WO2020077551A1 - 复合屏障膜及其制备方法 - Google Patents

复合屏障膜及其制备方法 Download PDF

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WO2020077551A1
WO2020077551A1 PCT/CN2018/110558 CN2018110558W WO2020077551A1 WO 2020077551 A1 WO2020077551 A1 WO 2020077551A1 CN 2018110558 W CN2018110558 W CN 2018110558W WO 2020077551 A1 WO2020077551 A1 WO 2020077551A1
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film
electrospinning
composite barrier
silk fibroin
solution
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PCT/CN2018/110558
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English (en)
French (fr)
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赵荟菁
王临博
蒋紫仪
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南通纺织丝绸产业技术研究院
苏州大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B9/00—Layered products comprising a layer of a particular substance not covered by groups B32B11/00 - B32B29/00
    • B32B9/04—Layered products comprising a layer of a particular substance not covered by groups B32B11/00 - B32B29/00 comprising such particular substance as the main or only constituent of a layer, which is next to another layer of the same or of a different material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B32—LAYERED PRODUCTS
    • B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B9/00—Layered products comprising a layer of a particular substance not covered by groups B32B11/00 - B32B29/00
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/02—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from cellulose, cellulose derivatives, or proteins
    • D—TEXTILES; PAPER
    • D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
    • D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
    • D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
    • D01F8/04—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers
    • D01F8/14—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from synthetic polymers with at least one polyester as constituent

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  • the invention relates to the field of medical materials, in particular to a composite barrier film and a preparation method thereof.
  • Silk fibroin is a natural polymer material extracted from silk. It has abundant sources in China, has good biocompatibility, is biodegradable, has good oxygen permeability and water permeability, and is an alternative material for bone and periodontal regeneration.
  • Poly-L-lactide- ⁇ -caprolactone also known as poly (L-lactic acid-caprolactone) (PLCL)
  • PLCL poly (L-lactic acid-caprolactone)
  • PLLA polylactic acid
  • PCL polycaprolactone
  • the electrospinning method can highly simulate the extracellular matrix (ECM).
  • ECM extracellular matrix
  • the prepared membrane materials have a high specific surface area, ultra-high porosity, and interconnection of pores, which can ensure the nutrients and waste. Transmission, and provides a good microenvironment for cell adhesion, differentiation and proliferation.
  • the object of the present invention is to provide a composite barrier film and a preparation method thereof, which have good biocompatibility, biodegradability, sufficient stability, good space retention and excellent mechanical properties.
  • the first object of the present invention is to provide a composite barrier film including an inner layer film and an outer layer film, the inner layer film is a first electrospinning film, and the outer layer film includes a casting film and a second electrospinning film, And the casting film is compounded outside the second electrospinning film, the material of the first electrospinning film or the second electrospinning film is independently selected from silk fibroin (SF) and / or biocompatible polymer, The material of the casting film is silk fibroin.
  • SF silk fibroin
  • biocompatible polymer The material of the casting film is silk fibroin.
  • the thickness of the composite barrier film is 0.35-0.74 mm, and the tensile breaking strength is 2.2-22 MPa.
  • the thickness ratio of the inner layer film and the outer layer film is 0.18-0.22.
  • the mass ratio of silk fibroin and biocompatible polymer is 0.1: 100-100: 0.1 .
  • the mass ratio of silk fibroin to biocompatible polymer is 25: 75-75: 25.
  • the first electrospinning film or the second electrospinning film is independently selected from pure silk fibroin film, pure biocompatible polymer or a mixed film of silk fibroin and biocompatible polymer (silk fibroin) (The mass ratio of protein to biocompatible polymer is 25:75, 50:50, 75:25).
  • the thickness ratio of the cast film and the second electrospinning film is 1: 4-1: 9.
  • the biocompatible polymer is poly (L-lactic acid-caprolactone) (PLCL), polycaprolactone (PCL), polylactic acid (PLA), polylactic acid / polyglycolic acid copolymer (PLGA), poly Ethylene glycol (PEG) or chitosan.
  • the biocompatible polymer is PLCL.
  • PLCL is a polymer formed by polymerizing poly-L-lactic acid and polycaprolactone with a mass ratio of 1:99, 30:70, and 50:50, and the molecular weight is 15000-85000.
  • the composite barrier membrane of the present invention is a composite membrane of an outer layer membrane and an inner layer membrane.
