Polyethylene glycol modified paclitaxel, and preparation method and application thereof

A technology of polyethylene glycol and paclitaxel, which can be applied to medical preparations without active ingredients, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve problems such as unsatisfactory effects of improving water solubility and bioavailability, and achieves High bioavailability, easy operation, improved solubility

Inactive Publication Date: 2018-03-13
湖南华腾制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Documents CN1283643, CN1895676 and CN101569747 disclose paclitaxel modified by linear polyethylene glycol, but their effects in improving water solubility and bioavailability are not satisfactory

Method used

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  • Polyethylene glycol modified paclitaxel, and preparation method and application thereof
  • Polyethylene glycol modified paclitaxel, and preparation method and application thereof
  • Polyethylene glycol modified paclitaxel, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Preparation of Compound I-1:

[0017]

[0018] In the above formula, the molecular weight of mPEG is 800.

[0019] Add II (1g) and PTX (0.5g) into dichloromethane (40ml), stir to dissolve, then add catalytic amounts of DMAP and DCC (0.13g) respectively, under argon protection, stir at room temperature for 24 hours, TLC plate detection The raw material PTX reacted completely. Filtrate, pour the filtrate into cold ether to obtain a white precipitate, filter, and vacuum-dry the filter cake to obtain a branched polyethylene glycol-modified paclitaxel compound (mPEG-PTX) white powder, re-dissolve the obtained solid in dichloromethane , then concentrated to 1ml, then added isopropanol to separate out a white solid (1.04g, yield 74%, paclitaxel content 32%), which is the target product I.

Embodiment 2

[0021] Preparation of Compound I-2:

[0022]

[0023] In the above formula, the molecular weight of mPEG is 1600.

[0024] Add II (1g) and PTX (0.25g) into dichloromethane (30ml), stir to dissolve, then add catalytic amounts of DMAP and DCC (0.09g) respectively, under argon protection, stir at room temperature for 24 hours, TLC plate detection The raw material PTX reacted completely. Filtrate, pour the filtrate into cold ether to obtain a white precipitate, filter, and vacuum-dry the filter cake to obtain a branched polyethylene glycol-modified paclitaxel compound (mPEG-PTX) white powder, re-dissolve the obtained solid in dichloromethane , then concentrated to 1ml, then added isopropanol to separate out a white solid (0.81g, yield 64.8%, paclitaxel content 19.2%), which is the target product I.

Embodiment 3

[0026] Preparation of Compound I-3:

[0027]

[0028] In the above formula, the molecular weight of mPEG is 2000.

[0029] Add II (2g) and PTX (0.3g) into dichloromethane (34ml), stir to dissolve, then add catalytic amounts of DMAP and DCC (1.2g) respectively, under argon protection, stir at room temperature for 24 hours, TLC plate detection The raw material PTX reacted completely. Filtrate, pour the filtrate into cold ether to obtain a white precipitate, filter, and vacuum-dry the filter cake to obtain a branched polyethylene glycol-modified paclitaxel compound (mPEG-PTX) white powder, re-dissolve the obtained solid in dichloromethane , then concentrated to 1ml, then added isopropanol to separate out a white solid (1.6g, yield 79%, paclitaxel content 12.8%), which is the target product I.

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PUM

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Abstract

The invention discloses a polyethylene glycol-modified paclitaxel and a preparation method thereof. The structure of the polyethylene glycol-modified paclitaxel is shown in formula I. The preparation method is to connect two amino groups of lysine to poly Polyethylene glycol formed from ethylene glycol and paclitaxel (PTX) are used as raw materials, 4-dimethylaminopyridine (DMAP) is used as a catalyst, and dicyclohexylcarbodiimide (DCC) is used as a condensation agent to obtain monomethoxy based peg-paclitaxel compound. The compound is used in the preparation of medicine for treating cancer.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to polyethylene glycol-modified paclitaxel and its preparation method and application. Background technique [0002] Many drugs such as Paclitaxel (PTX) have good activity, but because of their extremely poor water solubility, they often lead to extremely low bioavailability or cannot be formulated into solutions for injection. In order to increase the bioavailability of such drugs, it is necessary to increase the solubility of these drugs in water. Conventional methods currently used to solubilize these poorly soluble drugs include mixed solvent method, solubilizer and solubilization method, solubilizer solubilization method, soluble salt method, solid dispersion or clathrate method, etc. Different solubilization methods are often selected for different drug characteristics. [0003] Paclitaxel has good antitumor activity, but its water solubility is extremely poor ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/60A61K31/337A61P35/00C08G65/333
CPCA61K31/337C08G65/33327
Inventor 邓泽平罗容许慧
Owner 湖南华腾制药有限公司
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