Transdermal glabridin nano composition as well as preparation method and application thereof

Abstract

The invention provides a transdermal glabridin nano composition as well as a preparation method and application thereof. The transdermal glabridin nano composition is prepared from oil-phase raw materials: glabridin, soya bean lecithin, an emulsifier and butanediol; the water-phase raw materials comprise p-hydroxyacetophenone, an emulsifier, butanediol, bis (lauramide glutamine) sodium lysine and water. According to the glabridin liposome and the preparation method thereof, the stability of the glabridin liposome, especially the stability at a relatively high temperature, is effectively improved by selecting the proper emulsifier, the storage difficulty of related cosmetics and medical products is reduced, and a good foundation is provided for wider application of the related cosmetics and medical products.

Description

Field of the Invention

[0001] This application belongs to the field of cosmetics. Specifically, this application provides a transdermal glabridin nano-composition, its preparation method and application. Background Art

[0002] Glabridin is an isoflavone active ingredient extracted from the roots of Glycyrrhiza glabra L., which has a wide range of biological activities. In the field of medicine and health care, studies have shown that it has cardiovascular protective effects such as lowering blood pressure and blood lipids; in the field of cosmetics, it exhibits excellent multiple effects such as whitening, antioxidant, anti-inflammatory and soothing, antibacterial, anti-wrinkle and anti-glycation. Compared with traditional whitening ingredients (such as hydroquinone and arbutin), glabridin not only has significant effects, but also has low toxicity and good stability, so it is widely used in high-end skin care products.

[0003] However, glabridin still faces many challenges in cosmetic applications. Its low water solubility and poor water dispersibility limit the content of active ingredients in the formulation, affecting the efficacy; at the same time, this ingredient is sensitive to light, heat and pH, which easily leads to a decrease in product stability. At present, although technologies such as suspensions and liposomes have been tried to improve its formulation performance, the existing methods still have deficiencies in terms of stability, skin permeability and retention. Summary of the Invention

[0004] In view of the above problems, this application innovatively develops a transdermal glabridin nano-composition. Through advanced encapsulation processes and formulation optimization, this technology significantly improves the solubility, dispersibility and stability of glabridin, while achieving efficient skin delivery and long-term retention of active ingredients. The prepared nano-composition not only has a high drug loading and excellent stability, but its simple and controllable preparation process also has the potential for industrial application, providing a new solution for the application of glabridin in functional cosmetics.

[0005] On the one hand, this application provides a transdermal glabridin nano-composition, which is prepared using the following raw materials:

[0006] Oil phase raw materials: glabridin, soybean lecithin, emulsifier, butylene glycol;

[0007] Water phase raw materials: p-hydroxyacetophenone, emulsifier, butylene glycol, sodium bis(lauramidoglutamyl)lysinate, water.

[0008] Further, the raw materials are:

[0009] Oil phase raw materials: glabridin, soybean lecithin, hexyl decanol, polyglyceryl-10 laurate, butylene glycol;

[0010] Aqueous phase raw materials: p-Hydroxyacetophenone, PEG-6 caprylic / capric glycerides, Butylene glycol, Sodium bis(lauramidoglutamyl)lysinate, Water.

[0011] Furthermore, the raw materials are:

[0012] Oil phase raw materials: Glabridin 2 parts by weight, Soybean lecithin 3 parts by weight, Hexyldecanol 8 parts by weight, Polyglyceryl-10 laurate 8 parts by weight, Butylene glycol 20 parts by weight;

[0013] Aqueous phase raw materials: p-Hydroxyacetophenone 0.3 parts by weight, PEG-6 caprylic / capric glycerides 5 parts by weight, Butylene glycol 20 parts by weight, Sodium bis(lauramidoglutamyl)lysinate 0.5 parts by weight, Water 33.2 parts by weight.

[0014] Furthermore, the preparation method of the glabridin nano-composition is as follows:

[0015] (1) Mix the aqueous phase raw materials, heat with stirring to 70 - 80 °C to obtain an aqueous phase;

[0016] (2) Mix the oil phase raw materials, heat with stirring to 70 - 80 °C to obtain an oil phase;

[0017] (3) Add the aqueous phase to an emulsifying pot, add the oil phase with stirring at 70 - 80 °C, and emulsify and homogenize for 7 - 10 minutes to obtain a material;

[0018] (4) Stir the material obtained in step (3) evenly, evacuate, filter, and perform high-speed micro-jet treatment;

[0019] (5) Cool and filter to obtain the glabridin nano-composition.

[0020] Furthermore, the stirring speed in step (1), step (2), and step (3) is 30 revolutions per minute.

[0021] Furthermore, heat to 80 °C in step (1) and step (2), and add the oil phase with stirring at 80 °C in step (3).

[0022] Furthermore, emulsify and homogenize for 8 minutes in step (3).

[0023] On the other hand, the present application provides the use of the above glabridin nano-composition in the preparation of cosmetics.

[0024] Furthermore, the cosmetics are cosmetics with whitening, antioxidant and / or anti-aging effects.

[0025] Furthermore, the cosmetics are cream or essence.

[0026] The glabridin in the present application can use raw materials of various purities according to regulatory standards and actual needs.

[0027] Other whitening and anti-aging ingredients are not excluded in the cosmetics of the present application. The compatibility of these ingredients with the preparation / liposomes of the present application can be inferred by those skilled in the art using conventional knowledge in the art or verified by appropriate conventional experiments.

[0028] The present application effectively improves the stability of liquiritigenin liposomes, especially the stability at higher temperatures, by selecting suitable emulsifiers, reduces the storage difficulty of related cosmetics and pharmaceutical products, and provides a good basis for the wider application of related cosmetics and pharmaceutical products. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Showing the encapsulation efficiency data of Formulations 16 - 33;

[0030] Figure 2 Showing the particle size and PDI of Formulations 17 and 32 after long-term storage at 40 °C;

[0031] Figure 3 Showing the transdermal and skin retention properties of Formulations 17 and 32 for 24 hours. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0032] Example 1 Main Instruments and Reagents

[0033] Liquiritigenin: The purity was determined by HPLC to be 95%, from FangSheng Biotech;

[0034] Reagents used in other examples: Soybean lecithin, butanediol, hexyl decanol, behenyl alcohol polyether - 25, p - hydroxyacetophenone, polyglyceryl - 10 stearate, polyglyceryl - 10 laurate, sucrose stearate, polyoxyethylene hydrogenated castor oil, PEG - 40 hydrogenated castor oil, PEG - 6 caprylic / capric glycerides, polysorbate 20, sodium bis (lauramidoglutamyl) lysinate are all types available for domestic food / cosmetics.

[0035] Emulsifier: IKA magic plant;

[0036] Microfluidic homogenizer: ATS AMH - NANO;

[0037] Particle size analyzer: Malvem Nano - ZS90;

[0038] Drug transdermal diffusion apparatus: Fuxia TP - 6;

[0039] Pig skin of Bama minipig for transdermal test: Beijing Huachuang Zhizao;

[0040] HPLC: Shimadzu LC-10A; Eclipse XDB-C18, column temperature 25°C; mobile phase A: acetonitrile; mobile phase B: 0.05% trifluoroacetic acid; detection wavelength 282 nm.

[0041] Example 2 Basic Preparation Method

[0042] Unless otherwise specified, the preparation method used is as follows:

[0043] Mix the aqueous phase raw materials and heat to 80°C with stirring (30 revolutions per minute);

[0044] Mix the oil phase raw materials and heat to 80°C with stirring (30 revolutions per minute);

[0045] Add the aqueous phase to the emulsifying pot, add the oil phase with stirring (30 revolutions per minute) at 80°C, and emulsify and homogenize for 8 minutes; stir the material evenly, evacuate, filter, and perform high-speed micro-jet treatment;

[0046] Cool and filter to obtain glabridin liposomes.

[0047] Example 3 Partial Experimental Formulations

[0048] This application focuses on studying the effect of emulsifiers on the performance of liposomes. The components determined in the following technical solutions include:

[0049] Oil phase: 2% glabridin, 3% soybean lecithin, 20% butanediol;

[0050] Aqueous phase: 0.3% p-hydroxyacetophenone, 20% butanediol, 0.5% sodium bis(lauramidoglutamyl)lysinate, 33.2% water.

[0051] Unless otherwise specified, the percentages and parts in this application are by weight.

[0052] Table 1 Technical Solutions for Selecting Single Oil Phase Emulsifiers

[0053] oil phase aqueous phase Scheme 1 Hexyldecanol 16% Glycerol 5% Scheme 2 Behenyl Alcohol Polyether-25 16% Glycerol 5% Scheme 3 Polyglyceryl-10 Stearate 16% Glycerol 5% Scheme 4 Polyglyceryl-10 Laurate 16% Glycerol 5% Scheme 5 Sucrose Stearate 16% Glycerol 5% Scheme 6 Polyoxyethylene Hydrogenated Castor Oil 16% Glycerol 5% Scheme 7 PEG-40 Hydrogenated Castor Oil 16% Glycerol 5% Scheme 8 Polysorbate 20 16% Glycerol 5%

[0054] Table 2 Technical Solutions for Selecting Composite Oil Phase Emulsifiers

[0055]

[0056]

[0057] Table 3 Technical Solutions for Selecting Aqueous Phase Surfactants

[0058]

[0059]

[0060] Design of Glabridin Nanocomposite

[0061] Attempts were made to prepare glabridin liposomes according to Schemes 1 - 8 in Table 1 of Example 3. According to the general requirements for liposomes with a particle size below 200 nm and a PDI less than 0.3, the liposomes in Schemes 1, 2, 4, 6, and 7 in Table 1 had better states (average particle size 65 - 75 nm, PDI 0.26 - 0.28, encapsulation efficiency 92 - 95%), which were suitable for further research.

