CN-122010811-A - Retinoic acid derivative, preparation method and application thereof

Abstract

The invention discloses a retinoic acid derivative, a preparation method and application thereof, and belongs to the technical field of cosmetic raw materials. The derivative is raspberry ketone retinoic acid ester, and has a structural formula of The preparation method comprises dissolving retinoic acid and raspberry ketone in organic solvent, adding condensing agent, stirring at room temperature for reacting for 12-48 hr, monitoring reaction progress, quenching reaction after the raw material raspberry ketone is completely reacted, extracting, drying, concentrating and purifying to obtain raspberry ketone retinoic acid ester. The cosmetic is used for preparing cosmetics with at least one of anti-aging, anti-wrinkle, antioxidant or skin soothing effects. The compound has the advantages of innovative structure, integrated efficacy, remarkably reduced irritation, retained and enhanced bioactivity, easily available raw materials and simple preparation.

Inventors

• Huang Fanrui
• ZHANG SHULING
• ZHANG PING
• ZHANG YAQI
• WANG JING
• HUANG HU

Assignees

• 珀莱雅化妆品股份有限公司

Dates

Publication Date

20260512

Application Date

20260324

Claims (10)

1. 1. A retinoic acid derivative is characterized in that the retinoic acid derivative is raspberry ketone retinoic acid ester, tautomer thereof or pharmaceutically acceptable salt, prodrug, hydrate or solvate thereof, and the core structure is that 。
2. 2. A process for preparing a retinoic acid derivative as defined in claim 1, which comprises the steps of: S1, dissolving retinoic acid and raspberry ketone in an organic solvent, adding a condensing agent, and stirring at room temperature for reaction for 12-48 hours; S2, monitoring the reaction progress, quenching the reaction after the raw material raspberry ketone is completely reacted, and extracting, drying, concentrating and purifying to obtain the raspberry ketone retinoic acid ester.
3. 3. The method for preparing retinoic acid derivatives as defined in claim 2, wherein the amount of raspberry ketone added is 1.0-2.0 equivalents of retinoic acid.
4. 4. The method for producing retinoic acid derivatives as defined in claim 2, wherein the condensing agent is added in an amount of 1.0 to 3.0 equivalents of retinoic acid.
5. 5. The method of preparing retinoic acid derivatives as defined in claim 2, wherein said condensing agent is selected from one or more of Dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI), O-benzotriazol-tetramethyluronium Hexafluorophosphate (HBTU), O- (7-azabenzotriazol-1-yl) -N, N' -tetramethyluronium Hexafluorophosphate (HATU), benzotriazol-1-yl-oxy-tripyrrolidinyl phosphohexafluorophosphate (PyBOP).
6. 6. The method for preparing retinoic acid derivatives as defined in claim 2, wherein said organic solvent is selected from one or more of petroleum ether, ethyl acetate, methylene chloride, tetrahydrofuran, diethyl ether, acetone, toluene, N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO).
7. 7. Use of a retinoic acid derivative as defined in claim 1 for the preparation of cosmetics having at least one of anti-aging, anti-wrinkle, antioxidant or soothing skin.
8. 8. Use of a retinoic acid derivative as defined in claim 1 for the preparation of a formulation for promoting skin collagen synthesis and/or inhibiting matrix metalloproteinase expression.
9. 9. Use of a retinoic acid derivative as defined in claim 1 for the preparation of a formulation for inhibiting TRPV1 gene expression in skin keratinocytes.
10. 10. Use of a retinoic acid derivative as defined in claim 1 for preparing a preparation for scavenging active oxygen in skin cells.

Description

Retinoic acid derivative, preparation method and application thereof Technical Field The invention relates to the technical field of fine chemical engineering and cosmetic raw materials, in particular to a novel retinoic acid derivative, a preparation method thereof and application of the derivative in preparing cosmetics. Background With the continuous improvement of the efficacy requirements of consumers on skin care products and the deep development of skin science, the development of cosmetic raw materials is changed from a mode of 'single efficacy' to a mode of 'precise synergy and multiple effect integration'. The ideal active ingredients not only need to have a definite core efficacy (e.g., anti-aging), but also should be able to address a variety of related skin problems (e.g., oxidative damage, inflammation sensitivity, etc.) simultaneously to achieve a more comprehensive skin care effect and a better user experience. Retinoic acid is a "gold standard" component in the anti-aging field, and is effective in promoting normal differentiation of keratinocytes, stimulating collagen synthesis by fibroblasts, and inhibiting overexpression of Matrix Metalloproteinases (MMPs) by activating retinoic acid receptors (RAR/RXR) in the nucleus, thereby exhibiting excellent effects in resisting wrinkles and improving the texture of the skin. However, its strong irritation severely limits its wide application, common side effects including dry skin, redness, stinging and desquamation, which make most sensitive skin people intolerable. In order to reduce the irritation of retinoic acid, the prior art mainly adopts two strategies, namely, physical compounding, such as simple mixing of retinoic acid with ceramide, panthenol and other soothing and repairing components, and chemical modification, such as preparation of retinol or its ester derivatives (such as retinol palmitate). However, the physical compounding has the problems of unstable formula system and possible mutual influence among components, while the simple esterification modification has a certain effect on reducing the irritation, but is often accompanied by the great reduction of the biological activity, and other effects such as antioxidation, relieving and the like cannot be integrated. The raspberry ketone is an aromatic ketone compound derived from natural raspberries, and researches show that the raspberry ketone compound has good antioxidant activity, can effectively remove free radicals, and has potential anti-inflammatory and soothing properties. However, raspberry ketone alone has a weak effect in resisting skin aging, and it is difficult to achieve a structural anti-wrinkle tightening effect. Therefore, developing a novel single-molecule compound which can not only retain the anti-aging activity of retinoic acid core, but also has excellent antioxidant and soothing properties and remarkably reduces the irritation becomes a technical problem to be solved in the field. Disclosure of Invention Aiming at the defects of the prior art, the primary aim of the invention is to provide a retinoic acid derivative which has novel structure, low irritation and multiple effect. The invention also aims to provide a preparation method of the retinoic acid derivative, which has the advantages of easily available raw materials, simple steps and suitability for large-scale production. It is still another object of the present invention to provide the use of the retinoic acid derivatives as defined above for the preparation of cosmetics having anti-aging, antioxidant and soothing effects. The technical problems are mainly solved by the following technical proposal, which is characterized in that the retinoic acid derivative is raspberry ketone retinoic acid ester, tautomer thereof, or pharmaceutically acceptable salt, prodrug, hydrate or solvate thereof, and the core structure is that。 A process for preparing retinoic acid derivatives, comprising the steps of: S1, dissolving retinoic acid and raspberry ketone in an organic solvent, adding a condensing agent, and stirring at room temperature for reaction for 12-48 hours; S2, monitoring the reaction progress, quenching the reaction after the raw material raspberry ketone is completely reacted, and extracting, drying, concentrating and purifying to obtain the raspberry ketone retinoic acid ester. In the aforementioned method for producing retinoic acid derivatives, preferably, the amount of raspberry ketone added is 1.0 to 2.0 equivalents of retinoic acid. In the aforementioned method for producing a retinoic acid derivative, the condensing agent is preferably added in an amount of 1.0 to 3.0 equivalents of retinoic acid. In the aforementioned method for producing a retinoic acid derivative, preferably, the condensing agent is selected from one or more of Dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide, 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI), O-benzotriazol-tetramethyluronium Hexaf