A kind of right-lipoic acid lysine salt enteric-coated tablet and preparation method thereof

Abstract

The invention discloses a dextral lipoic acid-lysine salt enteric tablet and a preparation method thereof. With a novel crystal form of self-researched R(+)-lipoic acid-L-lysine salt as a main medicine, a related preparation is developed; by a twin-screw extrusion technology, the main medicine and an enteric carrier material are integrated under a strong shearing and kneading action and the medicine is coated by the enteric carrier, so that the effect that polymerization does not occur even if a small amount is released in a stomach is achieved; in addition, the medicine is released relativelyslowly in a small intestine, so that the blood concentration is more steady, and thus reduction in toxic and side effects of the medicine is facilitated.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a d-lipoic acid lysine salt enteric-coated tablet and a preparation method thereof. Background technique [0002] Lipoic acid (lipoic acid, LA), a natural antioxidant that is soluble in both water and fat, its chemical name is 1,2-dithiopentane-3-pentanoic acid, and its molecular formula is C 8 h 14 o 2 S 2 . It was first isolated and extracted from pig liver by Reed et al. in the United States in 1950. It is widely distributed in the liver, heart and kidney of animals. It is the strongest natural antioxidant and is known as the "universal antioxidant". agent". From the chemical structure analysis of lipoic acid, the presence of the asymmetric center of the No. 3 carbon atom of dithiolane has produced two corresponding R-type (dextrorotary) and S-type (left-handed) enantiomers, which have been shown The two enantiomers have different pharmaco...

AI Technical Summary

Problems solved by technology

However, R-lipoic acid has a low melting point, and it is very easy to polymerize under high temperature and acidic conditions, and has poor stability. After reacting with lysine to form a salt, it has a higher melting point and is more stable in storage. The R-enantiomer can be preferentially absorbed by the body, and has a higher concentration distribution in the body, so oral administration of D-lipoic acid lysine can achieve higher bioavailability

However, D-lipoic acid has its major defects, that is, it is unstable, and the melting point of lipoic acid is low (47-50 ° C), and polymerization can occur at relatively low temperatures, which affects the efficacy and safety of its clinical treatment.

And D-lipoic acid is insoluble in water, so the physical and chemical properties of D-lipoic acid directly limit its use in the preparation of various pharmaceutical preparations

[0004] At present, the preparations related to α-lipoic acid in the domestic and foreign markets mainly include injections, tablets, hard capsules, etc. The compliance of patients with injections is poor, and the bioavailability of tablets and hard capsules is low

Chinese patent (CN105001195A) discloses a new crystal form I of R(+)-lipoic acid-L-lysine salt, which is an innovative drug developed by the applicant in the early stage, and there is no D-lipoic acid lysine salt Marketing of related preparations

Compared with lipoic acid, D-lipoic acid lysine has better stability and high bioavailability, but studies have found that it is unstable under acidic, humid heat, high temperature and light conditions, and is more likely to polymerize under acidic and humid heat conditions. It not only reduces the content and affects the efficacy of the drug, but also has potential safety issues in polymers

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