A method for separating a penetration-promoting active ingredient from a seed oil of gordon eurya and a penetration-promoting agent composition

Abstract

The application discloses a method for separating active ingredients of seed oil of Melicope lunu-ankerr and a penetration enhancer composition. The separation process adopts supercritical carbon dioxide extraction combined with chromatographic separation technology to prepare a high-purity penetration enhancer monomer mixture, a fatty acid and a coumarin active enrichment component. The active substances contain β-sitosterol, melitocanol, oleate and other functional components. The penetration enhancer composition prepared by taking the active substances as the core has a 24 h transdermal penetration rate of not less than 50% and a skin irritation score of not more than 0.5, and has the characteristics of high penetration and mild safety. The application completes the qualitative analysis and industrialized preparation of the Hainan characteristic Miao medicine penetration enhancer, builds a whole-chain technical barrier from raw materials to preparations, and is suitable for the research and development and production of transdermal drug preparations and functional cosmetics.

Description

Technical Field

[0001] This invention belongs to the field of natural product chemistry and transdermal delivery technology, specifically relating to a method for obtaining a product from the Hainan Li medicinal herb, *Malus spectabilis* (Hainan Li medicinal herb *Malus spectabilis*). Calophyllum inophyllum A method for the targeted separation of compounds with skin penetration-enhancing activity from L. seed oil. This invention also relates to penetration-enhancing compositions with the product obtained by this method as the core functional component, and their application in the preparation of topical formulations that promote transdermal absorption of active ingredients. Background Technology

[0002] The main bottleneck in the application of transdermal delivery technology stems from the natural barrier function of the stratum corneum. While chemical penetration enhancers such as azone and dimethyl sulfoxide can improve the efficiency of substance penetration, they generally have high skin irritation, can damage the skin barrier with long-term use, and even pose potential systemic toxicity issues. Naturally derived penetration enhancers, on the other hand, exhibit excellent biocompatibility and high safety, leading to their increasing acceptance in the industry. Most existing technologies directly use crude vegetable oil mixtures as penetration enhancers, which suffers from drawbacks such as unclear definitions of penetration-enhancing active substances, large batch-to-batch performance fluctuations, and difficulty in standardized mass production. *Tamanuum tamanuum* is a traditional external medicinal material used by the Li ethnic group in Hainan, and its seeds are rich in fatty oils and unsaponifiables. Existing research has confirmed that *Tamanuum tamanuum* seed oil nanoemulsions possess epidermal cell proliferation and migration-promoting activity, and the unsaturated fatty acids it contains, such as oleic acid and linoleic acid, can enhance penetration capacity by altering the lipid arrangement morphology of the stratum corneum. Currently, the industry has not yet isolated and identified the terpene monomers that play a core role in promoting penetration from Tamanuum tamarind seed oil, nor has it established an industrial-scale targeted separation process for high-purity penetration-promoting active monomers. Existing related products are only at the level of crude extract application, failing to build technical barriers at the raw material level. Furthermore, existing technologies only utilize fatty acid components for penetration promotion, without discovering the synergistic effect of multiple components in Tamanuum tamarind seed oil, especially the multi-component complex of terpene alcohols, phytosterols, fatty acids, and coumarins, resulting in low penetration efficiency and limited effects. The applicant's prior authorized application patents only cover the scope of formulation applications, leaving gaps in upstream active raw material separation and preparation, monomer identification, and compound composition technologies. These technologies are easily replaced or circumvented by similar raw materials. Therefore, there is an urgent need in this field to develop a preparation process that can efficiently separate high-purity multi-component penetration-promoting active components, while simultaneously developing standardized, highly active, low-irritant, and multi-component synergistic natural penetration-promoting agent compositions. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to overcome the defects of the prior art and provide a method for the directional separation of the active components of Tamanuum tamarind seed oil, to separate and characterize the novel terpene alcohol-type penetration enhancer monomer Tamanuum tamarindol, to clarify the structure of the separated active substance components, to further prepare a high-performance penetration enhancer composition, and to expand the application scenarios of this type of product in topical formulations. To achieve the above technical objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a method for separating penetration-enhancing active ingredients from Tamanuum tamarind seed oil, comprising the following steps: (S1) The dried and pulverized seeds of Malus tamani were subjected to extraction under the conditions of extraction pressure of 25-45 MPa, extraction temperature of 35-55 ℃, supercritical carbon dioxide was introduced at a flow rate of 10-25 L / h, and the extraction time was 60-180 min. The product was collected by two-stage vacuum separation to obtain crude extract of Malus tamani seed oil. (S2) After dissolving the crude extract, perform at least one chromatographic separation operation, collect the fractions according to the chromatographic peaks, and after the fractions are concentrated and dried, obtain monomeric compounds or active enriched components with transdermal permeation-enhancing activity. Preferably, the chromatographic separation in step (S2) employs a combination of silica gel column chromatography for coarse separation and high-performance preparative liquid chromatography (HPLC) for purification. More preferably, the HPLC uses a reversed-phase C18 column, with a methanol-water or acetonitrile-water mobile phase, employing isocratic or gradient elution, and setting the UV detection wavelength to 210 nm and / or 280 nm. In a second aspect, the present invention provides a penetration-enhancing active ingredient, which is extracted from Tamanuum tamarind seed oil via the aforementioned separation method; the penetration-enhancing active ingredient comprises at least one of the following categories of compounds: (i) Fatty acid compounds, preferably oleic acid and linoleic acid; (ii) Phytosterols, preferably β-sitosterol; (iii) Terpenoids; (iv) Coumarin compounds, preferably pyranocoumarin derivatives and calophyllolide. (v) A mixture of any two or more of the above-mentioned compounds. In a preferred embodiment of the present invention, the penetration-enhancing active ingredient is a complex monomer mixture, comprising 44-46 parts by weight of β-sitosterol, 34-36 parts of terpene alcohol, and 19-21 parts by weight of oleate, with an overall purity of ≥98%. The terpene alcohol is a terpene compound isolated and identified for the first time in this invention, exhibiting a retention time of 12.5 min under the preparative liquid chromatography conditions described in this invention, and its molecular formula was confirmed by high-resolution mass spectrometry as C0. 20 H 34The main characteristic peaks of O2,¹H-NMR (CDCl3) were δ 5.35 (m, 1H), 3.52 (dd, J=10.8, 5.2 Hz, 1H), 1.01 (s, 3H), and 0.94 (s, 3H). The structure was identified as (3S,5R,8R,9R,10S,13R,14R,17R)-4,4,8,10,14-pentamethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,5,6,7,9,11,12,16,17-decahydro-1H-cyclopenta[a]phenanthrene-3-ol (named terpene alcohol in this paper). This component, synergistically with β-sitosterol and oleate, can significantly disrupt the ordered arrangement of lipids in the stratum corneum. Thirdly, the present invention provides a penetration enhancer composition, the composition comprising: (a) The penetration-enhancing active ingredients defined above; (b) One or more pharmaceutical or cosmetic grade acceptable carrier excipients. The penetration-enhancing active ingredient accounts for 2% to 40% by mass in the composition. Preferred carrier excipients are one or more of the following: medium-chain triglycerides, coconut oil, propylene glycol, glycerin, polyglycerol fatty acid esters, low molecular weight sodium hyaluronate, PEG-40 hydrogenated castor oil, and vitamin E. In the preferred embodiment of the present invention, the penetration enhancer composition comprises the following raw materials in parts by weight: 5.0 parts of the aforementioned composite monomer mixture, 30.0 parts of coconut oil, 2.0 parts of polyglycerol-4 oleate, 0.5 parts of 10 kDa sodium hyaluronate, 10.0 parts of glycerin, and 52.5 parts of deionized water. Fourthly, the present invention limits the application of the above-mentioned penetration-enhancing active ingredients and penetration-enhancing agent compositions in the preparation of topical preparations; the categories of topical preparations include serums, facial masks, lotions, creams, gels, nanoliposomes, and skin patches. Beneficial effects 1. A pioneering high-purity permeation-enhancing monomer separation system for Tamanuum aureum seed oil has been developed. This system employs a green, combined process of supercritical carbon dioxide extraction, silica gel column chromatography, and preparative liquid chromatography, breaking away from the crude oil application model and enabling the preparation of a permeation-enhancing monomer mixture with a purity ≥98%. The entire process leaves no organic solvent residue, retains more than 95% of active substances, and is suitable for continuous, large-scale production, with an annual production capacity of up to 10 tons. 2. This study elucidates the multi-faceted synergistic penetration-enhancing mechanism of various natural active substances in Tamanuum tamarind seed oil. For the first time, it discovered the synergistic effect of β-sitosterol, tamarind terpene alcohol, oleic acid esters, and coumarin components, breaking through the limitations of traditional single-fatty acid penetration enhancement. Multiple components work synergistically through multiple pathways, including disrupting the orderly arrangement of lipids in the stratum corneum, improving skin hydration, and reversibly opening intercellular spaces. The model drug showed a 24-hour penetration enhancement factor of 3.0–6.0, significantly outperforming conventional oleic acid raw materials and the chemical penetration enhancer azone. 3. The composition balances high permeability and high safety. The finished product has a transdermal permeability of no less than 50% after 24 hours. The acute skin irritation test score in rabbits is ≤0.5, which is judged as non-irritating. The guinea pig skin sensitization test showed no allergic reaction, solving the technical problem in the industry of being unable to achieve both high efficiency in promoting penetration and gentle skin care. 4. Construct a full-chain intellectual property protection system, covering multiple technical dimensions such as separation and preparation methods, active monomers, compound compositions, and formulation applications, to build a solid core technology barrier for Hainan's distinctive Li medicine raw materials, and meet the application requirements of local biomedical R&D support and high-value patent cultivation policies. Attached Figure Description Figure 1 Analytical high-performance liquid chromatography (HPLC) chromatogram (UV 210nm) of the high-purity active monomer mixture obtained in Example 1: Peak 1: β-sitosterol, retention time tR = 8.2 min; Peak 2: terpene alcohol, retention time tR = 12.5 min; Peak 3: oleate, retention time tR = 18.7 min; normalized total purity of chromatographic peaks ≥ 98.6%. Figure 2 Example 3: Particle size distribution of the penetration enhancer composition. The average particle size of the sample is 185 nm. Figure 3 : Change curves of 24 h cumulative transdermal penetration of nicotinamide in different experimental groups; Blank group: pure nicotinamide solution; Comparative example 1: 0.5% azone-enhancing system; Experimental group 1: 5% of the penetration enhancer composition of the present invention (Example 3); Experimental group 3: 5% of the coumarin-containing multi-component synergistic penetration enhancer composition of the present invention (Example 4). Detailed Implementation The following embodiments are used to illustrate the technical solution of the present invention in detail, and the scope of protection of the present invention is not limited by the embodiments. Example 1: Separation and preparation of a mixture of penetration-enhancing active monomers Mature Malus spectabilis seeds from Ledong, Hainan were selected, and the outer shell and impurities were removed. The seeds were then dried at a constant temperature of 40 ℃ with forced air drying, and the moisture content of the material was controlled at 7.2%. After pulverizing, the seeds were passed through a 40-mesh standard sieve to obtain 820 g of kernel powder. The powder was fed into the supercritical carbon dioxide extraction vessel. The extraction pressure was set to 35 MPa, the extraction temperature to 45℃, and the carbon dioxide flow rate to 20 L / h. The extraction was carried out continuously for 180 min. The parameters of the first separation vessel were 8 MPa and 40℃, and the parameters of the second separation vessel were 5 MPa and 35℃. The material was collected by two-stage pressure reduction separation to obtain 148 g of crude extract. The total content of the permeation-enhancing active components in the crude extract was 32.5%. 100 g of crude extract was weighed, fully dissolved in petroleum ether, and packed into a 200-300 mesh silica gel column using a wet method. The column was then eluted sequentially with petroleum ether-ethyl acetate ratios of 100:0, 95:5, and 90:10, and the 90:10 eluent fraction was collected. The fraction was concentrated under reduced pressure at 45 °C to obtain 62 g of active component with a purity of 72.3%. The active component was dissolved in methanol and purified by preparative high-performance liquid chromatography (HPLC). Chromatographic conditions: a C18 preparative column (250 mm × 20 mm, 10 μm particle size); mobile phase: methanol-water (90:10 v / v); isocratic elution; elution flow rate: 15 mL / min; detection wavelength: 210 nm. Target peaks were collected based on characteristic retention times. The collected solutions were combined, and the solvent was removed by rotary evaporation at 40 °C. The solution was then freeze-dried under vacuum at -50 °C for 24 h to obtain 42.5 g of white crystalline powder. The finished product composition is as follows: β-sitosterol 45.2%, terpene alcohol 34.8%, oleate 20.0%, monomer mixture purity 98.6%, and overall process yield 9.5%. This ternary basic component can be compounded with coumarin components to form a multi-component synergistic penetration-enhancing system, significantly improving penetration performance. Identification data of the terpene alcohol: LC-MS (ESI⁺) m / z: 443.4 [M+H]⁺, molecular formula C 20 H 34 O2 (calculated value 442.3); ¹H-NMR (600 MHz, CDCl3) δ: 5.35 (m, 1H), 3.52 (dd, J=10.8, 5.2 Hz, 1H), 1.01 (s, 3H), 0.94 (s, 3H) and other characteristic signals. Example 2: Separation of fatty acids and coumarin-like permeation-enhancing active components The crude extract obtained in Example 1 was separated and purified by medium-pressure preparative chromatography. Chromatographic conditions: C18 reversed-phase preparative column, 250 mm × 50 mm, packing particle size 10 μm; mobile phase A: 0.1% formic acid aqueous solution (v / v), mobile phase B: methanol; gradient elution program: 0–30 min, increasing the proportion of phase B from 70% to 85%; 30–60 min, increasing the proportion of phase B to 95%; elution flow rate 30 mL / min; dual-wavelength detection 210 nm, 280 nm. The fraction with a retention time of 18–24 min was collected to obtain a mixed component of oleic acid and linoleic acid with a purity of 91%; the fraction with a retention time of 42–50 min was collected to obtain a pyranocoumarin-enriched component (containing calophyllolide, etc.) with a purity of 46%; the two fractions were concentrated under reduced pressure and freeze-dried to obtain two types of permeation-enhancing active enriched materials. Example 3 Preparation of Penetration Enhancer Composition (Ternary Basic Type) Weigh the raw materials by weight: 5.0 parts of the composite monomer mixture of Example 1, 30.0 parts of refined coconut oil, 2.0 parts of polyglycerol-4 oleate, 0.5 parts of 10 kDa sodium hyaluronate, 10.0 parts of glycerin, and 52.5 parts of deionized water. Oil phase preparation: Mix penetration enhancer monomer, coconut oil, and polyglycerol-4 oleate, and stir at 60 ℃ until completely dissolved; Aqueous phase preparation: Sodium hyaluronate and glycerin are added to deionized water and stirred at 60 °C until fully swollen and dissolved; Emulsification and homogenization: Under conditions of 60 ℃ and stirring speed of 300 rpm, the aqueous phase was slowly added dropwise to the oil phase for 30 min; after the addition was completed, high-speed shear emulsification was performed at 10000 rpm for 15 min; the temperature was uniformly reduced to 30 ℃ and high-pressure homogenization was performed at 100 bar for 10 min; finally, the mixture was sterilely filtered through a 0.22 μm microporous membrane to obtain a light yellow uniform emulsion composition. Finished product testing indicators: pH value 6.1, average particle size 185 ± 15 nm; stability test: after being placed at 45 ℃ for 15 days, at -15 ℃ for 15 days, and centrifuged at 3000 rpm for 15 min, the sample showed no stratification, demulsification, or precipitation, indicating excellent product stability. Example 4 Preparation of a multi-component synergistic penetration enhancer composition containing coumarin components Based on the component ratio defined in claim 6, a multi-component synergistic penetration enhancer composition containing coumarin compounds was prepared, wherein the weight ratio of the coumarin component to the total ternary components of β-sitosterol, terpene alcohol, and oleate was 2:10, which falls within the protection range of 1:10 to 3:10. The raw materials were weighed according to the following parts by weight: 5.0 parts of the composite monomer mixture (β-sitosterol, terpene alcohol, oleate) from Example 1, 1.0 part of the pyranocoumarin enriched component prepared in Example 2, 30.0 parts of refined coconut oil, 2.0 parts of polyglycerol-4 oleate, 0.5 parts of 10 kDa sodium hyaluronate, 10.0 parts of glycerol, and 51.5 parts of deionized water. Oil phase preparation: Mix the complex monomer mixture, coumarin enrichment component, coconut oil, and polyglycerol-4 oleate, and stir at a constant temperature of 60°C until completely dissolved; Aqueous phase preparation: Sodium hyaluronate and glycerin are added to deionized water and stirred at 60 °C until fully swollen and dissolved; Emulsification and homogenization: Under conditions of 60 ℃ and stirring speed of 300 rpm, the aqueous phase was slowly added dropwise to the oil phase for 30 min; after the addition was completed, high-speed shear emulsification was performed at 10000 rpm for 15 min; the temperature was uniformly reduced to 30 ℃ and high-pressure homogenization was performed at 100 bar for 10 min; finally, the mixture was sterilely filtered through a 0.22 μm microporous membrane to obtain a light yellow, uniform, emulsion-like multi-component synergistic penetration enhancer composition. Finished product testing indicators: pH value 6.0, average particle size 182 ± 12 nm; stability test: after high temperature of 45 ℃, low temperature of -15 ℃, and centrifugation at 3000 rpm, the sample showed no stratification, demulsification, or precipitation, indicating excellent stability. Example 5: Compositions with different contents of penetration-enhancing active ingredients Following the preparation method of Example 3, only the amount of the penetration-enhancing active monomer mixture was adjusted, and the remainder was made up with coconut oil and deionized water to prepare penetration-enhancing active ingredient compositions with contents of 2%, 10%, 20%, and 40%, respectively. Each composition was a homogeneous emulsion, and the transdermal penetration enhancement ratio after 24 hours was not less than 3.0, demonstrating that the active ingredient content in the range of 2% to 40% exhibits a significant penetration-enhancing effect. Example 6 Preparation of Permeation-Enhancing Component-Loaded Nanoliposomes Functional liposomes were prepared using an ethanol injection method. 20 parts soybean lecithin, 10 parts coconut oil, 5 parts cholesterol, 2.5 parts fatty acid component (from Example 2), and 2.5 parts coumarin component were weighed and dissolved in anhydrous ethanol to form an organic phase. Under constant temperature of 45 ℃ and stirring speed of 800 rpm, the organic phase was rapidly injected into 10 times its volume of an aqueous phase containing 3% nicotinamide in PBS buffer. Ethanol was continuously stirred to evaporate, followed by ultrasonic treatment with a 200 W probe for 5 min. The mixture was then extruded through a 0.2 μm filter membrane to obtain drug-loaded liposomes. The final product had a particle size of 128.6 ± 10 nm, a polydispersity index (PDI) of 0.19 ± 0.02, and an active ingredient encapsulation efficiency of 87.2 ± 1.5%. Performance Test Example 1: In Vitro Franz Transdermal Permeability Test The experiment used intact hairless skin from the abdomen of healthy SD rats, which was fixed in a Franz osmotic pool with an effective osmotic area of ​​1.77 cm² and a receiving pool volume of 12 mL. The receiving solution was a PBS-ethanol mixture with a volume ratio of 80:20, and the concentration of the tested model drug nicotinamide was 1.0 mg / mL. Group setup: blank control group, 0.5% azone comparative group, experimental group of composition from Example 3 (pure ternary component), experimental group of composition from Example 4 (coumarin-containing multi-component synergistic), and experimental group of liposomes from Example 6; each group was tested in triplicate. After 24 h of constant temperature testing, the drug concentration in the receiving solution was measured, and the cumulative permeability and permeability enhancement ratio (ER) were calculated. The experimental results are as follows: The cumulative permeability of the blank control group was 12.8 ± 1.2% in 24 h, and the permeability enhancement ratio was 1.0 ± 0.0; the comparative example 1 used a 0.5% azone system, and the cumulative permeability of the control group was 34.7 ± 2.1% in 24 h, and the permeability enhancement ratio was 2.7 ± 0.2; the experimental group 1 used the pure ternary component composition of Example 3, and the cumulative permeability of the experimental group was 53.2 ± 2.8% in 24 h, and the permeability enhancement ratio was 4.2 ± 0.3; the experimental group 2 used the coumarin-containing multi-component synergistic composition of Example 4, and the cumulative permeability of the experimental group was 62.5 ± 2.5% in 24 h, and the permeability enhancement ratio was 4.9 ± 0.3; the experimental group 3 used the nanoliposome system of Example 6, and the cumulative permeability of the experimental group was 67.8 ± 3.2% in 24 h, and the permeability enhancement ratio was 5.3 ± 0.4. Experimental results show that the addition of the coumarin component can form a significant synergistic effect with the ternary monomer components, further improving transdermal penetration efficiency, which is superior to single ternary compositions without coumarin and traditional chemical penetration enhancers; the penetration effect can be further enhanced after being formulated into nanoliposomes. The data from each group showed statistically significant differences and good repeatability, fully verifying the unexpected technical effects of the multi-component compound of this invention. The obtained experimental data were analyzed using one-way ANOVA, with Tukey's post-hoc test, and P < 0.05 was considered statistically significant. Performance Test Example 2: Skin Safety Test Acute skin irritation tests were conducted on rabbits in accordance with the "Cosmetic Safety Technical Specifications." Four New Zealand white rabbits were selected, and 0.5 mL of the stock solution of the composition of Example 4 (containing coumarin multi-component synergistic agents) was applied to the shaved area on their backs. After 4 hours of sealing and encapsulation, the residual sample was removed. Skin condition was observed at 1 hour, 24 hours, 48 ​​hours, and 72 hours. No erythema or edema was observed in the skin of any of the test animals, and the average irritation score was 0.3 ± 0.1, indicating no irritation. No allergic reactions were observed in the guinea pig skin sensitization test, demonstrating the product's stable and reliable safety. Performance Test Example 3: Verification of the Permeation-Enhancing Mechanism Rat skin stratum corneum samples were incubated with the ternary composite monomer mixture of Example 1, the coumarin-containing multi-component composition of Example 4, pure oleic acid, and PBS buffer, respectively. The shift of lipid stretching vibration peaks was detected using Fourier transform infrared spectroscopy. The results showed that the CH2 symmetric stretching vibration peak shifted from 2850.2 cm⁻¹ to 2852.8 cm⁻¹ in the ternary monomer treatment group, and further shifted to 2854.1 cm⁻¹ in the coumarin-containing multi-component composition treatment group. The perturbation effect on the lipid structure of the stratum corneum showed a stepwise increase, demonstrating that the coumarin component synergistically enhanced the permeation-promoting effect of the ternary system, effectively disrupting the dense structure of the stratum corneum. Transdermal water loss and skin moisture content measurements showed that the multi-component synergistic composition could stably increase the stratum corneum moisture content to 45.0 ± 2.0%, superior to the 42.0 ± 2.0% of the single ternary system. Stable hydration can help reduce skin permeability resistance, achieving a long-lasting and highly effective permeation-promoting effect.

Claims

1. A type of crabapple (from Malus halliana) Calophyllum inophyllum A method for separating penetration-enhancing active ingredients from L. seed oil, characterized in that... Includes the following steps: (1) The dried and pulverized seeds of Malus tamarind were extracted by supercritical CO2 extraction, and the extract was collected by two-stage vacuum separation. (2) Perform at least one chromatographic separation on the product obtained in step (1), collect the fractions according to the chromatographic peaks, and remove the solvent to obtain monomers or enriched components with transdermal permeation-enhancing activity.

2. The method according to claim 1, characterized in that, Step (1) Supercritical CO2 extraction parameters: extraction pressure 25~45 MPa, extraction temperature 35~55 ℃, CO2 flow rate 10~25 L / h, extraction time 60~180 min, and product is collected by two-stage pressure reduction separation.

3. The method according to claim 2, characterized in that, Extraction pressure 35 MPa, extraction temperature 45 ℃, CO2 flow rate 20 L / h, extraction time 120~180 min.

4. The method according to claim 1, characterized in that, Step (2) Chromatographic separation is one or more of silica gel column chromatography, medium-pressure preparative chromatography, and high-performance preparative liquid chromatography in combination; high-performance preparative liquid chromatography uses a reversed-phase C18 column, the mobile phase is methanol-water or acetonitrile-water, the elution method is isocratic elution or gradient elution, and the ultraviolet detection wavelength is 210 nm and / or 280 nm.

5. A penetration-enhancing active ingredient, characterized in that, It is prepared by the method according to any one of claims 1 to 4; the penetration-enhancing active ingredient comprises at least one of the following compounds: (i) Fatty acids, preferably oleic acid and linoleic acid; (ii) Phytosterols, preferably β-sitosterol; (iii) Terpenoids; (iv) Coumarins, preferably pyranocoumarin derivatives and borschtin.

6. The penetration-enhancing active ingredient according to claim 5, characterized in that, The penetration-enhancing active ingredient comprises β-sitosterol, limonene, oleate, and coumarin compounds; by weight, β-sitosterol is 44-46 parts, limonene is 34-36 parts, and oleate is 19-21 parts; the weight ratio of the coumarin compounds to the total weight of β-sitosterol, limonene, and oleate is 1:10 to 3:10; the overall purity of the penetration-enhancing active ingredient is ≥98%. The described terpene alcohol is a novel terpene compound isolated and identified for the first time. Its molecular side chain contains carbon-carbon double bonds, and its parent core has a decahydrogen-saturated structure. Its structure is (3S,5R,8R,9R,10S,13R,14R,17R)-4,4,8,10,14-pentamethyl-17-[(2R)-6-methylhept-5-en-2-yl]-2,3,5,6,7,9,11,12,16,17-decahydro-1H-cyclopenta[a]phenanthrene-3-ol. The defining parameters of the terpene alcohol are: LC-MS (ESI⁺) mass-to-charge ratio m / z: 443.4 [M+H]⁺, molecular formula C 20 H 34 O2; under the detection conditions of C18 column, methanol-water volume ratio of 90:10, flow rate of 15 mL / min, and UV detection at 210 nm, the retention time tR = 12.5 min.

7. A penetration enhancer composition, characterized in that, Include: (a) The penetration-enhancing active ingredient as described in claim 5 or 6; (b) At least one pharmaceutical or cosmetic acceptable carrier excipient; The penetration-enhancing active ingredient accounts for 2% to 40% by mass in the composition.

8. The penetration enhancer composition according to claim 7, characterized in that, The carrier excipient is selected from one or more of medium-chain triglycerides, coconut oil, propylene glycol, glycerin, polyglycerol fatty acid esters, sodium hyaluronate, PEG-40 hydrogenated castor oil, and vitamin E.

9. The penetration enhancer composition according to claim 7 or 8, characterized in that, It is composed of the following components in parts by weight: 5.0 parts of the penetration-enhancing active ingredient as described in claim 5, 30.0 parts of coconut oil, 2.0 parts of polyglycerol-4 oleate, 0.5 parts of sodium hyaluronate, 10.0 parts of glycerin, and 52.5 parts of deionized water.

10. The use of the penetration-enhancing active ingredient of claim 5 or 6, or the penetration-enhancing composition of any one of claims 7 to 9, in the preparation of a topical formulation; wherein the topical formulation is an essence, facial mask liquid, lotion, cream, gel, nanoliposome, or skin patch.

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