Evaluation Of Shu-wei-xiao-yang Capsule In Pharmacodynamics And Safety

The mainly drugs in the treatment of peptic ulcer are proton pump inhibitors and H2receptor blockers and proprietary Chinese medicines market share is very small and does not form a variety of dominant position. But Chinese medicine has the experience accumulated in the understanding and treatment of the peptic ulcer and other gastrointestinal diseases in two thousands of years, so to develop the Chinese medicine will have certain advantages in the treatment of peptic ulcer. Shu-wei-xiao-yang Capsule is a new formulation of the TCM which was formed from clinical experience.The composition of the prescription contain ten herbs: Atractylodes, citrus aurantium, dried tangerine peel, woody, berberine, Evodia, Breit, Trichosanthes Bupleurum and betel, and has a good effect on the stomach or duodenal ulcer and gastritis in clinical. This prescriptionthe is effective in clinical, we run a drug R&D projects for pharmacodynamic、mechanism and the safety evaluation.Objective:1To provide the basis of the pharmacodynamic and the safety evaluation in the development of the Shu-wei-xiao-yang Capsule.2To find the pharmacodynamic mechanism of the Shu-wei-xiao-yang Capsule.3To explore the mechanism of the gastric and duodenal ulcers.Methods:On the clinical efficacy of Shu-wei-xiao-yang Capsule, this research focused on the protective role in the treatment of chronic gastritis, the acute gastric mucosal injury and on the role of in vivo and in vitro gastrointestinal.we made a safety evaluation of the the Shu-wei-xiao-yang Capsule though the acute toxicity tests and long-term toxicity tests.The main experimental method was as follows:1The acute impaired model of gastric mucous membrane on rat was made by absolute ethanol. The protective effect of acute gastric mucosal injury in rats was Observed.2The chronic gastritis model on rat was stimulated through sodium deoxycholate and ethanol. The acid index of gastric juice, Peptic activity, IL-1β、IL-8and TNF-a were tested. And the histological examination of stomach was also observed.3The function of gastrointestinal motility was observed through determining gastric emptying ability and gastric emptying rate by henolsulfonphthalein experiment on rats and carbo medicinalis experiment on mice. Based on the above two experiments we can evaluate the effect of Shu-wei-xiao-yang Capsule on gastrointestinal motility4The analgesia function of Shu-wei-xiao-yang Capsule was observed by testing the inhibition rate of writhing response with glacial acetic acid and pain threshold through hot plate experiment on mice.5The anti-inflammatory function of Shu-wei-xiao-yang Capsule was observed by testing ears’swelling degree with xylene on mice and granuloma weight with agar on rats.6Add the Shu-wei-xiao-yang Capsule solution to normal Isolated intestinal, the Isolated intestinal after adding acetylcholine function, the Isolated intestinal after adding neostigmine after and the Isolated intestinal after adding atropine function to observe the effect of Shu-wei-xiao-yang Capsule on the Isolated intestinal, and speculate its mechanism.7The safety evaluation of Shu-wei-xiao-yang CapsuleIn acute toxicity test on mice:First we did a pre-experimental preliminary estimate of the dose and test methods.Then the maximal tolerance dose (MTD) of Shu-wei-xiao-yang Capsule was determined, to find the acute toxicity and the administration of the maximum safe dose.In chronic toxicity test, rats were administered Shu-wei-xiao-yang Capsule for three months with different doses. Then the indexes which were responsible for safe were detected in half of the test animals.The last hslf animals were observed for another month to detect possible toxicity which did not been show in the period of administration and the reversiblity of toxic reaction. During the experiment we recorded the weight of animals, the food intake and general behavior every week.13indicators of hematologic and19indicators of biochemic were tested. And the main organs were weighed. Organ indexes were calculated and histological examinations of main organs were performed. The main organs in control group and high dose group were histological examined firstly. Other groups were stored and would not be histological examined unless there was abnormity in high dose group.Results:1Compared with model group, the index of stomach ulcer caused by absolute ethanolwas obviously decreased in the high and middle dose group of Shu-wei-xiao-yang Capsule (P<0.01). Shu-wei-xiao-yang Capsule could improve the gastric mucosa pathological change and mortification. It