  • the first or second electrospinning membrane includes SF and / or biocompatible polymer.
  • Silk fibroin (SF) is a The natural protein extracted from silkworm has good biocompatibility, good oxygen and water permeability, and is biodegradable. It is an alternative material for bone and periodontal regeneration.
  • SF has sufficient strength to provide sufficient stability, good space retention, prevent film collapse, and SF film has excellent wet tensile strength and good bone formation.
  • the degradation rate of the biocompatible polymer is controllable, the elasticity and mechanical properties are adjustable, and the tensile strength is good.
  • the composite barrier membrane has a porous structure, which can highly simulate the extracellular matrix (ECM).
  • ECM extracellular matrix
  • the prepared membrane material has a high specific surface area, ultra-high porosity, and interconnection of pores, which can ensure the transfer of nutrients and waste. It also provides a good microenvironment for cell adhesion, differentiation and proliferation.
  • As an outer film it plays a supporting role to prevent the film from collapsing.
  • the outer film is a second electrospun film wrapped by a casting film.
  • the casting film is dense and prevents the epithelial tissue and connective tissue from transferring to the defect.
  • the second electrospinning film in the outer layer film still plays a supporting role as the casting film degrades.
  • the double-layer membrane of the composite barrier membrane of the present invention plays a double supporting role, has good supporting performance, prevents the membrane from collapsing, can maintain good mechanical properties as it degrades in the body, can be used to guide tissue regeneration (GTR), and can be electrospun membrane Medium-loaded drugs, with the sustained release of drugs, play a role in promoting bone regeneration (GBR).
  • the second object of the present invention is to provide a method for preparing the above composite barrier film, which includes the following steps:
  • the first electrospinning film or the second electrospinning solution includes degummed silk fibroin and / Or the biocompatible polymer and organic solvent; the concentration of the first electrospinning solution or the second electrospinning solution is 4% -12%;
  • the outer layer film is an electrospinning film wrapped with a casting film, wherein the processing liquid is Silk fibroin solution;
  • the preparation method of the degummed silk fibroin includes the following steps:
  • the silk is boiled in an alkaline solution, dried and soaked in a lithium bromide solution for 4-6 hours, dialysis to remove molecules with a molecular weight below 3500 Da, centrifuged and dried to obtain degummed silk fibroin.
  • the organic solvent is one or more of hexafluoroisopropanol (HFIP), N, N-dimethylformamide (DMF), tetrachloroethylene and chloroform.
  • step (1) when the electrospinning solution contains both silk fibroin and biocompatible polymer, the mass ratio of silk fibroin and biocompatible polymer is 0.1: 100-100: 0.1 .
  • the electrospinning method can effectively adjust the structure and performance of the prepared electrospinning film by adjusting the spinning parameters, solution concentration, material ratio, etc.
  • step (2) the concentration of the silk fibroin aqueous solution is 8% -15%; the concentration of the biocompatible polymer solution is 2% -10%; the mixed solution of silk fibroin and biocompatible polymer The concentration is 4% -12%.
  • the biocompatible polymer is poly (L-lactic acid-caprolactone) (PLCL), polycaprolactone (PCL), polylactic acid (PLA), polylactic acid / polyglycolic acid copolymer (PLGA), poly Ethylene glycol (PEG) or chitosan.
  • PLCL poly (L-lactic acid-caprolactone)
  • PCL polycaprolactone
  • PLA polylactic acid
  • PLA polylactic acid / polyglycolic acid copolymer
  • PEG poly Ethylene glycol
  • chitosan chitosan.
  • the biocompatible polymer is PLCL.
  • the thickness of the composite barrier film is 0.35-0.74 mm, and the tensile breaking strength is 2.2-22 MPa.
  • step (3) the following method is used for compounding.
  • a bio-glue adhesive such as seaweed bio-glue, sheepskin glue, bone glue and dextrin
  • the concentration in the present invention refers to the mass concentration, which is the ratio of the mass of the solute to the total weight of the solution.
  • the present invention has at least the following advantages:
  • the composite barrier film of the present invention is composed of an electrospinning film and an outer layer film including a casting film.
  • the formed composite film has a stable shape, good space retention, and excellent dry and wet mechanical properties.
  • the preparation process of the double-layer film of the composite barrier film is relatively simple, the process flow is short, it is easy to realize mass production, and the single-layer film can be controlled by adjusting the conditions of the ratio and concentration of each substance.
  • the composite barrier film of the invention has excellent mechanical properties, high strength and good elasticity.
  • the composite barrier membrane of the present invention as the silk fibroin in the outer layer is degraded, the composite barrier membrane can still maintain high mechanical properties, and has potential application value in the field of biomedicine such as drug delivery and tissue engineering.
  • 1 is a schematic structural view of the composite barrier membrane of the present invention
  • FIG. 2 is a scanning electron micrograph of a silk fibroin / PLCL inner layer film of the present invention
  • FIG. 3 is an image of a silk fibroin / PLCL composite barrier membrane of the present invention.
  • a composite barrier film of the present invention includes an inner layer film 1 and an outer layer film 3, the inner layer film is a first electrospinning film, and the outer layer film 3 includes a casting film 2 and a second electrospinning film Membrane 4, and the casting film 2 is wrapped outside the second electrospinning membrane 4, the first electrospinning membrane or the second electrospinning membrane 4 can be made of silk fibroin (SF) and / or biocompatible polymer, respectively Produced by the electrospinning method, the casting film 2 is produced by the silk fibroin solution by the casting method.
  • the biocompatible polymer is preferably PLCL.
  • the obtained silk fibroin solution was formed into a film at normal temperature and placed in a refrigerator at 4 ° C for use.
  • the second electrospinning film is placed in an aqueous solution of SF with a concentration of 11.3%, and the SF is cast to form a casting film to obtain an electrospinning film wrapped with a casting film, namely For the outer membrane.
  • the inner layer film is combined with the outer layer film prepared in step (4) to obtain a silk fibroin / PLCL composite barrier film.
  • the inner film and outer film can be compounded by the following methods:
  • bio-adhesive to directly bond the inner and outer membranes, such as seaweed bio-adhesive, sheepskin glue, bone glue and dextrin, to prepare a composite barrier membrane.
  • the electrospinning film is placed on it and directly bonded into a composite barrier film.
  • the silk fibroin / PLCL composite barrier membrane is prepared according to the method of Example 2, except that in step (2), the solute is degummed SF and PLCL, and the mass ratio of SF: PLCL in the spinning solution is 25:75 .
  • the preparation method of the spinning solution is as follows: accurately weigh 0.35g SF, 1.05g PLCL with a precision balance, dissolve it in 12.6g of hexafluoroisopropanol, and stir thoroughly to mix until the spinning solution has no visible particles Thing.
  • the silk fibroin / PLCL composite barrier membrane was prepared according to the method of Example 3, except that in step (2), the mass ratio of SF: PLCL in the spinning solution was 50:50.
  • the preparation method of the spinning solution is as follows: accurately weigh 0.7g, SF, 0.7g PLCL with a precision balance, dissolve it in 12.6g of hexafluoroisopropanol, and stir thoroughly to mix until the spinning solution has no visible particles Thing.
  • the silk fibroin / PLCL composite barrier membrane was prepared according to the method of Example 3, except that in step (2), the mass ratio of SF: PLCL in the spinning solution was 75:25.
  • the preparation method of the spinning solution is as follows: accurately weigh 1.05g SF, 0.35g PLCL with a precision balance, dissolve it in 12.6g of hexafluoroisopropanol, and stir thoroughly to mix until the spinning solution has no visible particles Thing.
  • a composite barrier film was prepared according to the method of Example 2, except that in step (2), the spinning solution contained only SF except the solvent.
  • the preparation method of the spinning solution is as follows: accurately weigh 1.4g of SF with a precision balance, dissolve it in 12.6g of hexafluoroisopropanol, and stir thoroughly to mix evenly until there are no visible particles in the spinning solution.
  • Table 1 is the test results of the mechanical properties of different inner layer films prepared in Examples 1-6 above. The results show that the inner layer film of the present invention has good mechanical properties.
  • the silk fibroin / PLCL composite barrier membrane was prepared according to the method of Example 2, except that in step (2), the spinning voltage was 10 kV, the receiving distance was 10 cm, and the flow rate was 0.5 mL / h.
  • the silk fibroin / PLCL composite barrier membrane was prepared according to the method of Example 2, except that in step (2), the spinning voltage was 30 kV, the receiving distance was 18 cm, and the flow rate was 1.0 mL / h.
