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CN-121975024-A - Preparation and application of thermal-sensation repair type recombinant collagen

CN121975024ACN 121975024 ACN121975024 ACN 121975024ACN-121975024-A

Abstract

The invention discloses preparation and application of thermal repair type recombinant collagen, and relates to the technical field of bioengineering and biomedical materials. The invention innovatively fuses the functional domain segment of the I-type humanized collagen and the functional domain segment of the heat shock protein family through a flexible connector. The recombinant protein aims at the problems of protein denaturation, membrane structure damage, inflammatory factor release, damaged skin barrier function, aggravated water loss, sensitive weakness and the like caused by the photo-thermal damage of skin under photo-thermal stress conditions (such as ultraviolet irradiation, high-temperature environment or thermo-Maji and other medical and aesthetic photoelectric treatments), and utilizes the HSP molecular chaperone function to lead the damaged protein to be correctly folded, maintain the intracellular homeostasis and cooperate with the collagen part to accelerate the tissue repair. Experiments prove that the recombinant protein can effectively improve the skin compactness, the wrinkle resistance and the barrier repair capability after thermal injury. The invention can be widely applied to the fields of cosmetics, skin repair, medical and artistic post-care and the like.

Inventors

  • ZHAO XINYI
  • NIU MINGZE
  • YE CHENGLONG
  • Fu Bingqing
  • WU QIANG
  • XU MENGXIANG
  • ZHANG RAN
  • ZHANG XINGXING

Assignees

  • 欧诗漫生物股份有限公司

Dates

Publication Date
20260505
Application Date
20260409

Claims (11)

  1. 1. A recombinant collagen is characterized by comprising a first polypeptide a-linker- (second polypeptide) b, wherein the first polypeptide is a collagen-like functional domain with extracellular matrix generation activity, the second polypeptide is a heat shock protein functional domain with molecular chaperone activity, and the linker is a flexible peptide segment; The amino acid sequence of the first polypeptide is shown in any one of SEQ ID NO 1-3; The amino acid sequence of the second polypeptide is shown in any one of SEQ ID NO 7-9, a is an integer of 3-6, and b is an integer of 3-6.
  2. 2. The recombinant collagen according to claim 1, wherein the linker is selected from (GGGS) n, (GGGGS) n, (GSGS) n or (GGGGSGGGG) n, wherein n is an integer from 1 to 9.
  3. 3. The recombinant collagen is characterized in that the amino acid sequence of the recombinant collagen is shown as any one of SEQ ID NO 13-15.
  4. 4. A nucleic acid molecule encoding the recombinant collagen according to any one of claims 1 to 3.
  5. 5. A vector comprising the nucleic acid molecule of claim 4.
  6. 6. The vector of claim 5, further comprising a vector backbone selected from any one of pPIC9K, PUC and pARG 4.
  7. 7. A host cell comprising the nucleic acid molecule of claim 4 or the vector of claim 5 or 6; and/or the host cell is selected from pichia pastoris, saccharomyces cerevisiae, escherichia coli or bacillus subtilis.
  8. 8. A method for preparing recombinant collagen according to any one of claims 1 to 3, comprising culturing the host cell according to claim 7, inducing expression of the recombinant collagen, and separating and purifying the expression product to obtain the recombinant collagen.
  9. 9. A composition comprising a recombinant collagen for thermal remediation, characterized in that it comprises the recombinant collagen according to any one of claims 1 to 3 and pharmaceutically or dermatologically acceptable excipients.
  10. 10. A skin repair product, comprising the recombinant collagen according to any one of claims 1 to 3 or the composition according to claim 9; And/or the product is used for repairing skin after photo-thermal stress, wherein the photo-thermal stress comprises heat stress generated by ultraviolet radiation, environmental high temperature or medical and aesthetic photoelectric treatment; And/or the product is in a form selected from the group consisting of gel, essence, mask, medical dressing, spray, lyophilized powder, emulsion or paste.
  11. 11. The use of the recombinant collagen according to any one of claims 1 to 3 in the preparation of cosmetics, medical products or medicaments for wound tissue repair.

