A penetration-enhancing composition and its preparation method and application

Through the synergistic effect of hemolytic lecithin and compound plant extracts, the penetration problem of conus toxin in the skin is solved, and the efficient percutaneous absorption and skin improvement effect of conus peptide are achieved, which is suitable for cosmetic formulations.

CN119950380BActive Publication Date: 2025-09-09N O D TOPIA (GUANGZHOU) BIOTECHNOLOGY CO LTD
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Patent Information

Application Number
CN202510193596.X
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-02-21
Publication Date
2025-09-09
Estimated Expiration
2045-02-21

AI Technical Summary

Technical Problem

Existing technologies make it difficult to effectively promote the penetration of cone snail toxin (CTX) into the skin, especially due to the molecular weight and hydrophilic properties caused by its annular spatial structure. Traditional penetration enhancer systems are complex and not suitable for cosmetic formulations.

Method used

The synergistic effect of hemolysed lecithin and complex plant extracts (including angelica, clove, salvia miltiorrhiza and licorice) is used to affect skin proteins and lipids, open up trans-cell membrane and intercellular lipid penetration pathways, and enhance the transdermal absorption of cono peptides.

Benefits of technology

It significantly increases the transdermal absorption of conoside peptide, improves skin elasticity and wrinkles, provides a natural wrinkle removal effect, and avoids stiff facial expressions.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention discloses a penetration-promoting composition and its preparation method and application, relating to the field of cosmetic technology. The present invention provides a penetration-promoting composition, comprising the following components in parts by weight: 0.01-0.3 parts of cono peptide, 0.1-8 parts of lysolecithin and 0.1-8 parts of a composite plant extract; the composite plant extract comprises the following raw materials: angelica, cloves, salvia miltiorrhiza and liquorice. The present invention uses a specific amount of lysolecithin and a composite plant extract to synergize, while affecting skin proteins and lipids, opening up two pathways of transcellular membrane penetration and intercellular lipid penetration, effectively improving the transdermal absorption and intradermal accumulation of cono peptides, and compared with traditional penetration enhancers, the improvement effect is obvious.
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Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, in particular to a penetration-enhancing composition and a preparation method and application thereof. Background Art

[0002] In currently widely used products, peptides with anti-wrinkle properties, such as palmitoyl pentapeptide and acetyl hexapeptide, have been added, achieving significant results in wrinkle repair. Therefore, the use of peptide raw materials for anti-wrinkle has also become an extremely hot research direction in the field of skin anti-aging. Conotoxins are a series of bioactive peptides secreted by the venom glands on the inner wall of the venom tube and venom sac of the marine gastropod mollusk cone snail. Among them, μ-conotoxin CnIIIC (CTX) has been found to specifically block the Nav 1.4 subtype sodium ion channel in muscles to block the conduction of action potentials, thereby inhibiting muscle contraction and ultimately achieving the effect of preventing and reducing wrinkles. At the same time, CTX retains some neuromuscular current transmission, which can avoid facial expression paralysis and prevent the skin from being too tight and stiff, thereby achieving a natural wrinkle removal effect. CTX is a cyclic peptide with a ring-shaped spatial structure composed of 22 amino acid residues, with a molecular weight of 2375.8 Da, an isoelectric point of 8.29, and an average hydrophilicity coefficient of -0.864. Due to its medium molecular weight, low hydrophilicity, and cyclic structure, CTX is severely hindered by the dense, hydrophobic stratum corneum when entering the dermis to exert its anti-wrinkle properties. Therefore, to better exert the anti-wrinkle function of CTX, it is necessary to promote skin penetration through external means.

[0003] Current research on the skin penetration enhancement of CTX mainly focuses on the use of encapsulation systems, by preparing it into nanoparticles or using ionic liquids to assist penetration. These methods have increased the penetration of CTX in the skin to a certain extent, but the system preparation is relatively complex, and it is uncertain whether it can be applied to the further addition and application of subsequent cosmetic formulas. In contrast, if a penetration enhancer can be used to promote the penetration of CTX, it is a simple and convenient way and easy to add to the cosmetic formula. However, there are many and extensive substances with skin penetration enhancement properties, so how to select a system with a relatively large molecular weight cono peptide that enhances the penetration of hydrophilic molecules is one of the technical difficulties that can be overcome at present.

[0004] Currently, no suitable selection has been reported in the research on the permeation enhancer system for promoting the transdermal penetration of cyclic peptides having a ring-shaped spatial structure. Summary of the Invention

[0005] Based on this, the purpose of the present invention is to overcome the shortcomings of the above-mentioned prior art and provide a penetration-enhancing composition that simultaneously affects skin proteins and lipids, opens up two pathways of trans-cell membrane penetration and intercellular lipid penetration, as well as its preparation method and application.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is: a penetration-enhancing composition, comprising the following components in parts by weight: 0.01-0.3 parts of conoside peptide, 0.1-8 parts of lysolecithin and 0.1-8 parts of a composite plant extract; the composite plant extract comprises the following raw materials: angelica sinensis, cloves, salvia miltiorrhiza and liquorice.

[0007] Cono peptide is a cyclic peptide with a ring-shaped spatial structure, a low hydrophilic coefficient of -0.864 and a medium molecular weight of 2375.8Da. The specific structure makes it difficult to be absorbed through the skin. The present invention uses a specific amount of hemolytic lecithin and a composite plant extract to synergistically affect skin proteins and lipids at the same time, opening up two pathways: transcellular membrane penetration and intercellular lipid penetration, thereby effectively increasing the transcutaneous absorption and intradermal accumulation of cono peptide. Compared with traditional penetration enhancers, the improvement effect is significant.

[0008] Angelica sinensis is a commonly used medicinal herb in Traditional Chinese Medicine. Its main component, ligustilide, contains ester bonds that give it skin affinity. The ester ring is a hydrophilic group, while the unsaturated double bond chain outside the ring is a lipophilic group. The hydrophilic and lipophilic nature of the molecular structure facilitates insertion into the lipid bilayer of the stratum corneum, thereby forming a permeation channel. Cloves are the flower buds of the Myrtaceae tree, primarily containing clove oil and eugenol. The hydroxyl group and ether bond in eugenol are hydrophilic groups, while the long-chain alkyl group at the other end is a lipophilic group. This gives eugenol dual hydrophilic and lipophilic properties, facilitating the opening of skin channels. Cloves also contain other components that have analgesic, warming, and cold-dispelling properties, exerting dual functions of penetration enhancement and treatment. Salvia miltiorrhiza is a traditional Chinese medicine, whose main components are the fat-soluble tanshinone IIA and the water-soluble salvianolic acid B. The carbonyl group in Tanshinone IIA is hydrophilic, while the saturated cyclic hydrocarbon on the other side is lipophilic. This gives Tanshinone IIA dual hydrophilic and lipophilic properties, which facilitates opening skin channels. Glycyrrhizin, glycyrrhizin, sodium glycyrrhetinate, dipotassium glycyrrhetinate, and disodium glycyrrhetinate succinate, all isolated from licorice, promote mucosal absorption of drugs. In actual research, the inventors found that a mixture of angelica, cloves, salvia miltiorrhiza, and licorice showed enhanced penetration.

[0009] Preferably, the weight ratio of the cono peptide, lysophosphatidylcholine and the composite plant extract is cono peptide: lysophosphatidylcholine: composite plant extract = 0.025: (1-3): (4-6).

[0010] The inventors found in actual research that the weight ratio of the composite plant extract and lysolecithin affects the final penetration effect of conopeptide. When the weight ratio of conopeptide, lysolecithin and composite plant extract is within the above range, the penetration effect is better.

[0011] Preferably, the weight ratio of angelica sinensis, cloves, salvia miltiorrhiza, and liquorice in the composite plant extract is angelica sinensis: cloves: salvia miltiorrhiza: liquorice = (0.1-5): (0.1-5): (0.1-5). Further preferably, the weight ratio of angelica sinensis, cloves, salvia miltiorrhiza, and liquorice in the composite plant extract is angelica sinensis: cloves: salvia miltiorrhiza: liquorice = (0.5-1): 1: (1-1.5): (0.5-1).

[0012] The inventors found in actual research that the weight ratio of angelica, cloves, salvia miltiorrhiza and licorice in the raw materials of the composite plant extract affects the penetration effect of the final cono peptide. When the weight ratio of angelica, cloves, salvia miltiorrhiza and licorice is within the above range, the penetration effect is better.

[0013] Preferably, the method for preparing the composite plant extract comprises the following steps: preparing angelica extract, clove extract, salvia miltiorrhiza extract and liquorice extract respectively, and mixing the angelica extract, clove extract, salvia miltiorrhiza extract and liquorice extract to obtain the composite plant extract.

[0014] Preferably, the preparation method of the angelica extract is: ultrasonic extraction and concentration of angelica to obtain the angelica extract; and / or, the preparation method of the clove extract is: ultrasonic extraction and concentration of clove to obtain the clove extract; and / or, the preparation method of the salvia miltiorrhiza extract is: ultrasonic extraction and concentration of salvia miltiorrhiza to obtain the salvia miltiorrhiza extract; and / or, the preparation method of the licorice extract is: ultrasonic extraction and concentration of licorice to obtain the licorice extract.

[0015] Preferably, the material-liquid ratio of the ultrasonic extraction is 1:8-12, the temperature of the ultrasonic extraction is 25-35°C, the time of the ultrasonic extraction is 50-80min, and the power of the ultrasonic extraction is 250-350w.

[0016] Preferably, the extraction solvent is ethanol with a volume fraction of 60-80%.

[0017] Preferably, the raw material is soaked before ultrasonic extraction, the soaking time is 10-24 hours, and the soaking temperature is 2-6°C.

[0018] In one embodiment, the preparation method of the angelica extract is as follows: weigh dried angelica slices, take a clean beaker and add 70% ethanol at a solid-liquid ratio of 1:10, place it at 4°C and soak for 12 hours, then place the beaker in an ultrasonic extraction instrument at 300W power and 25°C, treat for 60 minutes, filter, and concentrate the filtrate using a rotary evaporator to obtain the angelica extract.

[0019] In one embodiment, the preparation method of the clove extract is as follows: weighing dried clove slices, taking a clean beaker, adding 70% ethanol at a solid-liquid ratio of 1:10, and soaking for 12 hours at 4°C. The beaker is placed in an ultrasonic extraction instrument at 300W power and 25°C for 60 minutes, then filtered, and the filtrate is concentrated using a rotary evaporator to obtain the clove extract;

[0020] In one embodiment, the preparation method of the salvia miltiorrhiza extract is as follows: weighing dried salvia miltiorrhiza slices, taking a clean beaker, adding 70% ethanol at a solid-liquid ratio of 1:10, placing it at 4°C and soaking it for 12 hours, placing the beaker in an ultrasonic extraction instrument at 300W power and 25°C, treating it for 60 minutes, filtering it, and concentrating the filtrate using a rotary evaporator to obtain the salvia miltiorrhiza extract;

[0021] In one embodiment, the preparation method of the licorice extract is as follows: weigh dry licorice, take a clean beaker, add 70% ethanol at a solid-liquid ratio of 1:10, soak at 4°C for 12 hours, place the beaker in an ultrasonic extraction instrument at 300W power and 25°C, treat for 60 minutes, filter, and concentrate the filtrate using a rotary evaporator to obtain the licorice extract.

[0022] Preferably, the preparation method of the composite plant extract comprises the following steps: extracting and concentrating angelica sinensis, cloves, salvia miltiorrhiza and liquorice in proportion to obtain the composite plant extract.

[0023] In one embodiment, angelica, cloves, salvia miltiorrhiza and licorice are weighed in proportion, 70% ethanol is added to a clean beaker at a solid-liquid ratio of 1:10, and the mixture is placed at 4°C and soaked for 12 hours. The beaker is placed in an ultrasonic extraction instrument at 300W power and 25°C, treated for 60 minutes, and then filtered. The filtrate is concentrated using a rotary evaporator to obtain the composite plant extract.

[0024] In addition, the present invention provides use of the penetration-enhancing composition in preparing skin products.

[0025] The present invention provides two methods for preparing composite plant extracts. One method is to prepare angelica extract, clove extract, salvia miltiorrhiza extract and liquorice extract separately and then mix them. The other method is to extract angelica, clove, salvia miltiorrhiza and liquorice by mixing them in proportion. The inventors found that the composite plant extract obtained by mixing angelica, clove, salvia miltiorrhiza and liquorice in proportion has a better penetration effect after being mixed with hemolysed lecithin.

[0026] Furthermore, the present invention provides a skin product, which includes the penetration-enhancing composition; the skin product is one of a lotion, an emulsion, a cream, a mask, an essence, and a spray.

[0027] Preferably, the skin product comprises the following components in percentage by mass: 0.01-5% of a penetration-enhancing composition, 5-40% of a cosmetic base, and the balance being deionized water.

[0028] Preferably, the cosmetic matrix includes at least one of a thickener, a moisturizer, an emulsifier, a preservative, a fragrance, and a pH adjuster.

[0029] Exemplarily, the thickener includes at least one of xanthan gum, carbomer 940, AVC, and high molecular weight cellulose; the moisturizer includes at least one of glycerin, butylene glycol, and low molecular weight sodium hyaluronate; the emulsifier includes at least one of PEG-40 hydrogenated castor oil, triglycerides, coconut oil-caprylate / caprate, polydimethylsiloxane, hydrogenated palm kernel oil, cetearyl alcohol, polyglyceryl-6 distearate, and polymethylsilsesquioxane; the preservative includes at least one of 1,2-pentanediol, 1,2-hexanediol, and parahydroxyacetophenone; the pH adjuster includes at least one of arginine and EDTA-2Na.

[0030] Compared with the prior art, the beneficial effects of the present invention are as follows: the present invention can simultaneously affect skin proteins and lipids through the synergistic effect of hemolysed lecithin and compound plant extracts, opening up two pathways of trans-cell membrane penetration and intercellular lipid penetration, effectively increasing the transdermal absorption and intradermal accumulation of active ingredients, and achieving a synergistic penetration-promoting effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Figure 1 is a VISIA wrinkle image of the right face; Figure (a) is a VISIA wrinkle image of the right face at T0 in comparative application example 9, and Figure (b) is a VISIA wrinkle image of the right face at T10 in comparative application example 9;

[0032] Figure 2 are the VISIA wrinkle images of the left face; among them, Figure (c) is the VISIA wrinkle image of the left face of T0 in Application Example 2, and Figure (d) is the VISIA wrinkle image of the left face of T10 in Application Example 2;

[0033] Figure 3 The Fourier transform infrared spectra of the skin after the compositions prepared in Examples 1-10 and Comparative Example 9 penetrate the skin. DETAILED DESCRIPTION

[0034] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below with reference to the accompanying drawings and specific examples. Its purpose is to understand the content of the present invention in detail, rather than to limit the present invention. All other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. Unless otherwise specified, the experimental reagents and instruments designed for the implementation and comparative examples of the present invention are all commonly used ordinary reagents and instruments, which can be obtained from commercial channels. In the implementation and comparative examples, the experimental methods used are all conventional methods unless otherwise specified; and unless otherwise specified, the raw materials used in parallel experiments are from the same batch of raw materials.

[0035] The raw materials used in the examples and comparative examples are described below, but are not limited to the following raw materials:

[0036] The raw materials used in the present invention, except for the composite plant extract, are all conventional commercial products, and the composite plant extract is homemade.

[0037] Composite plant extract-1: mixed and extracted: Angelica sinensis, cloves, salvia miltiorrhiza and liquorice are mixed according to a certain proportion, extracted and concentrated to obtain the composite plant extract.

[0038] Angelica sinensis, cloves, salvia miltiorrhiza and liquorice are weighed in proportion, 70% ethanol is added to a clean beaker at a solid-liquid ratio of 1:10, and the mixture is soaked at 4°C for 12 hours. The beaker is placed in an ultrasonic extraction instrument at 300W power and 25°C, treated for 60 minutes, and then filtered. The filtrate is concentrated using a rotary evaporator to obtain the composite plant extract.

[0039] The preparation methods of compound plant extracts 2-4 and 6-11 are exactly the same as those of compound plant extract-1. If there are no relevant components, they can be omitted. Only the raw materials are different, as shown in Table 1.

[0040] Composite plant extract-5: Compared with composite plant extract-1, the raw material ratio is exactly the same, only the preparation method is different. Angelica extract, clove extract, Salvia miltiorrhiza extract and licorice extract are prepared separately, and the Angelica extract, clove extract, Salvia miltiorrhiza extract and licorice extract are mixed to obtain the composite plant extract.

[0041] Weigh dried angelica slices, add 70% ethanol to a clean beaker at a solid-liquid ratio of 1:10, and soak at 4°C for 12 hours. Then, place the beaker in an ultrasonic extraction instrument at 300W power and 25°C for 60 minutes, filter, and concentrate the filtrate using a rotary evaporator to obtain the angelica extract.

[0042] Weigh dried clove slices, add 70% ethanol to a clean beaker at a solid-liquid ratio of 1:10, and soak at 4°C for 12 hours. Then, place the beaker in an ultrasonic extraction instrument at 300W power and 25°C for 60 minutes, filter, and concentrate the filtrate using a rotary evaporator to obtain the clove extract.

[0043] Weigh dried Danshen slices, add 70% ethanol to a clean beaker at a solid-liquid ratio of 1:10, and soak at 4°C for 12 hours. Then, place the beaker in an ultrasonic extraction instrument at 300W power and 25°C for 60 minutes, filter, and concentrate the filtrate using a rotary evaporator to obtain Danshen extract.

[0044] Weigh dried licorice, take a clean beaker and add 70% ethanol at a solid-liquid ratio of 1:10, soak it at 4°C for 12 hours, place the beaker in an ultrasonic extraction instrument at 300W power and 25°C, treat it for 60 minutes, then filter it, and concentrate the filtrate using a rotary evaporator to obtain the licorice extract.

[0045] Table 1

[0046]

[0047]

[0048] The present invention provides a penetration-enhancing composition. The components and weight portions of the penetration-enhancing composition are shown in Tables 2 and 3. The preparation method of the penetration-enhancing composition comprises the following steps: weighing cono peptide, a composite plant extract, and lysolecithin according to the weight portions shown in Table 2, stirring at room temperature, and obtaining the penetration-enhancing composition. Components missing from the comparative example are omitted, and the remaining components are mixed together.

[0049] Table 2

[0050]

[0051] Table 3

[0052]

[0053]

[0054] Comparative Example 10

[0055] The invention provides a penetration-promoting composition, which comprises the following components in percentage by mass: 0.025 parts of conopeptide and 3 parts of water-soluble azone.

[0056] Comparative Example 11

[0057] The invention provides a penetration-promoting composition, which comprises the following components in percentage by mass: 0.025 parts of conopeptide and 3 parts of isosorbide dimethyl ether.

[0058] Application Examples

[0059] The present invention provides an essence containing a penetration-enhancing composition. The components and mass percentages of the essence are shown in Table 4. The compositions used in Application Examples 1-10 are respectively the compositions prepared in Examples 1-10, for example, the composition used in Application Example 1 is the composition in Example 1, the composition used in Application Example 2 is the composition in Example 2, and so on. The compositions used in Comparative Application Examples 1-11 are respectively the compositions prepared in Comparative Examples 1-11; the composition used in Application Example 11 is the composition prepared in Example 2.

[0060] Table 4

[0061]

[0062] The preparation method of the above-mentioned essence containing the penetration-promoting composition is as follows:

[0063] Add all the raw materials of phase A into water, stir and mix evenly, and heat to 85℃ for later use;

[0064] Mix all the raw materials of phase B, heat to 85℃ and set aside;

[0065] Combine the ingredients of phase C, heat until dissolved, and set aside;

[0066] Add Phase B to Phase A and emulsify. Homogenize at 8000 RPM for 5 minutes. Add Phase C and mix thoroughly. Set aside.

[0067] Cool to 40°C, add phase D, replenish water, and homogenize at 5000 RPM for 2 minutes to prepare the essence.

[0068] Performance test-1 Penetration test.

[0069] Test sample: The penetration-enhancing composition prepared in Examples 1-10 and Comparative Examples 1-11 was diluted with deionized water to a mass percentage of 5% for use.

[0070] Testing steps: Frozen Bama pig skin was removed, thawed, and cut into appropriate sizes with scissors. The cut skin was placed with the stratum corneum facing upwards and fixed between a supply and receiving reservoir. 8 mL of PBS (pH 7.4) was added to the receiving reservoir, followed by 2 g of sample. The skin was then placed in a transdermal diffusion tester and incubated at 37°C for 24 hours. After the reaction, the conoin peptide content in the pig skin was determined using a modified tape stripping method combined with liquid chromatography: First, the supply solution was removed, the stratum corneum was rinsed twice with 2 mL of deionized water, and any residual liquid was gently wiped dry with cotton wool. The stratum corneum of the Bama pig skin was taped once, and the tape was removed. The treated skin was minced and collected in a centrifuge tube. Extraction was performed with an extractant. The extract was filtered through a 0.22 μm filter membrane, and the conoin peptide content was determined by liquid chromatography, which represents the cumulative permeation of conoin peptides in the pig skin.

[0071] The content of conoside peptide in the extract was determined by high performance liquid chromatography, and the intradermal accumulation was calculated.

[0072] Chromatographic conditions: The chromatographic column was a Waters C18 column (4.6 mm*150 mm, 3.5 μm), the mobile phase was a 0.1% trifluoroacetic acid acetonitrile solution-0.1% trifluoroacetic acid aqueous solution in a volume ratio of 15:85, the flow rate was 0.8 mL / min, the column temperature was 25°C, the injection volume was 10 μL, and the detection wavelength was 220 nm.

[0073] Preparation of conoside peptide standard working solution: Accurately pipette a certain amount of conoside peptide standard stock solution and dilute it stepwise with deionized water to obtain a series of standard working solutions (mass concentrations are 1.9 μg / mL, 3.9 μg / mL, 7.8 μg / mL, 15.6 μg / mL, 31.3 μg / mL, 62.5 μg / mL, 125 μg / mL, 250 μg / mL and 500 μg / mL, respectively).

[0074] Standard curve drawing: The standard working solution was measured according to the above chromatographic conditions, and the standard curve was drawn with the mass concentration of the standard working solution as the horizontal axis and the peak area as the vertical axis.

[0075] The results are shown in Table 5.

[0076] Table 5

[0077]

[0078] As can be seen from the above table, the weight ratio of cono peptide, hemolysine lecithin and composite plant extract will affect the final penetration effect of cono peptide. The weight ratio of angelica sinensis, clove, salvia miltiorrhiza and licorice in the raw materials of the composite plant extract will affect the final penetration effect of cono peptide. When the preferred range is further selected, the penetration effect is better.

[0079] As can be seen from the above table, the extraction method of the composite plant extract affects the penetration effect. The composite plant extract obtained by mixing angelica, cloves, salvia miltiorrhiza and licorice in proportion has a better penetration effect when mixed with hemolysed lecithin.

[0080] From the comparison of Examples 1-5, it can be seen that the weight ratio of conopeptide, lysolecithin and composite plant extract affects the penetration effect of conopeptide. When the weight ratio of conopeptide, lysolecithin and composite plant extract is within the preferred range, the penetration effect of conopeptide is better.

[0081] Comparison of Example 2 and Examples 6-8 shows that the weight ratio of angelica sinensis, clove, salvia miltiorrhiza and liquorice in the raw materials of the composite plant extract will affect the penetration effect of cono peptide. When the preferred range is further selected, the penetration effect of cono peptide is better.

[0082] Comparison of Example 2 and Example 9 shows that the extraction method of the composite plant extract affects the penetration effect of cono peptide. The composite plant extract obtained by mixing angelica, clove, salvia miltiorrhiza and liquorice in proportion and mixed with lysolecithin has a better penetration effect of cono peptide.

[0083] As can be seen from Example 2 and Comparative Examples 1-11, when one of the components of Angelica sinensis, Clove, Salvia miltiorrhiza, and Licorice is missing from the composite plant extract or is replaced by a component with similar efficacy, the penetration effect of the cono peptide is extremely poor. The components of the composite plant extract of the present invention are indispensable and cannot be replaced. When the weight ratio of cono peptide, lysolecithin, and composite plant extract is not within a specific range, the penetration effect of the cono peptide is extremely poor.

[0084] Performance Test-2 Total Reflection Fourier Transform Infrared Spectroscopy.

[0085] To reveal the molecular mechanism by which the composite plant extracts and lysolecithin enhance the skin penetration of conopeptide, total reflection Fourier transform infrared spectroscopy was used to investigate the effects of different samples on the arrangement of lipids and proteins in the stratum corneum.

[0086] Test sample: The penetration-enhancing composition prepared in Examples 1-10 and Comparative Examples 1-11 was diluted with deionized water to a mass percentage of 5% for use.

[0087] Test steps: Place Bama pig skin between the supply and receiving cells of a Franzs diffusion cell, add 2g of sample to the supply cell and place in a transdermal diffusion tester at 37°C for 24 hours. After the reaction, remove the supply solution and rinse the stratum corneum twice with 2mL of deionized water. Use cotton wool to gently wipe off the remaining liquid on the surface, and then place the skin in a ventilated place to dry for 24 hours. Use a reflection Fourier transform infrared spectrometer to detect the stratum corneum after transdermal transmission at 4000-600cm -1Infrared spectrum of 16 consecutive scans within the range;

[0088] The test results are as follows Figure 3 As shown in Table 6, Figure 3 This is the Fourier transform infrared spectrum of pig skin after the compositions prepared in Examples 1-10 and Comparative Example 9 were percutaneously injected.

[0089] Table 6

[0090]

[0091]

[0092] Among them, the lipid extraction and lipid fluidity data are the differences obtained by deconvolution calculation and comparison example 9.

[0093] ΔArea 2850cm -1 Infrared spectrum 2850cm -1 The smaller the value, the stronger the effect of the formula on the lipid extraction of the stratum corneum. -1 Infrared spectrum 2850cm -1 The center displacement value at ΔFWHM2850cm -1 Infrared spectrum 2850cm -1 The difference in half-peak width of the peak at ΔHeight 2920 / 2850cm is the difference in half-peak width of the peak at ΔHeight 2920 / 2850cm. The larger the value, the stronger the enhancement of the fluidity of the stratum corneum lipids by the modified formula. -1 Infrared spectrum 2850cm -1 、2920cm -1 The larger the value, the stronger the enhancement of the fluidity of stratum corneum lipids by the modified formula.

[0094] As can be seen from the above table, the composition formed by the cono peptide, lysolecithin and composite plant extract of the present invention is beneficial to the extraction of stratum corneum lipids and the enhancement of lipid fluidity.

[0095] The abscissa of the infrared hydroxyl absorption peak is the abscissa displacement of the hydroxyl absorption peak. The smaller the value, the more hydrogen bonds have occurred in the keratin of the stratum corneum of the formula, and the hydration has increased, which is conducive to making the keratin into a looser and more porous structure.

[0096] As can be seen from the above table, the composition formed by the cono peptide, lysolecithin and composite plant extract of the present invention is beneficial to enhancing the hydration of keratin.

[0097] From the comparison of Examples 1-5, it can be seen that the weight ratio of cono peptide, hemolysed lecithin and composite plant extract affects the lipid and keratin structure of the stratum corneum. When the weight ratio of cono peptide, hemolysed lecithin and composite plant extract is within the preferred range, lipid fluidization is more significant, keratin is looser, and the stratum corneum is easier to penetrate.

[0098] Comparison of Example 2 and Examples 6-8 shows that the weight ratio of angelica sinensis, clove, salvia miltiorrhiza, and liquorice in the raw materials of the composite plant extract affects the lipid and keratin structure of the stratum corneum. When the preferred range is further selected, the lipid fluidization is more significant, the keratin is looser, and the stratum corneum is easier to penetrate.

[0099] Comparison of Example 2 and Example 9 shows that the extraction method of the composite plant extract affects the lipid and keratin structure of the stratum corneum. The composite plant extract obtained by mixing angelica, clove, salvia miltiorrhiza and licorice in proportion, after mixing with hemolysine lecithin, has more significant lipid fluidization, looser keratin and easier penetration of the stratum corneum.

[0100] A comparison of Example 2 and Comparative Examples 1-11 shows that when one of the components of the composite plant extract, Angelica sinensis, Clove, Salvia miltiorrhiza, and Licorice is missing or replaced with a component of similar efficacy, the permeability of the stratum corneum is extremely poor. The components of the composite plant extract of the present invention are indispensable and cannot be replaced. When the weight ratio of conopeptide, lysolecithin, and composite plant extract is outside the specified range, the permeability of the stratum corneum is extremely poor.

[0101] Performance Test-3 Human Efficacy Evaluation.

[0102] This effectiveness test tested the effectiveness of the application and comparative application examples. The specific testing method is as follows: Volunteers aged 22-40 were selected according to the "Technical Specifications for Safety of Cosmetics" (2015) and randomly divided into 22 groups, with 5 participants in each group. The subjects applied the essence to their left and right eyes according to the instructions and gently massaged until absorbed. The changes in skin firmness (using a Cutometer MPA580, Courage and Khazaka, Germany) and skin wrinkle scores (using skin analyzers VISIA and RBX and software technology analysis) before application (T0) and 10 minutes after application (T10) were measured to evaluate whether the sample under these conditions had the effect of instantly tightening the skin and soothing wrinkles.

[0103] The test result is the difference between the average test results before and 10 minutes after use.

[0104] Improvement rate (%) = (T10 measurement value - T0 measurement value) / T0 measurement value × 100%

[0105] The skin elasticity tester measures skin elasticity based on the principles of suction and stretching. During the test, a negative pressure is generated on the skin's surface, drawing the skin into the probe. A non-contact optical testing system measures the depth of the skin's suction, thereby evaluating skin elasticity. During the test, a negative pressure is generated on the skin's surface, drawing the skin into the probe. This causes the skin to deform. When the negative pressure is removed, the skin does not immediately return to its original shape; there is a delay, known as the viscoelasticity of the skin. Skin firmness is measured by repeating the deformation 10 times. Lower values ​​indicate faster recovery and higher skin firmness.

[0106] The skin wrinkle score is detected using the skin detector VISIA, which measures and analyzes the skin's spots, pores, wrinkles, and texture. VISIA can capture images under three light source modes: natural light, ultraviolet light, and cross-polarized light. Cross-polarized light can filter out skin surface reflections, and the captured images are polarized photos, which facilitate better observation of the subcutaneous condition. This test collects images of the left, middle, and right sides of the subject's face. Image analysis of the natural light images is performed to obtain quantitative indicators such as forehead wrinkle scores and eye wrinkle scores, which are used as parameters to evaluate the improvement of facial wrinkles. Lower parameters indicate more soothing skin wrinkles.

[0107] Table 7

[0108]

[0109]

[0110] As can be seen from the above table, the products prepared according to the application examples of the present invention have a good effect of improving skin elasticity and wrinkles. Figure 1 are VISIA wrinkle images of the right face; wherein, Figure (a) is the VISIA wrinkle image of the right face at T0 in Comparative Application Example 9, and Figure (b) is the VISIA wrinkle image of the right face at T10 in Comparative Application Example 9; Figure 2 are the VISIA wrinkle images of the left face; among them, Figure (c) is the VISIA wrinkle image of the left face of T0 in Application Example 2, and Figure (d) is the VISIA wrinkle image of the left face of T10 in Application Example 2.

[0111] From the comparison of Application Examples 1-5, it can be seen that the weight ratio of conopeptide, lysolecithin and compound plant extract affects the effect of improving skin elasticity and wrinkles. When the weight ratio of conopeptide, lysolecithin and compound plant extract is within the preferred range, the effect of improving skin elasticity and wrinkles is better.

[0112] A comparison of Application Example 2 and Application Examples 6-8 shows that the weight ratio of angelica, clove, salvia miltiorrhiza and liquorice in the raw materials of the composite plant extract will affect the effect of improving skin elasticity and wrinkles. When the preferred range is further selected, the effect of improving skin elasticity and wrinkles is better.

[0113] Comparison between Application Examples 2 and 9 shows that the extraction method of the composite plant extract affects the effect of improving skin elasticity and wrinkles. The composite plant extract obtained by mixing angelica, cloves, salvia miltiorrhiza and licorice in a certain proportion and mixed with hemolysed lecithin has a better effect on improving skin elasticity and wrinkles.

[0114] A comparison of Application Example 2 and Comparative Application Examples 1-11 shows that when one of the components of Angelica sinensis, Clove, Salvia miltiorrhiza, and Licorice is missing from the composite plant extract or replaced with a component with similar efficacy, the effect of improving skin elasticity and wrinkles is extremely poor. The composite plant extract components of the present invention are indispensable and cannot be replaced. When the weight ratio of conopeptide, lysolecithin, and the composite plant extract is outside the specified range, the effect of improving skin elasticity and wrinkles is extremely poor.

[0115] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A penetration-enhancing composition, characterized in that The invention comprises the following components in parts by weight: 0.01-0.3 parts of conoside peptide, 0.1-8 parts of lysolecithin and 0.1-8 parts of a composite plant extract; the composite plant extract consists of angelica sinensis, cloves, salvia miltiorrhiza and liquorice; the weight ratio of angelica sinensis, cloves, salvia miltiorrhiza and liquorice in the composite plant extract is angelica sinensis: cloves: salvia miltiorrhiza: liquorice=(0.1-5):(0.1-5):(0.1-5); the composite plant extract is extracted with 70% by volume ethanol.

2. The penetration-enhancing composition according to claim 1, wherein The weight ratio of the cono peptide, hemolysed lecithin and the composite plant extract is cono peptide: hemolysed lecithin: composite plant extract = 0.025: (1-3): (4-6).

3. The penetration-enhancing composition according to claim 1, wherein The weight ratio of angelica sinensis, clove, salvia miltiorrhiza and liquorice in the composite plant extract is angelica sinensis: clove: salvia miltiorrhiza: liquorice=(0.5-1):1:(1-1.5):(0.5-1).

4. The penetration-promoting composition according to claim 1, wherein The preparation method of the composite plant extract comprises the following steps: preparing angelica extract, clove extract, salvia miltiorrhiza extract and liquorice extract respectively, and mixing the angelica extract, clove extract, salvia miltiorrhiza extract and liquorice extract to obtain the composite plant extract.

5. The penetration-enhancing composition according to claim 4, wherein The preparation method of the angelica extract comprises the following steps: extracting and concentrating the angelica extract through ultrasonication to obtain the angelica extract; And / or, the preparation method of the clove extract comprises: ultrasonically extracting and concentrating cloves to obtain the clove extract; And / or, the preparation method of the salvia miltiorrhiza extract comprises: ultrasonically extracting and concentrating salvia miltiorrhiza to obtain the salvia miltiorrhiza extract; And / or, the preparation method of the licorice extract is: ultrasonically extracting and concentrating licorice to obtain the licorice extract.

6. The penetration-enhancing composition according to claim 1, wherein The preparation method of the composite plant extract comprises the following steps: mixing angelica sinensis, cloves, salvia miltiorrhiza and liquorice in proportion, performing ultrasonic extraction and concentrating to obtain the composite plant extract.

7. Use of the penetration-enhancing composition according to any one of claims 1 to 6 in the preparation of skin products.

8. A skin care product, characterized in that: The skin product comprises the penetration-enhancing composition according to any one of claims 1 to 6; the skin product is one of lotion, emulsion, cream, mask, essence, and spray.

9. The skin care product according to claim 8, wherein The skin product comprises the following components in percentage by mass: 0.01-5% of a penetration-enhancing composition, 5-40% of a cosmetic base, and the balance being deionized water.

Citation Information

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