CN112206344A - Preparation method of hemostatic sponge - Google Patents
Preparation method of hemostatic sponge Download PDFInfo
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- CN112206344A CN112206344A CN201910628744.0A CN201910628744A CN112206344A CN 112206344 A CN112206344 A CN 112206344A CN 201910628744 A CN201910628744 A CN 201910628744A CN 112206344 A CN112206344 A CN 112206344A
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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
- A61L24/0036—Porous materials, e.g. foams or sponges
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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
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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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
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4244—Polycondensates having carboxylic or carbonic ester groups in the main chain containing oxygen in the form of ether groups
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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
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
- C08G18/428—Lactides
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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
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/44—Polycarbonates
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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
- C08G18/6633—Compounds of group C08G18/42
- C08G18/6637—Compounds of group C08G18/42 with compounds of group C08G18/32 or polyamines of C08G18/38
- C08G18/664—Compounds of group C08G18/42 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/64—Polyesters containing both carboxylic ester groups and carbonate groups
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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
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/66—Polyesters containing oxygen in the form of ether groups
- C08G63/664—Polyesters containing oxygen in the form of ether groups derived from hydroxy carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/0061—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof characterized by the use of several polymeric components
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/30—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by mixing gases into liquid compositions or plastisols, e.g. frothing with air
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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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2375/00—Characterised by the use of polyureas or polyurethanes; Derivatives of such polymers
- C08J2375/04—Polyurethanes
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2471/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
- C08J2471/02—Polyalkylene oxides
Abstract
The invention provides a preparation method of a hemostatic sponge, which comprises a block prepolymer synthesis reaction, a first precipitation purification treatment, a first drying treatment, a polyurethane synthesis reaction, a second precipitation purification treatment, a second drying treatment, a stirring foaming treatment, normal-pressure freezing, a freeze drying treatment and a sterilization treatment which are sequentially carried out. According to the preparation method of the hemostatic sponge, the product obtained through the block prepolymer synthesis reaction is subjected to the first precipitation purification treatment and the first drying treatment in sequence, then the subsequent polyurethane synthesis reaction is performed, and the product obtained through the polyurethane synthesis reaction is subjected to the second precipitation purification treatment and the second drying treatment in sequence, then the subsequent stirring foaming treatment is performed, so that harmful byproducts and residual monomers possibly existing in the block prepolymer synthesis reaction and the polyurethane synthesis reaction can be effectively removed, and the application safety of the hemostatic sponge is effectively improved.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to a preparation method of a hemostatic sponge.
Background
The otolaryngological operation is a common surgical operation in the medical and cosmetic industries, because the range of the operation position is small, the position is deep, especially the nasal sinuses and the like are mostly in a cavity structure, the postoperative can not be sutured to stop bleeding, the hemostasis is stuffed by gauze or expanded sponge and the like which are commonly used clinically, and meanwhile, the cavity can be supported, the wound can be prevented from being adhered or restenosis, so that the wound healing is promoted, and the pain of a patient is relieved.
Chinese patent application publication No. CN104031287A discloses a degradable nasal hemostatic sponge and a preparation method thereof, wherein the preparation method of the hemostatic sponge directly reacts the synthesized block prepolymer with a chain extender to prepare polyurethane, and the obtained polyurethane is directly added into dioxane and chitosan aqueous solution to form a solution for further preparing the hemostatic sponge. As is common knowledge in the art, since side reactions are easy to occur in chemical reactions and the reaction conversion rate is difficult to reach 100%, monomers and byproducts are easy to remain in the preparation method of CN104031287A, which in turn affects the safety of application of the hemostatic sponge.
Therefore, there is a need to develop a new method for preparing hemostatic sponge to solve the above problems of the prior art.
Disclosure of Invention
The invention aims to provide a preparation method of a hemostatic sponge, which aims to solve the problem that in the prior art, the application safety of the hemostatic sponge is affected due to the fact that monomers and harmful byproducts are easy to remain.
In order to achieve the above object, the preparation method of the hemostatic sponge of the present invention comprises:
s1: taking polyhydric alcohol and an ester monomer as reactants, taking stannous octoate or dibutyltin dilaurate as a catalyst, carrying out a block prepolymer synthesis reaction for 0.5-24 hours under anhydrous and oxygen-free conditions and at the temperature of 120-180 ℃, and then sequentially carrying out first precipitation purification treatment and first drying treatment on a product obtained by the block prepolymer synthesis reaction to obtain a dried polyester polyol block prepolymer;
s2: dissolving the polyester polyol block prepolymer obtained after the first drying treatment and an isocyanate monomer in an organic good solvent to form a mixed solution, carrying out pre-reaction on the mixed solution for 4-12 hours at a reaction temperature of 60-100 ℃ under the protection of inert gas, then adding stannous octoate or dibutyltin dilaurate as a catalyst into the mixed solution, adding 1, 4-butanediol as a chain extender, and continuously reacting for 4-12 hours at a temperature of 60-100 ℃ to complete a polyurethane synthesis reaction;
s3: sequentially carrying out second precipitation purification treatment and second drying treatment on a product obtained after the polyurethane synthesis reaction, mixing the obtained solid polyurethane with a foaming agent to form a polyurethane solution, adding a hydrophilic polymer into the polyurethane solution, and then carrying out stirring foaming treatment for 20-120 minutes to obtain a foaming solution;
s4: and (3) placing the foaming solution into a mold, freezing the foaming solution at the temperature of not higher than-200 ℃ for 3-24 hours under normal pressure, then carrying out freeze drying treatment for 6-24 hours, and then carrying out sterilization treatment on the obtained freeze-dried substance to obtain the hemostatic sponge.
The preparation method of the hemostatic sponge has the beneficial effects that: the method comprises the steps of sequentially carrying out first precipitation purification treatment and first drying treatment on a product obtained through the block prepolymer synthesis reaction, carrying out subsequent polyurethane synthesis reaction on the obtained dried polyester polyol block prepolymer, an isocyanate monomer and a chain extender, and sequentially carrying out second precipitation purification treatment and second drying treatment on the product obtained through the polyurethane synthesis reaction, and then configuring a polyurethane solution, so that harmful byproducts and residual monomers possibly existing in the block prepolymer synthesis reaction and the polyurethane synthesis reaction can be effectively removed, and the application safety of the hemostatic sponge is effectively improved.
Preferably, in the step S1, the molar ratio of the polyol to the ester monomer is 1:10-1:50, the mass of the catalyst accounts for 0.01-5% of the mass of the reactant, and the weight average molecular weight of the polyol is 200-20000. The beneficial effects are that: is favorable for improving the strength of the hemostatic sponge.
Further preferably, the polyhydric alcohol is any one or more of polyethylene glycol, polypropylene glycol, polytetramethylene glycol and polytetrahydrofuran glycol, and the ester monomer is any one or more of lactide, glycolide, caprolactone, trimethylene carbonate and p-dioxanone.
Preferably, in step S1, dichloromethane is added to the product obtained by the block prepolymer synthesis reaction to form a mixed solution, and then any one of absolute ethyl alcohol, methanol, ethanol or water is used as a precipitation washing solution to perform the first precipitation purification treatment, so as to obtain the wet polyester polyol block prepolymer. The beneficial effects are that: harmful byproducts and residual monomers possibly existing in the block prepolymer synthesis reaction and the polyurethane synthesis reaction can be effectively removed, and the application safety of the hemostatic sponge is effectively improved.
Further preferably, the polyester polyol block prepolymer in a wet state is vacuum-dried at 40 to 80 ℃ to complete the first drying treatment.
Preferably, the dried polyester polyol block prepolymer is stored frozen at-20 ℃ until use. The beneficial effects are that: prevent the deterioration of the dried polyester polyol block prepolymer and is beneficial to batch or centralized production.
Preferably, in the step S2, the molar ratio of the polyester polyol block prepolymer to the isocyanate monomer is 1:1-1:1.5, the molar ratio of the isocyanate monomer to the 1, 4-butanediol is 1:1-1:1.5, 2.7-5 g of the isocyanate monomer is added to 100ml of the good organic solvent, and the mass of the catalyst is 0.01% o to 5% o of the total mass of the polyester polyol block prepolymer and the isocyanate monomer. The beneficial effects are that: the reaction yield is improved, and the obtained hemostatic sponge has good strength and elasticity by adjusting the proportion of the hard segment to the soft segment.
Preferably, in the step S3, the second precipitation purification process is performed on the product obtained after the polyurethane synthesis reaction by using any one of absolute ethanol, methanol, ethanol or water as a precipitation washing solution, and then vacuum drying is performed at 40 to 80 ℃ to complete the second drying process. The beneficial effects are that: harmful byproducts and residual monomers possibly existing in the block prepolymer synthesis reaction and the polyurethane synthesis reaction can be effectively removed, and the application safety of the hemostatic sponge is effectively improved.
Preferably, in step S3, the solid polyurethane accounts for 1-50% by mass of the polyurethane solution, and the hydrophilic polymer accounts for not more than 30% by mass of the solid polyurethane. The beneficial effects are that: the hydrophilic property of the hemostatic sponge is improved through the hydrophilic polymer, so that the hemostatic sponge is favorably attached to the affected part better in the subsequent use process.
Further preferably, the hydrophilic polymer is polyethylene glycol, povidone or polyvinyl alcohol, the weight average molecular weights of the polyethylene glycol and the polyvinyl alcohol are both 600-.
Preferably, in step S3, after the hydrophilic polymer and the drug are added to the polyurethane solution, the stirring and foaming process is performed, where the drug accounts for 0.1% to 1.5% by mass of the solid polyurethane, and the drug is an antibacterial drug or an anti-inflammatory drug.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are a part of the embodiments of the present invention, but not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs. As used herein, the word "comprising" and similar words are intended to mean that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items.
Aiming at the problems in the prior art, the embodiment of the invention provides a preparation method of a hemostatic sponge, which comprises the following steps:
s1: taking polyhydric alcohol and an ester monomer as reactants, taking stannous octoate or dibutyltin dilaurate as a catalyst, carrying out a block prepolymer synthesis reaction for 0.5-24 hours under anhydrous and oxygen-free conditions and at the temperature of 120-180 ℃, and then sequentially carrying out first precipitation purification treatment and first drying treatment on a product obtained by the block prepolymer synthesis reaction to obtain a dried polyester polyol block prepolymer;
s2: dissolving the polyester polyol block prepolymer obtained after the first drying treatment and an isocyanate monomer in an organic good solvent to form a mixed solution, carrying out pre-reaction on the mixed solution for 4-12 hours at a reaction temperature of 60-100 ℃ under the protection of inert gas, then adding stannous octoate or dibutyltin dilaurate as a catalyst into the mixed solution, adding 1, 4-butanediol as a chain extender, and continuously reacting for 4-12 hours at a temperature of 60-100 ℃ to complete a polyurethane synthesis reaction;
s3: sequentially carrying out second precipitation purification treatment and second drying treatment on a product obtained after the polyurethane synthesis reaction, mixing the obtained solid polyurethane with a foaming agent to form a polyurethane solution, adding a hydrophilic polymer into the polyurethane solution, and then carrying out stirring foaming treatment for 20-120 minutes to obtain a foaming solution;
s4: and (3) placing the foaming solution into a mold, freezing the foaming solution at the temperature of not higher than-200 ℃ for 3-24 hours under normal pressure, then carrying out freeze drying treatment for 6-24 hours, and then carrying out sterilization treatment on the obtained freeze-dried substance to obtain the hemostatic sponge.
In step S1 of some embodiments of the present invention, the molar ratio of the polyol to the ester monomer is 1:10-1:50, the mass of the catalyst accounts for 0.01 ‰ -5 ‰ of the mass of the reactant, the weight average molecular weight of the polyol is 200-.
In some embodiments of the invention, the lactide is D, L-lactide.
