WO2022142350A1 - Injection filling material and preparation process - Google Patents

Injection filling material and preparation process Download PDF

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Publication number
WO2022142350A1
WO2022142350A1 PCT/CN2021/111380 CN2021111380W WO2022142350A1 WO 2022142350 A1 WO2022142350 A1 WO 2022142350A1 CN 2021111380 W CN2021111380 W CN 2021111380W WO 2022142350 A1 WO2022142350 A1 WO 2022142350A1
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filling material
sodium hyaluronate
injection
polyester
injection filling
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PCT/CN2021/111380
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French (fr)
Chinese (zh)
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金振华
王立杰
区京华
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广州益诚生物科技有限公司
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Publication of WO2022142350A1 publication Critical patent/WO2022142350A1/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
    • A61L27/14—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
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/20—Polysaccharides
    • 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
    • A61L27/24—Collagen
    • 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
    • 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
    • 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
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/622—Microcapsules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions

Definitions

  • the invention relates to the technical field of biotechnology, in particular to an injection filling material and a preparation process.
  • the materials used for the repair and reconstruction of human tissue functions include hyaluronic acid, collagen, acellular matrix, etc.
  • Hyaluronic acid and collagen have a single function, and acellular matrix can provide most of the nutrients and growth factors required by the tissue. , but its production process introduces a variety of toxic substances, and the current production process is difficult to ensure that the impurities or fragments containing immunogenicity can be removed on the premise of retaining functional components, so as to bring security risks.
  • the present invention provides a formula without adding harmful ingredients, which aims to provide a new type of implant that has no rejection reaction, excellent biocompatibility, is similar to human soft tissue in terms of physical and biological functions, and can promote tissue function repair. It can improve the living environment of soft tissue cells in the most gentle way, so as to protect and repair the function of soft tissue cells.
  • the purpose of the present invention is to provide an injection filling material and a preparation process.
  • an injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 0.1-2%, polyester microspheres 1-30%, silk fibroin 0.1-5% , Recombinant type III collagen 0.01-1%, and the balance is dispersion liquid.
  • the injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 1.2%, polyester microspheres 15%, silk fibroin 2%, recombinant type III collagen 0.05%, and the balance is dispersion liquid .
  • the polyester microspheres are homopolymers or copolymers of PLA, PCL, PGA, and PDO absorbable synthetic polyester materials, and the diameter of the polyester microspheres ranges from 100 nm to 100 ⁇ m.
  • the particle size range of the polyester microspheres is 5 ⁇ m-75 ⁇ m, and the optimum is 15-50 ⁇ m;
  • the sodium hyaluronate is cross-linked or uncross-linked high-molecular-weight sodium hyaluronate, with a molecular weight of ⁇ 1.2 million;
  • the sodium hyaluronate is uncross-linked sodium hyaluronate, and the molecular weight is 1.8-2.6 million, and the most optimal is 2.0-2.4 million.
  • the dispersion is buffer, physiological saline or water for injection.
  • the dispersion liquid is a PBS buffer, which provides the product with an osmotic pressure close to the cell liquid phase and a pH close to the tissue liquid phase.
  • a preparation process of an injection filling material S1.
  • the polyester material is prepared into polyester microspheres with a corresponding particle size range by an emulsification volatilization method or an electrostatic spray method or a microfluidic method;
  • the polyester material in the filling material is artificially synthesized, and sodium hyaluronate and recombinant protein are made by fermentation.
  • the silk fibroin is extracted from the secretions of silkworms instead of animal tissues.
  • Cell matrix has better biosafety;
  • polyester microspheres added to the filling material can form a slow-release effect on the system and prolong the effective time of the filling material, which is longer than that of the single-component material;
  • the filler material contains type I collagen (silk fibroin), type III collagen (recombinant protein), and carbohydrate nutrients (hyaluronic acid) required for tissue production, and can provide a complete external environment for tissue production.
  • Example 1-3 The injection filling materials are proportioned according to the mass ratio of raw materials in Table 1.
  • polyester microspheres in proportion, add them to a certain amount of dispersion, stir mechanically for 30 minutes, and stir at a rate of 500 rpm;
  • the cross-linked sodium hyaluronate gel was used as the control group, the normal saline was used as the blank control group, and the three groups of examples were used as the test group. Animal experiments were carried out with rabbits using different lesion modeling. , get the following data:

