A skin care water prepared based on a bidirectional poorly soluble substance microemulsification technology and a preparation method thereof

Abstract

The application discloses skin care water prepared based on a bidirectional poorly soluble substance microemulsification technology and a preparation method and application thereof. The application mainly overcomes bidirectional poorly soluble property of hydroxyl pinacolone retinoate, and obtains skin care water containing bidirectional poorly soluble substances through a microemulsification preparation process, thereby providing a new idea for development of the substances in the future. The microemulsion emulsion is prepared from polydimethylsiloxane, linoleic acid, lecithin, tocopherol, betaine, hydroxyl pinacolone retinoate and the like. The skin care water has smaller irritation, high efficacy, strong stability, is not easy to be oxidized and lost, and is very refreshing, and is a safe and effective anti-aging and freckle lightening skin care water.

Description

Technical Field

[0001] This invention relates to the field of skincare products, and in particular to a skincare water prepared based on a two-way microemulsification technology for poorly soluble substances and its preparation method. Background Technology

[0002] Bisammolytic substances are substances that are not easily soluble in either water or oil. Common examples include amphotericin B, vincristine, and hydroxypinazone retinyl ester. These substances are often found in artificially synthesized substances with good clinical value.

[0003] In pharmaceuticals, medical devices, and cosmetics, products prepared using these bidirectional poorly soluble substances are prone to crystallization, leading to formulation failure. However, developing new active pharmaceutical ingredient formulations remains a demand for many companies. Generally, to ensure formulation stability, special chemical reagents are added, such as dimethyl sulfoxide, isosorbide dimethyl ether, trichloroethylene, styrene, and methanol—organic solvents with strong solubility. These solvents are highly destructive to lipids and proteins. Oral administration can easily cause poisoning, injection can easily cause shock, and topical application can damage the stratum corneum of the skin. Since Guizhou Jiulide Biopharmaceutical Co., Ltd. primarily researches topical formulations, the main focus of this research is on how to prepare topically stable formulations using bidirectional poorly soluble substances as active ingredients.

[0004] Generally, these bidirectional poorly soluble substances can be stabilized in topical formulations in three ways: (1) Prepare a paste-like formulation, that is, prepare a formulation with high viscosity through a water-in-oil or oil-in-water process to prevent the poorly soluble substances from separating under high viscosity conditions. (2) Prepare a gel-like formulation with high viscosity by adding substances such as carbomer, xanthan gum, and guar gum to prevent the bidirectional poorly soluble substances from agglomerating or precipitating in the gel. (3) Add organic solvents to prepare an oil-in-water or oil-in-water emulsion to dissolve the bidirectional poorly soluble substances in the oil phase. To avoid precipitation, the amount of organic solvent added must be much greater than the amount used to saturate the bidirectional poorly soluble substances. However, it is very difficult to make a formulation that is miscible with water in any proportion and remains stable, like a skin care lotion, for bidirectional poorly soluble substances. This is because bidirectional poorly soluble substances have hydrophobic and lipophilic properties. If an excessive amount of organic solvent is used, it will cause some damage to the skin, and the organic solvent is also very difficult to stabilize in water.

[0005] Through extensive experimental research, the applicant developed a microemulsion formulation process specifically targeting the bidirectional poorly soluble substance hydroxypinazone retinyl ester. This process overcomes the bidirectional poor solubility of hydroxypinazone retinyl ester, ultimately producing a semi-transparent liquid skin care water with lower irritation, higher efficacy, stronger stability, and less susceptibility to oxidation and degradation. It also possesses anti-aging and anti-acne effects. This provides a new approach to the microemulsion formulation of bidirectional poorly soluble substances. Summary of the Invention

[0006] The purpose of this invention is to provide a skin care water prepared based on microemulsification technology for bidirectional poorly soluble substances and its preparation method. This invention overcomes the bidirectional poor solubility of hydroxypinazone retinyl ester, and obtains a skin care water containing bidirectional poorly soluble substances through a microemulsification process. This skin care water is less prone to stratification, less irritating, highly effective, and stable, and is not easily oxidized and degraded, making it a safe and effective anti-aging skin care water.

[0007] The technical solution of the present invention:

[0008] A skin care water prepared based on a two-way microemulsion technology for poorly soluble substances, mainly composed of, by weight, 0.02-0.2 parts of polydimethylsiloxane, 0.01-0.1 parts of linoleic acid, 0.01-0.1 parts of lecithin, 0.15-1.5 parts of betaine, 0.02-0.2 parts of tocopherol, 0.05-0.5 parts of hydroxypinacol retinate, 1-10 parts of glycerin, and 0. It is prepared from 5-5 parts of lipoic acid, 0.01-0.05 parts of sodium hyaluronate, 0.1-1 parts of polydimethylsiloxane, 0.1-1 parts of dipotassium glycyrrhizate, 0.01-0.04 parts of disodium ethylenediaminetetraacetate, 1-10 parts of hydroxyethyl urea, 0.01-0.1 parts of chlorphenesin, 0.01-0.05 parts of menthol ethylamine, and 0.15-0.25 parts of triethanolamine.

[0009] The aforementioned skin care water prepared based on the bidirectional microemulsion technology for poorly soluble substances is characterized by the following components, by weight: 0.1-0.2 parts polydimethylsiloxane, 0.05-0.1 parts linoleic acid, 0.02-0.08 parts lecithin, 0.5-1.2 parts betaine, 0.1-0.2 parts tocopherol, 0.08-0.4 parts hydroxypinazone retinyl ester, 2-5 parts glycerin, and 0 parts propylene glycol. It is prepared from 0.8-3 parts, 0.01-0.03 parts, sodium hyaluronate 0.2-0.8 parts, polydimethylsiloxane 2-5 parts, dipotassium glycyrrhizate 0.1-0.5 parts, disodium ethylenediaminetetraacetate 0.01-0.03 parts, hydroxyethyl urea 5-10 parts, chlorphenesin 0.05-0.1 parts, menthol methylformyl ethylamine 0.02-0.04 parts, and triethanolamine 0.1-0.2 parts.

