CN-117486704-B - Curcumin L-carnitine eutectic crystal and preparation method and application thereof

Abstract

The invention relates to a curcumin L-carnitine eutectic crystal and a preparation method and application thereof. The stoichiometric ratio of curcumin to L-carnitine in the curcumin L-carnitine eutectic crystal is 1:1, and belongs to a monoclinic system. Compared with curcumin, the invention changes intermolecular interaction and spatial arrangement mode of curcumin molecules from molecular level by adding L-carnitine as ligand to form eutectic with curcumin, increases dissolution and dissolution performance of curcumin, and further improves bioavailability. The preparation method of the curcumin L-carnitine eutectic crystal is simple, easy to control and good in reproducibility.

Inventors

• MEI XUEFENG
• WANG HAO
• ZHANG QI
• DAI WENJUAN
• LU LIYE

Assignees

• 共晶科技(嘉兴)有限责任公司

Dates

Publication Date

20260508

Application Date

20231102

Claims (16)

1. 1. A curcumin l-carnitine co-crystal, wherein the stoichiometric ratio of curcumin to l-carnitine in the co-crystal is 1:1, and an X-ray powder diffraction pattern of the curcumin l-carnitine co-crystal has characteristic peaks at 2 theta angles of 5.0 ° ± 0.2 °,6.4 ° ± 0.2 °,13.1 ° ± 0.2 °,16.8 ° ± 0.2 °,20.3 ° ± 0.2 ° and 23.9 ° ± 0.2 °.
2. 2. The curcumin l-carnitine co-crystal according to claim 1, characterized in that it belongs to monoclinic system, the unit cell parameters are a= 17.1370 (11) a, b= 5.6406 (4) a, c= 27.393 (2) a, α=90°, β= 101.063 (2) °, γ=90°.
3. 3. The curcumin l-carnitine eutectic crystal according to claim 1, wherein, The X-ray powder diffraction pattern of the curcumin L-carnitine eutectic also has characteristic peaks at the 2 theta angle of 18.2 degrees plus or minus 0.2 degrees, 18.6 degrees plus or minus 0.2 degrees, 22.1 degrees plus or minus 0.2 degrees and 22.6 degrees plus or minus 0.2 degrees.
4. 4. The curcumin l-carnitine eutectic crystal according to claim 1, wherein, The co-crystal of curcumin and L-carnitine has an X-ray powder diffraction pattern substantially as shown in figure 2.
5. 5. The curcumin l-carnitine co-crystal according to claim 1, wherein the differential scanning calorimetric analysis spectrogram of the curcumin l-carnitine co-crystal has a characteristic endothermic peak at 161 ± 2 ℃.
6. 6. The curcumin l-carnitine eutectic crystal according to claim 1, wherein, The curcumin l-carnitine co-crystal has a differential scanning calorimetric profile substantially as shown in figure 3.
7. 7. The curcumin l-carnitine co-crystal according to claim 1, wherein the infrared spectrum of the curcumin l-carnitine co-crystal has a characteristic peak at 3032 cm -1 ±2 cm -1 ,2980 cm -1 ±2 cm -1 ,2556 cm -1 ±2 cm -1 .
8. 8. The curcumin l-carnitine eutectic crystal according to claim 7, wherein, The infrared spectrum of the curcumin l-carnitine co-crystal also has a characteristic peak at 3069 cm -1 ±2 cm -1 ,2831 cm -1 ±2 cm -1 ,1563 cm -1 ±2 cm -1 ,1515cm -1 ±2 cm -1 ,1286 cm -1 ±2 cm -1 ,1240 cm -1 ±2 cm -1 ,1120 cm -1 ±2 cm -1 .
9. 9. The curcumin l-carnitine eutectic crystal according to claim 1, wherein, The curcumin l-carnitine co-crystal has an infrared spectrum substantially as shown in figure 4.
10. 10. A process for the preparation of the curcumin l-carnitine co-crystal according to any one of claims 1 to 9, said process being selected from one of the following processes: recrystallizing curcumin and L-carnitine with a stoichiometric ratio of 1:1-1:2 in a solvent, separating and drying the precipitate to obtain curcumin L-carnitine eutectic; ball milling curcumin and L-carnitine in a stoichiometric ratio of 1:1 in a solvent, and drying the obtained crystal to obtain the curcumin L-carnitine eutectic crystal.
11. 11. The method for preparing a curcumin l-carnitine eutectic crystal according to claim 10, wherein in the first and second methods, the solvents are one or more selected from the group consisting of water, alcohols, ketones, esters, alkanes, aromatic hydrocarbons and halogenated alkanes independently; And/or The crystallization drying method adopts vacuum drying, boiling drying or air blast drying.
12. 12. The method for preparing curcumin l-carnitine eutectic crystal according to claim 10, wherein in the first and second methods, The solvent is one or more selected from methanol, ethanol, isopropanol, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, methyl tert-butyl ether, n-hexane, n-heptane, and/or The crystallization drying method is vacuum drying, and the drying time is 3-36 h.
13. 13. The method for preparing the curcumin L-carnitine eutectic crystal according to claim 10, wherein, In the first method: the ratio of curcumin to L-carnitine mass and solvent volume is 1g (3-20) mL, and/or The temperature of the recrystallization is 10-70 ℃, the time of the recrystallization is 1-36h, In the second method: The mass ratio of curcumin to L-carnitine and the volume of the solvent is 1g (0.1-5) mL.
14. 14. The method for preparing the curcumin L-carnitine eutectic crystal according to claim 10, wherein, In the first method: The ratio of curcumin to L-carnitine mass and solvent volume is 1g (4-15) mL, and/or The temperature of the recrystallization is 20-40 ℃, the time of the recrystallization is 10-24 hours, In the second method: the mass ratio of curcumin to L-carnitine and the volume of the solvent is 1g (0.5-2) mL.
15. 15. A curcumin product comprising the curcumin l-carnitine co-crystal of any one of claims 1-9 or prepared by the preparation method of any one of claims 10-14, wherein the product is selected from the group consisting of health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds.
16. 16. Use of the curcumin l-carnitine co-crystal according to any one of claims 1-9, or prepared by the preparation method according to any one of claims 10-14, for the preparation of curcumin products selected from the group consisting of health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds.

