CN111333815A - Material with biological adhesive and biodegradable component, preparation method and application thereof - Google Patents
Material with biological adhesive and biodegradable component, preparation method and application thereof Download PDFInfo
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- CN111333815A CN111333815A CN202010234757.2A CN202010234757A CN111333815A CN 111333815 A CN111333815 A CN 111333815A CN 202010234757 A CN202010234757 A CN 202010234757A CN 111333815 A CN111333815 A CN 111333815A
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- 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
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/83—Chemically modified polymers
- C08G18/833—Chemically modified polymers by nitrogen containing compounds
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/36—Hydroxylated esters of higher fatty acids
-
- 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
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/48—Polyethers
- C08G18/4833—Polyethers containing oxyethylene units
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- 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
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
- C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
- C08G18/6666—Compounds of group C08G18/48 or C08G18/52
- C08G18/6696—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/36 or hydroxylated esters of higher fatty acids of C08G18/38
-
- 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
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/75—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic
- C08G18/751—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring
- C08G18/752—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group
- C08G18/753—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group
- C08G18/755—Polyisocyanates or polyisothiocyanates cyclic cycloaliphatic containing only one cycloaliphatic ring containing at least one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group containing one isocyanate or isothiocyanate group linked to the cycloaliphatic ring by means of an aliphatic group having a primary carbon atom next to the isocyanate or isothiocyanate group and at least one isocyanate or isothiocyanate group linked to a secondary carbon atom of the cycloaliphatic ring, e.g. isophorone diisocyanate
Abstract
The invention provides a material with biological adhesive and biodegradable components, a preparation method and application thereof, belonging to the field of medical adhesives, wherein castor oil and polyethylene glycol are taken, vacuum dehydration is carried out for 2.5-3h at the temperature of 105-. The novel polyurethane adhesive obtained by the invention can be rapidly cured, has high bonding strength and tensile strength, low swelling degree and better biodegradability and biocompatibility.
Description
Technical Field
The invention belongs to the field of medical adhesives, and particularly relates to a material with a biological adhesive and a biodegradable component, a preparation method and application thereof.
Background
The medical adhesive has the advantages of effectively stopping bleeding, isolating air, avoiding damage to human tissues due to body fluid leakage, being convenient to use, reducing operation time, not needing to be dismantled, and meeting requirements of clinical operation and biological adhesive application, namely, 78-cyanoacrylate adhesive for skin and rapid hemostasis, α -cyanoacrylate adhesive for clinical operation, 89910 adhesive for clinical operation, 910 adhesive for clinical operation, and no toxic or toxic and toxic biological adhesive, wherein the adhesive is developed by Eastman company, the medical adhesive is suitable for biological adhesive application, the adhesive is suitable for biological adhesive application, and the adhesive is suitable for biological adhesive application, and the medical adhesive is suitable for biological adhesive application, namely, the biological adhesive is suitable for biological adhesive application, and the biological adhesive is suitable for clinical operation, the biological adhesive application, the biological adhesive is suitable for clinical operation, and the biological adhesive is suitable for clinical operation, the biological adhesive is suitable for clinical adhesive, the biological adhesive is suitable for the biological adhesive application, the biological adhesive for the biological adhesive application, the biological.
In the prior art, for example, a chinese patent with an issued publication number of CN 104479598B discloses a waterproof medical adhesive and a preparation method thereof, which belong to the field of medical adhesives, and the waterproof medical adhesive comprises the following components in parts by weight: 15-26 parts of silicone-acrylic emulsion, 5-9 parts of natural rubber, 4-10 parts of potassium citrate, 10-16 parts of nano zinc oxide, 9-15 parts of nano silicon dioxide, 5-11 parts of sodium carboxymethylcellulose, 2-5 parts of camphor seed kernel oil, 8-14 parts of polyvinyl alcohol, 10-18 parts of ethanol and 12-19 parts of water. The adhesive disclosed by the invention has good adhesiveness and better waterproof performance.
Disclosure of Invention
The invention aims to provide a novel polyurethane adhesive and a preparation method thereof, the method can reduce the steric hindrance effect of a benzene ring on 2-amino-4-sulfobenzoic acid, improve the nucleophilicity of amino on 2-amino-4-sulfobenzoic acid, improve the grafting rate, and the obtained novel polyurethane adhesive can be quickly cured, has high shear strength and adhesive strength, low swelling degree and better biodegradability and biocompatibility.
