Studies On New Anticancer Drug PB With Antiangiogenic Anctivities

PDM, a herb of peperomia, is usually used to treating liver cancer, esophagus cancer and gastric cancer in folk. One of its main components, PB was extracted by our group,which has antiangiogenic activity. And expected to become a new Class I drug. For its orally and suitable for patients allergic to the protein, PB is potential to become a new class I antiangiogenic drug with independent intellectual property.Major study results:1) Study on the separation and purification method of PB.①Based on mono-factor experiment, Orthogonal Test was employed optimize the technology for extraction of PB. The optimum conditions for PB extraction were the liquid-solid ratio at14mL/g, reflux extraction with water for3times,1h per time.This technology has the advantage of low production costs, large amount of preparation, environmental pollution in small, and suitable for industrial production.②Macro porous adsorption resin and Silica column chromatography were used in phytochemistry. At last, the purity of PB in the total solid was above90%.2) Study on the precipitated technology of PB.①The solubility for poorly water-soluble PB can be raised18times by solid dispersion process.②Measurement of hygroscopicity, flowability, powder rate and dissolution, the formulations of prescription and process parameter were finally optimized.3) Study on the quality control of PB. According to the pharmacopoeia (2010edition), the items of PB about content, related substances and characteristics were inspected. Moreover, the items of PB tablet about characteristics, color, content uniformity, dissolution and weight variation were also inspected. PB and PB tablet were studied by the influence factor, accelerated and long-term test. The results showed that PB and PB tablet were stable in their corresponding conditions.4) Study on the pharmacodynamics of PB.①According to the endothelial cell proliferation assay and the endothelial cell tube formation assay, PB showed good activity. IC50value of PB against endothelial cell proliferation was6.81μmol/L, and in a dose-dependent manner.②PB exhibited strong cell growth inhibitory activity against SKOV3and K562, IC50value of PB was2.41and6.69μmol/L, respectively.③In model of tumor-bearing mice(H22, Leiws, C26), we observed certain antineoplastic effect of PB solid dispersion. It showed little side-effect, similar anti-tumor effect and highest doses produce30%effect, in a dose-dependent manner.It can be concluded that PB is potential to become a new class I antiangiogenic drug with independent intellectual property. This paper may solve the shortcomings of these drugs are never orally, not suitable for patients allergic to the protein and expensive.