A mild and stable temperature-responsive microemulsion composition, its preparation method and application

Abstract

This invention discloses a mild and stable temperature-responsive microemulsion composition, its preparation method, and its applications, belonging to the fields of cosmetics and pharmaceutical technology. This invention uses a nonionic decyl glucoside and anionic sodium lauroyl glutamate, introducing tocopherol polyethylene glycol succinate and disodium EDTA, forming a dual stabilizing mechanism of "antioxidant + metal ion chelation," effectively protecting unstable active ingredients such as glycyrrhizin. Experiments show that in an accelerated test at 60℃, the retention rate of glycyrrhizin increased by more than 20%. The microemulsion composition prepared by this invention exhibits high stability, low irritation, and skin-targeted sustained-release properties.

Description

Technical Field

[0001] This invention relates to the fields of cosmetics and pharmaceutical technology, specifically to a microemulsion composition containing a specific combination of emulsifiers and a temperature-responsive gel, which has high stability, low irritation, and skin-targeted sustained-release properties. Background Technology

[0002] Microemulsions, as thermodynamically stable and transparent dispersion systems, are widely used in cosmetics and topical drug delivery systems due to their ability to simultaneously solubilize both hydrophilic and lipophilic active ingredients and improve bioavailability. However, traditional microemulsion systems face several technical challenges that urgently need to be addressed: First, there's the issue of emulsifier irritation. To form stable microemulsions, high concentrations of single or compound emulsifiers are typically required, such as traditional polysorbates and fatty alcohol polyoxyethylene ethers. Long-term use of these emulsifiers may damage the skin's lipid barrier, leading to dryness, tightness, or even allergies, and they are especially unsuitable for sensitive skin.

[0003] Secondly, there is the issue of the stability of active ingredients. Many highly effective but sensitive active ingredients (such as glycyrrhizin) are easily degraded and deactivated in liquid systems due to factors such as light and oxidation, leading to product failure. To solve this problem, existing technologies often rely on high concentrations of organic solvents (such as propylene glycol, often used at concentrations as high as 10%-20%) to stabilize the system, but this further exacerbates the potential irritation of the formulation.

[0004] Secondly, the formulation has poor retention on the skin. Traditional microemulsions are highly fluid and easily wash away from the skin due to sweating or wiping, making it impossible to act on the target site for a long time and affecting the sustained efficacy.

[0005] In addition, there are some thermosensitive gel systems in the existing technology, such as using poloxamer 407 alone, but it mainly acts as a thickener and does not contribute to the emulsion system itself. Moreover, it usually requires a high concentration (>15%) to achieve phase transition, which increases costs and may cause stickiness.

[0006] Therefore, there is an urgent need in the field for a novel microemulsion delivery system that can balance stability, mildness, and long-lasting sustained release to overcome the aforementioned shortcomings of existing technologies. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide a mild and stable microemulsion composition with temperature-responsive characteristics and targeted sustained-release function.

[0008] To achieve the above objectives, the present invention adopts the following technical solution: A mild and stable temperature-responsive microemulsion composition comprising the following components by weight percentage:

[0009] Preferably, the active ingredient is glycyrrhizin.

[0010] Preferably, the composition further comprises no more than 5% propylene glycol.

[0011] The composition of the present invention has unique temperature response characteristics: it is a low-viscosity liquid at room temperature (below 25°C), which is convenient for dispensing and coating; when it comes into contact with the skin (the temperature rises to 35-40°C), it quickly transforms into a gel state, achieving skin retention and sustained release.

[0012] The present invention also provides a method for preparing the above-mentioned composition, and its application in the preparation of topical skin preparations, particularly for whitening, anti-oxidation, anti-inflammation and skin-targeted sustained-release drug delivery.

[0013] Beneficial effects Compared with the prior art, the present invention has the following significant advantages: A synergistic and gentle emulsifying system: Utilizing a combination of nonionic decyl glucoside and anionic sodium lauroyl glutamate, both naturally derived and with extremely low irritation. This combination, when formulated in specific proportions, forms stable, fine-particle-size emulsion droplets, eliminating the need for highly irritating traditional emulsifiers and significantly improving the formulation's gentleness.

[0014] Excellent stability: By introducing tocopherol polyethylene glycol succinate and disodium EDTA, a dual stabilization mechanism of "antioxidant + metal ion chelation" is formed, effectively protecting unstable active ingredients such as glycyrrhizin. Experiments have shown that in accelerated testing at 60℃, the retention rate of glycyrrhizin increased by more than 20%.

[0015] Reduced dependence on organic solvents: Due to the excellent stability of this emulsion system, the dependence on high concentrations of organic solvents such as propylene glycol is greatly reduced, and its dosage can be safely reduced to below 5%, further enhancing the mildness of the formulation.

[0016] Intelligent temperature response and targeted sustained release: Low concentrations of poloxamer 407 (only 2%-4%) synergize with this specific microemulsion system to achieve unique phase transition behavior. This property solves the problem of easy loss in traditional microemulsions, prolongs the residence time of active ingredients at the skin site, achieves a sustained release effect, and improves bioavailability.

[0017] Cost advantage: Through the clever combination and synergy of components, while achieving better technical results, the amount of high-cost components (such as high-concentration poloxamer and propylene glycol) used is reduced, resulting in lower raw material costs. Detailed Implementation

[0018] The above-described approach of the present invention will be specifically described below through embodiments. It should be noted that these embodiments are only used to further illustrate the present invention and do not constitute any limitation on the present invention. Those skilled in the art can make some non-essential improvements and adjustments based on the content of the present invention.

[0019] Example 1: Temperature-responsive microemulsion containing glycyrrhizin Prepare according to the following weight percentages: Decyl glucoside: 5% Sodium lauroyl glutamate: 3% Tocopherol polyethylene glycol succinate: 0.8% Disodium EDTA: 0.03% Polosham 407: 3% Glycyrrhizin: 0.5% Propylene glycol: 3% Purified water: Add to 100%.

[0020] Preparation method: Decyl glucoside, sodium lauroyl glutamate, TPGS, disodium EDTA, glycyrrhizin, and propylene glycol were mixed evenly at 25°C to form a transparent oil phase.

[0021] Poloxamer 407 was dispersed in approximately 70% of the total volume of purified water and magnetically stirred overnight in a 4°C refrigerator until a completely transparent aqueous gel matrix was formed.

[0022] Under slow stirring at 300 rpm, the oil phase mixture from step 1 was slowly added dropwise to the aqueous phase gel matrix from step 2.

[0023] Wash the container with the remaining purified water and bring it to 100%, then continue stirring for 15 minutes.

[0024] Finally, the microemulsion was homogenized three times at 50 MPa using a high-pressure homogenizer to obtain a clear and transparent microemulsion. The viscosity of this microemulsion was 45 mPa·s at 25°C, and the viscosity rapidly increased to 1250 mPa·s at 35°C, forming a gel.

[0025] Example 2: Microemulsions with different emulsifier ratios The decyl glucoside and sodium lauroyl glutamate were adjusted to 4%, while the remaining components and preparation method were the same as in Example 1. The resulting microemulsion also exhibited thermosensitive properties and good stability.

[0026] Example 3: Microemulsions with different emulsifier ratios The decyl glucoside was adjusted to 3%, sodium lauroyl glutamate to 1%, and the remaining components and preparation method were the same as in Example 1. The resulting microemulsion also exhibited thermosensitive properties and good stability.

[0027] Example 4: Microemulsions with different emulsifier ratios The decyl glucoside was adjusted to 8%, sodium lauroyl glutamate to 5%, and the remaining components and preparation method were the same as in Example 1. The resulting microemulsion also exhibited thermosensitive properties and good stability.

