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New crystal form of R(+)-thioctic acid-L-lysinate and preparation method thereof

A technology of lysine salt and lipoic acid, which is applied to a new crystal form of R-lipoic acid-L-lysine salt, in the application field of medicine, which can solve the problems that the crystal form state cannot solve well, and prepare The process is cumbersome and other problems, and the effect of high dissolution rate, simple preparation process and better stability is achieved.

Active Publication Date: 2015-10-28
河北迈科生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the above-mentioned racemic lipoic acid lysine is known, its preparation process is cumbersome, and the crystal form state cannot well solve the difficulties in preparation

Method used

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  • New crystal form of R(+)-thioctic acid-L-lysinate and preparation method thereof
  • New crystal form of R(+)-thioctic acid-L-lysinate and preparation method thereof
  • New crystal form of R(+)-thioctic acid-L-lysinate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Preparation of R(+)-lipoic acid-L-lysine salt crystal form I

[0039] At a temperature of 55-60°C, dissolve R(+)-lipoic acid (20.6g, 0.1mol) in a mixed solvent of ethanol 52mL and ethyl acetate 52mL; add dropwise L-lysine (14.6g, 0.1mol ) 40mL of 95% ethanol solution, dripping, keep warm for 2h, filter while hot; cool the filtrate to 0-10°C, stir and crystallize for 3h, filter and dry to obtain about 33.1g of yellow crystalline solid, yield 94%, HPLC 99.55% purity. The melting point is 185-186°C.

Embodiment 2

[0040] Example 2 Preparation of R(+)-lipoic acid-L-lysine salt crystal form I

[0041] At a temperature of 55-60°C, dissolve R(+)-lipoic acid (20.6g, 0.1mol) in a mixed solvent of ethanol 75mL and ethyl acetate 90mL; add dropwise L-lysine (17.5g, 0.12mol ) in 50mL of 90% ethanol solution, drop it, keep it warm for 2h, and filter it while it is hot; cool the filtrate to 0-10°C, stir and crystallize for 5h, filter and dry to obtain about 32.7g of yellow crystalline solid, with a yield of 92%, HPLC 99.60% purity. The melting point is 185-186°C.

Embodiment 3

[0042] Example 3 Preparation of R(+)-lipoic acid-L-lysine salt crystal form I

[0043] At room temperature, add sodium ethylate (15g, 0.22mol) to 120mL of ethanol solution of R(+)-lipoic acid (41.2g, 0.2mol), stir to dissolve, filter to obtain ethanol solution of R(+)-lipoic acid sodium , set aside; suspend L-lysine hydrochloride (38.4g, 0.21mol) in 150mL of acetone, control the temperature at 55-60°C, add R(+)-sodium lipoic acid solution dropwise under stirring, after the drop , keep stirring for 2 hours, and filter while hot; add 85 mL of isobutyl acetate to the filtrate, then cool down to 4°C, stir and crystallize for 3 hours, and filter and dry to obtain about 64.8 g of a yellow crystalline solid, with a yield of 92% and a purity of 99.86% by HPLC . The melting point is 187-188°C.

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Abstract

The invention relates to the field of pharmaceutical chemistry, specifically to a new crystal form of R(+)-thioctic acid-L-lysinate, namely its crystal form I and its preparation method. The invention also relates to a pharmaceutical composition containing the new crystal form and an application of the pharmaceutical composition in the preparation of drugs for treating paresthesia caused by diabetic peripheral neuropathy. By the use of Cu-K alpha radiation, the X-ray power diffraction of R(+)-thioctic acid-L-lysinate crystal form I has diffraction peaks at 5.012, 7.589, 10.072, 12.549, 15.036, 16.688, 18.627, 19.356, 25.064 and 27.611 when expressed with 2 theta degrees, wherein the error range of 2 theta value is + / - 0.2.

Description

technical field [0001] The present invention relates to polymorphs of pharmaceutical compounds, more specifically, to a new crystal form of R(+)-lipoic acid-L-lysine salt, and a method for preparing the new crystal form. The invention also relates to the application of the pharmaceutical composition containing the crystal form in the preparation of medicine for treating abnormal sensation caused by diabetic peripheral neuropathy. Background technique [0002] Diabetic neuropathy is one of the most common chronic complications of diabetes. Lesions can accumulate in the central nervous system and peripheral nerves, especially peripheral neuropathy complicated by diabetes can cause paresthesia, namely: Diabetes Peripheral Neuropathy, DPN is particularly common, and seriously affects the patient's Quality of Life. Clinically, when diabetic patients are complicated with peripheral neuropathy, acral paresthesia and hyperalgesia appear in the early stage, followed by hypoalgesia, ...

Claims

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Application Information

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IPC IPC(8): C07D339/04A61K31/385C07C229/26C07C227/42A61K31/198A61K9/20A61K9/08A61P3/10A61P25/02
CPCA61K9/0019A61K9/0053A61K9/2013A61K9/2054A61K9/2059A61K31/198A61K31/385C07B2200/13C07D339/04A61K2300/00
Inventor 刘晶郭彦飞袁尚胡永康魏丹李晶晶
Owner 河北迈科生物科技有限公司
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