WO2022199052A1 - Peripheral nerve regeneration repair material and preparation method therefor - Google Patents

Peripheral nerve regeneration repair material and preparation method therefor Download PDF

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WO2022199052A1
WO2022199052A1 PCT/CN2021/130481 CN2021130481W WO2022199052A1 WO 2022199052 A1 WO2022199052 A1 WO 2022199052A1 CN 2021130481 W CN2021130481 W CN 2021130481W WO 2022199052 A1 WO2022199052 A1 WO 2022199052A1
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polylactic acid
mixed solution
polycaprolactone
nerve regeneration
powder
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PCT/CN2021/130481
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French (fr)
Chinese (zh)
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崔孟龙
李洪景
刘洋
仇志烨
宋天喜
朱艳泽
崔云
朱金亮
何志敏
胡艳丽
李良才
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潍坊奥精医学研究有限公司
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Publication of WO2022199052A1 publication Critical patent/WO2022199052A1/en

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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
    • 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
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • 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
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/236—Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A61L2300/414—Growth factors
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A61L2300/604—Biodegradation
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction

Definitions

  • the invention relates to a peripheral nerve regeneration and repair material and a preparation method thereof, belonging to the field of biological materials.
  • the regeneration of peripheral nerves is affected by neurochemotaxis, neurotrophy and contact guidance. Therefore, in the prior art, the repair of nerves is generally effected by the neurochemotaxis of nerve growth factor (NGF).
  • NGF nerve growth factor
  • the catheter uses the regeneration ability of the nerve to achieve the purpose of repairing the severed nerve.
  • the appropriate degradation rate is closely related to the type, location and regeneration length of nerve regeneration. At the same time, the degradation products of the material should not have a great impact on the microenvironment of nerve regeneration. For biodegradable nerve conduits, the degradation rate of the conduit material is important. controllable factors.
  • Polylactic acid is currently the most widely used degradable material for peripheral nerve tissue engineering, and has good biocompatibility.
  • polylactic acid as a catheter material is difficult to control the degradation rate, and the acid product after degradation can cause cell damage and sterility. Inflammation, so some other materials need to be compounded to make the biodegradation rate of the catheter controllable and to neutralize the acidic products produced during the degradation process.
  • the purpose of the present invention is to provide a peripheral nerve regeneration and repair material and a preparation method thereof in view of the above problems, which can neutralize the acidic products in the degradation process of polylactic acid, and make the degradation rate controllable.
  • the present invention discloses a peripheral nerve regeneration repair material and a preparation method thereof.
  • the repair material is based on polylactic acid dissolved in ethyl acetate as a matrix, and is added with chitosan, nano- ⁇ -tricalcium phosphate and NGF frozen. Dry powder and polycaprolactone powder are mixed with ultrasonic vibration, and the mixed solution is volatilized to form a film; nano- ⁇ -tricalcium phosphate and chitosan can neutralize the acidic products produced during the degradation of polylactic acid, and polycaprolactone can Controlling the rate of biodegradation of the material, the nerve growth factor NGF promotes nerve repair.
  • the preparation method of the peripheral nerve regeneration and repair material is to dissolve polylactic acid in ethyl acetate to prepare a polylactic acid solution with a concentration of 10%. After the polylactic acid is completely dissolved, add ⁇ -tricalcium phosphate and chitosan to the polylactic acid solution.
  • Sugar, NGF freeze-dried powder and polycaprolactone powder the mass concentration of ⁇ -tricalcium phosphate in the mixed solution is 5wt%
  • the mass concentration of chitosan is 30wt%