The technical scheme adopted by the invention for realizing the purpose is as follows:
the preparation method of the polyurethane adhesive is characterized by comprising the following steps:
s1, drying of the polyol: taking castor oil and polyethylene glycol, vacuum dehydrating at the temperature of 105-115 ℃ for 2.5-3h, standing and cooling to 50-52 ℃ after the dehydration is finished;
s2, synthesis of prepolymer: under the protection of nitrogen, after the dehydrated and dried polyol is heated to 70-72 ℃, adding isophorone diisocyanate, and reacting for 6-7h under the condition of slow stirring;
s3, grafting of 2-amino-4-sulfobenzoic acid: adding an isopropanol solution containing 2-amino-4-sulfobenzoic acid and methyl propionate into the prepolymer obtained in the step S2, reacting at a constant temperature of 70-72 ℃ for 1-2h, cooling to room temperature after the reaction is finished, and storing the product in a water vapor-isolated manner for later use;
the castor oil: polyethylene glycol: isophorone diisocyanate: 2-amino-4-sulfobenzoic acid (m/m) ═ 6-9:73-84:33-42: 2-4. The methyl propionate is favorable for the reaction of amino on 2-amino-4-sulfobenzoic acid and carbon atoms in polyurethane terminal-NCO in the presence of methyl propionate to form an amido bond, a benzene ring with hydrophilic group-sulfonic group and carboxyl is introduced to accelerate the biodegradation of polyurethane, the sulfonic group and the carboxyl can react with amino and hydroxyl in the presence of water molecules to further crosslink, the curing speed is increased, the crosslinking degree is increased, and meanwhile, the sulfonic group and the carboxyl can react with amino and active hydroxyl groups on biological tissues to form covalent bonds, so that the shearing strength and the bonding strength are improved, the swelling degree is reduced, and the cytotoxicity is reduced.
Preferably, the addition amount of the methyl propionate is 0.08-0.17% of the mass of the 2-amino-4-sulfobenzoic acid.
Preferably, the isopropanol solution in the step S3 further includes sodium dehydroacetate, and the mass ratio of the methyl propionate to the sodium dehydroacetate is 40-47: 1. When the polyurethane is subjected to graft modification, due to the existence of a benzene ring on 2-amino-4-sulfobenzoic acid, the steric hindrance is large, grafting is not facilitated, the grafting rate of the 2-amino-4-sulfobenzoic acid is low, and when the mass ratio of methyl propionate to sodium dehydroacetate is 40-47:1, the sodium dehydroacetate can cooperate with methyl propionate, so that the steric hindrance effect of the benzene ring on the 2-amino-4-sulfobenzoic acid is reduced, the nucleophilicity of the amino group on the 2-amino-4-sulfobenzoic acid is improved, the sodium dehydroacetate has strong attack capability on a carbon atom in polyurethane terminal-NCO, the grafting rate can be improved, and the higher the grafting rate is, and the better the modification effect on the polyurethane is.
Preferably, the grafting rate of the methyl propionate can reach more than 11.9%.
Provides a polyurethane adhesive, which is prepared by the preparation method of the polyurethane adhesive.
The use of 2-amino-4-sulfobenzoic acid to increase the bond strength and/or biodegradability of polyurethane adhesives is provided.
Provides the application of methyl propionate and sodium dehydroacetate in improving the grafting rate of 2-amino-4-sulfobenzoic acid on a polyurethane adhesive.
There is provided the use of a polyurethane adhesive for closing a wound.
The invention has the beneficial effects that:
1) according to the invention, 2-amino-4-sulfobenzoic acid is used for modifying polyurethane, amino on 2-amino-4-sulfobenzoic acid can react with carbon atoms in-NCO at the tail end of the polyurethane to form an amido bond, a benzene ring with hydrophilic groups, namely sulfonic acid group and carboxyl group, is introduced, the biodegradation of the polyurethane can be accelerated, the sulfonic acid group and the carboxyl group can react with the amino and the hydroxyl group in the presence of water molecules to further crosslink, the curing speed is increased, the crosslinking degree is increased, and meanwhile, the sulfonic acid group and the carboxyl group can react with the amino and active hydroxyl groups on biological tissues to form a covalent bond, so that the shearing strength and the adhesive strength are improved, the swelling degree is reduced, and the cytotoxicity is reduced;
2) according to the invention, sodium dehydroacetate is used in cooperation with methyl propionate, so that the steric hindrance effect of a benzene ring on 2-amino-4-sulfobenzoic acid can be reduced, the nucleophilicity of an amino group on 2-amino-4-sulfobenzoic acid is improved, the strong attack capability on a carbon atom in polyurethane terminal-NCO is provided, the grafting rate can be improved, and the effect is better as the grafting rate is higher.
Drawings
FIG. 1 is a graph of the infrared spectra of the polyurethane adhesives of example 1 and example 4 in test example 1 of the present invention; FIG. 2 is a graph showing the results of the measurement of the graft ratio in test example 1 of the present invention;
FIG. 3 is the result of measuring the curing time in test example 2 of the present invention;
FIG. 4 is a result of measurement of gel content in test example 2 of the present invention;
FIG. 5 is a graph showing the results of testing the shear strength and the wound adhesive strength in test example 2 of the present invention;
FIG. 6 is a result of measurement of swelling ratio in test example 2 of the present invention;
FIG. 7 is a result of measurement of in vitro biodegradation rate in test example 2 of the present invention;
FIG. 8 is a graph showing the results of measurement of cell viability in test example 2 of the present invention.
Detailed Description
Unless otherwise indicated, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety as if set forth in their entirety.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.
When an amount, concentration, or other value or parameter is given as either a range, preferred range, or a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any larger range limit or preferred value and any smaller range limit or preferred value, regardless of whether ranges are separately disclosed. For example, when a range of "1 to 5" is described, the described range should be construed as including ranges of "1 to 4", "1 to 3", "1 to 2 and 4 to 5", "1 to 3 and 5", and the like. Where numerical ranges are described herein, unless otherwise stated, the stated ranges are intended to include the endpoints of the ranges and all integers and fractions within the ranges.
In addition, the words "a" and "an" preceding an element or component of the invention are intended to mean no limitation on the number of times that the element or component appears (i.e., occurs). Thus, "a" or "an" should be understood to include one or at least one and the singular forms of an element or component also include the plural unless the singular is explicitly stated.
Embodiments of the present invention, including embodiments of the invention described in the summary section and any other embodiments described herein below, can be combined arbitrarily.
The present invention is described in detail below.
The preparation method of the polyurethane adhesive is characterized by comprising the following steps:
s1, drying of the polyol: taking castor oil and polyethylene glycol, vacuum dehydrating at the temperature of 105-115 ℃ for 2.5-3h, standing and cooling to 50-52 ℃ after the dehydration is finished;
s2, synthesis of prepolymer: under the protection of nitrogen, after the dehydrated and dried polyol is heated to 70-72 ℃, adding isophorone diisocyanate, and reacting for 6-7h under the condition of slow stirring;
s3, grafting of 2-amino-4-sulfobenzoic acid: adding an isopropanol solution containing 2-amino-4-sulfobenzoic acid and methyl propionate into the prepolymer obtained in the step S2, reacting at a constant temperature of 70-72 ℃ for 1-2h, cooling to room temperature after the reaction is finished, and storing the product in a water vapor-isolated manner for later use;
the castor oil: polyethylene glycol: isophorone diisocyanate: 2-amino-4-sulfobenzoic acid (m/m) ═ 6-9:73-84:33-42: 2-4. The methyl propionate is favorable for the reaction of amino on 2-amino-4-sulfobenzoic acid and carbon atoms in polyurethane terminal-NCO in the presence of methyl propionate to form an amido bond, a benzene ring with hydrophilic group-sulfonic group and carboxyl is introduced to accelerate the biodegradation of polyurethane, the sulfonic group and the carboxyl can react with amino and hydroxyl in the presence of water molecules to further crosslink, the curing speed is increased, the crosslinking degree is increased, and meanwhile, the sulfonic group and the carboxyl can react with amino and active hydroxyl groups on biological tissues to form covalent bonds, so that the shearing strength and the bonding strength are improved, the swelling degree is reduced, and the cytotoxicity is reduced.
Preferably, the addition amount of the methyl propionate is 0.08-0.17% of the mass of the 2-amino-4-sulfobenzoic acid.