In step S1 according to some embodiments of the present invention, dichloromethane is added to the product obtained by the synthesis reaction of the block prepolymer to form a mixed solution, and then one of absolute ethanol, methanol, ethanol and water is used as a precipitation washing solution to separate the wet polyester polyol block prepolymer, so as to complete the first precipitation purification treatment, and the wet polyester polyol block prepolymer is vacuum-dried at 40-80 ℃ for 24-48 hours, so as to complete the first drying treatment.
In step S1 of some embodiments of the present invention, the dried polyester polyol block prepolymer is stored at-20 ℃ for future use, so as to prevent the dried polyester polyol block prepolymer from deteriorating, and facilitate batch production or centralized production.
In step S2 of some embodiments of the present invention, a molar ratio of the polyester polyol block prepolymer to the isocyanate monomer is 1:1-1:1.5, a molar ratio of the isocyanate monomer to the 1, 4-butanediol is 1:1-1:1.5, 2.7 to 5 g of the isocyanate monomer is added to 100ml of the good organic solvent, and a mass of the catalyst is 0.01% to 5% of a total mass of the polyester polyol block prepolymer and the isocyanate monomer.
In step S2 of some embodiments of the present invention, the organic good solvent is a good solvent of the polyester polyol block prepolymer, and specifically is N, N '-dimethylformamide or N, N' -dimethylacetamide.
In some embodiments of the present invention, the isocyanate monomer is lysine isocyanate or 1, 4-butylene diisocyanate.
In step S3 of some embodiments of the present invention, the second precipitation purification process is performed on the product obtained after the polyurethane synthesis reaction by using any one of absolute ethanol, methanol, ethanol, or water as a precipitation washing solution, and then vacuum drying is performed at 40 to 80 ℃ for 24 to 48 hours to complete the second drying process.
In step S3 of some embodiments of the present invention, the solid polyurethane accounts for 1-50% by mass of the polyurethane solution, and the hydrophilic polymer accounts for not more than 30% by mass of the solid polyurethane. The hydrophilic polymer is polyethylene glycol, polyvidone or polyvinyl alcohol, the weight average molecular weights of the polyethylene glycol and the polyvinyl alcohol are both 600-20000, the polyvidone is polyvidone K30, polyvidone K60 or polyvidone K90, and the foaming agent is water.
In step S3 of some embodiments of the present invention, the hydrophilic polymer and the drug are added to the polyurethane solution to enhance the antibacterial property of the hemostatic sponge. The medicine is an antibacterial medicine or an anti-inflammatory medicine and accounts for 0.1-1.5% of the solid polyurethane by mass. The antibacterial drug is helpful for enhancing the antibacterial performance of the hemostatic sponge, and the anti-inflammatory drug can endow the hemostatic sponge with an anti-inflammatory effect, so that the affected part can be rapidly healed.
The technical solutions of the embodiments of the present invention are explained in detail by the following embodiments 1 to 3.
Example 1
This example provides a method of making a first hemostatic sponge. The method specifically comprises the following steps:
in the step S1, 50 g of polyethylene glycol with the weight average molecular weight of 1500, 40 g of D, L-lactide, 60 g of trimethylene carbonate and 0.13 g of stannous octoate are added into a round-bottom flask and mixed uniformly; performing 3 times of vacuum-nitrogen filling replacement operations in the round-bottom flask so as to enable the round-bottom flask to be in an anhydrous and oxygen-free reaction environment; keeping the round-bottom flask in a nitrogen atmosphere, heating the round-bottom flask to enable the internal reaction temperature to reach 130 ℃, and then carrying out 6-hour block prepolymer synthesis reaction to obtain a block prepolymer mixture; adding dichloromethane into the block prepolymer mixture to form a mixed solution, and then performing first precipitation purification treatment by using purified water as a precipitation washing solution until a wet polyester polyol block prepolymer and a first clear solution are obtained; finally, vacuum drying the wet polyester polyol block prepolymer at 40 ℃ to finish the second drying treatment to obtain a dried polyester polyol block prepolymer; and (3) freezing and storing the dried polyester polyol block prepolymer at-20 ℃ for later use.