  • NGF freeze-dried powder is added in the ratio of 2000UNGF:1g polylactic acid
  • the mass concentration of polycaprolactone was 20 wt%, and the solution was shaken in an ultrasonic oscillator for 30 minutes.
  • the beneficial effects of the present invention are: by adding chitosan and ⁇ -tricalcium phosphate, the acidic substances produced during the degradation of polylactic acid are neutralized, the biodegradation rate of the material is controlled by adding polycaprolactone, and the growth of nerves Factors promote nerve repair.
  • the preparation method of the peripheral nerve regeneration and repair material is to dissolve polylactic acid in ethyl acetate to prepare a polylactic acid solution with a concentration of 10%. After the polylactic acid is completely dissolved, add ⁇ -tricalcium phosphate and chitosan to the polylactic acid solution.
  • Sugar, NGF freeze-dried powder and polycaprolactone powder the mass concentration of ⁇ -tricalcium phosphate in the mixed solution is 5wt%
  • the mass concentration of chitosan is 30wt%
  • NGF freeze-dried powder is added in the ratio of 2000UNGF:1g polylactic acid
  • the mass concentration of polycaprolactone was 20 wt%, and the solution was shaken in an ultrasonic oscillator for 30 minutes.
  • the temperature is related to the volatilization speed. If the volatilization speed is too fast, there will be a lot of bubbles on the surface of the film, which will be uneven. At a lower temperature, a uniform and smooth film surface will be formed, but the temperature is too low, and the volatilization speed is too slow. The volatilization rate is faster, and the surface of the formed film is uniform inside and outside.
  • Moisture in the air can accelerate the gelation of the membrane surface, resulting in a larger pore size of the micropores on the membrane surface; on the contrary, if the humidity is high, the solvent volatilization rate is slow, which can make the temperature change on the membrane surface slow, which in turn makes the aggregated macromolecular polymer easier. If the humidity in the air is low, the solvent volatilization rate will be high, and the temperature of the membrane surface will decrease rapidly, making the macromolecules on the membrane surface easy to aggregate.
  • the optimum humidity condition is 40%.
  • the effect of the concentration of the solution on the membrane material is mainly manifested in the following aspects: the thickness of the membrane and the distribution of membrane pores;
  • the porosity of the membrane prepared by the solution is larger, the pore size distribution range is larger, the thickness of the membrane prepared by the larger solution is larger, while the membrane prepared by the solution with higher concentration has less porosity and the pore size distribution is more concentrated, mainly because
  • the concentration of the solution directly affects its fluidity. It is determined that when the concentration of the polylactic acid solution is 10%, the thickness and porosity of the formed film are the most suitable.
  • Polylactic acid is an important biodegradable polymer, which is widely used in drug controlled release systems due to its excellent biocompatibility and bioabsorbability. It is degraded by simple hydrolysis of the ester bond, and the final product of degradation can be excreted from the body to generate carbon dioxide and water for human metabolism.
  • chitosan has biodegradability and biocompatibility, which can accelerate wound healing ability, induce special cells for injured organisms, accelerate wound healing, especially promote the growth of healing tension. The repair of nerves has an advantageous effect.
  • the repair material can avoid compressing the regenerated nerve, and at the same time, the thin-walled catheter has better elasticity, which can inhibit the formation of neuroma at the broken end, and the material is degradable.
  • the inner diameter of the nerve catheter is slightly larger than the diameter of the damaged nerve Can.
  • the role of biological conduits made of repair materials in peripheral nerve regeneration is to artificially build a microenvironment that is conducive to the growth of nerve fibers at the injury site, and use the repair function of the peripheral nerve itself to repair the injury.
  • the guiding mechanism of nerve conduit repair technology for nerve regeneration may be contact guidance, and the distal end has a directional guiding effect on nerve regeneration.