  • the silk fibroin / PLCL composite barrier membrane was prepared according to the method of Example 2, except that in step (2), the spinning voltage was 25 kV, the receiving distance was 12 cm, and the flow rate was 1.5 mL / h.
  • the silk fibroin / PLCL composite barrier membrane was prepared according to the method of Example 2, except that in step (2), the solvent was DMF.

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Abstract

一种复合屏障膜，包括内层膜（1）和外层膜（3），内层膜（1）为第一静电纺丝膜，外层膜（3）包括第二静电纺丝膜（4）及流延膜（2），第二静电纺丝膜（4）置于处理液中形成流延膜（2），第一或第二静电纺丝膜（4）的材质包括丝素蛋白和/或生物相容性聚合物，流延膜（2）的材质为丝素蛋白。该复合屏蔽膜的制备方法为：将脱胶后的丝素蛋白与生物相容性聚合物溶于有机溶剂，得到静电纺丝溶液，然后进行静电纺丝，得到第一或第二静电纺丝膜（4）；将第二静电纺丝膜（4）置于处理液中，采用流延法成膜，得到外层膜（3），其中，处理液为丝素蛋白水溶液；将第一静电纺丝膜作为内层膜（1），将外层膜（3）与内层膜（1）复合，得到复合屏障膜。

Description

复合屏障膜及其制备方法 技术领域
本发明涉及医用材料领域，尤其涉及一种复合屏障膜及其制备方法。
背景技术
丝素蛋白(SF)是从蚕丝中提取的天然高分子材料。在我国来源丰富，且有良好的生物相容性，可生物降解，透氧透水性好，是骨和牙周再生的备选材料。聚-L-丙交酯-ε-己内酯又称聚(左旋乳酸-己内酯)(PLCL)是PLLA(聚乳酸)和PCL(聚己内酯)以质量比1:1混合而成，兼具两者优势，可控的降解速率，灵活性好，抗拉强度好，生物相容性好。
静电纺丝法作为膜材料的制备方法，可高度模拟细胞外基质(ECM)，制备的膜材料具有较高比表面积和超高孔隙率以及孔道的互相连通性，能够保证营养物质和废弃物的传递，并为细胞黏附、分化、增殖提供了良好的微环境。
现有的屏障膜有许多不足，机械性能低，降解速率不可控等。天然聚合物通常缺乏足够的机械强度和降解曲线，然而合成聚合物生物活性差。培养有足够机械强度的，可预测降解速率，模仿与天然细胞外基质(ECM)相类似的结构的膜依然是问题。混纺两种或更多聚合物来弥补他们各自缺陷，表现出更好的协同作用。
发明内容
为解决上述技术问题，本发明的目的是提供一种复合屏障膜及其制备方法，其生物相容性良好、可生物降解、足够稳定、空间保持性好、力学性能优良。
本发明的第一个目的是提供一种复合屏障膜，包括内层膜和外层膜，内层膜为第一静电纺丝膜，外层膜包括流延膜和第二静电纺丝膜，且流延膜复合于第二静电纺丝膜外部，第一静电纺丝膜或第二静电纺丝膜的材质分别独立地选自丝素蛋白(SF)和/或生物相容性聚合物，流延膜的材质为丝素蛋白。
进一步地，复合屏障膜的厚度为0.35-0.74mm，拉伸断裂强度为2.2-22MPa。
进一步地，内层膜和外层膜的厚度比为0.18-0.22。
进一步地，第一静电纺丝膜或第二静电纺丝膜包括丝素蛋白和生物相容性聚合物时，丝素蛋白和生物相容性聚合物的质量比为0.1:100-100:0.1。优选地，丝素蛋白和生物相容性聚合物的质量比为25:75-75:25。
优选地，第一静电纺丝膜或第二静电纺丝膜分别独立地选自纯丝素蛋白膜、纯生物相容性聚合物或丝素蛋白和生物相容性聚合物混纺膜(丝素蛋白和生物相容性聚合物的质量比为25:75、50:50、75:25)。
进一步地，流延膜和第二静电纺丝膜的厚度比为1:4-1:9。
