_7 4 plant products 抗肿瘤植物药课件.ppt

Chapter 7. 4. Plant products 抗肿瘤植物药　 Chapter 7. 6. Anticancer Monoclonal Antibodies (单克隆抗体）　 * Chapter 7. 4. Plant products Paclitaxel (Taxol) 紫杉醇 Undisturbed Pacific Yew bark contains paclitaxel The bark is peeled and processed to provide paclitaxel Discovery of Paclitaxel On August 21st, 1962, botanists, Arthur S. Barclay, collected bark from a single Pacific yew tree, Taxus brevifolia, in a forest north of the town of Packwood in Washington State as part of a four month trip collecting material from over 200 different species. One of the Taxus samples was found to be cytotoxic in a cellular assay on 22 May 1964. Accordingly, in late 1964 or early 1965, the fractionation and isolation laboratory run by Monroe E. Wall in Research Triangle Park, North Carolina, began work on fresh Taxus samples, isolating the active ingredient in September 1966. They named the pure compound taxol in June 1967. Discovery of Paclitaxel By 1969 28kg of crude extract had been isolated from 2,600 pounds of bark, yielded only 10g of pure material. BMS filed an NDA which was given FDA approval at the very end of 1992. Taxol content varies in the Yew tree (0.001 to 0.01 % of the dry bark weight). It is generally considered to take 3 to 10 trees per patient. Based on data from the U.S. Forest Service from 1992, 36000 trees are required to provide 327200 kg of bark (about 9 kg/tree) from which 24 kg of taxol can be extracted. (about 0.66 g/tree). Approximately 1 kg is required for 480 cancer patients or 2.08 g per person or 3.15 trees per person. Others have claimed this number can be as high as 10 trees per person depending on the size of the trees Currently, all paclitaxel production for BMS uses plant cell fermentation (PCF) technology developed by the biotechnology company Phyton and carried out at their plant in Germany. This starts from a specific taxus cell line propagated in aqueous medium in large fermentation tanks. Paclitaxel is then