CN114732952A - Preparation method of hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating - Google Patents
Preparation method of hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating Download PDFInfo
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- CN114732952A CN114732952A CN202210468012.1A CN202210468012A CN114732952A CN 114732952 A CN114732952 A CN 114732952A CN 202210468012 A CN202210468012 A CN 202210468012A CN 114732952 A CN114732952 A CN 114732952A
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- chitosan
- gelatin
- hydroxybutyl
- hydroxybutyl chitosan
- composite gel
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- -1 hydroxybutyl Chemical group 0.000 title claims abstract description 103
- 239000008273 gelatin Substances 0.000 title claims abstract description 92
- 229920000159 gelatin Polymers 0.000 title claims abstract description 92
- 239000000499 gel Substances 0.000 title claims abstract description 48
- 210000004204 blood vessel Anatomy 0.000 title claims abstract description 45
- 239000002131 composite material Substances 0.000 title claims abstract description 44
- 239000002473 artificial blood Substances 0.000 title claims abstract description 43
- 239000011248 coating agent Substances 0.000 title claims abstract description 39
- 238000000576 coating method Methods 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 229920001661 Chitosan Polymers 0.000 claims abstract description 81
- 108010010803 Gelatin Proteins 0.000 claims abstract description 32
- 235000019322 gelatine Nutrition 0.000 claims abstract description 32
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 32
- 238000013329 compounding Methods 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 49
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- 238000003756 stirring Methods 0.000 claims description 24
- 238000001914 filtration Methods 0.000 claims description 18
- 239000002244 precipitate Substances 0.000 claims description 18
- 239000011259 mixed solution Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000012153 distilled water Substances 0.000 claims description 12
- 238000004108 freeze drying Methods 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 238000005303 weighing Methods 0.000 claims description 10
- 230000007935 neutral effect Effects 0.000 claims description 9
- RBACIKXCRWGCBB-UHFFFAOYSA-N 1,2-Epoxybutane Chemical compound CCC1CO1 RBACIKXCRWGCBB-UHFFFAOYSA-N 0.000 claims description 8
- 239000003792 electrolyte Substances 0.000 claims description 8
- 238000001652 electrophoretic deposition Methods 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 238000011033 desalting Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 3
- 230000002792 vascular Effects 0.000 claims 2
- 239000008280 blood Substances 0.000 abstract description 9
- 210000004369 blood Anatomy 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 9
- 230000023555 blood coagulation Effects 0.000 description 6
- 230000003405 preventing effect Effects 0.000 description 6
- 230000001737 promoting effect Effects 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 238000010612 desalination reaction Methods 0.000 description 4
- 230000004043 responsiveness Effects 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 230000021164 cell adhesion Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 239000003431 cross linking reagent Substances 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000002861 polymer material Substances 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 241000282412 Homo Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 239000004954 Polyphthalamide Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920006375 polyphtalamide Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
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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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
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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
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Abstract
The invention discloses a preparation method of a hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, which is implemented according to the following steps: step 1, preparing hydroxybutyl chitosan by taking chitosan as a raw material; and 2, compounding the hydroxybutyl chitosan prepared in the step 1 with gelatin to obtain the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating. The preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating solves the problems that the existing material for the medical blood vessel is difficult to be matched with blood compatibility and cannot meet the requirements.
Description
Technical Field
The invention belongs to the technical field of preparation of biomedical materials, and particularly relates to a preparation method of a hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
Background
Cardiovascular disease is one of the most serious diseases threatening mankind in the world today, and its morbidity and mortality have jumped first over neoplastic diseases. The research and analysis data of the death causes of the population in China also show that the death causes 40% of the death population caused by cardiovascular diseases in recent years, namely, 1 death population in every 3 death populations on average is caused by the cardiovascular diseases. Since vascular diseases account for the first cause of death in humans, the amount of artificial blood vessels used is increasing. Scholars at home and abroad screen out materials with good blood compatibility from the existing materials to prepare medical blood catheters, such as polyurethane, polyether ammonia, polyethylene, polyvinyl chloride, polystyrene, polyvinyl alcohol, polytetrafluoroethylene, polyphthalamide, polyvinyl acetate, polyamino acid, cellulose derivatives and the like, but the blood compatibility of the materials still does not meet the requirement, so that the development of the artificial blood vessel coating with good blood compatibility is necessary.
