CN110368515B - Preparation method of medical n-butyl ester adhesive with high bonding strength - Google Patents
Preparation method of medical n-butyl ester adhesive with high bonding strength Download PDFInfo
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- A—HUMAN NECESSITIES
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- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
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- A61L24/0042—Materials resorbable by the body
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- A—HUMAN NECESSITIES
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- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
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- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
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- C08F226/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen
- C08F226/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen by a single or double bond to nitrogen
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- C08F8/00—Chemical modification by after-treatment
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
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- C08F220/16—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms
- C08F220/18—Esters of monohydric alcohols or phenols of phenols or of alcohols containing two or more carbon atoms with acrylic or methacrylic acids
- C08F220/1804—C4-(meth)acrylate, e.g. butyl (meth)acrylate, isobutyl (meth)acrylate or tert-butyl (meth)acrylate
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Abstract
The invention discloses a preparation method of medical n-butyl ester glue with high bonding strength, which comprises the following steps: s1: copolymerizing hydroxydodecyl methacrylate, L-allyl glycine and 2, 3-dihydroxypropyl acrylate to obtain a hydroxyl acrylic copolymer containing a flexible chain segment; s2: quaternizing and modifying the hydroxyl acrylic copolymer containing the soft chain segment; s3: carrying out copolymerization reaction to obtain a cyano-containing triazinyl n-butyl acrylate copolymer; s4: and uniformly stirring and mixing the quaternized hydroxy acrylic copolymer containing the soft chain segment, the n-butyl acrylate copolymer containing the cyano-triazinyl acrylate and the alpha-n-butyl cyanoacrylate to obtain the medical n-butyl acrylate adhesive with high adhesive strength. The medical n-butyl ester has excellent performances of high adhesive bonding strength, high impact resistance, high hydrophilicity, strong heat resistance, antibiosis and the like, and also has the advantages of stable chemical property, no degradation of harmful substances, good biocompatibility and the like.
Description
Technical Field
The invention relates to the technical field of medical glue, in particular to a preparation method of medical n-butyl ester glue with high bonding strength.
Background
In the surgical operation, the antibiosis and the hemostasis are the foundation, and the repair, the sewing and the ligation of the organism tissue are two most basic operations; doctors also feel stranded for large areas of oozing blood where bleeding points cannot be found. If the suture can be replaced or partially replaced by glue, and the glue can stop the oozing of small blood vessels or seal the cancer serosal surface by spraying glue, the revolution of the surgical operation is made, and in the last century, people have diligent efforts for searching an ideal medical glue.
The alpha-cyanoacrylate adhesive is single-component, solvent-free, good in fluidity and capable of being rapidly cured at room temperature, and the curing time is only 6-15 s; has physical properties suitable for natural tissues; the chemical property is stable, and harmful substances are not degraded; the chemical medical adhesive has good biocompatibility, namely mechanical compatibility and histocompatibility, so that the chemical medical adhesive is rapidly developed and widely applied clinically in recent decades. However, the adhesive has the defects of poor impact resistance, low viscosity, poor gap filling performance on porous and rough surfaces, fast in-vivo degradation time, poor heat resistance, poor water resistance and the like, so that the application of the adhesive in medicine is limited to a certain extent.
Disclosure of Invention
In view of the defects of the prior art, the invention provides a preparation method of medical n-butyl rubber with high bonding strength, and aims to solve the technical problems of low bonding property, poor impact resistance, low heat resistance, poor water resistance and short degradation time of the conventional medical n-butyl rubber, so that the medical application range of the medical n-butyl rubber is expanded.
