Preparation method of hyaluronic acid filling agent

A technology of hyaluronic acid and hyaluronidase, which is applied in the field of material science, can solve the problems of difficulty in ensuring the mixing effect, rejection reaction, and uneven particles, so as to shorten the time for uniform mixing, prolong the time of action, and avoid Gathering effect

Pending Publication Date: 2021-12-31
BLOOMAGE BIOTECHNOLOGY CORP LTD
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Problems solved by technology

[0005] At present, when microspheres are mixed with cross-linked hyaluronic acid, the mixing effect is difficult to ensure. Microspheres are easy to aggregate, particles are not uniform, and fusion occurs during high-temperature sterilization, which leads to blockage of the needle during injection and rejection when injected into the human body. reaction

Method used

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  • Preparation method of hyaluronic acid filling agent
  • Preparation method of hyaluronic acid filling agent
  • Preparation method of hyaluronic acid filling agent

Examples

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preparation example Construction

[0036] The present invention provides a kind of preparation method of hyaluronic acid filler, and described preparation method comprises the following steps:

[0037] uniformly mixing the dried first hyaluronic acid or its salt with the dried degradable polymer microspheres to obtain starting materials;

[0038] Cross-linking the starting material with a cross-linking agent, purifying, and granulating to obtain hyaluronic acid gel containing microspheres;

[0039] The hyaluronic acid gel containing the microspheres is purified, filled, and sterilized to obtain a hyaluronic acid filler.

[0040] In a specific embodiment, the mass ratio of the first hyaluronic acid or its salt to the degradable polymer microspheres is 1:0.01˜1:1. For example, it can be 1:0.01, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.

[0041] In a specific embodiment, the mass ratio of the cross-linking agent to the first hyaluronic acid or its salt is 0.5-4:100, for example, it can ...

Embodiment 1

[0073] (1) Preparation of polycaprolactone microspheres

[0074] Weigh 1 g (60 kDa) of polycaprolactone and dissolve it in 10 ml of dichloromethane to obtain the first solution. Weigh 0.1 g of hyaluronic acid (molecular weight of hyaluronic acid is 1000 kDa) as the second hyaluronic acid and dissolve it in 100 g of water (the content of hyaluronic acid is 1 mg / g), and add 10000 IU of hyaluronidase to obtain the second solution. After the second solution is prepared, the first solution is sprayed into the second solution through an ultrasonic atomizer immediately, and the diameter of the droplet particles formed by ultrasonic atomization of the first solution is adjusted to 100 microns. During this process, the second solution was stirred and heated at the same time, wherein the reaction temperature was set at 42° C. until the organic solvent was completely volatilized, and crude polycaprolactone microspheres were obtained. The obtained crude polycaprolactone microspheres were...

Embodiment 2

[0078] The difference between Examples 2-4 and Example 1 is that the quality of polycaprolactone microspheres is different, and other reaction conditions are the same as Example 1. Specifically, in embodiment 2, the quality of polycaprolactone microsphere is 0.05g; In embodiment 3, the quality of polycaprolactone microsphere is 0.01g; In embodiment 4, the quality of polycaprolactone microsphere The mass of the ball is 1g. Specifically, the main reaction parameters are shown in Table 1.

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Abstract

The invention provides a preparation method of a hyaluronic acid filling agent. The preparation method comprises the following steps: uniformly mixing dried first hyaluronic acid or salt thereof with dried degradable polymer microspheres to obtain a starting raw material; carrying out a cross-linking reaction on the initial raw material by using a cross-linking agent, purifying and granulating to obtain hyaluronic acid gel containing microspheres; and purifying, filling and sterilizing the hyaluronic acid gel containing the microspheres to obtain the hyaluronic acid filling agent. The microspheres and the hyaluronic acid or the salt thereof are mixed in a dry powder state, so that materials can be uniformly mixed in a relatively short time, microsphere aggregation is effectively avoided, the uniform mixing time is shortened, deformation and fusion of the microspheres caused by aggregation and exposure in the sterilization and temperature rise process are avoided, Therefore, the occurrence rate of needle blockage in the injection process and postoperative adverse reaction is reduced.

Description

technical field [0001] The invention belongs to the field of material science, and in particular relates to a preparation method of a hyaluronic acid filler. Background technique [0002] Hyaluronic acid (Hyaluronic acid, HA), also known as hyaluronic acid, is a long-chain polymer mucopolysaccharide composed of D-glucuronic acid and N-acetylglucosamine alternately arranged. It is widely distributed in various parts of the human body and has good hydrophilicity. , viscoelasticity, lubricity and biocompatibility, the cross-linked sodium hyaluronate gel prepared by chemically modifying the HA structure is widely used in the field of medical cosmetology. The common products on the market for cosmetic filling are: Restylane , Juvéderm and other brands. However, the cross-linked sodium hyaluronate gel filler generally lasts for 6-12 months in the body and is gradually absorbed by the body. Multiple injections are required to maintain the filling effect. [0003] Mixing microsphe...

Claims

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Application Information

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IPC IPC(8): C08J3/24C08L5/08C08L67/04
CPCC08J3/24C08J2305/08C08J2467/04C08J2367/04C08J2405/08
Inventor 吴万福苏江伟刘建建沈延臻刘旭陈雯雯郭学平
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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