Preferably, the isopropanol solution in the step S3 further includes sodium dehydroacetate, and the mass ratio of the methyl propionate to the sodium dehydroacetate is 40-47: 1. When the polyurethane is subjected to graft modification, due to the existence of a benzene ring on 2-amino-4-sulfobenzoic acid, the steric hindrance is large, grafting is not facilitated, the grafting rate of the 2-amino-4-sulfobenzoic acid is low, and when the mass ratio of methyl propionate to sodium dehydroacetate is 40-47:1, the sodium dehydroacetate can cooperate with methyl propionate, so that the steric hindrance effect of the benzene ring on the 2-amino-4-sulfobenzoic acid is reduced, the nucleophilicity of the amino group on the 2-amino-4-sulfobenzoic acid is improved, the sodium dehydroacetate has strong attack capability on a carbon atom in polyurethane terminal-NCO, the grafting rate can be improved, and the higher the grafting rate is, and the better the modification effect on the polyurethane is.
Preferably, the grafting rate of the methyl propionate can reach more than 11.9%.
Provides a polyurethane adhesive, which is prepared by the preparation method of the polyurethane adhesive.
The use of 2-amino-4-sulfobenzoic acid to increase the bond strength and/or biodegradability of polyurethane adhesives is provided.
Provides the application of methyl propionate and sodium dehydroacetate in improving the grafting rate of 2-amino-4-sulfobenzoic acid on a polyurethane adhesive.
There is provided the use of a polyurethane adhesive for closing a wound.
The present invention is further described in detail with reference to the following examples:
example 1:
provided is a preparation method of a polyurethane adhesive, comprising the following steps:
s1, drying of the polyol: firstly, adding 0.6g of castor oil and 7.3g of polyethylene glycol into a container, carrying out vacuum dehydration for 2.5h at 110 ℃, standing and cooling to 50 ℃ after the dehydration is finished;
s2, synthesis of prepolymer: under the protection of nitrogen, after the dehydrated and dried polyol is heated to 70 ℃, 4.2g of isophorone diisocyanate is added, and the reaction is carried out for 6h under the condition of slow stirring;
s3, grafting of 2-amino-4-sulfobenzoic acid: and (3) adding 30mL of isopropanol solution containing 4g of 2-amino-4-sulfobenzoic acid and 5.8mg of methyl propionate into the prepolymer obtained in the step S2, reacting at the constant temperature of 70 ℃ for 1h, cooling to room temperature after the reaction is finished, and storing the product in a water vapor-isolated manner for later use.
Example 2:
methyl propionate was not added and the remainder was identical to example 1.
Example 3:
no 2-amino-4-sulfobenzoic acid was added, and the remainder was identical to example 1.
Example 4:
no 2-amino-4-sulfobenzoic acid and methyl propionate were added, the remainder being identical to example 1.
Example 5:
provided is a preparation method of a polyurethane adhesive, comprising the following steps:
s1, drying of the polyol: firstly, adding 0.6g of castor oil and 7.3g of polyethylene glycol into a container, carrying out vacuum dehydration for 2.5h at 110 ℃, standing and cooling to 50 ℃ after the dehydration is finished;
s2, synthesis of prepolymer: under the protection of nitrogen, after the dehydrated and dried polyol is heated to 70 ℃, 4.2g of isophorone diisocyanate is added, and the reaction is carried out for 6h under the condition of slow stirring;
s3, grafting of 2-amino-4-sulfobenzoic acid: and (3) adding 30mL of isopropanol solution containing 4g of 2-amino-4-sulfobenzoic acid, 5.8mg of methyl propionate and 0.13mg of sodium dehydroacetate into the prepolymer obtained in the step S2, reacting at the constant temperature of 70 ℃ for 1h, cooling to room temperature after the reaction is finished, and storing the product in a water vapor-isolated manner for later use.
Example 6:
the amount of sodium dehydroacetate added was 0.12mg, the remainder being identical to that of example 5.
Example 7:
the amount of sodium dehydroacetate added was 0.15mg, the remainder being identical to that of example 5.
Test example 1:
and (3) Fourier transform infrared spectrum characterization: adopting a potassium bromide tabletting method, carrying out sample application and coating, wherein the scanning range is 4000-5000 cm-1. The infrared spectra of the polyurethane adhesives of example 1 and example 4 are shown in FIG. 1.
Determination of the graft ratio: the grafting ratio of 2-amino-4-sulfobenzoic acid in the polyurethane adhesive was determined by infrared spectroscopy. The results of the graft ratio measurement are shown in FIG. 2.