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Public Health (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Disclosed are an injection filling material and a preparation process. The filling material comprises the following raw materials in terms of percentage by mass: 0.1-2% of sodium hyaluronate, 1-30% of polyester microspheres, 0.1-5% of silk fibroin, 0.01-1% of recombinant type III collagen, with the balance being a dispersion liquid. The polyester material is artificially synthesized; the sodium hyaluronate and recombinant protein are prepared by means of a fermentation method; the silk fibroin is extracted from secretions of mulberry silkworms instead of animal tissues, and compared with collagen extracted from animal tissues, a decellularized matrix is biologically safer; and the added polyester microspheres can produce a sustained-release effect on a system, prolong the duration of validity of the filling material, and the filling material lasts longer compared to a single-component material. The filling material comprises type I collagen (silk fibroin), type III collagen (recombinant protein) and a carbohydrate nutrient substance (hyaluronic acid), which are required for tissue production, and can provide a complete external environment for tissue production.

Description

一种注射填充材料及制备工艺A kind of injection filling material and preparation process 技术领域technical field
本发明涉及生物科技技术领域，具体为一种注射填充材料及制备工艺。The invention relates to the technical field of biotechnology, in particular to an injection filling material and a preparation process.
背景技术Background technique
目前用于人体组织功能修复、重建的材料有透明质酸、胶原蛋白、脱细胞基质等，透明质酸和胶原蛋白功能单一，脱细胞基质能够为组织提供大部分所需的营养成分、生长因子，但其生产工艺引入多种有毒害物质，且当前的生产工艺很难保障在保留功能成分的前提下去除干净其中的杂蛋白或含有免疫原性的片段，以至于带来安全隐患。At present, the materials used for the repair and reconstruction of human tissue functions include hyaluronic acid, collagen, acellular matrix, etc. Hyaluronic acid and collagen have a single function, and acellular matrix can provide most of the nutrients and growth factors required by the tissue. , but its production process introduces a variety of toxic substances, and the current production process is difficult to ensure that the impurities or fragments containing immunogenicity can be removed on the premise of retaining functional components, so as to bring security risks.
本发明提供一种不添加有害成分的配方，该配方旨在提供一种无排异反应、生物相容性优异、与人体软组织在物理、生物功能方面近似，且能够促进组织功能修复的新型植入材料，以一种最为温和的方式改善软组织细胞的生存环境，从而保护、修复软组织细胞的功能。The present invention provides a formula without adding harmful ingredients, which aims to provide a new type of implant that has no rejection reaction, excellent biocompatibility, is similar to human soft tissue in terms of physical and biological functions, and can promote tissue function repair. It can improve the living environment of soft tissue cells in the most gentle way, so as to protect and repair the function of soft tissue cells.
发明内容SUMMARY OF THE INVENTION
本发明的目的在于提供一种注射填充材料及制备工艺。The purpose of the present invention is to provide an injection filling material and a preparation process.
为实现上述目的，本发明提供如下技术方案：一种注射填充材料包含以下质量百多比原料：透明质酸钠0.1-2％、聚酯微球1-30％、丝素蛋白0.1-5％、重组三型胶原蛋白0.01-1％，余量为分散液。In order to achieve the above purpose, the present invention provides the following technical solutions: an injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 0.1-2%, polyester microspheres 1-30%, silk fibroin 0.1-5% , Recombinant type III collagen 0.01-1%, and the balance is dispersion liquid.
优选的，所述的注射填充材料包含以下质量百多比原料：透明质酸钠1.2％、聚酯微球15％、丝素蛋白2％、重组三型胶原蛋白0.05％，余量为分散液。Preferably, the injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 1.2%, polyester microspheres 15%, silk fibroin 2%, recombinant type III collagen 0.05%, and the balance is dispersion liquid .
优选的，所述的聚酯微球为PLA、PCL、PGA、PDO可吸收合成聚酯材料的均聚物或共聚物，聚酯微球粒径范围为100nm-100μm。Preferably, the polyester microspheres are homopolymers or copolymers of PLA, PCL, PGA, and PDO absorbable synthetic polyester materials, and the diameter of the polyester microspheres ranges from 100 nm to 100 μm.
进一步优选，所述的聚酯微球粒径范围为5μm-75μm，最优为15-50μm；Further preferably, the particle size range of the polyester microspheres is 5 μm-75 μm, and the optimum is 15-50 μm;
优选的，所述的透明质酸钠为交联或未交联的高分子量透明质酸钠，分子量≥120万；Preferably, the sodium hyaluronate is cross-linked or uncross-linked high-molecular-weight sodium hyaluronate, with a molecular weight of ≥1.2 million;
进一步优选，所述的透明质酸钠为未交联透明质酸钠，分子量180-260万，最优为 200-240万。Further preferably, the sodium hyaluronate is uncross-linked sodium hyaluronate, and the molecular weight is 1.8-2.6 million, and the most optimal is 2.0-2.4 million.
优选的，所述的分散液是缓冲液、生理盐水或注射用水。Preferably, the dispersion is buffer, physiological saline or water for injection.
进一步优选，所述的分散液是PBS缓冲液，为产品提供与细胞液相近的渗透压和与组织液相近的酸碱度。Further preferably, the dispersion liquid is a PBS buffer, which provides the product with an osmotic pressure close to the cell liquid phase and a pH close to the tissue liquid phase.
一种注射填充材料的制备工艺：S1、将聚酯材料通过乳化挥发法或静电喷雾法或微流控法制备成相应粒径范围的聚酯微球；A preparation process of an injection filling material: S1. The polyester material is prepared into polyester microspheres with a corresponding particle size range by an emulsification volatilization method or an electrostatic spray method or a microfluidic method;
S2、按照注射填充材料的质量百分比原料配比，将聚酯微球在分散液中搅拌，再用高速均质仪均质分散均匀；S2. According to the raw material ratio of the mass percentage of the injection filling material, stir the polyester microspheres in the dispersion liquid, and then use a high-speed homogenizer to homogenize and disperse evenly;
S3、将重组三型胶原蛋白加入分散液中溶解；S3, adding the recombinant type III collagen into the dispersion to dissolve;
S4、将丝素蛋白加入S3制备的溶液中，高速均质剪切分散为混合分散液；S4, adding silk fibroin to the solution prepared in S3, and dispersing it into a mixed dispersion by high-speed homogeneous shearing;
S5、将透明质酸钠，加入S4制备的混合分散液中，溶解、混合、分散，真空消泡；S5, adding sodium hyaluronate to the mixed dispersion prepared in S4, dissolving, mixing, dispersing, and vacuum defoaming;
S6、将S5除泡后的混合液真空灌装到预灌封注射器中。S6, vacuum filling the mixed solution after the defoaming of S5 into a pre-filled syringe.
与现有技术相比，本发明的有益效果如下：Compared with the prior art, the beneficial effects of the present invention are as follows:
填充材料中的聚酯材料通过人工合成，透明质酸钠和重组蛋白经过发酵法制成，丝素蛋白提取自桑蚕的分泌物而非动物组织，相比从动物组织中提取的胶原蛋白、脱细胞基质具有更好的生物安全性；The polyester material in the filling material is artificially synthesized, and sodium hyaluronate and recombinant protein are made by fermentation. The silk fibroin is extracted from the secretions of silkworms instead of animal tissues. Cell matrix has better biosafety;