In the step S2, 40 g of the dried polyester polyol block prepolymer is thawed and then added into a reaction bottle together with 2.7 g of lysine isocyanate, and 100mL of N, N' -dimethylformamide is added into the reaction bottle to dissolve the polyester polyol block prepolymer and the lysine isocyanate; performing 3 times of vacuum-nitrogen filling replacement operations in the reaction bottle so as to enable the reaction bottle to be in an anhydrous and oxygen-free reaction environment; keeping the reaction bottle in a nitrogen atmosphere, heating the reaction bottle until the internal reaction reaches 80 ℃, and then carrying out pre-reaction for 4 hours; after the pre-reaction is finished, adding 0.05 g of stannous octoate and 1 g of 1, 4-butanediol into the reaction bottle, and then performing 3 times of vacuum-nitrogen filling replacement operations in the reaction bottle so as to enable the reaction bottle to be in an anhydrous and oxygen-free reaction environment; the reaction flask was kept under a nitrogen atmosphere and at a reaction temperature of 80 ℃ for 6 hours to complete the polyurethane synthesis reaction.
In the step S3, performing a second precipitation purification treatment on the product obtained after the polyurethane synthesis reaction with absolute ethyl alcohol as a precipitation washing solution until a second clear solution and a precipitate are obtained by separation, and performing vacuum drying on the precipitate at 60 ℃ to complete the second drying treatment to obtain solid polyurethane; 10 g of the solid polyurethane, 0.5 g of polyethylene glycol having a weight average molecular weight of 4000 and 500mL of purified water were mixed and subjected to a stirring foaming treatment at a temperature of room temperature to 60 ℃ for 20 minutes to sufficiently dissolve the solid polyurethane and form a foaming liquid.
In the step S4, pouring the foaming liquid into a mold, and then transferring the mold into a freeze-dryer; after the temperature in the freeze dryer is reduced to-230 ℃, normal-pressure freezing is carried out for 3 hours; after the normal pressure freezing is finished, vacuumizing the freeze dryer, and carrying out freeze drying treatment for 12 hours at the temperature of-230 ℃; and packaging the freeze-dried substance obtained by the freeze drying treatment, and then irradiating the freeze-dried substance by using cobalt 60 for sterilization treatment to obtain the first hemostatic sponge.
Example 2
This example provides a method for preparing a second hemostatic sponge that differs from the method for preparing the first hemostatic sponge of example 1 in that:
in the step S1, the weight average molecular weight of the polyethylene glycol is 1,000, the mass of the D, L-lactide is 60 g, 40 g of caprolactone is added into the round-bottom flask to replace the trimethylene carbonate, the reaction temperature of the block prepolymer synthesis reaction is 170 ℃, the reaction time is 2 hours, the precipitation washing liquid used in the first precipitation purification treatment is absolute ethyl alcohol, and the temperature of the first drying treatment is 70 ℃.
In the step S2, adding N, N' -dimethylacetamide to the reaction flask to dissolve the polyester polyol block prepolymer and the lysine isocyanate; the reaction time of the pre-reaction is 5 hours; and keeping the reaction flask internally provided with a nitrogen atmosphere and at a reaction temperature of 80 ℃, and continuing the reaction for 8 hours to complete the polyurethane synthesis reaction.
In the step S3, the precipitation washing liquid of the second precipitation purification treatment is methanol, the temperature of the second drying treatment is 50 ℃, the mass of the polyethylene glycol is 0.2 g, the weight average molecular weight is 6000, the volume of the purified water is 400 ml, and the time of the stirring foaming treatment is 120 minutes.
In the step S4, the temperature in the freeze-drying machine is-200 ℃, the time of the normal-pressure freezing is 4 hours, the time of the freeze-drying treatment is 16 hours, and the sterilization treatment is performed by electron beams.
Example 3
This example provides a method for preparing a third hemostatic sponge that differs from the method for preparing the first hemostatic sponge of example 1 in that:
in the step S1, the mass of the D, L-lactide is 60 g, the mass of the trimethylene carbonate is 40 g, the reaction temperature of the block prepolymer synthesis reaction is 120 ℃, and the reaction time is 12 hours; the temperature of the first drying treatment was 50 ℃.
