Curcumin l-carnitine co-crystal and preparation method and use thereof

Abstract

The present application relates to a curcumin L-carnitine co-crystal and a preparation method and use thereof. The stoichiometric ratio of curcumin and L-carnitine in the curcumin L-carnitine co-crystal is 1:1, and the curcumin L-carnitine co-crystal belongs to a monoclinic system. Compared with curcumin, the present application adds L-carnitine as a ligand to form a co-crystal with curcumin, changes the intermolecular interaction and spatial arrangement of curcumin molecules at the molecular level, increases the solubility and dissolution performance of curcumin, and further improves the bioavailability of curcumin. Moreover, the preparation method of the curcumin L-carnitine co-crystal is simple, easy to control, and has good reproducibility.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical cocrystallization technology, and more specifically, to a curcumin-L-carnitine cocrystallization and its preparation method, as well as products containing the curcumin-L-carnitine cocrystallization and their uses. Background Technology

[0002] Curcumin is a natural polyphenolic compound extracted from the turmeric plant (Curcuma longa), a member of the ginger family. In recent years, numerous studies have shown that it possesses a wide range of pharmacological activities, including anti-inflammatory, antioxidant, lipid-regulating, antiviral, anti-infective, antitumor, anticoagulant, anti-liver fibrosis, and anti-atherosclerotic effects. Curcumin is a natural pigment with a bright color, strong coloring power, good antioxidant properties, and is safe and non-toxic. It has rich nutritional value and is widely used in food, health products, cosmetics, pharmaceuticals, tobacco, and animal feed. Curcumin is a food additive approved by the Codex Alimentarius Commission of the Food and Agriculture Organization of the United Nations (FAO / WHO-1995) and was one of the first natural pigments permitted for use in food in my country's "Hygienic Standards for the Use of Food Additives."

[0003] However, curcumin is a fat-soluble pigment, and in practical applications, it has been found to have certain drawbacks, such as poor solubility, low absorption rate, rapid metabolism, and short half-life. These problems lead to low bioavailability, limiting its application in the food and pharmaceutical fields. Currently, methods to improve the solubility and bioavailability of curcumin mainly involve preparing new drug formulations, such as microemulsions, microspheres, solid dispersions, liposomes, phospholipid complexes, micelle nanoparticles, cyclodextrin inclusion complexes, and pellets. However, microspheres, nanoparticles, solid dispersions, and liposomes require large amounts of carrier excipients; microemulsion formulations contain a large amount of surfactants, which have potential toxicity; and the preparation of phospholipid complexes requires a complex reaction between the drug and phospholipids at a certain temperature and the removal of the solvent, which may cause curcumin degradation. Therefore, finding a curcumin product that is convenient to use, has a high content, is chemically stable, has a simple preparation process, and is inexpensive is a continuously pursued goal. Summary of the Invention

[0004] To improve the absorption and bioavailability of curcumin products, this invention adds edible L-carnitine as a ligand to form a stable co-crystal 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.

[0005] Therefore, one of the objectives of this invention is to provide a curcumin-L-carnitine eutectic.

[0006] The second objective of this invention is to provide a method for preparing the curcumin-L-carnitine eutectic.

[0007] The third objective of this invention is to provide a product comprising the above-mentioned curcumin-L-carnitine cocrystal, wherein the product is selected from health products, food, cosmetics, pharmaceuticals, pharmaceutical excipients, and feed.

[0008] The fourth objective of this invention is to provide a use of the above-mentioned curcumin-L-carnitine eutectic in the preparation of products, wherein the products are selected from health products, food, cosmetics, pharmaceuticals, pharmaceutical excipients and feed.

[0009] To achieve the above objectives, this application adopts the following technical solution:

[0010] 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.

[0011] The curcumin-L-carnitine eutectic described above belongs to the monoclinic crystal system, with cell parameters of: α=90°, β=101.063(2)°, γ=90°.

[0012] In some embodiments, the X-ray powder diffraction pattern of the curcumin-L-carnitine cocrystal exhibits 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°; particularly, it also shows characteristic peaks at 2θ angles of 18.2°±0.2°, 18.6°±0.2°, and 22.1°±0.2°. Characteristic peaks are observed at 0.2° and 22.6°±0.2°; more specifically, characteristic peaks are also observed 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-L-carnitine eutectic exhibits substantially the following characteristics. Figure 2 The X-ray powder diffraction pattern shown is shown.

