Delivery system, delivery gel and preparation of a composition for multi-dimensionally synergistically solving skin aging problems

Abstract

The present application relates to the technical field of daily cosmetic composition, and more particularly to a delivery body of a composition for solving skin aging problem in multiple dimensions, comprising the following raw material components: phospholipid, cholesterol, edge activator, composition and water.The composition for solving skin aging problem in multiple dimensions comprises beta-arbutin, tranexamic acid, sodium hyaluronate, allantoin, vitamin B12 and hydroxyethyl urea.The present application further comprises a preparation for preparing a delivery body gel of the composition for solving skin aging problem in multiple dimensions, comprising the above-mentioned composition delivery body, carbomer and cosmetically acceptable adjuvants and solvents.The delivery body gel is convenient to use, easy to adhere to the skin, easy to apply, has strong skin penetration, can penetrate into deep skin, and has excellent synergistic antioxidant, anti-inflammatory, anti-black, anti-aging and other effects.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of daily cosmetic compositions, in particular to a delivery body of a composition for solving skin aging problems in multiple dimensions, a delivery body gel and preparation. BACKGROUND

[0002] Skin aging is an inevitable physiological change process, mainly caused by endogenous factors and exogenous factors. Endogenous aging is affected by genetic factors and time elapse, while exogenous aging is a significant morphological and physiological change of uneven skin color, pigmentation, dry and rough surface, skin relaxation and wrinkle formation, etc. due to long-term exposure to sunlight, pollution, ionizing radiation and other factors. With the gradual increase of the public's beauty consciousness, people pay more attention to skin aging, making people's demand for effective products to delay skin aging more and more vigorous. How to develop skin care products that can effectively delay skin aging and improve the symptoms of aging skin has become a hot spot of attention in the medical and cosmetic industries.

[0003] Delaying skin aging is a relatively complex concept, and how to delay skin aging has always been one of the research focuses in the field of cosmetics. Due to exposure to exogenous factors, skin cells undergo oxidative stress metabolism to produce excess reactive oxygen species, which is the main factor leading to skin aging. Excess reactive oxygen species not only leads to collagen degradation, making the skin lose elasticity, but also leads to the occurrence of skin inflammation and pigmentation. However, simply using antioxidant products is not enough. If the skin loses its function as a physicochemical barrier due to dryness and lack of water, it will also accelerate skin aging. In addition, inflammation and pigmentation caused by skin oxidative aging and skin dryness problems need to be actively addressed. Therefore, to better address people's needs to improve aging skin, it is necessary to start from multiple dimensions such as reducing skin oxidative stress, reducing inflammation, resisting pigmentation, and supplementing moisture, and combine active substances, so as to solve the problem of skin aging in multiple dimensions.

[0004] Even if the successful combination can solve the problem of skin aging, its effect is not ideal in practical application. This is because the active ingredients of cosmetics are difficult to absorb due to the barrier effect of the skin, most of which only stay in the stratum corneum or the surface layer of the skin, and cannot effectively play their role. For this reason, many nano-formulation technologies such as solid lipid nanoparticles, liposomes, transmitters, polymer nanoparticles and vesicles are used to improve the transdermal delivery of cosmetic active ingredients, among which the liposome technology has been widely used in many high-end cosmetics. Although the transdermal preparation with liposome as the carrier can improve the transdermal penetration of the substance compared with ordinary cream, emulsion, etc., the delivery depth of the skin is limited, so that the effect of active ingredients that need to work in the deeper layer of the skin cannot be well played. Transmitter is a liposome with edge activator added, which can easily undergo elastic deformation and enter the skin deep layer through several times smaller skin pores than itself, thus achieving a skin penetration depth that liposomes cannot reach, thereby playing a better effect.

[0005] Therefore, the present application provides a cosmetic composition that can solve the problem of skin aging from multiple dimensions such as reducing oxidative stress, reducing inflammatory response, resisting pigmentation, and supplementing moisture, and provides a preparation method of a transmitter and a gel thereof that can improve the transdermal absorption thereof. SUMMARY

[0006] In order to solve the urgent need of people for anti-aging care products, the present application provides an anti-aging composition. The anti-aging composition is a complex containing β-arbutin, tramine, sodium hyaluronate, allantoin, vitamin B12 and hydroxyethyl urea. The composition can solve the problem of skin aging in multiple dimensions and has good antioxidant, anti-inflammatory, depigmentation, moisturizing and moisturizing effects.

[0007] The present application also provides a preparation of a transmitter that can promote the skin absorption of the composition. The active ingredients are wrapped in the transmitter vesicle, and the transmitter has the characteristics of easy penetration of the skin by elastic deformation, so that the active ingredients are delivered to the deep layer of the skin and effectively play a role. The present application also provides a preparation of a transmitter gel based on the above-mentioned composition. The semi-solid characteristics of the gel make the preparation easy to adhere to the skin and easy to use, and better play its anti-aging effect.

[0008] The present application is realized by the following technical scheme: A transmitter for solving the problem of skin aging in multiple dimensions, comprising the following raw material components: phospholipid, cholesterol, edge activator, active ingredient and water.

[0009] The phospholipid is 0.49-9.00wt%, the cholesterol is 0.19-0.95wt%, the edge activator is 0-1.06wt%, and the active ingredient is 0.01-5wt%; wherein the edge activator is not 0.

[0010] The application further provides a delivery body of a composition for solving skin aging problems in multiple dimensions, which is composed of the following raw material components in percentage by weight: phospholipid 0.49-9.00 wt%, cholesterol 0.19-0.95 wt%, marginal activator 0-1.06 wt%, efficacy component 0.01-5 wt%, and the balance being water; wherein the marginal activator is not 0.

[0011] The application further provides a delivery body of a composition for solving skin aging problems in multiple dimensions, which is composed of the following raw material components in percentage by weight: phospholipid 0.98-4.71 wt%, cholesterol 0.39-0.90 wt%, marginal activator 0.17-0.87 wt%, efficacy component 0.09-2 wt%, and the balance being water.

[0012] The application provides a delivery body of a composition for solving skin aging problems in multiple dimensions, wherein the phospholipid is selected from soybean lecithin or egg yolk lecithin.

[0013] The application further provides a delivery body of a composition for solving skin aging problems in multiple dimensions, wherein the mass ratio of the phospholipid to cholesterol is 5:2.

[0014] The application provides a delivery body of a composition for solving skin aging problems in multiple dimensions, wherein the efficacy component comprises beta-arbutin, tranexamic acid, sodium hyaluronate, allantoin, vitamin B12 and hydroxyethyl urea.

[0015] The application provides a preparation method of a delivery body of a composition for solving skin aging problems in multiple dimensions, which comprises the following steps:

[0016] (1) the phospholipid and cholesterol are mixed and dissolved in an organic solvent, the organic solvent is evaporated under reduced pressure, a uniform lipid layer is formed on the wall of a container, and the organic solvent is completely volatilized under vacuum to form a deposited film;

[0017] (2) the efficacy component and the marginal activator are stirred and dissolved in water to form a mixed solution, which is added to the container containing the deposited film, and is hydrated;

[0018] (3) the lipid vesicle obtained by hydration is fully swollen, and is subjected to ultrasonic treatment under cooling;

[0019] (4) the obtained lipid vesicle is filtered through a microporous filter membrane to obtain the delivery body of the composition for solving skin aging problems in multiple dimensions.

[0020] The application further provides a delivery body gel of a composition for solving skin aging problems in multiple dimensions, which comprises the delivery body of the composition for solving skin aging problems in multiple dimensions, carbomer and cosmetically acceptable adjuvants and solvents.

[0021] The present application provides a preparation of a composition delivery gel for solving skin aging problems in multiple dimensions, comprising the following steps:

[0022] (1) Disperse carbomer in water with dissolved glycerol, add preservative after complete swelling and dissolving.

[0023] (2) Mix the solution of step (1) with the composition delivery body under gentle stirring.

[0024] (3) Adjust the pH of step (2) to 6.5-7.0 with triethanolamine, and stir until uniform to obtain the product.

[0025] In the present application, the related effects of various functional ingredients are as follows:

[0026] 1. β-arbutin. Effectively inhibits the activity of tyrosinase in the skin, blocks the formation of melanin, accelerates the decomposition and metabolism of melanin by directly combining with tyrosinase, thereby reducing skin pigmentation and removing freckles and chloasma, and has no toxic, irritating, sensitizing and other side effects on melanocytes. It also has antioxidant, bactericidal and anti-inflammatory effects.

[0027] 2. Tranexamic acid. Can inhibit the synthesis of tyrosinase, thereby inhibiting the formation of skin melanin, and is safe and non-toxic, without causing white spot sequelae, and can also eliminate internal free radicals in the human body, enhance white blood cell dynamics, etc., which is beneficial to human health, and also has the effects of preservation and moisturization.

[0028] 3. Sodium hyaluronate. The sodium hyaluronate described in the present application is a mixture of medium molecular weight sodium hyaluronate and small molecular weight sodium hyaluronate, and the preferred mass ratio of medium molecular weight sodium hyaluronate to small molecular weight sodium hyaluronate is 1:1, which has a synergistic complementary anti-aging effect. Medium molecular weight sodium hyaluronate can fill in fine lines and remove wrinkles, forming a breathable film on the skin epidermis, making the skin smooth and moist, and can block the invasion of external bacteria, dust and ultraviolet rays, protecting the skin from damage by free radicals, but is poorly absorbed by the skin. Small molecular weight hyaluronic acid can penetrate into the dermis to supplement the lost water, repair damaged skin, and has the effects of moisturizing and tenderizing the skin, anti-inflammatory, inhibiting the production of bacteria, maintaining the smoothness of the skin, and directly promoting cell growth, differentiation, reconstruction and repair, etc.

[0029] 4. Allantoin. Can promote water replenishment of the stratum corneum and increase the water retention of the skin. In the present application, it is used as a moisturizing agent.

[0030] 5. Vitamin B12. One of the essential raw materials for red blood cell production, which can promote the development and maturation of red blood cells, maintain a rosy complexion. It can also reduce the production of nitric oxide, reduce the production of pro-inflammatory cytokines, and prevent dermatitis.

[0031] 6. Hydroxyethyl urea. In the present invention it is used as a moisturizer and emollient.

[0032] The present invention has the following advantages and beneficial effects compared with the prior art:

[0033] 1. The composition of the present invention matches plant extracts, vitamins and chemical high-purity substances, promotes each other, and acts on the skin from different levels, having the effects of multi-level, multi-pathway, and synergistic anti-aging and improving the symptoms of aging skin. It has sodium hyaluronate which can clear free radicals, moisturize, supplement water, anti-inflammatory, and remove wrinkles, beta-arbutin and transaminic acid which can inhibit skin melanin, anti-inflammatory, and antioxidant, vitamin B12 which can resist skin inflammation and make the skin red, allantoin and hydroxyethyl urea which can moisturize and activate cells, further strengthening the anti-aging effect of the product, reducing the production of skin wrinkles, and increasing skin elasticity.

[0034] 2. Since the skin is the internal and external barrier of the human body, it is difficult for cosmetic active substances to penetrate the skin, so that their effects cannot be exerted. The present invention selects vitamin B12 with high molecular weight and difficult to penetrate the skin as a model component, and screens the delivery body prescription of the compound with high penetration rate, high cumulative penetration amount and skin retention amount, including the optimal edge activator and its content, as shown in Tables 1 and 2.

[0035] 3. The composition of the present invention is water-soluble, and when used as a cosmetic, an aqueous base can be directly used, avoiding emulsification operation. In the preparation of the composition delivery body, the active components and the edge activator are co-dispersed in the aqueous phase, instead of the traditional method of dissolving the edge activator in the lipid membrane material. During the hydration process, the active substance and the edge activator are transferred to the hydrophilic region of the lipid vesicle in the form of a complex, which is beneficial to the exertion of the skin penetration-promoting effect of the delivery body on the active substance, and is also beneficial to shielding the deeper color of vitamin B12.

[0036] 4. The delivery body gel prepared based on the above-mentioned composition has the excellent penetration-promoting effect of the delivery body and the multi-dimensional network structure of the gel, which is convenient to apply and adhere to the skin, further improving the exertion of the composition effect.

[0037] 5. The anti-aging compound delivery body gel of the present invention has simple preparation process, stable system, and dispersed and uniform texture, effectively making up for the defects of single action mechanism and difficult transdermal absorption of efficacy components of current anti-aging products. It has obvious synergistic antioxidant and anti-inflammatory effects on zebrafish oxidative stress and inflammation models, as shown in Figure 3 、 4 It has good whitening effect, as shown in Figure 5 For hydrogen peroxide-induced human skin fibroblasts, the efficacy component composition has obvious anti-aging effect, as shown in Figure 6The skin is safe, mild and non-irritating, as shown in the attached Figure 7 . BRIEF DESCRIPTION OF DRAWINGS

[0038] In order to more clearly illustrate the specific embodiments of the present application or the technical solutions in the prior art, the drawings required to be used in the specific embodiments or prior art description will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor on the basis of these drawings.

[0039] Figure 1 The schematic diagram of the appearance (A) and the transmission electron microscope microstructure (B) of the vitamin B12 delivery body described in Example 8.