填充材料中加入的聚酯微球，能够对体系形成缓释作用，延长填充材料的有效时间，相比单组分的材料持效时间更长；The polyester microspheres added to the filling material can form a slow-release effect on the system and prolong the effective time of the filling material, which is longer than that of the single-component material;
填充材料包含组织生产所需的一型胶原蛋白(丝素蛋白)、三型胶原蛋白(重组蛋白)、糖类营养物质(透明质酸)，能够为组织生产提供完整的外部环境。The filler material contains type I collagen (silk fibroin), type III collagen (recombinant protein), and carbohydrate nutrients (hyaluronic acid) required for tissue production, and can provide a complete external environment for tissue production.
具体实施方式Detailed ways
下面将结合本发明实施例中对本发明的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
实施例Example
实施例1-3注射填充材料按照表1质量比原料配比。Example 1-3 The injection filling materials are proportioned according to the mass ratio of raw materials in Table 1.
表1Table 1
Figure PCTCN2021111380-appb-000001
Figure PCTCN2021111380-appb-000001
实施例1-3注射填充材料的制备方法为:The preparation method of embodiment 1-3 injection filling material is:
S1、按比例称量聚酯微球，加入到一定量的分散液中，机械搅拌30min，搅拌速率500rpm；S1. Weigh polyester microspheres in proportion, add them to a certain amount of dispersion, stir mechanically for 30 minutes, and stir at a rate of 500 rpm;
S2、将重组蛋白加入分散液中，磁力搅拌40min至完全溶解；S2. Add the recombinant protein into the dispersion, and stir magnetically for 40min until it is completely dissolved;
S2、将丝素蛋白加入搅拌后的分散液中，持续搅拌40min；S2, adding silk fibroin to the stirred dispersion, and stirring continuously for 40min;
S3、将分散液置于均质器下，10000rpm均质乳化10min，形成悬浊液；S3, place the dispersion under a homogenizer, and homogeneously emulsify at 10000rpm for 10min to form a suspension;
S4、在悬浊液中边涡旋搅拌，边加入透明质酸钠粉末，持续搅拌至悬浊液呈胶状，表面不再形成涡旋；S4, while vortex stirring in the suspension, add sodium hyaluronate powder, and continue stirring until the suspension is gelatinous, and no vortex is formed on the surface;
S5、静置72-96h至透明质酸溶胀均匀；S5, stand for 72-96h until the hyaluronic acid swells evenly;
S6、将溶胀后的透明质酸钠放入乳化罐中，边搅拌边抽真空，消除其中物料中的气泡备用；S6, put the swollen sodium hyaluronate into the emulsification tank, vacuumize while stirring, and eliminate the bubbles in the material for subsequent use;
S7、将消泡后的物料经自动灌装机灌装到预灌封注射器中。S7. Fill the defoamed material into a pre-filled syringe through an automatic filling machine.
用交联透明质酸钠凝胶做对照组，生理盐水做空白对照组，三组实施例作为试验组，用兔子采用不同的病灶建模进行动物试验，并通过大体观察、对比病理切片染色分析，得到以下数据：The cross-linked sodium hyaluronate gel was used as the control group, the normal saline was used as the blank control group, and the three groups of examples were used as the test group. Animal experiments were carried out with rabbits using different lesion modeling. , get the following data:
Figure PCTCN2021111380-appb-000002
Figure PCTCN2021111380-appb-000002
由上表可得本实施例1-3制备的注射填充材料安全性能好，不管是应用在兔子的皮下组织还是皮外伤口涂覆均不会出现感染，且能延长填充材料的有效时间。From the above table, it can be seen that the injection filling materials prepared in Examples 1-3 have good safety performance, no infection will occur whether it is applied to the subcutaneous tissue of rabbits or extracutaneous wound coating, and the effective time of the filling materials can be prolonged.
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, and substitutions can be made in these embodiments without departing from the principle and spirit of the invention and modifications, the scope of the present invention is defined by the appended claims and their equivalents.

Claims (9)

  1. 一种注射填充材料，其特征在于：所述的填充材料包含以下质量百多比原料：透明质酸钠0.1-2％、聚酯微球1-30％、丝素蛋白0.1-5％、重组三型胶原蛋白0.01-1％，余量为分散液。An injection filling material, characterized in that: the filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 0.1-2%, polyester microspheres 1-30%, silk fibroin 0.1-5%, recombinant Type III collagen is 0.01-1%, and the balance is dispersion.
  2. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的注射填充材料包含以下质量百多比原料：透明质酸钠1.2％、聚酯微球15％、丝素蛋白2％、重组三型胶原蛋白0.05％，余量为分散液。The injection filling material according to claim 1, wherein the injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 1.2%, polyester microspheres 15%, silk fibroin 2% , Recombinant type III collagen 0.05%, and the balance is dispersion liquid.
  3. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的聚酯微球为PLA、PCL、PGA、PDO可吸收合成聚酯材料的均聚物或共聚物，聚酯微球粒径范围为100nm-100μm。An injection filling material according to claim 1, wherein the polyester microspheres are homopolymers or copolymers of PLA, PCL, PGA, and PDO absorbable synthetic polyester materials, and the polyester microspheres are The particle size range is 100nm-100μm.
  4. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的聚酯微球粒径范围为5μm-75μm，最优为15-50μm。The injection filling material according to claim 1, wherein the polyester microspheres have a particle size range of 5 μm-75 μm, and an optimum range of 15-50 μm.
  5. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的透明质酸钠为交联或未交联的高分子量透明质酸钠，分子量≥120万。The injection filling material according to claim 1, wherein the sodium hyaluronate is cross-linked or uncross-linked high-molecular-weight sodium hyaluronate, and the molecular weight is greater than or equal to 1.2 million.
  6. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的透明质酸钠为未交联透明质酸钠，分子量180-260万，最优为200-240万。The injection filling material according to claim 1, wherein the sodium hyaluronate is uncrosslinked sodium hyaluronate, and the molecular weight is 1.8-2.6 million, and the optimum is 2.0-2.4 million.
  7. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的分散液是缓冲液、生理盐水或注射用水。The filling material for injection according to claim 1, wherein the dispersion liquid is a buffer solution, physiological saline or water for injection.
  8. 根据权利要求1所述的一种注射填充材料，其特征在于：所述的分散液是PBS缓冲液。The filling material for injection according to claim 1, wherein the dispersion is a PBS buffer.
  9. 一种注射填充材料的制备工艺，其特征在于：具体工艺步骤为：S1、将聚酯材料通过乳化挥发法或静电喷雾法或微流控法制备成相应粒径范围的聚酯微球；A preparation process for injection filling material, characterized in that: the specific process steps are: S1, preparing polyester material into polyester microspheres with a corresponding particle size range by an emulsification volatilization method or an electrostatic spray method or a microfluidic method;
    S2、按照注射填充材料的质量百分比原料配比，将聚酯微球在分散液中搅拌，再用高速均质仪均质分散均匀；S2. According to the raw material ratio of the mass percentage of the injection filling material, stir the polyester microspheres in the dispersion liquid, and then use a high-speed homogenizer to homogenize and disperse evenly;
    S3、将重组三型胶原蛋白加入分散液中溶解；S3, adding the recombinant type III collagen into the dispersion to dissolve;
    S4、将丝素蛋白加入S3制备的溶液中，高速均质剪切分散为混合分散液；S4, adding silk fibroin to the solution prepared in S3, and dispersing it into a mixed dispersion by high-speed homogeneous shearing;
    S5、将透明质酸钠，加入S4制备的混合分散液中，溶解、混合、分散，真空消泡；S5, adding sodium hyaluronate to the mixed dispersion prepared in S4, dissolving, mixing, dispersing, and vacuum defoaming;
    S6、将S5除泡后的混合液真空灌装到预灌封注射器中。S6, vacuum filling the mixed solution after the defoaming of S5 into a pre-filled syringe.
PCT/CN2021/111380 2020-12-30 2021-08-09 Injection filling material and preparation process WO2022142350A1 (en)

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