[0010] 3. The skin care water prepared based on the bidirectional microemulsion technology for poorly soluble substances according to claim 2, characterized in that: by weight, it is mainly prepared from 0.2 parts of polydimethylsiloxane, 0.1 parts of linoleic acid, 0.05 parts of lecithin, 1.1 parts of betaine, 0.2 parts of tocopherol, 0.1 parts of hydroxypinazone retinyl ester, 3 parts of glycerin, 1 part of propylene glycol, 0.02 parts of lipoic acid, 0.5 parts of sodium hyaluronate, 3 parts of polydimethylsiloxane, 0.2 parts of dipotassium glycyrrhizate, 0.02 parts of disodium EDTA, 10 parts of hydroxyethylurea, 0.1 parts of chlorophenoxyether, 0.03 parts of menthol ethylformylamine, and 0.15 parts of triethanolamine.

[0011] 4. The method for preparing skin care water based on bidirectional poorly soluble microemulsion technology according to any one of claims 1-3, characterized in that: the preparation method includes the following steps:

[0012] (1) Weigh out polydimethylsiloxane, linoleic acid, lecithin, tocopherol and betaine in 1 / 11 of the ratio according to the proportion, put them into a vacuum emulsification tank, heat to 75-85℃ under stirring at 45-55 rpm to completely dissolve, and then quickly cool down to 40-50℃ to obtain product A.

[0013] (2) Stir product A at 45-55 rpm, then add the specified amount of hydroxypinazone retinate, and continue stirring for 0.5-1.5 hours until the hydroxypinazone retinate is completely dissolved. Turn on the vacuum emulsification tank and emulsify at 2000-3000 rpm. Quickly add 5-20 parts by weight of water to the vacuum emulsification tank. After emulsifying for 4-6 minutes, use cooling circulating water to lower the temperature to below 25°C within 8-12 minutes to obtain the microemulsion, i.e. product B.

[0014] (3) Weigh out glycerol, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol ethylamine and 10 / 11 of the amount of betaine according to the ratio, place them in a mixing tank, add 40-60 parts by weight of purified water and stir. After the mixture is completely dissolved, add the amount of triethanolamine according to the ratio and stir to dissolve. Finally, add product B, stir and make up to volume to obtain the final product.

[0015] 5. The method for preparing skin care water based on bidirectional insoluble microemulsion technology according to claim 4, characterized in that: in step (1), polydimethylsiloxane, linoleic acid, lecithin, tocopherol and betaine in 1 / 11 of the ratio are weighed according to the ratio, put into a vacuum emulsification tank, heated to 80°C under stirring at 50 rpm to completely dissolve, and then rapidly cooled to 45-50°C to obtain product A.

[0016] 6. The method for preparing skin care water based on bidirectional insoluble microemulsion technology according to claim 4, characterized in that: in step (2), product A is stirred at 50 rpm, and then the specified amount of hydroxypinazone retinate is added. Stirring is maintained for 1 hour until the hydroxypinazone retinate is completely dissolved. The vacuum emulsification tank is turned on at 2500 rpm for emulsification. 10 parts by weight of water are quickly added to the vacuum emulsification tank. After emulsification for 5 minutes, the temperature is lowered to below 25°C within 10 minutes using cooling circulating water to obtain the microemulsion emulsion, i.e., product B.

[0017] 7. The method for preparing skin care water based on bidirectional poorly soluble microemulsion technology according to claim 4, characterized in that: in step (3), glycerin, propylene glycol, thioctic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol carboxyethylamine and betaine in a ratio of 10 / 11 are weighed according to the ratio, placed in a mixing tank, 50 parts by weight of purified water are added and stirred. After the mixture is completely dissolved, triethanolamine in the ratio is added and stirred until dissolved. Finally, product B is added, stirred and then brought to a final volume to obtain the product.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] Hydroxypinazone retinyl ester (HPR) is a novel retinol-like substance. Studies show that compared to other vitamin A derivatives, it does not require metabolic conversion (retinol typically undergoes two conversions within the skin) and can directly exert its effects by stimulating receptors. It is less irritating, yet highly potent, more stable, and less prone to oxidation and degradation, making it a safe and effective anti-aging ingredient (effectively reducing fine lines and wrinkles, and fading age spots). However, it is poorly soluble in both water and oil. In commercially available products, it is generally formulated with a large amount of isosorbide dimethyl ether as a base solvent, then prepared into a thick, water-in-oil or oil-in-water cream or lotion formulation.

[0020] However, in hot weather, excessive oiliness in creams or lotions can make the skin feel suffocated. When used at night, the thick layer of oil can also cause discomfort, affecting its effectiveness. In an earlier patent application filed by Guizhou Jiulide Biopharmaceutical Co., Ltd., entitled "A Targeted Bilayer Lipid Microsphere Emulsion," we used hydroxypinazone retinate and utilized bilayer lipid microsphere technology to prepare a relatively thin emulsion, but it was still heavy and could not meet the requirement of customers not experiencing any suffocation after use in hot weather. Therefore, we developed a microemulsion skincare water containing a bidirectional poorly soluble substance—hydroxypinazone retinate.

[0021] The advantages of this formulation compared to other commercially available formulations containing the poorly soluble substance hydroxypinazone retinate are:

[0022] 1. It is a skin care water, and it does not have the same feel as creams or lotions. It is very refreshing.

