Application of silybin in preparation of retinol transdermal absorption enhancer

Abstract

The invention discloses an application of silybin in preparation of a retinol transdermal absorption enhancer, and silybin can increase the retention volume of retinol in skin so as to improve the transdermal absorption capacity of the skin to retinol. The invention also provides a skin external preparation which comprises retinol and a transdermal absorption enhancer, the transdermal absorption enhancer is silibinin.

Description

Technical Field

[0001] This invention relates to the field of retinol permeation enhancement technology, specifically to the use of silymarin in the preparation of retinol transdermal absorption enhancers. Background Technology

[0002] Retinol is a form of vitamin A, a fat-soluble vitamin. It is a component of photosensitive substances in visual cells and is crucial for maintaining vision in low light; a deficiency in retinol can lead to night blindness. Additionally, it is widely used in skincare, acting on the epidermis to promote cell proliferation, maintain normal skin circulation, repair lost collagen, reduce wrinkles, and alleviate signs of premature aging (such as abnormal pigmentation, rough spots, and dry skin).

[0003] The multiple hydroxyl groups and double bonds in the retinol molecule limit its ability to penetrate the skin. Additionally, retinol has high lipophilicity, which helps it penetrate the skin's lipid layer. However, excessive lipophilicity can also make it difficult for it to pass through the water-soluble environment behind the stratum corneum, thus limiting its further penetration into deeper layers of the skin. Summary of the Invention

[0004] One objective of the embodiments of the present invention is to solve the above-mentioned problems and provide corresponding beneficial effects.

[0005] Another objective of this invention is to provide a retinol transdermal absorption enhancer that can solve the problem of how to improve the skin's transdermal absorption capacity for retinol.

[0006] The embodiments of the present invention mainly adopt the following technical solutions to achieve the above objectives.

[0007] In a first aspect, embodiments of this application provide the use of silymarin in the preparation of retinol transdermal absorption enhancers.

[0008] In a second aspect, embodiments of this application provide a topical skin agent comprising: retinol and a transdermal absorption enhancer; wherein the transdermal absorption enhancer is silymarin; and the mass ratio of retinol to silymarin is 1:0.05 to 2.

[0009] In some embodiments, the mass ratio of retinol to silymarin is 1:0.1 to 1.

[0010] In some embodiments, the topical skin agent further includes water.

[0011] In some embodiments, the mass fraction of water is the balance.

[0012] In a third aspect, embodiments of this application provide the use of silymarin as a moisturizer or moisturizing enhancer in a retinol-containing composition; wherein the mass ratio of retinol to silymarin is 1:0.05 to 2.

[0013] In some embodiments, the mass ratio of retinol to silymarin is 1:0.1 to 1.

[0014] In a fourth aspect, embodiments of this application provide a topical skin care product, wherein the topical skin care product includes the aforementioned topical skin agent.

[0015] In some embodiments, the amount of retinol added is 0.01 to 0.3%.

[0016] In some embodiments, the amount of silymarin added is 0.02-0.3%.

[0017] In some embodiments, the topical skin care product is one of an emulsion, cream, ointment, or mask.

[0018] In some technical solutions, the topical skin care product also includes water.

[0019] The embodiments of this application include at least the following beneficial effects:

[0020] In some embodiments, this application provides the use of silymarin in the preparation of retinol transdermal absorption enhancers, wherein silymarin can increase the amount of retinol retained in the skin, thereby enhancing the skin's transdermal absorption capacity for retinol.

[0021] In some embodiments, this application provides a skin care product containing retinol, comprising at least two parts: retinol and a retinol transdermal absorption enhancer. The above-mentioned topical skin product uses retinol and silymarin in combination. While retinol and silymarin work together to combat aging, silymarin promotes the transdermal absorption of retinol, enhancing the efficacy of retinol and further improving the anti-aging effect.

[0022] In some embodiments, when retinol is added in combination with silymarin, it can also alleviate skin dryness that may be caused by retinol alone, reduce transepidermal water loss, achieve better moisturizing effect, and bring a better user experience.

[0023] Other advantages, objectives and features of the present invention will become apparent in part from the following description, and in part from those skilled in the art through study and practice of the invention. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the structure of silybin;

[0025] Figure 2 The 22-hour retention of epidermis and dermis in samples A to C of this application;

[0026] Figure 3 The 22h retention of epidermis and dermis in samples D to H of this application;

[0027] Figure 4 The 22h retention of epidermis and dermis in samples I-L of this application;

[0028] Figure 5 The 22h retention of the epidermis and dermis in samples M to O of this application. Detailed Implementation

[0029] To make the technical problems solved, the technical solutions, and the beneficial effects of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0030] The term "comprising" and any variations thereof in the embodiments of this application are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the steps or units listed, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to such process, method, product, or device.

[0031] In addition to the above, it should be emphasized that the reference to "embodiment" herein means that a specific feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0032] In this document, unless otherwise stated, “%” means “mass%”; “Mpa” means megapascal; “℃” means Celsius; “KD” means kilodalton; “D” means Dalton; and “μm” means micrometer.

[0033] In this document, unless otherwise stated, the term "%" refers to the total weight of the compositions of this application.

[0034] In this document, unless otherwise stated, all defined ranges refer to: each specific range within a given range as well as combinations of subranges between given ranges. For example, the range 1 to 5 specifically includes 1, 2, 3, 4, and 5, and also includes subranges such as 2 to 5, 3 to 5, 2 to 3, 2 to 4, 1 to 4, etc.

[0035] Silybin, molecular formula: C 25 H 22 O 10 Molecular weight: 482.44, is an extract of the fruit and seeds of milk thistle (Silybummarianum L. Gaertn), with the following structure: Figure 1 As shown in the image, silymarin possesses pharmacological effects such as scavenging reactive oxygen species (ROS), anti-free radical activity, anti-lipid peroxidation, inhibition of nitric oxide (NO) production, inhibition of 5'-lipoxygenase, protection of hepatocyte membranes, promotion of hepatocyte repair and regeneration, immunomodulation, anti-liver fibrosis, anti-glutathione (GSH) emptying, anti-inflammatory, anti-tumor, and lipid-lowering effects. In recent years, with the in-depth research on the application of silymarin in the dermatology field, especially in sun protection, anti-skin cancer, and delaying skin aging, its development and application in the cosmetics industry has become increasingly widespread. Many studies have shown that silymarin can resist photodamage, provide antioxidant effects, delay skin aging, whiten skin, protect hair, treat melasma, and repair scars, thus having rich applications in cosmetics. No existing technology discloses that silymarin has a penetration-enhancing effect.

[0036] Pentylene glycol is a common penetration enhancer widely used in cosmetics and skincare products. As an organic solvent, pentylene glycol typically functions as a multifunctional solvent and humectant, promoting the penetration of active ingredients into the skin. It helps dissolve other ingredients and improves the uniformity and stability of the formulation. This facilitates the absorption of active ingredients by the skin. Furthermore, it can promote the penetration of active ingredients into the skin layers by regulating the skin's lipid structure and improving skin permeability. It helps open the skin barrier, allowing other ingredients to more easily penetrate the skin surface and reach deeper tissues. This helps enhance the efficacy of the product. It is also used to adjust the viscosity of the formulation, improve texture, and increase moisturizing effects. Due to its excellent permeability and skin tolerance, pentylene glycol is often added to various cosmetics and is an important ingredient in many skincare products. In this invention, pentylene glycol is used as a positive control.

[0037] In the first aspect, the inventors discovered through research that silymarin can increase the amount of retinol retained in the skin, thereby enhancing the skin's transdermal absorption capacity of retinol, and providing the use of silymarin in the preparation of retinol transdermal absorption enhancers.

[0038] In some embodiments, silymarin can be used directly as a transdermal absorption enhancer of retinol, thereby increasing the amount of retinol retained in the skin and thus enhancing the skin's ability to absorb retinol transdermally.

[0039] In a second aspect, embodiments of this application provide the use of silymarin as a humectant or humectant enhancer in a retinol-containing composition, wherein the mass ratio of retinol to silymarin is 1:0.05–2, or 1:0.067, or 1:0.05, or 1:0.1, or 1:0.15, or 1:0.3, or 1:0.5, or 1:0.67, or 1:1, or 1:1.5, or 1:1.675, or 1:2, or 1:0.05–0.067, or 1:0.067–0.1, or 1:0.1–0.3, or 1:0.3–0.5, or 1:0.5–1, or 1:1–1.675, or 1:1.675–2.

[0040] Another effect of retinoids on the skin is causing dryness and peeling. Retinoids are mostly converted into retinoic acid to affect the skin. All-trans retinoic acid can increase the expression of aquaporin 3 (AQP3) in normal human skin. AQP3 expression in the epidermis plays a role in water transport and regulating epidermal differentiation, but excessive AQP3 expression increases TEWL (transdermal water loss, a common indicator of stratum corneum barrier function), causing dryness and sensitivity. The inventors found that when retinol is added in combination with silymarin, it achieves a better anti-water loss effect compared to samples with retinol alone. This may be because silymarin can inhibit inflammatory factors such as NF-κB, TNF-α, and leukotrienes, enhance skin barrier function, reduce skin sensitivity, and decrease water loss. Therefore, it can be concluded that the combined use of retinol and silymarin can alleviate the dryness that may be caused by retinol alone, achieving a better moisturizing effect and providing a better user experience.

[0041] In some embodiments, the mass ratio of retinol to silymarin is 1:0.1 to 1, or 1:0.1, or 1:0.15, or 1:0.3, or 1:0.5, or 1:0.67, or 1:1, or 1:1.5, or 1:1.675, or 1:2, or 1:0.05 to 0.067, or 1:0.067 to 0.1, or 1:0.1 to 0.3, or 1:0.3 to 0.5, or 1:0.5 to 1.

[0042] In a third aspect, a topical skin agent is provided, comprising: retinol and a transdermal absorption enhancer; wherein the transdermal absorption enhancer is silymarin; and the mass ratio of retinol to silymarin is 1:0.05–2, or 1:0.067, or 1:0.05, or 1:0.1, or 1:0.15, or 1:0.3, or 1:0.5, or 1:0.67, or 1:1, or 1:1.5, or 1:1.675, or 1:2, or 1:0.05–0.067, or 1:0.067–0.1, or 1:0.1–0.3, or 1:0.3–0.5, or 1:0.5–1, or 1:1–1.675, or 1:1.675–2.

[0043] The aforementioned topical skin formulation combines retinol and silymarin. Retinol and silymarin work synergistically to combat aging, while silymarin promotes the transdermal absorption of retinol, enhancing its efficacy and further improving its anti-aging effects. Furthermore, the combination of retinol and silymarin also achieves a significant anti-hydration effect, enhancing the moisturizing properties of the composition.

[0044] In some embodiments, the mass ratio of retinol to silymarin is 1:0.1 to 1. When retinol and silymarin are added in a ratio of 1:0.1 to 1, a better anti-dehydration effect can be achieved compared to samples with only retinol added.

[0045] In some embodiments, the topical skin agent further includes water.

[0046] In some technical solutions, the mass fraction of water is the margin.

[0047] In a fourth aspect, embodiments of this application provide a topical skin care product, wherein the topical skin care product includes the aforementioned topical skin agent.

[0048] In some embodiments, the amount of retinol added is 0.01 to 0.3%; preferably, the amount of retinol added is 0.05 to 0.3%.

[0049] In some embodiments, the amount of silybin added is 0.02-0.5%; preferably, the amount of silybin added is 0.02-0.3%, or 0.05-0.5%, or 0.05-0.3%.

[0050] In some embodiments, the topical skin care product further includes a solvent.

[0051] Furthermore, the solvent is a cosmetically acceptable solvent.

[0052] In some embodiments, the solvent may be selected from one or more of ethanol, isopropanol, glycerol, octanediol, 1,2-pentanediol, propylene glycol, butanediol, glycol, glycol ether, ethylene glycol, propylene glycol, butanediol, hexanediol, dipropylene glycol, diethylene glycol, 2-ethoxyethanol, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, and sorbitol.

[0053] In some embodiments, the topical skin care product may contain at least one cosmetically acceptable adjuvant. The adjuvant is selected from one or more of surfactants and / or emulsifiers, preservatives, buffers, chelating agents, denaturants, opacifiers, pH adjusters, reducing agents and stabilizers, thickeners, gelling agents, film-forming polymers, fillers, matting agents, gloss agents, pigments, dyes, fragrances, and mixtures thereof.

[0054] In some embodiments, the topical skin care product may contain at least one cosmetically acceptable active ingredient selected from caffeine, caffeic acid, cyclic peptides, vitamin A and its derivatives, retinol, vitamin C and its derivatives, vitamin E and its derivatives, arbutin, cinnamic acid and its derivatives, ferulic acid, ergothioneine, tetrahydromethylpyrimidine carboxylic acid, glycyrrhizin, bisabolol, ceramides, phenylethyl resorcinol, soluble collagen, adenosine, 4-butylresorcinol, hydrolyzed collagen, inositol, saccharide isomers, fibronectin, astaxanthin, asiaticoside, rhamnose, resveratrol, amino acids, hydroxypropyltetrahydropyrantriol, fermentation products, sodium hyaluronate, niacinamide, panthenol, and plant extracts, or one or more of these.

[0055] In some embodiments, the skin care product may be manufactured in the form of cream, liquid, powder, block, mud-like solid, wax-based, freeze-dried, spray, aerosol, substrate, etc.

[0056] Optionally, the cream or lotion may be further in the form of emulsion, paste, cream, honey, fat, lotion, milk, milk, milk liquid, etc.

[0057] Optionally, the liquid form may be further divided into dew, liquid, water, oil, oil-water separation, etc.

[0058] Optionally, the cream or lotion may be further in the form of emulsion, paste, cream, honey, fat, lotion, milk, milk, milk liquid, etc.

[0059] Alternatively, the powder form can be further divided into gels such as jelly and glue, loose powder, granules, etc.

[0060] Alternatively, the block form can be further divided into block powder, large solid blocks, etc.

[0061] Optionally, the wax base uses wax as the main base material.

[0062] Optionally, the freeze-drying form can be further divided into freeze-dried powder, freeze-dried tablets, etc.

[0063] Optionally, the spray does not contain propellant.

[0064] Optionally, the aerosol contains a propellant.

[0065] Optionally, the substrate may be a film, a paste, or other substrate used in conjunction with cosmetics.

[0066] In some implementations, topical skin care products can be applied topically to hair, body hair, torso, head, face, eyes, lips, hands, feet, whole body skin, fingers (toes), fingernails (toenails), etc.

[0067] In some embodiments, the topical skin care product further includes water.

[0068] In some embodiments, the water content in the topical skin care product is the balance.

[0069] It should be noted that, unless otherwise stated, when referring to the remainder, it means that the total mass fraction of the topical skin care product is 100%.

[0070] Transdermal permeation test

[0071] The following transdermal penetration experiments are used to verify the use of silymarin in the embodiments of this application, so as to further illustrate the technical solutions and beneficial effects provided by the embodiments of this application.

[0072] The main indicators of transdermal penetration are the amount of fluid retained in the epidermis and dermis at 22 hours and the rate of increase in the amount of fluid retained.

[0073] The 22-hour epidermal-dermal retention refers to the sum of the 22-hour epidermal retention and the 24-hour dermal retention.

[0074] The retention improvement rate is the increase in the 22-hour epidermal + dermal layer retention of the sample with added penetration enhancer (test sample) compared to the 22-hour epidermal + dermal layer retention of the sample with the same active ingredient but without penetration enhancer (blank control sample). The calculation formula is as follows:

[0075] Retention rate increase = [(Retention amount of test sample in epidermis + dermis at 22h - Retention amount of blank control sample in epidermis + dermis at 22h) / Retention amount of blank control sample in epidermis + dermis at 22h] × 100%

[0076] Transdermal permeation assays can be performed using conventional methods in this field. A specific exemplary method is given below, using a Franz diffusion cell to investigate the retention of retinol in different skin layers on pig skin from different sample solutions. The specific steps are shown in steps A through C:

[0077] Step A: Obtain skin treated with skin care products.

[0078] A transdermal diffusion device was selected, and the effective diffusion area of ​​the Franz transdermal diffusion cell was 1.54 cm². 2 The volume of the liquid to be received is 8 mL.

[0079] A fresh skin sample to be tested is fixed between the supply and receiving pools with the stratum corneum facing upwards. 0.5 mL of different sample solutions are placed in the supply pools respectively, and the pools are sealed with plastic wrap to prevent the solutions from evaporating.

[0080] Pure methanol was selected as the diffusion medium in the receiving cell, and the receiving liquid was continuously stirred with a magnetic stirrer in a constant temperature water bath at 32±0.5℃ (stirring speed was 350 r·min-1).

[0081] Step B: Determination of the amount of epidermal layer retention after 22 hours.

[0082] After 22 hours, skin tissue was collected and fixed in 4% paraformaldehyde for 24 hours. Then, it was dehydrated in 15% and 30% sucrose solutions until the tissue settled. After dehydration, the tissue was washed with PBS, embedded in 10% CMC-Na, and frozen for preservation.

[0083] The transdermal skin was transversely sectioned using a cryostat to separate the stratum corneum (0-20 μm) and the epidermis + dermis (remaining layer). The stratum corneum and the epidermis + dermis were then fragmented, weighed, and sonicated with water for 1 hour. After 22 hours, the remaining sample solution in the supply tank was recovered, and the recovery rate was calculated.

[0084] Step C: Determination of the amount of residue in the epidermis and dermis layers after 22 hours.

[0085] The drug content was determined by HPLC, and the retinol retention was calculated. The HPLC method was as follows: mobile phase: methanol:water (90:10); gradient elution program: 0-4 min, 0.8 mL / min; 4-8 min, 3.0 mL / min; 8-10 min, 0.8 mL / min; column temperature: 35℃; detection wavelength: 325 nm; injection volume: 10 μL.

[0086] Statistical methods

[0087] Data analysis was performed using Prism 8.0. Statistical analysis results are expressed as (x±s), and t-tests were conducted. The significance level was set at p<0.05, *p<0.05, and **p<0.01.

[0088] The instruments used in the experiment are shown in Table 1:

[0089] Table 1. Instruments used in the transdermal osmosis experiment

[0090] name company model C18 column Thermo Fisher C18 column (250mm × 4.6mm, 5μm) 1 / 100,000 analytical balance Sartorius, Germany MSXSDEE S / N34103055 High Performance Liquid Chromatography Thermo Fisher Vanquish Franz transdermal diffusion pool Shanghai Kaikai Technology TK-24BL transdermal transdermal device Cryo slicer Leica, Germany Leica CM1950 Skin surface moisture loss tester Courage & Khazaka, Germany Tewameter™ Hex

[0091] Raw materials used in the experiment:

[0092] Silybum Marianum Extract B98, Manufacturer: Chenfeng Natural Herbs (Beijing) Technology Co., Ltd., Trade Name: Silybum Marianum Extract B98.

[0093] Retinol, Manufacturer: Shanghai Keqin Technology Co., Ltd., Product Name:

[0094] Bama miniature pig skin (800-1000μm), purchased from Shenzhen Technology University.

[0095] Experimental sample preparation:

[0096] Prepare transdermal permeability test samples according to Table 2 below. The specific method for sample preparation is as follows:

[0097] Preparation steps:

[0098] 1. Add the penetration enhancer and solvent to a beaker, turn on the heating and stirring (30-50 r / min) to heat to 60-75℃, disperse until uniform and transparent, then cool to room temperature for later use;

[0099] 2. Add retinol to the above beaker, sonicate to dissolve until transparent, and then transfer to a light-proof container for storage for subsequent transdermal experiments.

[0100] Table 2 Composition of samples from transdermal penetration experiments

[0101]

[0102] The retention of retinol in different skin layers on pigskin was investigated using a transdermal permeation assay. The test results are shown in Table 3 below.

[0103] Table 3. Retinol retention in the epidermis and dermis layers of samples A-L after 22 hours.

[0104]

[0105]

[0106] As shown in Table 3, the amount of retinol (VA) added in samples A to C was the same. Only retinol (VA) was added in sample A as a blank control. In order to compare the penetration of sample C (with 0.5% silymarin added as a penetration enhancer), sample B with 4.5% pentanediol added was selected as a positive control.

[0107] The test results for samples A through C are shown in Table 3 and Figure 2As shown in the figure, we found that, compared with samples A to B, sample C showed a significant increase in the amount of retinol retained in the skin after 22 hours. The experimental results prove that silymarin can increase the amount of retinol retained in the skin, thereby enhancing the skin's transdermal absorption capacity of retinol.

[0108] The transdermal permeation test results for samples D-H, I-L, and M-O are shown in Table 3 and Figure 3-5 As shown, the permeation-enhancing ability and effect of silymarin were further verified. Comparison of samples D with samples E-H, samples I with samples J-H, and samples M with samples N-O demonstrated that when the mass ratio of retinol to silymarin was 0.5-6:0.2-5, silymarin could increase the amount of retinol retained in the skin, thereby enhancing the skin's transdermal absorption capacity of retinol.

[0109] Transdermal moisture loss change test experiment

[0110] The following transdermal moisture loss change test experiment is used to verify the use of the topical skin care product of this application embodiment, so as to further illustrate the technical solution and beneficial effects provided by this application embodiment.

[0111] The experimental method for the transdermal water loss change test adopts conventional methods, and some embodiments include the following steps:

[0112] Subjects were randomly selected from a pre-determined list of subjects, with one side of the subject's face designated as the experimental group; skin surface moisture was measured and recorded as the initial skin surface moisture data for the test.

[0113] The test substance was applied to the face of the subjects in the experimental group; then, the subjects were placed in a laboratory with constant temperature and humidity at the predetermined test temperature and humidity for the predetermined test time. After the test time was reached, the skin surface moisture of each group was measured and the data was recorded as the skin surface moisture data at the test terminal.

[0114] Combining the skin surface moisture data at the initial detection point and the skin surface moisture data at the end of the detection point, the transdermal water loss rate of the test sample is calculated according to the following formula (1);

[0115] Equation (1): Transdermal moisture loss rate = Transdermal moisture loss change (Δ difference) / Transdermal moisture loss at the beginning of detection; where, Transdermal moisture loss change (Δ difference) = Transdermal moisture loss at the end of detection - Transdermal moisture loss at the beginning of detection.

[0116] In addition, skin surface moisture can be tested using the Tewameter™ Hex (Courage & Khazaka, Germany) skin surface moisture loss tester.

[0117] Configure the sample according to the example in Table 4-5.

[0118] Table 4 Sample Formulations of Examples

[0119] Mutually name content(%) A Deionized water margin A p-Hydroxyacetophenone 0.5 A Hexanediol 0.6 A EDTA-2Na 0.02 A Acryloyldimethyltaurate ammonium / VP copolymer 0.5 B Dipropylene glycol 7 B Silybum Table 5 C Isononyl isononanoate 8 C Cetearyl alcohol 1 C PEG-100 stearate, glyceryl stearate 1.5 C Tocopheryl acetate 0.5 D Retinol Table 5

[0120] Preparation steps:

[0121] 3. Set the emulsification pot temperature to 80-90℃, put phase A into the emulsification pot, turn on the heating and stirring (30-50r / min) to disperse phase A evenly for later use;

[0122] 4. Add phase B to an external container, heat to 70-80℃, and after it melts and becomes transparent, keep it warm for later use;

[0123] 5. Add phase C to the oil phase pot and heat to 70-80℃. After dissolution, transfer it to the emulsification pot and start stirring (30-50 r / min) and homogenizing (1500-3000 r / min) for 5 minutes. After completion, keep stirring and keep warm for 10 minutes. Then start cooling to 45℃.

[0124] 6. After heating and dissolving phase D, add it to the emulsification pot, start homogenization (1500-3000r / min) for 5 minutes, and after completion, cool it down to 35-38℃, and discharge it after passing the inspection.

[0125] Table 5. Amounts of retinol and silymarin added in the example samples.

[0126] Retinol (%) Silymarin (%) Retinol: Silymarin Comparative Example 1 0 0 —— Comparative Example 2 0.1 0 —— Comparative Example 3 0.2 0 —— Comparative Example 4 0.3 0 —— Comparative Example 5 0.4 0 —— Comparative Example 6 0 0.2 —— Comparative Example 7 0 0.3 —— Example 1 0.1 0.01 1:0.1 Example 2 0.1 0.02 1:0.2 Example 3 0.1 0.1 1:1 Example 4 0.1 0.3 1:3 Example 5 0.2 0.01 1:0.05 Example 6 0.2 0.02 1:0.1 Example 7 0.2 0.1 1:0.5 Example 8 0.2 0.3 1:1.5 Example 9 0.3 0.1 1:0.33 Example 10 0.3 0.3 1:1 Example 11 0.3 0.5 1:1.67 Example 12 0.4 0.1 1:0.25 Example 13 0.4 0.4 1:1 Example 14 0.4 0.8 1:2

[0127] The test results are shown in Table 6 below.

[0128] Table 6 Results of the transdermal water loss test

[0129] Change rate of transdermal water loss (%) at room temperature over 4 hours Change rate of transdermal water loss (%) at room temperature over 8 hours Comparative Example 1 -24.12 -22.85 Comparative Example 2 -18.36 -15.13 Comparative Example 3 -17.65 -14.66 Comparative Example 4 -12.15 -10.03 Comparative Example 5 -7.15 -5.19 Comparative Example 6 -23.03 -22.12 Comparative Example 7 -23.96 -22.75 Example 1 -20.55 -18.65 Example 2 -21.52 -20.17 Example 3 -24.75 -22.53 Example 4 -25.13 -23.75 Example 5 -18.65 -15.43 Example 6 -18.73 -16.89 Example 7 -19.65 -17.63 Example 8 -20.75 -18.42 Example 9 -17.53 -15.23 Example 10 -18.79 -16.87 Example 11 -19.15 -17.23 Example 12 -13.12 -10.56 Example 13 -16.41 -14.32 Example 14 -17.33 -15.78

[0130] Comparing Examples 1-4 with Comparative Example 2, Comparative Examples 5-8 with Comparative Example 3, Comparative Examples 9-11 with Comparative Example 4, and Comparative Examples 12-14 with Comparative Example 5, it can be seen that adding silymarin can achieve a significant anti-water loss effect.

[0131] Comparing Comparative Example 2 and Examples 1-3, it can be seen that when retinol and silymarin are added in a ratio of 1:0.1 to 1, the anti-water loss effect is better as the silymarin content increases. Comparing the transdermal water loss change test results of Examples 3 and 4, it can be seen that as the silymarin content increases, the improvement in the anti-water loss effect slows significantly when the retinol to silymarin ratio is less than 1:1, and increasing the silymarin content has limited effect on improving the anti-water loss effect.

[0132] Comparing Comparative Example 3 and Example 5, it can be seen that when the amount of silymarin added is very small and the ratio of retinol to silymarin is greater than 1:0.1, the improvement in the anti-dehydration effect is not significant compared to Example 3. Comparing Example 8 and Examples 6-7, it can be seen that as the content of silymarin increases, when the ratio of retinol to silymarin is less than 1:1, the improvement in the anti-dehydration effect slows down significantly, and the increase in silymarin content has limited effect on improving the anti-dehydration effect.

[0133] Comparing Examples 14 and 12-13, it can be seen that as the content of silymarin increases, when the ratio of retinol to silymarin is less than 1:1, the improvement in the anti-water loss effect slows down significantly. Increasing the content of silymarin has limited effect on improving the anti-water loss effect.

[0134] Application Example 1: An emulsion

[0135]

[0136] Preparation method:

[0137] 1. Add phase A raw material to the emulsification tank, set the temperature to 80-90℃, and start stirring and heating; when the emulsification tank reaches 80-90℃, start homogenization at 1500-4000r / min until there are no lumps in the material.

[0138] 2. Mix the B phase raw material in the oil phase pot and heat it to 75-80℃. After the B phase is completely dissolved, add the B phase raw material to the emulsification tank and keep stirring to homogenize and disperse it evenly.

[0139] 3. Mix the C-phase raw materials in an external container and heat to 60-80℃. After the C-phase is completely dissolved, add the C-phase raw materials to the emulsification tank, keep stirring, and after evenly dispersing, turn on the cooling.

[0140] 4. Continue stirring and cooling the emulsification tank to 45℃. After dissolving the D phase raw material, add it to the emulsification pot. After stirring evenly, continue cooling. When the temperature is 30-38℃, discharge and test.

[0141] Application Example 2: A face cream

[0142]

[0143] Preparation method:

[0144] 1. Add phase A raw material to the emulsification tank, set the temperature to 80-90℃, and start stirring and heating; when the emulsification tank reaches 80-90℃, start homogenization at 1500-4000r / min until there are no lumps in the material.

[0145] 2. Mix the B phase raw material in the oil phase pot and heat it to 75-80℃. After the B phase is completely dissolved, add the B phase raw material to the emulsification tank and keep stirring to homogenize and disperse it evenly.

[0146] 3. Mix the C phase raw materials in an external container and heat to 60-80℃. After the C phase is completely dissolved, add the C phase raw materials to the emulsification tank, keep stirring, and after evenly dispersing, turn on the cooling.

[0147] 4. Continue stirring and cooling the emulsification tank to 45℃. After dissolving the D phase raw material, add it to the emulsification pot. After stirring evenly, continue cooling. When the temperature is 30-38℃, discharge and test.

[0148] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Use of silybin in the preparation of retinol transdermal absorption enhancer.

2. A skin external preparation comprising: Retinol and transdermal absorption enhancers; The transdermal absorption enhancer is silybin; The mass ratio of retinol to silybin is 1:0.05-2.

3. The skin external preparation according to claim 2, characterized in that The mass ratio of retinol to silybin is 1:0.1-1.

4. A use of silybin as a moisturizing agent or moisturizing enhancer in a composition containing retinol, characterized in that: The mass ratio of retinol to silybin is 1:0.05-2.

5. The use according to claim 4, characterized in that: The mass ratio of retinol to silybin is 1:0.1-1.

6. A topical skin care product, wherein: The external skin care product comprises the external skin preparation according to any one of claims 2 to 3.

7. The skin care product according to claim 6, characterized in that The added amount of retinol is 0.01-0.3%; the added amount of silybin is 0.02-0.3%.

8. The external skin care product according to claim 6, wherein The external skin care product includes: one or more of emulsions, creams, ointments, and facial masks.

Images