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CN-121991262-A - Ergothioneine heparin fusion molecule and preparation method and application thereof

CN121991262ACN 121991262 ACN121991262 ACN 121991262ACN-121991262-A

Abstract

The invention discloses an ergothioneine heparin fusion molecule, and a preparation method and application thereof, belonging to the technical field of medicines and cosmetics. The ergothioneine heparin fusion molecule has the structural formula: Wherein M is copper or zinc, M is a positive integer, n is a natural number, and R 1 and R 2 are each independently selected from a sodium sulfonate group (-SO 3 Na) or a hydrogen atom (H). According to the invention, chemical modification is carried out on the ergothioneine, heparin and the ergothioneine are fused, and degradation of the ergothioneine to generate trimethylamine is blocked from a molecular level in a covalent coupling mode. The ergothioneine heparin fusion molecule provided by the invention has good stability, does not generate fishy smell after illumination for four weeks, and remarkably improves the fishy smell problem of trimethylamine characteristic generated by ergothioneine degradation.

Inventors

  • JI SHENGLI
  • GUO KAI
  • Huang Jingzeng
  • WANG ZHEJIANG
  • LIU MINGJIE
  • ZHANG SHANSHAN
  • ZHAO YUETONG

Assignees

  • 润辉生物技术（威海）有限公司

Dates

Publication Date
20260508
Application Date
20260112

Claims (10)

  1. 1. An ergothioneine heparin fusion molecule, which is characterized by having the structural formula: Wherein M is copper or zinc, M is a positive integer, n is a natural number, and R 1 and R 2 are each independently selected from a sodium sulfonate group or a hydrogen atom.
  2. 2. The ergothioneine fusion molecule of claim 1, wherein the degree of substitution of the ergothioneine polypeptide in the ergothioneine fusion molecule is between 0.1 and 1.0; The structure of the ergothioneine polypeptide is as follows: 。
  3. 3. the ergothioneine heparin fusion molecule of claim 1, wherein the heparin has the structure: ; Wherein n is a natural number, R 1 and R 2 are each independently selected from a sodium sulfonate group or a hydrogen atom, and the substitution degree of the sodium sulfonate group in heparin is 2.0-3.0, preferably 2.0-2.5.
  4. 4. The ergothioneine fusion molecule of claim 1, having a weight average molecular weight of 3-4 kDa and an average molecular weight of 3.4-3.6 kDa.
  5. 5. A method of preparing a ergothioneine heparin fusion molecule according to any one of claims 1-4, comprising: The ergothioneine reacts with 2- ((tert-butoxycarbonyl) amino) ethyl (3-aminopropionyl) -L-histidine ester, and the ergothioneine polypeptide is obtained after deprotection, and the structure of the ergothioneine polypeptide is as follows: ; Heparin, 1-hydroxybenzotriazole and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride are added into a reaction system, and the pH is regulated to 6.0-7.0 for reaction; Adding the reaction solution after the reaction into water, regulating the pH to 1.8-2.2, filtering, washing, concentrating, adding copper hydroxide or zinc hydroxide, stirring, filtering, and freeze-drying the filtrate to obtain the ergothioneine heparin fusion molecule.
  6. 6. The preparation method according to claim 5, wherein the preparation method comprises: mixing ergothioneine, 2- ((tert-butoxycarbonyl) amino) ethyl (3-aminopropionyl) -L-histidine ester, 1-hydroxybenzotriazole and water, adding 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, regulating the pH to 6.0-7.0, regulating the pH of the reaction solution to below 1.0 after the reaction is finished, and continuing the reaction to obtain the ergothioneine polypeptide.
  7. 7. The process according to claim 6, wherein the mass ratio of ergothioneine, 2- ((tert-butoxycarbonyl) amino) ethyl (3-aminopropionyl) -L-histidine ester and heparin is 20-30:30-40:30-90, preferably 20-25:35-40:40-80.
  8. 8. The method of any one of claims 5-7, wherein the reaction temperature is 20-30 ℃.
  9. 9. The method of any one of claims 5-7, wherein the heparin has a weight average molecular weight of 3-8 kDa and an average molecular weight of 3.4-5 kDa; Preferably, the heparin has a weight average molecular weight of 3-4 kDa and an average molecular weight of 3.4-3.6 kDa.
  10. 10. Use of a ergothioneine heparin fusion molecule according to any one of claims 1-4 or prepared by a method according to any one of claims 5-9 for the preparation of an antioxidant product; preferably, the product is a cosmetic product.