[0023] 2. It is a very stable aqueous preparation. It will not separate into layers even after centrifugation at 5000 rpm for 30 minutes, and its various indicators will not change even after one month of accelerated centrifugation at 40 degrees Celsius.

[0024] 3. It contains no organic solvents and no typical surfactants, making it very skin-friendly.

[0025] 4. Because it is a microemulsion with a very small particle size (microemulsion particle size range 10-100 nanometers), it can easily penetrate the stratum corneum and granular layer, and has obvious anti-aging, firming and pigmentation fading effects.

[0026] 5. At the same time, this formulation provides a solution for the future development of aqueous formulations of bidirectional poorly soluble substances. Attached Figure Description

[0027] Figure 1 Product structure simulation diagram;

[0028] Figure 2 : Final formulation product diagram of Experimental Example 1;

[0029] Figure 3 : Final formulation product diagram of Experimental Example 2;

[0030] Figure 4 : Final formulation product diagram of Experimental Example 3;

[0031] Figure 5 : Final formulation product image of Experiment Example 3 (30 days of refrigerated storage);

[0032] Figure 6 Case 1: Before and after using the skin care toner in Example 1 (A: before use; B: after use);

[0033] Figure 7 Case 2: Before and after using the skin care toner from Example 1, the epidermis showed increased skin volume (A: before use; B: after use).

[0034] Figure 8 : Graphs showing the improvement of facial wrinkles after using the skin care water in Example 1 (A: Changes in skin appearance before use; B: Changes in skin appearance after 3 days of use before use; C: Changes in skin appearance after 7 days of use before use; D: Changes in skin appearance after 14 days of use before use);

[0035] Figure 9 Comparison chart of DPPH free radical scavenging rates. Detailed Implementation

[0036] The present invention will be further described below with reference to embodiments, but these embodiments are not intended to limit the scope of the invention.

[0037] Example 1.

[0038] (1) Preparation of microemulsions:

[0039] Formula: 0.2g polydimethylsiloxane, 0.1g linoleic acid, 0.05g lecithin, 0.2g tocopherol, 0.1g betaine, 0.1g hydroxypinacol retinyl ester.

[0040] Microemulsion emulsion preparation process:

[0041] Weigh out polydimethylsiloxane, linoleic acid, lecithin, tocopherol, and betaine according to the above proportions, and place them in a vacuum emulsifying tank. Under stirring at 50 rpm, heat to 80°C until completely dissolved, then rapidly cool to 45-50°C while maintaining stirring at 50 rpm. Add the specified amount of hydroxypinazone retinate and maintain stirring for 1 hour until the hydroxypinazone retinate is completely dissolved. Turn on the vacuum emulsifying tank and emulsify at 2500 rpm. Quickly add 10g of purified water to the vacuum emulsifying tank and emulsify for 5 minutes. Then, use cooling circulating water to lower the temperature to below 25°C within 10 minutes to obtain a microemulsion emulsion.

[0042] (2) Preparation of the finished skin care water:

[0043] Formula: 3g glycerin, 1g propylene glycol, 0.02g thioctic acid, 0.5g sodium hyaluronate, 3g polydimethylsiloxane, 0.2g dipotassium glycyrrhizate, 0.02g disodium EDTA, 10g hydroxyethyl urea, 0.1g chlorphenesin, 0.03g menthol carbamoyl ethylamine, 1g betaine, and the microemulsion prepared in step (1).

[0044] Skin care water preparation process: Weigh out glycerin, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol carbamoyl ethylamine, and betaine according to the specified ratio, place them in a mixing jar, add 50g of purified water and stir. After the mixture is completely dissolved, add the specified amount of triethanolamine and stir to dissolve. Finally, add product B, stir, and bring the volume to 100ml to obtain the skin care water.

[0045] Example 2.

[0046] (1) Preparation of microemulsions:

[0047] Formula: 0.02g polydimethylsiloxane, 0.01g linoleic acid, 0.01g lecithin, 0.02g tocopherol, 0.05g betaine, 0.05g hydroxypinacol retinyl ester.

[0048] Preparation process: Weigh out polydimethylsiloxane, linoleic acid, lecithin, tocopherol, and betaine according to the above ratio, and put them into a vacuum emulsifying tank. Under stirring at 45 rpm, heat to 75°C to completely dissolve, then rapidly cool to 40°C, and maintain stirring at 45 rpm. Then add the specified amount of hydroxypinacol retinate and maintain stirring for 0.5 hours until the hydroxypinacol retinate is completely dissolved. Turn on the vacuum emulsifying tank to 2000 rpm for emulsification, and quickly add 5g of purified water to the vacuum emulsifying tank. After emulsifying for 4 minutes, use cooling circulating water to lower the temperature to below 25°C within 8 minutes to obtain a microemulsion emulsion.

[0049] (2) Preparation of the finished skin care water:

[0050] Formula: 1g glycerin, 0.5g propylene glycol, 0.01g thioctic acid, 0.1g sodium hyaluronate, 1g polydimethylsiloxane, 0.1g dipotassium glycyrrhizate, 0.01g disodium EDTA, 1g hydroxyethyl urea, 0.01g chlorphenesin, 0.01g menthol carbamoyl ethylamine, 0.1g betaine, and the microemulsion prepared in step (1).

[0051] Preparation process: Weigh out glycerol, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol carbamoyl ethylamine, and betaine according to the specified ratio, place them in a mixing jar, add 40g of purified water and stir. After the mixture is completely dissolved, add the specified amount of triethanolamine and stir to dissolve. Finally, add product B, stir, and bring the volume to 100ml to obtain the final product.

[0052] Example 3.

[0053] (1) Preparation of microemulsions:

[0054] Formula: 0.2g polydimethylsiloxane, 0.1g linoleic acid, 0.1g lecithin, 0.02-0.2g tocopherol, 0.5g betaine, 0.5g hydroxypinacol retinyl ester.

[0055] Preparation process: Weigh out polydimethylsiloxane, linoleic acid, lecithin, tocopherol, and betaine according to the above ratio, and put them into a vacuum emulsifying tank. Under stirring at 55 rpm, heat to 85°C to completely dissolve, then rapidly cool to 50°C, and maintain stirring at 55 rpm. Then add the specified amount of hydroxypinazone retinate and maintain stirring for 1.5 hours until the hydroxypinazone retinate is completely dissolved. Turn on the vacuum emulsifying tank and emulsify at 3000 rpm. Quickly add 20g of purified water to the vacuum emulsifying tank. After emulsifying for 6 minutes, use cooling circulating water to lower the temperature to below 25°C within 12 minutes to obtain a microemulsion emulsion.

[0056] (2) Preparation of the finished skin care water:

[0057] Formula: 10g glycerin, 5g propylene glycol, 0.05g thioctic acid, 1g sodium hyaluronate, 15g polydimethylsiloxane, 1g dipotassium glycyrrhizate, 0.04g disodium EDTA, 10g hydroxyethyl urea, 0.1g chlorphenesin, 0.05g menthol carbamoyl ethylamine, 1g betaine, and the microemulsion prepared in step (1).

[0058] Preparation process: Weigh out glycerin, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol carbamoyl ethylamine, and betaine according to the specified ratio, place them in a mixing jar, add 60g of purified water and stir until completely dissolved. Then add the specified amount of triethanolamine and stir until dissolved. Finally, add product B, stir, and bring the volume to 100ml to obtain the final product.

[0059] Example 4.

[0060] (1) Preparation of microemulsions:

[0061] Formula: 0.1g polydimethylsiloxane, 0.02g linoleic acid, 0.05g lecithin, 0.15g tocopherol, 0.3g betaine, 0.2g hydroxypinacol retinyl ester.

[0062] Preparation process: Weigh out polydimethylsiloxane, linoleic acid, lecithin, tocopherol, and betaine according to the above ratio, and put them into a vacuum emulsifying tank. Under stirring at 45 rpm, heat to 85°C until completely dissolved, then rapidly cool to 50°C, and maintain stirring at 45 rpm. Then add the specified amount of hydroxypinazone retinate and maintain stirring for 1.5 hours until the hydroxypinazone retinate is completely dissolved. Turn on the vacuum emulsifying tank and emulsify at 3000 rpm. Quickly add 15g of purified water to the vacuum emulsifying tank. After emulsifying for 6 minutes, use cooling circulating water to lower the temperature to below 25°C within 8-12 minutes to obtain a microemulsion emulsion.

[0063] (2) Preparation of the finished skin care water:

[0064] Formula: 3g glycerin, 2.5g propylene glycol, 0.04g thioctic acid, 0.6g sodium hyaluronate, 5g polydimethylsiloxane, 0.2g dipotassium glycyrrhizate, 0.01g disodium EDTA, 10g hydroxyethyl urea, 0.1g chlorphenesin, 0.02g menthol carbamoyl ethylamine, 0.8g betaine, and the microemulsion prepared in step (1).

[0065] Preparation process: Weigh out glycerin, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol carbamoyl ethylamine, and betaine according to the specified ratio, place them in a mixing jar, add 50g of purified water and stir until completely dissolved. Then add the specified amount of triethanolamine and stir until dissolved. Finally, add product B, stir, and bring the volume to 100ml to obtain the final product.

[0066] Example 5.

[0067] (1) Preparation of microemulsions:

[0068] Formula: 0.09g polydimethylsiloxane, 0.05g linoleic acid, 0.1g lecithin, 0.15g tocopherol, 0.3g betaine, 0.25g hydroxypinacol retinyl ester.

[0069] Preparation process: Weigh out polydimethylsiloxane, linoleic acid, lecithin, tocopherol, and betaine according to the above ratio, and put them into a vacuum emulsifying tank. Under stirring at 55 rpm, heat to 75°C to completely dissolve, then rapidly cool to 45°C, and maintain stirring at 55 rpm. Then add the specified amount of hydroxypinacol retinate and maintain stirring for 1 hour until the hydroxypinacol retinate is completely dissolved. Turn on the vacuum emulsifying tank to 2000 rpm for emulsification, and quickly add 10g of purified water to the vacuum emulsifying tank. After emulsifying for 5 minutes, use cooling circulating water to lower the temperature to below 25°C within 12 minutes to obtain a microemulsion emulsion.

[0070] (2) Preparation of the finished skin care water:

[0071] Formula: 2g glycerin, 5g propylene glycol, 0.05g thioctic acid, 0.1g sodium hyaluronate, 10g polydimethylsiloxane, 0.2g dipotassium glycyrrhizate, 0.02g disodium EDTA, 2g hydroxyethyl urea, 0.05g chlorphenesin, 0.04g menthol carbamoyl ethylamine, 0.1g betaine, and the microemulsion prepared in step (1).

[0072] Preparation process: Weigh out glycerol, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane, dipotassium glycyrrhizate, disodium EDTA, hydroxyethyl urea, chlorphenesin, menthol ethylamine, and betaine according to the specified ratio, place them in a mixing jar, add 55g of purified water and stir. After the mixture is completely dissolved, add the specified amount of triethanolamine and stir to dissolve. Finally, add product B, stir, and bring the volume to 100ml to obtain the final product.

[0073] The inventor conducted numerous experiments; the following are some of the experimental studies.

[0074] 1. Research on Microemulsion Formulation Process

[0075] Initially, only a single cosolvent—lecithin—was considered, with the expectation that lecithin could bind hydroxypinazone retinate to form stable critical micelles or directly encapsulate it. However, the experiment failed (see Experiment 1). Subsequently, a surfactant (polysorbate-20) was added, hoping to form a stable emulsion, but this also failed (see Experiment 2). Analysis of the chemical structure of this raw material revealed that although hydroxypinazone retinate is neither hydrophilic nor lipophilic, its chemical structure is as follows:

[0076]

[0077] It is a substance formed by the dehydration condensation of retinoic acid and pinacol. The polarizability of retinoic acid is (10) -24 cm 3 The polarizability of pinacol is 37.87, indicating it is a water-insoluble substance but soluble in fats and oils. -24 cm 3 The polarizability of water is 13.02, indicating that it is a substance that is soluble in water but poorly soluble in oils. -24 cm 3 The polarizability is 1.45, which is generally lower than that of oils (10). -24 cm 3 (greater than 20). Therefore, although hydroxypinazone retinate is neither lipophilic nor hydrophilic as a whole, as the two condensed parts (retinoic acid and pinacol), they each have different hydrophilic and lipophilic properties. Thus, we attempted to develop a stable microemulsion formulation by utilizing the different properties of retinoic acid and pinacol, hoping to insert the retinoic acid portion into the oil and the pinacol portion into the water. Through numerous experiments, we finally succeeded, establishing a solubility system for the bidirectionally insoluble hydroxypinazone retinate composed of oils and aqueous substances. See the simulation diagram below. Figure 1 .

[0078] Finally, a stable microemulsion formulation was prepared using this system.

[0079] Because betaine has moisturizing properties for the skin and is also a water-soluble solubilizer, its safety and efficacy have been verified through long-term use. Therefore, we began to explore different ratios of betaine and lecithin, and conducted experiments (Experiment Example 3). The final determined ratio was lecithin:betaine = 1:2, at which hydroxypinazone retinate could be completely dissolved, and the final formulation was stable (see Experiment Example 3).

[0080] 1.1 Experimental Example 1: Results of using lecithin alone as a cosolvent 1.1.1 Preparation of microemulsions

[0081] Table 1. Raw material ratio and function of microemulsion in Experiment 1

[0082] 1 Linoleic acid 0.1 Strong oleophilic and weak hydrophilic solvents 2 Lecithin 0.05 lipophilic and hydrophilic cosolvents 3 Vitamin E (Tocopherol) 0.2 antioxidants 4 Hydroxypinazone Retinyl 0.1 Two-way insoluble active ingredients 5 water 10 emulsified water

[0083] Weigh materials 1-3 in sequence into a vacuum emulsifying tank. Heat to 80°C with stirring at 50 rpm until completely dissolved, then rapidly cool to 45-50°C. Add hydroxypinazone retinyl ester to the vacuum emulsifying tank with stirring at 50 rpm, maintain for approximately one hour, then turn the vacuum emulsifying tank on to 2500 rpm for emulsification, and quickly add water. Emulsify for 5 minutes. Using circulating cooling water, lower the temperature to below 25°C within 10 minutes.

[0084] 1.1.2 Preparation of the aqueous phase

[0085] Table 2. Aqueous phase raw material ratio and function in Experiment Example 1.

[0086] 1 glycerin 3 Moisturizer 2 Propylene glycol 1 Moisturizer 3 Alpha-lipoic acid 0.02 antioxidants 4 Sodium hyaluronate 0.5 Moisturizer 7 polydimethylsiloxane 3 Water-soluble solvents 8 Dipotassium glycyrrhizate 0.2 Anti-allergens 9 Disodium ethylenediaminetetraacetate 0.02 Chelating agents 10 Hydroxyethylurea 10 Moisturizer 11 Chlorphenesin 0.1 preservative 12 betaine 1 Moisturizers, solubilizers 13 Menthyl carbamate 0.03 Cooling agent 14 water 50 solvent 15 Triethanolamine 0.15 pH adjuster 16 Microemulsion emulsion —— ——

[0087] Weigh materials 1 through 14 into a mixing tank, stir until completely dissolved, then add triethanolamine and stir. Next, add the microemulsion, stir, and bring to a final volume.

[0088] See formulation photos Figure 2 Hydroxypinazone retinyl ester floats completely on the surface of the liquid, forming a layer of grease.

[0089] 1.2 Experimental Example 2: Polysorbate-20 and lecithin as surfactants 1.2.1 Preparation of microemulsions

[0090] Table 3. Raw material ratio and function of microemulsion emulsion in Experiment Example 2.

[0091] 1 Linoleic acid 0.1 Strong oleophilic and weak hydrophilic solvents 2 Lecithin 0.05 lipophilic and hydrophilic cosolvents 3 Polysorbate-20 0.1 surfactants 4 Vitamin E (Tocopherol) 0.2 antioxidants 5 Hydroxypinazone Retinyl 0.1 Two-way insoluble active ingredients 6 water 10 emulsified water

[0092] Weigh materials 1-4 in order into a vacuum emulsifying tank. Heat to 80°C with stirring at 50 rpm until completely dissolved, then rapidly cool to 45-50°C. Add hydroxypinazone retinyl ester to the vacuum emulsifying tank with stirring at 50 rpm, maintain this temperature for approximately one hour, then turn the vacuum emulsifying tank on to 2500 rpm and quickly add water. Emulsify for 5 minutes. Using circulating cooling water, lower the temperature to below 25°C within 10 minutes.