could decrease the infiltration of phlogocyte among gastric mucosa glands and the dropsy of gastric mucosa muscularis and serosa. It was indicated that Shu-wei-xiao-yang Capsule could protect gastric mucosa from acute injury.2Compared with model group, Shu-wei-xiao-yang Capsule could increase gastric acidity and stomach peptic activity of rats which having chronic gastritis (P<0.05). Serum content of IL-1β and IL-8in each groups of Shu-wei-xiao-yang Capsule were decreased significantly (P<0.05). The serum TNF-a levels made a downward trend.The pathological section revealed that Shu-wei-xiao-yang Capsule could significantly reduce the degree of imflammation. It could improve gastric mucosal lesion. It could also decrease tissue necrosis and exudation, to reduce the edema of gastric mucosa submucosa, muscularis, and serosa. All of these hinted the therapeutic effect of Shu-wei-xiao-yang Capsule on chronic gastritis.3Compared with normal group, Shu-wei-xiao-yang Capsule could decrease phenolsulfonphthalein concentration in stomach of rats in high and middle dose group (P<0.05～0.01). Each groups of Shu-wei-xiao-yang Capsule could extend carbo medicinalis besiegement distance obviously (P<0.05). All of these indicated that Shu-wei-xiao-yang Capsule could promote gastrointestinal motility.4Compared with normal group, Shu-wei-xiao-yang Capsule could inhibit writhing response on mice(P<0.01). Shu-wei-xiao-yang Capsule could increase pain threshold after being administered2hours (P<0.05). Shu-wei-xiao-yang Capsule was effective on analgesia. 5Compared with the normal group, the ears’swelling degree in high and middle dose groups of Shu-wei-xiao-yang Capsule were inhibited (P<0.05-0.001). It could reduce granuloma weight and inhibit granuloma growing (P<0.05). All of these indicated that Shu-wei-xiao-yang Capsule was effect on anti-inflammatory.6Shu-wei-xiao-yang Capsule can promote the bowel movements though increasing intestinal contraction amplitude and peristaltic frequency. It can suppress the abnormal contraction of the intestine to antispasmodic. Shu-wei-xiao-yang Capsule can inhibite the abnormal contraction caused by acetylcholine and neostigmine,and also can an antagonize the intestinal relaxant effect of atropine.This result prompted that the effect of Shu-wei-xiao-yang Capsule may have nothing to do with the M receptor,but may be associated with N1(Nn) receptor or the histamine receptor.7In acute toxicity test, the mice did not die or had apparent anomalism after being administered with The maximum dose. Two weeks later, the mice were showed no apparent pathological changes. The The maximum dose of Shu-wei-xiao-yang Capsule was about776times than the recommended clinical dose for human.In chronic toxicity test, compared with normal group, body weight, food-intake and organ index on rats of Shu-wei-xiao-yang Capsule did not have apparent change except rare exceptions. But after administered3months, the hematologic index results indicated that there was a significant increase in Hgb and PLT. The biochemical index results indicated that all indexs were within the normal range; Withdrawal after one month, the hematologic index results indicated that t all indexs were within the normal range.The biochemical index results indicated that ALT and AST Shown a increasing trend; After administered3months, a half animals of every group were detected the histological examinations,it indicated that one rat in normal group had hepatic steatosis in liver tissue, and there were no apparent changes in internal organs among other rats and not yet pathology change caused by toxicity. Withdrawal after one month,the histological examinations of another half animals indicated that one rat in normal group had hepatic steatosis in liver tissue,and there were no apparent change in internal organs among other rats and not yet pathology change caused by toxicity. Detected index and pathological section of acute toxicity test on mice and chronic toxicity test on rats indicated that Shu-wei-xiao-yang Capsule was safety. Although some index was changed, the main reason of these may be caused by abnormal index of some rats in normal group. It needed further study to expain these phenomenon.Conclusion:Shu-wei-xiao-yang Capsule could protect gastric mucosa from acute injury. It could treat chronic gastritis. It could promote gastrointestinal motility too. It could also relieve pain and eliminate inflammation. Toxicology test showed that Shu-wei-xiao-yang Capsule was safety if used in conventional dose. These results could provide certain reference for further clinical experiment and research.