Description

Curcumin L-carnitine eutectic crystal and preparation method and application thereof Technical Field The invention relates to the technical field of pharmaceutical co-crystals, in particular to a curcumin L-carnitine co-crystal and a preparation method thereof, a product containing the curcumin L-carnitine co-crystal and application thereof. Background Curcumin (curcumin) is a natural polyphenol compound extracted from Curcuma longa belonging to the family Zingiberaceae. In recent years, a great deal of research shows that the compound has wide pharmacological activities of anti-inflammatory, antioxidant, lipid-regulating, antiviral, anti-infective, anti-tumor, anticoagulative, anti-hepatic fibrosis, anti-atherosclerosis and the like. Curcumin is a natural pigment, has bright color, strong tinting strength, good oxidation resistance, safety, no toxicity and rich nutritional value, and is widely applied to various fields of food, health care products, cosmetics, medicines, tobacco, animal and poultry feeds and the like. Curcumin is a food additive (FAO/WHO-1995) approved by the food and agricultural organization code of the United nations, and is the natural pigment allowed to be used in foods as originally issued in food additive use sanitation Standard in China. However, curcumin belongs to fat-soluble pigment, and in practical application, it is found that curcumin has certain defects, such as poor solubility, low absorptivity, fast metabolism, short half-life and the like, and the problems result in low bioavailability, so that the curcumin has limited application in the fields of foods and medicines. The current methods for improving the solubility and bioavailability of curcumin are mainly by preparing new pharmaceutical dosage forms such as microemulsion, microsphere, solid dispersion, liposome, phospholipid complex, micelle nanoparticle, cyclodextrin inclusion compound and dripping pill. However, microspheres, nanoparticles, solid dispersions, liposomes and the like require a large amount of carrier auxiliary materials, the microemulsion preparation contains a large amount of surfactants and has potential toxicity, and the preparation of the phospholipid complex requires complex reaction of the drug and the phospholipid at a certain temperature and removal of the solvent, which may cause degradation of curcumin. Therefore, it is a continuous aim to find a curcumin product which is convenient to use, high in content, stable in chemistry, simple in preparation process and low in cost. Disclosure of Invention In order to improve the absorption and bioavailability of the curcumin product, the invention forms stable eutectic with the curcumin by adding the edible L-carnitine as a ligand, thereby changing intermolecular interaction and spatial arrangement modes of curcumin molecules from molecular level, increasing the dissolution and dissolution performance of the curcumin and further improving the bioavailability of the curcumin. In view of the above, it is an object of the present invention to provide a curcumin l-carnitine eutectic. The second purpose of the invention is to provide a preparation method of the curcumin L-carnitine eutectic. The third object of the present invention is to provide a product comprising the curcumin l-carnitine eutectic, wherein the product is selected from health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds. The fourth purpose of the invention is to provide the application of the curcumin L-carnitine eutectic crystal in preparing products, wherein the products are selected from health-care products, foods, cosmetics, medicines, pharmaceutical excipients and feeds. In order to achieve the above purpose, the present application adopts the following technical scheme: In one aspect of the invention, a curcumin l-carnitine eutectic is provided, wherein the stoichiometric ratio of curcumin to l-carnitine in the eutectic is 1:1. The curcumin L-carnitine eutectic belongs to monoclinic system, and the unit cell parameters areα=90°,β=101.063(2)°,γ=90°。 In some embodiments, the X-ray powder diffraction pattern of the curcumin L-carnitine co-crystal has characteristic peaks at angles of 2 theta of 5.0 DEG + -0.2 DEG, 6.4 DEG + -0.2 DEG, 13.1 DEG + -0.2 DEG, 16.8 DEG + -0.2 DEG, 20.3 DEG + -0.2 DEG, 23.9 DEG + -0.2 DEG, in particular, also at angles of 2 theta of 18.2 DEG + -0.2 DEG, 18.6 DEG + -0.2 DEG, 22.1 DEG + -0.2 DEG, 22.6 DEG + -0.2 DEG, more particularly, 9.0 DEG + -0.2 DEG, 15.0 DEG + -0.2 DEG, 18.2 DEG + -0.2 DEG, 18.6 DEG + -0.2 DEG, 22.1 DEG + -0.2 DEG, 27.9 DEG + -0.2 DEG, and preferably, the curcumin has a characteristic peak at angles of 2 DEG of 9.0.2 DEG, and the X-ray powder diffraction pattern of the curcumin L-carnitine is substantially as shown in FIG. 2. In some embodiments, the differential scanning calorimetry profile of the curcumin l-carnitine co-crystal has a characteristic endothermic peak at 161+ -2 ℃, preferably the curcumin