[0093] 1.2.2 Preparation of the aqueous phase

[0094] Table 4. Aqueous phase raw material ratio and function in Experiment Example 2

[0095] 1 glycerin 3 Moisturizer 2 Propylene glycol 1 Moisturizer 3 Alpha-lipoic acid 0.02 antioxidants 4 Sodium hyaluronate 0.5 Moisturizer 7 polydimethylsiloxane 3 Water-soluble solvents 8 Dipotassium glycyrrhizate 0.2 Anti-allergens 9 Disodium ethylenediaminetetraacetate 0.02 Chelating agents 10 Hydroxyethylurea 10 Moisturizer 11 Chlorphenesin 0.1 preservative 12 betaine 1 Moisturizers, solubilizers 13 Menthyl carbamate 0.03 Cooling agent 14 water 50 solvent 15 Triethanolamine 0.15 pH adjuster 16 Microemulsion emulsion —— ——

[0096] Weigh substances 1-14 into a mixing jar, stir until completely dissolved, then add triethanolamine and stir. Next, add the microemulsion, stir, and bring to a final volume.

[0097] See the formulation photo. Figure 3 Hydroxypinazone retinate partially floats on the surface of the liquid, forming a layer of oil. The liquid becomes significantly more milky white with almost no light transmittance; the liquid is an oil-in-water emulsion, rather than a microemulsion with translucent properties.

[0098] 1.3 Experiment Example 3: Experiment on the ratio of different proportions of betaine and lecithin and its investigation

[0099] 1.3.1 Preparation of Microemulsions

[0100] We conducted five gradient experiments, keeping the betaine content constant and gradually increasing the lecithin content. Because lecithin itself is susceptible to oxidation and unstable, its use was minimized to ensure product shelf life.

[0101] Table 5. Raw material ratio and function of microemulsion emulsion in Experiment 3.

[0102] 1 polydimethylsiloxane 0.2 0.2 0.2 0.2 0.2 2 Linoleic acid 0.1 0.1 0.1 0.1 0.1 3 Lecithin 0.05 0.1 0.2 0.3 0.5 4 betaine 0.1 0.1 0.1 0.1 0.1 5 Vitamin E (Tocopherol) 0.2 0.2 0.2 0.2 0.2 6 Hydroxypinazone Retinyl 0.1 0.1 0.1 0.1 0.1 7 water 10 10 10 10 10

[0103] Weigh materials 1-5 in sequence into a vacuum emulsifying tank. Heat to 80°C with stirring at 50 rpm until completely dissolved, then rapidly cool to 45-50°C. Add hydroxypinazone retinyl ester to the vacuum emulsifying tank with stirring at 50 rpm, maintain for approximately one hour, then turn on the vacuum emulsifying tank to 2500 rpm for emulsification, and quickly add water. Emulsify for 5 minutes. Using circulating cooling water, lower the temperature to below 25°C within 10 minutes.

[0104] 1.3.2 Preparation of the aqueous phase

[0105] Table 6. Aqueous phase raw material ratio and function in Experiment Example 3.

[0106] 1 glycerin 3 Moisturizer 2 Propylene glycol 1 Moisturizer 3 Alpha-lipoic acid 0.02 antioxidants 4 Sodium hyaluronate 0.5 Moisturizer 7 polydimethylsiloxane 3 Water-soluble solvents 8 Dipotassium glycyrrhizate 0.2 Anti-allergens 9 Disodium ethylenediaminetetraacetate 0.02 Chelating agents 10 Hydroxyethylurea 10 Moisturizer 11 Chlorphenesin 0.1 preservative 12 betaine 1 Moisturizers, solubilizers 13 Menthyl carbamate 0.03 Cooling agent 14 water 50 solvent 15 Triethanolamine 0.15 pH adjuster 16 Microemulsion emulsion —— ——

[0107] Weigh materials 1 through 14 into a mixing tank, stir until completely dissolved, then add triethanolamine and stir. Next, add the microemulsion, stir, and bring to a final volume.

[0108] See the formulation photo. Figure 4 ,Book Figure 4The images shown are of samples placed at 40 degrees Celsius for one week after formulation. From left to right, these are samples 1-5. The experiment shows that when the lecithin content is 0.05%, the liquid is completely clear. Layering begins to occur from a content of 0.1%. It should be noted that immediately after formulation, samples 1, 2, and 3 were basically clear; layering began to appear as the standing time increased.

[0109] 1.3.3 Continuous Investigation

[0110] For the continuous evaluation of the formulation, 400 ml sample 1 was prepared. Ignoring the effects of light, the sample was evaluated as follows:

[0111] Table 7. Durability Study of the Final Formulation Product in Experimental Example 3

[0112]

[0113] from Figure 5 The color changes of samples 1-4 were observed. Sample 1, stored under refrigeration for 30 days, had the least impact on the formulation, with virtually no color change. Sample 2, stored at room temperature for 30 days, showed a slight, but not significant, darkening of the color. Sample 3, stored at 40 degrees Celsius for 30 days, darkened in color, but not very noticeably. Sample 4, stored at alternating temperatures, showed a color essentially consistent with that stored at room temperature. Ultimately, we determined the ratio of lecithin to betaine in this formulation to be 1:2, with contents of 0.05% and 0.1%, respectively.

[0114] 1.4 Formulation Process Analysis

[0115] 1.4.1 Analysis of the microemulsion preparation process:

[0116] (1) After materials 1-5 are added to the vacuum emulsifying tank, they must be heated to about 80 degrees Celsius to obtain a uniform continuous phase. Only in this way will the system not separate into layers when it is rapidly cooled to about 50 degrees Celsius. If it is not heated to 80 degrees Celsius and completely dissolved, the system will rapidly separate into layers at 70 degrees Celsius.