Abstract

Disclosed in the present invention is a peripheral nerve regeneration repair material, characterized by using polylactic acid dissolved in ethyl acetate as a matrix, adding chitosan, nano-β-tricalcium phosphate, NGF freeze-dried powder and polycaprolactone powder, ultrasonically oscillating the mixed solution, and volatilizing the mixed solution into a film. By adding chitosan and β-tricalcium phosphate, acidic substances produced in the degradation process of polylactic acid are neutralized, the biodegradation rate of the material is controlled by adding polycaprolactone, and a nerve growth factor promotes nerve repair.

Description

一种外周神经再生修复材料及其制备方法A kind of peripheral nerve regeneration repair material and preparation method thereof 技术领域technical field
本发明涉及一种外周神经再生修复材料及其制备方法，属于生物材料领域。The invention relates to a peripheral nerve regeneration and repair material and a preparation method thereof, belonging to the field of biological materials.
背景技术Background technique
周围神经的再生受神经趋化性、神经营养性和接触引导三者的影响，因此，现有技术中对于神经的修复一般是利用神经生长因子（NGF）的神经趋化性作用影响，配合神经导管，利用神经的再生能力，达到修复断离神经的目的。The regeneration of peripheral nerves is affected by neurochemotaxis, neurotrophy and contact guidance. Therefore, in the prior art, the repair of nerves is generally effected by the neurochemotaxis of nerve growth factor (NGF). The catheter uses the regeneration ability of the nerve to achieve the purpose of repairing the severed nerve.
合适的降解速度与神经再生的类型、位置及再生长度密切相关，同时材料的降解产物对神经再生的微环境不应有很大影响，对于生物可降解型神经导管，导管材料的降解速度是重要的可控因素。The appropriate degradation rate is closely related to the type, location and regeneration length of nerve regeneration. At the same time, the degradation products of the material should not have a great impact on the microenvironment of nerve regeneration. For biodegradable nerve conduits, the degradation rate of the conduit material is important. controllable factors.
聚乳酸是目前周围神经组织工程应用最广泛的一种可降解材料，具有良好的生物相容性，但聚乳酸作为导管材料存在降解速率难控制，降解后酸性产物可引起细胞损伤和无菌性炎症，因此需要复合一些其他材料，使导管的生物降解速率可控，并中和降解过程中产生的酸性产物。Polylactic acid is currently the most widely used degradable material for peripheral nerve tissue engineering, and has good biocompatibility. However, polylactic acid as a catheter material is difficult to control the degradation rate, and the acid product after degradation can cause cell damage and sterility. Inflammation, so some other materials need to be compounded to make the biodegradation rate of the catheter controllable and to neutralize the acidic products produced during the degradation process.
技术问题technical problem
本发明的目的是针对以上问题提供一种外周神经再生修复材料及其制备方法，中和聚乳酸降解过程中的酸性产物，并使降解速率可控。The purpose of the present invention is to provide a peripheral nerve regeneration and repair material and a preparation method thereof in view of the above problems, which can neutralize the acidic products in the degradation process of polylactic acid, and make the degradation rate controllable.
技术解决方案technical solutions
为达到上述目的本发明公开了一种外周神经再生修复材料及其制备方法，该修复材料是以溶于乙酸乙酯的聚乳酸为基质，添加壳聚糖、纳米β-磷酸三钙、NGF冻干粉和聚已内脂粉末，再以超声波震荡混合溶液，混合溶液挥发成膜；纳米β-磷酸三钙和壳聚糖能够中和聚乳酸降解过程中产生的酸性产物，聚已内酯可控制材料的生物降解速度，神经生长因子NGF促进神经的修复。In order to achieve the above purpose, the present invention discloses a peripheral nerve regeneration repair material and a preparation method thereof. The repair material is based on polylactic acid dissolved in ethyl acetate as a matrix, and is added with chitosan, nano-β-tricalcium phosphate and NGF frozen. Dry powder and polycaprolactone powder are mixed with ultrasonic vibration, and the mixed solution is volatilized to form a film; nano-β-tricalcium phosphate and chitosan can neutralize the acidic products produced during the degradation of polylactic acid, and polycaprolactone can Controlling the rate of biodegradation of the material, the nerve growth factor NGF promotes nerve repair.