In order to achieve the above purposes, the technical scheme adopted by the invention is as follows:
a preparation method of medical n-butyl ester glue with high bonding strength comprises the following steps:
s1: preparation of a soft segment-containing hydroxyacrylic copolymer: dissolving hydroxydodecyl methacrylate and L-allyl glycine into ionic liquid under the atmosphere of inert gas to obtain a mixed solution A, adding an initiator, heating to 70-80 ℃ to start a polymerization reaction, slowly dropwise adding 2, 3-dihydroxypropyl acrylate in the reaction process, introducing vinyl chloride to perform an end-capping reaction after dropwise adding is finished, adding a polymerization inhibitor to terminate the reaction, separating out the ionic liquid and unreacted small molecular compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 80-90 ℃ to constant weight to obtain a hydroxyl acrylic copolymer containing a flexible chain segment;
s2: quaternization modification of soft segment-containing hydroxyacrylic copolymers: dissolving the hydroxyl acrylic copolymer containing the soft chain segment prepared in the step S1 in a mixed solution B consisting of dimethyl tertiary amine derivatives and absolute ethyl alcohol, stirring, heating, condensing, refluxing and reacting for 6-8 hours, precipitating in water, washing the product with ethyl alcohol for 3-5 times, and drying to constant weight to obtain the quaternized hydroxyl acrylic copolymer containing the soft chain segment;
s3: preparation of a N-butyl cyanoacrylate-containing Cyanotriazinyl copolymer: dissolving N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester and N-butyl acrylate into ionic liquid in an inert gas atmosphere to obtain a mixed solution C, adding an initiator, heating to 70-80 ℃, starting a polymerization reaction, slowly dropwise adding 2-cyanoethyl acrylate in the reaction process, adding a polymerization inhibitor to terminate the reaction after dropwise adding is completed, separating out the ionic liquid and unreacted small molecular compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 80-90 ℃ to constant weight to obtain the N-butyl acrylate copolymer containing the cyanotriazinyl acrylate;
s4: preparation of medical n-butyl ester glue: and (3) uniformly stirring and mixing the hydroxyl acrylic copolymer containing the soft chain segment obtained in the step S2, the n-butyl acrylate copolymer containing the cyano-triazinyl obtained in the step S3 and the alpha-n-butyl cyanoacrylate to obtain the medical n-butyl acrylate adhesive with high adhesive strength.
Further, in step S1, the total amount of the initiator added is 0.1 to 1% by mass of the mixed solution a.
Further, in step S2, the dimethyl tertiary amine derivative is at least one of decyl dimethyl tertiary amine, dodecyl dimethyl tertiary amine, tetradecyl dimethyl tertiary amine, and hexadecyl dimethyl tertiary amine.
Further, in step S2, the mass ratio of the soft segment-containing hydroxyacrylic acid-based copolymer, the dimethyl tertiary amine-based derivative, and the anhydrous ethanol is 1: 3-5: 10 to 25.
Further, in step S3, the total amount of the initiator added is 0.1 to 1% by mass of the mixed solution C.
Further, in step S1, the total amount of the hydroxydodecyl methacrylate and the L-allyl glycine dissolved accounts for 5 to 10wt% of the mixed solution a.
Further, in step S1, the molar ratio of hydroxydodecyl methacrylate to L-allyl glycine to 2, 3-dihydroxypropyl acrylate is 1: 3-5: 1 to 5.
Further, in step S1, the amount of vinyl chloride introduced is 0.1 to 1.2wt% based on the mass of the mixed solution A.
Further, in step S3, the total amount of N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester and N-butyl acrylate accounts for 1 to 8wt% of the mixed solution C.
Further, in step S3, the molar ratio of N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycinate ethyl ester, N-butyl acrylate and 2-cyanoethyl acrylate is 1: 8-12: 3 to 8.
Further, in step S4, the mass ratio of the soft segment-containing hydroxyacrylic acid-based copolymer, the n-butyl cyanoacrylate-containing triazinyl acrylate-based copolymer, and the n-butyl α -cyanoacrylate is 0.1 to 5: 0.5-15: 85-96.
Further, the ionic liquid is imidazole silicon-containing ionic liquid.
Further, the initiator is at least one of ethyl lithium, isopropyl lithium, phenyl lithium, 4-phenylbutyl lithium and cyclohexyl lithium.
Further, the polymerization inhibitor is at least one of isopropanol, n-butanol and glycerol.
The invention has the beneficial effects that:
the invention discloses a medical n-butyl ester adhesive which is compounded by quaternizing a hydroxyl acrylic copolymer containing a soft chain segment, a n-butyl acrylate copolymer containing cyano-triazine and alpha-n-butyl cyanoacrylate; the quaternized hydroxy acrylic copolymer containing the soft chain segment and the quaternized n-butyl acrylate copolymer containing the cyano-triazine group acrylic acid contain glycine and acrylic acid structures, so that the compatibility of the glycine and the acrylic acid structures is enhanced, and the biocompatibility of n-butyl ester glue is improved.