In the step S2, 5 g of 1, 4-butanediol is added to the reaction flask instead of 2.7 g of lysine isocyanate, and the mass of the 1, 4-butanediol is 2 g; the reaction flask was kept under a nitrogen atmosphere and maintained at a reaction temperature of 85 ℃ for further 5 hours to complete the polyurethane synthesis reaction.
In the step S3, the temperature of the second drying treatment is 45 ℃, the weight average molecular weight of the polyethylene glycol is 6000, the mass of the polyethylene glycol is 0.1 g, the volume of the purified water is 400 ml, and 0.09 g of amoxicillin is further added to the purified water as an antibacterial agent.
In the step S4, the temperature in the freeze-drying machine is-200 ℃, and the freeze-drying time is 24 hours.
Comparative example
This control example provides petrolatum gauze as a reference sample, which is manufactured by Ware, Inc. of New rural area, cat # 1810026.
The first hemostatic sponge of example 1, the second hemostatic sponge of example 2, the third hemostatic sponge of example 3, and the petrolatum gauze of the control example were each cut out into sub-samples of different sample numbers of the same size and weight, and were each characterized for water absorption. Specifically, the water absorption performance characteristics of the hemostatic sponge and the vaseline gauze are the same in dry weight.
The specific characterization method of the water absorption performance is as follows: each test sample was soaked in 20 ml of PBS buffer solution at 37 ℃ for 4 hours, taken out, sucked to dry the running water on the surface of the test sample, weighed to obtain a wet weight, and the water absorption of each test sample was calculated. The water absorption is the percentage of the added weight of the test sample to the dry weight of the test sample, and the specific test results are shown in table 1.
TABLE 1
As can be seen from table 1, the water absorption rate of the first, second and third hemostatic sponges can reach 2362% -2915%, while the water absorption rate of the vaseline gauze is only 152% -246%, which shows that the hemostatic sponge obtained by the preparation method of the embodiment of the present invention has good water absorption performance.
In the embodiment of the invention, 8 New Zealand white rabbits with the same breeding age and similar weight are randomly divided into 4 groups, each group comprises two rabbits, and the hemostatic performances of the first hemostatic sponge, the second hemostatic sponge, the third hemostatic sponge and the vaseline gauze with the same size and thickness are respectively characterized.
The specific characterization method of the hemostatic performance comprises the following steps: fixing the anesthetized New Zealand white rabbit on an operating table, and scratching the nasal septum of the New Zealand white rabbit by using a blade to cause wound bleeding; fixing a test sample on the surface of the wound surface, and recording the average hemostasis time of the wound surface for stopping bleeding; the test sample is taken down after two days, the difficulty degree of the taking-out process is recorded, and the condition of secondary bleeding is observed. The nasal septal scratch area was the same for each new zealand rabbit. See table 2 for statistical results.
TABLE 2
As can be seen from table 2, in the preparation method of the embodiment of the present invention, the foaming solution obtained by mixing the solid polyurethane, the foaming agent and the hydrophilic polymer is subjected to normal pressure freezing and freeze drying to obtain the hemostatic sponge, and the hydrophilic polymer is added, and the main component of the hemostatic sponge is polyurethane, which has a certain biocompatibility, so that the average hemostatic time is significantly better than that of the vaseline gauze, which is easy to take out and has no secondary bleeding phenomenon, while the vaseline gauze is difficult to take out and is easy to cause secondary damage to the healed wound, so that the secondary bleeding phenomenon is observed.
In the embodiment of the invention, escherichia coli ATCC25922 and staphylococcus aureus ATCC6538 are respectively used as strains, and the third hemostatic sponge and the vaseline gauze are respectively cut into three subsamples with the sizes of 1 cm multiplied by 1 cm so as to respectively perform antibacterial performance characterization.
The specific method for representing the antibacterial performance comprises the following steps: diluting the strain by 500 times with nutrient broth to obtain a bacterial suspension, wherein the OD600 value of the bacterial suspension is 1; adding 0.2 ml of the bacterial suspension to the surface of each subsample respectively, and culturing at 37 ℃ for 3 hours; after the culture is finished, washing each subsample by using 5 ml of PBS (phosphate buffer solution) buffered saline, coating 0.05 ml of obtained washing liquid on a culture medium plate, culturing for 18 hours at 35 ℃, and counting the number of colonies on the culture medium plate to calculate the bacteriostasis rate. The culture media are TSB and TSA. The counting method of the colony count and the calculating method of the bacteriostasis rate are conventional means of those skilled in the art, and are not described herein, and the counting result is shown in table 3.
TABLE 3
| Test sample | Antibacterial ratio of Escherichia coli/%) | Antibacterial Activity of Staphylococcus aureus/%) |
| Third hemostatic sponge | 80％ | 95％ |
| Vaseline gauze | 0 | 0 |
As can be seen from table 3, the third hemostatic sponge added with amoxicillin has significantly better antibacterial effect than the vaseline gauze.
Although the embodiments of the present invention have been described in detail hereinabove, it is apparent to those skilled in the art that various modifications and variations can be made to these embodiments. However, it is to be understood that such modifications and variations are within the scope and spirit of the present invention as set forth in the following claims. Moreover, the invention as described herein is capable of other embodiments and of being practiced or of being carried out in various ways.
Claims (11)
1. A method for preparing a hemostatic sponge, comprising:
s1: taking polyhydric alcohol and an ester monomer as reactants, taking stannous octoate or dibutyltin dilaurate as a catalyst, carrying out a block prepolymer synthesis reaction for 0.5-24 hours under anhydrous and oxygen-free conditions and at the temperature of 120-180 ℃, and then sequentially carrying out first precipitation purification treatment and first drying treatment on a product obtained by the block prepolymer synthesis reaction to obtain a dried polyester polyol block prepolymer;
s2: dissolving the polyester polyol block prepolymer obtained after the first drying treatment and an isocyanate monomer in an organic good solvent to form a mixed solution, carrying out pre-reaction on the mixed solution for 4-12 hours at a reaction temperature of 60-100 ℃ under the protection of inert gas, then adding stannous octoate or dibutyltin dilaurate as a catalyst into the mixed solution, adding 1, 4-butanediol as a chain extender, and continuously reacting for 4-12 hours at a temperature of 60-100 ℃ to complete a polyurethane synthesis reaction;
s3: sequentially carrying out second precipitation purification treatment and second drying treatment on a product obtained after the polyurethane synthesis reaction, mixing the obtained solid polyurethane with a foaming agent to form a polyurethane solution, adding a hydrophilic polymer into the polyurethane solution, and then carrying out stirring foaming treatment for 20-120 minutes to obtain a foaming solution;
s4: and (3) placing the foaming solution into a mold, freezing the foaming solution at the temperature of not higher than-200 ℃ for 3-24 hours under normal pressure, then carrying out freeze drying treatment for 6-24 hours, and then carrying out sterilization treatment on the obtained freeze-dried substance to obtain the hemostatic sponge.
2. The method as claimed in claim 1, wherein in step S1, the molar ratio of the polyol to the ester monomer is 1:10-1:50, the mass of the catalyst is 0.01-5% of the mass of the reactant, and the weight average molecular weight of the polyol is 200-.
3. The method according to claim 2, wherein the polyol is one or more selected from the group consisting of polyethylene glycol, polypropylene glycol, polybutylene glycol and polytetrahydrofuran glycol, and the ester monomer is one or more selected from the group consisting of lactide, glycolide, caprolactone, trimethylene carbonate and p-dioxanone.
4. The method according to claim 1, wherein in step S1, methylene chloride is added to the product obtained by the synthesis reaction of the block prepolymer to form a mixed solution, and then the first precipitation purification treatment is performed using any one of absolute ethanol, methanol, ethanol, and water as a precipitation washing solution to obtain the wet polyester polyol block prepolymer.
5. The method according to claim 4, wherein the first drying treatment is performed by vacuum-drying the polyester polyol block prepolymer in a wet state at 40 to 80 ℃.
6. The method of claim 1, wherein the dried polyester polyol block prepolymer is stored at-20 ℃ in a frozen state for use.
