Pharmaceutical Research Of Zaoqi Pills

Zao Qi pill is a compound preparation,composed of gleditsiae spina,cortex araliae and astragali radix,with detumescence and scattering kont,supplementing qi and fu zheng,etc.Mainly used for the treatment of colon cancer,rectal cancer and other solid tumors.In this study,the preparation technology,quality standard,stability,pharmacodynamics and toxicity were systematically investigated.1.Preparation of Zao Qi pillGleditsiae spina is used for the monarch drug,cortex araliae for minister and astragali radix for adjuvant.According to physical and chemical properties,active ingredients and pre-experiment,3/4 of astragali radix were crushed into powder,others decoctd.The extraction process and drying process were optimized by L₉?3⁴?orthogonal experiments,the factors of extraction process were water quantity,extracting time,and extracting times,indexes were extraction ratio and quercetin,while drying process considered the influences of drying temperature,drying time and material thickness on water content and disintegration time.The optimum extraction process is 2 times,8 times volume water,once 1.5 hours,whlie drying process is 70?,24h,2cm.In addition,the single factor experiment was used to investigate the soaking time and additives,and finally soaking time was 1h and the additive is 20%starch paste.The results show that the preparation process of Zao Qi pills is good and the operation is simple and easy according to the three batches of pilot tests with 10 times of prescription.2.Quality standard of Zao Qi pillIn the study of quality standards,quercetin,astragaloside and astragali radix were used as contrast to establish the identified methods of the three chinese medicine in Zao Qi pill by TLC,purchased from the seizure,the methods of are simple and reliable.Samples of the three batches of pilo met requirements according to the 2015 edition of China pharmacopoeia?fouth?under the general rule of 0108 pill.Established methods for determinating the content of quercetin and astragaloside by HPLC.The average recovery rates of quercetin and astragaloside are96.20%?96.45%,respectively.RSD are 4.14%?2.79%,respectively.RSD of repeatabilities are 2.37%?3.50%.The results show that the methods are simple,feasible,sensitive and specificity according to methodological investigation.Therefore,establishing quality standards of Zao Qi pill.3.Preliminary stability of Zao Qi PillIn accordance with the quality standards of Zao Qi Pill,accelerated stability experiment?1 month,2 months,3 months,6 months?and long-term stability experiment?0 months,3 months,6 months,9 months,12 months?were did for samples of three batches pilot,which the main projects concluded characters,identifications,moisture content,disintegration time,microbial limit and content.Those datas were compared with 0 months,respectively.Tests found no significant changes with the indicators,which indicated that samples are stable,So Zao Qi pill will be stable in 18 months.4.Pharmacodynamic action and acute toxicity study of Zao Qi pill4.1 Pharmacodynamic action of Zao Qi pillTo study the pharmacodynamic action of Zao Qi pill,establishing the transplant tumor model in nude mice for HCT116.Immunohistochemistry was used to detecte MVD and VEGF expression.Results show that Zao Qi pill inhibited tumor growth in nude mice in varying degrees.After the administration of each treatment group,TV,RTV,and T/C wre decreased significantly?P<0.05?.SABC assay showed that MVD of Zao Qi pill treatment group was sparse,MVD value was decreased compared with control group,the same as the positive expression of VEGF.The result show that Zao Qi pill can inhibit tumor growth of transplanted colon cancer cell line HCT116 in nude mice in varying degrees,reduce MVD value and the expression of VEGF in tumor tissue,so its antitumor activity may be related to inhibiting angiogenesis.4.2 Acute toxicity study of Zao Qi pillTo investigate the safety of Zao Qi pill,the acute toxicity test was designed.It was unable to measure LD₅₀ for low toxicity,so MTD was used.The MTD of mice was 12g/kg,and there was no significant change in body weight.After 14d,the rats were sacrificed and dissected,and the main organs were observed withou any problem.The results showed that the toxicity of Zao Qi pill was low,and it was safe and reliable in the prescribed dose.