Description

Ergothioneine heparin fusion molecule and preparation method and application thereof Technical Field The invention belongs to the technical field of medicines and cosmetics, and particularly relates to an ergothioneine heparin fusion molecule, a preparation method and application thereof. Background The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art. Ergothioneine is a natural antioxidant with a unique structure, and has the academic name of 2-mercapto-histidine-trimethyl inner salt, and has two isomer forms of thiol and thioketone. The ergothioneine has strong antioxidant capacity, can effectively remove free radicals, prevents cells from being damaged by oxides, has important protective effect on human cells, and has transport proteins which specifically absorb the ergothioneine in the human cells, so that the ergothioneine plays an important physiological function in the human body, has been widely applied to the fields of cosmetics and foods, and has wide growth space. However, the molecule of ergothioneine contains trimethyl amino groups, and under specific conditions such as illumination, alkalinity or high temperature, the trimethyl amino groups of ergothioneine can undergo beta-elimination reaction to generate trimethylamine, and even at extremely low concentration, strong smell (fishy smell) can be generated, so that the application of the product is influenced. At present, the aim of reducing fishy smell is mainly achieved through neutralizing or adsorbing trimethylamine. For example, the action of inhibiting ergothioneine odor is achieved by compounding persimmon fruit extract, ferulic acid, licorice extract and the like. However, the odor of ergothioneine is inhibited by compounding raw materials, so that the odor is inhibited for a short time, and the solution system turns yellow. And the ergothioneine is coated by liposome vesicles, and the phospholipid bilayer base material of the liposome vesicles is combined with trimethylamine, so that the leakage of trimethylamine gas is avoided, and the fishy smell is reduced. The above method for reducing fishy smell by neutralizing or adsorbing trimethylamine does not improve stability of ergothioneine and does not fundamentally avoid the generation of trimethylamine by degradation of ergothioneine. Disclosure of Invention In order to solve the defects of the prior art, the invention aims to provide the ergothioneine heparin fusion molecule, and the preparation method and the application thereof, the ergothioneine heparin fusion molecule provided by the invention has good stability, the covalent coupling mode blocks the degradation of ergothioneine to produce trimethylamine from the molecular level, thereby improving the problem of fishy smell of the characteristic of trimethylamine produced by the degradation of ergothioneine. In order to achieve the above purpose, the technical scheme of the invention is as follows: in a first aspect of the present invention, there is provided a ergothioneine heparin fusion molecule having the structural formula: Wherein M is copper or zinc, M is a positive integer, n is a natural number, and R 1 and R 2 are each independently selected from a sodium sulfonate group (-SO 3 Na) or a hydrogen atom (H). In some embodiments of the invention, the degree of substitution of the ergothioneine polypeptide structure in the ergothioneine heparin fusion molecule is 0.1-1.0; The structure of the ergothioneine polypeptide is as follows: 。 in some embodiments of the invention, the heparin is structured as follows: ; Wherein n is a natural number, R 1 and R 2 are each independently selected from sodium sulfonate group (-SO 3 Na) or hydrogen atom (H), and the substitution degree of sodium sulfonate group in heparin is 2.0-3.0, preferably 2.0-2.5. In some embodiments of the invention, the ergothioneine heparin fusion molecule has a weight average molecular weight of 3-4 kDa and an average molecular weight of 3.4-3.6 kDa. In a second aspect of the present invention, a method for preparing the ergothioneine heparin fusion molecule is provided, comprising: Reacting ergothioneine with 2- ((tert-butoxycarbonyl) amino) ethyl (3-aminopropionyl) -L-histidine ester, and deprotecting to obtain the ergothioneine polypeptide, wherein the ergothioneine polypeptide has a structure as follows: ; Heparin, 1-hydroxybenzotriazole and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride are added into a reaction system, and the pH is regulated to 6.0-7.0 for reaction; Adding the reaction solution after the reaction into water, regulating the pH to 1.8-2.2, filtering, washing, concentrating, adding copper hydroxide or zinc hydroxide, stirring, filtering, and freeze-drying the filtrate to obtain th