Kojic acid is also called aspergillic acid with its chemical name of 5-hydroxy-2-hydroxymethyl-4H-pyran-4-one, and its chemical structural formula is as follows. Kojic acid is a colorless prismatic crystal, which is easily soluble in water, alcohol and acetone, slightly soluble in ether, ethyl acetate, chloroform and pyridine, but hardly soluble in most other solvents. Kojic acid is unstable and sensitive to light and heat. It is easy to be oxidized in air, and can also form chelate compound with metal ions. Kojic acid can inhibit tyrosinase activity during the formation of melanin, and has obvious whitening effect without inhibiting other enzymes. Now it has been widely used in daily chemical industries such as skin whitening and sun care cosmetics, solvents and toothpastes.
1. Preparation for the fermentation of kojic acid
Kojic acid is a secondary metabolite derived from microorganisms, which has no physiological toxicity and simple structure. Due to the instability of its enol structure, however, it is often modified and derived as a skeleton, such as synthesizing kojic acid dipalmitate and kojic acid ester. These derivatives not only improve the solubility and stability of kojic acid in oily cosmetics, but also greatly improve its biological activity.
After kojic acid was first found in soy sauce brewed by aspergillus oryzae, many researchers started to isolate kojic acid from fermentation products of some strains of aspergillus flavus, and its yield was higher than that of aspergillus oryzae. However, while the fermentation of aspergillus flavus produces kojic acid, it also produces aflatoxin, a strong carcinogen. While conducting studies on 149 strains of aspergillus oryzae and 46 strains of aspergillus flavus, the researchers found that all aspergillus flavus produced kojic acid and 34 strains produced aflatoxin at the same time. However, only 105 strains of aspergillus oryzae produced kojic acid and none of them produced aflatoxin. Therefore, when choosing aspergillus flavus as strains to produce kojic acid, great importance should be attached to its security.
In order to improve the yield of kojic acid, scholars at home and abroad have done a lot of research, mainly including strain breeding and the optimization of fermentation method. Aspergillus strains, as kojic acid producing strains, were mutagenized by different physical and chemical methods, and the kojic acid yield was improved in different degrees. However, with further studies on mutagenesis, the effect of increasing yield by mutagenesis has obviously decreased. In the process of strain breeding, there are some limitations, such as random mutagenesis methods, difficulty in mastering the direction and difficulty in screening ideal individuals. In addition, the sensitivity of strains has been decreased and its tolerance has been improved through multiple rounds of screening. Therefore, it is necessary to find new approach to increase the yield of kojic acid.
2. Safety of kojic acid
In the early 1990s, Japan firstly added kojic acid to cosmetics as a skin whitening ingredient. It was used to whiten skin and remove color spots because it can inhibit tyrosinase and block the intermediate production produced by melanin. Subsequently, it was found that kojic acid may cause cancer. In 2003, the Japanese government banned the import and production of cosmetics containing kojic acid. However, due to insufficient evidence, the regulations on adding kojic acid to cosmetics were reopened in 2005. Although there was no clear restriction standard of kojic acid, its recommended dosage was between 0.1% and 1%. At present, kojic acid is listed in the list of three carcinogens published by the International Agency on Cancer Research of the World Health Organization, which has aroused great public concern about the safety of kojic acid. However, there is no management regulation for its use in cosmetics in China's current laws and regulations. There is no doubt that Cosmetics Raw Materials should be safe.
The toxicity kinetics of kojic acid in mice showed that it was rapidly absorbed and distributed to various organs after oral, skin or subcutaneous administration, and the metabolic...
(All Rights Reserved)