Cocrystal of curcumin and l-carnitine, and preparation method therefor and use thereof

Abstract

The present invention relates to a cocrystal of curcumin and L-carnitine, and a preparation method therefor and the use thereof. In the cocrystal of curcumin and L-carnitine of the present invention, the stoichiometric ratio of curcumin to L-carnitine is 1:1, and the cocrystal belongs to a monoclinic system. Compared with curcumin, by means of adding L-carnitine as a ligand to form a cocrystal with curcumin, the present invention changes the intermolecular interaction and spatial arrangement modes of curcumin molecules at the molecular level, which improves the solubility and dissolution performance of curcumin, thereby improving the bioavailability thereof. Furthermore, the method for preparing the cocrystal of curcumin and L-carnitine is simple and easily controllable, and has good reproducibility.

Description

A curcumin L-carnitine cocrystal and its preparation method and use Technical Field

[0001] The present invention relates to the technical field of pharmaceutical cocrystals, and in particular to a curcumin-L-carnitine cocrystal and a preparation method thereof, as well as products containing the curcumin-L-carnitine cocrystal and uses thereof. Background Art

[0002] Curcumin is a natural polyphenolic compound extracted from the ginger plant turmeric. In recent years, numerous studies have demonstrated its broad pharmacological activities, including anti-inflammatory, antioxidant, lipid-regulating, antiviral, anti-infective, anti-tumor, anticoagulant, anti-hepatic fibrosis, and anti-atherosclerotic properties. Curcumin is a natural pigment with vibrant color, strong tinting power, excellent antioxidant properties, safety, and nutritional value. It is widely used in food, health supplements, cosmetics, medicine, tobacco, and animal feed. Curcumin is a food additive approved by the Food and Agriculture Organization of the United Nations (FAO / WHO-1995) and the first natural pigment permitted for use in food under my country's "Hygienic Standards for the Use of Food Additives."

[0003] However, curcumin is a fat-soluble pigment. In practical applications, it has been found to have certain drawbacks, such as poor solubility, low absorption rate, rapid metabolism, and a short half-life. These issues result in low bioavailability, limiting its application in food and pharmaceutical applications. Current approaches to improving curcumin's solubility and bioavailability primarily involve the preparation of new pharmaceutical dosage forms, such as microemulsions, microspheres, solid dispersions, liposomes, phospholipid complexes, micellar nanoparticles, cyclodextrin inclusion complexes, and pills. However, microspheres, nanoparticles, solid dispersions, and liposomes require large amounts of carrier excipients; microemulsion formulations contain large amounts of surfactants, which are potentially toxic; and the preparation of phospholipid complexes requires a complex reaction between the drug and phospholipids at a certain temperature and subsequent solvent removal, which can cause curcumin degradation. Therefore, the search for a curcumin product that is convenient to use, high in content, chemically stable, simple to prepare, and low in cost is a constant pursuit.

[0004] Summary of the Invention

[0005] In order to improve the absorption and bioavailability of curcumin products, the present invention adds edible L-carnitine as a ligand to form a stable cocrystal with curcumin, thereby changing the intermolecular interactions and spatial arrangement of curcumin molecules at the molecular level, increasing the solubility and dissolution properties of curcumin, and thus improving its bioavailability.

[0006] In view of this, one of the objects of the present invention is to provide a curcumin-L-carnitine cocrystal.

[0007] A second object of the present invention is to provide a method for preparing the curcumin-L-carnitine cocrystal.

[0008] A third object of the present invention is to provide a product comprising the above-mentioned curcumin-L-carnitine cocrystal, wherein the product is selected from health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds.

[0009] A fourth object of the present invention is to provide a use of the above-mentioned curcumin-L-carnitine cocrystal in the preparation of products, wherein the products are selected from health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds.

[0010] In order to achieve the above objectives, this application adopts the following technical solutions:

[0011] In one aspect, the present invention provides a curcumin-L-carnitine cocrystal, wherein the stoichiometric ratio of curcumin to L-carnitine in the cocrystal is 1:1.

[0012] The curcumin L-carnitine cocrystal belongs to the monoclinic system, and the unit cell parameters are α=90°, β=101.063(2)°, γ=90°.

[0013] In some embodiments, the X-ray powder diffraction pattern of the curcumin L-carnitine cocrystal has characteristic peaks at 2θ 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°; in particular, the X-ray powder diffraction pattern of the curcumin L-carnitine cocrystal has characteristic peaks at 2θ angles of 18.2°±0.2°, 18.6°±0.2°, 22.1°±0.2°, 22.6 More particularly, it also has characteristic peaks at 2θ angles of 9.0°±0.2°, 15.0°±0.2°, 15.7°±0.2°, 18.2°±0.2°, 18.6°±0.2°, 22.1°±0.2°, 22.6°±0.2°, and 27.9°±0.2°; preferably, the curcumin and L-carnitine co-crystal has an X-ray powder diffraction pattern substantially as shown in Figure 2.

[0014] In some embodiments, the differential scanning calorimetry analysis spectrum of the Curcumin-L-carnitine co-crystal has a characteristic endothermic peak at 161±2° C.; preferably, the Curcumin-L-carnitine co-crystal has a differential scanning calorimetry analysis spectrum substantially as shown in FIG3 .

[0015] In some embodiments, the infrared spectrum of the curcumin-L-carnitine cocrystal is at 3032 cm -1 ±2cm -1 , 2980cm -1 ±2cm -1, 2556cm -1 ±2cm -1 There is a characteristic peak at 3069cm -1 ±2cm -1 , 2831cm -1 ±2cm -1 , 1563cm -1 ±2cm -1 , 1515cm -1 ±2cm -1 , 1286cm -1 ±2cm -1 , 1240cm -1 ±2cm -1 , 1120cm -1 ±2cm -1 There is a characteristic peak at; preferably, it has an infrared spectrum basically as shown in Figure 4.

[0016] In a second aspect, the present invention provides a method for preparing the curcumin-L-carnitine cocrystal, which is selected from one of the following methods:

[0017] Method 1: Curcumin and L-carnitine in a stoichiometric ratio of 1:1-1:2 are recrystallized in a solvent, and the precipitate is separated and dried to obtain curcumin-L-carnitine cocrystal;

[0018] Method 2: Curcumin and L-carnitine in a stoichiometric ratio of 1:1 are ball-milled in a solvent, and the resulting crystals are dried to obtain curcumin-L-carnitine cocrystals.

[0019] In the above-mentioned methods 1 and 2, the solvent is selected from a solvent that has a certain solubility for the raw materials and does not cause deterioration of the raw materials. Preferably, the solvents are each independently selected from one or more of water, alcohols, ketones, esters, alkanes, aromatic hydrocarbons, and halogenated alkanes; more preferably, the solvents are each independently selected from one or more of methanol, ethanol, isopropanol, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, methyl tert-butyl ether, n-hexane, and n-heptane.

[0020] According to the above method 1:

[0021] In some embodiments, the mass and volume ratio of curcumin to L-carnitine to solvent is 1 g: (3-20) mL, preferably 1 g: (4-15) mL.

[0022] In some embodiments, the recrystallization temperature is 10-70°C, preferably 20-40°C, for example, 20°C, 25°C, 30°C, 35°C, 40°C; the recrystallization time is 1-36h, preferably 10-24h, for example, 6h, 10h, 12h, 16h, 18h, 20h, 24h.

[0023] In some embodiments, the separation of crystals can be carried out by any separation method that does not adversely affect the co-crystal, for example, filtration, centrifugation, etc. can be used to separate the crystals and the solvent.

[0024] According to the above method 2:

[0025] In some embodiments, the mass and volume ratio of curcumin to L-carnitine to solvent is 1 g:(0.1-5) mL, preferably 1 g:(0.5-2) mL.

[0026] In some embodiments, the ball milling time is 10 min-180 min, preferably 30 min-60 min, for example 30 min, 40 min, 50 min, 60 min.

[0027] In the above-mentioned method 1 and method 2, the crystallization drying method can be any drying method that has no adverse effect on the eutectic, for example, vacuum drying, boiling drying or forced air drying, preferably vacuum drying, and the drying time can be 3-36 h, preferably 6-18 h, for example, 6 h, 8 h, 12 h, 16 h, 18 h, 22 h, 24 h, 28 h, 32 h, 36 h.

[0028] The preparation method of the present invention is simple to operate, the crystallization process is easy to control, the crystallinity is high, and the reproducibility is good, and curcumin L-carnitine cocrystal can be stably obtained.

[0029] In a third aspect, the present invention provides a curcumin product comprising the curcumin-L-carnitine cocrystal, wherein the product is selected from the group consisting of health products, foods, cosmetics, medicines, pharmaceutical excipients and feed.

[0030] In a fourth aspect, the present invention provides a use of the curcumin-L-carnitine cocrystal in preparing a curcumin product, wherein the product is selected from health products, foods, cosmetics, medicines, pharmaceutical excipients and feed.

[0031] The product may also contain other suitable raw materials required for the product, for example, food may contain food ingredients and edible food additives acceptable to food, such as sweeteners, flavorings, preservatives, fragrances, colorants, etc.; cosmetics may contain cosmetic main ingredients and additives acceptable to cosmetics, such as solvents, flavorings, preservatives, essences, colorants, etc.; medicines may contain medicinal active ingredients and pharmaceutically acceptable excipients, such as carriers, diluents, adjuvants, colorants, etc.; feed may contain feed main ingredients, such as soybean meal, hay, etc., and feed excipients acceptable to feed, such as sweeteners, flavorings, preservatives, fragrances, colorants, etc., but the present invention is not limited to this.

[0032] The above product is prepared by adding the curcumin-L-carnitine co-crystal of the present invention. Except for adding the curcumin-L-carnitine co-crystal of the present invention, the preparation method of the product can be prepared according to its conventional method.

[0033] The present invention has been described in detail above, but the above embodiments are merely illustrative in nature and are not intended to limit the present invention. In addition, the present invention is not limited by any theory described in the above prior art or invention summary or the following examples.

[0034] Unless otherwise expressly stated, the numerical ranges throughout the application include any subranges therein and any numerical values ​​incremented by the smallest subunit of a given value therein. Unless otherwise expressly stated, the numerical values ​​throughout the application represent approximate measurements or limitations of the range of embodiments including slight deviations from the given values ​​and having approximately the values ​​mentioned as well as having the exact values ​​mentioned. Except for the working examples provided at the end of the detailed description, all numerical values ​​of the parameters (e.g., quantities or conditions) in this application (including the appended claims) should be understood to be modified by the term "about" in all cases, regardless of whether "about" actually appears before the numerical value. "About" means that the numerical value described allows for slight imprecision (there is some close accuracy in the value; approximately or reasonably close to the value; approximately). If the imprecision provided by "about" is not understood in this art with this common meaning, then the "about" used herein at least represents the variation that can be produced by the common methods of measuring and using these parameters. For example, "about" can include a variation of less than or equal to 10%, less than or equal to 5%, less than or equal to 4%, less than or equal to 3%, less than or equal to 2%, less than or equal to 1%, or less than or equal to 0.5%, and in some aspects, a variation of less than or equal to 0.1%.

[0035] Unless expressly stated otherwise, the terms "comprising," "including," "having," "containing," or any similar terms used throughout this application are open-ended terms, meaning that a co-crystal or article may include, in addition to the elements listed herein, other elements not expressly listed but customary to the co-crystal or article. Furthermore, the terms "comprising," "including," "having," and "containing" are to be construed herein as specifically disclosing and encompassing closed or semi-closed conjunctions such as "consisting of" and "consisting essentially of." "Consisting essentially of" means that the elements listed herein comprise greater than 95%, greater than 97%, or, in some aspects, greater than 99%, of the co-crystal or article. Beneficial effects

[0036] (1) The present invention provides a stable curcumin-L-carnitine cocrystal. Compared with the curcumin crystal itself, the cocrystal increases the solubility and dissolution properties of curcumin, thereby significantly improving its absorption and bioavailability. This can further broaden the application range of curcumin, improve the use effect of curcumin, and reduce the dosage and cost of curcumin. Therefore, the cocrystal has strong practical application value.

[0037] (2) The method for preparing the curcumin-L-carnitine cocrystal of the present invention is simple, reproducible, low-cost, environmentally friendly, and easy to control. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] FIG1 is a single crystal structure diagram of the curcumin-L-carnitine cocrystal prepared in Example 1 of the present invention;

[0039] FIG2 is an X-ray powder diffraction (XRPD) pattern of the curcumin-L-carnitine cocrystal prepared in Example 1 of the present invention;

[0040] FIG3 is a differential scanning calorimetry (DSC) diagram of the curcumin-L-carnitine cocrystal prepared in Example 1 of the present invention;

[0041] FIG4 is an infrared spectrum (IR) of the curcumin-L-carnitine cocrystal prepared in Example 1 of the present invention;

[0042] FIG5 is an infrared spectrum (IR) of commercially available curcumin crystals in Example 1 of the present invention;

[0043] FIG6 is a comparative diagram of the dissolution curves of commercially available curcumin crystals and curcumin L-carnitine co-crystals prepared in Example 3 in a pH 2.0 buffer solution in a test example;

[0044] FIG7 is a comparative diagram of the dissolution curves of commercially available curcumin crystals and curcumin L-carnitine co-crystals prepared in Example 3 in a pH 4.5 buffer solution in a test example;

[0045] FIG8 is a comparative diagram of the drug-time curves of the commercially available curcumin crystals in Test Example 2 and the curcumin L-carnitine cocrystals prepared in Example 3. DETAILED DESCRIPTION

[0046] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0047] The present invention uses L-carnitine as a ligand to form a stable cocrystal with curcumin. The single crystal structures below show that the interactions and arrangement of curcumin molecules in the curcumin crystal and the curcumin L-carnitine cocrystal are completely different. In the curcumin crystal, the curcumin molecules form a two-dimensional network structure through hydrogen bonding between the phenolic hydroxyl groups and the carbonyl groups. In the curcumin L-carnitine cocrystal, the curcumin molecules form a one-dimensional chain structure through hydrogen bonding between the phenolic hydroxyl groups and the carboxylate groups, and between the hydroxyl groups and the carboxylate groups, with L-carnitine molecules as the medium.

[0048] The X-ray powder diffraction patterns in the present invention were obtained using a Bruker D8 Advanced model X-ray eutectic diffractometer, which uses Cu-Kα irradiation. The scanning range was from 3° to 40° in the 2θ interval, and the scanning speed was 5° / min.

[0049] X-ray single crystal data were collected on a Bruker D8 Venture single crystal X-ray diffractometer equipped with a Mo-Kα X-ray target. The test temperature is 170K, the voltage is 50kV, and the current is 30mA.

[0050] Differential scanning calorimetry was performed using a TADSC Q2000 instrument with a heating rate of 10 K / min.

[0051] Thermo Scientific Nicolet 6700 was used as the Fourier transform infrared spectrometer.

[0052] The ball mill used was a Jingxin JX-2G planetary ball mill.

[0053] Liquid chromatography was performed using an Agilent 1260 Infinity HPLC.

[0054] The reagents and sources used in the following examples are as follows:

[0055] L-carnitine: purity 99%, purchased from Aladdin Reagent Co., Ltd.

[0056] Curcumin (crystal): purity 98%, purchased from Aladdin Reagent Co., Ltd.

[0057] Ethanol: purity 99%, purchased from Sinopharm Chemical Reagent Co., Ltd.

[0058] Ethyl acetate: purity 99%, purchased from Sinopharm Chemical Reagent Co., Ltd.

[0059] Methanol: purity 99%, purchased from Sinopharm Chemical Reagent Co., Ltd.

[0060] Example 1

[0061] 1.61 g of L-carnitine and 3.69 g of curcumin were added to 60 ml of ethanol solvent, stirred and suspended at 30° C. for 12 hours, and a red solid was obtained by filtration. The red solid was vacuum dried overnight to obtain curcumin L-carnitine cocrystal.

[0062] The curcumin-L-carnitine cocrystal and the raw curcumin crystals and L-carnitine were characterized by X-ray powder diffraction (XRPD), respectively; and the curcumin-L-carnitine cocrystal was subjected to differential scanning calorimetry (DSC) and infrared (IR) spectroscopy analysis. The results are shown in Tables 1-3 and Figures 2-5, respectively.

[0063] As can be seen from Tables 1-3 and Figure 2, the curcumin-L-carnitine cocrystal has a completely different XRPD spectrum from curcumin and L-carnitine themselves. The curcumin-L-carnitine cocrystal has characteristic peaks at 2θ 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°.

[0064] As shown in Figures 4-5, the infrared spectra of curcumin-L-carnitine cocrystal and curcumin itself are completely different. In the infrared spectrum of curcumin-L-carnitine cocrystal, the infrared characteristic peak of curcumin phenolic hydroxyl group is from 3508cm -1 Red shift to 3165 cm -1 This indicates that there is a strong hydrogen bond between curcumin and L-carnitine in the cocrystal.

[0065] Table 1. XRPD data of curcumin-L-carnitine cocrystal

[0066] Table 2. XRPD data of commercially available curcumin

[0067] Table 3. L-Carnitine XRPD Data

[0068] Example 2

[0069] 1.61 g of L-carnitine and 3.69 g of curcumin were added to 60 ml of ethyl acetate solvent, stirred and suspended at 30° C. for 12 hours, and a red solid was filtered and vacuum dried overnight to obtain curcumin L-carnitine cocrystal.

[0070] The cocrystal was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR) spectroscopy. The results were generally consistent with those in Figures 2-4.

[0071] Example 3

[0072] 0.161 g of L-carnitine and 0.369 g of curcumin were added to a ball mill, and 1 ml of ethanol was added. The mixture was ball milled at room temperature for 0.5 h, and the solid was dried in a vacuum drying oven at room temperature for 12 h to obtain curcumin L-carnitine cocrystal.

[0073] The cocrystal was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR) spectroscopy. The results were generally consistent with those in Figures 2-4.

[0074] Example 4

[0075] 0.161 g of L-carnitine and 0.369 g of curcumin were added to a ball mill, and 1 ml of methanol was added. The mixture was ball milled at room temperature for 0.5 h, and the solid was dried in a vacuum drying oven at room temperature for 12 h to obtain curcumin L-carnitine cocrystal.

[0076] The cocrystal was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR) spectroscopy. The results were generally consistent with those in Figures 2-4.

[0077] Comparative Example 1

[0078] 0.131 g of leucine and 0.369 g of curcumin were added to a ball mill, and 1 ml of methanol or ethanol was added, and the mixture was ball milled for 0.5 h. The solid was dried in a vacuum drying oven at room temperature for 12 h to obtain a yellow powder.

[0079] The powder was analyzed by X-ray powder diffraction (XRPD) and found to have no co-crystals.

[0080] Comparative Example 2

[0081] 0.131 g of isoleucine and 0.369 g of curcumin were added to a ball mill, and 1 ml of methanol or ethanol was added, and the mixture was ball milled for 0.5 h. The solid was dried in a vacuum drying oven at room temperature for 12 h to obtain a yellow powder.

[0082] The powder was analyzed by X-ray powder diffraction (XRPD) and found to have no co-crystals.

[0083] Comparative Example 3

[0084] 0.139 g of methionine and 0.369 g of curcumin were added to a ball mill, and 1 ml of methanol or ethanol was added, and the mixture was ball milled for 0.5 h. The solid was dried in a vacuum drying oven at room temperature for 12 h to obtain a yellow powder.

[0085] The powder was analyzed by X-ray powder diffraction (XRPD) and found to have no co-crystals.

[0086] Comparative Example 4

[0087] 0.119 g of threonine and 0.369 g of curcumin were added to a ball mill, and 1 ml of methanol or ethanol was added, and the mixture was ball milled for 0.5 h. The solid was dried in a vacuum drying oven at room temperature for 12 h to obtain a yellow powder.

[0088] The powder was analyzed by X-ray powder diffraction (XRPD) and found to have no co-crystals.

[0089] Test Example 1. Dissolution test

[0090] Those skilled in the art can demonstrate that the curcumin-L-carnitine co-crystals described above and below have a significantly improved dissolution rate compared to curcumin crystals themselves; representative studies were conducted using commercially available curcumin crystals and the curcumin-L-carnitine co-crystals obtained in Example 3.

[0091] The powder dissolution of commercially available curcumin and the curcumin-L-carnitine cocrystal obtained in Example 3 was compared. Powder dissolution experiments were conducted in pH 2.0 and pH 4.5 buffer solutions (with 0.5% Tween 80) at 37°C and 50 rpm. The commercially available curcumin crystals and the curcumin-L-carnitine cocrystal powder obtained in Example 3 were sieved through a 100-mesh sieve to eliminate the effect of particle size on dissolution. Samples equivalent to 10 mg of curcumin were weighed and placed in the sample tank of the dissolution apparatus. The samples were stirred and collected at 3, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes, and the concentrations were determined using HPLC. The results are shown in Figures 6 and 7. In the pH 2.0 buffer solution, the dissolution of the cocrystal reached approximately 7 times that of the curcumin itself after 3 minutes; in the pH 4.5 buffer solution, the dissolution of the cocrystal reached approximately 8 times that of the curcumin itself after 3 minutes.

[0092] As shown in the above results, compared with conventional commercially available curcumin crystals, the curcumin co-crystals disclosed in the present invention have better solubility and dissolution rate.

[0093] Test Example 2. Bioavailability Test

[0094] A person skilled in the art can demonstrate that the curcumin-L-carnitine co-crystals described above and below have significantly improved bioavailability compared to commercially available curcumin crystals; a representative study was conducted using commercially available curcumin crystals and the curcumin-L-carnitine co-crystals obtained in Example 3.

[0095] The difference in bioavailability of commercially available curcumin and the curcumin L-carnitine co-crystal obtained in Example 3 was compared. Male SD rats (weighing 200-300 grams) were used for the test under well-fed conditions. A total of 12 rats were divided into 2 groups, with 6 rats in each group. The commercially available crystals of curcumin and the co-crystals obtained in Example 3 were evenly dispersed in soybean oil and administered orally in the form of a suspension. The dosage was 200 mg / kg in terms of curcumin. Blood was collected from the orbital venous plexus at 1 mL / time point 20 minutes, 40 minutes, 1 hour, 1.5 hours, 2.5 hours, 4 hours, 6 hours, and 8 hours after administration. Plasma was separated by centrifugation within 0.5 h after blood collection, and the centrifugation condition was 10,000 rpm for 5 minutes to obtain plasma. 100 μl of plasma was precisely pipetted, 50 μl of enzyme buffer was added, and the mixture was incubated at 37°C for 60 min. 0.45 ml of methanol (0.2% acetic acid) was then added, the mixture was shaken for 10 min, and centrifuged at 14,000 rpm for 3 min. The supernatant was collected for liquid chromatography analysis. The results are shown in Table 4 and Figure 8.

[0096] Table 4. Pharmacokinetic parameters of commercially available curcumin crystals and curcumin-L-carnitine cocrystals

[0097] As shown in the above results, compared with conventional commercially available curcumin crystals, the curcumin-L-carnitine co-crystals of the present invention have better bioavailability, and the maximum blood concentration of curcumin in rats administered with the co-crystals reaches 10.7 times that of commercially available curcumin crystals.

Claims

1. A curcumin-L-carnitine cocrystal, wherein the stoichiometric ratio of curcumin to L-carnitine in the cocrystal is 1:

1.

2. The curcumin L-carnitine cocrystal according to claim 1, characterized in that The curcumin L-carnitine cocrystal belongs to the monoclinic system, and the unit cell parameters are α=90°, β=101.063(2)°, γ=90°.

3. The curcumin L-carnitine cocrystal according to claim 1, characterized in that The X-ray powder diffraction pattern of the curcumin L-carnitine cocrystal has characteristic peaks at 2θ 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°; Preferably, the X-ray powder diffraction pattern of the curcumin L-carnitine cocrystal also has characteristic peaks at 2θ angles of 18.2°±0.2°, 18.6°±0.2°, 22.1°±0.2°, and 22.6°±0.2°; More preferably, the curcumin and L-carnitine co-crystal has an X-ray powder diffraction pattern substantially as shown in FIG. 2 .

4. The curcumin L-carnitine cocrystal according to claim 1, characterized in that The differential scanning calorimetry analysis spectrum of the curcumin L-carnitine cocrystal has a characteristic endothermic peak at 161±2°C; Preferably, the curcumin-L-carnitine co-crystal has a differential scanning calorimetry analysis spectrum substantially as shown in FIG3 .

5. The curcumin L-carnitine cocrystal according to claim 1, characterized in that The infrared spectrum of the curcumin L-carnitine cocrystal is at 3032 cm -1 ±2cm -1 , 2980cm -1 ±2cm -1 , 2556cm -1 ±2cm -1 There are characteristic peaks at In particular, the infrared spectrum of the curcumin L-carnitine cocrystal is also at 3069cm -1 ±2cm -1 , 2831cm -1 ±2cm -1 , 1563cm -1 ±2cm -1 , 1515cm -1 ±2cm -1 , 1286cm -1 ±2cm -1 , 1240cm -1 ±2cm -1 , 1120cm -1 ±2cm -1 There are characteristic peaks at Preferably, the curcumin-L-carnitine co-crystal has an infrared spectrum substantially as shown in FIG. 4 .

6. A method for preparing the curcumin L-carnitine cocrystal according to any one of claims 1 to 5, wherein the method is selected from one of the following methods: Method 1: Recrystallize curcumin and L-carnitine in a solvent at a stoichiometric ratio of 1:1-1:2, and separate and dry the precipitate to obtain curcumin L-carnitine cocrystal; Method 2: Curcumin and L-carnitine in a stoichiometric ratio of 1:1 are ball-milled in a solvent, and the resulting crystals are dried to obtain curcumin-L-carnitine cocrystals.

7. The method for preparing curcumin-L-carnitine cocrystal according to claim 6, characterized in that: In the above method 1 and method 2, the solvents are each independently selected from one or more of water, alcohols, ketones, esters, alkanes, aromatic hydrocarbons and halogenated alkanes; Preferably, the solvents are each independently selected from one or more of methanol, ethanol, isopropanol, ethyl acetate, isopropyl acetate, acetone, methyl ethyl ketone, methyl tert-butyl ether, n-hexane and n-heptane; and / or The crystallization drying method is vacuum drying, boiling drying or blast drying, preferably vacuum drying, and the drying time is 3 to 36 hours, preferably 6 to 18 hours.

8. The method for preparing curcumin-L-carnitine cocrystal according to claim 6, characterized in that: In method 1: The mass ratio of curcumin to L-carnitine and the volume of the solvent is 1 g: (3-20) mL, preferably 1 g: (4-15) mL; and / or The recrystallization temperature is 10-70°C, preferably 20-40°C; the recrystallization time is 1-36h, preferably 10-24h. Method 2: The mass ratio of curcumin to L-carnitine and the volume of the solvent is 1 g:(0.1-5) mL, and the preferred ratio is 1 g:(0.5-2) mL.

9. A curcumin product, comprising the curcumin L-carnitine co-crystal according to any one of claims 1 to 5 or the curcumin L-carnitine co-crystal prepared by the preparation method according to any one of claims 6 to 8, wherein the product is selected from health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds.

10. Use of the curcumin L-carnitine co-crystal according to any one of claims 1 to 5, or the curcumin L-carnitine co-crystal prepared by the preparation method according to any one of claims 6 to 8 in the preparation of curcumin products, wherein the products are selected from health products, foods, cosmetics, medicines, pharmaceutical excipients and feeds.

Images