[0040] Figure 2 The schematic diagram of the appearance (A) and the microstructure (B) of the complex delivery body gel described in Example 17.

[0041] Figure 3 The fluorescence images (A) and statistical results (B) of reactive oxygen species in zebrafish larvae under fluorescence microscope. In (A), CG represents the blank control group, H2O2 represents the hydrogen peroxide oxidative stress model group, H2O2+NC represents the group of giving the blank delivery body gel without active ingredients after oxidative stimulation, and H2O2+CTG represents the group of giving the complex delivery body gel after oxidative stimulation. In (B), VC represents the positive control group, AR represents arbutin, TA represents the trans-aminic acid, VB represents vitamin B12, HA represents hyaluronic acid, ALT represents allantoin, and HEU represents hydroxyethyl urea. “##” represents P<0.01 compared with the CG group, and “**” represents P<0.01 compared with the hydrogen peroxide model group, n=30.

[0042] Figure 4 The fluorescence images (A) and statistical results (B) of neutrophil migration in zebrafish larvae under fluorescence microscope. In (A), the blank control group (CG), the copper sulfate-induced inflammation model group (CuSO4), the ibuprofen positive drug group (IBU), the blank delivery body gel group without active ingredients (NC), and the different concentrations of complex delivery body gel groups (Examples 15, 16 and 17) are shown. The effect of the different groups on the number of neutrophils diffusing to the lateral line nerve ridge in the tail of zebrafish is shown. In (B), the statistical results of each single component are shown, in which AR represents arbutin, TA represents the trans-aminic acid, VB represents vitamin B12, HA represents hyaluronic acid, ALT represents allantoin, and HEU represents hydroxyethyl urea. “##” represents P<0.01 compared with the CG group, and “**” represents P<0.01 compared with the copper sulfate model group, n=30.

[0043] Figure 5 The pictures of local melanin pigmentation of zebra fish under microscope (A) and statistical results (B). In (A), CG represents the blank control group, PTU represents the positive control group, NC represents the blank delivery gel group without efficacy ingredients, and CTG represents the complex delivery gel group (Example 17). In (B), AR represents arbutin, TA represents anthranilic acid, VB represents vitamin B12, HA represents hyaluronic acid, ALT represents allantoin, and HEU represents hydroxyethyl urea; "##" represents P<0.01 compared with the CG group; "**" represents P<0.01 compared with the CG group, n=30.

[0044] Figure 6 The pictures of aging β-galactosidase staining of human skin fibroblasts under microscope. CG represents the blank control group, H2O2 represents the hydrogen peroxide oxidative stress model group, and H2O2+APC represents the group to which the efficacy ingredient composition is given after oxidative stimulation.

[0045] Figure 7 The micrographs of guinea pig skin and dermal tissue sections. (A) Normal skin; (B) given the complex delivery gel; (C) given the blank delivery gel without efficacy ingredients. DETAILED DESCRIPTION

[0046] The technical solutions of the present application are described below clearly and completely. Obviously, the described examples are part of the examples of the present application, rather than all the examples. Based on the examples in the present application, all the other examples obtained by those skilled in the art without creative labor fall within the protection scope of the present application.

[0047] The present application provides a specific embodiment of a delivery system of a composition for solving the problem of skin aging in multiple dimensions in coordination, which comprises the following raw material components: phospholipid, cholesterol, marginal activator, efficacy ingredient, and water.

[0048] The present application also provides another specific embodiment of a delivery system of a composition for solving the problem of skin aging in multiple dimensions in coordination, which comprises the following raw material components: phospholipid 0.49-9.00 wt%, cholesterol 0.19-0.95 wt%, marginal activator 0-1.06 wt%, and efficacy ingredient 0.01-5 wt%; wherein the marginal activator is not 0.

[0049] In one embodiment provided by the present application, the delivery system of a composition for solving the problem of skin aging in multiple dimensions in coordination is composed of the following raw material components in the following weight percentages: phospholipid 0.49-9.00 wt%, cholesterol 0.19-0.95 wt%, marginal activator 0-1.06 wt%, and efficacy ingredient 0.01-5 wt%, and the balance is water; wherein the marginal activator is not 0.

[0050] In another embodiment of the present application, the delivery body of the composition for solving skin aging problem in multi-dimension synergistically is composed of the following raw material components in percentage by weight: phospholipid 0.98-4.71 wt%, cholesterol 0.39-0.90 wt%, marginal activator 0.17-0.87 wt%, efficacy component 0.09-2 wt%, and the balance is water.

[0051] As a preferred solution, the phospholipid is selected from soybean lecithin or egg yolk lecithin.

[0052] As a preferred solution, the mass ratio of the phospholipid to cholesterol is 5:2.

[0053] The delivery body of the composition for solving skin aging problem in multi-dimension synergistically provided by the present application includes the efficacy component including β-arbutin, ophthalmic acid, sodium hyaluronate, allantoin, vitamin B12, and hydroxyethyl urea. Preferably, the efficacy component is composed of β-arbutin, ophthalmic acid, sodium hyaluronate, allantoin, vitamin B12, and hydroxyethyl urea. In the embodiment provided by the present application, the β-arbutin in the efficacy component is 0.2-0.5 parts, the ophthalmic acid is 0.2-0.5 parts, the sodium hyaluronate is 0.01-0.5 parts, the allantoin is 0.01-0.5 parts, the vitamin B12 is 0.01-0.5 parts, and the hydroxyethyl urea is 0.01-0.5 parts.

[0054] The delivery body of the composition for solving skin aging problem in multi-dimension synergistically provided by the present application can be prepared by using the film dispersion method.

[0055] The present application further provides a preparation method of the delivery body of the composition for solving skin aging problem in multi-dimension synergistically, which comprises the following steps:

[0056] (1) the phospholipid and cholesterol are mixed and dissolved in an organic solvent, the organic solvent is evaporated under reduced pressure, a uniform lipid layer is formed on the wall of the container, and the organic solvent is completely evaporated under vacuum to form a deposited film;

[0057] (2) the efficacy component and the marginal activator are stirred and dissolved in water to form a mixed solution, which is added to the container containing the deposited film, and is hydrated;

[0058] (3) the lipid vesicle obtained by hydration is fully swollen, and is subjected to ultrasonic treatment under cooling;

[0059] (4) the obtained lipid vesicle is passed through a microporous filter membrane to obtain the delivery body of the composition for solving skin aging problem in multi-dimension synergistically.

[0060] In an embodiment of the preparation method of the present application, the organic solvent is used to promote the uniform mixing of phospholipids and cholesterol, and the organic solvent used in this embodiment can be evaporated dry under a vacuum drying environment. Specifically, in this embodiment, the organic solvent can be chloroform, methanol or a mixed solvent of chloroform and methanol. When a mixed solvent of chloroform and methanol is used, the volume ratio of chloroform to methanol is 3:2.

