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CN-121990936-A - Acetyl L-carnitine hydrochloride crystal form and preparation, composition and application thereof

CN121990936ACN 121990936 ACN121990936 ACN 121990936ACN-121990936-A

Abstract

The invention discloses a crystal form A of acetyl L-carnitine hydrochloride, a preparation method thereof, and bulk drugs, food additives, feed additives and compositions containing the crystal form A. The crystal form A of the acetyl L-carnitine hydrochloride has good solubility, strong stability, high purity and regular shape, and is suitable for being applied to bulk drugs, food additives and feed additives. The preparation method provided by the invention is simple in process, and the crystal form A can be obtained in high yield by in-situ crystallization of the reaction solution and then ethanol dispersion, so that the preparation method is suitable for large-scale industrial production.

Inventors

  • JIANG RUYONG
  • SUN HUAJUN
  • LI YAN
  • LU ZHIPENG
  • CHEN Jin
  • SHI MINGXING
  • TANG JIALE
  • PENG JIANGBO
  • ZHOU JIACHANG
  • LI GANG

Assignees

  • 湖北远大生命科学与技术有限责任公司

Dates

Publication Date
20260508
Application Date
20251204

Claims (14)

  1. 1. Form a of acetyll-carnitine hydrochloride characterized in that the characteristic diffraction peaks of the X-ray powder diffraction pattern expressed in 2θ using Cu-Ka radiation comprise 11.746 ±0.2°, 23.464 ±0.2°, 20.824 ±0.2°, 14.965 ±0.2°, 26.373 ±0.2°, 30.066 ±0.2°, and do not comprise 17.935 ±0.2°, 18.148 ±0.2°.
  2. 2. Form a of claim 1, wherein the X-ray powder diffraction pattern of form a is substantially as shown in figure 1.
  3. 3. Form a of claim 1, wherein the differential scanning calorimetry pattern of form a has a single absorption peak at 197.8 ± 3 ℃.
  4. 4. Form a of claim 1, wherein the form a is in the shape of a rectangular prism.
  5. 5. Form a of claim 1, wherein the solubility of form a in pure water at ambient conditions is greater than 850mg/mL.
  6. 6. A method for preparing acetyl L-carnitine hydrochloride crystal form A is characterized by comprising the following steps of S1, preparing an acetyl L-carnitine hydrochloride solution by taking L-carnitine and excessive acetyl chloride as raw materials and acetic acid as a solvent, S2, removing the excessive acetyl chloride and 85% -95% of acetic acid, S3, crystallizing the acetyl L-carnitine hydrochloride in the rest 5% -15% of acetic acid solution, S4, adding ethanol dispersed crystals into an obtained solid-liquid mixture, and S5, performing solid-liquid separation to obtain the crystal form A.
  7. 7. The method according to claim 6, wherein in step S3, a seed crystal of form a is also added prior to crystallization.
  8. 8. The method of claim 6, wherein in step S4, the mass ratio of ethanol to acetic acid is 7:1 to 24:1.
  9. 9. A bulk drug, a food additive or a feed additive, characterized by comprising the crystalline form a of any one of claims 1 to 5 or the crystalline form a prepared by the method of any one of claims 6 to 8.
  10. 10. The bulk drug, food additive or feed additive according to claim 9, wherein the weight percentage of the crystal form a in the bulk drug, food additive or feed additive is 80.0% -100%.
  11. 11. The drug substance, food additive or feed additive of claim 9, wherein more than 30% of form a has a particle size of 425 μm to 825 μm by weight based on particle size.
  12. 12. A composition comprising form a of any one of claims 1-5 or prepared by the process of any one of claims 6-8, and one or more pharmaceutically acceptable excipients.
  13. 13. The use of form a according to any one of claims 1 to 5 or prepared by the method of any one of claims 6 to 8 for muscle augmentation, neurological health maintenance, male reproductive health maintenance.
  14. 14. The composition of claim 12 for use in increasing muscle, maintaining neurological health, maintaining male reproductive health.