The side chain of the quaternized hydroxy acrylic copolymer molecule containing the flexible chain segment contains a large amount of hydroxyl groups and carboxyl groups, so that the hydrophilic property of the medical adhesive is improved, and the flexible chain segment on the side chain of the polymer improves the impact resistance of the medical adhesive; by quaternization modification treatment, the medical adhesive has a certain sterilization effect, and the stability of the alpha-n-butyl cyanoacrylate in the medical adhesive is improved.
The molecular main chain of the cyano-containing triazinyl n-butyl acrylate copolymer also contains a triazinyl structure, so that the heat resistance of the medical adhesive is improved; the introduction of the cyano structure provides more reaction sites for the subsequent medical glue, and further improves the bonding strength of the medical glue.
The imidazole silicon-containing ionic liquid is used as a solvent, so that the reaction yield is improved, the reaction system is green and environment-friendly, the obtained reaction product has high purity and less impurities, and the exudation of harmful substances in the medical adhesive is reduced.
The medical n-butyl ester adhesive compounded by the invention has no significant significance in bleeding amount and bleeding time difference with the existing alpha-cyanoacrylate medical adhesive, the adhesive effect of the compounded and modified medical n-butyl ester adhesive is superior to that of the conventional needle suture, the adhesive film is not easy to fall off, the hemostasis is thorough, and no obvious adverse reaction exists.
Detailed Description
The following description is presented to disclose the invention so as to enable any person skilled in the art to practice the invention. The preferred embodiments in the following description are given by way of example only, and other obvious variations will occur to those skilled in the art.
Example 1
The preparation method of the medical n-butyl ester adhesive with high bonding strength comprises the following steps:
s1: preparation of a soft segment-containing hydroxyacrylic copolymer: under the atmosphere of inert gas, hydroxyl dodecyl methacrylate and L-allyl glycine are dissolved into ionic liquid to obtain a mixed solution A, an initiator is added, the temperature is raised to 70 ℃ to start polymerization reaction, 2, 3-dihydroxy propyl acrylate is slowly dripped in the reaction process, vinyl chloride is introduced to carry out end-capping reaction after dripping is finished, a polymerization inhibitor is added to stop the reaction, then the ionic liquid and small molecular compounds which do not participate in the reaction are separated by adopting a liquid phase separation method, and finally the mixture is placed in a vacuum drying oven to be dried to constant weight at 80 ℃ to obtain a hydroxyl acrylic acid copolymer containing a flexible chain segment; the total addition amount of the initiator is 0.5 percent of the mass of the mixed solution A; the total amount of the hydroxydodecyl methacrylate and the L-allyl glycine in the mixed solution A accounts for 8wt% of the mixed solution A; the molar ratio of the hydroxydodecyl methacrylate to the L-allyl glycine to the 2, 3-dihydroxypropyl acrylate is 1: 4: 3; the introduction amount of the chloroethylene is 0.6wt% of the mass of the mixed solution A;
s2: quaternization modification of soft segment-containing hydroxyacrylic copolymers: dissolving the hydroxyl acrylic copolymer containing the soft chain segment prepared in the step S1 in a mixed solution B consisting of dimethyl tertiary amine derivatives and absolute ethyl alcohol, stirring, heating, condensing, refluxing and reacting for 6 hours, precipitating in water, washing the product for 3 times by using ethyl alcohol, and drying to constant weight to obtain the quaternized hydroxyl acrylic copolymer containing the soft chain segment; the mass ratio of the hydroxyl acrylic copolymer containing the soft chain segment, the dimethyl tertiary amine derivative and the absolute ethyl alcohol is 1: 4: 16; the dimethyl tertiary amine derivative is decyl dimethyl tertiary amine;
s3: preparation of a N-butyl cyanoacrylate-containing Cyanotriazinyl copolymer: dissolving N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester and N-butyl acrylate into ionic liquid in an inert gas atmosphere to obtain a mixed solution C, adding an initiator, heating to 70 ℃ to start a polymerization reaction, slowly dropwise adding 2-cyanoethyl acrylate in the reaction process, adding a polymerization inhibitor to terminate the reaction after dropwise adding is finished, separating out the ionic liquid and unreacted micromolecule compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 80 ℃ to constant weight to obtain the N-butyl acrylate copolymer containing the cyanotriazinyl group; the total addition amount of the initiator is 0.5 percent of the mass of the mixed solution C; the total amount of the N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester and the N-butyl acrylate accounts for 4wt% of the mass of the mixed solution C; the mol ratio of the N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester to the N-butyl acrylate to the 2-cyanoethyl acrylate is 1: 10: 5;
s4: preparation of medical n-butyl ester glue: uniformly stirring and mixing the hydroxyl acrylic copolymer containing the soft chain segment obtained in the step S2, the n-butyl acrylate copolymer containing the cyano-triazinyl obtained in the step S3 and n-butyl alpha-cyanoacrylate to obtain the medical n-butyl acrylate adhesive with high adhesive strength; the mass ratio of the hydroxyl acrylic copolymer containing the soft chain segment, the n-butyl acrylate copolymer containing the cyano-triazinyl to the alpha-n-butyl cyanoacrylate is 2: 6: 92.
the ionic liquid is imidazole silicon-containing ionic liquid; the initiator is ethyl lithium; the polymerization inhibitor is isopropanol.
Example 2
The preparation method of the medical n-butyl ester adhesive with high bonding strength comprises the following steps:
s1: preparation of a soft segment-containing hydroxyacrylic copolymer: under the atmosphere of inert gas, hydroxyl dodecyl methacrylate and L-allyl glycine are dissolved into ionic liquid to obtain a mixed solution A, an initiator is added, the temperature is raised to 80 ℃, polymerization reaction is started, 2, 3-dihydroxy propyl acrylate is slowly dripped in the reaction process, vinyl chloride is introduced for end-capping reaction after dripping is finished, a polymerization inhibitor is added for termination reaction, then the ionic liquid and small molecular compounds which do not participate in the reaction are separated by adopting a liquid phase separation method, and finally the mixture is dried in a vacuum drying oven at 90 ℃ to constant weight to obtain a hydroxyl acrylic copolymer containing a flexible chain segment; the total addition amount of the initiator is 0.1 percent of the mass of the mixed solution A; the total amount of the hydroxydodecyl methacrylate and the L-allyl glycine in the mixed solution A accounts for 5wt% of the mixed solution A; the molar ratio of the hydroxydodecyl methacrylate to the L-allyl glycine to the 2, 3-dihydroxypropyl acrylate is 1: 3: 1; the introduction amount of the chloroethylene is 0.1wt% of the mass of the mixed solution A;
s2: quaternization modification of soft segment-containing hydroxyacrylic copolymers: dissolving the hydroxyl acrylic copolymer containing the soft chain segment prepared in the step S1 in a mixed solution B consisting of dimethyl tertiary amine derivatives and absolute ethyl alcohol, stirring, heating, condensing, refluxing and reacting for 8 hours, precipitating in water, washing the product with ethyl alcohol for 5 times, and drying to constant weight to obtain the quaternized hydroxyl acrylic copolymer containing the soft chain segment; the mass ratio of the hydroxyl acrylic copolymer containing the soft chain segment, the dimethyl tertiary amine derivative and the absolute ethyl alcohol is 1: 3: 10; the dimethyl tertiary amine derivative is dodecyl dimethyl tertiary amine;
s3: preparation of a N-butyl cyanoacrylate-containing Cyanotriazinyl copolymer: dissolving N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester and N-butyl acrylate into ionic liquid in an inert gas atmosphere to obtain a mixed solution C, adding an initiator, heating to 80 ℃ to start a polymerization reaction, slowly dropwise adding 2-cyanoethyl acrylate in the reaction process, adding a polymerization inhibitor to terminate the reaction after dropwise adding is finished, separating out the ionic liquid and unreacted micromolecule compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 90 ℃ to constant weight to obtain the N-butyl acrylate copolymer containing the cyanotriazinyl group; the total addition amount of the initiator is 0.1 percent of the mass of the mixed solution C; the total amount of the N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester and the N-butyl acrylate accounts for 1wt% of the mass of the mixed solution C; the mol ratio of the N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester to the N-butyl acrylate to the 2-cyanoethyl acrylate is 1: 8: 3;
s4: preparation of medical n-butyl ester glue: uniformly stirring and mixing the hydroxyl acrylic copolymer containing the soft chain segment obtained in the step S2, the n-butyl acrylate copolymer containing the cyano-triazinyl obtained in the step S3 and n-butyl alpha-cyanoacrylate to obtain the medical n-butyl acrylate adhesive with high adhesive strength; the mass ratio of the hydroxyl acrylic copolymer containing the soft chain segment, the n-butyl acrylate copolymer containing the cyano triazine group to the alpha-n-butyl cyanoacrylate is 0.5: 3.5: 96.
the ionic liquid is imidazole silicon-containing ionic liquid; the initiator is lithium isopropyl; the polymerization inhibitor is n-butyl alcohol.