[0061] In an embodiment of the preparation method of the present application, the operation of the reduced pressure evaporation is realized in a rotary evaporator, and the temperature of the reduced pressure evaporation can be not less than 42°C, and preferably the temperature of the reduced pressure evaporation is 45°C.

[0062] In an embodiment of the preparation method of the present application, the hydration temperature is higher than the phase transition temperature of phospholipids, and preferably the hydration temperature is 50°C. In order to accelerate the hydration process, preferably, a stirring speed of 60-75 rpm is used during the hydration process.

[0063] In an embodiment of the preparation method of the present application, the swelling is carried out at a temperature of not higher than 50°C, and specifically can be carried out directly at room temperature (22-25°C). Specifically, the swelling time can be selected according to the specific circumstances of the lipid vesicles, and when the swelling is carried out directly at room temperature, the swelling time is 2 h.

[0064] In an embodiment of the preparation method of the present application, the ultrasonic treatment time is 20 min. The ultrasonic treatment equipment used in this embodiment is a JY92-IIN ultrasonic cell crusher, which is purchased from Ningbo Xinzhi Biotechnology Co., Ltd. When the ultrasonic treatment is started, the mode of 3 s "on" and 3 s "off" is used.

[0065] In an embodiment of the preparation method of the present application, the microporous filter membrane used can be a filter membrane with a pore size of 0.80 μm, 0.45 μm and 0.22 μm. In order to improve the uniformity of the lipid vesicles, preferably, the lipid vesicles are sequentially passed through the microporous filter membranes with a pore size of 0.80 μm, 0.45 μm and 0.22 μm.

[0066] In order to increase the transdermal absorption of the functional ingredients, improve the stability of the delivery body, and improve the adhesion between the delivery body and the skin, the present application provides a delivery body gel of a composition for solving skin aging problems in multiple dimensions, which comprises the delivery body of the composition for solving skin aging problems in multiple dimensions, carbomer, and cosmetically acceptable adjuvants and solvents.

[0067] In the above composite delivery body gel, the carbomer can be carbomer 980, 940 or 910. The cosmetically acceptable adjuvant can be a preservative such as phenoxyethanol or p-hydroxyacetophenone, and preferably phenoxyethanol is used as the preservative. The cosmetically acceptable solvent can be water or a PBS solution, and preferably water is used as the gel solvent.

[0068] The present application also provides a preparation method of the composition delivery gel, specifically comprising:

[0069] 0.1-2% Carbomer 980 is scattered into a water solution with a glycerol concentration of 0.1-5%, after being fully swelled and dissolved, 0.01-1% phenoxyethanol is added, then the above composition delivery is slowly mixed with the above composition delivery at a mass ratio of 0.5-5:1 under gentle stirring, and triethanolamine is added dropwise to adjust the pH value to 6.5-7.0, and the mixture is stirred uniformly to obtain the composition delivery gel.

[0070] In the preparation method of the composition delivery gel, the percentage content of the glycerol, the supplementary efficacy component, the Carbomer 980 and the phenoxyethanol refers to the percentage content in the gel system.

[0071] In the above composition delivery gel, the glycerol is used as a humectant and a solvent. The phenoxyethanol is used as an antiseptic.

[0072] The evaluation method of the particle size, Zeta potential and morphology of the delivery body loaded with the efficacy component in the embodiment of the present application is as follows:

[0073] 1. Morphology evaluation method

[0074] An appropriate amount of the delivery body solution (or its gel) loaded with the efficacy component is diluted with water, dropped onto a copper mesh, negatively stained with a 1% phosphotungstic acid solution, the excess staining solution is absorbed by filter paper, dried and observed under a transmission electron microscope.

[0075] 2. Particle size and Zeta potential evaluation method

[0076] An appropriate multiple of the delivery body solution (or its gel) loaded with the efficacy component is diluted with deionized water, and the particle size and Zeta potential of the delivery body (or its gel) are determined by a laser particle size analyzer.

[0077] The technical solutions of the present application will be described in detail below through specific examples. In the embodiment examples of the delivery body prescription screening and the edge activator type and amount screening, vitamin B12 is used as a model substance, and other components in the composition are not added.

[0078] Example 1

[0079] Weigh 1g of soybean lecithin and 0.4g of cholesterol into a dry round-bottom flask, and add a small amount of a mixture of chloroform and methanol to dissolve them. Evaporate the solvent using a rotary evaporator at 45°C under reduced pressure until a uniform lipid layer forms on the flask wall. Then, dry under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.1g of vitamin B12 in 50g of deionized water. Hydrate the deposited film with the above solution for 1 hour at 50°C and 75 rpm. Allow the resulting lipid vesicles to fully expand at room temperature (22-25°C) for 2 hours, then sonicate them in an ice bath for 20 minutes, with the sonication cycle on for 3 seconds and off for 3 seconds. Finally, sequentially squeeze the obtained vesicle system through microporous membranes of 0.80μm, 0.45μm, and 0.22μm to obtain the vitamin B12-loaded transporter.

[0080] Example 2

[0081] Weigh 2.5g of soybean lecithin and 0.5g of cholesterol into a dry round-bottom flask, and add a small amount of a mixture of chloroform and methanol to dissolve them. Evaporate the solvent using a rotary evaporator at 45℃ under reduced pressure until a uniform lipid layer forms on the flask wall. Then, dry under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.1g of vitamin B12 in 50g of deionized water. Hydrate the deposited film with the above solution for 1 hour at 50℃ and 75 rpm. Allow the resulting lipid vesicles to fully expand at room temperature (22-25℃) for 2 hours, then sonicate them in an ice bath for 20 minutes, with the sonication cycle on for 3 seconds and off for 3 seconds. Finally, sequentially squeeze the obtained vesicle system through microporous membranes of 0.80μm, 0.45μm, and 0.22μm to obtain the vitamin B12-loaded transporter.

[0082] Example 3

[0083] Weigh 5g of soybean lecithin and 0.5g of cholesterol into a dry round-bottom flask, and add a small amount of a mixture of chloroform and methanol to dissolve them. Evaporate the solvent using a rotary evaporator at 45℃ under reduced pressure until a uniform lipid layer forms on the flask wall. Dry under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.1g of vitamin B12 in 50g of deionized water. Hydrate the deposited film with the above solution for 1 hour at 50℃ and 75 rpm. Allow the resulting lipid vesicles to fully expand at room temperature (22-25℃) for 2 hours, then sonicate in an ice bath for 20 minutes, with the sonication cycle on for 3 seconds and off for 3 seconds. Finally, sequentially squeeze the obtained vesicle system through microporous membranes of 0.80μm, 0.45μm, and 0.22μm to obtain the vitamin B12-loaded transporter.