进一步地，生物相容性聚合物为聚(左旋乳酸-己内酯)(PLCL)、聚己内酯(PCL)、聚乳酸(PLA)、聚乳酸/聚乙醇酸共聚物(PLGA)、聚乙二醇(PEG)或壳聚糖。优选地，生物相容性聚合物为PLCL。PLCL为聚左旋乳酸和聚己内酯以1:99、30:70、50:50的质量比聚合成的聚合物，分子量为15000-85000。
本发明的复合屏障膜，为外层膜和内层膜复合膜，第一或第二静电纺丝膜中包括SF和/或生物相容性聚合物，丝素蛋白(SF)是一种从蚕中提取的天然蛋白质，生物相容性好，透氧透水性好，可生物降解，是骨和牙周再生中的备选材料。此外，SF有足够的强度，可提供足够稳定，空间保持性好，防止膜崩塌，且SF膜的湿拉伸强度优越，骨形成好。生物相容性聚合物降解速率可控，弹性及力学性能可调，抗拉强度好。且该复合屏障膜为多孔结构，可高度模拟细胞外基质(ECM)，制备的膜材料具有较高比表面积和超高孔隙率以及孔道的互相连通性，能够保证营养物质和废弃物的传递，并为细胞黏附、分化、增殖提供了良好的微环境。作为外层膜，起到支撑作用，防止膜坍塌。外层膜为流延膜包裹的第二静电纺丝膜，流延膜具有致密性，防止上皮组织、结缔组织转移到缺陷部位。且外层膜中的第二静电纺丝膜随流延膜的降解依然起到支撑作用。本发明的复合屏障膜的双层膜起双重支撑作用，支撑性能好，防止膜坍塌，可随体内降解依然保持良好的机械性能，可用于引导组织再生(GTR)，并可在静电纺丝膜中负载药物，随着药物缓释起到促进骨再生(GBR)的作用。
本发明的第二个目的是提供一种上述复合屏障膜的制备方法，包括以下步骤：
(1)分别提供第一静电纺丝膜和第二静电纺丝膜，所述第一静电纺丝膜和第二静电纺丝膜分别通过第一静电纺丝溶液和第二静电纺丝溶液在电压10-30kV，接收距离10-18cm，流速0.5-2mL/h条件下进行静电纺丝后得到，所述第一静电纺丝溶液或第二静电纺丝溶液中包括脱胶后的丝素蛋白和/或所述生物相容性聚合物以及有机溶剂；所述第一静电纺丝溶液或第二静电纺丝溶液的浓度为4％-12％；；
(2)将第二静电纺丝膜置于处理液中，采用流延法使处理液成膜，得到外层膜，外层膜为流延膜包裹的静电纺丝膜，其中，处理液为丝素蛋白水溶液；
(3)将第一静电纺丝膜作为内层膜，将内层膜与外层膜复合，得到复合屏障膜。
进一步地，脱胶后的丝素蛋白的制备方法包括以下步骤：
将蚕丝在碱性溶液中煮沸，烘干后用溴化锂溶液浸泡4-6h，透析除去分子量3500Da以下的分子，离心、干燥后得到脱胶后的丝素蛋白。
进一步地，在步骤(1)中，有机溶剂为六氟异丙醇(HFIP)、N,N-二甲基甲酰胺(DMF)、四氯乙烯和三氯甲烷中的一种或几种。
进一步地，在步骤(1)中，静电纺丝溶液中同时含有丝素蛋白和生物相容性聚合物时，丝素蛋白和生物相容性聚合物的质量比为0.1:100-100:0.1。
静电纺丝法可通过调节纺丝参数、溶液浓度、材料配比等，有效地调节所制备静电纺丝膜的结构和性能。
进一步地，在步骤(2)中，丝素蛋白水溶液的浓度为8％-15％；生物相容性聚合物溶液浓度为2％-10％；丝素蛋白和生物相容性聚合物混合液的浓度为4％-12％。
进一步地，生物相容性聚合物为聚(左旋乳酸-己内酯)(PLCL)、聚己内酯(PCL)、聚乳酸(PLA)、聚乳酸/聚乙醇酸共聚物(PLGA)、聚乙二醇(PEG)或壳聚糖。优选地，生物相容性聚合物为PLCL。
进一步地，复合屏障膜的厚度为0.35-0.74mm，拉伸断裂强度为2.2-22MPa。
进一步地，在步骤(3)中，采用下述方法复合。
(1)用生物胶粘合剂直接粘合内层膜和外层膜，如海藻生物胶、羊皮胶、骨胶和糊精，制得复合屏障膜；
(2)在外层膜流延法未变干前，将静电纺丝膜置于其上，直接粘合成复合屏障膜；
(3)将外层膜置于静电纺丝接收装置上，直接制得复合屏障膜。
除非特别指明，本发明的浓度均指的是质量浓度，为溶质的质量占溶液总重的比例。
借由上述方案，本发明至少具有以下优点：
本发明的复合屏障膜中由静电纺丝膜和包括流延膜的外层膜复合，所形成的复合膜形态稳定，空间保持性好，具有优良的干态、湿态力学性能。
复合屏障膜的双层膜的制备工艺比较简单，工艺流程短，易于实现批量化生产，并且可以通过调节各物质的比例、浓度等条件，实现对单层膜的控制。
本发明的复合屏障膜具有极好的机械性能，强度高，弹性好。