该外周神经再生修复材料的制备方法是，将聚乳酸溶于乙酸乙酯制成浓度10%的聚乳酸溶液，待聚乳酸完全溶解后，在聚乳酸溶液中加入β-磷酸三钙、壳聚糖、NGF冻干粉和聚已内脂粉末，混合溶液中β-磷酸三钙质量浓度为5wt%，壳聚糖的质量浓度为30wt%，NGF冻干粉按2000UNGF：1g聚乳酸的比例加入混合溶液中，聚已内酯的质量浓度为20wt%，在超声波震荡器中震荡30分钟，将混合溶液倒在膜具上，在温度20℃、湿度40%的条件下挥发成膜。The preparation method of the peripheral nerve regeneration and repair material is to dissolve polylactic acid in ethyl acetate to prepare a polylactic acid solution with a concentration of 10%. After the polylactic acid is completely dissolved, add β-tricalcium phosphate and chitosan to the polylactic acid solution. Sugar, NGF freeze-dried powder and polycaprolactone powder, the mass concentration of β-tricalcium phosphate in the mixed solution is 5wt%, the mass concentration of chitosan is 30wt%, NGF freeze-dried powder is added in the ratio of 2000UNGF:1g polylactic acid In the mixed solution, the mass concentration of polycaprolactone was 20 wt%, and the solution was shaken in an ultrasonic oscillator for 30 minutes.
有益效果beneficial effect
综上所述，本发明的有益效果在于：通过添加壳聚糖和β-磷酸三钙，中和聚乳酸降解过程中产生的酸性物质，添加聚已内酯控制材料的生物降解速率，神经生长因子促进神经的修复。To sum up, the beneficial effects of the present invention are: by adding chitosan and β-tricalcium phosphate, the acidic substances produced during the degradation of polylactic acid are neutralized, the biodegradation rate of the material is controlled by adding polycaprolactone, and the growth of nerves Factors promote nerve repair.
本发明的最佳实施方式BEST MODE FOR CARRYING OUT THE INVENTION
下面结合附图和实施例，对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明，但不用来限制本发明的范围。The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and embodiments. The following examples are intended to illustrate the present invention, but not to limit the scope of the present invention.
该外周神经再生修复材料的制备方法是，将聚乳酸溶于乙酸乙酯制成浓度10%的聚乳酸溶液，待聚乳酸完全溶解后，在聚乳酸溶液中加入β-磷酸三钙、壳聚糖、NGF冻干粉和聚已内脂粉末，混合溶液中β-磷酸三钙质量浓度为5wt%，壳聚糖的质量浓度为30wt%，NGF冻干粉按2000UNGF：1g聚乳酸的比例加入混合溶液中，聚已内酯的质量浓度为20wt%，在超声波震荡器中震荡30分钟，将混合溶液倒在膜具上，在温度20℃、湿度40%的条件下挥发成膜。The preparation method of the peripheral nerve regeneration and repair material is to dissolve polylactic acid in ethyl acetate to prepare a polylactic acid solution with a concentration of 10%. After the polylactic acid is completely dissolved, add β-tricalcium phosphate and chitosan to the polylactic acid solution. Sugar, NGF freeze-dried powder and polycaprolactone powder, the mass concentration of β-tricalcium phosphate in the mixed solution is 5wt%, the mass concentration of chitosan is 30wt%, NGF freeze-dried powder is added in the ratio of 2000UNGF:1g polylactic acid In the mixed solution, the mass concentration of polycaprolactone was 20 wt%, and the solution was shaken in an ultrasonic oscillator for 30 minutes.
温度与挥发速度相关，挥发速度过快，膜表面会存在大量气泡，凹凸不平，而较低的温度下，形成均一、光滑的膜面，但是温度过低，挥发速度过慢，在20℃条件下，挥发速度较快，形成的膜表面内外均匀。The temperature is related to the volatilization speed. If the volatilization speed is too fast, there will be a lot of bubbles on the surface of the film, which will be uneven. At a lower temperature, a uniform and smooth film surface will be formed, but the temperature is too low, and the volatilization speed is too slow. The volatilization rate is faster, and the surface of the formed film is uniform inside and outside.
空气中的水分能加速膜面凝胶，导致膜面微孔孔径变大；相反，湿度大，溶剂挥发速率慢，可使膜表面的温度变化慢，这又使已聚集的大分子聚合物易于展开，导致膜表面的微孔孔径减小；若空气中湿度小，则溶剂挥发速率大，膜表面温度降低快，使膜面的大分子易于聚集，最佳的湿度条件为40%。Moisture in the air can accelerate the gelation of the membrane surface, resulting in a larger pore size of the micropores on the membrane surface; on the contrary, if the humidity is high, the solvent volatilization rate is slow, which can make the temperature change on the membrane surface slow, which in turn makes the aggregated macromolecular polymer easier. If the humidity in the air is low, the solvent volatilization rate will be high, and the temperature of the membrane surface will decrease rapidly, making the macromolecules on the membrane surface easy to aggregate. The optimum humidity condition is 40%.
