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CN-121990886-A - Reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal and preparation method thereof

CN121990886ACN 121990886 ACN121990886 ACN 121990886ACN-121990886-A

Abstract

The invention belongs to the technical field of coenzyme Q10 products, and particularly relates to a reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal and a preparation method thereof. The co-crystal of the reduced coenzyme Q10/gamma-aminobutyric acid is a co-crystal formed by the reduced coenzyme Q10 and the gamma-aminobutyric acid. The co-crystal of the reduced coenzyme Q10/gamma-aminobutyric acid provided by the invention takes gamma-aminobutyric acid as a co-crystal ligand of the reduced coenzyme Q10, not only can the melting point be increased to more than 70 ℃, but also the co-crystal has good physical and chemical stability, and simultaneously has higher bioavailability. In addition, the preparation method of the reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal is simple, good in repeatability and strong in operability, is beneficial to large-scale industrial production, and has important value for developing reduced coenzyme Q10 solid oral preparations in the future.

Inventors

  • LIU QIYUE
  • WANG MANMAN
  • JI JINYU
  • LI DAN

Assignees

  • 内蒙古金达威药业有限公司
  • 金达威生物技术(江苏)有限公司
  • 厦门金达威集团股份有限公司

Dates

Publication Date
20260508
Application Date
20260403

Claims (10)

  1. 1. The co-crystal of the reduced coenzyme Q10/gamma-aminobutyric acid is characterized in that the co-crystal of the reduced coenzyme Q10/gamma-aminobutyric acid is formed by the reduced coenzyme Q10 and the gamma-aminobutyric acid.
  2. 2. The reduced coenzyme Q10/gamma-aminobutyric acid co-crystal according to claim 1, wherein the reduced coenzyme Q10/gamma-aminobutyric acid co-crystal has an X-ray powder diffraction pattern obtained by Cu-K alpha radiation and has characteristic peaks at least at 2 theta angles of 2.9 DEG, 4.3 DEG, 8.6 DEG, 10.0 DEG, 11.5 DEG, 15.7 DEG, 17.2 DEG, 18.7 DEG, 23.3 DEG, 24.1 DEG and 2 theta angles of error of + -0.2 deg.
  3. 3. The reduced coenzyme Q10/gamma-aminobutyric acid co-crystal according to claim 1, characterized in that the differential scanning calorimetric profile of the reduced coenzyme Q10/gamma-aminobutyric acid co-crystal has a characteristic endothermic peak at least at 73 ± 2 ℃.
  4. 4. The reduced coenzyme Q10/gamma-aminobutyric acid co-crystal according to claim 1, wherein the particle size of the reduced coenzyme Q10/gamma-aminobutyric acid co-crystal is unimodal and is 0.01 μm to 20 μm.
  5. 5. The co-crystal of reduced coenzyme Q10/gamma-aminobutyric acid according to any of claims 1 to 4, characterized in that the stoichiometric ratio of reduced coenzyme Q10 to gamma-aminobutyric acid in the co-crystal of reduced coenzyme Q10/gamma-aminobutyric acid is 1 (0.5 to 2.5).
  6. 6. The method for producing a reduced coenzyme Q10/gamma-aminobutyric acid co-crystal according to any one of claims 1 to 5, characterized in that the method comprises subjecting reduced coenzyme Q10 and gamma-aminobutyric acid to co-crystallization in a solvent to obtain a reduced coenzyme Q10/gamma-aminobutyric acid co-crystal, or subjecting reduced coenzyme Q10 and gamma-aminobutyric acid to grinding to obtain a reduced coenzyme Q10/gamma-aminobutyric acid co-crystal.
  7. 7. The method for producing a co-crystal of reduced coenzyme Q10/gamma-aminobutyric acid according to claim 6, wherein the molar ratio of the amount of reduced coenzyme Q10 to the amount of gamma-aminobutyric acid fed is 1 (0.5 to 2.5).
  8. 8. The method for producing a reduced coenzyme Q10/gamma-aminobutyric acid co-crystal according to claim 6, wherein the solvent is at least one selected from the group consisting of water, alcohol solvents, nitrile solvents, ketone solvents, ester solvents, alkane solvents, aromatic hydrocarbon solvents and halogenated alkane solvents.
  9. 9. The method for producing a co-crystal of reduced coenzyme Q10/gamma-aminobutyric acid according to claim 6, characterized in that the method for recrystallization comprises stirring and dissolving reduced coenzyme Q10 and gamma-aminobutyric acid together in a solvent, and then stirring and cooling for crystallization or standing for volatilization for crystallization; preferably, the stirring and dissolving conditions comprise a temperature of 20-80 ℃ and a time of 0.1-2 h; Preferably, the conditions of stirring, cooling and crystallization comprise the temperature of 4-40 ℃ and the time of 1-48 hours; Preferably, the conditions of standing, volatilizing and crystallizing comprise the temperature of 4-40 ℃ and the time of 1-30 days; preferably, the grinding is dry grinding or wet grinding.
  10. 10. A coenzyme Q10 product, characterized in that the coenzyme Q10 product contains the reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal according to any one of claims 1 to 5.

