Optimization of Enzyme Reaction for Pilot Scale Production of Ginsenoside Metabolite Compound K and Enzyme-Processed Ginseng Extract

Abstract

Compound K is a ginsenoside metabolite synthesized by intestinal bacteria, and well known as the active pharmaceutical ingredient mediating the effects of ginseng. The medicinal efficacies of compound K were proven in a number of studies conducted in the 90s, and interest in this compound is growing rapidly. However, there are challenges associated with attempts to develop this compound for commercial production including preliminary studies, which are mainly focused on biological conversion from laboratory-scale that show low feasibility and reproducibility.

In this study, we developed a system for the commercial production of compound K, as well as the confirmation of the homogeneity of the manufactured material, and analytical methods for its validation. In addition, we conducted studies to develop a raw material for a health functional food using the compound K production technology established. The separation process for crude saponins used in the mass production system for compound K was optimized by designing relevant experiments, and the reaction conditions for the enzymatic conversion of separated crude saponin were optimized using statistical analysis. The developed process was applied in a pilot scale production. Finally, a production system for compound K was established from raw material production to the final product preparation. Compound K from different lots was evaluated for homogeneity with reference materials using various verification methods, and the analytical method was validated.

Furthermore, the bioconversion technique used for compound K was applied in the development of a raw material for a health functional food, which is a high content compound K-containing hydrolyzed ginseng extract. The reaction conditions were optimized by making relevant adjustments to the experimental design, and applied to commercial production. The results showed that the compound K content in the raw material and the process were standardized and acceptable according to the Korea Food and Drug Administration (KFDA) guideline. The technique for producing compound K not naturally found in ginseng was developed and applied to commercial production. Because of this study, the raw material was available for the development of pharmaceutical grade medicines from this natural product. Therefore, this study will reinforce the competitiveness of ginseng in the world market. The raw material developed for the health functional food is currently undergoing clinical trials for application in blood glucose control.