Pharmaceutical Preparation Research Of Anti-Helicobacter Pylori New Drug2-hexyl-3-methylquinolin-4(1H)-one(HMQ)

Helicobacter pylori is the main pathogenic factor of chronic gastritis and gastric ulcer, the World Health Organization classified H. pylori as a group I carcinogen responsible for its leading role in the development of gastric cancer. Currently, there are still few effective therapeutic drugs available in clinical practice. Research of anti-Helicobacter pylori new drugs is significant in drug development of gastritis gastrointestinal diseases.The pharmaceutical manufacturing and efficiency of new anti-Helicobacer pylori drug HMQ in vivo have been investigated. The main research results are as follow:1. The HPLC method of HMQ content determination were establishedThe system suitability and chromatogram condition: octadecyl bonded silica(4.6×150 mm,5 μm)were used as filler, mobile phase was methanol-water(80:20),determine wavelength was 240 nm, flow rate was 1 mL/min, detected at room temperature. HMQ showed a good linear between 0.00226~2.26μg(R2=0.9998), and stability in 24 h. The method is simple, reliable and reproducible; it can be used for HMQ content determination.2. The preformulation study of HMQ have been finishedThe parameter of physical and chemical properties, powder property and stability in different conditions was tested. The result indicated that HMQ is a stable,liposoluble and hard-soluble drug, hardly absorb moisture and poor fluidity.3. The tissue distribution and metabolism of HMQ in mice have been investigatedThe HPLC determination method of HMQ in mice was established, metabolism of HMQ after oral administration fitted to two compartment models. HMQ distributed in heart, liver, spleen, lung, kidney, brain and genitals, Cmax of majority of tissues are 1h,the mean residence time of liver and kidney are 6-8h, there is a few distribution in brain which proved HMQ can traverse blood-brain barrier. The result indicated that oral administration can be adopted.4. The formulation and preparation process of HMQ have been selectedThe formulation and preparation process was primarily selected by single factor experiment, uniform design was used to optimize, HMQ dripping pills and HMQ micro powder capsule were prepared according to the prescription, and quality wasevaluated. The dissolution rate of HMQ dripping pills is superior to micro powder capsule.5. The preferable therapeutical effect of HMQ dripping pills to H. pylori infectious mice have been detectedThe mice models of H. pylori infected gastric ulcer was setting, administrate 200,100, 50 mg/kg of HMQ dripping pills and micro powder capsule by oral for a week,amoxicilin as positive control, rapid urease test, smear and pathological slice are used to observe therapeutical effect of different dosage form. The Hp eradication rate of HMQ dripping pills is 90%, higher than amoxicilin of same dosage(P>0.05),eradication rate of micro powder capsule is relatively low, and there is a significant difference with model control. The pathology result shows that HMQ dripping pills can repair gastric mucosa, recovery effect of micro powder capsule and moxicilin are not good as dripping pills. The eradicate effect to H.pylori and recovery effect to damaged gastric mucosa of HMQ dripping pills is better than micro powder capsule.