Palmatine hydrochloride-pterostilbene eutectic crystal, preparation method thereof and application of palmatine hydrochloride-pterostilbene eutectic crystal as skin active component

Abstract

The invention discloses a palmatine hydrochloride-pterostilbene eutectic crystal, a preparation method thereof and application of the palmatine hydrochloride-pterostilbene eutectic crystal as a skin active component, and belongs to the technical field of biological medicines. The molecular formula of the palmatine hydrochloride-pterostilbene eutectic crystal is [2C16H16O3. 2C21H22ClNO3. H2O], and a basic structural unit is composed of two pterostilbene molecules, two palmatine hydrochloride molecules and a water molecule. The eutectic crystal belongs to a triclinic system, and the space group is P. Palmatine hydrochloride and pterostilbene are used as raw materials, the palmatine hydrochloride and the pterostilbene are mixed and dissolved in acetonitrile-water according to the molar ratio of 1: 1 to react, and the high-purity palmatine hydrochloride-pterostilbene eutectic crystal is obtained through slow volatilization. According to the co-crystal disclosed by the invention, the solubility of pterostilbene is improved, and the wet stability of palmatine hydrochloride is improved. The co-crystal effectively improves the anti-wrinkle, firming, whitening and other cosmetic effects, and provides an innovative solution for the combined application of palmatine hydrochloride and pterostilbene in the molecular level.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a palmatine-pterostilbene hydrochloride eutectic, its preparation method, and its application as a skin active ingredient. Background Technology

[0002] Co-crystallization refers to the bonding of two or more molecules together through intermolecular interactions (such as hydrogen bonds, van der Waals forces, and π-π interactions) to form a multi-component crystal with specific structure and properties. The two components are typically solids at room temperature, and there is a fixed stoichiometric ratio between them. Co-crystallization technology can significantly increase the number of crystalline forms of specific molecules without altering the covalent structure of the original compound, and can also improve the physicochemical properties of active ingredients, enhance bioavailability, and improve therapeutic efficacy.

[0003] Palmatine chloride (PCl), also known as berberine, is a typical isoquinoline alkaloid widely distributed in natural Chinese herbal medicines such as Phellodendron bark, Coptis chinensis, Gynostemma pentaphyllum, and Nandina domestica. It is highly soluble in water and possesses antibacterial, anti-inflammatory, antiviral, and antitumor medicinal properties. The structure of PCl contains one quaternary ammonium salt cation and a chloride ion (Cl...). - ), where Cl - As a potential hydrogen bond acceptor, it possesses low steric hindrance, good steric adaptability, and geometric ductility, enabling it to form strong charge-assisted hydrogen bonds with multiple hydrogen bond donors (such as amino, carboxyl, and hydroxyl groups). This characteristic makes it suitable for Cl-containing... - PCl has become an ideal candidate for drug cocrystal development. However, the presence of strong charge-assisted hydrogen bonds makes PCl highly hygroscopic, resulting in poor wet stability.

[0004] Pterostilbene (PTL), a methoxylated derivative of resveratrol, is a class of plant polyphenols with significant biological activity, widely distributed in blueberries, grapes, and sandalwood plants. This compound not only exhibits diverse pharmacological effects such as antitumor, anti-inflammatory, and cardiovascular protection, but its unique free radical scavenging ability can also activate the autophagy pathway, showing significant application potential in skin oxidative damage repair and anti-aging. Despite its significant biological activity, Pterostilbene's extremely low solubility severely limits its application. As a lipid-soluble molecule (LogP≈3.5), its poor water solubility directly restricts transdermal absorption. Therefore, improving the water solubility of Pterostilbene has become a key scientific challenge for its clinical translation. In recent years, researchers have focused on innovating nanodelivery systems to address the bottleneck in Pterostilbene's application. By developing carrier systems such as liposomes, nanoemulsions, lipid vesicles, and solid lipid particles, they have effectively improved its solubility, chemical stability, and in vitro and in vivo delivery efficiency, thereby broadening its application scenarios. Chinese invention patent CN115040420A discloses an improved scheme based on liposome encapsulation. While this technology effectively improves the solubility of pterostilbene in cosmetics and solves the problem of easy crystallization, its low drug loading capacity limits its application range. High concentrations are required to achieve efficacy, which weakens the practical value of the formulation system. Chinese invention patent CN118161410A proposes a pterostilbene lipid carrier based on exosome functionalization, which significantly improves transdermal efficiency. Another patent, CN117919107A, develops a pterostilbene nanocomposite carrier with a particle size distribution of 10-100 nm. Although both systems enhance transdermal drug delivery efficiency, their preparation processes involve complex steps and rely on a high proportion of excipients to maintain structural stability, limiting their practical application potential. Summary of the Invention

[0005] The purpose of this invention is to provide a palmatine hydrochloride-pterostilbene eutectic to improve the physicochemical properties of pterostilbene and palmatine hydrochloride.

