CN114159623B - Self-anti-coagulation elastomer material and preparation method thereof - Google Patents

Self-anti-coagulation elastomer material and preparation method thereof Download PDF

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CN114159623B
CN114159623B CN202011464096.9A CN202011464096A CN114159623B CN 114159623 B CN114159623 B CN 114159623B CN 202011464096 A CN202011464096 A CN 202011464096A CN 114159623 B CN114159623 B CN 114159623B
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self
elastomer material
antiplatelet agent
prepolymer
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CN114159623A (en
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张炜佳
王伟忠
马文锐
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Fudan University
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    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/68—Polyesters containing atoms other than carbon, hydrogen and oxygen
    • C08G63/688—Polyesters containing atoms other than carbon, hydrogen and oxygen containing sulfur
    • C08G63/6884—Polyesters containing atoms other than carbon, hydrogen and oxygen containing sulfur derived from polycarboxylic acids and polyhydroxy compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties

Abstract

The invention belongs to the technical field of high polymer material synthesis, and relates to a self-anti-coagulation elastomer material and a preparation method thereof. The molecular structure of the elastomer material of the invention is simultaneously grafted with sulfonic acid group (-SO) 3 ‑ ) And anticoagulant active ingredients such as an antiplatelet agent, and the preparation method comprises the following steps: the method comprises the steps of introducing sodium sulfonate of polyol into a melting system of dibasic acid and tribasic alcohol, and carrying out esterification polymerization to obtain-SO 3 ‑ Modifying the prepolymer; further to-SO 3 ‑ Carboxyl-containing antiplatelet agent is introduced into the modified prepolymer, and-SO is obtained through esterification polymerization 3 ‑ And an antiplatelet agent double-modified prepolymer; the obtained-SO 3 ‑ And curing and crosslinking the prepolymer which is modified by the antiplatelet agent to obtain the self-anticoagulation elastomer material. The elastomer material has double-channel anticoagulation performance for inhibiting coagulation cascade reaction and platelet activation simultaneously, and has good biocompatibility and biodegradability; the preparation method of the self-anti-coagulation elastomer material is biologically safe and has no risk of toxic reagent residue.

Description

Self-anti-coagulation elastomer material and preparation method thereof
Technical Field
The invention belongs to the field of synthesis of high polymer materials, and particularly relates to a self-anti-coagulation elastomer material and a preparation method thereof.
Background
It is reported that the development of small-caliber vascular grafts becomes a difficult point and a hot point in the current vascular tissue engineering field because small-caliber vascular blood flow is slow and thrombosis, intimal hyperplasia and the like are easy to occur. In recent years, with the development of tissue engineering, a plurality of degradable high polymer materials are developed and applied to the construction of small-bore vascular grafts, and these materials have either good biological activity or excellent mechanical properties, but they usually lack the most important and essential anticoagulation performance as vascular grafts, so the vascular grafts constructed by them still need to be subjected to anticoagulation modification treatment before being applied in vivo. At present, the anticoagulant modification of the vascular graft commonly used mainly comprises two modes of physical loading and chemical grafting, and the methods can endow the vascular graft with better anticoagulant performance in a short period of time, however, the anticoagulant active ingredients on the stent are influenced by factors such as blood scouring and polymer stent degradation and are finally released and exhausted over time, so that the vascular graft lacks the long-term continuous anticoagulant efficacy before being completely degraded and absorbed. In addition, the influence of the microstructure, the distribution of active groups, the surface modification treatment parameters and the like of the inner cavity surface of the vascular graft is easy to cause the formation of uneven modified surfaces and even the residue of unmodified areas. The above mentioned risk of vessel occlusion due to premature release of anticoagulant active ingredients or uneven surface modification will be further highlighted in the application of small-bore vascular grafts, which are more thrombogenic. However, if the degradable polymer material for constructing the vascular graft has good anticoagulation performance, the vascular graft constructed therefrom does not need additional anticoagulation modification, and can provide excellent anticoagulation efficacy before being completely degraded and absorbed so as to maintain the patency of the blood vessel. Therefore, the development of degradable elastomer materials with good anticoagulation performance can provide a more ideal polymer raw material for the construction of small-caliber vascular grafts.
Heparin is a high-efficiency anticoagulation reagent commonly used in clinic at present, is commonly used for modifying the inner cavity of a vascular graft to improve the anticoagulation performance of the vascular graft, and has rich sulfonic groups (-SO) on the molecular chain 3 - ) And carboxyl (-COOH) groups are believed to be the main reason why heparin has anticoagulant efficacy [ Acta biomaterials, 2013,9]And wherein-SO 3 - Are considered to be the primary anticoagulant active group [ Biomaterials,2002,23]Blood coagulation is prevented primarily by inhibiting the coagulation cascade. Inspired by this, -SO 3 - Are used to modify materials to improve their anticoagulant properties. Currently, the sulfonation modification is mainly performed by chlorosulfonic acid [ Biomaterials,2011,32]Or concentrated sulfuric acid [ Food Hydrocolloids,2019,96]Treatment of materials with strongly corrosive reagents to graft-SO 3 - The reaction conditions are severe. In addition, studies have been made [ Journal of Membrane Science,2018, 563; materials Science&Engineering C-Materials for Biological Applications,2017,78:1035-1045]By containing-SO 3 - The reagent is used as a reaction monomer to synthesize an anticoagulant material, however, an organic solvent reaction system is mostly adopted, even a virulent initiator or an organic tin catalyst is needed, so that the purification treatment difficulty of the synthetic material is increased, and the possibility that the toxic reagent in the final synthetic material is remained due to incomplete purification is increased, and the biocompatibility of the synthetic material is further influenced.For anticoagulant materials that are in direct contact with blood, the residual toxic agents can cause more serious toxic effects. Obviously, the exploration of a biosafety synthesis process without the risk of toxic reagent residue is more suitable for the development of anticoagulant materials.
In addition, in addition to the coagulation cascade caused by various intrinsic and extrinsic coagulation factors, thrombus formed by platelet activation aggregation is also an important factor causing vascular occlusion [ Acta biomaterials, 2019, 94. Various antiplatelet drugs are also commonly used for adjuvant anticoagulant therapy after vascular bypass grafting. It has been shown that inhibition of coagulation from both the coagulation cascade and the platelet activation pathway has a better anticoagulation effect than the single pathway [ Journal of Thrombosis and Haemostasis,2007,5 (suppl.1): 255-263]. However, there is no report of synthesizing dual-channel self-anticoagulation material from the two common coagulation pathways at the same time.
Disclosure of Invention
The invention aims to provide a self-anticoagulation elastomer material which can inhibit coagulation cascade reaction and platelet activation simultaneously and a biosafety preparation method thereof based on the current situation of the prior art 3 - The monomer and the anti-platelet agent are synthesized into the polyester elastomer material with double-channel self-anticoagulation performance. The elastomer material of the invention has good biocompatibility and can be biodegraded.
In order to achieve the above object, the present invention provides a self-anticoagulation elastomer material, which is characterized in that a sulfonic acid group (-SO) is grafted on the molecular structure of the self-anticoagulation elastomer material 3 - ) And anticoagulant active ingredients such as antiplatelet agents.
The invention provides a preparation method of the self-anticoagulation elastomer material, which is characterized by comprising the following steps:
the first step is as follows: adding dibasic acid, tribasic alcohol and sodium sulfonate salt of polyhydric alcohol into a reaction bottle, continuously stirring for 2-24 hours at 120-200 ℃ under the protection of inert gas, then reducing the pressure in the reaction bottle to be within 3000Pa, and continuously stirring and reacting for 1-7 days at 120-200 ℃ to obtain a sulfonated prepolymer system;
the second step is that: introducing an antiplatelet agent into the prepolymer system in the first step, continuously stirring for 2-24 hours at 80-200 ℃ under the protection of inert gas, then reducing the pressure to be within 3000Pa, and continuously stirring and reacting for 1-7 days at 80-200 ℃ to obtain a sulfonated and antiplatelet agent co-modified prepolymer system;
the third step: and curing the prepolymer obtained in the second step at 80-200 ℃ and under the pressure of less than 1000Pa for 4 hours-14 days to obtain the anticoagulation elastomer material.
Preferably, the dibasic acid in the first step is one or more of succinic acid, alpha-ketoglutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, tetradecanedioic acid and the like.
Preferably, the triol in the first step is one or more of glycerol, polycaprolactone triol and the like.
Preferably, the sodium salt of the polyhydric alcohol sulfonate in the first step is one or more of Tris (ethyl) sodium sulfonate, sodium N, N-bis (2-hydroxyethyl) -2-aminoethanesulfonate, sodium Tris (hydroxymethyl) methylaminopropanesulfonate, sodium 3-bis (2-hydroxyethyl) amino-2-hydroxypropanesulfonate, and sodium 3- [ N-Tris (hydroxymethyl) methylamino ] -2-hydroxypropanesulfonate.
Preferably, the molar amount of the sodium sulfonate-containing polyol in the first step is 0 to 10 times of that of glycerol, and is not 0 time; the ratio of the total molar weight of glycerol and the sodium salt of the polyhydric alcohol sulfonate to the molar weight of the sebacic acid is 2.
Preferably, the molecular structure of the antiplatelet agent in the second step contains carboxyl, which is one or more of aspirin, ferulic acid, danshensu, cinnamic acid, oleanolic acid, scutellarin, salvianolic acid B, tirofiban, etc.
Preferably, the molar ratio of the antiplatelet agent to the sodium salt of the polyhydric alcohol sulfonic acid is 0.1 to 10.
The invention utilizes the high-temperature melting characteristic of the reaction monomer of the dibasic acid and the tribasic alcohol to have good performanceThe sodium sulfonate of polyol with good biocompatibility is introduced into the system to participate in esterification polymerization reaction, SO that-SO 3 - Introducing into the molecular structure of synthetic polyester material; the use of the sodium sulfonate salt can be used for free-SO 3 - Protecting the hydroxyl group in the reaction system from being consumed due to esterification polymerization; in order to synergistically promote the anticoagulation performance of the material, a carboxyl-containing anti-platelet reagent is introduced into a system to be esterified and polymerized with hydroxyl on a molecular chain of the synthetic material, so that the carboxyl-containing anti-platelet reagent is introduced onto the molecular chain of the synthetic material to construct the self-anticoagulation elastomer material modified by both a sulfonic group and the anti-platelet reagent.
The invention has the following beneficial effects:
(1) The self-anti-coagulation elastomer material prepared by the invention simultaneously carries-SO 3 - And an antiplatelet agent, which can simultaneously inhibit coagulation cascade reaction and platelet activation to promote anticoagulation;
(2) The invention adopts a biologically safe melt esterification reaction system without using any catalytic reagent;
(3) The sodium polyalcohol sulfonate introduced by the invention is a biological buffering agent component, and the introduced anti-platelet agent is a clinical application medicament or a traditional Chinese medicine active component, so that the prepared self-anti-coagulation elastomer also has good biocompatibility;
(4) The self-anticoagulation elastomer prepared by the invention can be hydrolyzed and degraded, and the anticoagulation active ingredients are grafted on the molecular chain of the elastomer, so that the elastomer has good anticoagulation performance before complete degradation;
drawings
FIG. 1 is a tensile stress strain plot of elastomer materials obtained after curing at 120 ℃ for various times of a sulfonated prepolymer PGSB synthesized from sebacic acid, glycerol, N-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid sodium salt (BES sodium salt) as a reactive monomer, wherein the numbers behind the PGSB represent the molar ratio of glycerol to BES sodium salt, the molar amount of sebacic acid is equivalent to the total molar amount of glycerol and BES sodium salt, and PGS represents no reaction of BES sodium salt.
FIG. 2 shows the anticoagulation index APTT values of different synthetic elastomer materials, wherein the larger the value, the stronger the anticoagulation performance, PGSBA means the elastomer material synthesized by further introducing aspirin into the prepolymer PGSB system, and PGUB means the elastomer material synthesized by using undecanedioic acid, glycerin and BES sodium salt as reaction monomers.
Fig. 3 is the swelling degree of the synthetic elastomeric materials PGSB and PGSBA.
FIG. 4 shows the APTT value of the PPSB, which is a sulfonated elastomer material synthesized from sebacic acid, polycaprolactone triol and BES sodium salt as reaction monomers.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention can be made by those skilled in the art after reading the teaching of the present invention, and these equivalents also fall within the scope of the claims appended to the present application.
Example 1 preparation of self-anticoagulating elastomeric Material
An auto-anticoagulant elastomeric material prepared by a preparation method comprising:
(1) 0.1mol of sebacic acid, 0.06mol of glycerol and 0.04mol of BES sodium salt are added to a reaction flask at 150 ℃ and N 2 Continuously stirring and melting for 2 hours under protection, then reducing the pressure in the reaction bottle to be within 3000Pa, and continuously stirring and reacting for 40 hours at 130 ℃ to obtain a sulfonated prepolymer system (PGSB);
(2) The PGSB prepolymer system obtained in (1) was charged with 0.04mol of aspirin, initially at 120 ℃ and N 2 Continuously stirring and melting for 2 hours under protection, then reducing the pressure to be within 3000Pa, and continuously stirring and reacting for 8 hours at the temperature of 120 ℃ to obtain a sulfonated and aspirin co-modified prepolymer system (PGSBA for short);
(3) Curing the PGSBA prepolymer obtained in the step (2) at 120 ℃ under the pressure condition of less than 1000Pa for 6 days to obtain the degradable self-anticoagulation elastomer material PGSBA.
Example 2
An auto-anticoagulant elastomeric material prepared by a preparation method comprising:
(1) 0.1mol of sebacic acid, 0.04mol of polycaprolactone triol and 0.06mol of BES sodium salt are added into a reaction flask at 200 ℃ and N 2 Continuously stirring and melting for 3 hours under protection, then reducing the pressure in a reaction bottle to be within 3000Pa, and continuously stirring and reacting for 3 hours at 150 ℃ to obtain a sulfonated prepolymer system (PPSB for short);
(2) 0.035mol of aspirin was introduced into the PPSB prepolymer system obtained in (1), first at 120 ℃ and N 2 Continuously stirring and melting for 2 hours under protection, then reducing the pressure to be within 3000Pa, and continuously stirring and reacting for 2 hours at 120 ℃ to obtain a sulfonated and aspirin co-modified prepolymer system (PPSBA for short);
(3) And (3) curing the PPSBA prepolymer obtained in the step (2) at the temperature of 120 ℃ and under the pressure of less than 1000Pa for 3 days to obtain the degradable self-anticoagulation elastomer material PPSBA.
Example 3
A self-anticoagulating elastomeric material prepared by the following preparation method, comprising:
(1) 0.1mol of undecanedioic acid, 0.04mol of glycerol and 0.06mol of BES sodium salt are added to a reaction flask at 150 ℃ and N 2 Continuously stirring and melting for 2 hours under protection, then reducing the pressure in the reaction bottle to be within 3000Pa, and continuously stirring and reacting for 12 hours at 120 ℃ to obtain a sulfonated prepolymer system (PGUB for short);
(2) The PGSB prepolymer system obtained in (1) was charged with 0.03mol of aspirin, initially at 120 ℃ and N 2 Continuously stirring and melting for 2 hours under protection, then reducing the pressure to be within 3000Pa, and continuously stirring and reacting for 8 hours at the temperature of 120 ℃ to obtain a sulfonated and aspirin co-modified prepolymer system (PGUBA for short);
(3) Curing the PGSBA prepolymer obtained in the step (2) at 120 ℃ and under the pressure of less than 1000Pa for 4 days to obtain the degradable self-anticoagulation elastomer material PGUBA.

Claims (3)

1. Self-anti-coagulation elastomer materialThe method is characterized in that: the molecular structure of the self-anticoagulation elastomer material is simultaneously grafted with sulfonic groups (-SO) 3 - ) And an anticoagulant active ingredient of an antiplatelet agent; it is prepared by the following method:
the first step is as follows: adding dibasic acid, tribasic alcohol and sodium sulfonate of polyhydric alcohol into a reaction bottle, continuously stirring for 2 to 24 hours at the temperature of 120 to 200 ℃ under the protection of inert gas, then reducing the pressure in the reaction bottle to be within 3000Pa, and continuously stirring for reaction for 1 to 7 days at the temperature of 120 to 200 ℃ to obtain a sulfonated prepolymer system; wherein the dibasic acid is one or more of succinic acid, alpha-ketoglutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid and tetradecanedioic acid; the trihydric alcohol is one or more of glycerol and polycaprolactone triol; the sodium salt of the polyhydric alcohol sulfonate is one or more of Tris sodium ethanesulfonate, N-bis (2-hydroxyethyl) -2-aminoethanesulfonate, sodium trimethylolpropane sulfonate, 3-bis (2-hydroxyethyl) amino-2-hydroxypropanesulfonic acid sodium salt and 3- [ N-Tris (hydroxymethyl) methylamino ] -2-hydroxypropanesulfonic acid sodium salt;
the second step is that: introducing an antiplatelet agent into the prepolymer system in the first step, continuously stirring for 2-24 hours at 80-200 ℃ under the protection of inert gas, then reducing the pressure to within 3000Pa, and stirring and reacting for 1-7 days at 80-200 ℃ to obtain a sulfonated and antiplatelet agent co-modified prepolymer system; wherein the molecular structure of the antiplatelet agent contains carboxyl which is one or more of aspirin, ferulic acid, tanshinol, cinnamic acid, oleanolic acid, scutellarin, salvianolic acid B and tirofiban;
the third step: and curing the prepolymer obtained in the second step for 4 hours to 14 days at the temperature of 80 to 200 ℃ and under the pressure of less than 1000Pa to obtain the self-anti-coagulation elastomer material.
2. The self-setting resistant elastomer material as claimed in claim 1, wherein the molar amount of the sodium salt of a polyhydric alcohol sulfonic acid in the first step of the production method is 0 to 10 times, not 0 times, the molar amount of the glycerin; the ratio of the total molar weight of glycerol and the sodium salt of the polyalcohol sulfonic acid to the molar weight of sebacic acid is 2 to 3.
3. The self-anti-coagulation elastomer material as claimed in claim 1, wherein in the preparation method, the molar ratio of the antiplatelet agent to the sodium salt of the polyhydric alcohol sulfonic acid is 0.1 to 10.
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CN104368050A (en) * 2014-10-17 2015-02-25 南京师范大学 Method for preparing poly sulfoacid inner salt anticoagulant biomaterial via atom transfer radical polymerization
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CN111330090B (en) * 2020-03-02 2022-04-05 中国科学院宁波材料技术与工程研究所 Surface anticoagulation modification method of hemodialyzer and application thereof
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