CN-122010927-A - Palmatine hydrochloride-pterostilbene eutectic crystal, preparation method thereof and application thereof as skin active ingredient

Abstract

The invention discloses a palmatine hydrochloride-pterostilbene eutectic crystal, a preparation method thereof and application thereof as a skin active ingredient, and belongs to the technical field of biological medicines. The molecular formula of the palmatine hydrochloride-pterostilbene eutectic crystal is [2C 16 H 16 O 3 ·2C 21 H 22 ClNO 4 ·H 2 O ], and a basic structural unit is formed by two pterostilbene molecules, two palmatine hydrochloride molecules and one water molecule. The eutectic belongs to a triclinic system, and the space group is P . The palmatine hydrochloride and the pterostilbene are taken as raw materials, mixed and dissolved into acetonitrile-water to react according to the mol ratio of 1:1, and the palmatine hydrochloride-pterostilbene eutectic with high purity is obtained through slow volatilization. The eutectic crystal improves the solubility of pterostilbene and improves the wet stability of palmatine hydrochloride. The eutectic effectively improves the effects of cosmetics such as wrinkle resistance, compactness and whitening, and provides an innovative solution for the combined application of palmatine hydrochloride and pterostilbene in a molecular level.

Inventors

• ZHAO YABIN
• DAI MENGXUAN
• FAN LIN
• LIU LU
• CHEN XIANGZHU
• JIANG FEI
• YU YUEMING
• ZHANG ZENGTAO
• ZHANG CHUN

Assignees

• 临沂大学

Dates

Publication Date

20260512

Application Date

20260127

Claims (7)

1. 1. The palmatine hydrochloride-pterostilbene eutectic crystal is characterized in that the molecular formula is [2C 16 H 16 O 3 ·2C 21 H 22 ClNO 4 ·H 2 O ], and a basic structural unit is formed by two pterostilbene molecules, two palmatine hydrochloride molecules and one water molecule.
2. 2. The palmatine hydrochloride-pterostilbene co-crystal of claim 1, wherein the co-crystal belongs to a triclinic system and the space group is 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. 3. The palmatine hydrochloride-pterostilbene co-crystal of claim 1, wherein PXRD characteristic diffraction peaks of the co-crystal occur 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, 25.18 ° ± 0.2.
4. 4. A process for the preparation of the palmatine hydrochloride-pterostilbene co-crystal of any one of claims 1 to 3, comprising the steps of: (1) Mixing palmatine hydrochloride and pterostilbene according to a molar ratio of 1:1 to obtain mixed powder; (2) And adding an acetonitrile-water mixed solvent into the mixed powder, stirring at 45-55 ℃ for 3-5 h hours, filtering, standing filtrate, and slowly evaporating for 3-5 days to obtain a solid product, namely the palmatine hydrochloride-pterostilbene eutectic.
5. 5. The method for preparing palmatine hydrochloride-pterostilbene co-crystal according to claim 4, wherein the volume ratio of acetonitrile to water in the acetonitrile-water mixed solvent is (1-2): 1.
6. 6. The method for preparing a palmatine hydrochloride-pterostilbene co-crystal according to claim 4, wherein the solid-to-liquid ratio of the mixed powder to the acetonitrile-water mixed solvent is 63mg (8-16) mL.
7. 7. Use of a palmatine hydrochloride-pterostilbene co-crystal as claimed in any one of claims 1 to 3 as a skin active ingredient.

Description

Palmatine hydrochloride-pterostilbene eutectic crystal, preparation method thereof and application thereof as skin active ingredient Technical Field The invention relates to the technical field of biological medicines, in particular to a palmatine hydrochloride-pterostilbene eutectic crystal, a preparation method thereof and application thereof as a skin active ingredient. Background Co-crystallization refers to the bonding together of two or more molecules by intermolecular interactions (e.g., hydrogen bonds, van der Waals forces, pi-pi interactions, etc.), forming multicomponent crystals having specific structures and properties. Wherein the two components are typically solid at room temperature and there is a fixed stoichiometric ratio between the components. The co-crystallization technology can not only greatly increase the number of crystal forms of specific molecules without changing the covalent structure of the original compound, but also improve the physicochemical properties of the active ingredients, bioavailability, curative effect and the like. Palmatine hydrochloride (PALMATINE CHLORIDE, PCl), which is known as fibrauretine, belongs to a typical isoquinoline alkaloid and is widely distributed in natural Chinese herbal medicines such as cortex phellodendri, rhizoma coptidis, radix berberidis, nandinae Domesticae, etc. It has good solubility in water, and has antibacterial, antiinflammatory, antiviral and antitumor effects. The structure of PCL contains 1 quaternary ammonium salt cation and chloride ion (Cl -), wherein Cl - is used as a potential hydrogen bond acceptor, has small steric hindrance, good space adaptability and geometric ductility, and can form stronger charge-assisted hydrogen bonds with a plurality of hydrogen bond donors (such as amino, carboxyl, hydroxyl and the like), so that PCL containing Cl - becomes an ideal candidate for pharmaceutical eutectic development. Meanwhile, the PCl has strong water absorbability due to the existence of strong charge-assisted hydrogen bonds, so that the PCl has the defect of poor wet stability. Pterostilbene (Pterostilbene, PTL) is a plant polyphenol with remarkable biological activity as a methoxy modified product of resveratrol, and is widely distributed in blueberry, grape and santalum plants. The compound not only shows multiple pharmacological actions such as anti-tumor, anti-inflammatory and cardiovascular protection, but also has the unique free radical scavenging capability and can show important application prospects in the fields of skin oxidative damage repair and aging resistance by activating cell autophagy paths. Although pterostilbene has significant biological activity, its extremely low solubility severely limits the range of applications. As a fat-soluble molecule (logp≡3.5), the poor water solubility of pterostilbene directly restricts transdermal absorption. Therefore, increasing the water solubility of pterostilbene is a key scientific challenge to achieve its clinical transformation. Aiming at the application bottleneck of pterostilbene, researchers focus on the innovation of a nano delivery system in recent years, and the dissolution characteristic, chemical stability and in-vivo and in-vitro delivery efficiency of the pterostilbene are effectively improved by developing carrier systems such as liposome, nanoemulsion, lipid-like vesicles and solid lipid plasmids, so that the application scene of the pterostilbene is widened. The Chinese patent No. 115040420A discloses an improved scheme based on liposome encapsulation, which can effectively improve the solubility of pterostilbene in cosmetics and solve the problem of easy crystallization. However, the low drug loading rate limits the application range, and the efficacy is realized by adding the drug in high concentration, so that the practical value of the formula system is weakened. The Chinese patent CN118161410A proposes a pterostilbene lipid carrier based on exosome functionalization, and the transdermal efficiency of the pterostilbene lipid carrier is obviously improved. Another patent CN117919107A develops a pterostilbene nano composite carrier, and the particle size distribution is 10-100nm. Although both systems enhance the transdermal delivery efficiency of the drug, the preparation process involves complex process steps, and relies on high proportion of auxiliary materials to maintain structural stability, limiting the practical application potential. Disclosure of Invention The invention aims to provide a palmatine hydrochloride-pterostilbene eutectic to improve physicochemical properties of pterostilbene and palmatine hydrochloride. In order to achieve the technical purpose, the invention adopts the following technical scheme: The invention creatively constructs a palmatine hydrochloride-pterostilbene (PCl-PTL) eutectic system based on a crystal engineering strategy. According to the technology, through intermolecular interaction regulation and control, the pa