Description

Reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal and preparation method thereof Technical Field The invention belongs to the technical field of coenzyme Q10 products, and particularly relates to a reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal and a preparation method thereof. Background Coenzyme Q10 (Coenzyme Q, simply CoQ 10) is a fat-soluble compound that is widely present in human cell mitochondria and is a core substance for energy metabolism and antioxidant defense. CoQ10 plays a key role in energy metabolism and antioxidant defense as an essential substance in human cells. As a key component of mitochondrial electron transport chain, coQ10 is directly involved in Adenosine Triphosphate (ATP) synthesis, providing energy for high energy-consuming organs such as heart, brain, etc. CoQ10 can neutralize free radicals, protect cell membranes, lipoproteins and DNA from oxidative damage, delay cell aging, improve myocardial cell function, and assist in maintaining blood pressure and vascular elasticity. CoQ10 can be used as adjuvant for cardiovascular diseases, and has effects in improving heart failure, relieving hypertension, managing diabetes and preventing neurodegenerative diseases. CoQ10 can be used as food nutritional supplement, and has effects in resisting oxidation, resisting aging, relieving fatigue, and improving athletic performance. Currently, coQ10 is widely applied to the industries of foods, health products, cosmetics and medicines and is favored by vast scholars and consumers. Coenzyme Q10 is divided into two existing forms, oxidized and reduced. Reduced coenzyme Q10 is commonly referred to as coenzyme QH, a major form of presence in the human blood circulation, and can directly participate in energy metabolism and antioxidant processes. Coenzyme QH has better oxidation resistance and more efficient absorption than oxidized coenzyme Q10. However, the chemical property of the coenzyme QH is extremely unstable, the melting point is low, the high temperature is not resisted, the coenzyme QH is highly sensitive to oxygen and light, and the coenzyme QH is extremely easy to be oxidized and failed in the production and transportation process, the stability is poor, and the quality of the coenzyme QH is seriously influenced. In addition, coenzyme QH may be oxidized in advance in the gastrointestinal environment, resulting in a great decrease in its actual absorption effect, and the core symptom of the problem is that its crystal form is not stable enough, which affects its dissolution and absorption in the gastrointestinal tract. Oxidized coenzyme Q10 is difficult to dissolve in gastrointestinal fluids due to poor hydrophilicity and high lattice energy, and limits the bioavailability thereof. Although coenzyme QH is theoretically more absorbed than oxidized coenzyme Q10, its absorption rate is difficult to reach an ideal level and bioavailability is poor due to stability problems. Disclosure of Invention The first aim of the invention is to overcome the defects of low melting point, poor stability and low bioavailability of coenzyme QH and provide a reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal with high melting point, high stability and high bioavailability. The second object of the present invention is to provide a method for producing the reduced coenzyme Q10/gamma-aminobutyric acid co-crystal. The third object of the present invention is to provide a coenzyme Q10 product, wherein the coenzyme Q10 product contains the reduced coenzyme Q10/gamma-aminobutyric acid eutectic. The co-crystal of reduced coenzyme Q10/gamma-aminobutyric acid (QH-GABA-CCIII) provided by the invention is a co-crystal formed by reduced coenzyme Q10 (QH) and gamma-aminobutyric acid (GABA). The preparation method of the reduced coenzyme Q10/gamma-aminobutyric acid eutectic comprises the steps of recrystallizing the reduced coenzyme Q10 and gamma-aminobutyric acid in a solvent to obtain the reduced coenzyme Q10/gamma-aminobutyric acid eutectic, or grinding the reduced coenzyme Q10 and gamma-aminobutyric acid to obtain the reduced coenzyme Q10/gamma-aminobutyric acid eutectic. The invention surprisingly discovers that the gamma-aminobutyric acid is used as the eutectic ligand of the reduced coenzyme Q10 in the research and development process, and the obtained reduced coenzyme Q10/gamma-aminobutyric acid eutectic not only has a melting point higher than 70 ℃, but also has good physical and chemical stability and higher bioavailability. In addition, the preparation method of the reduced coenzyme Q10/gamma-aminobutyric acid eutectic crystal is simple, good in repeatability and strong in operability, is beneficial to large-scale industrial production, and has important value for developing reduced coenzyme Q10 solid oral preparations in the future. Drawings FIG. 1 is an X-ray powder diffraction (XRPD) pattern of coenzyme QH obtained in preparation example; FIG. 2 is a Differential Scann