[0006] To achieve the above-mentioned technical objectives, the present invention adopts the following technical solution: This invention, based on crystal engineering strategies, innovatively constructs a palmatine hydrochloride-pterostilbene (PCl-PTL) co-crystallization system. This technology, through the regulation of intermolecular interactions, directionally co-crystallizes the highly water-soluble palmatine hydrochloride with the poorly soluble pterostilbene, achieving a dual optimization objective: firstly, leveraging the strong hydrophilicity of palmatine hydrochloride to simultaneously enhance the solubility of pterostilbene; secondly, significantly improving the hygroscopic stability of palmatine hydrochloride through lattice rearrangement. This co-crystallization process, while fully preserving the original pharmacological activity of pterostilbene, not only overcomes the inherent limitations of its physicochemical properties, providing a structural basis for improved stability and enhanced efficacy of palmatine hydrochloride, but also exhibits synergistic benefits in anti-wrinkle, firming, and whitening effects.

[0007] Specifically, a palmatine hydrochloride-pterostilbene eutectic has the molecular formula [2C]. 16 H 16 O3·2C 21 H 22 [ClNO4·H2O] consists of two pterostilbene molecules, two palmatine hydrochloride molecules, and one water molecule as its basic structural unit.

[0008] Preferably, the eutectic belongs to the triclinic crystal system and has space group P. The unit cell parameters are: a = 13.66~14.02 Å, b = 15.70~16.10 Å, c = 17.49~17.89 Å, α = 91.61~92.02°, β = 108.26~108.62°, γ = 98.63~99.02°.

[0009] Preferably, the PXRD characteristic diffraction peaks of the eutectic appear at 5.42°±0.2, 7.31°±0.2, 13.88°±0.2, 16.12°±0.2, 16.44°±0.2, 24.08°±0.2, and 25.18°±0.2.

[0010] Preferably, the characteristic PXRD diffraction peaks of the eutectic appear at 5.42°±0.1, 7.31°±0.1, 13.88°±0.1, 16.12°±0.1, 16.44°±0.1, 24.08°±0.1, and 25.18°±0.1.

[0011] Preferably, the PXRD characteristic diffraction peaks of the eutectic appear at 5.42°, 7.31°, 13.88°, 16.12°, 16.44°, 24.08°, and 25.18°.

[0012] This invention provides a method for preparing the above-mentioned palmatine hydrochloride-pterostilbene eutectic, comprising the following steps: (1) Mix palmatine hydrochloride and pterostilbene hydrochloride in a 1:1 molar ratio to obtain a mixed powder; (2) Add acetonitrile-water mixed solvent to the mixed powder, stir at 45-55℃ for 3-5 h and then filter. Let the filtrate stand for 3-5 days and then slowly evaporate. The solid product is the eutectic of palmatine hydrochloride-pterostilbene hydrochloride.

[0013] Preferably, the volume ratio of acetonitrile to water in the acetonitrile-water mixed solvent is (1-2):1.

[0014] Preferably, the solid-liquid ratio of the mixed powder to the acetonitrile-water mixed solvent is 63 mg:(8-16) mL.

[0015] This invention also provides an application of the palmatine hydrochloride-pterostilbene cocrystal prepared by the above method as a skin active ingredient. When used as an active ingredient in skin care products, it has excellent anti-wrinkle, firming and whitening effects.

[0016] Compared with the prior art, the beneficial effects of the present invention are: (1) This invention is the first to prepare a stable eutectic of palmatine hydrochloride and pterostilbene hydrochloride by mixing palmatine hydrochloride and pterostilbene hydrochloride. The prepared drug eutectic powder has high purity and crystallinity. Furthermore, the eutectic of palmatine hydrochloride has a high dissolution rate and improves the wet stability of palmatine hydrochloride.