Disclosure of Invention
The invention aims to provide a preparation method of a hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, which solves the problems that the existing material for the medical blood vessel is difficult to adapt to blood compatibility and cannot meet the requirements.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: a preparation method of a hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating is implemented according to the following steps:
step 1, preparing hydroxybutyl chitosan by taking chitosan as a raw material;
and 2, compounding the hydroxybutyl chitosan prepared in the step 1 with gelatin to obtain the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
As a preferred technical solution of the present invention, in the step 1, when chitosan is used to prepare hydroxybutyl chitosan, the hydroxybutyl chitosan is firstly purified, and the purification process is as follows: firstly, dissolving chitosan in HCl solution with the concentration of 1-1.5%, and filtering insoluble substances; then slowly dripping 1-1.5 percent NaOH solution into the filtrate while stirring until the generated floccules are not increased any more; finally, collecting the precipitate, washing the precipitate to neutrality with distilled water, washing the precipitate with ethanol to complete desalting and dewatering, and freeze drying at-60 deg.c to-65 deg.c.
As a preferred technical solution of the present invention, in the step 1, the preparation of hydroxybutyl chitosan specifically comprises: dispersing the purified chitosan obtained in the step 1 in NaOH solution with the concentration of 50-55%, stirring at room temperature for 24-26 h to fully alkalize the chitosan, then filtering to remove redundant alkali liquor, adding isopropanol, stirring for 24-26 h to completely disperse the alkalized chitosan in an isopropanol system; then adding 1, 2-butylene oxide, and reacting with oil bath at 60-65 ℃ for 12-14 h; then, dropwise adding HCl solution with the concentration of 10-15% into the reaction system to make the pH value of the HCl solution neutral; finally filtering insoluble substances, dialyzing for 3 to 4 days by distilled water, and freeze-drying at the temperature of minus 60 to minus 65 ℃.
As a preferred technical scheme of the invention, in the preparation process of the hydroxybutyl chitosan in the step 1, for every 2g-3g of chitosan, 20ml-25ml of NaOH solution is required, 40ml-45ml of isopropanol is required, and 40ml-45ml of 1, 2-butylene oxide is required.
As a preferred technical solution of the present invention, in the step 2, the preparation of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating is specifically performed as follows: according to the following steps of 1: 1, respectively weighing hydroxybutyl chitosan and gelatin, dissolving the hydroxybutyl chitosan and the gelatin in an acid solution, and heating and stirring the solution to fully dissolve the hydroxybutyl chitosan and the gelatin to obtain a hydroxybutyl chitosan-gelatin mixed solution; and taking the obtained hydroxybutyl chitosan-gelatin mixed solution as electrolyte, constructing a two-electrode system, and performing electrophoretic deposition to deposit the hydroxybutyl chitosan-gelatin composite gel to form the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
The invention has the beneficial effects that: (1) according to the preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, the hydroxybutyl chitosan-gelatin mixed solution is prepared to serve as the electrolyte, and the hydroxybutyl chitosan-gelatin composite gel is prepared by the electrophoretic deposition technology, so that the whole preparation process is green, rapid, convenient and fast, and mass production can be realized, and the requirements of practical application can be met. (2) According to the preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, the hydroxybutyl chitosan-gelatin mixed solution without salt ions is prepared, so that the chitosan gel formed in an electrophoresis state and the gelatin gel formed after cooling are interpenetrated and inserted to form an interpenetrating network structure by utilizing the electronic responsiveness of the hydroxybutyl chitosan and the temperature responsiveness of the gelatin, the influence of salt ions on the chitosan hydrogel structure can be avoided, and the prepared hydroxybutyl chitosan-gelatin composite gel has high crystallinity and strong mechanical properties when used as the artificial blood vessel coating. (3) According to the preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, the used chitosan and gelatin are both natural medical high polymer materials, and no toxic cross-linking agent is used, so that the prepared artificial blood vessel has good biocompatibility; in addition, chitosan also has the functions of removing heavy metals in vivo, resisting free radicals, preventing radiation, resisting inflammation, stopping bleeding, promoting wound healing and the like, and gelatin also has the functions of promoting cell adhesion and growth and preventing blood coagulation, so that the prepared artificial blood vessel can induce intima formation after implantation, can prevent blood coagulation, is not easy to generate thrombus, and has high application safety.
Detailed Description
The technical solution of the present invention will be described in further detail with reference to the following embodiments.
The preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating is implemented according to the following steps:
step 1, firstly, dissolving chitosan in 1-1.5% HCl solution, and filtering insoluble substances; then slowly dripping NaOH solution with the concentration of 1-1.5% into the filtrate while stirring until the generated floccule is not increased any more; finally, collecting the precipitate, washing the precipitate to neutrality by using distilled water, washing the precipitate by using ethanol to complete desalination and dehydration, and then performing freeze drying at the temperature of between 60 ℃ below zero and 65 ℃ below zero;
weighing 2g to 3g of purified chitosan, dispersing the purified chitosan in 20ml to 25ml of NaOH solution with the concentration of 50 percent to 55 percent, stirring the mixture for 24h to 26h at room temperature to fully alkalize the chitosan, then filtering the mixture to remove redundant alkali liquor, adding isopropanol, stirring the mixture for 24h to 26h to completely disperse the alkalized chitosan in a 40ml to 45ml isopropanol system; then adding 40ml to 45ml of 1, 2-epoxybutane, and carrying out oil bath reaction at the temperature of between 60 and 65 ℃ for 12 to 14 hours; then, dropwise adding HCl solution with the concentration of 10-15% into the reaction system to make the pH value of the HCl solution neutral; finally filtering insoluble substances, dialyzing with distilled water for 3 to 4 days, and freeze-drying at-60 to-65 ℃ to obtain hydroxybutyl chitosan;
step 2, according to the step 1: 1, respectively weighing hydroxybutyl chitosan and gelatin, dissolving the hydroxybutyl chitosan and the gelatin in an acid solution, and heating and stirring the solution to fully dissolve the hydroxybutyl chitosan and the gelatin to obtain a hydroxybutyl chitosan-gelatin mixed solution; and taking the obtained hydroxybutyl chitosan-gelatin mixed solution as electrolyte, constructing a two-electrode system, and performing electrophoretic deposition to deposit the hydroxybutyl chitosan-gelatin composite gel to form the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
In order to improve the current situation that the blood compatibility of the existing artificial blood vessel is poor, the preparation method of the hydroxybutyl chitosan-gelatin hydrogel for the artificial blood vessel coating has the advantages of good cell compatibility, good blood compatibility and the like. Firstly, the chitosan adopted as the base material has no toxic or side effect, has good cell affinity, has the functions of removing heavy metals in vivo, resisting free radicals, preventing radiation, resisting inflammation, stopping bleeding, promoting wound healing and the like, and is known as a human body environment-friendly agent, a human body soft gold, human body antivirus software and a human body immune guardian by the experts in the world. The gelatin is a natural medical high polymer material, no toxic cross-linking agent is used, and the gelatin also has the functions of promoting cell adhesion and growth and preventing blood coagulation, so that the prepared artificial blood vessel coating can induce intimal formation after implantation, prevent blood coagulation, is not easy to generate thrombus and has high safety. Based on the above, the invention aims to form a composite gel by compounding the hydroxybutyl chitosan and the gelatin, so as to achieve good blood compatibility, and thus the invention is expected to be applied to a coating on the surface of an artificial blood vessel.
Example 1
The invention relates to a preparation method of a hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, which is implemented according to the following steps:
step 1, firstly, dissolving chitosan in 1% HCl solution, and filtering insoluble substances; then slowly dripping 1 percent NaOH solution into the filtrate while stirring until the generated floccule is not increased any more; finally, collecting the precipitate, washing the precipitate to be neutral by using distilled water, washing the precipitate by using ethanol to complete desalination and dehydration, and then performing freeze drying at the temperature of-60 ℃;
weighing 2g of purified chitosan, dispersing the chitosan in 20ml of NaOH solution with the concentration of 50%, stirring the solution at room temperature for 24 hours to fully alkalize the chitosan, then filtering the solution to remove redundant alkali liquor, adding isopropanol, and stirring the solution for 24 hours to completely disperse the alkalized chitosan in a 40ml isopropanol system; then adding 40ml of 1, 2-butylene oxide, and carrying out oil bath reaction at 60 ℃ for 12 h; then, dropwise adding HCl solution with the concentration of 10% into the reaction system to enable the pH value of the HCl solution to be neutral; finally filtering out insoluble substances, dialyzing with distilled water for 3 days, and freeze-drying at-60 deg.C to obtain hydroxybutyl chitosan;
step 2, according to the step 1: 1, respectively weighing hydroxybutyl chitosan and gelatin, dissolving the hydroxybutyl chitosan and the gelatin in an acid solution, and heating and stirring the solution to fully dissolve the hydroxybutyl chitosan and the gelatin to obtain a hydroxybutyl chitosan-gelatin mixed solution; and taking the obtained hydroxybutyl chitosan-gelatin mixed solution as electrolyte, constructing a two-electrode system, and performing electrophoretic deposition to deposit the hydroxybutyl chitosan-gelatin composite gel to form the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
Example 2
The preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating is implemented according to the following steps:
