Search

CN-121494937-B - Cyclic octapeptide derivative for improving alpha-crystallin expression and preparation method and application thereof

CN121494937BCN 121494937 BCN121494937 BCN 121494937BCN-121494937-B

Abstract

The invention relates to a cyclic octapeptide derivative with a structure shown in a formula (I), a salt or a stereoisomer thereof, a preparation method and application thereof, wherein each R is independently selected from C 5 ~C 13 alkyl and C 5 ~C 13 unsaturated chain alkyl. The cyclic octapeptide derivative or the salt or the stereoisomer thereof provided by the invention has good skin permeability, can obviously improve the expression of alpha-crystallin, silk fibroin and hyaluronic acid in epidermal cells, has an effect obviously superior to that of cyclic tetrapeptide derivatives, is more obviously superior to that of commercially available linear peptide palmitoyl tetrapeptide-10, can more effectively repair and strengthen skin barriers, and improves skin smoothness and skin penetration brightness. In addition, the cyclopeptide derivative has high biological activity and good stability and safety. (I)。

Inventors

  • LIANG WEIZHOU
  • WU SHAOJUAN
  • HUANG SHIHAO
  • ZHENG QINGQUAN

Assignees

  • 广州同隽医药科技有限公司

Dates

Publication Date
20260505
Application Date
20260106

Claims (12)

  1. 1. A cyclic octapeptide derivative having a structure represented by the formula (I) or a salt thereof, ; Wherein each R is independently selected from C 5 ~C 13 alkyl.
  2. 2. The cyclic octapeptide derivative or salt thereof according to claim 1, wherein each R is independently selected from the group consisting of C 9 ~C 11 alkyl groups.
  3. 3. The cyclic octapeptide derivative or salt thereof according to claim 2, wherein each R is independently selected from the group consisting of C 9 alkyl.
  4. 4. The cyclic octapeptide derivative or salt thereof according to claim 1, wherein each R is independently selected from the group consisting of n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, and n-tridecyl.
  5. 5. The cyclic octapeptide derivative or salt thereof according to claim 1, wherein the cyclic octapeptide derivative is selected from the group consisting of: ; ; ; 。
  6. 6. The cyclic octapeptide derivative or salt thereof according to any one of claims 1-5, wherein the salt of the cyclic octapeptide derivative is selected from acetate, trifluoroacetate, hydrochloride, sulfate, citrate, ascorbate, lactate, maleate, fumarate, succinate, gluconate or salicylate thereof.
  7. 7. Use of the cyclic octapeptide derivative or salt thereof as claimed in any one of claims 1 to 6 as an active ingredient in the preparation of a cosmetic capable of repairing skin.
  8. 8. Use of the cyclic octapeptide derivative or salt thereof as claimed in any one of claims 1 to 6 as an active ingredient in the manufacture of a cosmetic capable of enhancing skin barrier, delaying skin aging and/or combating oxidative damage.
  9. 9. Use according to claim 7 or 8, characterized in that the cosmetic is capable of increasing the content of filaggrin, hyaluronic acid and/or alpha-crystallin in cells.
  10. 10. A cosmetic, characterized in that an effective component in the cosmetic contains the cyclic octapeptide derivative or salt thereof according to any one of claims 1 to 6.
  11. 11. The cosmetic product according to claim 10, wherein the cosmetic product comprises a face lotion, a pack, a face cream and an essence.
  12. 12. A process for the preparation of a cyclic octapeptide derivative or salt thereof as claimed in any one of claims 1 to 6, comprising the steps of: 1) Synthesis of the linear octapeptide RCO-N 6 - [ RCO-Lys-Thr (tBu) -Phe-Lys (Boc) ] -Lys-Thr (tBu) -Phe-Lys (Boc) -OH starting from Fmoc-Lys (Boc) -OH, fmoc-Phe-OH, fmoc-Thr (tBu) -OH and RCO-Lys (Fmoc) -OH, wherein R is as defined in any one of claims 1 to 5; 2) Cyclizing the linear octapeptide RCO-N 6 - [ RCO-Lys-Thr (tBu) -Phe-Lys (Boc) ] -Lys-Thr (tBu) -Phe-Lys (Boc) -OH and then deprotecting to obtain the cyclooctapeptide derivative or the salt thereof.