As can be seen from FIG. 1, 2250cm in example 1 is compared with that in example 4-1The infrared absorption peak of the site-NCO is reduced and is 1547cm at 1532--1The absorption peaks of free-state and associated-state-C ═ O in the intermediate amide were found at 800-900cm-1The absorption peak of the bending vibration of the tri-substituted aromatic ring surface is at 17520cm-1Found therein as a stretching vibration absorption peak of-C ═ O of the carboxyl group, 2642cm-1An O-H absorption peak of the carboxyl group was found, 1174cm-1And 1062cm-1Antisymmetric and symmetric telescopic vibration absorption peaks of sulfonic acid group-S ═ O are found, and the 2-amino-4-sulfonic benzoic acid structure is proved to be grafted into polyurethane in an amido bond forming mode. As can be seen from FIG. 2, the grafting ratio of examples 3 and 4 is 0, the grafting ratio of example 1 is significantly higher than that of example 2, the grafting ratio of example 5 is significantly higher than that of examples 1, 6 and 7, and the grafting ratio of examples 1, 6 and 7 is significantly higher than that of examples 1, 6 and 7There is no obvious difference between them, which means that,
test example 2:
1. determination of the curing time: the measurement was performed by stirring (also by vial tilting). Briefly, the polymer solution was added to a glass vial having a diameter of 30mm, and a Teflon stirring magneton was added, and magnetically rotated at 300 rpm. Then, a 5mol/L aqueous sodium hydroxide solution and a 0.1mol/L solution of di-n-butylamine were added to the vial. The time(s) from the start of the addition of the di-n-butylamine solution to the stop of the rotation of the magnetons was recorded. The results of the curing time measurements are shown in FIG. 3.
2. Preparing a polyurethane adhesive film: weighing a proper amount of adhesive sample in a round flat-bottom polytetrafluoroethylene mold with a wet surface, uniformly leveling the adhesive sample by utilizing the self fluidity of the colloid, naturally drying the adhesive sample at room temperature, forming the adhesive film, drying the adhesive film in a vacuum drying oven at 60 ℃, taking out the adhesive film, and storing the adhesive film in a vacuum dryer.
3. Determination of the degree of crosslinking: at 25 ℃, taking the polyurethane film, weighing and recording as W0And then the mixture was placed in a 20-fold mass of solvent N, N-Dimethylformamide (DMF). Taking out a polyurethane sample every 10min, sucking a solvent on the surface of the polyurethane sample by using filter paper, weighing the mass of the sample by using a precision balance, recording the mass of the sample, and immersing the polyurethane sample in deionized water with the mass of 50 times when the weight of the sample does not change any more. Soaking at 40 deg.C for 2 d. The solvent DMF in the polyurethane sample is fully replaced, and the sample after solvent removal is dried in an air-blast drying oven at the temperature of 80 ℃. After the solvent replacement and the drying step are repeated for two times, the quality of the dried polyurethane sample is not changed any more, and the drying quality W of the sample is recorded1。
The gel content (GR) is calculated as follows:
GR＝(W1/W0)×100％
the results of the gel content measurement are shown in FIG. 4.
4. And (3) testing mechanical strength:
the shear strength, wound bond strength and burst strength of the adhesive samples were determined according to the American society for testing and materials ASTM F2255-05, ASTM F2458-05 and ASTM F2392-04 standards, respectively. The repeated test times n are more than or equal to 5.
4.1 shear strength test with fresh pigskin having a wet surface, cut to a size of 25mm × 50mm the adhesive product solution (50 μ L) is applied to the end zone (25mm × 10mm) of one pigskin, then the end of the other pigskin is carefully aligned with the coated area to allow the two pigskins to be tightly fitted, a weight is pressed perpendicular to the fitting site and then cured at 37℃ after which time the test is carried out on a universal material testing machine at a tensile speed of 5mm/min and the maximum shear strength (kPa) during separation of the two pigskins is recorded.
4.2 wound adhesion strength test-fresh pigskin with wet surface was used to simulate a torn tissue with a cut size of 25mm × 50mm cut to break at the middle of the pigskin using a sharp blade and then applied with an adhesive sample solution (50 μ L) at the cut cross-section (25mm × 5 mm.) two small pieces of pigskin separated were bonded by the product coated on the cross-section, set with a slight pressure applied perpendicular to the cross-section and then left to cure at ambient or 37 deg.C.