[0017] (2) The preparation method used in this invention is simple, with high yield and purity, low cost, and is suitable for large-scale production.

[0018] (3) The prepared palmatine hydrochloride-pterostilbene cocrystal can significantly enhance the anti-wrinkle, firming and whitening effects of cosmetics when used as a skin active ingredient. Attached Figure Description

[0019] Figure 1 This is a hydrogen bond diagram of the palmatine hydrochloride-pterostilbene eutectic of the present invention; Figure 2 The images show two-dimensional planar views of the palmatine hydrochloride-pterostilbene eutectic of the present invention, (a) a chain-like structure extending along the c-axis, and (b) a two-dimensional planar structure. Figure 3 This is a three-dimensional hydrogen bond packing diagram of the palmatine hydrochloride-pterostilbene eutectic of the present invention; Figure 4 Comparison of infrared spectra of pterostilbene raw material, palmatine hydrochloride and palmatine hydrochloride-pterostilbene cocrystal; Figure 5 Comparison of PXRD spectra of pterostilbene raw material, palmatine hydrochloride, and palmatine hydrochloride-pterostilbene eutectic; Figure 6 Comparison of the solubility of palmatine hydrochloride-pterostilbene eutectic and pterostilbene raw material in water; Figure 7 Comparison of the hygroscopic stability of palmatine hydrochloride-pterostilbene eutectic and palmatine hydrochloride raw material. Detailed Implementation

[0020] The technical solution of the present invention will be further described below with reference to specific embodiments, but it is not limited thereto.

[0021] Example 1 A palmatine hydrochloride-pterostilbene eutectic is prepared by the following method: (1) Mix palmatine hydrochloride and pterostilbene hydrochloride in a 1:1 molar ratio to obtain a mixed powder; (2) Add acetonitrile-water mixed solvent (volume ratio 1:1) to the mixed powder at a solid-liquid ratio of 63 mg: 8 mL, stir at 45 °C for 5 h and filter. Let the filtrate stand for 5 days and evaporate slowly. Collect the solid product to obtain palmatine hydrochloride-pterostilbene eutectic, with a yield of 88.6%.

[0022] Example 2 A palmatine hydrochloride-pterostilbene eutectic is prepared by the following method: (1) Mix palmatine hydrochloride and pterostilbene hydrochloride in a 1:1 molar ratio to obtain a mixed powder; (2) Add acetonitrile-water mixed solvent (volume ratio 2:1) to the mixed powder according to the solid-liquid ratio of 63 mg: 10 mL, stir at 50℃ for 4 h and filter. Let the filtrate stand for 4 days and slowly evaporate. Collect the solid product to obtain the eutectic of palmatine hydrochloride-pterostilbene hydrochloride with a yield of 88.9%.

[0023] Example 3 A palmatine hydrochloride-pterostilbene eutectic is prepared by the following method: (1) Mix palmatine hydrochloride and pterostilbene hydrochloride in a 1:1 molar ratio to obtain a mixed powder; (2) Add acetonitrile-water mixed solvent (volume ratio 1:1) to the mixed powder at a solid-liquid ratio of 63 mg: 16 mL, stir at 55°C for 5 h, filter, let the filtrate stand for 5 days and slowly evaporate, collect the solid product to obtain palmatine hydrochloride-pterostilbene eutectic, with a yield of 88.1%.

[0024] Product structure characterization and results The palmatine hydrochloride-pterostilbene eutectic prepared by this invention is a colorless, elongated crystal. Single crystal samples can be selected from it for X-ray single crystal diffraction to determine the accurate structure of the pterostilbene-palmatine hydrochloride eutectic.

[0025] Select high-quality single-crystal samples of suitable size from the palmatine-pterostilbene hydrochloride eutectic product prepared in Example 1 for X-ray single-crystal diffraction. An Agilent Xcalibur Eos diffractometer was used, employing Cu-Kα ray scanning monochromated with a graphite monochromator in ω-scan mode. The required current and voltage for the diffraction experiment were set to 40 mA and 50 kV, respectively.

[0026] The results showed that the molecular formula of the palmatine hydrochloride-pterostilbene eutectic in this embodiment was [2C]. 16 H 16 O3·2C 21 H 22[ClNO4·H2O] consists of two pterostilbene molecules, two palmatine hydrochloride molecules, and one water molecule as its basic structural unit. This palmatine hydrochloride-pterostilbene eutectic belongs to the triclinic crystal system with space group P. The unit cell parameters are: a = 13.66~14.02 Å, b = 15.70~16.10 Å, c = 17.49~17.89 Å, α = 91.61~92.02°, β = 108.26~108.62°, γ = 98.63~99.02°. Its characteristic PXRD diffraction peaks appear at 5.42°, 7.31°, 13.88°, 16.12°, 16.44°, 24.08°, and 25.18°.

[0027] Single-crystal structure analysis shows that 2PTE-2PCl·H2O is a triclinic crystal system, P The space group contains 2 PTE molecules, 2 PCl molecules, and 1 water molecule in its crystal structure. For example... Figure 1 The phenolic hydroxyl group in the pterostilbene structure shown forms an O1-H1···O15 hydrogen bond with one O atom in a water molecule. The water molecule also simultaneously forms a Cl atom. − Formation of O15-H15···Cl2A − Hydrogen bonding. Pterostilbene molecules, water molecules, and Cl... − They are connected by the various hydrogen bonds mentioned above, forming a one-dimensional chain structure. Figure 2 a). The formed chains are connected to each other through the OH···O interaction between different pterostilbene molecules, thus forming a two-dimensional layered structure ( Figure 2 b). Under the influence of weak intermolecular forces, a stacking structure is formed between the layers ( Figure 3 ).

[0028] Infrared characterization of palmatine hydrochloride-pterostilbene eutectic: Infrared spectroscopy was performed using a Bruner Tensor 27 Fourier transform infrared spectrometer. The scanning wavelength range was 4000–400 cm⁻¹. -1 The sample obtained in Example 1 was prepared using KBr solid pellets. The obtained spectral data are as follows: Figure 4 As shown, in PCl·3H2O, the stretching vibration peak of water molecules is 3602~3222 cm⁻¹. -1 The stretching vibration peak of -OH in pterostilbene is at 3347 cm⁻¹. −1 At this point, the stretching vibration peak of -OH in the eutectic hydrate is significantly red-shifted to 3004 cm⁻¹. −1 This indicates a strong hydrogen bond interaction between PTE and PCl molecules through the -OH group. Furthermore, after the formation of the eutectic hydrate, the bending vibration peak of the -OH group in PTE changes from 1201 cm⁻¹.-1 Moved to 1145 cm -1 This is because hydrogen bonds are formed between the -OH group on PTE and PCl and water molecules.

[0029] Purity determination of palmatine hydrochloride-pterostilbene eutectic: Powder X-ray diffraction data were determined using a BRUKER D8 X-ray diffractometer (Germany). Test conditions: Cu-Kα target tube voltage 40 kV, tube current 10 mA, scan rate 2 ° / min. Figure 5 As shown, by comparing the palmatine-pterostilbene hydrochloride eutectic obtained in Example 1 with the two raw materials, it can be seen that the positions and intensities of its characteristic diffraction peaks have changed significantly, indicating the formation of a new phase. To further determine the phase and purity of the palmatine-pterostilbene hydrochloride eutectic sample obtained in this invention, the PXRD spectrum of the obtained palmatine-pterostilbene hydrochloride eutectic sample was measured in this example. The spectrum was compared with the theoretical spectrum of the palmatine-pterostilbene hydrochloride eutectic obtained by simulating the crystal data using Mercury software based on X-ray single-crystal diffraction experiments. Figure 5 The characteristic diffraction peaks shown appear at 5.42°, 7.31°, 13.88°, 16.12°, 16.44°, 24.08°, and 25.18°. The powder diffraction peaks are sharp and consistent with the theoretical diffraction peaks of the palmatine hydrochloride-pterostilbene eutectic sample, indicating that the prepared palmatine hydrochloride-pterostilbene eutectic has high crystallinity and purity. The eutectic was prepared by combining palmatine hydrochloride and pterostilbene through intermolecular hydrogen bonds, with a molar ratio of 1:1 and a solid-liquid ratio of 63 mg to (8-16) mL. This ratio range is the core parameter for ensuring the stability and property improvement effect of the eutectic of this invention; any result exceeding this ratio will not form the eutectic product described in this invention and achieve the corresponding application effects.

[0030] Performance testing 1. Solubility determination An excess of the sample to be tested was added to purified water and shaken at 37°C for 24 hours to obtain a supersaturated solution. The supernatant was filtered through a 0.45 μm filter membrane, and its mass concentration was measured to obtain the saturated equilibrium solubility of the sample. The results are as follows: Figure 6 As shown, the solubility of pterostilbene in pure water is 0.02 mg / mL, while the solubility in cocrystallized pterostilbene increases to 1.44 mg / mL. These results clearly demonstrate that cocrystallization with palmatine hydrochloride significantly improves the solubility of pterostilbene. These findings lay the foundation for improving the bioavailability of pterostilbene.

[0031] 2. Stability determination Hygroscopicity tests were conducted by placing the samples in a stability testing chamber maintained at 25 °C with relative humidity (RH) of 98%, 80%, and 75%. The eutectic and PCl samples were ground into powder and placed in open glass bottles. The powders were weighed every 24 hours using an electronic balance until the weight stabilized (n = 3). The results are as follows: Figure 7 As shown. From Figure 7 As can be seen, the moisture absorption rates of PCl were 8.07%, 16.77%, and 19.11% at relative humidity of 75%, 80%, and 98%, respectively. Under the same environmental conditions, the moisture absorption rates of the eutectic were 2.54%, 3.08%, and 5.11%, respectively, indicating that the formation of the eutectic effectively improved the moisture absorption stability of palmatine hydrochloride.

[0032] 3. Application effect verification 1) Verification of anti-wrinkle and firming effects To further verify the application effect of the palmatine hydrochloride-pterostilbene cocrystal prepared in this invention, anti-wrinkle and firming effects were tested. The physical mixing group was obtained by physically mixing palmatine hydrochloride and pterostilbene at a 1:1 molar ratio. The anti-wrinkle and firming effects of the cocrystal were evaluated by the content of fibrous collagen I and matrix metalloproteinase 1 (MMP-1). The experiment was grouped according to Table 1, as detailed below: Table 1. Anti-wrinkle and firming experimental grouping table

[0033] Specific experimental methods: (1) Cell seeding: The cells were seeded at a rate of 8 × 10⁶ cells / year. 4 The cells were seeded at a density of / wells in 24-well plates and incubated overnight at 37°C in a 5% CO2 incubator.

[0034] (2) Experimental grouping: The experiment was set up with blank control group, negative control group, positive control group, physical mixing group and eutectic group obtained in Example 1.

[0035] (3) Preparation of working solution: Prepare working solutions of test substances of various concentrations according to the experimental design table.

[0036] (4) Drug administration: When the cell plating rate reaches 40% to 60%, add 1 mL of basic culture medium to each well for blank group and negative group; add 1 mL of culture medium containing 100 μg / mL vitamin C and 8 μg / mL vitamin E to each well for positive group; add 1 mL of culture medium containing the corresponding concentration of test substance to each well for sample group.

[0037] (5) UVA radiation treatment: 24 h after drug administration, the control group was subjected to UVA radiation at a dose of 0 J / cm. 2 In the environment; other groups: received 10 J / cm2 UVA radiation.

[0038] (6) Collection of supernatant: After incubation for 24 h, collect the cell supernatant into EP tubes and freeze at -80℃ for later use.

[0039] (7) Collagen I detection: Determine the content of Collagen I in the sample according to the instructions of the ELISA kit.

[0040] (8) MMP-1 detection: Determine the MMP-1 content in the sample according to the instructions of the ELISA kit.

[0041] The test results are shown in Tables 2-3.

[0042] Table 2 Summary of Collagen I Detection and Analysis Results

[0043] Note: When performing statistical analysis using the t-test, the significance of the NC group compared to the BC group is expressed as follows: # P < 0.05 indicates that # P<0.01 indicates that ## Compared with the NC group, the PC group and the sample group showed significant differences. P < 0.05 indicates that P<0.01 indicates that .

[0044] Table 3 Summary of MMP-1 Detection Results

[0045] Note: When performing statistical analysis using the t-test, the significance of the NC group compared to the BC group is expressed as follows: # P < 0.05 indicates that # P<0.01 indicates that ## Compared with the NC group, the PC group and the sample group showed significant differences. P < 0.05 indicates that P<0.01 indicates that .

[0046] The results in Table 2 show that the cocrystal group significantly increased the Collagen I content level compared to the positive control group and the physical mixture group; Table 3 shows that the group also had a significantly stronger inhibitory effect on MMP-1 content level than the latter two. These results collectively demonstrate that the palmatine hydrochloride-pterostilbene cocrystal has superior anti-wrinkle and firming effects.

[0047] 2) Whitening efficacy verification To further evaluate its whitening efficacy, the palmatine hydrochloride-pterostilbene cocrystal and their physical mixture from Example 1 were selected. The cell melanin inhibition rate was used as the evaluation index, and experiments were conducted according to the groups listed in Table 4. The specific procedures are as follows: Table 4 Experimental Design for Inhibiting Cellular Melanin Synthesis

[0048] Specific experimental method: Logarithmic growth phase cells were subjected to a 3×10⁻⁶... 5 Cells were seeded at a density of [number] cells / well in 24-well plates and incubated at 37°C with 5% CO2 for 24 hours. Samples were then added according to the groups listed in Table 4, with untreated cells serving as a blank control. Each group had three replicates. After sample addition, the plates were incubated for another 24 hours under the same conditions. The culture medium was discarded, and 1 mL of 1M NaOH solution containing 10% DMSO was added to each well. The plates were then transferred to an 80°C oven for 2 hours. After returning to room temperature, 200 μL of the solution was transferred from each well to a 96-well microplate. Using the 1M NaOH solution containing 10% DMSO as a blank control, the absorbance was measured at 405 nm, and the relative inhibition rate of melanin production was calculated. The results are shown in Table 5.

[0049] Cellular melanin inhibition rate % ×100% Table 5 Summary of Cellular Melanin Synthesis Inhibition Rate Results

[0050] Note: When performing statistical analysis using t-test, the significance of the sample group, PC group, and BC group is expressed as follows: P < 0.05 indicates that P<0.01 indicates that .

[0051] As can be seen from the results in Table 5 above, the cocrystal group can significantly inhibit melanin synthesis, which indicates that the whitening effect of palmatine hydrochloride-pterostilbene cocrystal is more significant.

[0052] It should be noted that the above embodiments are merely some preferred embodiments of the present invention, and not all embodiments. Obviously, based on the above embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

Claims

1. A palmatine hydrochloride-pterostilbene eutectic, characterized in that, Its molecular formula is [2C] 16 H 16 O3·2C 21 H 22 [ClNO4·H2O] consists of two pterostilbene molecules, two palmatine hydrochloride molecules, and one water molecule as its basic structural unit.

2. The palmatine-pterostilbene hydrochloride eutectic according to claim 1, characterized in that, The eutectic belongs to the triclinic crystal system and has space group P. The unit cell parameters are: a = 13.66~14.02 Å, b = 15.70~16.10 Å, c = 17.49~17.89 Å, α = 91.61~92.02°, β = 108.26~108.62°, γ = 98.63~99.02°.

3. The palmatine-pterostilbene hydrochloride eutectic according to claim 1, characterized in that, The characteristic PXRD diffraction peaks of the eutectic appear at 5.42°±0.2, 7.31°±0.2, 13.88°±0.2, 16.12°±0.2, 16.44°±0.2, 24.08°±0.2, and 25.18°±0.

2.

4. A method for preparing palmatine-pterostilbene hydrochloride eutectic according to any one of claims 1-3, characterized in that, Includes the following steps: (1) Mix palmatine hydrochloride and pterostilbene hydrochloride in a 1:1 molar ratio to obtain a mixed powder; (2) Add acetonitrile-water mixed solvent to the mixed powder, stir at 45-55℃ for 3-5 h and then filter. Let the filtrate stand for 3-5 days and then slowly evaporate. The solid product is the eutectic of palmatine hydrochloride-pterostilbene hydrochloride.

5. The method for preparing palmatine hydrochloride-pterostilbene eutectic according to claim 4, characterized in that, The volume ratio of acetonitrile to water in the acetonitrile-water mixed solvent is (1-2):

1.

6. The method for preparing palmatine hydrochloride-pterostilbene eutectic according to claim 4, characterized in that, The solid-liquid ratio of the mixed powder to the acetonitrile-water mixed solvent is 63 mg:(8-16) mL.

7. The use of palmatine hydrochloride-pterostilbene eutectic as a skin active ingredient according to any one of claims 1-3.

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