Description

Cyclic octapeptide derivative for improving alpha-crystallin expression and preparation method and application thereof Technical Field The invention belongs to the technical field of cosmetics, relates to a cyclopeptide derivative, and in particular relates to a cyclopeptide derivative for improving alpha-crystallin expression, and a preparation method and application thereof. Background Skin is the first line of defense of the human body against the external environment (e.g., ultraviolet light, pollutants). Healthy skin barriers rely on the synergistic action of a variety of key proteins and molecules. The alpha-crystallin is used as a micromolecular heat shock protein, plays a key role in maintaining cell homeostasis and resisting stress injury, and has important significance in strengthening skin barrier and delaying skin aging by improving expression quantity. Polypeptide components are widely used in functional cosmetics due to their high biological activity. In order to overcome the defects that the linear peptide is easy to be degraded by protease and has poor stability in biological environment, the inventor of the present invention previously proposed to cyclize tetrapeptides with specific sequences and introduce a certain length of hydrophobic side chains at the same time, so as to obtain a series of hydrophobic side chain modified cyclic tetrapeptide derivatives. The cyclic tetrapeptide derivative remarkably improves the structural rigidity and enzyme stability of polypeptide molecules by forming a cyclic structure, and improves the skin permeability by introducing a hydrophobic side chain with a certain length, thereby obtaining good effect on enhancing skin barrier (CN 119735635A). However, with the increasing demands of the market for cosmetic efficacy, those skilled in the art are always pursuing new generation active ingredients with higher activity and more remarkable effects. Disclosure of Invention Based on this, the object of the present invention is to provide a cosmetic active ingredient capable of improving the expression of alpha-crystallin with high activity. The technical scheme for achieving the purpose comprises the following steps. In a first aspect, the present invention provides a cyclic octapeptide derivative having the structure of formula (I) or a salt or stereoisomer thereof, (I) Wherein each R is independently selected from C 5~C13 alkyl and C 5~C13 unsaturated chain alkyl. In a second aspect, the present invention provides the use of said cyclic octapeptide derivative or salt or stereoisomer thereof as an active ingredient in the preparation of a cosmetic product capable of repairing or improving skin conditions, for example, capable of enhancing skin barrier and/or delaying skin aging. In a third aspect, the present invention provides a cosmetic, wherein the cosmetic comprises the cyclic octapeptide derivative or salt or stereoisomer thereof according to the present invention as an active ingredient. In a fourth aspect, the present invention provides a method for preparing a cyclic octapeptide derivative or a salt thereof according to the present invention, comprising the steps of: 1) The method comprises the steps of taking Fmoc-Lys (Boc) -OH, fmoc-Phe-OH, fmoc-Thr (tBu) -OH and RCO-Lys (Fmoc) -OH as raw materials to synthesize linear octapeptide RCO-N 6 - [ RCO-Lys-Thr (tBu) -Phe-Lys (Boc) ] -Lys-Thr (tBu) -Phe-Lys (Boc) -OH, wherein each R is independently selected from C 5~C13 alkyl and C 5~C13 unsaturated chain alkyl; 2) Cyclizing the linear octapeptide RCO-N 6 - [ RCO-Lys-Thr (tBu) -Phe-Lys (Boc) ] -Lys-Thr (tBu) -Phe-Lys (Boc) -OH and then deprotecting to obtain the cyclooctapeptide derivative or the salt thereof. The invention has the following beneficial effects: According to the cyclopeptide derivative or the salt or the stereoisomer thereof, the size of the cyclopeptide is optimized, and the hydrophobic side chain with a specific length is introduced, so that the oil-water distribution coefficient of the cyclopeptide is optimized, the cyclopeptide derivative has good skin permeability, the expression of alpha-crystallin, silk fibroin and hyaluronic acid in epidermal cells can be remarkably improved, the effect is remarkably superior to that of the cyclopeptide derivative, the effect is remarkably superior to that of the commercially available linear peptide palmitoyl tetrapeptide-10, the skin barrier can be more effectively repaired and enhanced, the skin is protected from oxidative damage, and the skin smoothness and the skin penetration brightness are improved. In addition, the cyclopeptide derivative has high biological activity and good stability and safety. Detailed Description The present invention will be described more fully hereinafter in order to facilitate an understanding of the present invention. This invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided s