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CN114053474A - Medical adhesive with hemostatic function and use method thereof - Google Patents

Medical adhesive with hemostatic function and use method thereof Download PDF

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Publication number
CN114053474A
CN114053474A CN202111403289.8A CN202111403289A CN114053474A CN 114053474 A CN114053474 A CN 114053474A CN 202111403289 A CN202111403289 A CN 202111403289A CN 114053474 A CN114053474 A CN 114053474A
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CN
China
Prior art keywords
component
medical adhesive
adhesive
hemostatic function
curing agent
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Pending
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CN202111403289.8A
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Inventor
施雪涛
张照国
宣承楷
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South China University of Technology SCUT
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South China University of Technology SCUT
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Priority to CN202111403289.8A priority Critical patent/CN114053474A/en
Publication of CN114053474A publication Critical patent/CN114053474A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001Use of materials characterised by their function or physical properties
    • A61L24/0015Medicaments; Biocides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/02Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/046Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30Low-molecular-weight compounds
    • C08G18/32Polyhydroxy compounds; Polyamines; Hydroxyamines
    • C08G18/3203Polyhydroxy compounds
    • C08G18/3206Polyhydroxy compounds aliphatic
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30Low-molecular-weight compounds
    • C08G18/32Polyhydroxy compounds; Polyamines; Hydroxyamines
    • C08G18/3225Polyamines
    • C08G18/3228Polyamines acyclic
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40High-molecular-weight compounds
    • C08G18/48Polyethers
    • C08G18/4833Polyethers containing oxyethylene units
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00Polymeric products of isocyanates or isothiocyanates
    • C08G18/06Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/65Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
    • C08G18/66Compounds of groups C08G18/42, C08G18/48, or C08G18/52
    • C08G18/6666Compounds of group C08G18/48 or C08G18/52
    • C08G18/667Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38
    • C08G18/6681Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/32 or C08G18/3271 and/or polyamines of C08G18/38
    • C08G18/6685Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/32 or C08G18/3271 and/or polyamines of C08G18/38 with compounds of group C08G18/3225 or polyamines of C08G18/38
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/418Agents promoting blood coagulation, blood-clotting agents, embolising agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/06Flowable or injectable implant compositions

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

Abstract

The invention discloses a medical adhesive with a hemostatic function and a use method thereof, and the medical adhesive comprises A, B components, wherein the A component is a polyurethane prepolymer based on polyethylene glycol and micromolecular polyol, and the B component is a modified secondary amine curing agent containing clay; the component A is obtained by the following steps: reacting polyethylene glycol (PEG) with Diisocyanate (DI) to obtain an intermediate, and adding a micromolecular polyol chain extender to obtain a polyurethane prepolymer; the component B is obtained by the following steps: reacting a diprimary amine withAlpha, beta-unsaturated carbonyl compound-NH in terms of molar ratio of functional groups2: reacting under the catalysis of a transition metal, extracting and rotary steaming after the reaction is completed to obtain a curing agent precursor, wherein the mass ratio of the curing agent precursor to clay is 0.02-0.2: 1 to obtain the component B. The medical adhesive prepared by the invention has the advantages of quick curing, good biocompatibility, high adhesive strength and good procoagulant effect, and is suitable for quickly plugging and repairing wounds under bleeding conditions.

Description

Medical adhesive with hemostatic function and use method thereof
Technical Field
The invention relates to the technical field of biomedical materials, tissue engineering and regenerative medicine, in particular to a medical adhesive with a hemostatic function and a use method thereof.
Background
At present, a suture and an anastomat are mostly adopted for wound closure of human tissue wounds, the wound closure method is complex to operate, secondary injury during operation brings great pain to a patient, meanwhile, tissues are damaged in different degrees, the commercialized medical adhesive which is used as a substitute of the suture and the anastomat at present has single function and does not have the function of procoagulant blood, and the continuous bleeding of the wound causes adverse effects on the adhesion of the medical adhesive.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a medical adhesive which is simple and convenient to operate, does not cause secondary damage and has a good hemostatic effect and a using method thereof.
In order to achieve the purpose, the technical scheme provided by the invention is as follows: a medical adhesive with hemostatic function comprises A, B components, wherein the A component is a polyurethane prepolymer based on polyethylene glycol and micromolecular polyol, and the B component is a modified secondary amine curing agent containing clay;
the component A is obtained by the following steps: reacting polyethylene glycol (PEG) with Diisocyanate (DI) to obtain an intermediate, and adding a micromolecular polyol chain extender to obtain a polyurethane prepolymer; wherein the R value (the ratio of-NCO functional group number to-OH functional group number in the raw material synthesized by the component A) is 1.2-1.8, and the OH value (the ratio of-OH functional group number to the sum of PEG molecule number and micromolecular polyol chain extender molecule number in the raw material synthesized by the component A) is 2.4-2.9;
the component B is obtained by the following steps: reacting diprimary amine with alpha, beta-unsaturated carbonyl compound according to the mole ratio of functional groups-NH2: under the catalysis of transition metal, the reaction is carried out, and after the reaction is completed, the curing agent is obtained by extraction and rotary evaporationAnd driving the body, namely, mixing the curing agent precursor with clay according to the mass ratio of 0.02-0.2: 1 to obtain the component B.
Preferably, the PEG is one or a combination of more of PEG200, PEG400, PEG600, PEG800 and PEG 1000; the diisocyanate is one or a combination of L-lysine diisocyanate, isophorone diisocyanate and dimethylene bis (phenyl isocyanate); the micromolecular polyalcohol chain extender is one or a combination of glycerol, pentaerythritol and glucose.
Preferably, the diprimary amine is one or a combination of several of N' -bis (3-aminopropyl) methylamine, 1, 3-diaminopentane, 1, 5-diamino-2-methylpentane and bis (hexamethylene) triamine; the alpha, beta-unsaturated carbonyl compound is one or a combination of methyl acrylate, butyl acrylate and diethyl maleate; the transition metal is one or a combination of more of ceric ammonium nitrate, yttrium nitrate, cobalt chloride and ferric chloride.
Preferably, the clay is one or a combination of more of kaolin, montmorillonite, diatomite and hectorite.
Preferably, a small amount of stabilizer is added to the polyurethane prepolymer to be used.
Preferably, the stabilizer is one or two of phosphoric acid and benzoyl chloride.
The invention also provides a use method of the medical adhesive with the hemostatic function, when in use, A, B components are mixed by a double-cavity syringe according to the molar weight ratio of functional groups (-NCO: -NH) 1: 0.8-1 and then coated on the surface of wound tissue.
Preferably, the double-cavity syringe comprises two cavities with different inner diameters, a push rod and a mixing nozzle, when the double-cavity syringe is used, A, B components are respectively loaded in the two cavities, then the components are pushed out to a target part through the mixing nozzle by the push rod, and clay in the adhesive can initiate coagulation cascade reaction to realize wound hemostasis, so that the adhesive effect of the adhesive is prevented from being influenced by continuous bleeding, and quick hemostasis and plugging under the condition of wound bleeding are realized; reacting-NCO functional groups in the component A with-NH in the component B for crosslinking and curing to generate carbamate bonds and urea bonds, and finally realizing tissue adhesion of the wound bleeding part by forming hydrogen bond action between the carbamate bonds and the urea bonds and active hydrogen in human tissues.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the medical adhesive with the procoagulant effect can be obtained through the invention, the clay in the adhesive can rapidly cause coagulation cascade reaction after contacting blood, the rapid hemostasis and plugging under the condition of wound bleeding can be met, and the influence of continuous bleeding on the adhesive effect of the adhesive is avoided. In addition, the clay and the hydrophilic carbon-oxygen macromolecule long chain in the medical adhesive enable the adhesive to have good water absorption, and can rapidly absorb moisture on the surface of a wet wound when the adhesive is in contact with the wet wound, so that the adhesive is fully in contact with the surface of the wound, and the adhesion to the wet tissue is enhanced. The medical adhesive has lower modulus after being cured, and when tissues at the wound move, the junction of the adhesive and the tissues is not easy to cause stress concentration, so that secondary damage to the tissues can be avoided. The medical adhesive has good elasticity after being cured, and can reduce the restriction on the movement of tissues at the wound under the scenes such as lung respiration, penile erection and the like. The medical adhesive does not contain a small molecular solvent and has good biological safety. The medical adhesive is simple to operate when in use, and can effectively reduce the operation time.
Detailed Description
The technical solution of the present invention is further described in detail with reference to the following specific examples, but the scope and implementation of the present invention are not limited thereto.
Example 1
In a first step, 4.34g of lysine diisocyanate (0.019mol) was dissolved in 11mL of tetrahydrofuran according to the R value 1.2 and the OH value 2.4, and added to a round-bottomed flask with stirring; 1.6g of polyethylene glycol (Mn 200, 0.008mol) was dissolved in 3.2ml of tetrahydrofuran and slowly added to a round-bottomed flask to react with lysine diisocyanate for 3 hours at a reaction temperature of 20 ℃ to obtain an isocyanate group-terminated intermediate.
In the second step, 0.491g of glycerol (0.005mol) was dissolved in 20ml of tetrahydrofuran according to the R value of 1.2 and the OH value of 2.4, and slowly added to the intermediate in the first step, and reacted at 20 ℃ for 3 hours to obtain a medical polyurethane adhesive containing a solvent.
And thirdly, transferring the product obtained in the second step into a rotary steaming instrument, carrying out rotary steaming for 1h at the temperature of 50 ℃ to obtain a polyurethane prepolymer of the medical adhesive with the hemostatic function, adding trace phosphoric acid, and storing the prepolymer in a dry environment for later use.
In the fourth step, 5.81g of 1, 5-diamino-2-methylpentane (0.05mol) and 17.22g of diethyl maleate (0.1mol) were dissolved in 100mL of ethanol to obtain a reaction mixture solution.
In the fifth step, 2g of ammonium cerium nitrate was dissolved in 100mL of water to obtain an aqueous catalyst solution.
And sixthly, mixing the reactant mixed solution obtained in the fourth step with the catalyst aqueous solution obtained in the fifth step, and reacting for 24 hours at room temperature.
And seventhly, extracting the reaction liquid obtained in the sixth step by using ether, then carrying out rotary evaporation on the curing agent ether solution obtained by extraction at 50 ℃ for 1h, then adding kaolin powder accounting for 2% of the mass of the product into the rotary evaporation product, and uniformly mixing to obtain the curing agent of the medical adhesive with the hemostatic function for later use.
When in use, the polyurethane prepolymer and the curing agent are mixed according to the ratio of the molar weight of functional groups (-NCO: -NH) of 1:0.8 mixing by a double-cavity injector, wherein the double-cavity injector comprises two cavities with different inner diameters, a push rod and a mixing nozzle, when in use, A, B components are respectively arranged in the two cavities, then the materials are pushed out to a target position by the push rod through the mixing nozzle, a-NCO functional group in the A component reacts with-NH in the B component to be crosslinked and solidified to generate a urethane bond and a urea bond, and finally the bonding between human soft tissues is realized by the hydrogen bond action formed by the urethane bond and the urea bond and active hydrogen in the human tissues; the clay in the curing agent can contact with the blood of a human body to initiate a blood coagulation reaction, so that the effect of promoting blood coagulation is realized. Wherein, the curing is completed within 2-10 minutes, and a good bonding effect can be obtained.
Example 2
In a first step, 47.24g of lysine diisocyanate (0.209mol) was dissolved in 50mL of tetrahydrofuran according to the R value 1.8 and the OH value 2.9 and added to a round-bottomed flask; 8g of polyethylene glycol (Mn 1000, 0.008mol) was dissolved in 40ml of tetrahydrofuran and slowly added to a round-bottomed flask to react with lysine diisocyanate for 12 hours at a reaction temperature of 60 ℃ to obtain an isocyanate group-terminated intermediate.
In the second step, 6.63g of glycerol (0.072mol) was dissolved in 20ml of tetrahydrofuran according to the R value 1.8 and the OH value 2.9, and slowly added to the intermediate in the first step, and reacted at 60 ℃ for 22 hours to obtain a medical polyurethane adhesive containing a solvent.
And thirdly, transferring the product obtained in the second step into a rotary steaming instrument, carrying out rotary steaming for 1h at 50 ℃ to obtain a polyurethane prepolymer of the medical adhesive with the hemostatic function, adding a trace amount of benzoyl chloride, and storing the prepolymer in a dry environment for later use.
In the fourth step, 5.38g of bis (hexamethylene) triamine (0.025mol) and 4.30g of methyl acrylate (0.05mol) were dissolved in 100mL of ethanol to obtain a reaction mixture solution.
In the fifth step, 2g of yttrium nitrate was dissolved in 100mL of water to obtain an aqueous catalyst solution.
And sixthly, mixing the reactant mixed solution obtained in the fourth step with the catalyst aqueous solution obtained in the fifth step, and reacting for 24 hours at room temperature.
And seventhly, extracting the reaction liquid obtained in the sixth step by using ether, then carrying out rotary evaporation on the curing agent ether solution obtained by extraction at 50 ℃ for 1h, then adding montmorillonite powder accounting for 20% of the mass of the product into the rotary evaporation product, and uniformly mixing to obtain the curing agent of the medical adhesive with the hemostatic function for later use.
When the polyurethane adhesive is used, the polyurethane prepolymer and the curing agent are mixed by a double-cavity injector according to the molar weight ratio of functional groups (-NCO: -NH) ═ 1:1, the double-cavity injector comprises two cavities with different inner diameters, a push rod and a mixing nozzle, when the polyurethane adhesive is used, A, B components are respectively loaded into the two cavities, then the components are pushed out to a target position by the mixing nozzle through the push rod, the-NCO functional groups in the A component and the-NH in the B component react and crosslink and cure to generate urethane bonds and urea bonds, and finally the bonding between human soft tissues is realized by the hydrogen bond action formed by the urethane bonds and the urea bonds and active hydrogen in the human tissues; the clay in the curing agent can contact with the blood of a human body to initiate a blood coagulation reaction, so that the effect of promoting blood coagulation is realized. Wherein, the curing is completed within 2-10 minutes, and a good bonding effect can be obtained.
Example 3
In a first step, 7.56g of isophorone diisocyanate (0.034mol) were dissolved in 18mL of tetrahydrofuran according to the R value 1.7 and OH value 2.5 and added to a round-bottom flask with stirring; 3.2g of polyethylene glycol (Mn 400, 0.008mol) was dissolved in 4.8ml of tetrahydrofuran and slowly added to a round-bottomed flask to react with lysine diisocyanate for 8 hours at a reaction temperature of 30 ℃ to obtain an isocyanate group-terminated intermediate.
In the second step, 0.36g of pentaerythritol (0.0027mol) was dissolved in 20ml of tetrahydrofuran according to the R value of 1.7 and the OH value of 2.5, and slowly added to the intermediate in the first step, and reacted at 30 ℃ for 5 hours to obtain a medical polyurethane adhesive containing a solvent.
And thirdly, transferring the product obtained in the second step into a rotary steaming instrument, carrying out rotary steaming for 1h at the temperature of 40 ℃ to obtain a polyurethane prepolymer of the medical adhesive with the hemostatic function, adding a trace amount of benzoyl chloride, and storing the prepolymer in a dry environment for later use.
In the fourth step, 3.63g N' N-bis (3-aminopropyl) methylamine (0.025mol) and 8.609g diethyl maleate (0.05mol) were dissolved in 100mL of ethanol to obtain a reactant mixture solution.
In the fifth step, 2g of ammonium cerium nitrate was dissolved in 100mL of water to obtain an aqueous catalyst solution.
And sixthly, mixing the reactant mixed solution obtained in the fourth step with the catalyst aqueous solution obtained in the fifth step, and reacting for 24 hours at the temperature of 30 ℃.
And seventhly, adding diatomite powder accounting for 20 percent of the mass of the product into the rotary evaporation product, and uniformly mixing to obtain the curing agent of the medical adhesive with the hemostatic function for later use.
When the polyurethane adhesive is used, the polyurethane prepolymer and the curing agent are mixed by a double-cavity injector according to the molar weight ratio of functional groups (-NCO: -NH) ═ 1:0.9, the double-cavity injector comprises two cavities with different inner diameters, a push rod and a mixing nozzle, when the polyurethane adhesive is used, A, B components are respectively arranged in the two cavities, then the polyurethane adhesive is pushed out to a target position by the mixing nozzle through the push rod, the-NCO functional group in the A component reacts with-NH in the B component to be crosslinked and cured to generate a urethane bond and a urea bond, and finally the bonding between human soft tissues is realized by the hydrogen bond action formed by the urethane bond and the urea bond and active hydrogen in the human tissues; the clay in the curing agent can contact with the blood of a human body to initiate a blood coagulation reaction, so that the effect of promoting blood coagulation is realized. Wherein, the curing is completed within 2-10 minutes, and a good bonding effect can be obtained.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.

Claims (8)

1. The medical adhesive with the hemostatic function is characterized in that: the adhesive comprises A, B components, wherein the A component is a polyurethane prepolymer based on polyethylene glycol and small molecular polyol, and the B component is a modified secondary amine curing agent containing clay;
the component A is obtained by the following steps: reacting polyethylene glycol (PEG) with Diisocyanate (DI) to obtain an intermediate, and adding a micromolecular polyol chain extender to obtain a polyurethane prepolymer; wherein, the ratio of-NCO functional group number to-OH functional group number in the raw material synthesized by the component A, namely R value, is 1.2-1.8, and the ratio of-OH functional group number to the sum of PEG molecule number and micromolecular polyalcohol chain extender molecule number in the raw material synthesized by the component A, namely OH value, is 2.4-2.9;
the component B is obtained by the following steps: reacting diprimary amine with alpha, beta-unsaturated carbonyl compound according to the mole ratio of functional groups-NH2: reacting under the catalysis of a transition metal, extracting and rotary steaming after the reaction is completed to obtain a curing agent precursor, wherein the mass ratio of the curing agent precursor to clay is 0.02-0.2: 1 to obtain the component B.
2. The medical adhesive with hemostatic function according to claim 1, wherein: the PEG is one or a combination of more of PEG200, PEG400, PEG600, PEG800 and PEG 1000; the diisocyanate is one or a combination of L-lysine diisocyanate, isophorone diisocyanate and dimethylene bis (phenyl isocyanate); the micromolecular polyalcohol chain extender is one or a combination of glycerol, pentaerythritol and glucose.
3. The medical adhesive with hemostatic function according to claim 1, wherein: the diprimary amine is one or a combination of more of N' N-bis (3-aminopropyl) methylamine, 1, 3-diaminopentane, 1, 5-diamino-2-methylpentane and bis (hexamethylene) triamine; the alpha, beta-unsaturated carbonyl compound is one or a combination of methyl acrylate, butyl acrylate and diethyl maleate; the transition metal is one or a combination of more of ceric ammonium nitrate, yttrium nitrate, cobalt chloride and ferric chloride.
4. The medical adhesive with hemostatic function according to claim 1, wherein: the clay is one or more of kaolin, montmorillonite, diatomite and hectorite.
5. The medical adhesive with hemostatic function according to claim 1, wherein: adding a trace amount of stabilizer into the polyurethane prepolymer to be used.
6. The medical adhesive with hemostatic function according to claim 5, wherein: the stabilizer is one or two of phosphoric acid and benzoyl chloride.
7. The method for using the medical adhesive with hemostatic function according to any one of claims 1-6, wherein the method comprises the following steps: when used, the A, B components are mixed according to the molar ratio of the functional groups-NCO: mixing the-NH-1: 0.8-1 by a double-cavity injector, and coating the mixture on the surface of the wound tissue.
8. The method for using the medical adhesive with hemostatic function according to claim 7, wherein the method comprises the following steps: the double-cavity injector comprises two cavities with different inner diameters, a push rod and a mixing nozzle, when the double-cavity injector is used, A, B components are respectively loaded in the two cavities, then the components are pushed out to a target part by the mixing nozzle through the push rod, clay in the adhesive can initiate coagulation cascade reaction to realize wound hemostasis, the adhesive effect of the adhesive is prevented from being influenced by continuous bleeding, and rapid hemostasis and plugging under the condition of wound bleeding are realized; reacting-NCO functional groups in the component A with-NH in the component B for crosslinking and curing to generate carbamate bonds and urea bonds, and finally realizing tissue adhesion of the wound bleeding part by forming hydrogen bond action between the carbamate bonds and the urea bonds and active hydrogen in human tissues.
CN202111403289.8A 2021-11-24 2021-11-24 Medical adhesive with hemostatic function and use method thereof Pending CN114053474A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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CN115212342A (en) * 2022-07-07 2022-10-21 中国地质大学(武汉) Kaolin composite hemostatic material and preparation method thereof
CN116392627A (en) * 2023-03-21 2023-07-07 北京大清生物技术股份有限公司 Medical adhesive for soft tissue repair, product and preparation method thereof
CN116474157A (en) * 2023-04-28 2023-07-25 广州迅合医疗科技有限公司 Preparation method and system of hard tissue biological adhesive for continuous adhesion in wet environment
CN116589652A (en) * 2023-04-28 2023-08-15 广州迅合医疗科技有限公司 Preparation method and system of soft tissue biological adhesive based on polyurethane
CN116474157B (en) * 2023-04-28 2023-09-15 广州迅合医疗科技有限公司 Preparation method and system of hard tissue biological adhesive for continuous adhesion in wet environment
CN116589652B (en) * 2023-04-28 2023-10-27 广州迅合医疗科技有限公司 Preparation method and system of soft tissue biological adhesive based on polyurethane

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