[0117] (2) Hydroxypinazone retinate needs to be added to the system at 50 degrees Celsius, and the stirring should not be turned off after addition. At 50 degrees Celsius, the system temperature is already below the phase transition temperature (PIT), and stirring is necessary to provide potential energy to reduce the formation of stratification.

[0118] (3) When adding water to the system, it should not be too slow. It needs to be added quickly in one go, and stirring and emulsification should be started to allow microemulsion to form quickly. If the water is added too slowly, an oil-in-water paste will be formed initially, and when water is added again, the oil and water will not be immiscible.

[0119] (4) The water added must be at room temperature to quickly lower the system temperature and reach stability as quickly as possible. If isothermal water at 50 degrees Celsius is added, the probability of collision in the later stage of the microemulsion will increase due to the excessively high temperature, and the microemulsion will aggregate and form a floating oil layer.

[0120] (5) After the microemulsion is prepared, the system temperature still needs to be rapidly cooled to below 25 degrees Celsius. This is because the formation of a microemulsion is an exothermic process. During the formation of a microemulsion, there will be localized high temperatures, which will cause the microemulsion to re-aggregate and separate.

[0121] 1.4.2 Basic requirements for the aqueous phase in formulations:

[0122] To prepare microemulsions, an aqueous phase needs to be generated, and the preparation process is not significantly different from that of conventional aqueous phases. However, to obtain a stable microemulsion formulation, the following requirements apply.

[0123] (1) The pH of the aqueous system should be between 4 and 6.0. This is the optimal pH range for topical skin preparations; too low a pH can cause allergies, while too high a pH can increase the growth rate of skin bacteria. Furthermore, a pH between 5 and 6 is the optimal stable pH for hydroxypinazone retinyl ester.

[0124] (2) The salt concentration conductivity of the aqueous system is below 1000 micro Siemens. Excessively high salt concentration conductivity will cause the microemulsion to aggregate and harden, so the final product is not easy to aggregate and harden.

[0125] (3) The redox potential of the aqueous system is below 50mV. This is because the product preparation process avoids the addition of metal ions such as zinc ions, iron ions, silver ions, etc., to avoid oxidation of the product during storage, and to ensure that the product's storage period is not too short and its properties remain unchanged.

[0126] 2. Clinical efficacy testing of the formulation

[0127] Hydroxypinazone retinyl esters are primarily known for their anti-aging effects. Through the action of a series of enzymes in the body, they are converted into retinoic acid, which has more complex reactive properties. Retinic acid can bind to corresponding nucleoprotein receptors within cells. These receptors, after binding to retinoic acid, can directly or indirectly act on DNA, affecting the expression of specific genes and thus regulating cell differentiation, proliferation, and apoptosis, effectively increasing epidermal thickness.

[0128] 2.1 Effects of the formulation on facial epidermal thickening

[0129] Having confirmed the effect of the developed formulation on increased epidermal thickness, facial skin was examined using the Danish Dermalab skin analyzer to study the increase in epidermal thickness after a period of use of this formulation.

[0130] We selected a 43-year-old woman and a 72-year-old woman as experimental subjects. They used the formulation (skin care lotion of Example 1) twice daily, morning and evening, for 14 consecutive days, and observed the increase in epidermal thickness. The results are as follows:

[0131] (1) Case 1: Epidermal increase in a 43-year-old woman after 14 days of continuous use.

[0132] from Figure 6 This is a comparison image showing the before and after use. From... Figure 6 As can be seen, after 14 days of continuous use, twice a day, the yellowish, shiny areas (epidermis) showed significant thickening. The stratum corneum in the left image has pores, which is suspected to be related to menstruation.

[0133] (2) Case 2: Epidermal increase in a 72-year-old woman after 14 days of continuous use.

[0134] Figure 7 This is a comparison image showing the before and after use. From... Figure 7 As can be seen, after 14 consecutive days of use, twice a day, the yellowish shiny area (epidermis) showed a significant thickening.

[0135] 2.2 Changes in skin appearance after use

[0136] We tracked changes in skin appearance in 72-year-old female participants using the skincare lotion from Example 1. Since the 43-year-old woman's wrinkles were not noticeable, she only verbally reported a lifting and firming effect after a short 14-day use; photographs could not reflect the specific changes. However, for the 72-year-old woman, there was a significant improvement.

[0137] Improvement in facial wrinkles after 14 consecutive days of use by a 72-year-old woman.

[0138] Figure 8 (A) represents the change in skin appearance before use. Figure 8 (B) Represents changes in skin appearance 3 days after initial use. Figure 8 (C) represents changes in skin appearance 7 days after initial use. Figure 8 (D) represents the changes in skin appearance 14 days after use. As can be clearly seen from the image, after 14 days of use, forehead wrinkles, eye bags, and frown lines have all significantly faded, and facial pigmentation has decreased.

[0139] 3. In vitro anti-wrinkle efficacy verification

[0140] To verify the product's anti-wrinkle effect, we commissioned Guangdong Jianxun Testing Technology Co., Ltd., which has China Metrology Accreditation (CMA) qualification, to test the product's anti-wrinkle effect. Their report is as follows:

[0141] 3.1 Experimental Principles and Basis

[0142] According to the free radical theory, excessive production of free radicals is the main cause of natural skin aging and photoaging, leading to wrinkles. Therefore, the ability to scavenge free radicals is one of the important indicators for evaluating anti-aging and anti-wrinkle cosmetics (raw materials).

[0143] This experiment follows the laboratory method (free radical scavenging method): QTTZ-XZ-37 "Detailed Rules for Verification and Testing of Anti-wrinkle, Anti-aging, Antioxidant and Firming Efficacy of Cosmetics". The results of the DPPH free radical scavenging test were compared between the test sample and the negative control. If the scavenging rate of the test sample is higher than that of the negative control and there is a significant difference (P<0.05), the test sample can be considered to have a certain anti-wrinkle effect.

