A nicotinamide-salicylic acid co-crystal, and a preparation method and use thereof

Abstract

This invention discloses a nicotinamide-salicylic acid cocrystal, its preparation method, and its uses, relating to the field of cocrystal technology. The nicotinamide-salicylic acid cocrystal comprises nicotinamide and salicylic acid molecules, and the molecular formula of the nicotinamide-salicylic acid is C0. 13 H 12 N2O4, wherein the molar ratio of nicotinamide to salicylic acid is 1:1; the eutectic is monoclinic, space group P21 / n, with cell parameters a=11.080(2)Å, b=5.0000(10)Å, c=22.820(5)Å, α=90°, β=97.60(3)°, γ=90°, V=1253.1(4)Å. 3 The differential scanning calorimetry (DSC) spectrum of the eutectic showed a characteristic endothermic peak around 142.4 ± 2 °C. This invention addresses the problems of poor stability of nicotinamide, low solubility of salicylic acid, and strong irritation in existing technologies by optimizing intermolecular interactions to form a specific crystal form, thus providing a novel raw material with superior performance for the cosmetics industry. This is achieved through the preparation of a structurally stable, simple, and chemically superior nicotinamide-salicylic acid eutectic with excellent physicochemical properties.

Description

Technical Field

[0001] This invention relates to the field of eutectic technology, specifically to a nicotinamide-salicylic acid eutectic, its preparation method, and its uses. Background Technology

[0002] Niacinamide, a cosmetic ingredient with multiple benefits including whitening, spot removal, moisturizing, and oil control, has always faced challenges in its chemical stability. Under high temperature, high humidity, or light exposure, it easily decomposes into nicotinic acid, leading to reduced efficacy and potential skin irritation. Salicylic acid, on the other hand, holds a significant position in skincare products and topical acne treatments due to its remarkable antioxidant, anti-inflammatory, whitening, and acne-removing effects. However, its low solubility and strong acidity limit its application in formulations.

[0003] Cocrystals, as crystalline materials formed through intermolecular hydrogen bonds and π-π interactions, can effectively alter the physicochemical properties of components, such as solubility, melting point, and stability, showing broad application prospects in industries like cosmetics and health products. While there are reports on nicotinamide-salicylic acid cocrystals in the market, existing technologies still have shortcomings in the controllability of preparation methods, the completeness of cocrystal structure characterization, and the targeted nature of performance optimization. Some technologies fail to achieve precise control over the cocrystal crystal form, resulting in limited stability improvement; furthermore, solubility improvement has not reached an ideal state, making it difficult to meet the formulation requirements of different dosage forms.

[0004] Therefore, we propose a nicotinamide-salicylic acid eutectic, its preparation method, and its applications to address the aforementioned problems.

[0005] The information disclosed above in this background section is only for enhancing the understanding of the background section of this invention, and therefore may include prior art that is not known to those skilled in the art. Summary of the Invention

[0006] The purpose of this invention is to provide a nicotinamide-salicylic acid co-crystal, its preparation method, and its uses, in order to solve the problems mentioned in the background art, namely, the poor stability and easy decomposition of nicotinic acid to produce irritating nicotinic acid, low solubility, and strong acidity and irritation of nicotinic acid in cosmetic applications, and the existing related co-crystal technologies still have problems with insufficient controllability of preparation, crystal form regulation, and performance optimization, making it difficult to meet the needs of cosmetic formulations.

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

[0008] A nicotinamide-salicylic acid cocrystal, the cocrystal comprising nicotinamide and salicylic acid molecules, wherein the molecular formula of the nicotinamide-salicylic acid is C1. 13 H 12 N2O4, wherein the molar ratio of nicotinamide to salicylic acid is 1:1;

[0009] The eutectic is a monoclinic crystal system, space group P21 / n, with cell parameters a = 11.080(2) Å, b = 5.0000(10) Å, c = 22.820(5) Å, α = 90°, β = 97.60(3)°, γ = 90°, and V = 1253.1(4) Å. 3 .

