CN112587721A

CN112587721A - Injection filling material and preparation process thereof

Info

Publication number: CN112587721A
Application number: CN202011610786.0A
Authority: CN
Inventors: 金振华; 区京华; 王立杰
Original assignee: Guangzhou Yicheng Biotechnology Co ltd
Current assignee: Guangzhou Yicheng Biotechnology Co ltd
Priority date: 2020-12-30
Filing date: 2020-12-30
Publication date: 2021-04-02
Also published as: WO2022142350A1

Abstract

The invention discloses an injection filling material and a preparation process thereof, wherein the filling material comprises the following raw materials in percentage by mass: 0.1-2% of sodium hyaluronate, 1-30% of polyester microsphere, 0.1-5% of silk fibroin, 0.01-1% of recombinant triple collagen and the balance of dispersion. The polyester material is artificially synthesized, the sodium hyaluronate and the recombinant protein are prepared by a fermentation method, and the silk fibroin is extracted from the secretion of the silkworm but not from animal tissues, so that the silk fibroin has better biological safety compared with collagen and acellular matrix extracted from the animal tissues; the added polyester microspheres can form a slow release effect on a system, prolong the effective time of the filling material and have longer lasting time compared with a single-component material; the filling material comprises type I collagen (silk fibroin), type III collagen (recombinant protein) and carbohydrate nutrient (hyaluronic acid) required by tissue production, and can provide a complete external environment for the tissue production.

Description

Injection filling material and preparation process thereof

Technical Field

The invention relates to the technical field of biotechnology, in particular to an injection filling material and a preparation process thereof.

Background

The existing materials for repairing and reconstructing the functions of human tissues comprise hyaluronic acid, collagen, acellular matrixes and the like, the hyaluronic acid and the collagen have single functions, the acellular matrixes can provide most of required nutrient components and growth factors for the tissues, but a plurality of toxic substances are introduced into the production process, and the current production process is difficult to ensure that foreign proteins or fragments containing immunogenicity are removed on the premise of keeping functional components, so that potential safety hazards are brought.

The invention provides a formula without adding harmful components, and aims to provide a novel implant material which has no rejection reaction, excellent biocompatibility, is similar to human soft tissue in physical and biological functions and can promote tissue function repair, and improve the living environment of soft tissue cells in a mildest mode so as to protect and repair the functions of the soft tissue cells.

Disclosure of Invention

The invention aims to provide an injection filling material and a preparation process thereof.

In order to achieve the purpose, the invention provides the following technical scheme: an injection filling material comprises the following raw materials in mass percentage: 0.1-2% of sodium hyaluronate, 1-30% of polyester microsphere, 0.1-5% of silk fibroin, 0.01-1% of recombinant triple collagen and the balance of dispersion.

Preferably, the injection filling material comprises the following raw materials in percentage by mass: 1.2% of sodium hyaluronate, 15% of polyester microspheres, 2% of silk fibroin, 0.05% of recombinant triple collagen and the balance of dispersion.

Preferably, the polyester microspheres are homopolymers or copolymers of absorbable synthetic polyester materials such as PLA, PCL, PGA and PDO, and the particle size of the polyester microspheres ranges from 100nm to 100 μm.

Further preferably, the particle size range of the polyester microspheres is 5-75 μm, and optimally is 15-50 μm;

preferably, the sodium hyaluronate is crosslinked or uncrosslinked high molecular weight sodium hyaluronate, and the molecular weight is more than or equal to 120 ten thousand;

further preferably, the sodium hyaluronate is uncrosslinked sodium hyaluronate, and the molecular weight is 180-.

Preferably, the dispersion is a buffer, physiological saline or water for injection.

Further preferably, the dispersion is PBS buffer solution, which provides the product with the osmotic pressure similar to the cell fluid and the pH value similar to the tissue fluid.

A preparation process of an injection filling material comprises the following steps: s1, preparing the polyester material into polyester microspheres with corresponding particle size ranges by an emulsification volatilization method, an electrostatic spraying method or a microfluidic method;

s2, stirring the polyester microspheres in the dispersion liquid according to the mass percentage of the injection filling material, and then homogenizing and dispersing the mixture uniformly by using a high-speed homogenizer;

s3, adding the recombinant triple-type collagen into the dispersion liquid for dissolving;

s4, adding silk fibroin into the solution prepared in the S3, and carrying out high-speed homogenizing, shearing and dispersing to obtain a mixed dispersion liquid;

s5, adding sodium hyaluronate into the mixed dispersion prepared in the S4, dissolving, mixing, dispersing and defoaming in vacuum;

and S6, vacuum filling the mixed solution subjected to defoaming in the S5 into a pre-filling syringe.

Compared with the prior art, the invention has the following beneficial effects:

the polyester material in the filling material is artificially synthesized, sodium hyaluronate and recombinant protein are prepared by a fermentation method, and silk fibroin is extracted from secretions of silkworm instead of animal tissues, so that the silk fibroin has better biological safety compared with collagen and acellular matrix extracted from animal tissues;

the polyester microspheres added into the filling material can form a slow release effect on a system, prolong the effective time of the filling material and have longer lasting time compared with a single-component material;

the filling material comprises type I collagen (silk fibroin), type III collagen (recombinant protein) and carbohydrate nutrient (hyaluronic acid) required by tissue production, and can provide a complete external environment for the tissue production.

Detailed Description

The technical solutions of the present invention will be described clearly and completely in the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Examples

Examples 1-3 injection filling materials were prepared according to the mass ratio of raw materials in table 1.

TABLE 1

Examples 1-3 injection filling materials were prepared by the following method:

s1, weighing the polyester microspheres in proportion, adding the polyester microspheres into a certain amount of dispersion liquid, and mechanically stirring for 30min at a stirring speed of 500 rpm;

s2, adding the recombinant protein into the dispersion liquid, and magnetically stirring for 40min until the recombinant protein is completely dissolved;

s2, adding silk fibroin into the stirred dispersion liquid, and continuously stirring for 40 min;

s3, placing the dispersion liquid under a homogenizer, homogenizing and emulsifying for 10min at 10000rpm to form a suspension;

s4, adding sodium hyaluronate powder into the suspension while stirring the suspension in a vortex manner, and continuously stirring until the suspension is colloidal and no vortex is formed on the surface of the suspension;

s5, standing for 72-96h until the hyaluronic acid is uniformly swelled;

s6, putting the swelled sodium hyaluronate into an emulsification tank, stirring and vacuumizing to eliminate bubbles in the materials for later use;

and S7, filling the defoamed materials into a pre-filling and sealing injector through an automatic filling machine.

The cross-linked sodium hyaluronate gel is used as a control group, the physiological saline is used as a blank control group, three groups of examples are used as test groups, animals are tested by rabbits through different lesion modeling, and the following data are obtained through general observation and contrast pathological section staining analysis:

from the above table, it can be seen that the injectable filling materials prepared in examples 1 to 3 are excellent in safety, do not cause infection when applied to the subcutaneous tissue of rabbits or applied to the external wound, and can prolong the effective time of the filling materials.

Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims

1. An injectable filling material, characterized by: the filling material comprises the following raw materials in percentage by mass: 0.1-2% of sodium hyaluronate, 1-30% of polyester microsphere, 0.1-5% of silk fibroin, 0.01-1% of recombinant triple collagen and the balance of dispersion.

2. An injectable filling material according to claim 1, wherein: the injection filling material comprises the following raw materials in mass percentage: 1.2% of sodium hyaluronate, 15% of polyester microspheres, 2% of silk fibroin, 0.05% of recombinant triple collagen and the balance of dispersion.

3. An injectable 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 particle size range of the polyester microspheres is 100nm-100 mu m.

4. An injectable filling material according to claim 1, wherein: the particle size range of the polyester microsphere is 5-75 μm, and the optimal particle size range is 15-50 μm.

5. An injectable filling material according to claim 1, wherein: the sodium hyaluronate is cross-linked or non-cross-linked high molecular weight sodium hyaluronate, and the molecular weight is more than or equal to 120 ten thousand.

6. An injectable filling material according to claim 1, wherein: the sodium hyaluronate is uncrosslinked sodium hyaluronate, and the molecular weight is 180-260 ten thousand, and the optimal molecular weight is 200-240 thousand.

7. An injectable filling material according to claim 1, wherein: the dispersion is buffer solution, physiological saline or water for injection.

8. An injectable filling material according to claim 1, wherein: the dispersion was PBS buffer.

9. A preparation process of an injection filling material is characterized by comprising the following steps: the specific process steps are as follows: s1, preparing the polyester material into polyester microspheres with corresponding particle size ranges by an emulsification volatilization method, an electrostatic spraying method or a microfluidic method;