical grafting polymerization for 10-60 min to obtain a copolymer containing carboxylic acid groups and sulfonic acid groups, wherein the copolymer can form a netty interpenetrating stable structure with cross-linking points with PVC chain segments, the carboxylic acid group monomer comprises vinyl acetic acid, and the sulfonic acid group monomer comprises any one or two of 2-acrylamide-2-methylpropanesulfonic acid and alpha-olefin sodium sulfonate;
and placing the obtained copolymer into vulcanizing equipment, and performing crosslinking reaction for 10-120min at 130-170 ℃ to obtain the in-situ anticoagulation modified medical PVC material.
In some embodiments, the preparation method specifically includes:
and fully blending PVC resin, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant in a high-speed dispersing device at 30-100 ℃ for 1-6 h to form the mixture.
In some embodiments, the mass ratio of the sum of the mass of the crosslinker monomer, carboxylic acid-based monomer, sulfonic acid-based monomer to the PVC resin is from 0.05:10 to 1:10.
Further, the mass ratio of the cross-linking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer is (15-40): (10-30): (30-65), and the total mass parts of the three is 100.
The embodiment of the invention also provides the in-situ anticoagulation modified medical PVC material obtained by the method, which comprises a reticular interpenetrating stable structure with cross-linking points formed by the copolymer and the PVC chain segment.
The embodiment of the invention also provides application of the in-situ anticoagulation modified medical PVC material in preparing medical instruments.
Compared with the prior art, the invention has the beneficial effects that:
1) The preparation method of the in-situ anticoagulation modified medical PVC material provided by the invention adopts the copolymer containing carboxylic acid groups and sulfonic acid groups to graft and polymerize and modify the PVC material, and the copolymer and the PVC material are crosslinked at high temperature to form a stable network interpenetrating stable structure with crosslinking points. The method does not use solvents, is environment-friendly, has simple preparation method, and completes modification and preparation in one step;
2) The in-situ anticoagulation modified medical PVC material prepared by the invention has good biocompatibility, less dissolution, no teratogenesis and no anaphylactic reaction; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property. The copolymer containing carboxylic acid groups and sulfonic acid groups has good chemical stability and high temperature resistance, and the addition of the copolymer does not change the physical appearance characteristics of PVC materials such as color, transparency and the like.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and other drawings may be obtained according to the drawings without inventive effort to those skilled in the art.
FIG. 1 is a comparative graph of Activated Partial Thromboplastin Time (APTT), thrombin Time (TT), prothrombin Time (PT) of an in situ anticoagulation modified medical PVC material prepared in example 1 according to the invention and a medical PVC material of comparative example 1;
FIG. 2 is a graph showing the mechanical properties of the in-situ anticoagulation modified medical PVC material prepared in example 1 according to the invention and that of the medical PVC material of comparative example 1.
Detailed Description
As described above, in view of the shortages of poor blood compatibility and the like of the medical polymer materials in the prior art, the inventor of the present invention has provided a technical scheme of the present invention through long-term research and a great deal of practice, and provides an in-situ anticoagulation modified medical PVC material and a preparation method thereof. The technical scheme, the implementation process, the principle and the like are further explained as follows.
One aspect of the embodiments of the present invention provides a method for preparing an in-situ anticoagulation modified medical PVC material, which includes:
uniformly mixing PVC resin, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant to form a mixture;
putting the mixture into banburying equipment, plasticizing and mixing at 110-160 ℃ and 20-80 r/min, and fully and uniformly dispersing;
in an anaerobic environment, adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator into the banburying equipment, and carrying out free radical grafting polymerization for 10-60 min to obtain a copolymer containing carboxylic acid groups and sulfonic acid groups, wherein the copolymer can form a netty interpenetrating stable structure with cross-linking points with PVC chain segments, the carboxylic acid group monomer comprises vinyl acetic acid, and the sulfonic acid group monomer comprises any one or two of 2-acrylamide-2-methylpropanesulfonic acid and alpha-olefin sodium sulfonate;
and placing the obtained copolymer into vulcanizing equipment, and performing crosslinking reaction for 10-120min at 130-170 ℃ to obtain the in-situ anticoagulation modified medical PVC material.
In some embodiments, the preparation method specifically includes:
and fully blending PVC resin, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant in a high-speed dispersing device at 30-100 ℃ for 1-6 h to form the mixture.
In some embodiments, the PVC resin, primary plasticizer, secondary plasticizer, stabilizer to lubricant mass ratio is (60-80): (10-50): (5-30): (3-10): (0.5-1). That is, the aforementioned components include at least, in parts by weight: 60-80 parts of PVC resin, 10-50 parts of primary plasticizer, 5-30 parts of auxiliary plasticizer, 3-10 parts of stabilizer and 0.5-1 part of lubricant.
In some embodiments, the primary plasticizer includes DOP, trioctyl citrate, and the like, but is not limited thereto.
Further, the auxiliary plasticizer includes epoxidized soybean oil, epoxidized flax oil, etc., but is not limited thereto.
Further, the stabilizer comprises zinc laurate, calcium stearate and the like; specifically, the stabilizer comprises 50-70 wt% of zinc laurate and 30-50 wt% of calcium stearate.
Further, the lubricant includes polyethylene wax, but is not limited thereto.
In some embodiments, the mass ratio of the sum of the mass of the crosslinker monomer, carboxylic acid-based monomer, sulfonic acid-based monomer to the PVC resin is from 0.05:10 to 1:10.
In some embodiments, the mass ratio of the crosslinker monomer, carboxylic acid-based monomer, and sulfonic acid-based monomer is (15-40): (10-30): (30-65). Namely, the mass ratio of the cross-linking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer is as follows: 15-40% of cross-linking agent monomer, 10-30% of carboxylic acid group monomer and 30-65% of sulfonic acid group monomer, wherein the mass percentage of the three components is 100%.
In some embodiments, the mass ratio of the sum of the masses of the crosslinker monomer, carboxylic acid-based monomer, and sulfonic acid-based monomer to the initiator is 100:0.1 to 1, that is, the initiator accounts for 0.1 to 1 percent of the total mass of the three monomers.
In some embodiments, the crosslinker monomer includes any one or a combination of two or more of acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-methylolacrylamide, diacetone acrylamide, and the like, but is not limited thereto. When the ratio is plural, the ratio is arbitrary.
Further, the initiator includes any one or a combination of two or more of azobisisobutyronitrile, azobisisoheptonitrile, dibenzoyl peroxide, etc., but is not limited thereto.
In some more specific embodiments, the preparation method specifically includes:
(1) Blending PVC resin powder, a plasticizer, a stabilizer and a lubricant in an internal mixer; (2) Adding a carboxylic acid group monomer, a sulfonic acid group monomer, a cross-linking agent and an initiator into a closed system of an internal mixer, and realizing free radical grafting polymerization reaction in an anaerobic environment of the internal mixer, wherein a polymerization product is a polymer containing a carboxylic acid group and a sulfonic acid group, and the polymer and a PVC chain segment form a reticular interpenetrating stable structure with cross-linking points; (3) And (3) after the polymer and PVC are subjected to crosslinking reaction on a vulcanizing machine, obtaining the in-situ anticoagulation modified medical PVC material.
As one of more specific embodiments, the preparation method of the in-situ anticoagulation modified medical PVC material includes the following steps:
step (1): fully blending PVC resin powder, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant in a high-speed dispersing machine at 30-100 ℃ for 1-6 h to form the mixture;
the PVC resin powder, the plasticizer, the stabilizer and the lubricant comprise the following components in parts by weight:
60-80 parts of PVC resin
10-50 parts of primary plasticizer
5-30 parts of auxiliary plasticizer
3-10 parts of stabilizer
0.5-1 part of lubricant
The primary plasticizer is DOP and/or trioctyl citrate; the auxiliary plasticizer is epoxidized soybean oil and/or epoxidized linseed oil;
the stabilizer comprises 50-70 wt% of zinc laurate and 30-50 wt% of calcium stearate;
the lubricant is polyethylene wax.
