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Preparation method of canagliflozin hemihydrate pharmaceutical crystal form

A technology of canagliflozin hemihydrate and crystal form, which is applied in the field of drug crystal form preparation, can solve the problems not involved in the crystal form preparation method, etc., and achieve the effects of improving yield and purity, low cost, and easy operation

Active Publication Date: 2016-08-17
安徽联创生物医药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The PCT patent application documents with the publication number WO2008069327A1 and the publication date on June 12, 2008, and the Chinese patent application documents with the publication number CN101573368A and the publication date on November 04, 2009 all disclose compound (I) hemihydrate and Its specific crystal form, but does not involve the preparation method of the specific crystal form

Method used

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  • Preparation method of canagliflozin hemihydrate pharmaceutical crystal form
  • Preparation method of canagliflozin hemihydrate pharmaceutical crystal form
  • Preparation method of canagliflozin hemihydrate pharmaceutical crystal form

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Take 10g of the crude product of canagliflozin, add 20ml of ethyl acetate, heat to dissolve, then add 10ml of water, cool to 30°C, under stirring, add 20ml of petroleum ether, stir for 30 minutes, stir and crystallize at 10°C for 4 h, filter , dried in vacuo at 60°C to obtain 8.0 g of canagliflozin crystalline product with a yield of 80% and a purity of 99.6%. Its X-ray pattern is as follows: figure 1 As shown, its TGA-DSC spectrum is as figure 2 shown.

Embodiment 2

[0023] Take 10g of the crude product of canagliflozin, add 30ml of ethyl acetate, heat to dissolve, then add 20ml of water, cool to 35°C, add 40ml of n-hexane under stirring, stir for 45 min, stir and crystallize at 20°C for 6 h, filter , 7.5g of canagliflozin hemihydrate medicinal crystalline product was obtained after vacuum drying at 55°C, with a yield of 75% and a purity of 99.9%. Its X-ray pattern is as follows: figure 1 As shown, its TGA-DSC spectrum is as figure 2 shown.

Embodiment 3

[0025] Take 10g of the crude product of canagliflozin, add 50ml of ethyl acetate, heat to dissolve, then add 10ml of water, cool to 40°C, add 50ml of methyl tert-butyl ether under stirring, stir for 60 min, and crystallize at 30°C After 10 h, filter, and vacuum-dry at 50°C, 6.8 g of the crystalline product of canagliflozin was obtained, with a yield of 68% and a purity of 99.3%. Its X-ray pattern is as follows: figure 1 As shown, its TGA-DSC spectrum is as figure 2 shown.

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Abstract

The invention discloses a preparation method of a pharmaceutical crystal form of canagliflozin hemihydrate. The steps are as follows: step 1, take the raw material drug of canagliflozin, add an organic solvent, heat to dissolve, and then add water to cool to 30-40 ℃; step 2, add an organic solvent under stirring conditions or add seed crystals after stirring for 30-60 minutes; step 3, under the condition of temperature 10-30 ℃, stir for 4-10 hours to crystallize, filter, and collect the precipitated Crystallization, vacuum drying at 40~60°C, the crystal form of canagliflozin that meets the requirements of pharmaceutical preparations can be obtained, with a purity of up to 99.9%. The present invention greatly improves the crystallization temperature, time and the amount of solvent used in the process. The yield of the crystal form of canagliflozin is high, and the operation is simple, the cost is low, and the product purity is high, which is suitable for the industrial production of canagliflozin.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical crystal form preparation, in particular to a preparation method of canagliflozin hemihydrate medicinal crystal form. Background technique [0002] Canagliflozin, English name Canagliflozin, molecular formula C 24 h 25 FO 5 S, the molecular weight is 444.52, the structural formula is as follows: [0003] [0004] Canagliflozin is the first SGLT2 inhibitor approved by the FDA for the treatment of type 2 diabetes in adult patients. SGLT is a glucose transporter with two subtypes, SGLT1 and SGLT2, which are distributed in the small intestinal mucosa and renal tubules respectively, and can transport glucose into the blood. Canagliflozin can inhibit SLCT2, so that the glucose in the renal tubule cannot be successfully reabsorbed into the blood and excreted with the urine, thereby reducing the blood sugar concentration. Since glucose is excreted into urine through the kidneys, it is accomp...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D409/10
CPCC07D409/10
Inventor 葛德培吴其华
Owner 安徽联创生物医药股份有限公司