CN115607750A - 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
- Publication number
- CN115607750A CN115607750A CN202110805957.3A CN202110805957A CN115607750A CN 115607750 A CN115607750 A CN 115607750A CN 202110805957 A CN202110805957 A CN 202110805957A CN 115607750 A CN115607750 A CN 115607750A
- Authority
- CN
- China
- Prior art keywords
- acid group
- pvc
- monomer
- situ
- pvc material
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000463 material Substances 0.000 title claims abstract description 73
- 230000010100 anticoagulation Effects 0.000 title claims abstract description 52
- 238000011065 in-situ storage Methods 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000000178 monomer Substances 0.000 claims abstract description 71
- 229920001577 copolymer Polymers 0.000 claims abstract description 41
- 238000002156 mixing Methods 0.000 claims abstract description 38
- 125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 32
- 239000004014 plasticizer Substances 0.000 claims abstract description 32
- 239000011347 resin Substances 0.000 claims abstract description 29
- 229920005989 resin Polymers 0.000 claims abstract description 29
- 125000000542 sulfonic acid group Chemical group 0.000 claims abstract description 28
- 238000004132 cross linking Methods 0.000 claims abstract description 24
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 20
- 239000003381 stabilizer Substances 0.000 claims abstract description 18
- 239000000314 lubricant Substances 0.000 claims abstract description 17
- 239000008280 blood Substances 0.000 claims abstract description 14
- 210000004369 blood Anatomy 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 239000003999 initiator Substances 0.000 claims abstract description 12
- 238000010559 graft polymerization reaction Methods 0.000 claims abstract description 5
- 150000003254 radicals Chemical class 0.000 claims abstract description 5
- 238000004073 vulcanization Methods 0.000 claims abstract description 4
- 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
- 235000013539 calcium stearate Nutrition 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 16
- 229940098697 zinc laurate Drugs 0.000 claims description 16
- GPYYEEJOMCKTPR-UHFFFAOYSA-L zinc;dodecanoate Chemical compound [Zn+2].CCCCCCCCCCCC([O-])=O.CCCCCCCCCCCC([O-])=O GPYYEEJOMCKTPR-UHFFFAOYSA-L 0.000 claims description 16
- 239000004698 Polyethylene Substances 0.000 claims description 15
- -1 polyethylene Polymers 0.000 claims description 15
- 229920000573 polyethylene Polymers 0.000 claims description 15
- 239000003549 soybean oil Substances 0.000 claims description 14
- 235000012424 soybean oil Nutrition 0.000 claims description 14
- 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 13
- PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 claims description 11
- 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 compound CCC(=O)C1CC(C(C)C)CC=C1C DZSVIVLGBJKQAP-UHFFFAOYSA-N 0.000 claims description 8
- 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 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 7
- 239000004711 α-olefin Substances 0.000 claims description 7
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 claims description 4
- 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
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- 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
- QZPSOSOOLFHYRR-UHFFFAOYSA-N 3-hydroxypropyl prop-2-enoate Chemical compound OCCCOC(=O)C=C QZPSOSOOLFHYRR-UHFFFAOYSA-N 0.000 claims description 4
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-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
- CCJAYIGMMRQRAO-UHFFFAOYSA-N 2-[4-[(2-hydroxyphenyl)methylideneamino]butyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCCCN=CC1=CC=CC=C1O CCJAYIGMMRQRAO-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 206010002198 Anaphylactic reaction Diseases 0.000 abstract description 5
- 206010018910 Haemolysis Diseases 0.000 abstract description 5
- 208000031320 Teratogenesis Diseases 0.000 abstract description 5
- 208000003455 anaphylaxis Diseases 0.000 abstract description 5
- 238000004090 dissolution Methods 0.000 abstract description 5
- 230000008588 hemolysis Effects 0.000 abstract description 5
- 238000012986 modification Methods 0.000 abstract description 5
- 230000004048 modification Effects 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 4
- 230000036783 anaphylactic response Effects 0.000 abstract description 2
- 239000003146 anticoagulant agent Substances 0.000 abstract description 2
- 229940127219 anticoagulant drug Drugs 0.000 abstract description 2
- 229920000915 polyvinyl chloride Polymers 0.000 description 95
- 239000006185 dispersion Substances 0.000 description 14
- 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
- 229960004072 thrombin Drugs 0.000 description 11
- 238000006116 polymerization reaction Methods 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 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
- 239000002861 polymer material Substances 0.000 description 6
- 229920012485 Plasticized Polyvinyl chloride Polymers 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 4
- 208000005623 Carcinogenesis Diseases 0.000 description 3
- 239000004971 Cross linker Substances 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000036952 cancer formation Effects 0.000 description 3
- 231100000504 carcinogenesis Toxicity 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 2
- CNCOEDDPFOAUMB-UHFFFAOYSA-N N-Methylolacrylamide Chemical compound OCNC(=O)C=C CNCOEDDPFOAUMB-UHFFFAOYSA-N 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000004593 Epoxy Substances 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
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency 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
- 239000012633 leachable Substances 0.000 description 1
- 230000007774 longterm 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
- 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
Images
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, and a preparation method and application thereof. The preparation method comprises the following steps: PVC resin, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant are blended in an internal mixing device, a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator are added, free radical graft polymerization is carried out in an anaerobic environment, a copolymer containing the carboxylic acid group and the sulfonic acid group is prepared, 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 vulcanization device, so that the in-situ anticoagulation modified medical PVC material is obtained. The preparation method is simple, does not use solvents, is environment-friendly, completes modification and preparation in one step, and the obtained anticoagulant medical PVC material has good biocompatibility, is less in dissolution, does not cause teratogenesis and anaphylaxis; 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 instruments, 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. However, the existing devices still have the problems of biocompatibility and blood compatibility in the using process, and often cause non-specific adsorption of some biomolecules such as proteins, cells, bacteria and the like on the surface of a material, thereby causing coagulation. As a biomedical polymer material, a material having excellent biocompatibility is required, and a material which is in direct contact with blood is required to have not only excellent histocompatibility but also excellent anticoagulation property.
Patent publication No. CN103965639A, CN105194742A adopts heparin as an anticoagulant, and heparin is added to a high polymer material to obtain a medical high polymer material with excellent anticoagulation effect, and CN207384541U discloses heparin which is uniformly distributed in an anticoagulation hemodialysis management pipeline, and heparin is stably released in the use process to prevent blood coagulation and thrombosis. However, long-term use of heparin is easy to cause diseases such as bleeding, thrombocytopenia, heparin resistance, osteoporosis and the like, and excessive heparin dosage can cause spontaneous bleeding with large side effect; the heparin micromolecules are easy to activate and dissolve out in the using process, CN103524752A discloses a fluorosilicone-POSS acrylate block copolymer, a blood compatibility coating and a preparation method.
Disclosure of Invention
Aiming at the problem of poor blood compatibility of medical high polymer materials in the prior art, the invention mainly aims to provide an in-situ anticoagulation modified medical PVC material and a preparation method thereof, thereby overcoming the defects of the prior art.
The invention also aims to provide application of the in-situ anticoagulation modified medical PVC material.
In order to achieve the purpose, 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, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant to form a mixture;
placing the mixture into banburying equipment, plasticizing and mixing under the conditions that the temperature is 110-160 ℃ and the rotating speed is 20-80 r/min, and fully and uniformly dispersing;
in an oxygen-free environment, adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator into the banburying device, and carrying out free radical graft polymerization for 10-60 min to obtain a copolymer containing a carboxylic acid group and a sulfonic acid group, wherein the copolymer can form a reticular interpenetrating stable structure with cross-linking points with a PVC chain segment, the carboxylic acid group monomer comprises vinyl acetic acid, and the sulfonic acid group monomer comprises any one or a combination of two of 2-acrylamide-2-methylpropanesulfonic acid and alpha-olefin sodium sulfonate;
and placing the obtained copolymer in vulcanization equipment, and carrying out 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 comprises:
fully blending PVC resin, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant for 1-6 h at 30-100 ℃ in a high-speed dispersion device to form the mixture.
In some embodiments, the mass ratio of the sum of the mass of the crosslinking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the mass of the PVC resin is 0.05.
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 sum of the 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, and the in-situ anticoagulation modified medical PVC material comprises a reticular interpenetrating stable structure with crosslinking 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 preparation of 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 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 solvent, 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, is less in dissolution, does not cause teratogenesis or carcinogenesis, and does not cause anaphylactic reaction; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property. The adopted copolymer containing carboxylic acid groups and sulfonic acid groups has better chemical stability and high temperature resistance, and the addition of the copolymer does not change the physical appearance characteristics of the PVC material, 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 used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments described in the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a graph comparing Activated Partial Thromboplastin Time (APTT), thrombin Time (TT), prothrombin Time (PT) of the in situ anticoagulation modified medical PVC material prepared in example 1 of the present invention and the medical PVC material of comparative example 1;
FIG. 2 is a comparison graph of mechanical properties of the in-situ anticoagulation modified medical PVC material prepared in example 1 of the present invention and the medical PVC material in comparative example 1.
Detailed Description
As described above, in view of the deficiencies of poor blood compatibility of the medical polymer material in the prior art, the inventors of the present invention have made extensive studies and practice to provide a technical solution of the present invention, which provides an in-situ anticoagulation modified medical PVC material and a preparation method thereof. The technical solution, its implementation and principles, etc. will be further explained as follows.
One aspect of the embodiment of the present invention provides a preparation method of an in-situ anticoagulation modified medical PVC material, which comprises:
uniformly mixing PVC resin, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant to form a mixture;
placing the mixture into banburying equipment, plasticizing and mixing under the conditions that the temperature is 110-160 ℃ and the rotating speed is 20-80 r/min, and fully and uniformly dispersing;
adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator into the banburying device in an oxygen-free environment, and carrying out free radical graft polymerization for 10-60 min to obtain a copolymer containing a carboxylic acid group and a sulfonic acid group, wherein the copolymer can form a reticular interpenetrating stable structure with cross-linking points with a PVC chain segment, the carboxylic acid group monomer comprises vinyl acetic acid, and the sulfonic acid group monomer comprises any one or a combination of two of 2-acrylamide-2-methylpropanesulfonic acid and alpha-olefin sodium sulfonate;
and placing the obtained copolymer in vulcanization equipment, and carrying out 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 comprises:
fully blending PVC resin, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant for 1-6 h at 30-100 ℃ in a high-speed dispersing device to form the mixture.
In some embodiments, the mass ratio of the PVC resin, the primary plasticizer, the secondary plasticizer, the stabilizer, and the lubricant is (60 to 80): (10-50): (5-30): (3-10): (0.5-1). That is, the aforementioned components include at least: 60-80 parts of PVC resin, 10-50 parts of main 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 secondary plasticizer includes epoxidized soybean oil, epoxidized linseed oil, etc., but is not limited thereto.
Further, the stabilizer includes 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 crosslinking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the mass of the PVC resin is 0.05.
In some embodiments, the mass ratio of the crosslinker monomer, carboxylic acid group monomer, and sulfonic acid group monomer is (15-40): (10-30): (30-65). That is, 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 sum of the mass percentages is 100%.
In some embodiments, the mass ratio of the sum of the mass of the crosslinker monomer, carboxylic acid group monomer, and sulfonic acid group monomer to the initiator is 100:0.1 to 1, namely, 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 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 plural, the ratio is an arbitrary ratio.
Further, the initiator includes any one or a combination of two or more of azobisisobutyronitrile, azobisisoheptonitrile, dibenzoyl peroxide, and the like, but is not limited thereto.
In some more specific embodiments, the preparation method specifically includes:
(1) Mixing PVC resin powder, a plasticizer, a stabilizer and a lubricant in an internal mixer; (2) Adding a carboxylic acid group monomer, a sulfonic group monomer, a cross-linking agent and an initiator into a closed system of an internal mixer, and realizing free radical graft polymerization reaction in the oxygen-free environment of the internal mixer, wherein a polymerization product is a polymer containing a carboxylic acid group and a sulfonic group, and the polymer and a PVC chain segment form a reticular interpenetrating stable structure with cross-linking points; (3) The polymer and PVC are subjected to cross-linking reaction on a vulcanizer to obtain the in-situ anticoagulation modified medical PVC material.
As a more specific embodiment, the preparation method of the in-situ anticoagulation modified medical PVC material comprises the following steps:
step (1): fully blending PVC resin powder, a primary plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant for 1-6 hours at 30-100 ℃ in a high-speed dispersion machine 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 to 1 portion of lubricant
The main 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;
and (3): keeping the temperature and the rotating speed unchanged, adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic group monomer and an initiator into an internal mixer for polymerization reaction for 10-60 min.
The mass ratio of the total mass of the crosslinking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the mass of the PVC is (0.05;
the mass ratio of the cross-linking agent monomer to the carboxylic acid group monomer to the sulfonic acid group monomer is as follows:
15-40% of cross-linking agent monomer
10 to 30 percent of carboxylic acid based monomer
30 to 65 percent of sulfonic monomer
The mixture ratio is mass percent, and the sum of the three is 100 percent;
the ratio of the initiator to the total mass of the three monomers is 0.1-1%.
And (4): taking out the copolymer, putting the copolymer into a mold, putting the mold on a vulcanizing machine preheated to 130-170 ℃, and carrying out crosslinking reaction for 10-120min to obtain the in-situ anticoagulation modified medical PVC material product.
The cross-linking agent monomer adopted in the step (3) comprises one or a mixture of more of acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-methylolacrylamide, diacetone acrylamide and the like, and when the number of the cross-linking agent monomers is multiple, the proportion is any ratio.
The carboxylic acid group 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 more than one, the proportion is any ratio.
In another aspect of the embodiments of the present invention, there is also provided an in-situ anticoagulation modified medical PVC material obtained by the foregoing method, which comprises a network interpenetrating stable structure with crosslinking points formed by a copolymer and PVC chain segments.
Furthermore, the in-situ anticoagulation modified medical PVC material prepared by the invention has good biocompatibility, is less in dissolution, does not cause teratogenesis and anaphylaxis; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property. The adopted copolymer containing carboxylic acid groups and sulfonic acid groups has better chemical stability and high temperature resistance, and the addition of the copolymer does not change the physical appearance characteristics of the PVC material, such as color, transparency and the like.
The embodiment of the invention also provides application of the in-situ anticoagulation modified medical PVC material obtained by the method in preparation of 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 prepared from the in situ anticoagulation modified medical PVC material.
In conclusion, the preparation method of the in-situ anticoagulation modified medical PVC material provided by the invention adopts the copolymer containing the carboxylic acid group and the sulfonic 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 solvent, 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, little dissolution, no teratogenesis or carcinogenesis, 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 is further described in conjunction with the following detailed description and the accompanying drawings so that those skilled in the art can implement the present invention with reference to the description. It should be understood that the specific embodiments described herein are merely illustrative of the invention, and that experimental conditions and set parameters therein are not to be considered as limitations of the basic embodiments of the invention. And the scope of the present invention is not limited to the following examples. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
Physical, mechanical, leachables, biological properties were tested as specified in GB15593-1995 in the examples which follow.