Example 3
The preparation method of the medical n-butyl ester adhesive with high bonding strength comprises the following steps:
s1: preparation of a soft segment-containing hydroxyacrylic copolymer: under the atmosphere of inert gas, hydroxyl dodecyl methacrylate and L-allyl glycine are dissolved into ionic liquid to obtain a mixed solution A, an initiator is added, the temperature is raised to 70 ℃ to start polymerization reaction, 2, 3-dihydroxy propyl acrylate is slowly dripped in the reaction process, vinyl chloride is introduced to carry out end-capping reaction after dripping is finished, a polymerization inhibitor is added to stop the reaction, then the ionic liquid and small molecular compounds which do not participate in the reaction are separated by adopting a liquid phase separation method, and finally the mixture is placed in a vacuum drying oven to be dried to constant weight at 80 ℃ to obtain a hydroxyl acrylic acid copolymer containing a flexible chain segment; the total adding amount of the initiator is 1% of the mass of the mixed solution A; the total amount of the hydroxydodecyl methacrylate and the L-allyl glycine in the mixed solution A accounts for 10wt% of the mixed solution A; the molar ratio of the hydroxydodecyl methacrylate to the L-allyl glycine to the 2, 3-dihydroxypropyl acrylate is 1: 5: 5; the introduction amount of the chloroethylene is 1.2wt% of the mass of the mixed solution A;
s2: quaternization modification of soft segment-containing hydroxyacrylic copolymers: dissolving the hydroxyl acrylic copolymer containing the soft chain segment prepared in the step S1 in a mixed solution B consisting of dimethyl tertiary amine derivatives and absolute ethyl alcohol, stirring, heating, condensing, refluxing and reacting for 8 hours, precipitating in water, washing the product with ethyl alcohol for 5 times, and drying to constant weight to obtain the quaternized hydroxyl acrylic copolymer containing the soft chain segment; the mass ratio of the hydroxyl acrylic copolymer containing the soft chain segment, the dimethyl tertiary amine derivative and the absolute ethyl alcohol is 1: 5: 25; the dimethyl tertiary amine derivative is tetradecyl dimethyl tertiary amine;
s3: preparation of a N-butyl cyanoacrylate-containing Cyanotriazinyl copolymer: dissolving N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester and N-butyl acrylate into ionic liquid in an inert gas atmosphere to obtain a mixed solution C, adding an initiator, heating to 70 ℃ to start a polymerization reaction, slowly dropwise adding 2-cyanoethyl acrylate in the reaction process, adding a polymerization inhibitor to terminate the reaction after dropwise adding is finished, separating out the ionic liquid and unreacted micromolecule compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 80 ℃ to constant weight to obtain the N-butyl acrylate copolymer containing the cyanotriazinyl group; the total adding amount of the initiator is 1% of the mass of the mixed solution C; the total amount of the N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester and the N-butyl acrylate accounts for 8wt% of the mass of the mixed solution C; the mol ratio of the N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester to the N-butyl acrylate to the 2-cyanoethyl acrylate is 1: 12: 8;
s4: preparation of medical n-butyl ester glue: uniformly stirring and mixing the hydroxyl acrylic copolymer containing the soft chain segment obtained in the step S2, the n-butyl acrylate copolymer containing the cyano-triazinyl obtained in the step S3 and n-butyl alpha-cyanoacrylate to obtain the medical n-butyl acrylate adhesive with high adhesive strength; the mass ratio of the hydroxyl acrylic copolymer containing the soft chain segment, the n-butyl acrylate copolymer containing the cyano-triazinyl acrylate to the alpha-n-butyl cyanoacrylate is 5: 10: 85.
the ionic liquid is imidazole silicon-containing ionic liquid; the initiator is phenyl lithium; the polymerization inhibitor is glycerol.
Example 4
The preparation method of the high-bonding-strength medical n-butyl ester adhesive of the embodiment is basically similar to that of the embodiment 1, and mainly differs in that, in the step S1, the molar ratio of the hydroxydodecyl methacrylate to the L-allyl glycine to the 2, 3-dihydroxypropyl acrylate is 1: 3: 1; the introduction amount of the chloroethylene is 0.3wt% of the mass of the mixed solution A;
in step S2, the mass ratio of the soft segment-containing hydroxyacrylic copolymer, the dimethyl tertiary amine derivative, and the anhydrous ethanol is 1: 3: 10;
in step S3, the molar ratio of N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester, N-butyl acrylate and 2-cyanoethyl acrylate is 1: 8: 3;
in step S4, the mass ratio of the soft segment-containing hydroxyacrylic acid-based copolymer, the n-butyl cyanoacrylate-containing triazine group-containing copolymer, and the n-butyl α -cyanoacrylate is: 0.5: 9.5: 90.
example 5
The preparation method of the high-bonding-strength medical n-butyl ester adhesive of the embodiment is basically similar to that of the embodiment 1, and mainly differs in that, in the step S1, the molar ratio of the hydroxydodecyl methacrylate to the L-allyl glycine to the 2, 3-dihydroxypropyl acrylate is 1: 5: 5; the introduction amount of the chloroethylene is 1.0wt% of the mass of the mixed solution A;
in step S2, the mass ratio of the soft segment-containing hydroxyacrylic copolymer, the dimethyl tertiary amine derivative, and the anhydrous ethanol is 1: 5: 25;
in step S3, the molar ratio of N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester, N-butyl acrylate and 2-cyanoethyl acrylate is 1: 11: 6;
in step S4, the mass ratio of the soft segment-containing hydroxyacrylic acid-based copolymer, the n-butyl cyanoacrylate-containing triazine group-containing copolymer, and the n-butyl α -cyanoacrylate is 5: 8: 93.
the medical n-butyl ester feet prepared in the examples 1-5 and the commercially available medical n-butyl ester glue are used as comparative examples to carry out performance tests, and the performance results are shown in the following table 1:
adhesion and bond strength testing: fixing the pigskin with the diameter of 6mm on a cylindrical fixture of a universal tester, coating 3mg of medical N-butyl ester adhesive between the front surfaces of the two pigskins, pulling the two pigskins back and forth and bonding for 10 times, then pressing the two pigskins for 10min by 20N force to ensure that the bonding surfaces of the two pigskins are uniformly and closely contacted, pulling the two pigskins apart at the speed of 1mm/min to measure the bonding force and the bonding strength of the medical N-butyl ester adhesive, and repeating the five times to obtain an average value.
And (3) testing the hemostatic effect: puncturing the liver of a male rat (weighing 30-35 g), immediately taking 10mg of medical glue to a bleeding part, weighing the mass of bleeding within 30s, and repeating five times to obtain an average value.
And (3) testing the impact resistance: a free falling impact stripping test device is adopted, a pair of pigskins are glued by medical n-butyl ester glue to form a T-shaped impact stripping sample, and under the specified condition, impact force is applied to the non-glued end of the sample, so that the sample is stripped along the glue line. The impact resistance of the medical n-butyl ester adhesive is evaluated by measuring the stripping length of the sample.
And (3) testing antibacterial performance: the medical glue is cultured in 2mL of culture solution with the bacterial concentration of 1 x 10^6cells/mL for 24h at 37 ℃, then the sterilization effect of the medical n-butyl glue is observed by adopting a laser scanning confocal microscope, the antibacterial performance is evaluated by observing the number of bacteria, the bacteria are excellent if no obvious bacteria appear, good if few bacteria appear and poor if a large number of bacteria appear.
And (3) testing heat resistance: a pair of pigskins are glued by medical n-butyl ester glue, then the sample is placed in a water bath at 60 ℃ for soaking for 12 hours, then the impact resistance test is carried out on a free fall type impact stripping test device, the difference is that the stripping length is larger than 25mm, and the advantage is that the stripping length is smaller than 20 mm.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the invention, but that various changes and modifications may be made without departing from the spirit and scope of the invention, which fall within the scope of the invention as claimed.
Claims (10)
1. A preparation method of medical n-butyl ester glue with high bonding strength is characterized by comprising the following steps:
s1: preparation of a soft segment-containing hydroxyacrylic copolymer: dissolving hydroxydodecyl methacrylate and L-allyl glycine into ionic liquid under the atmosphere of inert gas to obtain a mixed solution A, adding an initiator, heating to 70-80 ℃ to start a polymerization reaction, slowly dropwise adding 2, 3-dihydroxypropyl acrylate in the reaction process, introducing vinyl chloride to perform an end-capping reaction after dropwise adding is finished, adding a polymerization inhibitor to terminate the reaction, separating out the ionic liquid and unreacted small molecular compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 80-90 ℃ to constant weight to obtain a hydroxyl acrylic copolymer containing a flexible chain segment;
s2: quaternization modification of soft segment-containing hydroxyacrylic copolymers: dissolving the hydroxyl acrylic copolymer containing the soft chain segment prepared in the step S1 in a mixed solution B consisting of dimethyl tertiary amine derivatives and absolute ethyl alcohol, stirring, heating, condensing, refluxing and reacting for 6-8 hours, precipitating in water, washing the product with ethyl alcohol for 3-5 times, and drying to constant weight to obtain the quaternized hydroxyl acrylic copolymer containing the soft chain segment;
s3: preparation of a N-butyl cyanoacrylate-containing Cyanotriazinyl copolymer: dissolving N- [4- (allylamino) -6-chloro-1, 3, 5-triazine-2-yl ] glycine ethyl ester and N-butyl acrylate into ionic liquid in an inert gas atmosphere to obtain a mixed solution C, adding an initiator, heating to 70-80 ℃, starting a polymerization reaction, slowly dropwise adding 2-cyanoethyl acrylate in the reaction process, adding a polymerization inhibitor to terminate the reaction after dropwise adding is completed, separating out the ionic liquid and unreacted small molecular compounds by adopting a liquid phase separation method, and finally drying in a vacuum drying oven at 80-90 ℃ to constant weight to obtain the N-butyl acrylate copolymer containing the cyanotriazinyl acrylate;
s4: preparation of medical n-butyl ester glue: and (3) uniformly stirring and mixing the hydroxyl acrylic copolymer containing the soft chain segment obtained in the step S2, the n-butyl acrylate copolymer containing the cyano-triazine radical obtained in the step S3 and the alpha-n-butyl cyanoacrylate to obtain the medical n-butyl acrylate adhesive with high bonding strength.
2. The method for preparing medical n-butyl ester adhesive with high bonding strength as claimed in claim 1, wherein in step S1, the total amount of hydroxydodecyl methacrylate and L-allyl glycine is 5-10 wt% of the mixed solution a.
3. The method for preparing medical n-butyl ester adhesive with high bonding strength as claimed in claim 1, wherein in step S1, the molar ratio of hydroxydodecyl methacrylate, L-allyl glycine and 2, 3-dihydroxypropyl acrylate is 1: 3-5: 1 to 5.
4. The method for preparing medical n-butyl ester adhesive with high bonding strength as claimed in claim 1, wherein in step S1, the amount of vinyl chloride introduced is 0.1-1.2 wt% of the mass of the mixed solution A.
5. The method for preparing medical N-butyl ester adhesive with high bonding strength according to claim 1, wherein in step S3, the total amount of N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester and N-butyl acrylate accounts for 1-8 wt% of the mixed solution C.
6. The method for preparing medical N-butyl ester adhesive with high bonding strength according to claim 1, wherein in step S3, the molar ratio of N- [4- (allylamino) -6-chloro-1, 3, 5-triazin-2-yl ] glycine ethyl ester, N-butyl acrylate and 2-cyanoethyl acrylate is 1: 8-12: 3 to 8.
7. The method for preparing medical n-butyl ester adhesive with high bonding strength according to claim 1, wherein in step S4, the mass ratio of the soft segment-containing hydroxyacrylic acid copolymer, the cyano group-containing n-butyl triazinylacrylate-based copolymer and the α -n-butyl cyanoacrylate is 0.1 to 5: 0.5-15: 85-96.
8. The preparation method of high-bonding-strength medical n-butyl ester glue as claimed in claim 1, wherein the ionic liquid is imidazole-based silicon-containing ionic liquid.
9. The method for preparing high bonding strength medical n-butyl ester glue according to claim 1, wherein the initiator is at least one of ethyllithium, isopropyllithium, phenyllithium, 4-phenylbutyllithium and cyclohexyllithium.
10. The method for preparing medical n-butyl ester adhesive with high bonding strength as claimed in claim 1, wherein the polymerization inhibitor is at least one of isopropanol, n-butanol and glycerol.
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