溶液的浓度对膜材料的影响主要表现在如下方面，膜的厚度和膜孔隙的分布状况；浓度小的溶液铺成的膜的厚度较小，制备的膜的表层孔隙率比浓度大的溶液制备的膜孔隙率大，孔径分布范围较大，大的溶液铺成的膜的厚度较大，而浓度较大的溶液制备的膜的孔隙率要少一些，并且孔径分布较集中，这主要是因为溶液的浓度直接影响其流动性的原因，经过确定，聚乳酸溶液浓度为10%时，形成的膜的厚度、孔隙率最合适。The effect of the concentration of the solution on the membrane material is mainly manifested in the following aspects: the thickness of the membrane and the distribution of membrane pores; The porosity of the membrane prepared by the solution is larger, the pore size distribution range is larger, the thickness of the membrane prepared by the larger solution is larger, while the membrane prepared by the solution with higher concentration has less porosity and the pore size distribution is more concentrated, mainly because The concentration of the solution directly affects its fluidity. It is determined that when the concentration of the polylactic acid solution is 10%, the thickness and porosity of the formed film are the most suitable.
聚乳酸是一种重要的生物可降解的聚合物，以其优良的生物相容性和生物可吸收性而广泛用于药物控制释放系统，聚乳酸最大的特点是在体液的水性环境中能靠酯键的简单水解而进行降解，而且降解的最终产物能够为人体新陈代谢生成二氧化碳和水而排出体外。Polylactic acid is an important biodegradable polymer, which is widely used in drug controlled release systems due to its excellent biocompatibility and bioabsorbability. It is degraded by simple hydrolysis of the ester bond, and the final product of degradation can be excreted from the body to generate carbon dioxide and water for human metabolism.
一般材料的亲水性越好，则材料的细胞亲和性就更好，聚乳酸富含疏水性酯键，缺乏亲水性基团，壳聚糖的加入能够改变聚乳酸的亲水性，同时，壳聚糖具有生物可降解性、生物相容性，能够加快伤口愈合能力，对受损伤的生物体能诱生特殊细胞，加快创伤愈合，特别是促进愈合张力的增长，这些特点对于断离神经的修复具有优势作用。Generally, the better the hydrophilicity of the material, the better the cell affinity of the material. Polylactic acid is rich in hydrophobic ester bonds and lacks hydrophilic groups. The addition of chitosan can change the hydrophilicity of polylactic acid. At the same time, chitosan has biodegradability and biocompatibility, which can accelerate wound healing ability, induce special cells for injured organisms, accelerate wound healing, especially promote the growth of healing tension. The repair of nerves has an advantageous effect.
本修复材料作为生物可降解材料，能够避免压迫再生神经，同时薄壁导管有更好的弹性，可以抑制断端神经瘤生成，且材料可降解，制成神经导管的内径略大于损伤神经直径即可。As a biodegradable material, the repair material can avoid compressing the regenerated nerve, and at the same time, the thin-walled catheter has better elasticity, which can inhibit the formation of neuroma at the broken end, and the material is degradable. The inner diameter of the nerve catheter is slightly larger than the diameter of the damaged nerve Can.
修复材料制成的生物导管在周围神经再生中的作用，主要是在损伤局部人为构建一个利于神经纤维生长的微环境，利用周围神经本身具有的修复功能对损伤进行修复。神经导管修复技术对神经再生的引导机理可能为接触引导，远端对神经再生具有趋向性引导作用。The role of biological conduits made of repair materials in peripheral nerve regeneration is to artificially build a microenvironment that is conducive to the growth of nerve fibers at the injury site, and use the repair function of the peripheral nerve itself to repair the injury. The guiding mechanism of nerve conduit repair technology for nerve regeneration may be contact guidance, and the distal end has a directional guiding effect on nerve regeneration.
在神经再生中暂时固定并支持损伤神经的两端，引导神经元的轴突轴向生长，避免外生和形成神经瘤，为神经再生提供一个相对隔绝的微环境，富集神经再生所需的神经营养因子，减少细胞入侵，防止疤痕的形成，用生物可降解材料制成的导管可在体内降解，无需二次手术去除，同时能避免使用非生物降解导管时可能出现的神经压迫等问题。Temporarily fix and support both ends of damaged nerves during nerve regeneration, guide the axial growth of neuronal axons, avoid exogenesis and neuroma formation, provide a relatively isolated microenvironment for nerve regeneration, and enrich the necessary Neurotrophic factor, reducing cell invasion and preventing scar formation, catheters made of biodegradable materials can be degraded in the body without the need for secondary surgical removal, while avoiding problems such as nerve compression that may occur when using non-biodegradable catheters.
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和替换，这些改进和替换也应视为本发明的保护范围。The above are only the preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, without departing from the technical principle of the present invention, several improvements and replacements can be made. These improvements and replacements It should also be regarded as the protection scope of the present invention.