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 dispersion machine at the temperature of 30 ℃, and fully blending for 4 hours to obtain a mixture; adding 99g of the mixture into an internal mixer, plasticizing and mixing for 7min at 130 ℃ and 30 r/min; keeping the temperature and the rotating speed unchanged in the step (3), adding 0.3g N-hydroxymethyl acrylamide, 0.3g vinyl acetic acid, 0.4g 2-acrylamide-2-methylpropanesulfonic acid and 0.01g azobisisobutyronitrile into an internal mixer for polymerization reaction for 30min; and (4) taking out the copolymer, putting the copolymer into a mold, putting the mold on 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 prepared in-situ anticoagulation modified medical PVC material reaches 14.8MPa, and the elongation at break reaches 560%; activating Partial Thromboplastin Time (APTT) reaches up to 600s, thrombin Time (TT) reaches 26.8s, prothrombin Time (PT) reaches 36s, and performance is not reduced after washing at 121 ℃ for 30min; the extract 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 dispersion machine at the temperature of 30 ℃, and fully blending for 4 hours to obtain a mixture; adding the mixture into an internal mixer, plasticizing and mixing for 7min at 130 ℃ and 30 r/min; and (3) putting the plasticized PVC into a mold, and putting the mold on a vulcanizing machine preheated to 150 ℃ for 50min to obtain an unmodified PVC flat sheet. The tensile strength of the prepared PVC material is 15.2MPa and the elongation at break is 570 percent; the Activated Partial Thromboplastin Time (APTT) was 40s, the Thrombin Time (TT) was 16.6s, and the Prothrombin Time (PT) was 29s. The extract 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 dispersion 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 110 ℃ and 30 r/min; keeping the temperature and the rotating speed unchanged in the step (3), adding 0.6g of hydroxypropyl acrylate, 0.6g of vinyl acetic acid, 0.8g of 2-acrylamide-2-methylpropanesulfonic acid and 0.016g of azobisisoheptonitrile into an internal mixer for polymerization reaction for 20min; and (4) taking out the copolymer, putting the copolymer into a mold, putting the mold on a vulcanizing machine preheated to 130 ℃, and performing crosslinking reaction for 40min to obtain the in-situ anticoagulation modified PVC flat material. The tensile strength of the prepared PVC material reaches 15MPa, and the elongation at break reaches 567%; activating Partial Thromboplastin Time (APTT) to 600s, thrombin Time (TT) to 30s, prothrombin Time (PT) to 38s, and cleaning at 121 ℃ for 30min without reducing performance; the extract 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 dispersion machine at 100 ℃, and fully blending for 3 hours to obtain a mixture; 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 mold, and placing the mold on a vulcanizing machine preheated to 150 ℃ for 50min to obtain an unmodified PVC flat material. The tensile strength of the prepared PVC material is 15.2MPa and the elongation at break is 570 percent; the Activated Partial Thromboplastin Time (APTT) was 40s, the Thrombin Time (TT) was 16.6s, and the Prothrombin Time (PT) was 29s. The extract 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 dispersion 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; keeping the temperature and the rotating speed unchanged in the step (3), adding 0.4g of hydroxyethyl acrylate, 0.4g of vinyl acetic acid, 1.2g of alpha-olefin sodium sulfonate and 0.008g of azobisisobutyronitrile into an internal mixer for polymerization reaction for 40min; and (4) taking out the copolymer, putting the copolymer into a mold, putting the mold on a vulcanizing machine preheated to 140 ℃, and carrying out crosslinking reaction for 10min to obtain the in-situ anticoagulation modified PVC flat material. The tensile strength of the prepared PVC material reaches 13.8MPa through testing, and the elongation at break reaches 544%; activating Partial Thromboplastin Time (APTT) reaches up to 600s, thrombin Time (TT) reaches 30.2s, prothrombin Time (PT) reaches 39s, and performance is not reduced after washing at 121 ℃ for 30min; the extract 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 dispersion machine at 90 ℃, and fully blending for 3 hours to obtain a mixture; adding the mixture into an internal mixer, plasticizing and mixing for 5min at the temperature of 150 ℃ and at the speed of 20 r/min; and (3) putting the plasticized PVC into a mold, and putting the mold on a vulcanizing machine preheated to 160 ℃ for 10min to obtain an unmodified PVC flat material. The tensile strength of the prepared PVC material 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 extract 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 dispersion machine at the temperature of 50 ℃, and fully blending for 5 hours to obtain a mixture; step (2), adding 99.2g of the mixture into an internal mixer, and plasticizing and mixing for 5min at 160 ℃ and 20 r/min; keeping the temperature and the rotating speed unchanged in the step (3), and adding 0.2g of acrylic acid, 0.2g of vinyl acetic acid, 0.6g of 2-acrylamide-2-methylpropanesulfonic acid and 0.005g of azobisisobutyronitrile into an internal mixer for polymerization reaction for 40min; and (4) taking out the copolymer, putting the copolymer into a mold, putting the mold on a vulcanizing machine preheated to 170 ℃, and carrying out crosslinking reaction for 10min to obtain the in-situ anticoagulation modified PVC flat material. The tensile strength of the prepared PVC material reaches 15MPa, and the elongation at break reaches 560%; activating Partial Thromboplastin Time (APTT) reaches up to 580s, thrombin Time (TT) reaches 25.0s, prothrombin Time (PT) reaches 35s, and performance is not reduced after washing at 121 ℃ for 30min; the extract 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 dispersion machine at 50 ℃, and fully blending for 5 hours to obtain a mixture; adding the mixture into an internal mixer, plasticizing and mixing for 5min at 170 ℃ and 10 r/min; and (3) putting the plasticized PVC into a mold, and putting the mold on a vulcanizing machine preheated to 170 ℃ for 10min to obtain an unmodified PVC flat material. The tensile strength of the prepared PVC material is 15MPa and the elongation at break is 560 percent; the Activated Partial Thromboplastin Time (APTT) was 40s, the Thrombin Time (TT) was 15.1s, and the Prothrombin Time (PT) was 24s. The extract 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 dispersion machine at the temperature of 60 ℃, and fully blending for 5 hours to obtain a mixture; adding 99g of the mixture into an internal mixer, plasticizing and mixing for 5min at 110 ℃ and 80 r/min; keeping the temperature and the rotating speed unchanged, and 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 mold, putting the mold on a vulcanizing machine preheated to 170 ℃, and performing crosslinking reaction for 10min to obtain the in-situ anticoagulation modified PVC flat material. The tensile strength of the prepared PVC material reaches 15MPa through testing, and the elongation at break reaches 550%; activating Partial Thromboplastin Time (APTT) is up to 590s, thrombin Time (TT) is up to 27s, prothrombin Time (PT) is up to 36s, and performance is not reduced after washing at 121 ℃ for 30min; the extract 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 dispersion machine at the temperature of 60 ℃, and fully blending for 5 hours to obtain a mixture; adding the mixture into an internal mixer, plasticizing and mixing for 5min at 170 ℃ and 10 r/min; and (3) putting the plasticized PVC into a mold, and putting the mold on a vulcanizing machine preheated to 170 ℃ for 10min to obtain an unmodified PVC flat sheet. The tensile strength of the prepared PVC material 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 extract is qualified, and the specific results are shown in table 1.
TABLE 1 results of Performance test of PVC materials prepared in examples 1-5 and comparative examples 1-5
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 dispersion machine at the temperature of 90 ℃, and fully blending for 1 hour to obtain a mixture; adding 99g of the mixture into an internal mixer, and plasticizing and mixing for 5min at 120 ℃ and 80 r/min; keeping the temperature and the rotating speed unchanged in the step (3), adding 0.4g of hydroxyethyl methacrylate, 0.3g of vinyl acetic acid, 0.3g of alpha-olefin sodium sulfonate and 0.001g of azobisisobutyronitrile into an internal mixer for polymerization reaction for 60min; and (4) taking out the copolymer, putting the copolymer into a mold, putting the mold on a vulcanizing machine preheated to 130 ℃, and performing crosslinking reaction for 120min to obtain the in-situ anticoagulation modified PVC flat 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 parts of calcium stearate and 0.5 part of polyethylene wax into a high-speed dispersion machine at the temperature of 50 ℃, and fully blending for 6 hours to obtain a mixture; adding 99g of the mixture into an internal mixer, plasticizing and mixing for 5min at the temperature of 130 ℃ and at the speed of 50 r/min; keeping the temperature and the rotating speed unchanged in the step (3), adding 0.2g of diacetone acrylamide, 0.15g of vinyl acetic acid, 0.65g of alpha-olefin sodium sulfonate and 0.01g of azobisisobutyronitrile into an internal mixer for polymerization reaction for 10min; and (4) taking out the copolymer, putting the copolymer into a mold, putting the mold on a vulcanizing machine preheated to 160 ℃, and carrying out crosslinking reaction for 50min to obtain the in-situ anticoagulation modified PVC flat material.
The properties of the in-situ anticoagulation modified PVC flat plate materials obtained in examples 6-7 are tested to be basically consistent with 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 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 solvent, 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, little dissolution, no teratogenesis or carcinogenesis, and no anaphylactic reaction; has excellent blood compatibility, low hemolysis, good anticoagulation and excellent mechanical property.
In addition, the inventors of the present invention have also made experiments with other materials, process operations, and process conditions described in the present specification with reference to the above examples, and have obtained preferable results.
While the invention has been described with reference to illustrative embodiments, 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 its scope. 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 (10)
1. A preparation method of an in-situ anticoagulation modified medical PVC material is characterized by comprising the following steps:
uniformly mixing PVC resin, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant to form a mixture;
placing the mixture into an internal mixing device, plasticizing and mixing under the conditions that the temperature is 110-160 ℃ and the rotating speed is 20-80 r/min, and fully dispersing uniformly;
adding a cross-linking agent monomer, a carboxylic acid group monomer, a sulfonic acid group monomer and an initiator into the banburying device in an oxygen-free environment, and carrying out free radical graft polymerization for 10-60 min to obtain a copolymer containing a carboxylic acid group and a sulfonic acid group, wherein the copolymer can form a reticular interpenetrating stable structure with cross-linking points with a PVC chain segment, the carboxylic acid group monomer comprises vinyl acetic acid, and the sulfonic acid group monomer comprises any one or a combination of two of 2-acrylamide-2-methylpropanesulfonic acid and alpha-olefin sodium sulfonate;
and placing the obtained copolymer in vulcanization equipment, and carrying out crosslinking reaction for 10-120min at 130-170 ℃ to obtain the in-situ anticoagulation modified medical PVC material.
2. The method according to claim 1, comprising: fully blending PVC resin, a main plasticizer, an auxiliary plasticizer, a stabilizer and a lubricant for 1-6 h at 30-100 ℃ in a high-speed dispersing device to form the mixture.
3. The method of claim 1, wherein: the mass ratio of the PVC resin, the main plasticizer, the auxiliary plasticizer, the stabilizer and the lubricant is (60-80): (10-50): (5-30): (3-10): (0.5-1).
4. The method of claim 1, wherein: the primary plasticizer comprises DOP and/or trioctyl citrate; and/or, the secondary plasticizer comprises epoxidized soybean oil and/or epoxidized linseed oil; and/or, the stabilizer comprises 50-70 wt% of zinc laurate and 30-50 wt% of calcium stearate; and/or, the lubricant comprises polyethylene wax.
5. The production method according to claim 1, characterized in that: the mass ratio of the mass sum of the crosslinking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the PVC resin is 0.05.
6. The production method according to claim 1, characterized in that: the mass ratio of the cross-linking agent monomer to the carboxylic acid group monomer to the sulfonic acid group monomer is (15-40): (10-30): (30-65), and the sum of the mass parts of the three is 100.
7. The method of claim 1, wherein: the mass ratio of the sum of the mass of the crosslinking agent monomer, the carboxylic acid group monomer and the sulfonic acid group monomer to the mass of the initiator is 100:0.1 to 1.
8. The method of claim 1, wherein: the cross-linking agent monomer comprises any one or the combination of two of acrylic acid, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-hydroxymethyl acrylamide and diacetone acrylamide; and/or the initiator comprises any one or the combination of two of azodiisobutyronitrile, azodiisoheptonitrile and dibenzoyl peroxide.
9. An in situ anticoagulation modified medical PVC material prepared by the method according to any one of claims 1-8, which comprises a reticular interpenetrating stable structure with crosslinking points formed by copolymer and PVC chain segments.
10. Use of the in situ anticoagulation modified medical PVC material according to claim 9 in the field of medical devices, preferably, said medical devices comprise PVC blood bags or catheters.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110805957.3A CN115607750B (en) | 2021-07-16 | 2021-07-16 | In-situ anticoagulation modified medical PVC material, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110805957.3A CN115607750B (en) | 2021-07-16 | 2021-07-16 | In-situ anticoagulation modified medical PVC material, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115607750A true CN115607750A (en) | 2023-01-17 |
| CN115607750B CN115607750B (en) | 2024-02-23 |
Family
ID=84854909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110805957.3A Active CN115607750B (en) | 2021-07-16 | 2021-07-16 | In-situ anticoagulation modified medical PVC material, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115607750B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US20040234575A1 (en) * | 2002-05-09 | 2004-11-25 | Roland Horres | Medical products comprising a haemocompatible coating, production and use thereof |
| US20150190551A1 (en) * | 2012-09-20 | 2015-07-09 | Toyobo Co., Ltd. | Pellet-shaped composition for medical use, and molded product |
| 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 |
-
2021
- 2021-07-16 CN CN202110805957.3A patent/CN115607750B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US20040234575A1 (en) * | 2002-05-09 | 2004-11-25 | Roland Horres | Medical products comprising a haemocompatible coating, production and use thereof |
| US20150190551A1 (en) * | 2012-09-20 | 2015-07-09 | Toyobo Co., Ltd. | Pellet-shaped composition for medical use, and molded product |
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115607750B (en) | 2024-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4370450A (en) | Process for the production of polar-modified polypropylene and its use | |
| CN109942839B (en) | In-situ free radical polymerization gel with antibacterial and self-adhesive properties, and preparation method and application thereof | |
| JP4100452B1 (en) | Treatment liquids and medical materials for medical materials | |
| CN109675134A (en) | A kind of anticoagulant method of modifying of haemodialyser and its application | |
| US4021509A (en) | Production of impact-resistant, thermoplastic resin compositions | |
| CN112175365A (en) | Modified gutta-percha/polylactic acid thermoplastic elastomer with shape memory effect and preparation method thereof | |
| JP2724908B2 (en) | Method for producing polyolefin-vinyl polymer composition | |
| CN115607750B (en) | In-situ anticoagulation modified medical PVC material, and preparation method and application thereof | |
| CN112480312A (en) | Preparation method of high-elasticity high-strength double-crosslinking porous hydrogel | |
| CN107501888B (en) | High-performance PC/ABS alloy material and preparation method thereof | |
| CN109053968B (en) | Injectable water-absorbing expansion bone cement with high expansion ratio and preparation method thereof | |
| CN104311751B (en) | Method for preparing surface hydrophilic modifier for hydrophobic material | |
| KR19980033977A (en) | Method for producing a thermoplastic resin excellent in impact resistance | |
| DE3742103A1 (en) | POLYMER MIXTURE AND THEIR USE AS A POLYVINYL CHLORIDE MODIFICATOR | |
| JPS5858369B2 (en) | Method for manufacturing acrylic foam | |
| CN109280129B (en) | Injectable hydrogel polymer based on salt response under physiological conditions and preparation method thereof | |
| CN112940303A (en) | High-adhesion slow-release crosslinked hydrogel and preparation method thereof | |
| JPH0481443A (en) | Polyvinyl chloride resin composition | |
| CN111647331A (en) | Bi-component emulsion and preparation method thereof | |
| JPH06511041A (en) | Method for producing gloss reducing agent for thermoplastic resin | |
| CN114533941B (en) | Preparation method of polymer hemostatic material | |
| CN117511010B (en) | Medical surgical glove based on deproteinized natural concentrated latex and preparation method thereof | |
| CN112852009B (en) | Method for modifying porous polymer film, modified porous polymer film, and medical article | |
| CN1454911A (en) | Polarized SDS and preparing method thereof | |
| DE2508416A1 (en) | Membrane for medical-biological uses - comprising copolymer of vinyl sulphonic acid and acrylonitrile |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |