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Method for preparing water-soluble taxane medicament and application thereof

A taxane, water-soluble technology, applied in the field of water-soluble taxane drugs, can solve problems such as drug dissociation, achieve the effects of reducing toxicity, avoiding toxic side effects and irritation, and improving curative effect

Inactive Publication Date: 2011-01-05
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is a patent (Chinese Patent Publication No. CN1629150) to report that a paclitaxel prodrug of a polyethylene glycol aliphatic polyester block copolymer has been synthesized, and its polymer carrier has biodegradability. The drug is easily dissociated from the binding site

Method used

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  • Method for preparing water-soluble taxane medicament and application thereof
  • Method for preparing water-soluble taxane medicament and application thereof
  • Method for preparing water-soluble taxane medicament and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Embodiment 1: Preparation of PEG-VC-PTX

[0063] Preparation of PEG-succinic acid:

[0064] PEG (20gl), succinic anhydride (0.40g) and triethylamine (1mL) were added to CH 2 Cl 2 (100mL), reflux for 2h, add 100mL of distilled water, with CH 2 Cl 2 Extract (50mL×2), combine CH 2 Cl 2 layer, dried over anhydrous sodium sulfate, filtered, concentrated, added a large amount of diethyl ether to precipitate a solid, filtered with suction, and dried to obtain the product as a white solid, 15.10 g, with a yield of 74.02%.

[0065] Preparation of Fmoc-Val-Cit:

[0066] Dissolve Fmoc-Val (5.06g) and HOSu (1.72g) in THF (100mL), add DCC (3.08g), react for 1h, add Cit (2.74g) and NaHCO 3 (1.32g), reaction 4h.. Add aqueous citric acid solution (30%, 75mL) to the reaction system, extract with ethyl acetate (50mL×2), combine the organic phases, wash with water (50mL×2), evaporate the solvent under reduced pressure, and add Diethyl ether (80 mL) precipitated the product, sucti...

Embodiment 2

[0071] Embodiment 2: Preparation of PEG-VC-PABC-VC-PTX

[0072] Preparation of Fmoc-Val-Cit-PABOH:

[0073] Add Fmoc-Val-Cit (1.04g), EEDQ (0.52g) and PABOH (0.26mg) to CH 2 Cl 2 , reacted for 10 h, evaporated the solvent under reduced pressure, added diethyl ether, stirred, filtered with suction, washed with diethyl ether, and dried to obtain a light purple solid, 1.10 g, with a yield of 81.84%.

[0074] Preparation of Fmoc-Val-Cit-PABC-PNP:

[0075] Fmoc-Val-Cit-PABOH (0.30g) and PNPCOCl (0.10gl) were added to THF (15mL), triethylamine (300uL) was added dropwise with stirring, and reacted overnight at room temperature. Flash column separation (CHCl 3 :CH 3 OH=20:1→10:1) to obtain a pink foamy solid, 0.20 g, yield 52.31%.

[0076] Preparation of Fmoc-Val-Cit-PABC-PTX:

[0077] Add Fmoc-Val-Cit-PABC-PNP (160 mg), PTX (214 mg) and DMAP (31 mg, 0.25 mmol) sequentially to CH 2 Cl 2 (20mL), react at room temperature for 100h. Flash column (CHCl 3 :CH 3 OH=30:1→20:1) is...

Embodiment 3

[0080] Embodiment 3: Preparation of PEG-VC-DTX

[0081] Preparation of PEG-succinic acid:

[0082] PEG (20gl), succinic anhydride (0.40g) and triethylamine (1mL) were added to CH 2 Cl 2 (100mL), reflux for 2h, add 100mL of distilled water, with CH 2 Cl 2 Extract (50mL×2), combine CH 2 Cl 2 layer, dried over anhydrous sodium sulfate, filtered, concentrated, added a large amount of diethyl ether to precipitate a solid, filtered with suction, and dried to obtain the product as a white solid, 15.10 g, with a yield of 74%.

[0083] Preparation of Fmoc-Val-Cit:

[0084] Dissolve Fmoc-Val (5.06g) and HOSu (1.72g) in THF (100mL), add DCC (3.08g), react for 1h, add Cit (2.74g) and NaHCO 3 (1.32g), reaction 4h.. Add aqueous citric acid solution (30%, 75mL) to the reaction system, extract with ethyl acetate (50mL×2), combine the organic phases, wash with water (50mL×2), evaporate the solvent under reduced pressure, and add Diethyl ether (80 mL) precipitated the product, suction ...

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Abstract

The invention relates to a method for preparing a water-soluble taxane medicament and application thereof. In the water-soluble taxane compounds with a formula I structure, R1 is phenyl or alkoxide, R2 is acetyl or hydrogen atoms, and R3 is directly directed or 4-amino benzyloxy formyl.

Description

Technical field: [0001] The invention relates to a preparation method and application of water-soluble drugs, in particular to a water-soluble taxane drug, their preparation method and their application in clinical tumor treatment. Background technique: [0002] Taxane drugs generally include paclitaxel and its derivatives, docetaxel and its derivatives. Paclitaxel is white or off-white powder, its molecular formula is C 47 h 51 NO 14 , with a molecular weight of 853.9, strong fat solubility, easily soluble in organic solvents such as chloroform and ethanol; docetaxel is white or off-white powder, and its molecular formula is C 43 h 55 NO 13 , strong fat solubility, easily soluble in organic solvents such as chloroform, ethanol, acetone; the solubility of taxanes is very low, among which the solubility of paclitaxel is less than 0.004g / L, while the solubility of docetaxel is less than 0.01g / L. [0003] Paclitaxel (Taxol ) and docetaxel (Taxotere ) were approved by ...

Claims

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Application Information

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IPC IPC(8): C07K5/062A61K31/337A61K47/48A61P35/00A61K47/61A61K47/65
Inventor 张强李润涛梁良林松文王坚成
Owner PEKING UNIV
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