Description

Acetyl L-carnitine hydrochloride crystal form and preparation, composition and application thereof Technical Field The invention relates to the fields of bulk drugs, food additives and feed additives, in particular to a compound crystal form and a preparation method, a composition and application thereof. Background Acetyl L-carnitine hydrochloride commonly called acetyl L-carnitine chloride or acetyl L-carnitine hydrochloride is a natural substance existing in a human body, has particularly rich content in muscles, brains and sperms, is involved in a series of important metabolic processes in the human body, takes acetyl from cells and assists in energy transfer, has the functions of increasing muscles, improving memory, protecting nerves, improving male sperm activity and the like, and is therefore often applied to food additives, health-care products and medicines. A plurality of animal experiments prove that the supplementation of the acetyl-L-carnitine hydrochloride can obviously improve the sperm motility, the density and the normal-morphology sperm proportion of animals, so that the acetyl-L-carnitine hydrochloride has wide application in the aspect of poultry breeding. Food, health products, feed containing acetyl-L-carnitine hydrochloride are usually made into solid mixture, liquid beverage package or capsule for convenient eating, and medicine containing acetyl-L-carnitine hydrochloride is usually liquid injection or solid particles. Therefore, the purity, solubility and stability of the acetyl L-carnitine hydrochloride raw material are critical to the quality of food, medicine and feed. According to the method disclosed in Chinese patent CN102557972A, the crude product of acetyl L-carnitine hydrochloride is crystallized by isopropanol to obtain a powdery acetyl L-carnitine hydrochloride essence (crystal form I), the crude product of acetyl L-carnitine hydrochloride is crystallized by ethanol to obtain an irregular small granular acetyl L-carnitine hydrochloride essence (crystal form II), and the fine product of acetyl L-carnitine hydrochloride is recrystallized by acetone to obtain a powdery acetyl L-carnitine hydrochloride essence (crystal form III). The three forms of acetyl L-carnitine hydrochloride solid have low content, solubility and stability. Other dominant crystalline forms have not been reported. Disclosure of Invention The present invention provides a solution to the above problems existing in the prior art. In a first aspect of the invention, there is provided crystalline form A of acetyl l-carnitine hydrochloride, which uses Cu-Ka radiation, wherein the characteristic diffraction peak of the X-ray powder diffraction pattern expressed by 2 theta comprises 11.746 +/-0.2 degrees, 23.464 +/-0.2 degrees, 20.824 +/-0.2 degrees, 14.965 +/-0.2 degrees, 26.373 +/-0.2 degrees, 30.066 +/-0.2 degrees, and does not comprise 17.935 +/-0.2 degrees, 18.148 +/-0.2 degrees, and preferably, the differential scanning calorimeter pattern has a single absorption peak at 197.8+/-3 ℃ when synchronous thermal analysis is carried out, and the solubility of the crystalline form A in pure water is preferably greater than 850mg/mL under normal temperature and normal pressure conditions, and the crystalline form A is preferably in a rectangular columnar shape. In a second aspect of the present invention, a preparation method of acetyl l-carnitine hydrochloride crystal form a is provided, which specifically comprises the following steps: S1, preparing acetyl L-carnitine hydrochloride solution by taking L-carnitine and excessive acetyl chloride as raw materials and acetic acid as a solvent; s2, removing redundant acetyl chloride and 85% -95% of acetic acid; S3, crystallizing acetyl L-carnitine hydrochloride in the rest 5% -15% acetic acid solution; S4, adding ethanol dispersed crystals into the obtained solid-liquid mixture; S5, carrying out solid-liquid separation to obtain a crystal form A. Preferably, in step S3, seeds of form a are added prior to crystallization. In a third aspect of the invention, a bulk drug is provided, which comprises the acetyl-L-carnitine hydrochloride crystal form A or the acetyl-L-carnitine hydrochloride crystal form A prepared by the method. According to a fourth aspect of the invention, there is provided a food additive comprising the crystalline form a of acetyll-carnitine hydrochloride of the invention or comprising the crystalline form a of acetyll-carnitine hydrochloride prepared by the method of the invention. In a fifth aspect of the invention, a feed additive is provided, which comprises the acetyl-l-carnitine hydrochloride crystal form A or the acetyl-l-carnitine hydrochloride crystal form A prepared by the method. In a sixth aspect, the application provides the application of the crystal form A, the bulk drug or the composition in muscle enhancement, nerve health maintenance and male reproductive health maintenance, preferably the application in preparation of drugs, health