[0010] Preferably, the characteristic peaks of the nicotinamide-salicylic acid eutectic X-ray powder diffraction pattern are at 2θ angles of 7.7°±0.2°, 8.3°±0.2°, 9.3°±0.2°, 13.1°±0.2°, 15.0°±0.2°, 15.5°±0.2°, 15.9°±0.2°, and 16.7°±0.2°. Characteristic peaks are present at 0.2°, 18.7°±0.2°, 20.6°±0.2°, 22.0°±0.2°, 23.4°±0.2°, 23.7°±0.2°, 24.4°±0.2°, 25.1°±0.2°, 26.4°±0.2°, 27.4°±0.2°, 28.2°±0.2°, 28.7°±0.2°, and 29.7°±0.2°.

[0011] Preferably, the differential scanning calorimetry spectrum of the eutectic has a characteristic endothermic peak around 142.4±2℃.

[0012] Preferably, the infrared spectrum of the eutectic is at 3383.87 cm⁻¹. -1 ±2cm -1 3208.94cm -1 ±2cm -1 1668.96cm -1 ±2cm -1 1619.35cm -1 ±2cm -1 1308.30cm -1 ±2cm -1 1126.01cm -1 ±2cm -1 700.09cm -1 ±2cm -1 565.76cm -1 ±2cm -1 957.23cm -1 ±2cm -1 1155.36cm -1 ±2cm -1 934.39cm -1 ±2cm -1 523.65cm -1 ±2cm -1644.72cm -1 ±2cm -1 760.23cm -1 ±2cm -1 793.83cm -1 ±2cm -1 821.74cm -1 ±2cm -1 850.40cm -1 ±2cm -1 1487.69cm -1 ±2cm -1 1448.60cm -1 ±2cm -1 1403.18cm -1 ±2cm -1 1363.17cm -1 ±2cm -1 1252.88cm -1 ±2cm -1 1190.52cm -1 ±2cm -1 1048.23cm -1 ±2cm -1 It has a characteristic peak.

[0013] A method for preparing nicotinamide-salicylic acid eutectic includes the following steps:

[0014] Method 1: Solid-state synthesis method

[0015] Weigh 50 mg of nicotinamide into a sample vial and add the corresponding solvent to suspend it. Then add 1 eq. of salicylic acid and stir overnight at room temperature. If no solid precipitates, precipitate the solid by volatilization crystallization or dissolution crystallization. Collect the solid by centrifugation or filtration for XRPD testing.

[0016] Method 2: Wet grinding method

[0017] Weigh out a certain amount of nicotinamide and mix it with salicylic acid, then add 200 μL of the corresponding solvent, grind the solid with it in a mortar, and then collect the powder for PXRD testing.

[0018] As a further optimization of the present invention, in method two, the stoichiometric ratio of nicotinamide to salicylic acid is 1:1.

[0019] As a further optimization of the present invention, in method one, the solvent is one or more of methanol, ethanol, ethyl acetate, and acetone / water mixed solvent;

[0020] In Method 2, the solvent is one or more of methanol, ethanol, ethyl acetate, and acetone / water mixed solvent.

[0021] The use of a niacinamide-salicylic acid eutectic in cosmetics.

[0022] Compared with the prior art, the beneficial effects of the present invention are:

[0023] The eutectic structure of this invention forms a stable monoclinic P21 / n space group lattice through intermolecular hydrogen bonds and other interactions. Compared to nicotinamide monomer, under conditions such as 60°C high temperature and 25°C & 90%RH high humidity, the rate of nicotinamide decomposition into nicotinic acid is significantly reduced, and the nicotinic acid content fluctuates less. This is due to the intermolecular interactions in the eutectic structure inhibiting the hydrolysis of amide bonds. In addition, after preparation into a eutectic structure, the solubility of "highly soluble" nicotinamide is significantly reduced, thereby improving its bioavailability and tolerability on human skin. In terms of preparation process, this invention adopts a combination of room temperature stirring and volatilization crystallization or dissolution crystallization, using common solvents such as ethyl acetate as a medium. It does not require high temperature, high pressure or complex equipment, and is simple to operate with low energy consumption.

