Application of glabridin as a skin penetration enhancer in topical skin preparations

Abstract

Embodiments of the present disclosure disclose the application of glabridin as a skin penetration enhancer in topical skin preparations. The topical skin preparation in this application includes: arbutin and a skin penetration enhancer. This application can promote the skin penetration of arbutin by glabridin, and at the same time can further improve the whitening effect of arbutin.

Description

Technical Field

[0001] Embodiments of the present disclosure relate to the field of biotechnology, and more particularly to the application of glabridin as a skin penetration enhancer in topical skin preparations. Background Art

[0002] Arbutin, also known as arbutin, has the chemical formula C 12 H 16 O 7 and is a natural active substance extracted from the leaves of Arctostaphylos uva-ursi, a plant of the Ericaceae family. It can effectively inhibit the activity of tyrosinase in skin melanocytes and block the formation of melanin, thereby reducing skin pigment deposition.

[0003] The skin epidermis is mainly composed of a sebum film and a stratum corneum. Among them, the sebum film is a transparent, weakly acidic film on the skin surface, which is mainly formed by the fusion of the oil secreted by the sebaceous glands and the water secreted by the sweat glands. The stratum corneum is a complex composed of proteins and lipids. In addition, in the extracellular space of the stratum corneum cells, there is also a lamellar membrane formed by highly hydrophobic lipids surrounding the stratum corneum. Therefore, the skin epidermis has a certain water resistance.

[0004] However, when arbutin is applied to the skin, due to the hydrophilicity conferred by the glucose residue in the arbutin structure, there is the following technical problem 1: The penetration ability of arbutin on the skin surface is limited (for example, the logP value of α-arbutin is low, that is, α-arbutin is highly hydrophilic and poorly lipophilic), which in turn limits the bioavailability and the ability of targeted action, and weakens the whitening effect of arbutin.

[0005] Continuing, current research on improving the permeability of arbutin mainly focuses on physical penetration enhancement methods, etc. For example, micro-needle technology is used for arbutin administration to achieve the purpose of penetration enhancement. However, since micro-needle technology belongs to a physical beauty method, that is, it is necessary to pierce the skin epidermis through micro-needles to achieve the purpose of transdermal drug delivery, there is the following technical problem 2: It may cause side effects such as skin allergies, itching, redness, scarring, and closed comedones.

[0006] The above information disclosed in this background art section is only used to enhance the understanding of the background of the inventive concept, and therefore, it may include information that does not form the prior art known to those of ordinary skill in the art. Summary of the Invention

[0007] This summary of the disclosure is intended to introduce, in a brief form, concepts that will be described in detail in the following detailed description section. This summary of the disclosure is not intended to identify key features or essential features of the claimed technical solution, nor is it intended to be used to limit the scope of the claimed technical solution.

[0008] Some embodiments of the present disclosure provide the application of glabridin as a skin penetration enhancer in topical skin preparations and topical skin care products to solve one or more of the technical problems mentioned in the above background art section.

[0009] In a first aspect, some embodiments of the present disclosure provide an application of glabridin as a skin penetration enhancer in topical skin preparations, wherein the topical skin preparation includes: arbutin and a skin penetration enhancer.

[0010] Optionally, the mass fraction of the skin penetration enhancer is: 0.001% - 0.2%.

[0011] Optionally, the mass fraction of the skin penetration enhancer is: 0.02% - 0.2%.

[0012] Optionally, the arbutin is at least one of α - arbutin, β - arbutin, and deoxyarbutin.

[0013] Optionally, the mass fraction of the arbutin is: 0.1% - 2%.

[0014] Optionally, the skin penetration enhancer is an alcohol solution of glabridin, and a short - chain alcohol or a short - chain polyol is used as a solvent in the alcohol solution; the short - chain polyol is one of butanediol, propylene glycol, and dipropylene glycol.

[0015] Optionally, the skin penetration enhancer is one of a glabridin lipid inclusion, a glabridin lipid microemulsion inclusion, and a glabridin lipid microcapsule inclusion.

[0016] Optionally, the mass ratio of the arbutin to the skin penetration enhancer is 0.1 - 2:0.01 - 0.2.

[0017] Optionally, the skin penetration enhancer further includes: inositol, wherein the mass ratio of the arbutin, glabridin, and inositol is 0.1 - 2:0.01 - 0.2:0.1 - 2.

[0018] Optionally, the mass ratio of the arbutin, glabridin, and inositol is 0.5 - 2:0.01 - 0.1:0.1 - 2.

[0019] In a second aspect, some embodiments of the present disclosure provide a topical skin care product, wherein the topical skin care product includes the topical skin preparation as described in the first aspect.

[0020] Optionally, the topical skin care product includes one or more of an emulsion, a cream, an ointment, and a facial mask.

[0021] Optionally, in addition to the above-mentioned topical skin care products containing the above-mentioned topical skin agents, it may further include: colorants, depigmenting agents, emollients, film-forming agents, fragrances, moisturizers, lubricants, thickening agents, preservatives, stabilizers, surfactants, thickeners, viscosity improvers, vitamins, solvents, pH modifiers, sunscreens, bioactive agents, rheology modifiers. Among them, the above components and / or active ingredients can be neutral, acidic, alkaline or in the form of salts, etc. The exact dosage can be adjusted by those skilled in the art according to actual needs, such as dosage, ratio, etc.

[0022] The above-mentioned various embodiments of the present disclosure have the following beneficial effects: Through the application of glabridin as a skin penetration enhancer in topical skin agents in some embodiments of the present disclosure, that is, through glabridin, not only the skin permeability of arbutin is promoted, but also since glabridin can inhibit the activity of tyrosinase and prevent the binding of the substrate to tyrosinase, therefore, the topical skin agent combining arbutin and glabridin can further enhance the whitening effect. In addition, the topical skin agent of the present disclosure can directly act on the skin without using methods such as microneedles to apply arbutin, thereby overcoming the side effects such as skin allergy, itching, redness, scarring, closed comedones, etc. that may be caused by physical beauty methods such as microneedle technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Combined with the drawings and referring to the following specific embodiments, the above and other features, advantages and aspects of each embodiment of the present disclosure will become more obvious. Throughout the drawings, the same or similar reference numerals represent the same or similar elements. It should be understood that the drawings are schematic and the elements are not necessarily drawn to scale.

[0024] Figure 1 It is a comparison chart of the cumulative permeation amount of arbutin in the sample solutions corresponding to different embodiments for 20 hours;

[0025] Figure 2 It is a comparison chart of the retention amount of arbutin in the epidermis + dermis in the sample solutions corresponding to different embodiments for 20 hours;

[0026] Figure 3 It is another comparison chart of the cumulative permeation amount of arbutin in the sample solutions corresponding to different embodiments for 20 hours;

[0027] Figure 4 It is another comparison chart of the retention amount of arbutin in the epidermis + dermis in the sample solutions corresponding to different embodiments for 20 hours shown;

[0028] Figure 5 It is a comparison chart of the cumulative permeation amount of arbutin in the sample solutions corresponding to different embodiments for 6 hours;

[0029] Figure 6Another cumulative permeation amount comparison chart of arbutin in the sample solutions corresponding to different embodiments for 20 hours;

[0030] Figure 7 Retention amount comparison chart of arbutin in the sample solutions corresponding to different embodiments for 20 hours. Detailed implementation manners

[0031] Embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although some embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure can be implemented in various forms and should not be construed as limited to the embodiments set forth herein. On the contrary, these embodiments are provided to more thoroughly and completely understand the present disclosure. It should be understood that the drawings and embodiments of the present disclosure are only for exemplary purposes and are not used to limit the protection scope of the present disclosure.

[0032] In addition, it should be noted that for the convenience of description, only parts related to the relevant invention are shown in the drawings. Without conflict, the embodiments in the present disclosure and the features in the embodiments can be combined with each other.

[0033] It should be noted that the modifications of "one" and "multiple" mentioned in the present disclosure are illustrative rather than restrictive. Those skilled in the art should understand that unless otherwise clearly specified in the context, it should be understood as "one or more".

[0034] It should be noted that "about" mentioned in the present disclosure, when used to limit a numerical value, means ±5% of the specified numerical value.

[0035] It should be noted that the term "%" mentioned in the present disclosure, unless otherwise specified, means mass %.

[0036] It should be noted that "normal temperature" mentioned in the present disclosure refers to the ambient temperature, that is, without special heating or cooling treatment.

[0037] Term explanations

[0038] "Glabridin" is a natural whitening agent isolated from licorice flavonoids and has no side effects on the human body. It is a reddish-brown powder at normal temperature, insoluble in water, and easily soluble in organic solvents such as ethanol, propylene glycol, and 1,3-butanediol. Among them, glabridin has antibacterial effects, can prevent dermatitis and pigmentation caused by ultraviolet rays, and skin roughness, etc., can scavenge superoxide ions, and inhibit hemolysis caused by hydrogen peroxide.

[0039] "Polyethylene glycol 400", also known as PEG, is a non-ionic inert solvent. It is a colorless viscous liquid at room temperature and can fully dissolve vitamin C, vitamin E, and hydroquinone. At a high temperature of 100 °C, it can completely dissolve titanium dioxide, completely dissolve undecylenic acid and its zinc salt. At room temperature, it remains stable and does not react with active substances such as transdermal agents. It can be used as a plasticizer, softener, wetting agent, lubricant, solvent, adhesive, etc.

[0040] "Paraformaldehyde", also known as polyoxymethylene, is a polymer of formaldehyde. Among them, paraformaldehyde is often used for disinfection, sterilization, etc., and can also be used to prepare pure formaldehyde.

[0041] "Inositol" (Inositol) Chemical name: Cyclohexanehexol, Molecular formula: C 6 H 12 O 6 , is a naturally occurring carbohydrate and is part of the vitamin B complex. Inositol can be added to skin care products as a moisturizer and antioxidant to improve skin health.

[0042] Description of experimental materials

[0043] Among them, the description of the experimental materials is specifically shown in Table 1 below: .

[0044] Description of experimental instruments

[0045] Among them, the description of the experimental instruments is specifically shown in Table 2 below: .

[0046] Description of experimental methods

[0047] Among them, the test method uses an in vitro permeation experiment. Specifically, a Franz diffusion cell is used to measure arbutin in different sample solutions, and the in vitro percutaneous permeation and retention in different skin layers on porcine skin (skin of Bama mini-pig) are measured. The specific experimental steps are as follows:

[0048] First step, provide a biological membrane with a thickness of 800 - 100 μm through the skin of Bama mini-pig.

[0049] Second step, set the effective diffusion area of the Franz diffusion cell to 1.54 cm 2 , and set up the supply pool and the receiving pool.

[0050] Among them, the volume of the receiving solution is 8 mL.

[0051] Step 3: Fix the fresh skin sample (skin of Bama mini-pig) between the supply pool and the receiving pool, place the sample solution in the supply pool respectively, and seal it with plastic wrap to prevent the volatilization of the sample solution.

[0052] Step 4: Add 8 mL of receiving solution (Phosphate Buffered Saline, PBS) to the receiving pool.

[0053] Among them, the pH value of the phosphate buffer solution is 7.4. The phosphate buffer solution serves as the diffusion medium in the receiving pool. Four replicates are set for each sample. Stirring is carried out at a temperature of 32 °C and a rotation speed of 350 rpm during the experiment.

[0054] Step 5: At predetermined time intervals (6 hours and 20 hours), withdraw 1 mL of the receiving solution respectively, and supplement the same volume of the pre-set phosphate buffer solution in the receiving pool.

[0055] Step 6: After 20 hours, collect the skin tissue (taken from the skin sample) in 4% paraformaldehyde, fix it for 24 hours, and then dehydrate the skin tissue in 15% and 30% sucrose solutions in sequence until the skin tissue sinks to the bottom, then the dehydration is completed. Rinse it with phosphate buffer solution. After rinsing, embed the skin tissue in 10% CMC-Na (sodium carboxymethyl cellulose) and store it frozen.

[0056] Step 7: Use a cryostat to transversely cut the skin at the transdermal site in the frozen skin tissue into the stratum corneum (0 - 20 μm), and the epidermis + dermis (the part except the stratum corneum in the transdermal site).

[0057] Step 8: Cut the stratum corneum and the epidermis + dermis into pieces respectively, weigh them, then perform ultrasonic treatment in water for 1 hour. After ultrasonic treatment in water, centrifuge at a rotation speed of 13000 rpm for 15 minutes to obtain the supernatant, filter it with a filter membrane with a pore size of 0.22 μm, and then use HPLC (High Performance Liquid Chromatography) to detect the retention amount of arbutin in the stratum corneum after 20 hours, and the reflux amount of arbutin in the epidermis and dermis after 20 hours.

[0058] Among them, the HPLC liquid configuration is as follows: mobile phase (water: methanol = 95:5), flow rate: 1.0 mL / min, detection wavelength: 284 nm.

[0059] Description of the concentration ratio of the sample solution corresponding to different embodiments

[0060] Among them, the concentration ratios of arbutin and skin penetration enhancer (glabridin) included in the sample solutions corresponding to different embodiments are shown in Table 3 below: 。

[0061] Among them, ethanol is used as the solvent for dissolving glabridin. Water is used as the solvent for dissolving arbutin.

[0062] Among them, statistical methods are adopted, and data analysis is carried out through the Prism 8.0 data analysis tool. Statistical analysis is expressed as (x±s), and t-tests are performed. The test criterion is p < 0.05. Among them, *p < 0.05, **p < 0.01.

[0063] Experimental results

[0064] Among them, for arbutin in the sample solutions corresponding to different embodiments at 20 hours, the retention amounts and cumulative permeation amounts in different skin layers are specifically shown in Table 4 below: 。

[0065] Specifically, first, refer to Figure 1 the comparison chart of the cumulative permeation amounts of arbutin in the sample solutions corresponding to different embodiments at 20 hours shown in, and refer to Figure 2 the comparison chart of the retention amounts of arbutin in the sample solutions corresponding to different embodiments at 20 hours in the epidermis + dermis shown in. Among them, by comparing Figure 1 、 Figure 2 and Table 4, it is found that compared with the permeation amount of the arbutin aqueous solution in Example A, the skin permeation amounts and retention amounts of the arbutin aqueous solutions in Examples B, C, D, and E at 20 hours are significantly increased. Among them, the average skin retention amounts in Examples C, D, and E are increased by 433.21%, 6817.99%, and 6034.05% respectively, showing significant advantages. It can be found from this that glabridin has an obvious permeation-promoting effect on arbutin. In addition, further refer to Figure 3 another comparison chart of the cumulative permeation amounts of arbutin in the sample solutions corresponding to different embodiments at 20 hours shown in, and Figure 4 another comparison chart of the retention amounts of arbutin in the sample solutions corresponding to different embodiments at 20 hours in the epidermis + dermis shown in. Among them, by comparing Figure 3 、 Figure 4 and Examples F and G in Table 4, it is found that when the addition concentration of arbutin is 0.1%, after adding 0.1% of glabridin, the skin permeation amount and the retention amount in the epidermis + dermis at 20 hours are also significantly increased.

[0066] Furthermore, continue to explore the effect of the combination of skin penetration enhancers adding glabridin and inositol on the transdermal penetration of arbutin. The concentration ratios of arbutin and skin penetration enhancers (glabridin, inositol) included in the sample solutions corresponding to different embodiments are shown in detail in Table 5 below: 。

[0067] Experimental results

[0068] Among them, for arbutin in the sample solutions corresponding to different embodiments at 6 hours, the retention amounts and cumulative permeation amounts in different skin layers, and for arbutin in the sample solutions corresponding to different embodiments at 20 hours, the retention amounts and cumulative permeation amounts in different skin layers are specifically shown in Table 6 below: 。

[0069] Analyze Table 6, and refer to Figure 5 a cumulative permeation amount comparison chart of arbutin in the sample solutions corresponding to different embodiments at 6 hours shown in Figure 6 another cumulative permeation amount comparison chart of arbutin in the sample solutions corresponding to different embodiments at 20 hours shown in Figure 7 and an epidermis + dermis retention amount comparison chart of arbutin in the sample solutions corresponding to different embodiments at 20 hours shown in

[0070] Application Example 1

[0071] Among them, Application Example 1 is an external skin care product in the form of essence water. The components of the essence water are shown in detail in Table 7 below: 。

[0072] Preparation process:

[0073] First step, heat the corresponding components of A to 85°C and swell them evenly.

[0074] Second step, heat the corresponding components of B to 85°C and dissolve them evenly.

[0075] Third step, add the components dissolved evenly in the first step to the components dissolved evenly in the second step and homogenize for 2 - 3 min.

[0076] Step 4: Add the component corresponding to C to the components homogenized in Step 3, and homogenize for 1 - 2 min. Stir and cool down to below 40°C, then add the component corresponding to D and the dissolved component corresponding to E, and stir evenly to obtain the above essence water.

[0077] Application Example 2

[0078] Among them, Application Example 2 is an external skin care product in the form of an emulsion. The components of the emulsion are shown in Table 8 below: 。

[0079] Preparation process:

[0080] Step 1: Heat the component corresponding to A to 85°C and swell it evenly.

[0081] Step 2: Heat the component corresponding to B to 85°C and dissolve it evenly.

[0082] Step 3: Add the components dissolved evenly in Step 1 to the components dissolved evenly in Step 2 and homogenize for 2 - 3 min.

[0083] Step 4: Add the component corresponding to C to the components homogenized in Step 3, and homogenize for 1 - 2 min. Stir and cool down to below 40°C, then add the component corresponding to D and the dissolved component corresponding to E, and stir evenly to obtain the above emulsion.

[0084] Application Example 3

[0085] Among them, Application Example 3 is an external skin care product in the form of an essence water. The components of the essence water are shown in Table 9 below: 。

[0086] Preparation process:

[0087] Step 1: Heat the component corresponding to A to 85°C and swell it evenly.

[0088] Step 2: Heat the component corresponding to B to 85°C and dissolve it evenly.

[0089] Step 3: Add the components dissolved evenly in Step 1 to the components dissolved evenly in Step 2 and homogenize for 2 - 3 min.

[0090] Step 4: Add the component corresponding to C to the components homogenized in Step 3, and homogenize for 1 - 2 min. Stir and cool down to below 40°C, then add the component corresponding to D and the dissolved component corresponding to E, and stir evenly to obtain the above essence water.

[0091] Application Example 4

[0092] Among them, Application Example 4 is an external skin care product in the form of an emulsion. The components of the emulsion are shown in Table 10 below: 。

[0093] Preparation process:

[0094] First step, heat the corresponding components of A to 85°C and swell them evenly.

[0095] Second step, heat the corresponding components of B to 85°C and dissolve them evenly.

[0096] Third step, add the components dissolved evenly in the first step to the components dissolved evenly in the second step and homogenize for 2 - 3 min.

[0097] Fourth step, add the corresponding components of C to the components homogenized in the third step, and homogenize for 1 - 2 min. Stir and cool down to below 40°C, then add the corresponding components of D and the dissolved corresponding components of E, and stir evenly to obtain the above emulsion.

[0098] The above description is only some preferred embodiments of the present disclosure and an explanation of the applied technical principles. Those skilled in the art should understand that the scope of the invention involved in the embodiments of the present disclosure is not limited to the technical solutions formed by the specific combination of the above technical features, but should also cover other technical solutions formed by any combination of the above technical features or their equivalent features without departing from the above inventive concept. For example, the technical solutions formed by mutually replacing the above features with the (but not limited to) technical features having similar functions disclosed in the embodiments of the present disclosure.

Claims

1. Use of glabridin as a skin penetration enhancer for increasing the retention of arbutin in the epidermis and dermis of the skin in the preparation of a skin external preparation, wherein: The skin external preparation comprises arbutin and a skin penetration enhancer, wherein the skin penetration enhancer comprises glabridin and inositol, and the mass ratio of the arbutin, glabridin and inositol is 0.1-2:0.01-0.2:0.1-2.

2. The use according to claim 1, wherein: The arbutin is at least one of α-arbutin, β-arbutin and deoxyarbutin.

3. A topical skin care product, wherein: The external skin care product comprises the external skin preparation according to any one of claims 1 to 2.

4. The external skin care product according to claim 3, wherein The external skin care product includes: one or more of emulsions, creams, ointments, and facial masks.

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