[0013] In some embodiments, the differential scanning calorimetry (DSC) spectrum of the curcumin-L-carnitine eutectic exhibits a characteristic endothermic peak at 161±2℃; preferably, the curcumin-L-carnitine eutectic has essentially the following characteristics. Figure 3 The differential scanning calorimetry (DSC) spectrum is shown.

[0014] In some embodiments, the infrared spectrum of the curcumin-L-carnitine cocrystal is at 3032 cm⁻¹. -1 ±2cm -1 2980cm -1 ±2cm -1 2556cm -1±2cm -1 It has a characteristic peak; in particular, it also has a peak at 3069 cm⁻¹. -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 It has a characteristic peak; preferably, it has a basic like Figure 4 The infrared spectrum shown.

[0015] Secondly, the present invention provides a method for preparing the curcumin-L-carnitine cocrystal, wherein the method is selected from one of the following methods:

[0016] Method 1: Recrystallize curcumin and L-carnitine in a solvent with a stoichiometric ratio of 1:1 to 1:2. After separation and drying, the precipitate is used to obtain curcumin-L-carnitine cocrystal.

[0017] Method 2: Curcumin and L-carnitine with a stoichiometric ratio of 1:1 are ball-milled in a solvent, and the resulting crystals are dried to obtain curcumin-L-carnitine eutectic.

[0018] In methods one and two above, the solvent is selected from solvents that have a certain solubility in the raw material and do not cause deterioration of the raw material. Preferably, each solvent is independently selected from one or more of water, alcohols, ketones, esters, alkanes, aromatic hydrocarbons, and haloalkanes; more preferably, each solvent is 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.

[0019] Based on Method 1 above:

[0020] In some embodiments, the mass ratio of curcumin to L-carnitine and the volume ratio of curcumin to solvent is 1 g : (3-20) mL, preferably 1 g : (4-15) mL.

[0021] In some embodiments, the recrystallization temperature is 10-70°C, preferably 20-40°C, such as 20°C, 25°C, 30°C, 35°C, or 40°C; and the recrystallization time is 1-36 hours, preferably 10-24 hours, such as 6 hours, 10 hours, 12 hours, 16 hours, 18 hours, 20 hours, or 24 hours.

[0022] In some implementations, the separation of crystals can be achieved using any separation method that does not adversely affect the eutectic, such as using filtration, centrifugation, or other methods to separate the crystals and solvent.

[0023] According to Method Two above:

[0024] In some embodiments, the mass ratio of curcumin to L-carnitine and the volume ratio of curcumin to solvent is 1 g:(0.1-5) mL, preferably 1 g:(0.5-2) mL.

[0025] In some embodiments, the ball milling time is 10 min to 180 min, preferably 30 min to 60 min, for example 30 min, 40 min, 50 min, or 60 min.

[0026] In Method 1 and Method 2 above, the crystallization drying method can be any drying method that does not adversely affect the eutectic, such as vacuum drying, boiling drying or forced air drying, preferably vacuum drying, and the drying time can be 3-36h, preferably 6-18h, for example 6h, 8h, 12h, 16h, 18h, 22h, 24h, 28h, 32h, 36h.

[0027] 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.

[0028] Thirdly, the present invention provides a curcumin product comprising the curcumin-L-carnitine cocrystal, wherein the product is selected from health products, food, cosmetics, pharmaceuticals, pharmaceutical excipients and feed.

[0029] Fourthly, the present invention provides the use of the curcumin-L-carnitine cocrystal in the preparation of curcumin products, wherein the products are selected from health products, food, cosmetics, pharmaceuticals, pharmaceutical excipients and feed.

[0030] The product may also contain other suitable raw materials required for the product. For example, food may contain main food ingredients and food-acceptable edible food additives, such as sweeteners, flavoring agents, preservatives, fragrances, and colorings; cosmetics may contain cosmetic-acceptable main cosmetic ingredients and additives, such as solvents, fragrances, preservatives, flavorings, and colorings; pharmaceuticals may contain pharmaceutically active ingredients and pharmaceutically acceptable excipients, such as carriers, diluents, adjuvants, and colorings; feed may contain feed main ingredients, such as soybean meal and hay, and feed-acceptable feed excipients, such as sweeteners, flavoring agents, preservatives, fragrances, and colorings, but the present invention is not limited thereto.

[0031] The above-mentioned product is prepared by adding the curcumin-L-carnitine cocrystal of the present invention. Apart from adding the curcumin-L-carnitine cocrystal of the present invention, the product can be prepared according to conventional methods.

[0032] The present invention has been described in detail above; however, the above embodiments are merely illustrative in nature and are not intended to limit the invention. Furthermore, this document is not limited to the foregoing prior art or the invention itself, or to any theory described in the following embodiments.

[0033] Unless otherwise expressly stated, numerical ranges throughout the application include any subranges therein and any numerical values ​​incremented by the smallest subunit of a given value. Unless otherwise expressly stated, numerical values ​​throughout the application represent approximate measures or limitations on the range of embodiments including minor deviations from a given value and having approximately the mentioned value as well as having the mentioned precise value. Except in the detailed description of the working embodiments provided at the end, all numerical values ​​of parameters (e.g., quantities or conditions) in this application (including the appended claims) should in all cases be understood to be modified by the term “about,” regardless of whether “about” actually precedes the numerical value. “About” indicates that the stated numerical value allows for slight inaccuracies (some close to precision at that value; approximately or reasonably close to the value; approximate). If the inaccuracy provided by “about” is not understood in this common sense in the art, then “about” as used herein at least refers to variations that can be produced by common methods of measuring and using these parameters. For example, “about” can include variations 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 respects, less than or equal to 0.1%.

[0034] Unless otherwise expressly stated, the terms “comprising,” “including,” “having,” “containing,” or any other similar terms used throughout the application are open-ended terms that indicate that a eutectic or article of manufacture may include, in addition to the elements listed herein, other elements not expressly listed but which are typically inherent in the eutectic or article of manufacture. Furthermore, in this document, the terms “comprising,” “including,” “having,” and “containing” should be interpreted as specifically disclosed and simultaneously encompassing closed or semi-closed conjunctions such as “consisting of” and “substantially composed of.” “Substantially composed of” indicates that the elements listed herein constitute 95%, 97%, or, in some respects, 99% or more of the eutectic or article of manufacture.

[0035] Beneficial effects

[0036] (1) The present invention provides a stable curcumin-L-carnitine cocrystal. Compared with curcumin crystals themselves, the cocrystal increases the solubility of curcumin, which significantly improves its absorption and bioavailability. It can further broaden the application range of curcumin, improve the effect of curcumin, and reduce the amount and cost of curcumin. Therefore, it has strong practical application value.

[0037] (2) The method for preparing curcumin-L-carnitine cocrystal of the present invention is simple, reproducible, and has the advantages of low cost, environmental friendliness and easy control. Attached Figure Description

[0038] Figure 1 This is a single-crystal structure diagram of the curcumin-L-carnitine eutectic prepared in Example 1 of this invention;

[0039] Figure 2 This is an X-ray powder diffraction (XRPD) pattern of the curcumin-L-carnitine cocrystal prepared in Example 1 of this invention;

[0040] Figure 3 This is a differential scanning calorimetry (DSC) image of the curcumin-L-carnitine eutectic prepared in Example 1 of this invention;

[0041] Figure 4 This is the infrared (IR) spectrum of the curcumin-L-carnitine cocrystal prepared in Example 1 of this invention;

[0042] Figure 5 This is the infrared (IR) spectrum of the commercially available curcumin crystals in Example 1 of this invention;

[0043] Figure 6 This is a comparison of the dissolution curves of commercially available curcumin crystals in the test examples and the curcumin-L-carnitine cocrystals prepared in Example 3 in pH 2.0 buffer solution;

[0044] Figure 7 This is a comparison of the dissolution curves of commercially available curcumin crystals in the test examples and the curcumin-L-carnitine cocrystals prepared in Example 3 in a pH 4.5 buffer solution;

[0045] Figure 8 This is a comparison graph of the drug-time curves of commercially available curcumin crystals in Example 2 and curcumin-L-carnitine cocrystals prepared in Example 3. Detailed Implementation

[0046] To make the objectives, technical solutions, and advantages of this invention clearer, the 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 merely illustrative and not intended to limit the invention.

[0047] This invention uses L-carnitine as a ligand to form a stable co-crystal with curcumin. As can be seen from the following single-crystal structures, the interactions and arrangement of curcumin molecules in the curcumin crystal and the curcumin-L-carnitine co-crystal are completely different. In the curcumin crystal, curcumin molecules form a two-dimensional network structure through hydrogen bonds between phenolic hydroxyl groups and carbonyl groups; in the curcumin-L-carnitine co-crystal, curcumin molecules form a one-dimensional chain structure through hydrogen bonds between phenolic hydroxyl groups and carboxylate groups, and between hydroxyl groups and carboxylate groups, with L-carnitine molecules as the medium.

[0048]

[0049] The X-ray powder diffraction pattern in this invention was obtained using a Bruker D8 Advanced X-ray eutectic diffractometer, which employs Cu-Kα irradiation. The scanning range is from 3° to 40° in the 2θ interval, and the scanning speed is 5° / minute.

[0050] X-ray single-crystal data were collected using a Bruker D8 Venture X-ray single-crystal diffractometer equipped with a Mo-Kα X-ray target. The test temperature was 170K, the voltage was 50kV, and the current was 30mA.

[0051] Differential scanning calorimetry was performed using a TA DSC Q2000 instrument with a heating rate of 10 K / min.

[0052] The Fourier transform infrared spectrometer used was a Thermo Scientific Nicolet 6700.

[0053] The ball milling was performed using a Jingxin JX-2G planetary ball mill.

[0054] Liquid chromatography was performed using an Agilent 1260 Infinity HPLC.

[0055] The reagents and their sources used in the following examples are as follows:

[0056] L-carnitine: 99% purity, purchased from Aladdin Reagent Co., Ltd.

[0057] Curcumin (crystals): 98% purity, purchased from Aladdin Reagent Co., Ltd.

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

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

[0060] Methanol: 99% purity, purchased from Sinopharm Chemical Reagent Co., Ltd.

[0061] Example 1

[0062] 1.61 g of L-carnitine and 3.69 g of curcumin were added to 60 mL of ethanol solvent and stirred and suspended at 30 °C for 12 hours. The mixture was filtered to obtain a red solid, which was then vacuum dried overnight to obtain a curcumin-L-carnitine cocrystal.

[0063] The curcumin-L-carnitine cocrystal, raw curcumin crystals, and L-carnitine were characterized by X-ray powder diffraction (XRPD). Differential scanning calorimetry (DSC) and infrared spectroscopy (IR) analyses were performed on the curcumin-L-carnitine cocrystal. The results are shown in Tables 1-3. Figure 2-5 As shown.

[0064] From Table 1-3, Figure 2 It can be seen that 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°.

[0065] Depend on Figure 4-5 It can be seen that the curcumin-L-carnitine cocrystal has a completely different infrared spectrum from curcumin itself. In the infrared spectrum of the curcumin-L-carnitine cocrystal, the characteristic infrared peak of the phenolic hydroxyl group of curcumin is from 3508 cm⁻¹. -1 Redshifted to 3165cm -1 The presence of this information indicates that curcumin and L-carnitine in the eutectic exhibit strong hydrogen bonding.

[0066] Table 1. XRPD data of curcumin-L-carnitine cocrystal

[0067]

[0068]

[0069] Table 2. XRPD data of commercially available curcumin

[0070]

[0071] Table 3. L-carnitine XRPD data

[0072]

[0073] Example 2

[0074] 1.61 g of L-carnitine and 3.69 g of curcumin were added to 60 mL of ethyl acetate solvent and stirred and suspended at 30 °C for 12 hours. The mixture was filtered to obtain a red solid, which was then dried under vacuum overnight to obtain a curcumin-L-carnitine cocrystal.

[0075] This eutectic was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR) spectroscopy. The results are consistent with... Figures 2-4 Basically the same.

[0076] Example 3

[0077] 0.161 g of L-carnitine and 0.369 g of curcumin were added to a ball mill jar, along with 1 mL of ethanol. The mixture was ball milled at room temperature for 0.5 hours, and the solid was dried in a vacuum drying oven at room temperature for 12 hours to obtain curcumin-L-carnitine cocrystal.

[0078] This eutectic was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR) spectroscopy. The results are consistent with... Figures 2-4 Basically the same.

[0079] Example 4

[0080] 0.161 g of L-carnitine and 0.369 g of curcumin were added to a ball mill jar, along with 1 mL of methanol. The mixture was ball milled at room temperature for 0.5 hours, and the solid was dried in a vacuum drying oven at room temperature for 12 hours to obtain curcumin-L-carnitine eutectic.

[0081] This eutectic was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR) spectroscopy. The results are consistent with... Figures 2-4 Basically the same.

[0082] Comparative Example 1

[0083] Add 0.131 g of leucine and 0.369 g of curcumin to a ball mill jar, add 1 ml of methanol or ethanol, ball mill for 0.5 hours, and then dry the solid in a vacuum drying oven at room temperature for 12 hours to obtain a yellow powder.

[0084] X-ray powder diffraction (XRPD) analysis revealed that no eutectic was formed in this powder.

[0085] Comparative Example 2

[0086] 0.131 g of isoleucine and 0.369 g of curcumin were added to a ball mill jar, along with 1 ml of methanol or ethanol. The mixture was ball milled for 0.5 hours, and the solid was dried in a vacuum drying oven at room temperature for 12 hours to obtain a yellow powder.

[0087] X-ray powder diffraction (XRPD) analysis revealed that no eutectic was formed in this powder.

[0088] Comparative Example 3

[0089] Add 0.139 g of methionine and 0.369 g of curcumin to a ball mill jar, add 1 ml of methanol or ethanol, ball mill for 0.5 hours, and then dry the solid in a vacuum drying oven at room temperature for 12 hours to obtain a yellow powder.

[0090] X-ray powder diffraction (XRPD) analysis revealed that no eutectic was formed in this powder.

[0091] Comparative Example 4

[0092] Add 0.119 g of threonine and 0.369 g of curcumin to a ball mill jar, add 1 ml of methanol or ethanol, ball mill for 0.5 hours, and then dry the solid in a vacuum drying oven at room temperature for 12 hours to obtain a yellow powder.

[0093] X-ray powder diffraction (XRPD) analysis revealed that no eutectic was formed in this powder.

[0094] Test Example 1. Dissolution Test

[0095] Those skilled in the art can demonstrate that the curcumin-L-carnitine cocrystal described in the context has a significantly improved dissolution rate compared to curcumin crystals themselves; representative studies were conducted using commercially available curcumin crystals and the curcumin-L-carnitine cocrystal obtained in Example 3.

[0096] The differences in powder dissolution between commercially available curcumin and the curcumin-L-carnitine cocrystal obtained in Example 3 were compared. The powder dissolution experiment was conducted in buffer solutions at pH 2.0 and pH 4.5 (with 0.5% Tween 80), at a temperature of 37°C, and at a rotation speed of 50 rpm. Both the commercially available curcumin crystals and the curcumin-L-carnitine cocrystal obtained in Example 3 were passed through a 100-mesh sieve to eliminate the influence of particle size on dissolution. Samples equivalent to 10 mg of curcumin were weighed and placed in the sample chamber of the dissolution apparatus, stirred, and samples were taken at 3, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes. The concentration was determined using HPLC. The results are as follows: Figure 6 , 7 As shown. In a buffer solution with pH 2.0, the cocrystal dissolution reached approximately 7 times that of curcumin itself after 3 minutes; in a buffer solution with pH 4.5, the cocrystal dissolution reached approximately 8 times that of curcumin itself after 3 minutes.

[0097] As the results above show, the curcumin cocrystal disclosed in this invention has superior solubility and dissolution rate compared with conventional commercially available curcumin crystals.

[0098] Test Example 2. Bioavailability Test

[0099] Those skilled in the art can demonstrate that the curcumin-L-carnitine cocrystal described in this context has significantly improved bioavailability compared to commercially available curcumin crystals; representative studies were conducted using commercially available curcumin crystals and the curcumin-L-carnitine cocrystal obtained in Example 3.

[0100] The bioavailability differences between commercially available curcumin and the curcumin-L-carnitine cocrystal obtained in Example 3 were compared. Male SD rats (weighing 200-300 g) were used in the experiment under well-fed conditions. A total of 12 rats were randomly divided into two groups of 6 each. The commercially available curcumin crystals and the cocrystal obtained in Example 3 were uniformly dispersed in soybean oil and administered via gavage as a suspension. The dosage was 200 mg / kg (calculated as curcumin). Blood samples were collected via the orbital venous plexus at 20 min, 40 min, 1 hour, 1.5 hours, 2.5 hours, 4 hours, 6 hours, and 8 hours post-administration, at a rate of 1 mL per time point. Plasma was separated by centrifugation within 0.5 h after blood collection at 10,000 rpm for 5 minutes. Accurately transfer 100 μL of plasma, add 50 μL of enzyme buffer, incubate at 37°C for 60 min, then add 0.45 mL of methanol (0.2% acetic acid), shake for 10 min, centrifuge at 14000 rpm for 3 min, and collect the supernatant for liquid chromatography analysis. Results are shown in Table 4. Figure 8 As shown.

[0101] Table 4. Pharmacokinetic parameters of commercially available curcumin crystals and curcumin-L-carnitine cocrystals

[0102]

[0103] As the results above show, compared with conventional commercially available curcumin crystals, the curcumin-L-carnitine cocrystal of the present invention has superior bioavailability, and the maximum blood concentration of curcumin in rats administered with the cocrystal reached 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, and 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°.

2. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, The curcumin-carnitine eutectic belongs to the monoclinic crystal system, with cell parameters a = 17.1370(11) Å, b = 5.6406(4) Å, c = 27.393(2) Å, α = 90°, β = 101.063(2)°, and γ = 90°.

3. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, 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°.

4. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, The curcumin-L-carnitine eutectic has an X-ray powder diffraction pattern that is essentially as shown in Figure 2.

5. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, The differential scanning calorimetry spectrum of the curcumin-L-carnitine eutectic showed a characteristic endothermic peak at 161±2 °C.

6. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, The curcumin-L-carnitine eutectic has a differential scanning calorimetry spectrum as shown in Figure 3.

7. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, The infrared spectrum of the curcumin-L-carnitine cocrystal was at 3032 cm⁻¹. -1 ±2 cm -1 2980 cm -1 ±2 cm -1 2556 cm -1 ±2 cm -1 It has a characteristic peak.

8. The curcumin-L-carnitine eutectic according to claim 7, characterized in that, The infrared spectrum of the curcumin-L-carnitine cocrystal was still at 3069 cm⁻¹. -1 ±2 cm -1 2831 cm -1 ±2 cm -1 1563cm -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 It has a characteristic peak.

9. The curcumin-L-carnitine eutectic according to claim 1, characterized in that, The curcumin-L-carnitine eutectic has an infrared spectrum as shown in Figure 4.

10. A method for preparing curcumin-L-carnitine eutectic according to any one of claims 1-9, wherein the method is selected from one of the following methods: Method 1: Recrystallize curcumin and L-carnitine in a solvent with a stoichiometric ratio of 1:1-1:2, and obtain curcumin-L-carnitine cocrystal after separation and drying of the precipitate; Method 2: Curcumin and L-carnitine with a stoichiometric ratio of 1:1 are ball-milled in a solvent, and the resulting crystals are dried to obtain curcumin-L-carnitine eutectic.

11. The method for preparing curcumin-L-carnitine eutectic according to claim 10, characterized in that, In both methods one and two above, the solvent is independently selected from one or more of water, alcohols, ketones, esters, alkanes, aromatic hydrocarbons, and haloalkanes; and / or The crystallization drying method employs vacuum drying, boiling drying, or forced-air drying.

12. The method for preparing curcumin-L-carnitine eutectic according to claim 10, characterized in that, In the above methods one and two, Each of the solvents is 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 method for drying the crystals is vacuum drying, and the drying time is 3~36 hours.

13. The method for preparing curcumin-L-carnitine eutectic according to claim 10, characterized in that, In Method 1: The mass ratio of curcumin to L-carnitine and the volume ratio of curcumin to solvent is: 1 g : (3-20) mL; and / or The recrystallization temperature is 10-70℃; the recrystallization time is 1-36 hours. In Method Two: The mass ratio of curcumin to L-carnitine and the volume ratio of curcumin to solvent is 1 g : (0.1-5) mL.

14. The method for preparing curcumin-L-carnitine eutectic according to claim 10, characterized in that, In Method 1: The mass ratio of curcumin to L-carnitine and the volume ratio of curcumin to solvent is: 1 g : (4-15) mL; and / or The recrystallization temperature is 20-40℃; the recrystallization time is 10-24 hours. In Method Two: The ratio of the mass of curcumin to L-carnitine and the volume of solvent used is 1 g : (0.5-2) mL.

15. A curcumin product comprising curcumin-L-carnitine cocrystal as described in any one of claims 1-9 or curcumin-L-carnitine cocrystal prepared by the preparation method described in any one of claims 10-14, wherein the product is selected from health products, food, cosmetics, pharmaceuticals, pharmaceutical excipients and feed.

16. The use of curcumin-L-carnitine cocrystal according to any one of claims 1-9, or the curcumin-L-carnitine cocrystal prepared by the preparation method according to any one of claims 10-14, in the preparation of curcumin products, wherein the products are selected from health products, food, cosmetics, pharmaceuticals, pharmaceutical excipients, and feed.

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