本发明的复合屏障膜中，随着外层膜中丝素蛋白的降解，复合屏障膜依旧可保持较高的力学性能，在药物递送、组织工程等生物医药领域具有潜在的应用价值。
上述说明仅是本发明技术方案的概述，为了能够更清楚了解本发明的技术手段，并可依照说明书的内容予以实施，以下以本发明的较佳实施例并配合附图详细说明如后。
附图说明
图1是本发明复合屏障膜的结构示意图；
图2是本发明的一种丝素/PLCL内层膜的扫描电镜图；
图3是本发明的一种丝素/PLCL复合屏障膜的图像；
附图标记说明：
1-内层膜；2-流延膜；3-外层膜；4-第二静电纺丝膜。
具体实施方式
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。
实施例1
参见图1，本发明的一种复合屏障膜，包括内层膜1和外层膜3，内层膜为第一静电纺丝膜，外层膜3包括流延膜2和第二静电纺丝膜4，且流延膜2包裹于第二静电纺丝膜4外部，第一静电纺丝膜或第二静电纺丝膜4分别可由丝素蛋白(SF)和/或生物相容性聚合物通过静电纺丝法制得，流延膜2由丝素蛋白溶液通过流延法制得。生物相容性聚合物优选为PLCL。
实施例2
(1)制备脱胶丝素蛋白：将2L去离子水加热至沸腾，加入4.24g无水碳酸钠粉末，待其完全溶解后，将预先用精密天平称取的5g家蚕丝放入其中，边煮边搅拌30min。随后取出丝并用去离子水清洗干净，放置于60℃的烘箱中烘干得到纯丝素纤维。将烘干的丝素纤维用浓度为9.3mol/L的溴化锂溶液在60℃下溶解约4-6h，浴比2.7:10。冷却后装入透析袋(截留分子量3500)中密封，去离子水中透析72h，再用离心机在9000r/min的转速下离心20min，重复两次。为了便于放置和使用，将得到的丝素蛋白溶液在常温下成膜，放置于4℃冰箱中备用。
(2)制备纺丝溶液：室温下，配置10％质量浓度的纺丝溶液，溶质PLCL。纺丝溶液的制备方法如下：用精密天平准确称取1.4g PLCL，溶解在12.6g的六氟异丙醇中，充分搅拌使其混合均匀，直至纺丝溶液中无可见颗粒状物，最终获得浓度为10％的纺丝溶液。
(3)静电纺丝膜的制备：室温下，将上述制备的纺丝溶液在电压20kV，接收距离15cm，流速2mL/h下进行静电纺丝，得到单层的静电纺丝膜，将其分别作为第一静电纺丝膜和第二静电纺丝膜。
(4)外层膜的制备：将第二静电纺丝膜放置于浓度为11.3％的SF水溶液中，用流延法 使SF形成流延膜，得到流延膜包裹的静电纺丝膜，即为外层膜。
(5)将步骤(3)制得的第一静电纺丝膜作为内层膜，将内层膜与步骤(4)制得的外层膜复合，得到丝素/PLCL复合屏障膜。
内层膜与外层膜可采用下述方法复合：
(1)用生物胶粘合剂直接粘合内层膜和外层膜，如海藻生物胶、羊皮胶、骨胶和糊精，制得复合屏障膜。
(2)在外层膜流延法未变干前，将静电纺丝膜置于其上，直接粘合成复合屏障膜。
(3)将外层膜置于静电纺丝接收装置上，直接制得复合屏障膜。
对上述单层静电纺丝膜进行SEM测试，对上述内层膜进行SEM测试，另外对复合屏障膜进行观察，结果如图2-3所示，图2结果表明内层静电纺丝膜微观下，纤维粗细均匀，形貌良好；图3表明外层膜有良好的支撑作用，粘合紧密，阻止上皮组织、结缔组织转移至缺损部位；复合屏障膜起双重支撑作用，可防止膜坍塌，可随体内降解，静电纺丝膜依然维持较好的力学性能。
实施例3
按照实施例2的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，溶质为脱胶后的SF和PLCL，纺丝溶液中SF:PLCL的质量比为25:75。纺丝溶液的制备方法如下：用精密天平准确称取0.35g SF，1.05g PLCL，溶解在12.6g的六氟异丙醇中，充分搅拌使其混合均匀，直至纺丝溶液中无可见颗粒状物。
实施例4
按照实施例3的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，纺丝溶液中SF:PLCL的质量比为50:50。纺丝溶液的制备方法如下：用精密天平准确称取0.7g SF，0.7g PLCL，溶解在12.6g的六氟异丙醇中，充分搅拌使其混合均匀，直至纺丝溶液中无可见颗粒状物。
实施例5