[0024] The above overview is for illustrative purposes only and is not intended to be limiting in any way. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features of the invention will become readily apparent from the accompanying drawings and the following detailed description. Attached Figure Description

[0025] Figure 1 This is one of the characterization results of the nicotinamide-salicylic acid eutectic of the present invention;

[0026] Figure 2 The second figure shows the characterization results of the nicotinamide-salicylic acid eutectic of the present invention.

[0027] Figure 3 Figure 3 shows the characterization results of the nicotinamide-salicylic acid eutectic of this invention.

[0028] Figure 4 Figure 4 shows the characterization results of the nicotinamide-salicylic acid eutectic of this invention.

[0029] Figure 5 This is a single-crystal structure diagram of the nicotinamide-salicylic acid eutectic of the present invention;

[0030] Figure 6 This is an infrared overlay image of the eutectic formation of nicotinamide salicylic acid according to the present invention;

[0031] Figure 7 This is a comparison of simulated PXRD patterns of the nicotinamide-salicylic acid eutectic and single crystal of this invention; Detailed Implementation

[0032] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0033] The sample was tested under the following conditions:

[0034] (1) XRPD

[0035] Testing instrument: Rigaku SmartLab SE

[0036] Detection conditions: X-ray tube voltage 400V, X-ray tube current 40mA, scanning range 3-40° (2θ), step size 0.02°, scan speed 5° / min.

[0037] Testing basis: Appendix IX, X-ray powder diffraction method, People's Republic of China (2010 Edition, Part II).

[0038] (2) TGA

[0039] Testing instrument: Netzsch STA 449 F3

[0040] Detection conditions: Nitrogen gas, 50 mL / min

[0041] Scanning program: 30~400℃, heating rate: 10℃ / min

[0042] Sample weight tested: ~5 mg (alumina sample dish)

[0043] Testing standard: JY / T 014-1996 General Rules for Thermal Analysis

[0044] (3) DSC

[0045] Testing instrument: Netzsch STA 449 F3

[0046] Detection conditions: Nitrogen gas, 50 mL / min

[0047] Scanning program: 30~400℃, heating rate: 10℃ / min

[0048] Sample mass tested: ~3 mg (alumina sample dish)

[0049] Testing standard: JY / T 014-1996 General Rules for Thermal Analysis

[0050] (4) Micro ED

[0051] Testing instrument: JEOL 2100PLUS

[0052] Detection conditions: ambient temperature 100 K, accelerating voltage 200 kV, wavelength 0.0251 Å.

[0053] (5) Infrared spectrum

[0054] Testing instrument: PE Fourier transform infrared microscope system (Spotlight 200i)

[0055] Detection conditions: Potassium bromide tablet method

[0056] Testing standard: GB / T 6040-2002 General Rules for Infrared Spectroscopic Analysis

[0057] The technical solution provided by this invention:

[0058] Example 1

[0059] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of methanol to suspend it. After adding 1 eq. of salicylic acid and clarifying, stir overnight at room temperature to volatilize the solid and perform XRPD test to obtain nicotinamide-salicylic acid cocrystal.

[0060] PXRD pattern, DSC / TGA pattern, IR pattern, NMR pattern, and single crystal structure diagram of the eutectic are as follows: Figures 1-5 As shown in the attached image. The infrared spectra of the nicotinamide monomer, salicylic acid monomer, and the resulting cocrystal are overlaid. Figure 6 As shown, the crystal structure data are shown in Tables 1-7.

[0061] Table 1 Crystallographic parameters and structural refinement parameters

[0062]

[0063] Table 2 Atomic coordinates and isotropic parameters

[0064]

[0065] Table 3 Bond Lengths

[0066]

[0067] Table 4 Bond angles

[0068]

[0069] Table 5 Hydrogen Bonds

[0070]

[0071] Table 6 Twist Angle

[0072]

[0073] Table 7 Hydrogen atom coordinates

[0074]

[0075] Example 2

[0076] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of ethanol to suspend it. After adding 1 eq. of salicylic acid, it still thickens. Then stir overnight at room temperature. The solid is collected by centrifugation and XRPD test to obtain nicotinamide-salicylic acid cocrystal.

