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Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins

A paclitaxel and mixture technology, applied in the field of purifying biological extracts containing one or more paclitaxel, can solve problems such as separation difficulties

Active Publication Date: 2006-06-21
菲艾腾(亚洲)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, separation of paclitaxel A from cephalommanine (paclitaxel B) is difficult as described in the literature

Method used

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  • Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins
  • Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins
  • Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins

Examples

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preparation example Construction

[0067] In an alternative embodiment, the present invention aims to provide a method for isolating one or more paclitaxel from a substance comprising a paclitaxel compound obtained by a semi-synthetic or total synthesis method, the isolating method comprising the following steps: ( a) treating the substance with PBS resin; wherein the molecules used as reactants in the semi-synthetic or total synthetic approach are not only derived from Taxus brevifolia; (b) eluting the one or more paclitaxel; and (c) recovering the eluted one or more paclitaxels.

[0068] In another embodiment, the present invention aims to provide a method for isolating one or more paclitaxel from a substance comprising a paclitaxel compound obtained by a semi-synthetic or total synthesis method, the isolating method comprising the following steps: (a ) treating the substance with PBS resin; wherein the substance comprises a total amount of 2' benzoate esters of paclitaxel A, B, C, D, E, F or G of less than a...

Embodiment 1

[0102] This example shows the purification of paclitaxel A (paclitaxel) and paclitaxel B (cephalomannine) from a semi-purified extract of Taxus densif mimandia using PEI resin. Here, a 75 liter column was packed with 24.5 kg of J.T. Baker PEI resin (40 micron particle size, 275 Angstrom pore size, J.T. Baker Item #7264). The resin was equilibrated with 2 column volumes (ie 150 liters) of acetone containing 0.5% acetic acid at a flow rate of 3.2 L / min. The column was then loaded with semi-purified yew extract at a concentration of approximately 250 mg / mL in acetone at a flow rate of 0.5 L / min. The concentration of paclitaxel was 2.5% by weight, or 2.5 g of injected solids per 100 g of PEI resin. The weight percent of paclitaxel A and paclitaxel B in the injected solid was 10.8% by weight. The injection was eluted with acetone containing 0.5% acetic acid at a flow rate of 3.2 L / min (superficial velocity = 4.4 cm / min). A total of 10 fractions were collected. Fraction 1 and Fr...

Embodiment 2

[0104] This example shows the separation of paclitaxel A (paclitaxel), paclitaxel B (cephalomannine) and paclitaxel C present in a semi-purified extract of Taxus brevifolia using PEI resin. Here, a solid injection of semi-purified Taxus brevifolia extract was dissolved in acetone containing 0.6% acetic acid. The solution was loaded onto J.T. Baker PEI resin (40 micron particle size, 275 Angstrom pore size, J.T. Baker Item #7264). The loading of the injection was 3%, or 3 g of injected solids per 100 g of PEI resin. The elution solvent was acetone with 0.6% acetic acid. When the injected components are eluted from the column, approximately one sample is collected for every 1 / 20 of the column volume. These fractions were analyzed by HPLC and the data plotted as shown in FIG. 3 . This run showed that Paclitaxel A, Paclitaxel B, and Paclitaxel C had been separated from impurities.

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Abstract

The present invention aims to provide a method for isolating and / or purifying one or more paclitaxel from paclitaxel-containing substances. In one embodiment, the method comprises the steps of: (a) treating paclitaxel with an amino group-containing material attached to a solid substrate, such as silica chromatographic resin bonded with polyethyleneimine or the like; (b) eluting the paclitaxel compound of interest from the resin; and (c) recovering the eluted paclitaxel compound.

Description

technical field [0001] The present invention relates to a method for separating or isolating one or more taxane compounds from a substance containing taxane and the composition or compound obtained by the method. The invention also relates to a method of purifying a biological extract comprising one or more paclitaxel. In one embodiment, the method involves the use of a material containing one or more amino groups, including but not limited to, a silica chromatography resin bonded to polyethyleneimine, attached to a substrate (e.g., a solid substrate). (PBS resin). These resins facilitate the purification of paclitaxel in high yield and high purity. In one embodiment, the chromatographic resin comprises a non-functionalized and / or non-derivatized polyethyleneimine ("PEI") polymer bonded to silica of various particle or pore sizes. In another embodiment, polyethyleneimine is methylated to form diethylaminomethyl-bonded silica ("DEAM"). In an alternative embodiment of the in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D305/14
Inventor 詹姆斯·H·约翰逊T·G·桑班丹巴里·J·汉德克里斯多佛·D·豪罗兰·R·弗兰克斯布赖恩·A·布赫约翰·S·尤哈姆雷克斯·T·加拉格尔梅尔·A·普兰特爱德华·M·德西蒙三世东·S·杨
Owner 菲艾腾(亚洲)有限公司