Claims (2)

  1. 一种外周神经再生修复材料，其特征在于,所述材料是以溶于乙酸乙酯的聚乳酸为基质，添加壳聚糖、纳米β-磷酸三钙、NGF冻干粉和聚已内脂粉末，再以超声波震荡混合溶液，混合溶液挥发成膜。A peripheral nerve regeneration and repair material, characterized in that the material is based on polylactic acid dissolved in ethyl acetate, and added with chitosan, nano-β-tricalcium phosphate, NGF freeze-dried powder and polycaprolactone powder , and then mix the solution with ultrasonic vibration, and the mixed solution volatilizes to form a film.
  2. 如权利要求1所述的外周神经再生修复材料的制备方法，其特征在于，所述聚乳酸溶于乙酸乙酯制成浓度10%的聚乳酸溶液，待聚乳酸完全溶解后，在聚乳酸溶液中加入β-磷酸三钙、壳聚糖、NGF冻干粉和聚已内脂粉末，混合溶液中β-磷酸三钙质量浓度为5wt%，壳聚糖的质量浓度为30wt%，NGF冻干粉按2000UNGF：1g聚乳酸的比例加入混合溶液中，聚已内酯的质量浓度为20wt%，在超声波震荡器中震荡30分钟，将混合溶液倒在膜具上，在温度20℃、湿度40%的条件下挥发成膜。The method for preparing a peripheral nerve regeneration repair material according to claim 1, wherein the polylactic acid is dissolved in ethyl acetate to prepare a polylactic acid solution with a concentration of 10%. Add β-tricalcium phosphate, chitosan, NGF freeze-dried powder and polycaprolactone powder to the mixed solution, the mass concentration of β-tricalcium phosphate in the mixed solution is 5wt%, the mass concentration of chitosan is 30wt%, NGF freeze-dried The powder was added to the mixed solution at the ratio of 2000UNGF:1g of polylactic acid, the mass concentration of polycaprolactone was 20wt%, and the solution was shaken in an ultrasonic oscillator for 30 minutes. % under the conditions of volatilization to form a film.
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1562383A (en) * 2004-03-16 2005-01-12 武汉理工大学 Aretificial nerve canula material of slow operating complex type poly lactic acid and preparation method
CN102727931A (en) * 2012-07-06 2012-10-17 武汉理工大学 Construction and preparation of three-dimensional bionic electropolarized gradient pore nerve conduit
CN106620898A (en) * 2017-01-13 2017-05-10 北京奥精医药科技有限公司 High-molecular based transmitting tissue regeneration membrane as well as preparation method and application thereof
CN107412857A (en) * 2017-07-26 2017-12-01 武汉理工大学 A kind of polycaprolactone/chitosan/hydroxyapatite composite conduit support and preparation method thereof
US20180185541A1 (en) * 2016-12-29 2018-07-05 Industrial Technology Research Institute Method for manufacturing a porous film, porous film and method for tissue adhesion
CN111632193A (en) * 2020-05-15 2020-09-08 中国科学院深圳先进技术研究院 Chitosan-based nerve fiber membrane, preparation method, nerve conduit and application
CN112957536A (en) * 2021-03-23 2021-06-15 潍坊奥精医学研究有限公司 Peripheral nerve regeneration and repair material and preparation method thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1562383A (en) * 2004-03-16 2005-01-12 武汉理工大学 Aretificial nerve canula material of slow operating complex type poly lactic acid and preparation method
CN102727931A (en) * 2012-07-06 2012-10-17 武汉理工大学 Construction and preparation of three-dimensional bionic electropolarized gradient pore nerve conduit
US20180185541A1 (en) * 2016-12-29 2018-07-05 Industrial Technology Research Institute Method for manufacturing a porous film, porous film and method for tissue adhesion
CN106620898A (en) * 2017-01-13 2017-05-10 北京奥精医药科技有限公司 High-molecular based transmitting tissue regeneration membrane as well as preparation method and application thereof
CN107412857A (en) * 2017-07-26 2017-12-01 武汉理工大学 A kind of polycaprolactone/chitosan/hydroxyapatite composite conduit support and preparation method thereof
CN111632193A (en) * 2020-05-15 2020-09-08 中国科学院深圳先进技术研究院 Chitosan-based nerve fiber membrane, preparation method, nerve conduit and application
CN112957536A (en) * 2021-03-23 2021-06-15 潍坊奥精医学研究有限公司 Peripheral nerve regeneration and repair material and preparation method thereof

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