[0084] Example 4

[0085] Example 1

[0086] Example 2

[0087] Example 3

[0088] Example 4

[0089] Example 5

[0090] Example 6

[0091] Example 1

[0092] Example 2

[0093] Example 3

[0094] Example 4

[0095] Example 5

[0096] Example 6

[0097] Example 1

[0098] Example 2

[0099] Example 3

[0100] Example 4

[0101] Example 5

[0102] Example 6

[0103] Weigh 1g of soybean lecithin and 0.4g of cholesterol into a dry round-bottom flask, add a small amount of chloroform to dissolve them, and evaporate the solvent under reduced pressure at 45°C using a rotary evaporator until a uniform lipid layer forms on the flask wall. Then, dry under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.1g of vitamin B12 and 0.45g of Tween 80 in 50g of deionized water. Hydrate the deposited film in the above solution for 1 hour at 50°C and 75 rpm. Allow the resulting lipid vesicles to fully expand at room temperature (22-25°C) for 2 hours, then sonicate in an ice bath for 20 minutes, with a 3-second "on" and 3-second "off" cycle. Finally, sequentially squeeze the obtained vesicle system through microporous membranes of 0.80μm, 0.45μm, and 0.22μm to obtain the vitamin B12-loaded transporter.

[0104] Example 14

[0105] Weigh 1g of soybean lecithin and 0.4g of cholesterol into a dry round-bottom flask, add a small amount of chloroform to dissolve them, and evaporate the solvent under reduced pressure at 45℃ using a rotary evaporator until a uniform lipid layer forms on the flask wall. Then, dry under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.1g of vitamin B12 and 0.55g of Tween 80 in 50g of deionized water. Hydrate the deposited film in the above solution for 1 hour at 50℃ and 75rpm. Allow the resulting lipid vesicles to fully expand at room temperature (22-25℃) for 2 hours, then sonicate in an ice bath for 20 minutes, with a 3-second "on" and 3-second "off" cycle. Finally, sequentially squeeze the obtained vesicle system through microporous membranes of 0.80μm, 0.45μm, and 0.22μm to obtain the vitamin B12-loaded transporter.

[0106] Example 15

[0107] Take 0.5 g of soy lecithin and 0.2 g of cholesterol in a dry round bottom flask, and add a small amount of chloroform to dissolve it, evaporate the solvent under reduced pressure with a rotary evaporator at 45°C until a uniform lipid layer forms on the wall of the flask, and dry it under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.25 g of arbutin, 0.2 g of tannic acid, 0.05 g of sodium hyaluronate, 0.05 g of allantoin, 0.05 g of vitamin B12, 0.025 g of hydroxyethyl urea and 0.175 g of Tween 80 in 51.5 g of deionized water, and hydrate the deposited film with the above solution at 50°C with a rotation speed of 75 rpm for 1 h. The obtained lipid vesicles are fully inflated at room temperature (22-25°C) for 2 h, and then ultrasonic treated in an ice bath for 20 min, 3 s "on", 3 s "off". Finally, the obtained vesicle system is further extruded through 0.80 μm, 0.45 μm and 0.22 μm microporous filter membranes in turn to obtain the delivery body loaded with the functional ingredients. Mix 2.12 g of glycerol with 48.23 g of deionized water to swell 2.65 g of carbomer 980, slowly add the above delivery body to the swollen carbomer, add 0.1 g of phenoxyethanol, and then add triethanolamine dropwise to adjust the pH value to 6.5-7.0, and stir uniformly to obtain a complex delivery gel.

[0108] Example 16

[0109] Take 0.5 g of soy lecithin and 0.2 g of cholesterol in a dry round bottom flask, and add a small amount of chloroform to dissolve it, evaporate the solvent under reduced pressure with a rotary evaporator at 45°C until a uniform lipid layer forms on the wall of the flask, and dry it under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.25 g of arbutin, 0.2 g of tannic acid, 0.05 g of sodium hyaluronate, 0.05 g of allantoin, 0.05 g of vitamin B12, 0.025 g of hydroxyethyl urea and 0.175 g of Tween 80 in 51.5 g of deionized water, and hydrate the deposited film with the above solution at 50°C with a rotation speed of 75 rpm for 1 h. The obtained lipid vesicles are fully inflated at room temperature (22-25°C) for 2 h, and then ultrasonic treated in an ice bath for 20 min, 3 s "on", 3 s "off". Finally, the obtained vesicle system is further extruded through 0.80 μm, 0.45 μm and 0.22 μm microporous filter membranes in turn to obtain the delivery body loaded with the functional ingredients. Mix 2.12 g of glycerol with 48.23 g of deionized water to swell 2.65 g of carbomer 980, slowly add the above delivery body to the swollen carbomer, add 0.1 g of phenoxyethanol, and then add triethanolamine dropwise to adjust the pH value to 6.5-7.0, and stir uniformly to obtain a complex delivery gel.

[0110] Example 17

[0111] Take 1 g of soybean lecithin and 0.4 g of cholesterol in a dry round bottom flask, and add a small amount of chloroform to dissolve it, evaporate the solvent under reduced pressure with a rotary evaporator at 45°C, until a uniform lipid layer forms on the wall of the flask, and dry it under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.5 g of arbutin, 0.4 g of tannic acid, 0.1 g of sodium hyaluronate, 0.1 g of allantoin, 0.1 g of vitamin B12, 0.05 g of hydroxyethyl urea and 0.35 g of Tween 80 in 50 g of deionized water, and hydrate the deposited film with the above solution at 50°C with a rotation speed of 75 rpm for 1 h. The obtained lipid vesicles are fully inflated at room temperature (22-25°C) for 2 h, and then ultrasonically treated in an ice bath for 20 min, 3 s "on" and 3 s "off". Finally, the obtained vesicle system is further extruded through 0.80 μm, 0.45 μm and 0.22 μm microporous filter membranes in sequence to obtain the delivery body loaded with the efficacy ingredients. Mix 2.12 g of glycerol with 48.23 g of deionized water to swell 2.65 g of carbomer 980, slowly add the above delivery body to the swollen carbomer, add 0.1 g of phenoxyethanol, and then add triethanolamine dropwise to adjust the pH value to 6.5-7.0, and stir uniformly to obtain a complex delivery body gel.