Description

Preparation and application of thermal-sensation repair type recombinant collagen Technical Field The invention relates to the technical field of bioengineering and biomedical materials, in particular to preparation and application of thermal-sensation repair type recombinant collagen. Background Skin is the primary physical barrier against external environmental attack, and its structural integrity and functionality are critical to maintaining body health. With the increasing demands of consumers on skin care efficacy and the popularization of photoelectric medical projects (such as radio frequency, laser, heat-mason, etc.), the market is increasingly pressing on the demand of biological materials capable of repairing skin barriers and promoting tissue regeneration efficiently and safely after heat stress or injury. Collagen, particularly type I collagen, is the major structural protein that makes up the extracellular matrix of the dermis layer of the skin, imparting strength and toughness to the skin. However, the main collagen raw materials in the current market have obvious limitations that animal-derived collagen has the problems of immunogenicity, virus transmission risk, unstable functions among batches and the like, and the conventional recombinant collagen solves the problems of virus risk and immunogenicity, but the recombinant collagen prepared by the prior art is mostly a functional fragment or lacks a complete triple helix structure, so that the collagen has poor thermal stability and insufficient biological activity, and is difficult to play an ideal repairing role in a damaged microenvironment. Therefore, there is an urgent need in the art to develop a novel biomaterial having high biocompatibility, high stability and high repair activity, so as to overcome the shortcomings of the prior art. Disclosure of Invention The invention aims to provide a preparation and application of thermal repair type recombinant collagen. The invention is realized in the following way: in a first aspect, an embodiment of the present invention provides a recombinant collagen, wherein the first polypeptide is a collagen-like domain having extracellular matrix-producing activity, the second polypeptide is a heat shock protein domain having chaperone activity, and the linker is a flexible peptide. In a second aspect, the embodiment of the invention provides recombinant collagen, and the amino acid sequence of the recombinant collagen is shown in any one of SEQ ID NO 13-15. In a third aspect, embodiments of the present invention provide a nucleic acid molecule encoding the recombinant collagen according to the previous embodiments. In a fourth aspect, embodiments of the present invention provide a vector comprising a nucleic acid molecule as described in the previous embodiments. In a fifth aspect, embodiments of the present invention provide a host cell comprising a nucleic acid molecule as described in the previous embodiments or a vector as described in the previous embodiments. In a sixth aspect, an embodiment of the present invention provides a method for preparing a recombinant collagen according to the previous embodiment, comprising culturing the host cell according to the previous embodiment, inducing the expression of the recombinant collagen, and separating and purifying an expression product to obtain the recombinant collagen. In a seventh aspect, embodiments of the present invention provide a composition comprising a thermosensory-repair recombinant collagen, comprising any one of the aforementioned first to sixth aspects of the invention and combinations thereof. In an eighth aspect, embodiments of the present invention provide a skin repair product comprising the recombinant collagen according to the previous embodiment or the composition according to the previous embodiment. In a ninth aspect, embodiments of the present invention provide the use of recombinant collagen according to the previous embodiments for the preparation of a cosmetic, medical product or a medicament for wound tissue repair. The invention has the following beneficial effects: according to the invention, the collagen-like functional domain with extracellular matrix generation activity and the heat shock protein functional domain with molecular chaperone activity are fused accurately through genetic engineering, and the fusion protein shows non-additive synergistic effect in the fields of skin tightening, repairing, wrinkle resistance and thermal injury post-repair. The biological safety and stability are higher, the preparation is carried out by adopting a genetic engineering technology, and the virus and immunogenicity risks possibly carried by animal source materials are avoided from the source. Meanwhile, the fusion protein in the form of a polymer is designed to have higher thermal stability compared with a single peptide segment. Drawings In order to more clearly illustrate the technical solutions of the embodiments of the pre