7. The preparation method according to claim 1, wherein in step S2, the molar ratio of the polyester polyol block prepolymer to the isocyanate monomer is 1:1-1:1.5, the molar ratio of the isocyanate monomer to the 1, 4-butanediol is 1:1-1:1.5, 2.7 to 5 g of the isocyanate monomer is added to 100ml of the good organic solvent, and the mass of the catalyst is 0.01 to 5% of the total mass of the polyester polyol block prepolymer and the isocyanate monomer.
8. The method according to claim 1, wherein in step S3, the second precipitation purification treatment is performed on the product obtained after the polyurethane synthesis reaction by using any one of absolute ethanol, methanol, ethanol, or water as a precipitation washing solution, and then vacuum drying is performed at 40 to 80 ℃ to complete the second drying treatment.
9. The method according to claim 1, wherein in step S3, the solid polyurethane is 1 to 50% by mass of the polyurethane solution, and the hydrophilic polymer is not more than 30% by mass of the solid polyurethane.
10. The method according to claim 9, wherein the hydrophilic polymer is polyethylene glycol, povidone or polyvinyl alcohol, the weight average molecular weights of the polyethylene glycol and the polyvinyl alcohol are both 600-.
11. The method according to claim 1, wherein in step S3, the hydrophilic polymer and the drug are added to the polyurethane solution, and then the stirring foaming process is performed, wherein the drug accounts for 0.1% to 1.5% by mass of the solid polyurethane, and the drug is an antibacterial drug or an anti-inflammatory drug.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115487343A (en) * | 2022-11-16 | 2022-12-20 | 合肥启灏医疗科技有限公司 | Medicine-carrying polyurethane hemostatic cotton and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6566576B1 (en) * | 2000-01-04 | 2003-05-20 | James F. Komerska | Hydrocolloid foam medical dressings and method of making the same |
| US20060008419A1 (en) * | 2003-01-09 | 2006-01-12 | Polyganics B.V. | Biomedical foams |
| US20130295081A1 (en) * | 2008-10-30 | 2013-11-07 | Vanderbilt University | Polyurethane Composite for Wound Healing and Methods Thereof |
| CN104031287A (en) * | 2014-06-19 | 2014-09-10 | 山东赛克赛斯药业科技有限公司 | Preparation method of biodegradable nasal hemostatic sponge |
| CN106046309A (en) * | 2015-11-20 | 2016-10-26 | 徐永祥 | Completely-biodegradable cross-linked polyurethane and preparation method thereof, and porous sponge prepared from completely-biodegradable cross-linked polyurethane |
| CN107286313A (en) * | 2017-07-10 | 2017-10-24 | 陕西瑞盛生物科技有限公司 | A kind of degradable polyurethane foam and its application |
-
2019
- 2019-07-12 CN CN201910628744.0A patent/CN112206344B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6566576B1 (en) * | 2000-01-04 | 2003-05-20 | James F. Komerska | Hydrocolloid foam medical dressings and method of making the same |
| US20060008419A1 (en) * | 2003-01-09 | 2006-01-12 | Polyganics B.V. | Biomedical foams |
| US20130295081A1 (en) * | 2008-10-30 | 2013-11-07 | Vanderbilt University | Polyurethane Composite for Wound Healing and Methods Thereof |
| CN104031287A (en) * | 2014-06-19 | 2014-09-10 | 山东赛克赛斯药业科技有限公司 | Preparation method of biodegradable nasal hemostatic sponge |
| CN106046309A (en) * | 2015-11-20 | 2016-10-26 | 徐永祥 | Completely-biodegradable cross-linked polyurethane and preparation method thereof, and porous sponge prepared from completely-biodegradable cross-linked polyurethane |
| CN107286313A (en) * | 2017-07-10 | 2017-10-24 | 陕西瑞盛生物科技有限公司 | A kind of degradable polyurethane foam and its application |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115487343A (en) * | 2022-11-16 | 2022-12-20 | 合肥启灏医疗科技有限公司 | Medicine-carrying polyurethane hemostatic cotton and preparation method thereof |
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