An adenosine co-crystal, and a preparation method and application thereof

Abstract

The application provides an adenosine co-crystal and a preparation method and application thereof, and belongs to the technical field of biological medicines.The adenosine co-crystal is formed by adenosine and ikar or nicotinamide according to a molar ratio of 1:0.2-16.9, and overcomes the problem of poor bioavailability of adenosine in the prior art.The adenosine co-crystal provided by the application has a significantly higher solubility compared with adenosine, can improve the blood drug concentration in vivo as a medicine to further play a more effective therapeutic role, can avoid the influence of the hydrophobicity of the stratum corneum to further improve the skin permeability of the product as a skin care product or a cosmetic product, and can improve the solubility of the effective component in the product to better play a hair growth effect as a hair growth product, and has wide application potential.The preparation method of the co-crystal has simple steps, high efficiency, low cost, and the advantages of being suitable for large-scale production.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to an adenosine cocrystal, its preparation method, and its application. Background Technology

[0002] Adenosine, also known as adenosine nucleoside, is a water-soluble small molecule composed of the N-9 nucleotide of adenine and the C-1 nucleotide of D-ribose linked by a β-glycosidic bond. Adenosine possesses various pharmacological activities, including analgesia, anti-inflammation, antiarrhythmia, hypotension, wound healing, and immune enhancement. It also plays a role in cosmetics and daily chemical products, such as promoting collagen production in human dermal fibroblasts, improving skin elasticity, reducing wrinkles around the eyes and between the eyebrows, moisturizing, repairing, and stimulating hair growth. However, the short half-life and duration of action of adenosine in vivo, the hydrophobicity of the stratum corneum leading to relatively poor permeability of hydrophilic adenosine, and its very low solubility in water (less than 1% at room temperature) all limit its effectiveness. Solving the problem of adenosine solubility could effectively improve the anti-aging effects of products.

[0003] To overcome the above problems, the selection of appropriate formulations and administration methods to improve the bioavailability of adenosine has received widespread attention.

[0004] A prior art facial cream using adenosine-loaded microneedles has been disclosed, which is more effective than facial creams containing adenosine directly as a component in improving skin elasticity, dermal density, and wrinkles, and can also reduce the dosage of adenosine used. However, in daily skincare, the presence of microneedles affects the user experience and does not improve the solubility of adenosine in water / ethanol.

[0005] Chinese patent CN115337283A discloses a nano-encapsulation material for adenosine encapsulated by molecular motor vesicles, its preparation method, composition, and application of the composition. This technical solution effectively improves the bioavailability and ease of use of adenosine by processing adenosine preparations into nano-encapsulation materials using molecular motor vesicles. However, it does not improve the solubility of adenosine in water / ethanol, and the preparation process is complex and costly, making it unsuitable for industrial applications. Summary of the Invention

[0006] The purpose of this invention is to provide an adenosine co-crystal, its preparation method, and its application, in order to solve the problem of poor bioavailability of adenosine in the prior art.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] This invention provides an adenosine co-crystal, which is formed by adenosine and a co-crystal forming agent in a molar ratio of 1:0.2~16.9.

[0009] The eutectic forming agent is ectoine or nicotinamide.

[0010] Preferably, the co-crystal forming agent is ectoine, and the adenosine co-crystal is adenosine-ectoine co-crystal;

[0011] The PXRD pattern of the adenosine-ectoine cocrystal is at least in 2 θ Characteristic peaks are observed at 18.99, 23.02, 23.83, 25.56, and 39.93.

[0012] Preferably, the adenosine ectoine co-crystal is obtained by means of, for example Figure 2 The PXRD spectrum shown is used to characterize it.

[0013] Preferably, the co-crystal forming agent is nicotinamide, and the adenosine co-crystal is adenosine-nicotinamide co-crystal;

[0014] The PXRD spectrum of the adenosine nicotinamide cocrystal is at least 2 θ Characteristic peaks are observed at 22.09, 22.90, 23.68, and 28.46.

[0015] Preferably, the adenosine nicotinamide cocrystal is obtained by means of, for example Figure 4 The PXRD spectrum shown is used to characterize it.