step 1, firstly, dissolving chitosan in 1.2% HCl solution, and filtering insoluble substances; then slowly dripping NaOH solution with the concentration of 1.2 percent into the filtrate while stirring until the generated floccules are not increased any more; finally, collecting the precipitate, washing the precipitate to be neutral by using distilled water, washing the precipitate by using ethanol to complete desalination and dehydration, and then performing freeze drying at the temperature of-63 ℃;
weighing 2.5g of purified chitosan, dispersing the purified chitosan in 23ml of NaOH solution with the concentration of 53%, stirring the mixture at room temperature for 25 hours to fully alkalize the chitosan, then filtering the mixture to remove redundant alkali liquor, adding isopropanol, and stirring the mixture for 25 hours to completely disperse the alkalized chitosan in a 43ml isopropanol system; then 43ml of 1, 2-butylene oxide is added and reacted for 13 hours in an oil bath at 63 ℃; then, dropwise adding 13% HCl solution into the reaction system to make the pH value of the reaction system neutral; finally filtering out insoluble substances, dialyzing with distilled water for 3.5 days, and freeze-drying at-63 deg.C to obtain hydroxybutyl chitosan;
step 2, according to the step 1: 1, respectively weighing hydroxybutyl chitosan and gelatin, dissolving the hydroxybutyl chitosan and the gelatin in an acid solution, and heating and stirring the solution to fully dissolve the hydroxybutyl chitosan and the gelatin to obtain a hydroxybutyl chitosan-gelatin mixed solution; and taking the obtained hydroxybutyl chitosan-gelatin mixed solution as electrolyte, constructing a two-electrode system, and performing electrophoretic deposition to deposit the hydroxybutyl chitosan-gelatin composite gel to form the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
Example 3
The preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating is implemented according to the following steps:
step 1, firstly, dissolving chitosan in 1.5 percent HCl solution, and filtering insoluble substances; then slowly dripping NaOH solution with the concentration of 1.5 percent into the filtrate while stirring until the generated floccule does not increase any more; finally, collecting the precipitate, washing the precipitate to be neutral by using distilled water, washing the precipitate by using ethanol to complete desalination and dehydration, and then performing freeze drying at the temperature of-65 ℃;
weighing 3g of purified chitosan, dispersing the chitosan in 25ml of NaOH solution with the concentration of 55%, stirring the mixture for 26 hours at room temperature to fully alkalize the chitosan, then filtering the mixture to remove redundant alkali liquor, adding isopropanol, and stirring the mixture for 26 hours to completely disperse the alkalized chitosan in a 45ml isopropanol system; then adding 45ml of 1, 2-butylene oxide, and carrying out oil bath reaction at 65 ℃ for 14 h; then, dropwise adding a 15% HCl solution into the reaction system to make the pH value of the reaction system neutral; finally filtering out insoluble substances, dialyzing with distilled water for 4 days, and freeze-drying at-65 ℃ to obtain hydroxybutyl chitosan;
step 2, according to the step 1: 1, respectively weighing hydroxybutyl chitosan and gelatin, dissolving the hydroxybutyl chitosan and the gelatin in an acid solution, and heating and stirring the solution to fully dissolve the hydroxybutyl chitosan and the gelatin to obtain a hydroxybutyl chitosan-gelatin mixed solution; and taking the obtained hydroxybutyl chitosan-gelatin mixed solution as electrolyte, constructing a two-electrode system, and performing electrophoretic deposition to deposit the hydroxybutyl chitosan-gelatin composite gel to form the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
Therefore, compared with the prior art, the preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating provided by the invention has the advantages that the hydroxybutyl chitosan-gelatin mixed solution is prepared to be used as the electrolyte, and the hydroxybutyl chitosan-gelatin composite gel is prepared by utilizing the electrophoretic deposition technology, so that the whole preparation process is green, rapid, convenient and fast, and can be produced in mass, and the requirements of practical application can be met. In addition, according to the preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, the hydroxybutyl chitosan-gelatin mixed solution without salt ions is prepared, so that the chitosan gel formed in an electrophoresis state and the gelatin gel formed after cooling are interpenetrated and inserted to form an interpenetrating network structure by utilizing the electronic responsiveness of the hydroxybutyl chitosan and the temperature responsiveness of the gelatin, the influence of salt ions on the chitosan hydrogel structure can be avoided, and the prepared hydroxybutyl chitosan-gelatin composite gel has high crystallinity and strong mechanical properties when used as the artificial blood vessel coating. In addition, according to the preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating, the used chitosan and gelatin are both natural medical high polymer materials, and no toxic cross-linking agent is used, so that the prepared artificial blood vessel has good biocompatibility; in addition, chitosan also has the functions of removing heavy metals in vivo, resisting free radicals, preventing radiation, resisting inflammation, stopping bleeding, promoting wound healing and the like, and gelatin also has the functions of promoting cell adhesion and growth and preventing blood coagulation, so that the prepared artificial blood vessel can induce intima formation after implantation, prevent blood coagulation and is not easy to generate thrombus, and the application safety is high.