[0028] Comparative Example 1: Microemulsions using traditional emulsifiers In Example 1, decyl glucoside and sodium lauroyl glutamate were replaced with an equal total amount (8%) of polysorbate 80, and poloxamer 407 was removed. This comparative microemulsion was liquid at both room temperature and skin temperature, and did not exhibit thermosensitive gel properties.

[0029] Comparative Example 2: Microemulsion with a single mild emulsifier Using only 8% decyl glucoside, sodium lauroyl glutamate and poloxamer 407 were removed. This system failed to form a stable microemulsion and exhibited stratification upon standing.

[0030] Comparative Example 3: High-concentration poloxamer gel Instead of using decyl glucoside and sodium lauroyl glutamate, the amount of poloxamer 407 was increased to 18% to form a conventional thermosensitive gel. This formulation is costly, has a highly sticky feel after application, and poor loading capacity for oil-soluble ingredients.

[0031] Example of effect: Performance test The following performance comparison tests were conducted between Examples 1-4 of the present invention and Comparative Examples 1-3.

[0032] Test 1: Stability test (glycyrrhizin retention rate) Each sample was placed in a 60℃ constant temperature chamber for accelerated testing. Samples were taken at 0 days and 30 days, and the content of glycyrrhizin was determined by HPLC, and the retention rate was calculated. The glycyrrhizin retention rate of the composition of this invention is significantly higher than that of the comparative example, demonstrating the excellent effect of its dual stabilization mechanism, with a retention rate increase of more than 20%.

[0033] Test 2: Mildness Test (Chicken Embryo Villi Allantoic Membrane Test) The irritant properties of the samples were assessed using the chicken embryo chorioallantoic membrane test. The mild emulsifier combination used in this invention significantly reduces the irritation of the formulation to mucous membranes.

[0034] Test 3: In vitro release and retention performance The release behavior of glycyrrhizin was investigated using a Franz diffusion cell and pigskin as a model.

[0035] Cumulative release rate: At 12 hours, the cumulative release rate of Example 1 was 75%, while that of Comparative Example 1 was as high as 95%. This indicates that the present invention has a significant sustained-release effect.

[0036] Skin retention: After the experiment, the amount of drug retained in the skin was measured. The retention of Example 1 was 2.3 times that of Comparative Example 1, which proves that its temperature-responsive gel properties effectively improve the retention of active ingredients on the skin surface.

[0037] In summary, this invention, through a specific combination of components, synergistically solves the problem of the inability to simultaneously achieve irritation, stability, and retention in traditional technologies, achieving unexpected technical effects.

[0038] The embodiments described above merely illustrate the implementation methods of this application, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of this patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A mild and stable temperature-responsive microemulsion composition, characterized in that, It consists of the following components by weight percentage: 。 2. The composition according to claim 1, characterized in that, The active ingredient is glycyrrhizin.

3. The composition according to claim 1 or 2, characterized in that, The composition also contains no more than 5% propylene glycol.

4. The composition according to claim 1 or 2, characterized in that, The composition is a low-viscosity liquid below 25°C and transforms into a gel state at 35-40°C.

5. A topical skin preparation, characterized in that, The mild and stable temperature-responsive microemulsion composition comprising any one of claims 1 to 4.

6. The topical skin preparation according to claim 5, characterized in that, The formulation is used for whitening, anti-oxidation, or anti-inflammation.

7. Use of the composition of any one of claims 1 to 4 in the preparation of a formulation for achieving targeted sustained-release drug delivery.

8. A method for preparing the composition according to any one of claims 1 to 4, characterized in that, Includes the following steps: a) Decyl glucoside, sodium lauroyl glutamate, tocopherol polyethylene glycol succinate, disodium EDTA and active ingredients are mixed at room temperature to form an oil phase mixture; b) Disperse poloxamer 407 in a portion of water and stir at 4°C until completely dissolved to form a transparent aqueous gel matrix; c) Add the oil phase mixture obtained in step a) to the aqueous phase gel matrix obtained in step b) under slow stirring; d) Add water to the total volume, homogenize, and form a microemulsion.

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