Improvement Of Carbenoxolone Sodium Production Technique

Hydrolysis of Licorice extract produces glycyrrhetinic acid.Glycyrrhetinic acid shows anti-inflammatory,anti-ulcer,anti-virus and other effects,long-term or large doses produce false aldosteronism medication side effects,caused by drug-induced hypertension and edema.Structural modification of glycyrrhetinic acid may enhance its pharmacological activity and reduce or eliminate false aldosterone effects. Carbenoxolone sodium succinate as glycyrrhetinic acid disodium salt, is one of glycyrrhetinic acid derivatives.It can increase gastric mucus secretion,reduce gastric epithelial cell shedding,inhibit pepsinogen in gastric mucosal cells.In the stomach, carbenoxolone sodium succinate was used to inhibit about50%enzyme activity by combining with pepsin,which protected the ulcer to promote tissue regeneration and healing. Carbenoxolone sodium is used as a stomach ulcers,duodenal ulcers and oral medication, esp. for the inoperable patients.Carbenoxolone sodium preparation and related technologies are discussed in this paper mainly from the following three aspects:(1) Glycyrrhetinic acid is an essential raw material for the preparation of carbenoxolone sodium succinate,and the glycyrrhetinic acid’s purity directly affects the preparation and purification of carbenoxolone sodium.We explored the glycyrrhetinic acid’s preparation and purification method.Finally,the optimized experimental conditions were achieved for mass production.(2) Conventionally,in the synthesis of carbenoxolone sodium succinate,pyridine was used not only solvent but also catalyst in order to obtain good yields and conversions.However,using pyridine lead to the corrosion of equipment by and solvent is difficult recycled.Therefore,conditions including solvent,methods and catalyst were studied as the impact of carbenoxolone sodium succinate preparation process in this paper.(3) Using low toxicity dichloridemethan as the reaction medium,4-dimethylaminopyridine as catalyst,the glycyrrhetinic acid was esterificated with succinic anhydride,to convert into carbenoxolone succinic acid.Purification by recrystallization in water,carbenoxolone reacted with sodium hydroxide to give carbenoxolone sodium,which can be dried by spray drying. Finally was obtained environmental processing of carbenoxolone sodium succinate with higher conversion rate after the post-processing.Furthermore,a new production technology of carbenoxolone sodium was established.On the basis,the analytical detection methods for carbenoxolone sodium was set,and further quality control methods of carbenoxolone sodium were studied.