[0112] Example 18

[0113] Take 1 g of soybean lecithin and 0.4 g of cholesterol in a dry round bottom flask, and add a small amount of chloroform to dissolve it, evaporate the solvent under reduced pressure with a rotary evaporator at 45°C, until a uniform lipid layer forms on the wall of the flask, and dry it under vacuum overnight to completely evaporate the organic solvent. Dissolve 0.35 g of Tween 80 in 51.25 g of deionized water, and hydrate the deposited film with the above solution at 50°C with a rotation speed of 75 rpm for 1 h. The obtained lipid vesicles are fully inflated at room temperature (22-25°C) for 2 h, and then ultrasonically treated in an ice bath for 20 min, 3 s "on" and 3 s "off". Finally, the obtained vesicle system is further extruded through 0.80 μm, 0.45 μm and 0.22 μm microporous filter membranes in sequence to obtain the blank delivery body. Mix 2.12 g of glycerol with 48.23 g of deionized water to swell 2.65 g of carbomer 980, slowly add the above blank delivery body to the swollen carbomer, add 0.1 g of phenoxyethanol, and then add triethanolamine dropwise to adjust the pH value to 6.5-7.0, and stir uniformly to obtain a complex delivery body gel.

[0114] Experimental Example 1

[0115] With vitamin B12 as the model substance, vitamin B12 aqueous solution (SOL) as the control, and examples 1, 4 and 8 as the evaluation objects, an in vitro penetration experiment through guinea pig skin was carried out to evaluate the influence of the preparation factors on the penetration ability.

[0116] Ex vivo guinea pig skin was fixed in the Franz static vertical diffusion chamber (effective diffusion area 1.789 cm²) of the YB-P6 intelligent transdermal testing instrument. 2 With the stratum corneum facing the supply pool, and deionized water as the receiving medium, the mixture was kept in a constant temperature water bath at 37±0.1℃ and stirred at a constant speed of 350rpm for 1 hour. Then, 1.5g of SOL and samples from Examples 1, 4, and 8 were added (each sample was tested in parallel six times). 1.0mL of transdermal receiving solution was collected at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours, and an equal volume of fresh receiving solution was added. The solutions were filtered through a 0.22μm microporous membrane, and the filtrate was collected for HPLC analysis to determine the vitamin B12 content. The cumulative transdermal permeation of vitamin B12 (Q) was calculated using the following formula. n ).

[0117]

[0118] In the formula, V0 is the volume of the receiving pool, V i For the sampling volume, C n The concentration at the nth sampling point (μg·mL) -1 ), C i The concentration at the i-th sampling point (μg·mL) -1 ), where A is the transdermal diffusion area. Let Q be the area of ​​transdermal diffusion. n Performing a linear regression on time t, the slope of the resulting regression line is the steady-state permeation rate J. ss (μg·cm -2 ·h -1 The effective surface area of ​​the cut skin was soaked in methanol for 24 hours to fully extract residual vitamin B12 from the skin, and its retention amount in each group was measured. The results are shown in Table 1.

[0119] Compared with the control group, the steady-state permeation rate and intradermal retention of vitamin B12 through guinea pig skin in Examples 1, 4, and 8 were significantly better than those in the control group, indicating that both liposomes (Example 1) and delivery systems (Examples 4 and 8) can promote transdermal absorption of the substance. Compared with Example 1, the J in Example 8... ss The intradermal retention was significantly increased in Example 8, while there was no significant difference in Example 4. This result indicates that the transdermal absorption of the delivery body (Example 8) prepared by adding the edge activator Tween 80 to the aqueous phase is significantly better than that of liposomes; while the delivery body of Example 4 added the edge activator to the lipids. Since this method is not conducive to the transfer of the highly hydrophilic vitamin B12 from the aqueous phase to the hydrophilic region of the lipid vesicles during hydration, it cannot enter the deep layers of the skin through the stratum corneum and epidermis along with the vesicles during transdermal delivery, resulting in a lower transdermal absorption capacity than that of Example 8.

[0120] Table 1 Vitamin B1 in different carriers12 In vitro skin permeability and intradermal retention amount (n=6)

[0121]

[0122] Note: "##" means a significant difference compared with Example 1 (P<0.01); "*" means a significant difference compared with the SOL group (P<0.05); "**" means a significant difference compared with the SOL group (P<0.01);

[0123] Experimental Example 2

[0124] The particle size, Zeta potential characterization and skin permeability evaluation of Examples 1-10 are shown in Table 2.

[0125] Table 2 Characterization and skin permeability evaluation of Examples 1-10

[0126]

[0127]

[0128] The second column indicates that "-" means that the group has no edge activator, and the edge activator in the 4th group is added to the lipid, and the edge activator in the remaining 5-10 groups is added to the aqueous phase.

[0129] The results in Table 2 show that:

[0130] (1) The results of Examples 1, 2 and 3 show that the particle size of Example 1 is the smallest, the Zeta potential is the largest, and the Q n and J ss are higher than those of the other two examples, indicating that when the mass ratio of phospholipid to cholesterol is 5:2, the preparation has high stability and skin permeability.

[0131] (2) The particle size of Examples 7, 9 and 10 is large, the Zeta potential is small, the preparation is unstable, and obvious stratification occurs after a period of storage, and the steady-state permeation rate (J ss ) and the cumulative permeation amount (Q n ) are also significantly reduced; while the particle size of Examples 5, 6 and 8 is smaller, the Zeta potential is larger, the preparation is stable, and no stratification is found after storage. This indicates that the type of edge activator has a significant effect on the physicochemical properties of the transferosome and its transdermal permeability, and sodium dodecyl sulfate, Tween 80 and sodium deoxycholate with a high HLB value as edge activators have better stability and promote skin absorption.

[0132] (3) Compared with Example 1, only Example 8 with Tween 80 as the edge activator has a smaller particle size, a larger Zeta potential, and a higher steady-state permeation rate and cumulative permeation amount, indicating that Tween 80 is the best choice for the edge activator.

[0133] (4) Example 4 has larger particle size and smaller Zeta potential than Example 8, further indicating that the method of adding edge activator to the lipids is not only unfavorable for the transdermal delivery ability of the transference body, but also unfavorable for the stability of the preparation.

[0134] In summary, Examples 1-10, the preparation method of the transference body and the type of edge activator are optimized, and the results show that the particle size of Example 8 is small, the stability is good, and the steady-state permeation rate and cumulative permeation amount are higher than those of other examples, which is beneficial to the transdermal of the efficacy component.

[0135] Experimental Example 3

[0136] Characterization of Example 8 and Example 17.

[0137] The average particle size of the vitamin B12-loaded transference body prepared in Example 8 is (113.46±0.51) nm, and the PDI is (0.20±0.19), indicating that the particle size distribution is concentrated; the average Zeta potential is (-38.23±0.14) mV, and the absolute value is greater than 30 mV, indicating that it has high physical stability. The appearance is a pink translucent solution, which is clear and transparent, without precipitate and flocculent, as shown in Figure 1 (A). The micro-morphology of the transference body observed under transmission electron microscope is shown in Figure 1 (B), from which it can be seen that the transference body is spherical, near-spherical vesicular, without aggregation, and uniformly dispersed in the solution.

