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CN-122010688-A - Method for reducing farnesol content in (-) -alpha-bisabolol based on oxidation process

CN122010688ACN 122010688 ACN122010688 ACN 122010688ACN-122010688-A

Abstract

The invention provides a method for reducing farnesol content in (-) -alpha-bisabolol based on an oxidation process, belonging to the technical fields of pharmaceutical chemistry and biosynthesis. The method comprises the steps of (1) impurity removal, namely mixing (-) -alpha-bisabolol or a (-) -alpha-bisabolol solution, an organic solvent and metal salt for reaction, and (2) post-treatment, adding an alkaline aqueous solution into the reaction solution obtained in the step (1) after the reaction is finished, phase-separating, and distilling and concentrating an organic phase to obtain a purified (-) -alpha-bisabolol product, wherein the content of farnesol is less than or equal to 0.05%. Compared with the prior art, the method has the advantages of simple operation, no byproducts, low cost, easy amplified production and the like, provides a brand new solution for improving the quality of the bisabolol and the use safety, and also provides a high-efficiency, green and safe industrialization scheme for the application of the bisabolol in the cosmetic field.

Inventors

  • ZHANG BAOXIN
  • ZHANG HAILEI
  • NUERMAIMAITI.KUDABAERDI
  • MA YANFANG
  • WANG RUITING
  • Alimire Yilihamu
  • Muyaseer Ablimiti
  • ZHANG FANGFANG
  • ZHANG TING

Assignees

  • 伊犁川宁生物技术股份有限公司
  • 伊犁疆宁生物技术有限公司

Dates

Publication Date
20260512
Application Date
20260122

Claims (9)

  1. 1. A method for reducing farnesol content in (-) -alpha-bisabolol is characterized by comprising the following steps: (1) Removing impurities by mixing (-) -alpha-bisabolol or (-) -alpha-bisabolol solution, organic solvent and metal salt for reaction; (2) And (3) after the reaction is finished, adding an alkaline aqueous solution into the reaction solution obtained in the step (1), separating phases, and taking an organic phase for distillation and concentration to obtain a purified (-) -alpha-bisabolol product.
  2. 2. The method according to claim 1, wherein the (-) - α -bisabolol or the (-) - α -bisabolol solution in the step (1) has a content of (-) - α -bisabolol not less than 10% and a content of farnesol not less than 1.5%, and the solvent in the (-) - α -bisabolol solution is not an alcoholic solvent.
  3. 3. The method according to claim 1, wherein the (-) - α -bisabolol in the step (1) is prepared by solvent extraction, decolorization, concentration and molecular distillation of (-) - α -bisabolol fermentation broth, and the (-) - α -bisabolol solution is an extract obtained by solvent extraction of (-) - α -bisabolol fermentation broth or a concentrated solution obtained by decolorization and concentration of the extract.
  4. 4. The method according to claim 1, wherein the metal salt in the step (1) is selected from any one of ferric chloride, ferric chloride hexahydrate, ferric sulfate, ferric nitrate, cupric chloride, cupric sulfate, aluminum isopropoxide, or a mixed reagent of any two or more of them; The alkali is selected from any one of calcium carbonate, sodium bicarbonate, triethylamine and diethylamine, or a mixed reagent of any two or more than two of the above; the alkaline aqueous solution in the step (2) is selected from any one of sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium carbonate, potassium hydroxide, disodium hydrogen phosphate and dipotassium hydrogen phosphate, or an aqueous solution of a mixed reagent of any two or more.
  5. 5. The method according to claim 1 to 4, wherein the organic solvent in the step (1) is selected from any one of a C 5-12 alkane solvent and a C 3-6 ketone solvent, or a mixed reagent of any two or more.
  6. 6. The method according to claim 5, wherein the organic solvent in the step (1) is selected from any one of n-hexane, n-heptane, isododecane, n-dodecane, ketone, ethanone, acetone, and a mixture of any two or more of them.
  7. 7. The method according to claim 1, wherein the distillation concentration in the step (2) is preceded by decoloring; The method of distillation concentration in step (2) is atmospheric distillation or reduced pressure distillation, preferably reduced pressure distillation.
  8. 8. The method according to claim 7, wherein the decolorization is performed by activated carbon.
  9. 9. The method according to claim 7, wherein the reduced pressure distillation in the step (2) is one or a combination of distillation modes of a rectifying column and molecular distillation.

Description

Method for reducing farnesol content in (-) -alpha-bisabolol based on oxidation process Technical Field The invention belongs to the technical field of pharmaceutical chemistry and biosynthesis, and particularly relates to a method for reducing farnesol content in (-) -alpha-bisabolol based on an oxidation process. Background (-) -Alpha-bisabolol (abbreviated as bisabolol) is a natural sesquimushroom alcohol with wide biological activity, and is mainly contained in plant essential oils such as German chamomile (MATRICARIA RECUTITA). Due to its excellent anti-inflammatory, antibacterial, wound healing and skin repair promoting effects, bisabolol is widely used in cosmetics, medicines and skin care products, especially in sensitive muscle care, anti-aging and soothing repair products. However, bisabolol of natural origin is often accompanied by a variety of structurally similar sesquiterpene-like impurities, with farnesol (Farnesol) being one of the most predominant co-existing components. Because the two biological synthesis pathways in the plant body are closely related (both are derived from farnesyl pyrophosphate), the traditional extraction method is difficult to effectively separate, so that the farnesol residue in the commercialized bisabolol product is high, and the application safety and the market value of the product are seriously affected. Farnesol is a known contact allergen and has been classified as a limiting ingredient by European Union cosmetic regulations (EC No 1223/2009) and the like, and its content in resident cosmetics is severely limited. If the farnesol residue in the bisabolol is too high, the sensitization risk of the product can be increased, the safety of consumers is affected, and the application of the farnesol is strictly limited in high-risk products such as infants, sensitive muscles and the like. Bisabolol and farnesol have highly similar chemical properties (the same molecular weight, both of which are isomers of C 15H26 O), and conventional separation methods face significant challenges. The boiling points of the two are close, the conventional distillation is difficult to separate efficiently, and the heat sensitive components are degraded due to high temperature. The existing industrial method for reducing the content of farnesol in the bisabolol mainly comprises precise molecular distillation, silver ion chromatography, enzymatic selective conversion and supercritical CO 2 extraction, and the problems of low separation efficiency, complex process, high cost or introduction of new impurities and the like generally exist in the methods, so that the requirement of industrial production of high-purity bisabolol is difficult to meet. Patent application CN101400650a discloses a process for preparing pure bisabolol or enriched bisabolol by separating a mixture comprising bisabolol and farnesol by separating and purifying bisabolol by a process of "selective esterification-distillation". The scheme has the following defects of complicated steps, high raw material requirements, high vacuum resistance of used equipment, high energy consumption, continuous evaporation tower requirement, high industrial production cost, possibly residual harmful solvents, high separation difficulty of byproducts after esterification and the like, and potential risks affecting the safety of the bisabolol product. Patent application CN118084616a discloses a scheme for separating and purifying (-) - α -bisabolol from fermentation broth by a "solvent extraction-activated carbon decolorization-two-stage molecular distillation" process. However, the scheme has the advantages of expensive molecular distiller, small treatment capacity, multiple parallel connection for amplification and high cost. Therefore, the development of the method which is green, environment-friendly, convenient to operate, high in safety and low in cost has important significance in reducing the content of farnesol in the bisabolol. Disclosure of Invention Aiming at the defects existing in the prior art, the invention aims to provide a method for reducing the content of farnesol in (-) -alpha-bisabolol, which has the advantages of simple operation, no byproducts, low cost and easy mass production. The invention provides a method for reducing farnesol content in (-) -alpha-bisabolol, which comprises the following steps: (1) Removing impurities by mixing (-) -alpha-bisabolol or (-) -alpha-bisabolol solution, organic solvent and metal salt for reaction; (2) And (3) after the reaction is finished, adding an alkaline aqueous solution into the reaction solution obtained in the step (1), separating phases, and taking an organic phase for distillation and concentration to obtain a purified (-) -alpha-bisabolol product. Further, in the step (1), the content of (-) -alpha-bisabolol in the (-) -alpha-bisabolol or the (-) -alpha-bisabolol solution is more than or equal to 10%, the content of farnesol is less than or equal to 1.5%, and the solv