Recombinant collagen biphasic gel as well as preparation method and application thereof

Abstract

The invention discloses recombinant collagen biphasic gel as well as a preparation method and application thereof, and relates to the technical field of biomedical materials. According to the invention, through a synchronous emulsification and crosslinking mode, in an emulsification process, a crosslinking agent is dropped into a system being emulsified at the same time, the crosslinking agent is directly wrapped in collagen emulsion particles by a part of emulsion droplets, the internal crosslinking degree of the emulsion particles is high, and the internal crosslinking degree of a part of emulsion droplets which are not wrapped by the crosslinking agent or wrapped by a small amount of the crosslinking agent is small, and therefore emulsion particles with multiple crosslinking degree distributions can be formed. The collagen microspheres with different cross-linking degrees are prepared at the same time through one-time emulsification cross-linking reaction, so that the cross-linking degrees of the collagen microspheres in the recombinant collagen two-phase gel are different, and gradient degradation can be realized.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a recombinant collagen biphasic gel and its preparation method and application. Background technique [0002] With age or photoaging, the skin becomes loose or wrinkled, forming wrinkles or depressions such as nasolabial folds and crow's feet. Soft tissue fillers can be used to correct wrinkles or fill in depressions. Soft tissue filling materials currently used in clinical practice mainly include hyaluronic acid, hydroxyapatite, polylactic acid, polymethyl methacrylate, collagen, etc., among which collagen is the most ideal filling material. Collagen is an important part of human tissue, with good histocompatibility, and no obvious foreign body sensation after implantation; its unique cell adhesion and cell proliferation induction can induce cell proliferation in the filling site after long-term implantation. Achieve tissue repair. [0003] Collagen products curr...

AI Technical Summary

Problems solved by technology

However, the above products still have the following technical problems: 1. Collagen raw materials are mainly derived from animal tissues, such as bovine Achilles tendon, pig skin, etc., and there are risks of virus and immunogenicity; 2. Non-permanent filling products generally degrade too quickly in the body 1. Multiple injections are required, which increases the burden on consumers; 3. For permanent implants in the body (such as Aibeifu), on the one hand, the collagen components in them are gradually degraded and reduced, and repeated injections are required to keep the number of polymer particles at half. The above can achieve a relatively long-term cosmetic effect. On the other hand, non-degradable PMMA microspheres have the risk of foreign body granuloma, and it will also form crystals in the deep layer of the skin that cannot be degraded, foreign body stimulation and poor biocompatibility.

[0004] In terms of collagen gel biphasic system technology, there are currently related disclosed technologies; for example, Patent Publication No. CN103834053A discloses an injectable cross-linked hyaluronic acid gel and its preparation method, which adopts emulsification and cross-linking to obtain granular For microspheres with a diameter greater than 250 μm, the gel obtained by the initial crosslinking is dried and then redissolved, then mixed with a crosslinking agent, and then dispersed through emulsification. This method adds a crosslinking agent and mixes again before emulsification, which will lead to Hyaluronic acid cross-links again, resulting in a plate shape and increasing the subsequent emulsification pressure. The degree of cross-linking is difficult to control, the particle size distribution range is wide, and the microspheres larger than 250 μm have a strong foreign body sensation; Patent Publication No. CN111840638A discloses a A method for preparing a cross-linked hyaluronic acid filler for injection, but the preparation of the water phase in the above method needs to be carried out at a low temperature of 2-8°C, the process conditions are harsh, and a large amount of cross-linked The agent is wrapped in the microspheres, which is difficult to clean thoroughly, and there is a safety risk; on the other hand, the preparation of the filler uses uncrosslinked hyaluronic acid as the carrier and blends with the hyaluronic acid microspheres, the carrier is easily degraded, and the overall volume is rapid. Reduced, supplemented to achieve ideal volume support effect

[0005] It can be seen that there are still certain shortcomings in the currently disclosed collagen gel fillers, and there is still room for improvement.

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