[0138] The average particle size of the compound transference body gel prepared in Example 17 is (131.6±0.28) nm, and the PDI is (0.21±0.08), indicating that the particle size is uniform; the average Zeta potential is (-48.38±0.55) mV, and the absolute value is greater than 30 mV, indicating that the physical stability is high; the average viscosity is (43.85±0.25) Pa·s, indicating that the viscosity is suitable, easy to adhere to the skin surface and uniformly coated; the pH is (6.82±0.01), suitable for skin use. The appearance is a pink gel, with fine and uniform texture, without visible particles or lumps. The micro-morphology observed under transmission electron microscope is shown in Figure 2 , the transference body gel is near-spherical vesicular, without aggregation, and uniformly dispersed, and the particle size presented is basically consistent with the determination result of the particle size analyzer.

[0139] Experimental Example 4

[0140] The particle size and Zeta potential of Examples 8, 11, 12, 13 and 14 were determined by Malvern particle size analyzer. The entrapment efficiency (EE) and drug loading (DL) were determined by ultracentrifugation method.

[0141] Precise pipetting of the vitamin B12-loaded transferosome solution, adding methanol for 5 min to destroy the vesicles, and detecting on HPLC to analyze and calculate the total amount of drug (W 总 ) The vitamin B12-loaded transferosome solution 400 μL was placed in an ultrafiltration centrifuge tube, centrifuged at 3500 r / min for 45 min, and the upper layer of the encapsulating solution was taken and detected on HPLC to analyze and calculate the amount of drug (W 包 ) encapsulated in the transferosome

[0142]

[0143]

[0144] wherein W is the mass of vitamin B12 added in the weighing.

[0145] Table 3 Screening of the amount of edge activator

[0146]

[0147]

[0148] As can be seen from Table 3, with the increase of the amount of Tween 80, the particle size of the transferosome slightly increases, while the Zeta potential, the encapsulation rate and the drug loading capacity show a trend of first increasing and then decreasing. When the ratio of Tween 80 to phospholipid is 0.35:1, the Zeta potential, the encapsulation rate and the drug loading capacity reach the maximum, and the ratio is selected as the optimal amount.

[0149] Experimental Example 5

[0150] There are many literatures reporting the moisturizing and nourishing effects of sodium hyaluronate, allantoin and hydroxyethyl urea in the composition. Here, the basic effects of moisturizing, nourishing and the like are not evaluated, and only the four special effects of antioxidant, anti-inflammatory, whitening and anti-aging of the composition system are evaluated.

[0151] Zebrafish antioxidant evaluation: zebrafish embryos were incubated to 8 hours after fertilization (8hpf), and blank control group, hydrogen peroxide oxidative stress model group, negative control group (Example 18), test group (Example 17) and each single ingredient group with the same content of corresponding ingredients in the same preparation were set. Except the blank group and the model group, the rest of the groups were respectively given corresponding reagent pre-protection for 1 h. After 1 h, except the blank control group, each group was added with hydrogen peroxide for 16 h. After the end, the treatment liquid was discarded, and fish water was added to each well for continued incubation. When the zebrafish was incubated to 48hpf, the egg membrane was torn off with a special sharp-tipped forceps. DCFH-DA probe staining liquid was added to each well, and after staining for 1 h, an appropriate amount of anesthetic was added to take photos under an inverted fluorescence microscope, and the level of reactive oxygen species was counted by software. The results are shown in FIG. 8. Figure 3 ​

[0152] From the appendix Figure 3 (A) It was clearly observed that the blank group of zebrafish exhibited only weak green fluorescence, while the zebrafish juveniles showed strong green fluorescence after hydrogen peroxide-induced stimulation, indicating that oxidative stress occurred in the fish. After exposure to the negative control solution, no significant decrease in the intensity of green fluorescence was observed in the same areas; however, in the complex delivery gel treatment group, the fluorescence intensity observed in the same areas of the zebrafish juveniles was significantly reduced overall. These results indicate that the complex delivery gel plays a protective role against hydrogen peroxide-induced oxidative stress in the zebrafish model.

[0153] From the appendix Figure 3 (B) It can be seen that, compared with the hydrogen peroxide model group, the arbutin (AR) and sodium hyaluronate (HA) groups significantly reduced the level of reactive oxygen species (ROS) (P < 0.01), while the other single-component groups showed no significant differences. Since the reduction in ROS level in the complex gel CTG group was greater than that in each single-component group, it indicates that the antioxidant effect of the complex gel CTG group is the result of the combined action of arbutin and sodium hyaluronate.

[0154] Evaluation of the anti-inflammatory effect of zebrafish: Tg(Lyz:DsRed2) zebrafish embryos were incubated for 3 days post-fertilization (3dpf). A blank control group, a copper sulfate inflammation model group, a positive control group, a negative control group (Example 18), test groups with different concentrations (Examples 15, 16, 17), and single-component groups with the same content of the corresponding component as in Example 17 were set up. First, all zebrafish in all groups were pre-protected for 6 hours. After 6 hours, except for the blank control group, copper sulfate was added to all groups to induce the inflammation model. One hour after modeling, each group of zebrafish was washed, and an appropriate amount of tricaine anesthetic was added to each well. Abnormalities and neutrophil distribution in the zebrafish were observed and recorded under a fluorescence inverted microscope, and the number of neutrophils migrating to the lateral line thalamus and above was statistically analyzed. The results are attached. Figure 4 As shown.

[0155] From the appendix Figure 4As shown in (A) and (B), compared with the blank control group, the number of fluorescent spots (neutrophils) near the lateral line nerve thalamus of zebrafish tails in the model group was significantly increased (P < 0.01). The number of fluorescent spots near the lateral line nerve thalamus of zebrafish pre-protected with the positive control drug ibuprofen (IBU) was reduced compared with the model group (P < 0.01). These results indicate that the zebrafish inflammation model can be used for the anti-inflammatory activity study of this invention. Compared with the model group, there was no statistically significant difference in the blank excipient negative control group, proving that the excipient in the complex delivery gel had no anti-inflammatory activity. All groups of complex delivery gel at different concentrations inhibited the migration of neutrophils from the zebrafish tail to the lateral line nerve, showing a concentration-dependent trend, and all showed highly significant differences compared with the model group (P < 0.01). These results indicate that the complex delivery gel has an anti-inflammatory effect on neutrophil-transgenic zebrafish larvae.