5. Measurement of swelling ratio:
preparation of Phosphate Buffered Saline (PBS): 80g NaCl, 2g KCl and 2.4g KH were weighed2PO4And 14.4gNa2HPO4Dissolving the mixture in 800mL of deionized water, adding a proper amount of hydrochloric acid to adjust the pH value to 7.4, and adding deionized water to a constant volume of 1L.
Placing the adhesive film cut into 30mm × 30mm in a 60 deg.C oven to dry to constant weight, and accurately weighing the dry weight of the film and recording as WdThen, the gelatin membrane is soaked in PBS buffer solution at 37 ℃, and is taken out and weighed (Ws) after being soaked for 4 hours, 12 hours, 24 hours and 48 hours respectively. Each sample was assayed in 3 replicates and the average was calculated. The water absorption swelling ratio was as follows:
swelling ratio (%) - (W)s-Wd)/Wd×100％
The measurement results of the swelling ratio are shown in FIG. 6.
6. Determination of biodegradation rate: the sample film dried to constant weight is weighed (M)1) And cut to 2cm × 2cm, then placed in 1.5mg/mL egg white in PBS buffer, maintained at 37 ℃ in the test environment, samples were taken at set time intervals (1 week), washed with distilled water and dried in a vacuum oven for 48h, and then weighed again (M2) to obtain weight changes, and three replicates were performed for each sample.
And stopping monitoring the quality of the glue film after 7 weeks of degradation. Calculating the in vitro biodegradation rate:
the percent degradation rate (%) - (M1-M2)/M2 × 100 was 100%.
The results of the in vitro biodegradation rate measurements are shown in FIG. 7.
7. Cytotoxicity test:
preparing a glue film sample: a0.2 g film sample was placed in a sterile sample tube. Then, 1mL of absolute ethanol was added to each tube and sterilized under uv light for 1 h. After the excess alcohol on the sample had evaporated, the sample was washed several times with sterile PBS buffer (pH 7.4).
Cell culture and toxicity assay cell culture medium (DMEM high glucose medium containing 10% by volume Fetal Bovine Serum (FBS) and 1% streptomycin) was added to sample tubes and the samples were incubated with medium at 37 ℃ for 72h, during which time fresh L929 mouse fibroblasts were treated with 2 × 103Cell/well Density was seeded into 96-well plates each containing 1mL of cell culture medium and allowed to stand at 37 ℃ with 5% CO2And performing adherent culture for 24 hours in the environment. After the end of the incubation, 100. mu.L of sample medium was added to each well by changing to fresh medium, and the fresh medium of the uncultured sample was placed at 37 ℃ for incubation for 24 hours as a control, and 100. mu.L of fresh medium containing 1% MTT (5mg/mL MTT in PBS buffer) was pipetted into the wells. After 4h, the medium was aspirated and 100 μ L DMSO was removed to dissolve formazan crystals. Finally, the light absorbance values were read on a microplate reader based on the linear absorbance of the number of viable cells in the culture. The results of the cell viability assay are shown in FIG. 8.
As can be seen from fig. 3, the curing time of the polyurethane adhesive in example 1 is significantly lower than that of examples 2, 3 and 4, the curing time of example 5 is significantly lower than that of examples 1, 6 and 7, and there is no significant difference in the curing time of examples 1, 6 and 7; as can be seen from fig. 4 and 5, the gel content, the shear strength and the wound adhesion strength of the polyurethane adhesive film prepared in example 1 are significantly greater than those of examples 2, 3 and 4, the gel content, the shear strength and the wound adhesion strength of example 5 are significantly greater than those of examples 1, 6 and 7, and there is no significant difference between examples 1, 6 and 7; as can be seen from fig. 6, the swelling ratios of the polyurethane adhesive films prepared in example 1 are significantly lower than those of examples 2, 3 and 4, the swelling ratio of example 5 is significantly lower than those of examples 1, 6 and 7, and there is no significant difference in the swelling ratios of examples 1, 6 and 7; as can be seen from fig. 7, the in vitro degradation rate of the polyurethane adhesive film prepared in example 1 after 7 weeks is more than 44%, and is significantly higher than that of examples 2, 3 and 4, and the examples 2, 3 and 4 have no significant difference, the curves of examples 3 and 4 are partially overlapped, the in vitro degradation rate of the polyurethane adhesive film prepared in example 5 after 7 weeks is more than 60%, and is significantly higher than that of examples 1, 6 and 7, and the curves of examples 1, 6 and 7 have no significant difference, and the curves of examples 6 and 7 are partially overlapped; as can be seen from fig. 8, the cell survival rate of the polyurethane gel film prepared in example 1 is significantly higher than that of examples 2, 3 and 4, the cell survival rate of example 5 is significantly higher than that of examples 1, 6 and 7, and there is no significant difference among examples 1, 6 and 7; this shows that, the methyl propionate is favorable for the amino group on the 2-amino-4-sulfobenzoic acid to react with the carbon atom in the polyurethane terminal-NCO in the presence of amide bond, the benzene ring with hydrophilic group-sulfonic group and carboxyl group is introduced, which can accelerate the biodegradation of polyurethane, the sulfonic group and carboxyl group can react with the amino group and hydroxyl group in the presence of water molecule to further crosslink, increase the curing speed and crosslinking degree, and can react with the amino group and active hydroxyl group on biological tissue to form covalent bond, thereby improving the shearing strength and adhesive strength, reducing the swelling degree, and reducing the cytotoxicity; when the mass ratio of the methyl propionate to the sodium dehydroacetate is 40-47:1, the sodium dehydroacetate can cooperate with the methyl propionate to reduce the steric hindrance of a benzene ring on the 2-amino-4-sulfobenzoic acid, improve the nucleophilicity of an amino group on the 2-amino-4-sulfobenzoic acid, have strong attack capacity on a carbon atom in polyurethane terminal-NCO and can improve the grafting rate, the higher the grafting rate is, the better the modification effect on polyurethane is, and when the addition amount of the sodium dehydroacetate is larger than or smaller than the range, no obvious effect is produced on the grafting of the 2-amino-4-sulfobenzoic acid and the modification of the polyurethane.
Conventional techniques in the above embodiments are known to those skilled in the art, and therefore, will not be described in detail herein.
The above embodiments are merely illustrative, and not restrictive, and those skilled in the art can make various changes and modifications without departing from the spirit and scope of the invention. Therefore, all equivalent technical solutions also belong to the scope of the present invention, and the protection scope of the present invention should be defined by the claims.
Claims (8)
1. A preparation method of a polyurethane adhesive is characterized by comprising the following steps:
s1, drying of the polyol: taking castor oil and polyethylene glycol, vacuum dehydrating at the temperature of 105-115 ℃ for 2.5-3h, standing and cooling to 50-52 ℃ after the dehydration is finished;
s2, synthesis of prepolymer: under the protection of nitrogen, after the dehydrated and dried polyol is heated to 70-72 ℃, adding isophorone diisocyanate, and reacting for 6-7h under the condition of slow stirring;
s3, grafting of 2-amino-4-sulfobenzoic acid: adding an isopropanol solution containing 2-amino-4-sulfobenzoic acid and methyl propionate into the prepolymer obtained in the step S2, reacting at a constant temperature of 70-72 ℃ for 1-2h, cooling to room temperature after the reaction is finished, and storing the product in a water vapor-isolated manner for later use;
the castor oil: polyethylene glycol: isophorone diisocyanate: 2-amino-4-sulfobenzoic acid (m/m) ═ 6-9:73-84:33-42: 2-4.
2. The method of claim 1, wherein: the addition amount of the methyl propionate is 0.08-0.17% of the mass of the 2-amino-4-sulfobenzoic acid.
3. The method of claim 1, wherein: the isopropanol solution in the step S3 further comprises sodium dehydroacetate, and the mass ratio of the methyl propionate to the sodium dehydroacetate is 40-47: 1.
4. The method of claim 3, wherein: the grafting rate of the methyl propionate can reach more than 11.9 percent. .
5. A polyurethane adhesive, characterized by: the preparation is carried out by the preparation method described in any one of claims 1 to 4.
Use of 2-amino-4-sulfobenzoic acid to increase the bond strength and or biodegradability of a polyurethane adhesive.
7. The application of methyl propionate and sodium dehydroacetate in improving the grafting rate of 2-amino-4-sulfobenzoic acid on a polyurethane adhesive.
8. Use of a polyurethane adhesive of claim 5 to close a wound.
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| CN112266456A (en) * | 2020-11-05 | 2021-01-26 | 中国科学院长春应用化学研究所 | Biodegradable carbon dioxide-based polyurethane elastomer and preparation method thereof |
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