[0144] 3.2 Materials and Methods

[0145] 3.2.1 Instruments and Equipment

[0146] 0.1% electronic balance: Shanghai Puchun Metrology Instrument Co., Ltd., JA2003

[0147] 0.01% electronic balance: Shanghai Puchun Metrology Instrument Co., Ltd., FA2004

[0148] Microplate reader: Thermo Fisher Scientific (Shanghai) Instruments Co., Ltd., Multiskan FC

[0149] (1) Accurately weigh the sample;

[0150] (2) Pre-treat the sample and set aside for later use;

[0151] (3) The pretreated sample reacts with DPPH reagent;

[0152] (4) The OD value was measured at 517 nm after the reaction.

[0153] 3.3 Experimental Indicators

[0154] Scavenging rate (%) = (A2 + A3 - A1) / A2 × 100 A1 - OD value of the DPPH reaction system of the sample solution

[0155] A2-Anhydrous ethanol has an OD value in the DPPH reaction system.

[0156] A3 - OD value of the reaction system without DPPH (anhydrous ethanol substitution)

[0157] The results of this experiment are characterized by the scavenging rate of free radicals by the sample. If the test sample has a higher scavenging rate than the negative control, and the difference between the test sample and the negative control is statistically significant, it indicates that the test product has anti-wrinkle efficacy. To ensure the accuracy of the test system, the average scavenging rate of the positive control group should be greater than 25%. Significant differences are statistically analyzed using SPSS software, and a significance factor P < 0.05 is considered statistically significant.

[0158] 3.4 Experimental Results

[0159] Following the laboratory method (free radical scavenging method): QTTZ-XZ-37 "Detailed Rules for Verification and Testing of Anti-wrinkle, Anti-aging, Antioxidant and Firming Efficacy of Cosmetics", the anti-wrinkle efficacy of the sample Genid Skin Vitality Awakening Liquid was tested using the laboratory method. The DPPH free radical scavenging rate is shown in Table 8. Figure 9 .

[0160] Table 8. Results of Sweep Rate Measurement

[0161] negative control 7.67％±0.61％ / Positive control 53.54％±1.41％ <0.05 Test sample 74.84％±1.82％ <0.05

[0162] Note: Clearance rates are rounded to two decimal places; P < 0.05 is considered statistically significant.

[0163] The test results showed that the average DPPH free radical scavenging rate of the test samples under laboratory conditions was 74.84% ± 1.82%, which was significantly different from the negative control (P < 0.05). The positive control had a DPPH free radical scavenging rate > 25%, indicating that the reaction system was effective and that the samples had anti-wrinkle effects.

Claims

1. A skin care water prepared based on bidirectional microemulsion technology for poorly soluble substances, characterized in that: The product, by weight, is prepared from 3.2 parts of polydimethylsiloxane, 0.1 parts of linoleic acid, 0.05 parts of lecithin, 1.1 parts of betaine, 0.2 parts of tocopherol, 0.1 parts of hydroxypinazone retinate, 3 parts of glycerin, 1 part of propylene glycol, 0.02 parts of lipoic acid, 0.5 parts of sodium hyaluronate, 0.2 parts of dipotassium glycyrrhizate, 0.02 parts of disodium EDTA, 10 parts of hydroxyethylurea, 0.1 parts of chlorphenesin, 0.03 parts of menthol carboxyethylamine, 0.15 parts of triethanolamine, and purified water. The preparation method of the skin care water includes the following steps: (1) Weigh out 0.2 / 3.2 of polydimethylsiloxane, linoleic acid, lecithin, tocopherol and 1 / 11 of betaine according to the ratio, put them into a vacuum emulsification tank, heat to 80°C under stirring at 50 rpm to completely dissolve, and then quickly cool to 45-50°C to obtain product A; (2) Stir product A at 50 rpm, then add the specified amount of hydroxypinazone retinate, and continue stirring for 1 hour until the hydroxypinazone retinate is completely dissolved. Turn on the vacuum emulsifier and emulsify at 2500 rpm. Quickly add 10 parts by weight of water to the vacuum emulsifier and emulsify for 5 minutes. Then, use cooling circulating water to lower the temperature to below 25°C within 10 minutes to obtain a microemulsion, namely product B. (3) Weigh out glycerol, propylene glycol, lipoic acid, sodium hyaluronate, polydimethylsiloxane (3 / 3.2 of the amount), dipotassium glycyrrhizate, disodium ethylenediaminetetraacetate, hydroxyethyl urea, chlorphenesin, menthol ethylamine, and betaine (10 / 11 of the amount) according to the proportions, place them in a mixing tank, add 40-60 parts by weight of purified water and stir. After the mixture is completely dissolved, add the proportion of triethanolamine and stir to dissolve. Finally, add product B, stir and make up to volume to obtain the final product. The skin care water has anti-aging and skin-lightening effects.

2. The skin care water prepared based on the bidirectional microemulsion technology for poorly soluble substances according to claim 1, characterized in that: In step (3), glycerol, propylene glycol, thioctic acid, sodium hyaluronate, polydimethylsiloxane (3 / 3.2), dipotassium glycyrrhizate, disodium ethylenediaminetetraacetate, hydroxyethyl urea, chlorphenesin, menthol carboxyethylamine, and betaine (10 / 11) are weighed according to the specified ratio and placed in a mixing tank. 50 parts by weight of purified water are added and stirred until completely dissolved. Then, triethanolamine (the specified ratio) is added and stirred until dissolved. Finally, product B is added, stirred, and the volume is adjusted to obtain the final product.

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