[0077] Example 3

[0078] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of ethyl acetate to suspend it. After adding 1 eq. of salicylic acid, it still thickened. Then, stir overnight at room temperature. The solid was collected by centrifugation and XRPD test to obtain nicotinamide-salicylic acid cocrystal.

[0079] Example 4

[0080] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of acetone / water mixed solvent to suspend it. After adding 1 eq. of salicylic acid and clarifying, stir overnight at room temperature to evaporate the solid and perform XRPD test to obtain nicotinamide-salicylic acid eutectic.

[0081] Example 5

[0082] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of methanol to suspend it. After adding 0.5 eq. of salicylic acid and clarifying, stir overnight at room temperature to volatilize the solid and perform XRPD test to obtain nicotinamide-salicylic acid eutectic (containing a small amount of nicotinamide).

[0083] Example 6

[0084] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of ethanol to suspend it. After adding 0.5 eq. of salicylic acid, it still thickened. Then, stir overnight at room temperature. The solid was collected by centrifugation and XRPD test was performed to obtain nicotinamide-salicylic acid cocrystal.

[0085] Example 7

[0086] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of ethyl acetate to suspend it. After adding 0.5 eq. of salicylic acid, it still thickened. Then, stir overnight at room temperature. The solid was collected by centrifugation and XRPD test was performed to obtain nicotinamide-salicylic acid cocrystal.

[0087] Example 8

[0088] Weigh 50 mg of nicotinamide into a sample vial and add 1 mL of acetone / water mixed solvent to suspend it. After adding 0.5 eq. of salicylic acid and clarifying, stir overnight at room temperature to evaporate the solid and perform XRPD test to obtain nicotinamide-salicylic acid eutectic.

[0089] Example 9

[0090] Weigh 50 mg of nicotinamide, add 200 μL of methanol, and grind it with 1 eq of salicylic acid in a mortar. Then collect the powder and perform PXRD test to obtain nicotinamide-salicylic acid eutectic.

[0091] Example 10

[0092] Weigh 50 mg of nicotinamide, add 200 μL of ethanol, and grind it with 1 eq of salicylic acid in a mortar. Then collect the powder and perform PXRD test to obtain nicotinamide-salicylic acid cocrystal.

[0093] Example 11

[0094] Weigh 50 mg of nicotinamide, add 200 μL of acetonitrile, and grind with 1 eq of salicylic acid in a mortar. Then collect the powder and perform PXRD test to obtain nicotinamide-salicylic acid cocrystal.

[0095] Example 12

[0096] Weigh 50 mg of nicotinamide, add 200 μL of ethyl acetate and grind in a mortar, then grind with 1 eq of salicylic acid in a mortar. Collect the powder and perform PXRD test to obtain nicotinamide-salicylic acid eutectic.

[0097] Example 13

[0098] Weigh 50 mg of nicotinamide, add 200 μL of acetone / water mixed solvent, and grind with 1 eq of salicylic acid in a mortar. Then collect the powder and perform PXRD test to obtain nicotinamide-salicylic acid eutectic.

[0099] Example 14

[0100] To prepare a nicotinamide-salicylic acid cocrystal on a large scale, 1 g of nicotinamide was weighed into a sample vial and 20 mL of ethanol was added to form a suspension. Then, 1 eq of salicylic acid was added, and the suspension was maintained. The mixture was stirred overnight at room temperature. The solid was collected by vacuum filtration and subjected to XRPD analysis to obtain the nicotinamide-salicylic acid cocrystal.

[0101] In this embodiment, the comparison results of the glycyrrhizin-salicylic acid eutectic amplification and single-crystal simulated PXRD are as follows: Figure 7 As shown.

[0102] Example 15

[0103] Physical stability test of nicotinamide-salicylic acid cocrystal: Approximately 30 mg of the cocrystal sample prepared in Example 14 was placed in environments at 60°C (closed), 25°C & 90%RH (open), under light irradiation (5000 Lux ± 500 Lux; closed), and under accelerated conditions at 40°C & 75%RH (open) for 5, 10, 20, and 30 days, respectively, and XRPD analysis was performed. The test results are shown in Table 8.

[0104] Table 8

[0105]

[0106] As shown in Table 8, the nicotinamide-salicylic acid eutectic exhibited no significant changes in crystal form and maintained stable physical properties after 5, 10, 20, and 30 days under various conditions, including 60℃ (closed), 25℃ & 90%RH (open), light irradiation (5000 Lux ± 500 Lux; closed), and accelerated conditions at 40℃ & 75%RH (open). This indicates that the nicotinamide-salicylic acid eutectic of this invention exhibits good solid-state stability.

[0107] Example 16

[0108] Stability test of nicotinamide: Approximately 30 mg of nicotinamide monomer and the cocrystal sample of Example 14 were placed in environments of 60°C (closed), 25°C & 90%RH (open), light irradiation (5000 Lux ± 500 Lux; closed), and accelerated conditions of 40°C & 75%RH (open) for 5 days, 10 days, 20 days, and 30 days, respectively, and the nicotinic acid content was determined.

[0109] Nicotinic acid content was determined by high performance liquid chromatography (HPLC). Chromatographic conditions: XBridge® C18 column, 4.6 x 250 mm (5 μm); mobile phase: potassium dihydrogen phosphate-acetonitrile-methanol (0-2 min, 90:5:5; 6 min, 35:10:55; 10 min, 35:20:45; 12 min, 35:55:10; 20 min, 35:55:10; 25 min, 95:5:5); detection wavelength: 262 nm; flow rate: 1.0 mL / min. －1 The column temperature was 35℃, and the injection volume was 5μL. The test results are shown in Table 9.

[0110] Table 9

[0111]

[0112] As shown in Table 9, compared to niacinamide alone, nicotinic acid was not detected in the niacinamide-salicylic acid cocrystal samples under conditions of high temperature, high humidity, light exposure, and accelerated aging. This result indicates that the formation of the cocrystal effectively inhibits the conversion of niacinamide to nicotinic acid, thereby significantly reducing the potential skin irritation caused by niacinamide.

[0113] Example 17

[0114] Biological solubility test: A certain mass of salicylic acid monomer and the cocrystal sample of Example 14 were weighed into sample bottles, and then 1-2 mL of water was added to form suspensions. All suspensions were shaken at 200 rpm at 37 °C, and samples were taken at 0.5 h, 2 h, 6 h, and 24 h. The filtrates were then analyzed by HPLC. The test results are shown in Table 10.

[0115] Table 10

[0116]

[0117] As shown in Table 10, the solubility of the cocrystal in aqueous solvents is significantly improved compared to that of the salicylic acid monomer. This increased solubility helps the cocrystal raw material to be more uniformly dispersed in aqueous solvents during application, enhancing its efficacy. Furthermore, after preparation as a cocrystal, the solubility of the "highly soluble" nicotinamide is significantly reduced, thereby improving its bioavailability and tolerability on human skin.

[0118] Example 18

[0119] The salicylic acid monomer and the cocrystal sample from Example Fourteen were subjected to a transdermal permeation test, as follows:

[0120] Step 1: Add water to the receiving cell and preheat it (the sample solubility must meet the leakage conditions during the experiment, with a temperature of 37±1℃).

[0121] Step 2: Secure the appropriately sized pigskin between the supply pool and the receiving pool;

[0122] Step 3: Replenish the receiving tank liquid, remove air bubbles, and place it in the diffusion tank for stirring;

[0123] Step 4: Prepare the test sample into a test cream according to a certain ratio, and add the cream to the supply tank;

[0124] Step 5: Take samples at regular intervals, collect / replenish the solution (1-6 hours), and then perform HPLC testing on the filtrate.

[0125] The test results are shown in Table 11.

[0126] Table 11

[0127]

[0128] As can be seen from Table 11, compared with salicylic acid monomer, the nicotinamide-salicylic acid cocrystal prepared in this invention can slow down the transdermal penetration rate of salicylic acid, reduce the cumulative penetration amount per unit time, achieve sustained release of salicylic acid, and reduce the irritation of salicylic acid to the skin.

