Study On Quality Control For Novel Medicine Tn-101 And Tn-101 Capsules

Study on quality control for novel medicine TN-101 and TN-101 Capsules.According to the World Health Organization(WHO)'s data,12 million people worldwide are diagnosed with cancer each year, while 7.6 million people are died of cancer. In the mean time, there are about 1.8 million people died of cancer in China every year, cancer have become to be the biggest incentive of human death. New anti-cancer drug has become the key study issue of domestic and international institutions. In recent years, while molecular oncology and molecular pharmacology keep fast developing and the nature of the tumor is being clarified, advanced inventions and applications, such as large-scale, rapid screening of combinatorial chemistry, genetic engineering, etc. accelerate the discovery and development process of drug. Moreover, besides the traditional cellular toxic drugs, new anti-cancer drugs against mechanism which have multi-part function are also being discovered. Among the new anti-neoplastic drugs, inhibitors for tumor angiogenesis is currently a popular study area.Cancer is an angiogenesis-dependent disease, the growth, invasion and metastasis of primary tumor all require angiogenesis. With tumor's growing, tumor tissue can produce vascular endothelial growth factor (VEGF). Consequently, this factor and receptors for vascular endothelial growth factor (VEGFR) are combined to stimulate angiogenesis, making which to provide needed nutrients for tumor growth. Therefore, by blocking the path of VEGF/VEGFR, inhibition of angiogenesis has become a most important strategy for the drug development of anti-tumor therapy. TN-101 is a small molecule compound with new pattern, independently developed by HL company with a world chemical patent. TN-101 is a selective tyrosine kinase inhibitor, with vascular endothelial cell growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) as target spots. Pre-clinical study shows TN-101 can effectively inhibit tumor angiogenesis. Meanwhile, this project has received clinical trial approval, and Phase I clinical trail is ongoing.This thesis tries to establish the quality standard of TN-101. Based on the experimental results, such as the study of Sulftainib characterization, identification tests, the detection of related substances, residual organic solvent and assay of TN-101, this thesis establishes methods to identify TN-101 by chemical reaction, UV spectroscopy and infrared spectrometry. The related substances are detected by using HPLC. The method for detecting Etoh, Meoh, ACN, TOL and DMF are established by using gas chromatography and the analytical method for determining content of TN-101 by HPLC and capacity method are validated. Based on all the above experimental results, this thesis develops the standards for quality control of TN-101.Furthermore, this thesis also tries to establish the quality standard of TN-101 capsules. Based on the experimental results, this thesis establishes the methods to identify the TN-101 capsules by UV spectrometry and chromatography (HPLC). By using HPLC, the related substance, dissolution, and content of TN-101 are detected. With all the experimental results, this thesis develops the standards for quality control of TN-101 capsules.