While the foregoing description shows and describes several preferred embodiments of the invention, it is to be understood, as noted above, that the invention is not limited to the forms disclosed herein, but is not to be construed as excluding other embodiments and is capable of use in various other combinations, modifications, and environments and is capable of changes within the scope of the inventive concept as expressed herein, commensurate with the above teachings, or the skill or knowledge of the relevant art.
Claims (5)
1. The preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating is characterized by comprising the following steps of:
step 1, preparing hydroxybutyl chitosan by taking chitosan as a raw material;
and 2, compounding the hydroxybutyl chitosan prepared in the step 1 with gelatin to obtain the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
2. The method for preparing hydroxybutyl chitosan-gelatin composite gel vascular prosthesis coating according to claim 1, wherein in step 1, when chitosan is used to prepare hydroxybutyl chitosan, it is purified first, and the purification process comprises: firstly, dissolving chitosan in HCl solution with the concentration of 1-1.5%, and filtering insoluble substances; then slowly dripping NaOH solution with the concentration of 1-1.5% into the filtrate while stirring until the generated floccule is not increased any more; finally, collecting the precipitate, washing the precipitate to neutrality with distilled water, washing the precipitate with ethanol to complete desalting and dewatering, and freeze drying at-60 deg.c to-65 deg.c.
3. The preparation method of the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating of claim 2, wherein in the step 1, the preparation of hydroxybutyl chitosan is specifically: dispersing the purified chitosan obtained in the step 1 in NaOH solution with the concentration of 50-55%, stirring at room temperature for 24-26 h to fully alkalize the chitosan, then filtering to remove redundant alkali liquor, adding isopropanol, stirring for 24-26 h to completely disperse the alkalized chitosan in an isopropanol system; then adding 1, 2-butylene oxide, and reacting with oil bath at 60-65 ℃ for 12-14 h; then, dropwise adding HCl solution with the concentration of 10-15% into the reaction system to enable the pH value of the HCl solution to be neutral; finally filtering insoluble substances, dialyzing for 3 to 4 days by distilled water, and freeze-drying at the temperature of minus 60 to minus 65 ℃.
4. The method for preparing hydroxybutyl chitosan-gelatin composite gel vascular prosthesis coating according to claim 3, wherein for every 2g-3g chitosan, NaOH solution is required to be 20ml-25ml, isopropanol is required to be 40ml-45ml, and 1, 2-butylene oxide is required to be 40ml-45 ml.
5. The method for preparing the hydroxybutyl chitosan-gelatin composite gel coating for artificial blood vessels of claim 4, wherein in the step 2, the preparation of the hydroxybutyl chitosan-gelatin composite gel coating for artificial blood vessels is specifically performed as follows: according to the following steps of 1: 1, respectively weighing hydroxybutyl chitosan and gelatin, dissolving the hydroxybutyl chitosan and the gelatin in an acid solution, and heating and stirring the solution to fully dissolve the hydroxybutyl chitosan and the gelatin to obtain a hydroxybutyl chitosan-gelatin mixed solution; and taking the obtained hydroxybutyl chitosan-gelatin mixed solution as electrolyte, constructing a two-electrode system, and performing electrophoretic deposition to deposit the hydroxybutyl chitosan-gelatin composite gel to form the hydroxybutyl chitosan-gelatin composite gel artificial blood vessel coating.
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