[0129] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0130] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. A nicotinamide-salicylic acid eutectic, characterized in that: The eutectic comprises nicotinamide and salicylic acid molecules, and the molecular formula of nicotinamide-salicylic acid is C2. 13 H 12 N2O4, wherein the molar ratio of nicotinamide to salicylic acid is 1:1; The eutectic is a monoclinic crystal system, space group P21 / n, with cell parameters a = 11.080(2) Å, b = 5.0000(10) Å, c = 22.820(5) Å, α = 90°, β = 97.60(3)°, γ = 90°, and V = 1253.1(4) Å. 3 .

2. The nicotinamide-salicylic acid eutectic according to claim 1, characterized in that: The characteristic peaks of the nicotinamide-salicylic acid eutectic X-ray powder diffraction pattern are located at 2θ angles of 7.7°±0.2°, 8.3°±0.2°, 9.3°±0.2°, 13.1°±0.2°, 15.0°±0.2°, 15.5°±0.2°, 15.9°±0.2°, 16.7°±0.2°, 18.7°±0.2°, 20.6°±0.2°, 22.0°±0.2°, 23.4°±0.2°, 23.7°±0.2°, 24.4°±0.2°, 25.1°±0.2°, 26.4°±0.2°, 27.4°±0.2°, 28.2°±0.2°, 28.7°±0.2°, and 29.7°±0.2°.

3. The nicotinamide-salicylic acid eutectic according to claim 1, characterized in that: The differential scanning calorimetry spectrum of the eutectic showed a characteristic endothermic peak around 142.4±2℃.

4. The nicotinamide-salicylic acid eutectic according to claim 1, characterized in that: The infrared spectrum of the eutectic is at 3383.87 cm⁻¹. -1 ±2cm -1 3208.94cm -1 ±2cm -1 1668.96cm -1 ±2cm -1 1619.35cm -1 ±2cm -1 1308.30cm -1 ±2cm -1 1126.01cm -1 ±2cm -1 700.09cm -1 ±2cm -1 565.76cm -1 ±2cm -1 957.23cm -1 ±2cm -1 1155.36cm -1 ±2cm -1 934.39cm -1 ±2cm -1 523.65cm -1 ±2cm -1 644.72cm -1 ±2cm -1 760.23cm -1 ±2cm -1 793.83cm -1 ±2cm -1 821.74cm -1 ±2cm -1 850.40cm -1 ±2cm -1 1487.69cm -1 ±2cm -1 1448.60cm -1 ±2cm -1 1403.18cm -1 ±2cm -1 1363.17cm -1 ±2cm -1 1252.88cm -1 ±2cm -1 1190.52cm -1 ±2cm -1 1048.23cm -1 ±2cm -1 It has a characteristic peak.

5. A method for preparing a nicotinamide-salicylic acid eutectic, characterized in that, The method is selected from one of the following two methods: Method 1: Solid-state synthesis method Weigh 50 mg of nicotinamide into a sample vial and add the corresponding solvent to suspend it. Then add 1 eq. of salicylic acid and stir overnight at room temperature. If no solid precipitates, precipitate the solid by volatilization crystallization or dissolution crystallization. Collect the solid by centrifugation or filtration for XRPD testing. Method 2: Wet grinding method Weigh out a certain amount of nicotinamide and mix it with salicylic acid, then add 200 μL of the corresponding solvent, grind the solid with it in a mortar, and then collect the powder for PXRD testing.

6. The method for preparing nicotinamide-salicylic acid eutectic according to claim 5, characterized in that: In Method 2, the stoichiometric ratio of nicotinamide to salicylic acid is 1:

1.

7. The method for preparing nicotinamide-salicylic acid eutectic according to claim 5, characterized in that: In Method 1, the solvent is one or more of methanol, ethanol, ethyl acetate, and acetone / water mixed solvent; In Method 2, the solvent is one or more of methanol, ethanol, ethyl acetate, and acetone / water mixed solvent.

8. Use of a nicotinamide-salicylic acid eutectic as described in any one of claims 1 to 4 in the preparation of cosmetics.

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