Taxanes dimer, preparation method and preparation thereof

A technology of paclitaxel and dimer, which is applied in the field of biomedicine and can solve the problems of low solubility and the like

Active Publication Date: 2017-01-25
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
View PDF5 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to solve the problem of low solubility in water of existing pac

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Taxanes dimer, preparation method and preparation thereof
  • Taxanes dimer, preparation method and preparation thereof
  • Taxanes dimer, preparation method and preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0032] The present invention also provides a method for preparing paclitaxel dimer, which method includes:

[0033] Step 1: Mix the paclitaxel solution and the linking molecule to obtain a mixed solution;

[0034] Step 2: Add EDC and DMAP to the mixed solution obtained in Step 1 for reaction to obtain paclitaxel dimer;

[0035] According to the present invention, first dissolve paclitaxel in an organic solvent to obtain a paclitaxel solution. The organic solvent is not particularly limited and can dissolve paclitaxel, preferably methylene chloride, chloroform, dimethyl sulfoxide Or dimethylformamide; the mass concentration of the paclitaxel solution is preferably 10-20 mg mL -1 .

[0036] According to the present invention, the paclitaxel solution and the linking molecule are mixed and fully dissolved to obtain a mixed solution; the molar ratio of the paclitaxel to the linking molecule is preferably 1: (0.55-0.56).

[0037] According to the present invention, EDC (1-(3-dimethylaminopro...

Example Embodiment

[0052] Example 1: Synthesis of paclitaxel dimer coupled by suberic acid

[0053] Weigh paclitaxel (molecular weight 853.92) (136mg, 0.16mmol) in dichloromethane, then add suberic acid (15.5mg, 0.089mmol), EDC (67.1mg, 0.35mmol) and DMAP (2.2mg, 0.018mmol) After 1 hour, add EDC (32.6mg, 0.17mmol) and DMAP (2.2mg, 0.018mmol) again. After reacting at room temperature for 24 hours, filter with an oil phase filter, and then use dichloro and ethyl acetate from 8 :1 to 2:1 Slowly increase the polarity and wash the column until the product flows down. Finally, the dichloromethane and ethyl acetate in the product are spin-dried to obtain a solid powder.

[0054] figure 1 Is the mass spectrum of the paclitaxel dimer prepared in Example 1 of the present invention, figure 1 It shows that the present invention successfully prepared suberic acid coupled paclitaxel dimer.

Example Embodiment

[0055] Example 2: Synthesis of Paclitaxel Dimer Containing Disulfide Bonds

[0056] Weigh paclitaxel (molecular weight 853.92) (204.9mg, 0.24mmol) dissolved in dichloromethane, and then add 3,3'-dihydrooxolinic acid (27.3mg, 0.13mmol), EDC (97.77mg, 0.51mmol) and DMAP (3.05mg, 0.025mmol), 1 hour later, add EDC (47.93mg, 0.25mmol) and DMAP (3.05mg, 0.025mmol) again, react at room temperature for 48 hours, filter with an oil phase filter, and then use two Chlorine and ethyl acetate slowly increase the polarity from 8:1 to 2:1 to wash the column until the product flows down, and finally the organic solvent in the product is spin-dried to obtain a solid powder.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a taxanes dimer, a preparation method and a preparation thereof and belongs to the field of biological medicine. The problem of low solubleness of the present taxanes drug in water can be solved. The dimer is composed of taxanes and a joint molecule. The taxanes is taxol or docetaxel and the joint molecule is dicarboxylic acid or dicarboxylic acid containing a disulfide bond. The invention also provides the preparation method for the taxanes dimer. The invention also provides the preparation. The preparation contains an amphiphilic polymer and the taxanes dimer. The taxanes dimer provided by the invention has high solubleness in water or injection; the solution has higher storage stability; the taxanes dimer has hydrolysis reaction under a physiological condition; the taxanes drug is released, so that the curative effect can be achieved.

Description

technical field [0001] The invention belongs to the field of biomedicine, and specifically relates to a paclitaxel dimer, a preparation method and a preparation thereof. Background technique [0002] Paclitaxel is an anti-microtubule agent extracted from the needles and bark of Taxus brevifolia, which has been isolated for the first time since Wani et al. in 1971 and determined by chemical and X-ray crystallography. Since its structure, Phase I clinical studies and Phase II and Phase III clinical trials have shown significant antitumor effects on human cancers. This effect was originally discovered in advanced ovarian and breast tumors, and it has been reported in a large number of literatures to have a significant effect on small cell and non-small cell lung cancer, head and neck cancer, and metastatic melanoma. However, the main difficulty in clinical use is that its chemical structure is high in fat, almost insoluble in water, and its solubility in water is only 0.25 μg ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07D305/14A61K31/337A61K9/107A61P35/00
CPCA61K9/0019A61K9/1075A61K31/337C07D305/14
Inventor 谢志刚裴晴胡秀丽柳时景遐斌
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap