Skin transparentizing reagent and preparation method thereof

Abstract

The invention provides a skin transparentizing reagent and a preparation method thereof, and belongs to the technical field of biomedicine. The skin transparentizing reagent provided by the invention is prepared from the following components in parts by mass: 0.5 to 70 parts of penetration enhancer; 0-25 parts of a penetrant; 0 to 50 parts of a surfactant; 0-30 parts of a humectant; 0.1 to 20 parts of an antioxidant; 0.1 to 15 parts of an emulsifier; 0-20 parts of a thickening agent; 0.5 to 30 parts of a solubilizer; 0.1 to 30 parts of a diluent; the penetration enhancer is azone or at least two of azone, sodium sulfide and thiazone. According to the invention, at least two of azone, sodium sulfide and thiazone or azone is adopted as a penetration enhancer, so that the skin can be transparent, subcutaneous blood vessels can be exposed more clearly, and fundamental research and clinical treatment application in the field of biomedicine are facilitated.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a skin clearing agent and a preparation method thereof. Background Art

[0002] At present, in the biomedical field, when injecting preparations or conducting other research on the skin of an organism, the location of blood vessels in the relevant skin area is usually determined based on naked eye observation. In this way, only large blood vessels visible to the naked eye can be avoided, and secondary blood vessels cannot be seen clearly, which is not conducive to the smooth conduct of basic research and clinical treatment applications in the biomedical field. For example, in the medical beauty industry, if secondary blood vessels are not avoided when injecting fine-tuning injections on the skin surface, it is easy to cause bleeding, bruising, redness, swelling, inflammation, nerve damage, local asymmetry, lumps in the affected area and other problems on the skin surface. Summary of the invention

[0003] The purpose of the present invention is to provide a skin clearing agent and a preparation method thereof. The skin clearing agent provided by the present invention can make the skin transparent, thereby exposing the subcutaneous blood vessels more clearly, which is helpful for basic research and clinical treatment applications in the biomedical field.

[0004] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0005] The present invention provides a skin clearing agent, which comprises the following components by weight:

[0006] 0.5-70 parts of penetration enhancer; 0-25 parts of penetrant; 0-50 parts of surfactant; 0-30 parts of moisturizer; 0.1-20 parts of antioxidant; 0.1-15 parts of emulsifier; 0-20 parts of thickener; 0.5-30 parts of solubilizer; 0.1-30 parts of diluent;

[0007] The penetration enhancer is azone, or at least two of azone, sodium sulfide and thiazone.

[0008] Preferably, the penetration enhancers are sodium sulfide and thiazide; the mass ratio of sodium sulfide to thiazide is 0.01-20:0.5-50.

[0009] Preferably, the penetrant comprises urea and / or plant essential oil.

[0010] Preferably, the surfactant comprises an anionic surfactant and / or a nonionic surfactant.

[0011] Preferably, the anionic surfactant includes sodium lauryl sulfate; and the nonionic surfactant includes polyethylene glycol octylphenyl ether.

[0012] Preferably, the moisturizer comprises one or more of glycerin, shea butter, avocado oil and olive oil.

[0013] Preferably, the antioxidant comprises vitamin E and / or isooctyl ferulate.

[0014] Preferably, the emulsifier comprises vaseline and / or tretinoin cream.

[0015] Preferably, the thickener comprises one or more of sodium alginate, xanthan gum and gelatin.

[0016] Preferably, the solubilizer comprises propylene glycol and / or dipolyhydroxystearate.

[0017] Preferably, the dipolyhydroxystearate includes one or more of dipolyhydroxystearate-400, dipolyhydroxystearate-200, dipolyhydroxystearate-100, dipolyhydroxystearate-75, dipolyhydroxystearate-30 and dipolyhydroxystearate-7.

[0018] The present invention provides a method for preparing the skin clearing agent described in the above technical solution, comprising the following steps:

[0019] The components of the skin clearing agent are mixed to obtain the skin clearing agent.

[0020] The present invention provides a skin transparent agent, which includes the following components by mass: 0.5-70 parts of a penetration enhancer; 0-25 parts of a penetrant; 0-50 parts of a surfactant; 0-30 parts of a moisturizer; 0.1-20 parts of an antioxidant; 0.1-15 parts of an emulsifier; 0-20 parts of a thickener; 0.5-30 parts of a solubilizer; 0.1-30 parts of a diluent; the penetration enhancer is azone, or at least two of azone, sodium sulfide and thiophene. The present invention uses at least two of azone, sodium sulfide and thiophene, or uses azone as a penetration enhancer, which can make the skin transparent, thereby making the subcutaneous blood vessels more clearly exposed, which is helpful for basic research and clinical treatment applications in the biomedical field.

[0021] Furthermore, when the skin clearing agent in the present invention uses PEG and / or propylene glycol as a solubilizer, it also has a repairing and whitening effect on the skin, which is more conducive to the application in the medical beauty industry and the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The photographs are of the mouse abdominal skin test area after being wiped and disinfected with alcohol and before being applied with the skin clearing reagents in Examples 1 to 6 (0 min) and 10 min and 15 min after being applied;

[0023] Figure 2The photographs are of the mouse abdominal skin test area after applying the skin clearing reagents of Examples 1 to 6 for 20 minutes, 25 minutes, and after 20 minutes of recovery;

[0024] Figure 3 The photos are of the mouse abdominal skin test area after being wiped and disinfected with alcohol and before being applied with the reagents in Comparative Examples 1 to 3 (0 min) and 15 min after being applied;

[0025] Figure 4 The photographs are taken before (0 min), 15 min and 20 min after the skin clearing agents in Comparative Examples 4 to 6 and Examples 7 to 9, Example 1 and Example 10 were applied to the test area of ​​the abdominal skin of mice;

[0026] Figure 5 The photographs are taken before (0 min), 15 min and 25 min after applying the skin clearing agent in Examples 11 to 14 to the test area of ​​the mouse abdominal skin;

[0027] Figure 6 The photographs are of the rat abdominal skin test area before (0 min) and 10 min and 25 min after application of the skin clearing agent in Examples 15 to 16;

[0028] Figure 7 These are photos of the rat abdominal skin test area after application of the skin clearing agent of Examples 15-16 for 35 minutes, 45 minutes, and after recovery for 20 minutes. DETAILED DESCRIPTION

[0029] The present invention provides a skin clearing agent, which comprises the following components by weight:

[0030] 0.5-70 parts of penetration enhancer; 0-25 parts of penetrant; 0-50 parts of surfactant; 0-30 parts of moisturizer; 0.1-20 parts of antioxidant; 0.1-15 parts of emulsifier; 0-20 parts of thickener; 0.5-30 parts of solubilizer; 0.1-30 parts of diluent;

[0031] The penetration enhancer is azone, or at least two of azone, sodium sulfide and thiazone.

[0032] In the present invention, unless otherwise specified, the raw materials used are commercially available products well known to those skilled in the art or are prepared by methods well known to those skilled in the art.

[0033] In the present invention, the skin clearing agent includes 0.5 to 70 parts of a permeation enhancer, further 1 to 30 parts, further 2 to 25 parts, specifically 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18 or 20 parts by mass. The permeation enhancer of the present invention is azone, or at least two of azone, sodium sulfide and thiophene; for example, the permeation enhancer in the embodiment of the present invention can be azone alone, or a mixture of azone and sodium sulfide, or a mixture of azone and thiophene, or a mixture of sodium sulfide and thiophene, or a mixture of azone, sodium sulfide and thiophene; in the embodiment of the present invention, when the permeation enhancer is a mixture of azone and sodium sulfide, the mass ratio of azone to sodium sulfide can be 0.01-20:0.5-50, further can be 0.04-2:3-13, specifically can be 0.04:2.5, 0.04:5, 0.08:9.5, 0.067:7.5, 0.125:9.5 or 3:9.5. The present invention adopts the above-mentioned types of permeation enhancers, which can affect the stratum corneum of the active biological surface, increase the gaps between cells on the surface of the active tissue, reduce the defense ability, and facilitate the various components to play a role through the epidermis.

[0034] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0 to 25 parts of the penetrant, further 0.5 to 20 parts, and further 1 to 5 parts, specifically 1.5 parts, 2 parts or 2.5 parts. The penetrant in the embodiment of the present invention may include urea and / or plant essential oil; the plant essential oil may specifically be clove oil. The above-mentioned types of penetrants are used in the embodiment of the present invention to break the skin barrier, promote rapid penetration of each component, and improve the efficacy of the skin clearing agent.

[0035] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0 to 50 parts of a surfactant, further 0.01 to 35 parts, and further 0.03 to 20 parts, specifically 0.05 parts, 0.1 parts, 0.15 parts, 0.2 parts, 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts. The surfactant in the embodiment of the present invention may include anionic surfactants and / or nonionic surfactants, specifically anionic surfactants or nonionic surfactants, or anionic surfactants and nonionic surfactants; the anionic surfactant may include sodium lauryl sulfate, and the nonionic surfactant may include polyethylene glycol octylphenyl ether. That is, the surfactant in the embodiment of the present invention may include sodium dodecyl sulfate and / or polyethylene glycol octylphenyl ether (Trition x-100), specifically sodium dodecyl sulfate or Trition x-100, or a mixture of sodium dodecyl sulfate and Trition x-100; when the surfactant is a mixture of sodium dodecyl sulfate and Trition x-100, the mass ratio of sodium dodecyl sulfate to Trition x-100 in the surfactant may be 0.1-20:1-30, further may be 0.1-0.2:2-8, specifically may be 0.11:3 or 0.1:6. The use of the above-mentioned types of surfactants in the embodiment of the present invention can enable the components in the skin clearing agent to form a stable dispersion system, which is beneficial to maintaining the stability and effectiveness of the skin clearing agent.

[0036] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0 to 30 parts of a moisturizer, further 1 to 25 parts, and further 2 to 20 parts, specifically 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 12 parts or 15 parts. The moisturizer in the embodiment of the present invention may include one or more of glycerin, shea butter, avocado oil and olive oil, specifically glycerin. The above-mentioned moisturizer is used in the embodiment of the present invention to increase the moisture content of the skin, improve the dry skin condition, help improve the protection against external stimuli, and promote the repair of damaged skin.

[0037] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0.1 to 20 parts of antioxidants, further 0.5 to 15 parts, and further 0.1 to 10 parts, specifically 0.3 parts, 0.4 parts, 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts or 8 parts. The antioxidant described in the embodiment of the present invention may include vitamin E and / or isooctyl ferulate, specifically vitamin E or isooctyl ferulate. The above-mentioned types of antioxidants are used in the embodiment of the present invention, which can react with free radicals, neutralize harmful oxidative molecules, thereby reducing the damage of free radicals to the skin and the active ingredients in the skin clearing agent, which is beneficial to reduce the oxidative damage of skin cells, prolong the shelf life of the skin clearing agent, and maintain the activity and effect of the skin clearing agent.

[0038] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0.1 to 15 parts of emulsifier, further 0.2 to 11 parts, and further 0.4 to 6 parts, specifically 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 4 parts or 5 parts. The emulsifier described in the embodiment of the present invention may include vaseline and / or retinoic acid cream, specifically vaseline or retinoic acid cream. The above-mentioned types of emulsifiers are used in the embodiment of the present invention, so that the components in the skin clearing agent can be evenly dispersed, forming an emulsified state, increasing stability, and being conducive to softening the skin, reducing surface tension, and improving absorption capacity, so that it is not easy to stratify or deteriorate.

[0039] In the present invention, based on the mass fraction of the penetration enhancer, the skin transparent agent includes 0 to 20 parts of thickener, further 0.1 to 15 parts, and further 0.3 to 10 parts, specifically 0.5 parts, 1 parts, 1.5 parts, 2.5 parts, 3 parts, 3.5 parts, 5 parts or 7 parts. The thickener in the embodiment of the present invention may include one or more of sodium alginate, xanthan gum and gelatin, specifically sodium alginate, xanthan gum or gelatin. The above-mentioned types of thickeners are used in the embodiment of the present invention, which can play a supporting skeleton role, help increase the contact area between the skin transparent agent and the skin, improve the ductility and smoothness of the skin transparent agent, and make it easier to be evenly distributed on the skin; at the same time, it can increase the adhesion and cohesion of the skin transparent agent, prevent the phase separation or deposition of various components during use, and maintain the uniformity and consistency of the skin transparent agent.

[0040] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0.5 to 30 parts of a solubilizer, further 1 to 20, further 1.3 to 10 parts, specifically 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8 or 9 parts. The solubilizer in the embodiment of the present invention may include propylene glycol and / or dipolyhydroxystearate (PEG), specifically PEG or propylene glycol, or a mixture of PEG and propylene glycol; when the solubilizer is a mixture of PEG and propylene glycol, the mass ratio of PEG to propylene glycol may be 1 to 20:1 to 10, further 3 to 6:4, specifically 4 to 5:4. The dipolyhydroxystearate described in the embodiment of the present invention can include one or more of dipolyhydroxystearate-400 (PEG-400), dipolyhydroxystearate-200 (PEG-200), dipolyhydroxystearate-100 (PEG-100), dipolyhydroxystearate-75 (PEG-75), dipolyhydroxystearate-30 (PEG-30) and dipolyhydroxystearate-7 (PEG-7), specifically PEG-400, PEG-200, PEG-100, PEG-75, PEG-30 or PEG-7. The above-mentioned solubilizing agent is used in the embodiment of the present invention to protect and whiten the skin. The PEG (such as PEG-30, etc.) described in the embodiment of the present invention is purchased from DIY Research Institute.

[0041] In the present invention, based on the mass fraction of the penetration enhancer, the skin clearing agent includes 0.1 to 30 parts of diluent, further 0.2 to 20 parts, and further 0.4 to 10 parts, specifically 0.5 parts, 1 parts, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 4 parts, 5 parts or 6 parts. The diluent in the embodiment of the present invention may include water and / or phosphate buffer, specifically water or phosphate buffer; the concentration of the phosphate buffer may specifically be 0.01M.

[0042] In an embodiment of the present invention, the mass fractions of the penetrant, surfactant, humectant and thickener in the skin clearing agent are not all 0. Specifically, in the skin clearing agent, only the mass fraction of the penetrant may be 0, only the mass fraction of the humectant may be 0, only the mass fraction of the thickener may be 0, or both the mass fractions of the penetrant and the surfactant may be 0.

[0043] The skin clearing agent of the present invention can be applied to living organisms, such as animals or human bodies, and the animals can be mice or rats. In the embodiments of the present invention, mouse skin tissue and rat skin tissue are used as examples for illustration.

[0044] In an embodiment of the present invention, the formula of the skin clearing agent may be any one of the following formulas by weight:

[0045] Formula 1: 0.01-20 parts of sodium sulfide, 1-50 parts of thiophene, 0.01-20 parts of sodium dodecyl sulfate, 1-30 parts of glycerol, 1-15 parts of vitamin E, 0.1-11 parts of vaseline, 1-10 parts of sodium alginate, 1-20 parts of PEG (for example, PEG-30, PEG-7, PEG-75, PEG-100 or PEG-200), and 0.1-30 parts of phosphate buffer; wherein sodium sulfide can be specifically 0.04 parts, 0.08 parts, 0.1 parts or 0.2 parts, thiophene can be specifically 5 parts, 6 parts, 8 parts, 10 parts, 11 parts, 12 parts or 13 parts, dodecane The amount of sodium thiosulfate may be 0.05, 0.1, 0.12 or 0.2 parts, the amount of glycerol may be 5, 6, 7, 8, 10 or 12 parts, the amount of vitamin E may be 4, 5 or 6 parts, the amount of petrolatum may be 2, 2.5 or 3 parts, the amount of sodium alginate may be 2.5, 3 or 3.5 parts, the amount of PEG (for example, PEG-30, PEG-7, PEG-75, PEG-100 or PEG-200) may be 1.5, 2 or 2.5 parts, and the amount of phosphate buffer may be 0.5, 1, 1.5, 2 or 2.5 parts.

[0046] Formula 2: 0.1-20 parts of sodium sulfide, 0.5-30 parts of thiazone, 1-25 parts of glycerol, 0.1-5 parts of isooctyl ferulate, 0.1-11 parts of vaseline, 1-10 parts of sodium alginate, 1-20 parts of PEG (for example, PEG-200 or PEG-30), and 1-30 parts of water; wherein sodium sulfide can specifically be 1 part, 1.5 parts or 2 parts, thiazone can specifically be 3 parts, 4 parts or 5 parts, glycerol can specifically be 7 parts, 8 parts or 9 parts, isooctyl ferulate can specifically be 0.3 parts, 0.4 parts or 0.5 parts, vaseline can specifically be 2 parts, 2.5 parts or 3 parts, sodium alginate can specifically be 2.5 parts, 3 parts or 3.5 parts, PEG (for example, PEG-200 or PEG-30) can specifically be 3 parts, 4 parts or 5 parts, and water can specifically be 4 parts, 5 parts or 6 parts.

[0047] Formula 3: 0.1-20 parts of sodium sulfide, 0.5-30 parts of thiophene, 0.1-20 parts of sodium dodecyl sulfate, 1-25 parts of glycerol, 1-15 parts of vitamin E, 0.1-11 parts of vaseline, 1-10 parts of sodium alginate, 1-20 parts of PEG (for example, PEG-200 or PEG-30), and 1-30 parts of water; wherein sodium sulfide can be specifically 1 part, 1.5 parts or 2 parts, and thiophene can be specifically 3 parts, 4 parts or 5 parts. The amount of sodium lauryl sulfate may be 1.5, 2 or 2.5 parts, the amount of glycerol may be 7, 8 or 9 parts, the amount of vitamin E may be 4, 5 or 6 parts, the amount of petrolatum may be 2, 2.5 or 3 parts, the amount of sodium alginate may be 2.5, 3 or 3.5 parts, the amount of PEG (for example, PEG-200 or PEG-30) may be 3, 4 or 5 parts, and the amount of water may be 4, 5 or 6 parts.

[0048] Formula 4: 0.01-20 parts of sodium sulfide, 0.5-30 parts of thiophene, 0.1-20 parts of sodium dodecyl sulfate, 1-20 parts of glycerol, 1-15 parts of vitamin E, 0.1-11 parts of vaseline, 1-10 parts of sodium alginate, 1-10 parts of propylene glycol, 1-20 parts of PEG (for example, PEG-200 or PEG-30), and 0.1-30 parts of phosphate buffer; wherein sodium sulfide can be specifically 0.05 parts, 0.1 parts or 0.15 parts, thiophene can be specifically 7 parts, 8 parts or 9 parts, and ten parts The amount of sodium dialkyl sulfate may be 1.5, 2 or 2.5 parts, the amount of glycerol may be 3, 4 or 5 parts, the amount of vitamin E may be 4, 5 or 6 parts, the amount of vaseline may be 2, 2.5 or 3 parts, the amount of sodium alginate may be 2.5, 3 or 3.5 parts, the amount of propylene glycol may be 3, 4 or 5 parts, the amount of PEG (for example, PEG-200 or PEG-30) may be 3, 4 or 5 parts, and the amount of phosphate buffer may be 0.5, 1 or 1.5 parts.

[0049] Formula 5: 0.01-20 parts of sodium sulfide, 0.5-30 parts of thiazone, 1-20 parts of urea, 0.01-20 parts of sodium dodecyl sulfate, 1-15 parts of Trition x-100, 1-15 parts of vitamin E, 0.1-11 parts of vaseline, 1-20 parts of PEG (for example, PEG-30 or PEG-30), and 0.1-30 parts of phosphate buffer; wherein sodium sulfide can be specifically 0.05 parts, 0.08 parts, 0.1 parts or 0.15 parts, thiazone can be specifically 8 parts, 10 parts, 11 parts or 12 parts, urea can be specifically 1.5 parts, 2 parts or 2.5 parts, sodium dodecyl sulfate can be specifically 0.05 parts, 0.1 parts or 0.15 parts, Trition Specifically, x-100 can be 5 parts, 6 parts, 7 parts or 8 parts, specifically, vitamin E can be 4 parts, 5 parts or 6 parts, specifically, petroleum jelly can be 2 parts, 2.5 parts or 3 parts, specifically, PEG (for example, PEG-30 or PEG-200) can be 1.5 parts, 2 parts or 2.5 parts, and specifically, phosphate buffer can be 0.5 parts, 1 part or 1.5 parts.

[0050] Formula 6: 10-40 parts of azone, 1-20 parts of clove oil, 0.1-20 parts of sodium lauryl sulfate, 1-30 parts of Trition x-100, 1-20 parts of vitamin E, 0.1-15 parts of tretinoin cream, 0.1-20 parts of xanthan gum, 1-20 parts of PEG (for example, PEG-30), and 1-30 parts of phosphate buffer; wherein azone can be 15 parts, 20 parts, or 25 parts, clove oil can be 1.5 parts, 2 parts, or 2.5 parts, sodium lauryl sulfate can be 0.11 parts, 0.15 parts, or 0.2 parts, Trition x-100 can be 2 parts, 3 parts, or 4 parts, vitamin E can be 1.5 parts, 2 parts, or 2.5 parts, tretinoin cream can be 0.5 parts, 1 part, or 1.5 parts, xanthan gum can be 0.5 parts, 1 part, or 1.5 parts, PEG 1 to 20 parts (for example, PEG-30) can be specifically 1.5 parts, 2 parts or 2.5 parts, and phosphate buffer can be specifically 1.5 parts, 2 parts or 2.5 parts.

[0051] In the embodiments of the present invention, the above-mentioned formula 1 specifically uses rats and mice to verify the skin tissue transparent effect and the skin protective effect, formulas 2 to 5 specifically use mice to verify the skin tissue transparent effect, and formula 6 specifically uses rats to verify the skin tissue transparent effect and the skin protective effect.

[0052] The present invention provides a method for preparing the skin clearing agent described in the above technical solution, comprising the following steps:

[0053] The components of the skin clearing agent are mixed to obtain the skin clearing agent.

[0054] The present invention has no particular limitation on the mixing method and sequence, as long as uniform mixing of the components can be achieved.

[0055] In an embodiment of the present invention, when the skin is transparentized using the skin clearing agent, specifically, the skin clearing agent is applied to the skin surface, and the skin can be transparentized within 10 to 45 minutes, which makes the subcutaneous blood vessels more clearly exposed, thereby facilitating observation, injection, in vivo imaging and other experiments; after the transparentization treatment is completed, a sodium chloride solution (specifically, saline solution, the concentration of the saline solution can be 0.9g / 100mL, recorded as 0.9% saline solution) can be used to clean the skin, and the skin transparency can be restored to its original state after 20 minutes. When the skin clearing agent uses PEG and / or propylene glycol as a solubilizer, it also has a repairing and whitening effect on the skin, which is more conducive to the application in the medical beauty industry and the biomedical field. As shown in the results of the examples, the skin clearing agent in the examples of the present invention can make the mouse skin clear within 10 to 25 minutes, and promote clearer exposure of blood vessels; after the skin is cleared, it is cleaned with a sodium chloride solution and allowed to recover for 20 minutes, and it also has a repairing and whitening effect on the skin; moreover, the skin clearing agent in the examples of the present invention can make the rat skin clear within 10 to 45 minutes, and promote clearer exposure of blood vessels; after the skin is cleared, it is cleaned with a sodium chloride solution and allowed to recover for 20 minutes, and it also has a repairing and whitening effect on the skin.

[0056] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0057] The "1×PBS" referred to in the following embodiments of the present invention refers to a phosphate buffer solution with a concentration of 0.01 M.

[0058] Example 1 Skin clearing agent for mice

[0059] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.158 g of sodium dodecyl sulfate (1% by mass in the mother liquor), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0060] Example 2 Skin clearing agent for mice

[0061] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.078 g of sodium dodecyl sulfate (the mass content in the mother liquor is 0.5%), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0062] Example 3 Skin clearing agent for mice

[0063] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.039 g of sodium dodecyl sulfate (the mass content in the mother liquor is 0.25%), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0064] Example 4 Skin clearing agent for mice

[0065] Mix 1 g of 1×PBS, 0.067 g of sodium sulfide, 0.034 g of sodium dodecyl sulfate (the mass content in the mother liquor is 0.25%), 5 g of glycerol and 7.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0066] Example 5 Skin clearing agent for mice

[0067] Mix 1 g of 1×PBS, 0.04 g of sodium sulfide, 0.021 g of sodium dodecyl sulfate (the mass content in the mother liquor is 0.25%), 5 g of glycerol and 2.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0068] Example 6 Skin Clearing Agent for Mice

[0069] Mix 1 g of 1×PBS, 0.04 g of sodium sulfide, 0.05 g of sodium dodecyl sulfate (the mass content in the mother liquor is 0.5%), 5 g of glycerol and 5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0070] Test Example 1

[0071] The mice were weighed, and anesthetized with a 3.5wt% chloral hydrate solution injected intraperitoneally according to the weight of the mice, with an injection volume of 10 mL / kg; hair removal cream was used to remove the hair in the experimental area of ​​the mouse abdominal skin, and the residual hair removal cream was washed with 0.9% saline, and then wiped and disinfected with 75% alcohol by volume; the skin clearing agents in Examples 1 to 6 were applied respectively (the application amount was 1 g / cm 2 ) In the mouse abdominal skin test area, skin changes were observed at different times and photographed and recorded; 25 minutes after the skin clearing reagent was applied, the photographs were taken, and then the mouse abdominal skin test area was cleaned with 0.9% saline to allow the skin to recover, and photographed and recorded 20 minutes after cleaning.

[0072] Figure 1 The photos are of the mouse abdominal skin test area after being wiped and disinfected with alcohol and before (0 min) and 10 min and 15 min after application of the skin clearing reagent in Examples 1 to 6. Figure 2 The photos are of the mouse abdominal skin test area after applying the skin clearing reagents in Examples 1 to 6 for 20 minutes, 25 minutes, and after 20 minutes of recovery; No. 1 to No. 6 correspond to the skin clearing reagents in Examples 1 to 6, respectively. The results show that compared with 0 minutes, the original blood vessels are clearer, the capillaries increase, the permeability increases, and more blood vessels can be observed after applying the skin clearing reagent for 10 minutes, 15 minutes, 20 minutes, and 25 minutes; after washing with sodium chloride solution for 20 minutes, the skin recovers, which has the effect of protection and whitening. At the same time, according to Figure 1 and Figure 2 It can be seen that the skin clearing agents in Examples 3 to 4 have better blood vessel exposure effect and whitening effect.

[0073] Comparative Example 1

[0074] Mix 1.5g of gelatin with 10g of water, heat in a water bath to dissolve, then add 3g of sodium sulfide, 0.898g of isooctyl ferulate (the mass content in the mother liquor is 2%), 20g of glycerol and 9.5g of thiophene to obtain a mother liquor; mix 20g of the mother liquor with 2.5g of vaseline and 3g of sodium alginate, and the resulting reagent is recorded as reagent #1.

[0075] Comparative Example 2

[0076] Mix 1.5g of gelatin with 10g of water, heat in a water bath to dissolve, then add 0.837g of isooctyl ferulate (the mass content in the mother liquor is 2%), 20g of glycerol and 9.5g of thiazide to obtain a mother liquor; mix 20g of the mother liquor with 2.5g of vaseline and 3g of sodium alginate, and the resulting reagent is recorded as reagent 2#.

[0077] Comparative Example 3

[0078] Mix 1.5 g of gelatin with 10 g of water, heat in a water bath to dissolve, then add 0.423 g of sodium dodecyl sulfate (1% by mass in the mother liquor), 0.846 g of isooctyl ferulate (2% by mass in the mother liquor), 20 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 2.5 g of vaseline, 3 g of sodium alginate and 4 g of PEG-400, and the resulting reagent is recorded as reagent #3.

[0079] Test Example 2

[0080] Referring to the method of Test Example 1, the vascular exposure effect and skin protection effect of the reagents obtained in Comparative Examples 1 to 3 were tested on mice.

[0081] Figure 3 The photos are of the mouse abdominal skin test area after being wiped and disinfected with alcohol and before (0min) and 15min after the application of the reagents in Comparative Examples 1 to 3; No. 1 to No. 3 correspond to the reagents in Comparative Examples 1 to 3, respectively. The results show that the sodium sulfide dosage of reagent 1# in Comparative Example 1 is relatively large, and no solubilizing agent such as PEG reagent is added to protect the skin, which will cause skin ulceration and damage in mice; reagent 2# in Comparative Example 2 does not add sodium sulfide, and the overall experiment has no effect, that is, the transparency effect cannot be achieved; after reagent 3# in Comparative Example 3 is added with PEG-400, it is found that the skin is almost undamaged, judging that PEG-400 has a protective effect on the skin (such as Figure 3 The right side of the medium thick black line shows smooth and delicate skin, and the left side of the thick black line is the test result under the same conditions when PEG-400 is omitted in reagent 3#).

[0082] Comparative Example 4

[0083] Mix 12g of water, 0.428g of sodium dodecyl sulfate (1% by mass in the mother liquor), 0.856g of isooctyl ferulate (2% by mass in the mother liquor), 20g of glycerol and 9.5g of thiophene to obtain a mother liquor; mix 20g of the mother liquor with 2.5g of vaseline and 3g of sodium alginate, and the resulting reagent is recorded as reagent 4#.

[0084] Comparative Example 5

[0085] Mix 12g of water, 4.715g of sodium dodecyl sulfate (10% by mass in the mother liquor), 0.943g of isooctyl ferulate (2% by mass in the mother liquor), 20g of glycerol and 9.5g of thiophene to obtain a mother liquor; mix 20g of the mother liquor with 2.5g of vaseline, 3g of sodium alginate and 4g of PEG-400, and the resulting reagent is recorded as reagent #5.

[0086] Comparative Example 6

[0087] Mix 12g of water, 4.715g of sodium dodecyl sulfate (10% by mass in the mother liquor), 0.943g of isooctyl ferulate (2% by mass in the mother liquor), 20g of glycerol and 9.5g of thiophene to obtain a mother liquor; mix 20g of the mother liquor, 2.5g of vaseline, 3g of sodium alginate and 4g of PEG-200, and the resulting reagent is recorded as reagent # 6.

[0088] Example 7 Skin Clearing Agent for Mice

[0089] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.158 g of sodium dodecyl sulfate (1% by mass in the mother liquor), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-200 to obtain a skin clearing agent.

[0090] Example 8 Skin Clearing Agent for Mice

[0091] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.158 g of sodium dodecyl sulfate (1% by mass in the mother liquor), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-100 to obtain a skin clearing agent.

[0092] Example 9 Skin Clearing Agent for Mice

[0093] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.158 g of sodium dodecyl sulfate (1% by mass in the mother liquor), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-75 to obtain a skin clearing agent.

[0094] Example 10 Skin clearing agent for mice

[0095] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.158 g of sodium dodecyl sulfate (1% by mass in the mother liquor), 5 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-7 to obtain a skin clearing agent.

[0096] Test Example 3

[0097] Referring to the method of Test Example 1, the vascular exposure effect and whitening effect of the reagents obtained in Comparative Examples 4 to 6 and the skin clearing reagents in Examples 7 to 9, Example 1 and Example 10 were tested on mice.

[0098] Figure 4 The photos are taken before (0min), 15min and 20min of recovery after applying the reagents obtained in Comparative Examples 4 to 6 and the skin clearing reagents in Examples 7 to 9, Example 1 and Example 10 to the test area of ​​the abdominal skin of mice, wherein No. 1 to No. 8 correspond to the reagents obtained in Comparative Examples 4 to 6 and the skin clearing reagents in Examples 7 to 9, Example 1 and Example 10, respectively. The results show that compared with Comparative Example 4 (blank), PEG-400 and PEG-200 are added to Comparative Examples 5 to 6, respectively. Comparing the protective effects of PEG-400 and PEG-200 on the skin, the color and state of the skin after adding PEG-200 are better. In addition, according to Examples 7 to 9, Example 1 and Example 10, it can be seen that the addition of PEG-30 in Example 1 is the best in terms of vascular clarity at 15min and skin recovery after 20min of recovery compared with the other four groups (Examples 7 to 10), so PEG-30 is preferably used as an auxiliary material.

[0099] Example 11 Skin clearing agent for mice

[0100] Mix 12 g of water, 3 g of sodium sulfide, 0.908 g of isooctyl ferulate (the mass content in the mother liquor is 2%), 20 g of glycerol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 2.5 g of vaseline, 3 g of sodium alginate and 4 g of PEG-200 to obtain a skin clearing agent.

[0101] Example 12 Skin clearing agent for mice

[0102] Mix 12g of water, 3g of sodium sulfide, 4.944g of sodium dodecyl sulfate (10% by mass in the mother liquor), 20g of glycerol and 9.5g of thiophene to obtain a mother liquor; mix 20g of the mother liquor with 5g of vitamin E, 2.5g of vaseline, 3g of sodium alginate and 4g of PEG-200 to obtain a skin clearing agent.

[0103] Example 13 Skin clearing agent for mice

[0104] Mix 1 g of 1×PBS, 0.125 g of sodium sulfide, 2.292 g of sodium dodecyl sulfate (the mass content in the mother liquor is 10%), 5 g of glycerol, 5 g of propylene glycol and 9.5 g of thiophene to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 4 g of PEG-200 to obtain a skin clearing agent.

[0105] Example 14 Skin clearing agent for mice

[0106] Mix 1 g of 1×PBS, 0.08 g of sodium sulfide, 0.100 g of sodium dodecyl sulfate (the mass content in the mother liquor is 0.5%), 6 g of Tritionx-100, 2 g of urea and 9.5 g of thiazide to obtain a mother liquor; mix 20 g of the mother liquor with 5 g of vitamin E, 2.5 g of vaseline and 2 g of PEG-30 to obtain a skin clearing agent.

[0107] Test Example 4

[0108] Referring to the method of Test Example 1, the vascular exposure effects of the skin clearing agents in Examples 11 to 14 were tested on mice.

[0109] Figure 5 The photos are taken before (0 min), 15 min and 25 min after applying the skin clearing agents in Examples 11 to 14 to the test area of ​​the mouse abdominal skin, where No. 1 to No. 4 correspond to the skin clearing agents in Examples 11 to 14, respectively. The results show that the skin clearing agents in Examples 11 to 14 all have a certain vascular exposure effect, and the skin clearing agent in Example 14 has the best effect.

[0110] Example 15 Skin clearing agent for rats

[0111] 2 g 1×PBS, 1 g xanthan gum, 0.11 g sodium dodecyl sulfate, 3 g Trition x-100 and 20 g azone were mixed to obtain a mother solution; all of the mother solution was mixed with 2 g clove oil, 2 g vitamin E, 1 g tretinoin cream and 2 g PEG-30 to obtain a skin clearing agent.

[0112] Example 16 Skin clearing agent for rats

[0113] Mix 1 g of 1×PBS, 0.04 g of sodium sulfide, 0.12 g of sodium dodecyl sulfate, 5 g of glycerol and 5 g of thiophene to obtain a mother solution; mix all of the mother solution with 5 g of vitamin E, 2.5 g of vaseline, 3 g of sodium alginate and 2 g of PEG-30 to obtain a skin clearing agent.

[0114] Test Example 5

[0115] The rats were weighed, and anesthetized with 3.5wt% chloral hydrate solution injected intraperitoneally according to the rats' weight, and the injection volume was 10mL / kg; the hair of the experimental area of ​​the rats' abdominal skin was removed with a depilatory cream, and the residual depilatory cream was washed with 0.9% saline, and then wiped and disinfected with 75% alcohol by volume; the skin clearing agents in Examples 1 and 2 were applied respectively (the application amount was 1g / cm 2) In the rat abdominal skin test area, skin changes were observed at different times and photographed and recorded; 25 minutes after the skin clearing reagent was applied, the photographs were taken, and then the rat abdominal skin test area was cleaned with 0.9% saline to allow the skin to recover, and photographed and recorded 20 minutes after cleaning.

[0116] Figure 6 These are photos of the rat abdominal skin test area before (0 min) and 10 min and 25 min after application of the skin clearing agent in Examples 15 to 16. Figure 7 The photos are of the rat abdominal skin test area after applying the skin clearing agent in Examples 15-16 for 35 minutes, 45 minutes and after 20 minutes of recovery; No. 1 and No. 2 correspond to the skin clearing agent in Example 15, and No. 3 and No. 4 correspond to the skin clearing agent in Example 16. The results show that compared with 0 minutes, the original blood vessels are clear, the capillaries increase, the permeability increases, and more blood vessels can be observed after applying the skin clearing agent in Examples 15-16 for 10 minutes, 25 minutes, 35 minutes, and 45 minutes; after washing with sodium chloride solution for 20 minutes, the skin recovers and has a whitening effect.

[0117] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A skin clearing agent, comprising the following components by weight: 0.5-70 parts of penetration enhancer; 0-25 parts of penetrant; 0-50 parts of surfactant; 0-30 parts of moisturizer; 0.1-20 parts of antioxidant; 0.1-15 parts of emulsifier; 0-20 parts of thickener; 0.5-30 parts of solubilizer; 0.1-30 parts of diluent; The penetration enhancer is azone, or at least two of azone, sodium sulfide and thiazone.

2. The skin clearing agent according to claim 1, characterized in that The penetration enhancers are sodium sulfide and thiazide; the mass ratio of sodium sulfide to thiazide is 0.01-20:0.5-50.

3. The skin clearing agent according to claim 1 or 2, characterized in that: The penetrant includes urea and / or plant essential oil.

4. The skin clearing agent according to claim 1 or 2, characterized in that: The surfactant includes anionic surfactant and / or nonionic surfactant.

5. The skin clearing agent according to claim 4, characterized in that: The anionic surfactant includes sodium lauryl sulfate; the nonionic surfactant includes polyethylene glycol octylphenyl ether.

6. The skin clearing agent according to claim 1 or 2, characterized in that: The moisturizer includes one or more of glycerin, shea butter, avocado oil and olive oil; the antioxidant includes vitamin E and / or isooctyl ferulate.

7. The skin clearing agent according to claim 1 or 2, characterized in that: The emulsifier includes vaseline and / or tretinoin cream; the thickener includes one or more of sodium alginate, xanthan gum and gelatin.

8. The skin clearing agent according to claim 1 or 2, characterized in that: The solubilizer includes propylene glycol and / or dipolyhydroxystearate.

9. The skin clearing agent according to claim 8, characterized in that The dipolyhydroxystearate includes one or more of dipolyhydroxystearate-400, dipolyhydroxystearate-200, dipolyhydroxystearate-100, dipolyhydroxystearate-75, dipolyhydroxystearate-30 and dipolyhydroxystearate-7.

10. A method for preparing the skin clearing agent according to any one of claims 1 to 9, comprising the following steps: The components of the skin clearing agent are mixed to obtain the skin clearing agent.

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