[0016] The present invention also provides a method for preparing the above-mentioned adenosine co-crystal, comprising the following steps:

[0017] Adenosine and a co-crystal forming agent are mixed and mechanically ground to obtain adenosine co-crystals;

[0018] The molar ratio of adenosine to co-crystal forming agent is 1:0.2~16.9;

[0019] The eutectic forming agent is ectoine or nicotinamide.

[0020] Preferably, the molar ratio of adenosine to cocrystal forming agent is 1:0.8~2.

[0021] Preferably, the mechanical grinding time is 10 minutes or more.

[0022] The present invention also provides the application of the above-mentioned adenosine co-crystal or the adenosine co-crystal obtained by the above preparation method in the preparation of analgesic drugs, anti-inflammatory drugs, antiarrhythmic drugs, antihypertensive drugs, and drugs that promote wound healing.

[0023] The present invention also provides the application of the above-mentioned adenosine co-crystal or the adenosine co-crystal obtained by the above preparation method in the preparation of moisturizing cosmetics, anti-aging cosmetics, antioxidant products, anti-wrinkle cosmetics, repair cosmetics or hair growth products.

[0024] The beneficial effects of this invention are:

[0025] The adenosine cocrystal provided by this invention has significantly higher solubility than adenosine. As a drug, it can increase the blood drug concentration in vivo, thereby exerting a more effective therapeutic effect. As a skin care or cosmetic product, it can avoid the influence of the hydrophobicity of the stratum corneum, thereby improving the skin penetration performance of the product. As a hair growth product, it can increase the dissolved dosage of the active ingredients in the product, thereby better exerting the hair growth effect. It has broad application potential.

[0026] The preparation method of adenosine co-crystal provided by this invention has simple steps, high efficiency, low cost, and is suitable for large-scale production. Attached Figure Description

[0027] Figure 1 The PXRD pattern of adenosine, ectoine, and the cocrystal is shown.

[0028] Figure 2 PXRD pattern of adenosine ectoine cocrystal;

[0029] Figure 3 The PXRD pattern of the cocrystal of adenosine, adenosine, and nicotinamide;

[0030] Figure 4 The PXRD pattern of the adenosine nicotinamide cocrystal is shown.

[0031] Figure 5 Infrared spectra of adenosine, ectoine, and the co-crystal;

[0032] Figure 6 The infrared spectra are those of adenosine, nicotinamide, and the cocrystal. Detailed Implementation

[0033] The present invention provides an adenosine co-crystal, which is formed by adenosine and a co-crystal forming agent in a molar ratio of 1:0.05~5; wherein the co-crystal forming agent is ectoine or nicotinamide.

[0034] In this invention, the co-crystal forming agent is preferably ectoine, and the adenosine co-crystal is an adenosine-ectoine co-crystal; the PXRD spectrum of the adenosine-ectoine co-crystal is at least in the range of 2. θ Characteristic peaks are found at 18.99, 23.02, 23.83, 25.56, and 39.93. Further optimization can be achieved through methods such as... Figure 2 The PXRD spectrum shown is used to characterize it.

[0035] In this invention, the co-crystal forming agent is nicotinamide, and the adenosine co-crystal is an adenosine-nicotinamide co-crystal; the PXRD spectrum of the adenosine-nicotinamide co-crystal is at least 2 θCharacteristic peaks are found at 22.09, 22.90, 23.68, and 28.46, and further optimization is achieved through methods such as... Figure 4 The PXRD spectrum shown is used to characterize it.

[0036] The present invention also provides a method for preparing the above-mentioned adenosine co-crystal, comprising the following steps: mixing adenosine and a co-crystal forming agent, and mechanically grinding to obtain adenosine co-crystal, wherein the co-crystal forming agent is ectoine or nicotinamide; the molar ratio of adenosine to the co-crystal forming agent is 1:0.05~5, more preferably 1:0.5~1.24, and even more preferably 1:0.6~1.1; the mechanical grinding time is preferably 10 min or more, more preferably 20~40 min.

[0037] This invention also provides the application of the above-mentioned adenosine cocrystal or the adenosine cocrystal obtained by the above preparation method in the preparation of analgesic drugs, anti-inflammatory drugs, antiarrhythmic drugs, antihypertensive drugs, and wound healing promoting drugs; the dosage form of the drug is preferably powder, tablet, granule, capsule, solution, emulsion, suspension, injection, spray, aerosol, or powder inhaler; the drug also preferably contains other excipients and / or active ingredients. This invention does not have special requirements for the type of excipients, as long as they do not affect the activity of the adenosine cocrystal; the drug also preferably contains a pharmaceutically acceptable carrier, the carrier including diluents, buffers, suspensions, emulsions, granules, encapsulation agents, excipients, fillers, binders, sprays, transdermal absorbents, humectants, disintegrants, absorption promoters, surfactants, colorants, flavoring agents, or adsorbents.

[0038] This invention also provides the application of the above-mentioned adenosine co-crystal or the adenosine co-crystal obtained by the above preparation method in the preparation of moisturizing cosmetics, anti-aging cosmetics, antioxidant products, anti-wrinkle cosmetics, repairing cosmetics or hair growth products. The dosage form of the cosmetics or antioxidant products is preferably cream, face mask, lotion, toner, shower gel, facial cleanser or hand soap / hand gel, etc., and the dosage form of the hair growth products is preferably shampoo, hair oil or hair conditioner, etc.

[0039] In this invention, the cosmetic or antioxidant product further includes excipients acceptable to cosmetics and skincare products, including humectants, emulsifiers, thickeners, skin conditioning agents, pH adjusters, preservatives, and water; the emulsifier is preferably sodium lauroyl glutamate, lauramidopropyl betaine, isopropyl myristate, or cocoyl glucoside; the humectant is preferably sodium hyaluronate, glycerin, propylene glycol, butylene glycol, dipropylene glycol, sorbitol, inositol, β-glucan, or trehalose; the thickener is preferably EDTA dimethyl ether. Sodium, carbomer, xanthan gum, or ammonium acryloyldimethyl taurate / VP copolymer or sodium polyacrylate grafted starch; the skin conditioning agent is preferably capryloyl hydroxamic acid, allantoin, ceramide, nicotinamide, vitamin C derivative, arbutin, tranexamic acid, or yeast / hydrolyzed yeast; the pH adjuster is preferably arginine, sodium citrate, citric acid, phosphoric acid, tartaric acid, sodium dihydrogen phosphate, or triethanolamine; the preservative is preferably methylparaben, butylparaben, ethylparaben, isobutylparaben, propylparaben, potassium sorbate, or sodium benzoate.

[0040] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0041] Example 1

[0042] Adenosine and ectoine with a molar ratio of 1:0.2 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0043] Example 2

[0044] Adenosine and ectoine with a molar ratio of 1:0.5 were accurately weighed using an electronic balance. The adenosine and ectoine were mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0045] Example 3

[0046] Adenosine and ectoine with a molar ratio of 1:0.8 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0047] Example 4

[0048] Adenosine and ectoine in a molar ratio of 1:1 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0049] Example 5

[0050] Adenosine and ectoine with a molar ratio of 1:1.5 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0051] Example 6

[0052] Adenosine and ectoine with a molar ratio of 1:2 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0053] Example 7

[0054] Adenosine and ectoine with a molar ratio of 1:3 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0055] Example 8

[0056] Adenosine and ectoine with a molar ratio of 1:4 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0057] Example 9

[0058] Adenosine and ectoine with a molar ratio of 1:8 were accurately weighed using an electronic balance. The adenosine and ectoine were then mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0059] Example 10

[0060] Adenosine and ectoine with a molar ratio of 1:16.9 were accurately weighed using an electronic balance, mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0061] Example 11

[0062] Adenosine and nicotinamide with a molar ratio of 1:1.5 were accurately weighed using an electronic balance, mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0063] Comparative Example 1

[0064] Adenosine and betaine with a molar ratio of 1:1.5 were accurately weighed using an electronic balance, mixed evenly using a vortex mixer, placed in a mortar, and ground directly for 30 minutes to obtain adenosine cocrystals.

