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Dextral lipoic acid-lysine salt enteric tablet and preparation method thereof

A technology of lipoic acid lysine salt and lysine salt, which is applied in the directions of pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve the problem of reducing the content, low melting point and stable It can prevent easy polymerization, stabilize blood drug concentration, and improve thermal stability.

Active Publication Date: 2018-10-02
NANJING HERON PHARMA SCI & TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

Method used

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  • Dextral lipoic acid-lysine salt enteric tablet and preparation method thereof
  • Dextral lipoic acid-lysine salt enteric tablet and preparation method thereof
  • Dextral lipoic acid-lysine salt enteric tablet and preparation method thereof

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Effect test

Embodiment 1

[0058] The present invention tests the stability data of the above-mentioned D-lipoic acid lysine salt under acidic, high temperature, humid heat and light conditions. see details Figure 1~4 , It is unstable under acidic conditions, and the content will drop obviously after being placed for 1 hour, and the content will drop less after continued storage, mainly due to the rapid polymerization after contact with acid, which will cause the content to drop, and the content will no longer drop significantly after polymerization. Under hot and humid conditions, the content gradually decreased over time and was obvious. When placed under high temperature and dry conditions, the content decreased relatively little, indicating that D-lipoic acid lysine was unstable under conditions of heat, humidity, high temperature and light, especially in acidic and humid conditions. Polymerization is more likely to occur under these conditions.

Embodiment 2

[0060] 1. Screening of enteric-coated carriers

[0061] In this experiment, M-type HPMCAS, L-type HPMCAS, HPMCP, Eudragit L100 and Eudragit L100-55 with a dissolved pH between 5 and 6 were selected as enteric-coated materials, and the effects of different enteric-coated materials on the extrusion process and drug release in vitro were investigated. Impact. Among them, M-type HPMCAS has the smallest torque during extrusion, and the color of the extruded product is the most similar to that of the raw material drug, and there is no polymerization phenomenon in the medium of pH 1.0, indicating that the enteric-coated material has a better wrapping effect on the main drug , preventing the ring-opening polymerization of the main drug. Therefore, M-type HPMCAS is preferred as the enteric carrier material.

[0062] 2. Screening of enteric-coated carrier ratio

[0063] The ratio of carrier to drug usually affects the feasibility of extrusion, the dissolution and stability of the dru...

Embodiment 3

[0066] The screening of embodiment 3 fillers

[0067] The filler mainly plays the role of increasing the volume and facilitating its molding in the tablet, and the filler is selected from one or more of lactose, microcrystalline cellulose, mannitol, and calcium hydrogen phosphate. Considering the particularity of medication for diabetic patients, sugars such as lactose should not be used as fillers. Similarly, mannitol will increase the burden on the kidneys of diabetic patients, so it is also not suitable for use. Microcrystalline cellulose, which is not absorbed in the body, has good compressibility and fluidity, and is widely used in powder direct compression and wet granulation compression, and has a certain capillary action, allowing water to enter quickly after contact with water The tablet core breaks the bonds between the particles and contributes to the rapid disintegration of the tablet. Therefore, microcrystalline cellulose is preferably used as the filler of the t...

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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...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/36A61K9/30A61K47/18A61K47/38A61K47/32A61K47/10A61K31/385A61P3/10A61P25/02
CPCA61K9/2013A61K9/2027A61K9/2054A61K9/284A61K9/2866A61K9/2886A61K31/385A61P3/10A61P25/02
Inventor 包玉胜杨小萍张爱洁马冲陶莉郑慧娟
Owner NANJING HERON PHARMA SCI & TECH CO LTD
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