[0156] Compared with the copper sulfate model group, except for HEU, the number of neutrophils migrating to the lateral line colliculus in the other single-component groups (AR, TA, VB, HA, and ALT) was significantly reduced (P < 0.05). The reduction in neutrophil count in the complex gel CTG group was much greater than that in the single-component groups, and its anti-inflammatory effect was the result of the combined action of each individual factor. It is worth mentioning that the humectant allantoin (ALT) played a synergistic anti-inflammatory role here.

[0157] Evaluation of the whitening effect of zebrafish: Zebrafish embryos were incubated to 24 hpf. A blank control group, a positive control group, a negative control group (Example 18), a test group (Example 17), and single-component groups with the same content of corresponding components in the same preparation were set up and administered the corresponding reagents. The embryos were covered and placed in an incubator to continue development. 48 hours after administration, an appropriate amount of tricaine anesthetic was added. Local melanin in the zebrafish was observed under a microscope, and images were acquired for statistical analysis of the local melanin area. Results are attached. Figure 5 As shown.

[0158] From the appendix Figure 5 (A) It can be seen that in the blank control group, a large number of black spots, i.e., deposited melanin, can be clearly observed on both sides of the spine and the middle part of the trunk of zebrafish juveniles; in the negative control group, no significant reduction in melanin deposition can be observed on the same parts of zebrafish juveniles; while in the positive control and complex delivery gel treatment groups, the melanin deposition observed on the same parts of zebrafish juveniles is significantly reduced, indicating that the complex delivery gel can inhibit the synthesis of melanin in zebrafish juveniles, thereby playing a whitening role.

[0159] Appendix Figure 5(B)It can be seen that compared with the blank control group CG, the order of single components which can significantly reduce the local melanin area is AR > VB > TA. The anti-melanin effect of the complex delivery gel is significantly greater than that of each single component group, and the effect is the result of the combined action of the three single factors. Since vitamin B12 has a significant effect on reducing melanin (P < 0.01), it is explained that vitamin B12 plays a synergistic role in this experimental model.

[0160] Cell anti-aging efficacy evaluation: human skin fibroblasts were inoculated in the hole plate after adhesion, and the blank control group, the hydrogen peroxide-induced aging model group, and the test group of the efficacy component composition were set. After 24 h of pre-protection of the corresponding reagent, except for the blank control group, hydrogen peroxide was added to each hole for modeling for 1 h, then the liquid in the hole plate was discarded, complete culture medium was added, and after 2 d of incubation under suitable conditions, staining was performed according to the instructions of the cell aging β-galactosidase staining kit, and images were collected under a microscope. The results are shown in the attached Figure 6

[0161] As can be seen from the attached Figure 6 , the cells in the blank control group are normal spindle-shaped, in good condition, and almost no blue-stained cells, while the number of positive blue-stained senescent cells in the model group is significantly increased, showing an increase in cell nucleus volume and a more rounded cell morphology, indicating that the cells are in a senescent state. After treatment with the efficacy substance composition, the number of positive blue-stained cells is significantly reduced, indicating that the number of senescent cells is significantly reduced. It is indicated that the treatment of the efficacy substance composition can alleviate the aging of human skin fibroblasts.

[0162] Experimental Example 6

[0163] The safety of Examples 17 and 18 was evaluated by guinea pig skin irritation test and histopathology.

[0164] The back hair of each guinea pig was shaved 24 h before the experiment, and the skin was ensured to be intact. 0.5 g of Example 17 and Example 18 were applied on both sides of the guinea pig's back as self-control, respectively. The skin irritation and erythema were observed at 1, 24, 48 and 72 h after administration. The skin irritation was evaluated by Draize scale, and the irritation score between 0 and 4 was used to evaluate the irritation intensity, ranging from no reaction to severe reaction. After the skin irritation test, the histopathological changes of the skin were observed.

[0165] The results of the skin irritation test in Table 4 show that Examples 17 and 18 have no irritation to guinea pigs within 1, 24, 48 and 72 h. As can be seen from the attached Figure 7 , normal skin shows complete stratum corneum, epidermis, dermis and hair follicle structure. Compared with normal skin ( Figure 7 A), Example 17 ( Figure 7 B) and Example 18 ( Figure 7 ​C) The treated skin showed no significant changes. The sebaceous gland structure was intact, there was no dermal edema, and there was no obvious neutrophil or inflammatory cell infiltration, indicating that the invented complex delivery gel had no irritation effect on the guinea pig back skin and could be safely used as a cosmetic.

[0166] Table 4 Guinea pig skin irritation score

[0167]

[0168] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present application, and are not limited thereto; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that the technical solutions described in the foregoing examples can still be modified, or some or all of the technical features can be replaced by equivalents; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A delivery vehicle for a composition that addresses skin aging problems in multiple dimensions, characterized in that, The composition is made of the following raw material components by weight percentage: phospholipid 0.98-4.71wt%, cholesterol 0.39-0.90wt%, edge activator 0.17-0.87wt%, efficacy component 0.09-2wt%, and the rest is water; The phospholipid is selected from soybean lecithin or egg yolk lecithin, the edge activator is Tween 80, the mass ratio of the phospholipid to cholesterol is 5:2; the efficacy component includes 0.2-0.5 parts of β-arbutin, 0.2-0.5 parts of tranexamic acid, 0.01-0.5 parts of sodium hyaluronate, 0.01-0.5 parts of allantoin, 0.01-0.5 parts of vitamin B12 and 0.01-0.5 parts of hydroxyethyl urea; The preparation method of the delivery body of the composition for solving the skin aging problem in multiple dimensions includes the following steps: (1) the phospholipid and cholesterol are mixed and dissolved in an organic solvent, the organic solvent is evaporated under reduced pressure, a uniform lipid layer is formed on the container wall, and the organic solvent is completely volatilized under vacuum to form a deposited film; (2) the efficacy component and the edge activator are stirred and dissolved in water to form a mixed solution, which is added to the container containing the deposited film for hydration; (3) the obtained lipid vesicle is fully swollen and cooled for ultrasonic treatment; (4) the obtained lipid vesicle is filtered through a microporous filter to obtain the delivery body of the composition.

2. A multi-dimensional synergistic composition delivery gel for addressing skin aging problems, characterized in that, The delivery body of the composition for solving the skin aging problem in multiple dimensions, the cosmetic acceptable adjuvant, and the cosmetic acceptable adjuvant including carbomer and solvent.

3. A multi-dimensional synergistic composition delivery gel for skin aging prepared according to claim 2, characterized in that, The preparation method includes the following steps: (1) the carbomer is dispersed in water in which glycerol is dissolved, and after complete swelling and dissolution, a preservative is added; (2) the solution of step (1) is mixed with the composition delivery body under gentle stirring; (3) the pH of step (2) is adjusted to 6.5-7.0 with triethanolamine, and the mixture is stirred uniformly to obtain the product.

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