按照实施例3的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，纺丝溶液中SF:PLCL的质量比为75:25。纺丝溶液的制备方法如下：用精密天平准确称取1.05g SF，0.35g PLCL，溶解在12.6g的六氟异丙醇中，充分搅拌使其混合均匀，直至纺丝溶液中无可见颗粒状物。
实施例6
按照实施例2的方法制备复合屏障膜，不同之处在于，在步骤(2)中，纺丝溶液中除溶 剂外，只含有SF。纺丝溶液的制备方法如下：用精密天平准确称取1.4g SF，溶解在12.6g的六氟异丙醇中，充分搅拌使其混合均匀，直至纺丝溶液中无可见颗粒状物。
表1是以上实施例1-6制备的不同内层膜的力学性能的测试结果。结果表明，本发明的内层膜具有良好的力学性能。
表1 不同内层膜的力学性能的测试结果
质量比(SF:PLCL) 拉伸断裂强度(MPa) 断裂伸长率(％)
0/100 3.8±0.6 661.4±44.79
25/75 4.5±0.4 366.7±42.48
50/50 4.6±0.3 285.3±13.19
75/25 7.0±0.8 31.5±22.15
100/0 12.3±4.2 5.9±1.00
按照实施例2的方法制备不同的复合屏障膜，并且在制备过程中，按照实施例2步骤(3)的方法分别制备第一静电纺丝膜和第二静电纺丝膜，其中，第一静电纺丝膜中SF和PLCL的质量比为25:75，改变第二静电纺丝膜中SF和PLCL的质量比(依次为0:100、25:75、50:50、75:25、100:0)，对其进行力学性能测试，结果如表2所示。
表2 不同复合屏障膜的力学性能的部分测试结果
Figure PCTCN2018110558-appb-000001
实施例7
按照实施例2的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，纺丝电压为10kV，接收距离10cm，流速0.5mL/h。
实施例8
按照实施例2的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，纺丝电压为30kV，接收距离18cm，流速1.0mL/h。
实施例9
按照实施例2的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，纺丝电压为25kV，接收距离12cm，流速1.5mL/h。
实施例10
按照实施例2的方法制备丝素/PLCL复合屏障膜，不同之处在于，在步骤(2)中，溶剂 为DMF。
以上所述仅是本发明的优选实施方式，并不用于限制本发明，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变型，这些改进和变型也应视为本发明的保护范围。

Claims (10)

  1. 一种复合屏障膜，其特征在于：包括内层膜和外层膜，所述内层膜为第一静电纺丝膜，所述外层膜包括第二静电纺丝膜及流延膜，且所述流延膜复合于所述第二静电纺丝膜外部，所述第一静电纺丝膜或第二静电纺丝膜的材质分别独立地选自丝素蛋白和/或生物相容性聚合物，所述流延膜的材质为丝素蛋白。
  2. 根据权利要求1所述的复合屏障膜，其特征在于：所述复合屏障膜的厚度为0.35-0.74mm，拉伸断裂强度为2.2-22MPa。
  3. 根据权利要求1所述的复合屏障膜，其特征在于：所述内层膜和外层膜的厚度比为0.18-0.22:1。
  4. 根据权利要求1所述的复合屏障膜，其特征在于：所述第一静电纺丝膜或第二静电纺丝膜包括丝素蛋白和生物相容性聚合物时，丝素蛋白和生物相容性聚合物的质量比为0.1:100-100:0.1。
  5. 根据权利要求1所述的复合屏障膜，其特征在于：所述流延膜和第二静电纺丝膜的厚度比为1:4-1:9。
  6. 根据权利要求1所述的复合屏障膜，其特征在于：所述生物相容性聚合物为聚(左旋乳酸-己内酯)、聚己内酯、聚乳酸、聚乳酸/聚乙醇酸共聚物、聚乙二醇或壳聚糖。
  7. 一种权利要求1-6中任一项所述的复合屏障膜的制备方法，其特征在于，包括以下步骤：
    (1)分别提供第一静电纺丝膜和第二静电纺丝膜，所述第一静电纺丝膜和第二静电纺丝膜分别通过第一静电纺丝溶液和第二静电纺丝溶液在电压10-30kV，接收距离10-18cm，流速0.5-2mL/h条件下进行静电纺丝后得到，所述第一静电纺丝溶液或第二静电纺丝溶液中包括脱胶后的丝素蛋白和/或所述生物相容性聚合物以及有机溶剂；所述第一静电纺丝溶液或第二静电纺丝溶液的浓度为4％-12％；
    (2)将所述第二静电纺丝膜置于处理液中，采用流延法使处理液成膜，得到外层膜，所述外层膜为流延膜包裹的第二静电纺丝膜，其中，所述处理液为丝素蛋白水溶液；
    (3)将所述第一静电纺丝膜作为内层膜，将所述内层膜与所述外层膜复合，得到所述复合屏障膜。
  8. 根据权利要求7所述的方法，其特征在于：在步骤(1)中，所述有机溶剂为六氟异丙醇、N,N-二甲基甲酰胺、四氯乙烯和三氯甲烷中的一种或几种。
  9. 根据权利要求7所述的方法，其特征在于：在步骤(2)中，所述丝素蛋白水溶液的浓度为8％-15％；所述生物相容性聚合物溶液浓度为2％-10％；所述丝素蛋白和生物相容性 聚合物混合液的浓度为4％-12％。
  10. 根据权利要求7所述的方法，其特征在于：所述生物相容性聚合物为聚(左旋乳酸-己内酯)、聚己内酯、聚乳酸、聚乳酸/聚乙醇酸共聚物聚乙二醇或壳聚糖。
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101474430A (zh) * 2009-01-13 2009-07-08 武汉大学 一种生物活性组织再生膜及其制备方法
CN104474589A (zh) * 2014-12-23 2015-04-01 山东国际生物科技园发展有限公司 一种引导组织再生膜及其制备方法与应用
CN106039402A (zh) * 2016-07-12 2016-10-26 上海纳米技术及应用国家工程研究中心有限公司 一种双层仿骨膜材料及其制备方法
CN107349473A (zh) * 2017-07-24 2017-11-17 武汉理工大学 一种可降解聚乳酸/丝素/壳聚糖复合神经导管及其制备方法
CN107693845A (zh) * 2017-08-08 2018-02-16 上海纳米技术及应用国家工程研究中心有限公司 内外层分别负载HAp和VEGF的双层仿骨膜材料
WO2018033744A1 (en) * 2016-08-17 2018-02-22 Globalacorn Ltd. Carrier

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102277737A (zh) * 2011-04-27 2011-12-14 南昌大学 聚己内酯/天然高分子复合多孔支架的制备方法及应用
CN102499800B (zh) * 2011-11-17 2014-07-16 苏州大学 血管支架及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101474430A (zh) * 2009-01-13 2009-07-08 武汉大学 一种生物活性组织再生膜及其制备方法
CN104474589A (zh) * 2014-12-23 2015-04-01 山东国际生物科技园发展有限公司 一种引导组织再生膜及其制备方法与应用
CN106039402A (zh) * 2016-07-12 2016-10-26 上海纳米技术及应用国家工程研究中心有限公司 一种双层仿骨膜材料及其制备方法
WO2018033744A1 (en) * 2016-08-17 2018-02-22 Globalacorn Ltd. Carrier
CN107349473A (zh) * 2017-07-24 2017-11-17 武汉理工大学 一种可降解聚乳酸/丝素/壳聚糖复合神经导管及其制备方法
CN107693845A (zh) * 2017-08-08 2018-02-16 上海纳米技术及应用国家工程研究中心有限公司 内外层分别负载HAp和VEGF的双层仿骨膜材料

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