[0065] Experimental Example 1: Solubility Determination

[0066] At room temperature, 30 mL of deionized water was added to a 50 mL Erlenmeyer flask with a glass stopper. Then, excess eutectic crystals prepared in Examples 1-10 and Comparative Example 1 were added to the Erlenmeyer flask. The mixture was stirred and shaken for 6 hours to ensure solid-liquid equilibrium was reached. After standing for 30 minutes, approximately 2 mL of saturated supernatant was taken from each round-bottom flask using a preheated pipette and placed in a pre-weighed beaker. The total weight of the filtrate in the beaker was immediately measured. The beaker was then placed in a sealed, dry environment and allowed to dry completely before being weighed again. Each experiment was repeated three times, and the average value was used to calculate the solubility.

[0067] The formulas for calculating the solubility of adenosine in each cocrystal are as follows:

[0068]

[0069] The results are shown in Table 1 below:

[0070] Table 1 Solubility Results

[0071]

[0072] The results show that the solubility of adenosine is 0.73%. Compared with adenosine, Examples 1-10 can significantly improve the solubility of adenosine, with Examples 3, 4, 5 and 6 being the best.

[0073] In the test results of cocrystals formed by combining adenosine with ectoine, nicotinamide and betaine in a 1:1.5 ratio (Example 5, Example 11 and Comparative Example 1), only the solubility of adenosine was significantly improved in Example 4 and Example 10.

[0074] Therefore, the adenosine ectoine cocrystal and adenosine nicotinamide cocrystal provided by the present invention can significantly improve the solubility of adenosine.

[0075] Experiment Example 2: DPPH Free Radical Scavenging Capacity Test

[0076] Adenosine and the cocrystals prepared in Examples 5 and 11 were dissolved in distilled water to prepare a 0.15% solution. 0.5 mL of each sample solution was taken and 2.5 mL of 0.06 mM DPPH methanol solution was added. After thorough mixing, the solution was sealed and allowed to stand in the dark at room temperature for 30 min, and the absorbance was measured at 517 nm. Each sample was repeated three times. The DPPH free radical scavenging rate was calculated using the following formula:

[0077]

[0078] In the formula:

[0079] A0—Absorbance of distilled water + DPPH methanol solution;

[0080] A1 — Absorbance of the sample solution + DPPH methanol solution;

[0081] A2 — Absorbance of the sample solution + methanol solution;

[0082] Anhydrous methanol was used as a blank control.

[0083] The DPPH method is an antioxidant evaluation method based on hydrogen atom transfer. The DPPH radical scavenging rates of each sample are shown in Table 2.

[0084] Table 2 Summary of DPPH free radical scavenging rates

[0085]

[0086] As shown in Table 2, compared with the DPPH free radical scavenging rate of adenosine, the cocrystal provided by the present invention can significantly improve the DPPH free radical scavenging rate of adenosine.

[0087] Experimental Example 3: Powder X-ray Diffraction (PXRD) Analysis

[0088] PXRD analysis was performed on the cocrystal samples prepared in Examples 5 and 11, containing adenosine, ectoine, and others. If the bright diffraction peaks in the sample spectra disappeared and new peaks appeared, it indicated the formation of a new phase and a change in its crystal structure. The test conditions were: 50-100 mg of solid sample was placed on the sample stage, and the scanning range was 10°-90° (2...). θ The step size is 0.02°, the scanning speed is 0.2 seconds / step, the copper target voltage is 40KV, and the current is 40mA.

[0089] The solid product obtained by liquid-free milling and crystallization of a solid mixture of adenosine and ectoine at a molar ratio of 1:1.5, and the PXRD spectra of adenosine and ectoine are shown below. Figure 1 As shown.

[0090] from Figure 1 The characteristic peaks of adenosine are 11.47°, 15.16°, 17.46°, 18.87°, 20.50°, 21.21°, and 22.94°, while those of ectoine are 11.53°, 12.12°, 13.45°, 15.52°, 16.87°, 17.92°, 19.49°, 20.40°, 21.39°, 23.12°, 24.43°, 25.04°, 25.78°, 26.55°, 27.03°, 28.58°, and 30.94°. After liquid-free grinding and crystallization, the PXRD spectra of adenosine and ectoine changed, with the characteristic peaks of both raw materials showing a certain degree of weakening or disappearance. This also shows that in the PXRD spectrum of the co-crystal, the characteristic peaks of adenosine and ectoine decreased.θ Strong new characteristic peaks appeared at angles of 18.99°, 23.02°, 23.83°, 25.56°, and 39.93°, indicating that crystalline substances different from the active pharmaceutical ingredient were generated during the liquid-free grinding process for preparing the cocrystal. This demonstrates that the adenosine-ectoine cocrystal was successfully prepared in this invention. The individual PXRD spectra of the cocrystal are shown below. Figure 2 As shown.

[0091] The solid product obtained by liquid-free milling and crystallization of a solid mixture of adenosine and nicotinamide at a molar ratio of 1:1.5, and the PXRD spectra of adenosine and nicotinamide are shown below. Figure 3 As shown. From Figure 3 The characteristic peaks of adenosine are 11.47°, 15.16°, 17.46°, 18.87°, 20.50°, 21.21°, and 22.94°. Literature review shows that the characteristic peaks of nicotinamide are 14.7°, 23.3°, 25.3°, 25.8°, and 27.2°. After liquid-free grinding and crystallization, the PXRD spectra of both adenosine and nicotinamide changed, with the characteristic peaks of the raw materials adenosine and nicotinamide showing a certain weakening or disappearance. The resulting cocrystal spectrum showed strong new characteristic peaks at 22.09°, 22.90°, 23.68°, and 28.46°, indicating the formation of a crystalline substance different from adenosine and nicotinamide. This demonstrates that the present invention successfully prepared an adenosine-nicotinamide cocrystal. The individual PXRD spectrum of the cocrystal is shown below. Figure 4 As shown.

[0092] Experiment Example 4: Infrared Spectroscopy Analysis

[0093] Infrared spectroscopy can characterize changes in the chemical structure of substances. Specific functional groups of molecules will absorb electromagnetic radiation of specific wavelengths in the infrared region, producing an infrared absorption spectrum corresponding to the structure of the substance.

[0094] Before testing, the samples prepared in Examples 5 and 11 were placed in an oven with KBr for 24 hours to completely remove moisture. The eutectic sample prepared in Example 5 or 11 was then mixed with KBr at a ratio of 1:100 in a mortar and ground thoroughly. The mixture was then pressed into a pellet and tested at 4000 cm⁻¹. -1 ~400cm -1 Infrared spectrum in the band.

[0095] The interaction distance of a covalent bond is shorter than that between the acceptor and donor in a hydrogen bond, and the force of a hydrogen bond is much weaker than that of a covalent bond; therefore, the degree of electron transfer in a hydrogen bond is also weaker. The characteristic peaks of the compound itself do not disappear with the formation of a hydrogen bond, but the bond energy and bond length of the covalent bond will change accordingly, causing some characteristic peaks in the infrared spectrum to undergo a blue shift or red shift. The strength of the hydrogen bond also affects the degree of shift of characteristic peaks in the infrared spectrum; the strength of the hydrogen bond is directly proportional to the magnitude of the shift in the characteristic peaks in the infrared spectrum. That is, the stronger the hydrogen bond, the wider the red shift range. Therefore, the strength of hydrogen bonds can be qualitatively determined through infrared spectroscopy.

[0096] Adenosine, ectoine, and cocrystallization of adenosine and ectoine at 4000-500 cm⁻¹ -1 The infrared spectrum is shown below. Figure 5 When adenosine and ectoine form a eutectic, intermolecular hydrogen bonds and π…π stacking interactions occur, leading to a decrease in the electron cloud density of the carbonyl group in the molecule and a redshift of the characteristic peak of the stretching vibration towards a lower wavenumber. Figure 5 It can be seen that the C=O group of ectoin carboxyl group is at 1922 cm⁻¹ -1 There is an absorption band at 3763 cm⁻¹, where OH⁻ is at 3763 cm⁻¹. -1 Stretching vibrations are observed at 3521 cm⁻¹; the OH group of adenosine is at 3521 cm⁻¹. -1 The characteristic peaks are relatively broad; after the formation of adenosine-ectoine cocrystal, the C=O group of ectoine decreases from 1922 cm⁻¹. -1 Redshifted to 1876 cm -1 The stretching vibration peak of the NH bond also shifted to lower wavenumbers, from 3648 cm⁻¹. -1 Redshifted to 3577 cm -1 3498 cm -1 These are the stretching vibration absorption peaks of hydroxyl groups in the eutectic and associated hydroxyl groups.

[0097] Adenosine, nicotinamide, and adenosine-nicotinamide cocrystals at 4000-500 cm⁻¹ -1 The infrared spectrum is shown below. Figure 6 The NH group of adenosine-NH2 is at 3763 cm⁻¹. -1 and 3632.8 cm -1 The vibration is symmetrical stretching at 3521.05 cm⁻¹. -1 Stretching vibrations are observed at this point, with the unsaturated N-ring at 1713.22 cm⁻¹. -1 The adenosine exhibits stretching vibrations, forming a clear absorption band. After adenosine forms a eutectic with nicotinamide, the OH group of adenosine changes from 3521.05 cm⁻¹. -1 The redshift reached 3476.7 cm. -1 The NH content of nicotinamide was 1655.23 cm⁻¹. -1Blue shifted to 1673.9 cm -1 and from 3614.94 cm -1 The blue color shifted to 3574.68 cm. -1 This indicates that the two molecules participated in the formation of eutectic intermolecular hydrogen bonds.

[0098] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. An adenosine co-crystal, characterized in that, Adenosine co-crystals are formed by combining adenosine and a co-crystal forming agent in a molar ratio of 1:0.2~16.9; The eutectic forming agent is ectoine or nicotinamide; When the co-crystal forming agent is ectoine, the adenosine co-crystal is an adenosine-ectoine co-crystal; The PXRD pattern of the adenosine-ectoine cocrystal is at least 2 θ Characteristic peaks are observed at 18.99, 23.02, 23.83, 25.56, and 39.

93. When the co-crystal forming agent is nicotinamide, the adenosine co-crystal is an adenosine-nicotinamide co-crystal; The PXRD spectrum of the adenosine nicotinamide cocrystal is at least 2 θ Characteristic peaks are observed at 22.09, 22.90, 23.68, and 28.

46. The preparation method of the adenosine co-crystal includes the following steps: Adenosine and a co-crystal forming agent are mixed and mechanically ground to obtain adenosine co-crystals; The molar ratio of adenosine to cocrystal forming agent is 1:0.2~16.

9.

2. The adenosine co-crystal according to claim 1, characterized in that, The adenosine ectoine cocrystal was characterized by the PXRD spectrum shown in Figure 2.

3. The adenosine co-crystal according to claim 1, characterized in that, The adenosine nicotinamide cocrystal was characterized by the PXRD pattern shown in Figure 4.

4. The method for preparing adenosine co-crystal according to any one of claims 1 to 3, characterized in that, Includes the following steps: Adenosine and a co-crystal forming agent are mixed and mechanically ground to obtain adenosine co-crystals; The molar ratio of adenosine to co-crystal forming agent is 1:0.2~16.9; The eutectic forming agent is ectoine or nicotinamide.

5. The method for preparing adenosine co-crystal according to claim 4, characterized in that, The molar ratio of adenosine to cocrystal forming agent is 1:0.8~2.

6. The method for preparing adenosine co-crystal according to claim 4, characterized in that, The mechanical grinding time is more than 10 minutes.

7. The use of the adenosine cocrystal according to any one of claims 1 to 3 or the adenosine cocrystal obtained by the preparation method according to any one of claims 4 to 6 in the preparation of analgesic drugs, anti-inflammatory drugs, antiarrhythmic drugs, antihypertensive drugs or wound healing promoting drugs.

8. The use of the adenosine cocrystal according to any one of claims 1 to 3 or the adenosine cocrystal obtained by the preparation method according to any one of claims 4 to 6 in the preparation of moisturizing cosmetics, anti-aging cosmetics, antioxidant products, anti-wrinkle cosmetics, repairing cosmetics or hair growth products.

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