Study On The Pharmacodynamics, Toxicology And Preliminary Clinical Trial Of Rehmannia Glutinosa Oligosaccharide Capsule

Objective:Rehmannia glutilosa Libosch. (Dihuang) refers to the fresh or dry root of Rehmannia glutilosa, a herb of the Scrophulariaceae family. Rehmannia dride rhizome (Sheng Dihuang), has the effect of removing pathogenic heat from blood, nourishing Yin and promoting the production of body fluids. With the foundation of the past work, according to the standard related to the fifth category of new Chinese drug in Annex1 of the Drug Registration Regulation, Pharmacodynamics toxicology and preliminary clinical trial Rehmannia glutinosa oligosaccharide (ROS) capsule has been studied on the by using the modern pharmaceutical techniques in this thesis.Methods:1. Hypoglycemic effect of Rehmannia glutinosa oligosaccharide capsule was investigated in glucose-or adrenaline-induced hyperglycemic and alloxan-induced diabetic rat models. The animals were divided into control group, alloxan diabetic model group or hyperglycemia model group, Rehmannia glutinosa oligosaccharide (ROS) capsule (375,750 mg·kg-1·d-1) treated group and Yunquan Wan (750mg·kg-1·d-1) treated group. All drugs were administered by intragastric administration. 2.The acute toxicity study of ROS capsule was conducted with the maximum tolerance dose method at the oral dose of 20 g·kg-1. For the repeated dose toxicity study, once daily, at the doses of 5 g·kg-1,10 g·kg-1 and 20 g·kg-1 for 3 consecutive groups and control group for 14 days. All drugs were administered by intragastric administration.3. Fifty patients were randomly divided into two groups:experimental group (n=30) and control group (n=20). The two groups received orally Rehmannia glutinosa oligosaccharide capsule,1.5 g, tid, and Yu Quan Wan 9 g, tid, respectively for 4-8 weeks. Fasted glucose level, post prandial glucose level, plasma insulin level, and lipid level of the subjects were determined before and after the drug administration.Results:1. Compared with that of positive control group of Yu Quan Wan, plasma fasted glucose level as well as hepatic glucogen content was slightely reduced in the high and low dose groups of ROS capsule treated rats. The peak glucose levels of 30 min,60 min after administration in glucose-and adrenaline-induced hyperglycemic rats were significantly lower than that's of positive control group rats.2. ROS capsule showed a significant hypoglycemic effect at the high and low doses in alloxan-induced diabetic rats. In addition, plasma lipid level was decreased.3. In the acute toxicity study of ROS capsule, it was found that ROS capsule was very safe and the maximum tolerance dose was 20 g·kg-1 (i.g) in mice.4.For patients with type 2 diabetes, the symptoms were significantly improved, glucose level and lipid level (total cholesterol and triglyceride) were significantly decreased after ROS capsule treatment. Total efficiency rate of ROS capsule reached up to 86.7%.Conclusion:1. Plasma glucose level and plasma lipid level in ROS capsule treated groups were decreased compared with control group and hyperglycemic model group.2. Plasma glucose level and plasma lipid level in Rehmannia glutinosa oligosaccharide capsule treated groups were decreased compared with ALX group.3.Rehmannia glutinosa oligosaccharide capsule was safe and innocuous.4. Treatment of type 2 diabetic patients with Rehmannia glutinosa oligosaccharide capsule is effective to treat type 2 diabetes patients.