Step (2): plasticizing and mixing the mixture in an internal mixer at 110-160 ℃ and 20-80 r/min, and fully and uniformly dispersing;
step (3): the temperature and the rotating speed are kept unchanged, and a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator are added into an internal mixer to carry out polymerization reaction for 10-60 min.
The mass ratio of the total mass of the cross-linking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the PVC is (0.05:10) - (1:10);
the cross-linking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer are prepared from the following components in parts by mass:
crosslinking agent monomer 15-40%
10 to 30 percent of carboxylic acid group monomer
Sulfonic acid group monomer 30-65%
The weight percentage of the mixture ratio is 100 percent;
the ratio of the initiator to the total mass of the three monomers is 0.1-1%.
Step (4): taking out the copolymer, putting the copolymer into a mould, putting the mould into a vulcanizing machine preheated to 130-170 ℃ for crosslinking reaction for 10-120min, and obtaining the in-situ anticoagulation modified medical PVC material product.
The cross-linking agent monomer used in the step (3) comprises one or a mixture of a plurality of acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-methylolacrylamide, diacetone acrylamide and the like, and when the cross-linking agent monomer is a plurality of cross-linking agent monomers, the ratio is an arbitrary ratio.
The carboxylic acid-based monomer used in the step (3) is vinyl acetic acid.
The sulfonic acid group monomer adopted in the step (3) is one or a mixture of more than one of 2-acrylamide-2-methylpropanesulfonic acid and alpha-olefin sodium sulfonate, and when the sulfonic acid group monomer is a plurality of sulfonic acid groups, the ratio is an arbitrary ratio.
Another aspect of the embodiments of the present invention also provides an in-situ anticoagulation modified medical PVC material obtained by the foregoing method, which comprises a mesh interpenetrating stable structure having crosslinking points formed by a copolymer and a PVC segment.
Furthermore, the in-situ anticoagulation modified medical PVC material prepared by the method has good biocompatibility, is less in dissolution, does not cause teratogenesis and anaphylactic reaction; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property. The copolymer containing carboxylic acid groups and sulfonic acid groups has good chemical stability and high temperature resistance, and the addition of the copolymer does not change the physical appearance characteristics of PVC materials such as color, transparency and the like.
The invention also provides an application of the in-situ anticoagulation modified medical PVC material obtained by the method in preparing medical instruments, and the in-situ anticoagulation modified medical PVC material is applied to the field of medical instruments and can be used for producing PVC blood bags, catheters and the like.
For example, another aspect of the invention provides a PVC blood bag or catheter formed from the in situ anticoagulation modified medical PVC material.
In summary, the preparation method of the in-situ anticoagulation modified medical PVC material provided by the invention adopts the copolymer containing carboxylic acid groups and sulfonic acid groups to graft-polymerize and modify the PVC material, and the copolymer and the PVC material are crosslinked at high temperature to form a stable network interpenetrating stable structure with crosslinking points. The method does not use solvents, is environment-friendly, has simple preparation method, and completes modification and preparation in one step; the prepared in-situ anticoagulation modified medical PVC material has good biocompatibility, less dissolution, no teratogenesis and no anaphylactic reaction; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further described with reference to the detailed description and the accompanying drawings, so that those skilled in the art can implement the present invention by referring to the text of the specification. It should be understood that the specific embodiments described herein are merely illustrative of the present invention, and the experimental conditions and setting parameters thereof should not be construed as limiting the basic technical scheme of the present invention. And the scope of the present invention is not limited to the following examples. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.
The physical, mechanical, dissolution and biological properties of the examples below were measured according to GB 15593-1995.
Example 1
Adding 62.4g of PVC resin, 20g of DOP, 10g of epoxy linseed oil, 3.6g of zinc laurate, 2.4g of calcium stearate and 0.6g of polyethylene wax into a high-speed dispersing machine at the temperature of 30 ℃ and fully blending for 4 hours to obtain a mixture; step (2) adding 99g of the mixture into an internal mixer, plasticizing and mixing for 7min at 130 ℃ and 30 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.3g g N-methylolacrylamide, 0.3g vinyl acetic acid, 0.4g 2-acrylamide-2-methylpropanesulfonic acid and 0.01g azodiisobutyronitrile into an internal mixer for polymerization reaction for 30min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 150 ℃, and carrying out crosslinking reaction for 50min to obtain the in-situ anticoagulation modified medical PVC material. The tensile strength of the in-situ anticoagulation modified medical PVC material prepared by the test reaches 14.8MPa, and the elongation at break reaches 560%; the Activated Partial Thromboplastin Time (APTT) is up to 600s, the Thrombin Time (TT) is up to 26.8s, the Prothrombin Time (PT) is up to 36s, and the performance is not reduced after the washing at the high temperature of 121 ℃ for 30min; the dissolution product is qualified, and the specific results are shown in Table 1.
Comparative example 1
Adding 63.4 parts of PVC resin, 20 parts of trioctyl citrate, 10 parts of epoxidized soybean oil, 3.6 parts of zinc laurate, 2.4 parts of calcium stearate and 0.6 part of polyethylene wax into a high-speed dispersing machine at the temperature of 30 ℃ and fully blending for 4 hours to obtain a mixture; step (2) adding the mixture into an internal mixer, plasticizing and mixing for 7min at 130 ℃ and 30 r/min; and (3) placing the plasticized PVC into a die, and placing the die on a vulcanizing machine preheated to 150 ℃ for 50min to obtain an unmodified PVC sheet material. The tensile strength of the PVC material prepared by the test is 15.2MPa, and the elongation at break is 570%; the Activated Partial Thromboplastin Time (APTT) was 40s, thrombin Time (TT) was 16.6s, and Prothrombin Time (PT) was 29s. The dissolution product is qualified, and the specific results are shown in Table 1.
Example 2
Adding 62.4 parts of PVC resin, 20 parts of trioctyl citrate, 10 parts of epoxidized soybean oil, 3.6 parts of zinc laurate, 2.4 parts of calcium stearate and 0.6 part of polyethylene wax into a high-speed dispersing machine at the temperature of 100 ℃ and fully blending for 3 hours to obtain a mixture; step (2) adding 98g of the mixture into an internal mixer, plasticizing and mixing for 7min at the temperature of 110 ℃ and the speed of 30 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.6g of hydroxypropyl acrylate, 0.6g of vinyl acetic acid, 0.8g of 2-acrylamide-2-methylpropanesulfonic acid and 0.016g of azodiisoheptonitrile into an internal mixer for polymerization reaction for 20min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 130 ℃, and carrying out crosslinking reaction for 40min to obtain the in-situ anticoagulation modified PVC sheet material. The tensile strength of the PVC material prepared by the test reaches 15MPa, and the elongation at break reaches 567%; the Activated Partial Thromboplastin Time (APTT) is up to 600s, the Thrombin Time (TT) is up to 30s, the Prothrombin Time (PT) is up to 38s, and the performance is not reduced after the washing at the high temperature of 121 ℃ for 30min; the dissolution product is qualified, and the specific results are shown in Table 1.
Comparative example 2
Adding 63.4 parts of PVC resin, 20 parts of trioctyl citrate, 10 parts of epoxidized soybean oil, 3.6 parts of zinc laurate, 2.4 parts of calcium stearate and 0.6 part of polyethylene wax into a high-speed dispersing machine at the temperature of 100 ℃ and fully blending for 3 hours to obtain a mixture; step (2) adding the mixture into an internal mixer, plasticizing and mixing for 7min at 130 ℃ and 30 r/min; and (3) placing the plasticized PVC into a die, and placing the die on a vulcanizing machine preheated to 150 ℃ for 50min to obtain an unmodified PVC sheet material. The tensile strength of the PVC material prepared by the test is 15.2MPa, and the elongation at break is 570%; the Activated Partial Thromboplastin Time (APTT) was 40s, thrombin Time (TT) was 16.6s, and Prothrombin Time (PT) was 29s. The dissolution product is qualified, and the specific results are shown in Table 1.
Example 3
Adding 70.4 parts of PVC resin, 15 parts of trioctyl citrate, 10 parts of epoxidized soybean oil, 1.5 parts of zinc laurate, 1.5 parts of calcium stearate and 0.8 part of polyethylene wax into a high-speed dispersing machine at 90 ℃ and fully blending for 3 hours to obtain a mixture; step (2) adding 98g of the mixture into an internal mixer, plasticizing and mixing for 5min at 150 ℃ and 20 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.4g of hydroxyethyl acrylate, 0.4g of vinyl acetic acid, 1.2g of alpha-olefin sodium sulfonate and 0.008g of azodiisobutyronitrile into an internal mixer for polymerization reaction for 40min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 140 ℃, and carrying out crosslinking reaction for 10min to obtain the in-situ anticoagulation modified PVC sheet material. The tensile strength of the PVC material prepared by the test reaches 13.8MPa, and the elongation at break reaches 544%; the Activated Partial Thromboplastin Time (APTT) is up to 600s, the Thrombin Time (TT) is up to 30.2s, the Prothrombin Time (PT) is up to 39s, and the performance is not reduced after the washing at the high temperature of 121 ℃ for 30min; the dissolution product is qualified, and the specific results are shown in Table 1.
Comparative example 3
Adding 70.4 parts of PVC resin, 15 parts of trioctyl citrate, 10 parts of epoxidized soybean oil, 1.5 parts of zinc laurate, 1.5 parts of calcium stearate and 0.8 part of polyethylene wax into a high-speed dispersing machine at 90 ℃ and fully blending for 3 hours to obtain a mixture; step (2) adding the mixture into an internal mixer, plasticizing and mixing for 5min at 150 ℃ and 20 r/min; and (3) placing the plasticized PVC into a die, and placing the die on a vulcanizing machine preheated to 160 ℃ for 10min to obtain an unmodified PVC sheet material. The tensile strength of the PVC material prepared by the test is 14MPa, and the elongation at break is 550%; the Activated Partial Thromboplastin Time (APTT) was 41s, the Thrombin Time (TT) was 15.2s, and the Prothrombin Time (PT) was 24s. The dissolution product is qualified, and the specific results are shown in Table 1.
Example 4
Adding 65.4 parts of PVC resin, 18 parts of DOP, 10 parts of epoxidized soybean oil, 2.5 parts of zinc laurate, 2.5 parts of calcium stearate and 0.8 part of polyethylene wax into a high-speed dispersing machine at 50 ℃ for fully blending for 5 hours to obtain a mixture; step (2), adding 99.2g of the mixture into an internal mixer, plasticizing and mixing for 5min at 160 ℃ and 20 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.2g of acrylic acid, 0.2g of vinyl acetic acid, 0.6g of 2-acrylamide-2-methylpropanesulfonic acid and 0.005g of azodiisobutyronitrile into an internal mixer for polymerization reaction for 40min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 170 ℃, and carrying out crosslinking reaction for 10min to obtain the in-situ anticoagulation modified PVC sheet material. The tensile strength of the PVC material prepared by the test reaches 15MPa, and the elongation at break reaches 560%; the Activated Partial Thromboplastin Time (APTT) is up to 580s, the Thrombin Time (TT) is up to 25.0s, the Prothrombin Time (PT) is up to 35s, and the performance is not reduced after the washing at the high temperature of 121 ℃ for 30min; the dissolution product is qualified, and the specific results are shown in Table 1.
Comparative example 4
Adding 65.4 parts of PVC resin, 18 parts of DOP, 10 parts of epoxidized soybean oil, 2.5 parts of zinc laurate, 2.5 parts of calcium stearate and 0.8 part of polyethylene wax into a high-speed dispersing machine at 50 ℃ for fully blending for 5 hours to obtain a mixture; step (2) adding the mixture into an internal mixer, plasticizing and mixing for 5min at 170 ℃ and 10 r/min; and (3) placing the plasticized PVC into a die, and placing the die on a vulcanizing machine preheated to 170 ℃ for 10min to obtain an unmodified PVC sheet material. The tensile strength of the PVC material prepared by the test is 15MPa, and the elongation at break is 560%; the Activated Partial Thromboplastin Time (APTT) was 40s, the Thrombin Time (TT) was 15.1s, and the Prothrombin Time (PT) was 24s. The dissolution product is qualified, and the specific results are shown in Table 1.
Example 5
Adding 65.2 parts of PVC resin, 18 parts of DOP, 10 parts of epoxidized soybean oil, 2.5 parts of zinc laurate, 2.5 parts of calcium stearate and 0.8 part of polyethylene wax into a high-speed dispersing machine at 60 ℃ and fully blending for 5 hours to obtain a mixture; step (2) adding 99g of the mixture into an internal mixer, plasticizing and mixing for 5min at 110 ℃ and 80 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.4g of hydroxypropyl methacrylate, 0.1g of vinyl acetic acid, 0.5g of 2-acrylamide-2-methylpropanesulfonic acid and 0.01g of dibenzoyl peroxide into an internal mixer for polymerization reaction for 40min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 170 ℃, and carrying out crosslinking reaction for 10min to obtain the in-situ anticoagulation modified PVC sheet material. The tensile strength of the PVC material prepared by the test reaches 15MPa, and the elongation at break reaches 550%; the Activated Partial Thromboplastin Time (APTT) is up to 590s, the Thrombin Time (TT) is up to 27s, the Prothrombin Time (PT) is up to 36s, and the performance is not reduced after the washing at the high temperature of 121 ℃ for 30min; the dissolution product is qualified, and the specific results are shown in Table 1.
Comparative example 5
Adding 65.2 parts of PVC resin, 18 parts of DOP, 10 parts of epoxidized soybean oil, 2.5 parts of zinc laurate, 2.5 parts of calcium stearate and 0.8 part of polyethylene wax into a high-speed dispersing machine at 60 ℃ and fully blending for 5 hours to obtain a mixture; step (2) adding the mixture into an internal mixer, plasticizing and mixing for 5min at 170 ℃ and 10 r/min; and (3) placing the plasticized PVC into a die, and placing the die on a vulcanizing machine preheated to 170 ℃ for 10min to obtain an unmodified PVC sheet material. The tensile strength of the PVC material prepared by the test is 16MPa, and the elongation at break is 556%; the Activated Partial Thromboplastin Time (APTT) was 42s, the Thrombin Time (TT) was 13s, and the Prothrombin Time (PT) was 25s. The dissolution product is qualified, and the specific results are shown in Table 1.
TABLE 1 results of Performance test of PVC materials prepared in examples 1 to 5 and comparative examples 1 to 5
Example 6
Adding 80 parts of PVC resin, 10 parts of trioctyl citrate, 5 parts of epoxidized soybean oil, 1.5 parts of zinc laurate, 1.5 parts of calcium stearate and 1 part of polyethylene wax into a high-speed dispersing machine at 90 ℃ and fully blending for 1h to obtain a mixture; step (2) adding 99g of the mixture into an internal mixer, plasticizing and mixing for 5min at 120 ℃ and 80 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.4g of hydroxyethyl methacrylate, 0.3g of vinyl acetic acid, 0.3g of alpha-olefin sodium sulfonate and 0.001g of azodiisobutyronitrile into an internal mixer for polymerization reaction for 60min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 130 ℃, and carrying out crosslinking reaction for 120min to obtain the in-situ anticoagulation modified PVC sheet material.
Example 7
Adding 60 parts of PVC resin, 50 parts of DOP, 30 parts of epoxidized soybean oil, 5 parts of zinc laurate, 5 calcium stearate and 0.5 part of polyethylene wax into a high-speed dispersing machine at 50 ℃ and fully blending for 6 hours to obtain a mixture; step (2) adding 99g of the mixture into an internal mixer, plasticizing and mixing for 5min at 130 ℃ and 50 r/min; step (3) keeping the temperature and the rotating speed unchanged, adding 0.2g of diacetone acrylamide, 0.15g of vinyl acetic acid, 0.65g of alpha-olefin sodium sulfonate and 0.01g of azodiisobutyronitrile into an internal mixer for polymerization reaction for 10min; and (4) taking out the copolymer, putting the copolymer into a die, putting the die into a vulcanizing machine preheated to 160 ℃, and carrying out crosslinking reaction for 50min to obtain the in-situ anticoagulation modified PVC sheet material.
Through testing, the properties of the in-situ anticoagulation modified PVC sheet material obtained in examples 6-7 are basically the same as those of examples 1-5.
By the technical scheme, the preparation method of the in-situ anticoagulation modified medical PVC material adopts the copolymer containing the carboxylic acid group and the sulfonic acid group to graft-polymerize and modify the PVC material, and the copolymer and the PVC material are crosslinked at high temperature to form a stable network interpenetrating stable structure with crosslinking points. The method does not use solvents, is environment-friendly, has simple preparation method, and completes modification and preparation in one step; the prepared in-situ anticoagulation modified medical PVC material has good biocompatibility, less dissolution, no teratogenesis and no anaphylactic reaction; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property.
In addition, the inventors have conducted experiments with other materials, process operations, and process conditions as described in this specification with reference to the foregoing examples, and have all obtained desirable results.
While the invention has been described with reference to an illustrative embodiment, it will be understood by those skilled in the art that various other changes, omissions and/or additions may be made and substantial equivalents may be substituted for elements thereof without departing from the spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims.
Claims (12)
1. The preparation method of the in-situ anticoagulation modified medical PVC material is characterized by comprising the following steps:
uniformly mixing PVC resin, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant to form a mixture;
putting the mixture into banburying equipment, plasticizing and mixing at 110-160 ℃ and 20-80 r/min, and fully and uniformly dispersing;
in an anaerobic environment, adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator into the banburying equipment, and carrying out free radical graft polymerization for 10-60 min to obtain a copolymer containing carboxylic acid groups and sulfonic acid groups, wherein the copolymer can form a reticular interpenetrating stable structure with cross-linking points with a PVC chain segment, the carboxylic acid group monomer is selected from vinyl acetic acid, and the sulfonic acid group monomer is selected from 2-acrylamide-2-methylpropanesulfonic acid; the mass ratio of the sum of the masses of the cross-linking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the PVC resin is 0.05:10-1:10;
and placing the obtained copolymer into vulcanizing equipment, and performing crosslinking reaction for 10-120min at 130-170 ℃ to obtain the in-situ anticoagulation modified medical PVC material.
2. The preparation method according to claim 1, characterized by comprising the following steps: and fully blending PVC resin, primary plasticizer, auxiliary plasticizer, stabilizer and lubricant in a high-speed dispersing device at 30-100 ℃ for 1-6 h to form the mixture.
3. The method of manufacturing according to claim 1, characterized in that: the mass ratio of the PVC resin to the primary plasticizer to the auxiliary plasticizer to the stabilizer to the lubricant is (60-80): (10-50): (5-30): (3-10): (0.5-1).
4. The method of manufacturing according to claim 1, characterized in that: the primary plasticizer is selected from DOP and/or trioctyl citrate.
5. The method of manufacturing according to claim 1, characterized in that: the auxiliary plasticizer is selected from epoxidized soybean oil and/or epoxidized linseed oil.
6. The method of manufacturing according to claim 1, characterized in that: the stabilizer comprises 50-70 wt% of zinc laurate and 30-50 wt% of calcium stearate.
7. The method of manufacturing according to claim 1, characterized in that: the lubricant is selected from polyethylene waxes.
8. The method of manufacturing according to claim 1, characterized in that: the mass ratio of the cross-linking agent monomer to the carboxylic acid monomer to the sulfonic acid monomer is (15-40): (10-30): (30-65), and the total mass parts of the three is 100.
9. The method of manufacturing according to claim 1, characterized in that: the mass ratio of the sum of the masses of the crosslinking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the mass ratio of the initiator is 100:0.1 to 1.
10. The method of manufacturing according to claim 1, characterized in that: the cross-linking agent monomer is selected from any one or two of acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-methylolacrylamide and diacetone acrylamide; and/or the initiator is selected from any one or two of azodiisobutyronitrile, azodiisoheptonitrile and dibenzoyl peroxide.
11. An in situ anticoagulation modified medical PVC material prepared by the method of any of claims 1-10, comprising a network interpenetrating stable structure with cross-linking points formed by copolymer and PVC segments.
12. Use of an in situ anticoagulation modified medical PVC material according to claim 11 in the field of medical devices, wherein the medical device is selected from PVC blood bags or catheters.
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| JPH09108331A (en) * | 1995-10-19 | 1997-04-28 | Koji Yamashita | Macromolecule material with antithrombogenesity and method of producing the same |
| EP0887356A1 (en) * | 1997-06-24 | 1998-12-30 | Hüls Aktiengesellschaft | Bactericidal, blood compatible, NCO-reactive modified copolymer |
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| CN109734839A (en) * | 2019-01-04 | 2019-05-10 | 中国科学院宁波材料技术与工程研究所 | A kind of high anti-coagulation type polystyrene microsphere and the preparation method and application thereof |
| CN111195485A (en) * | 2020-02-17 | 2020-05-26 | 天津工业大学 | Preparation method of polyvinyl chloride blood purification membrane |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ536330A (en) * | 2002-05-09 | 2007-08-31 | Hemoteq Ag | Medical devices such as stents comprising haemocompatible coating, production and use thereof |
| JP6115834B2 (en) * | 2012-09-20 | 2017-04-19 | 東洋紡株式会社 | Medical pellet-like composition and molded body |
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| US4337768A (en) * | 1980-02-26 | 1982-07-06 | Toray Industries, Inc. | Polyvinyl chloride sheet and method of making the same |
| JPH09108331A (en) * | 1995-10-19 | 1997-04-28 | Koji Yamashita | Macromolecule material with antithrombogenesity and method of producing the same |
| EP0887356A1 (en) * | 1997-06-24 | 1998-12-30 | Hüls Aktiengesellschaft | Bactericidal, blood compatible, NCO-reactive modified copolymer |
| CN105175939A (en) * | 2015-09-09 | 2015-12-23 | 深圳恒方大高分子材料科技有限公司 | High-oxygen-permeability medical PVC (polyvinyl chloride) material and preparation method of high-oxygen-permeability medical PVC material |
| CN109734839A (en) * | 2019-01-04 | 2019-05-10 | 中国科学院宁波材料技术与工程研究所 | A kind of high anti-coagulation type polystyrene microsphere and the preparation method and application thereof |
| CN111195485A (en) * | 2020-02-17 | 2020-05-26 | 天津工业大学 | Preparation method of polyvinyl chloride blood purification membrane |
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