[0062] The changes in particle size and PDI values of the liposomes in Schemes 1, 2, 4, 6, and 7 were verified at 25°C, 4°C, -20°C, and 40°C (humidity 40%). The results showed that on a 30-day time scale, the liposomes in each scheme could maintain a stable state (average particle size 68 - 78 nm, PDI 0.27 - 3.10). However, when stored at high temperatures for a longer time, these liposomes all had aggregation problems (as shown in Table 4).

[0063] Table 4 Particle size and PDI of Schemes 1, 2, 4, 6, and 7 during long-term storage at 40°C

[0064]

[0065] Subsequently, the better emulsifiers in Schemes 1, 2, 4, 6, and 7 were combined to obtain Schemes 9 - 15 in Table 2. The average particle size of the liposomes was 63 - 76 nm, the PDI was 0.27 - 0.27, and the encapsulation efficiency decreased slightly to 85 - 91% compared with the method in Table 1. Their room temperature and low temperature storage performances could be guaranteed at a good level within 90 days. Their high temperature storage performance is shown in Table 5:

[0066] Table 5 Particle size and PDI of Schemes 9 - 15 during long-term storage at 40°C

[0067]

[0068] The results showed that the high temperature preservation performances of Schemes 9, 12 - 15 were all improved to a certain extent. Among them, Schemes 9 and 14 had better effects and could still remain stable at 90 days, basically meeting the quality requirements of liposomes.

[0069] To further improve the quality and encapsulation efficiency of liposomes, the applicant further attempted to replace the surfactant in the aqueous phase and the ratio of the surfactant in the oil phase (Schemes 16 - 33 in Table 3). The encapsulation efficiency is as Figure 1 shown. The encapsulation efficiencies of Schemes 17 and 32 using PEG-6 caprylic / capric glycerides were better than others, reaching 98.2% and 98.6%; as Figure 2 shown, their high temperature preservation performances were also not inferior to those of Schemes 9 and 14 (as Figure 2 shown).

[0070] Example 5 Transdermal Experiment

[0071] Actual transdermal experiments were carried out using the products of formulation 17 and 32: The pig skin was fixed between the receiving chamber and the supply chamber, 0.1 M PBS at pH 7 was used as the receiving solution, the amount of liposomes added to the supply chamber was 1 g, the rotation speed was 150 revolutions per minute, the temperature was 37 °C, the permeation amount of glabridin in 24 hours was determined by HPLC, and after the pig skin was ground, it was extracted with methanol to determine the retention amount of glabridin in the skin per unit area. The results are as Figure 3 shown. Formulation 17 showed slightly better performance than Formulation 32 in terms of both permeation amount and retention amount; indicating that the liposome has better affinity with the skin.

Claims

1. A transdermal glabridin nanocomposition, characterized in that: The glabridin nanocomposite is prepared using the following raw materials: Oil phase raw materials: glycyrrhizin, soybean lecithin, emulsifier, butanediol; Aqueous phase raw materials: p-hydroxyacetophenone, emulsifier, butylene glycol, sodium di(laurylamide glutamine) lysine, water.

2. The glabridin nanocomposition according to claim 1, wherein the raw material is: Oil phase raw materials: glycyrrhizin, soybean lecithin, hexyldecanol, polyglycerol-10 laurate, butylene glycol; Aqueous phase ingredients: p-hydroxyacetophenone, PEG-6 caprylic / capric glycerides, butylene glycol, sodium di(laurylamide glutamine) lysine, water.

3. The glabridin nanocomposition according to claim 1, wherein the raw material is: Oil phase raw materials: 2 parts by weight of glabridin, 3 parts by weight of soybean lecithin, 8 parts by weight of hexyldecanol, 8 parts by weight of polyglycerol-10 laurate, and 20 parts by weight of butanediol; Aqueous phase raw materials: 0.3 parts by weight of p-hydroxyacetophenone, 5 parts by weight of PEG-6 caprylic / capric glycerides, 20 parts by weight of butylene glycol, 0.5 parts by weight of sodium di(laurylamide glutamine) lysine, and 33.2 parts by weight of water.

4. The glabridin nanocomposition according to any one of claims 1 to 3, wherein the preparation method of the glabridin nanocomposition is: (1) mixing water phase raw materials and heating to 70-80° C. with stirring to obtain a water phase; (2) mixing the oil phase raw materials and heating to 70-80° C. with stirring to obtain an oil phase; (3) Add the water phase into the emulsifier, add the oil phase while stirring at 70-80°C, and emulsify and homogenize for 7-10 minutes; (4) stirring the material evenly, evacuating, filtering, and high-speed microfluidization treatment; (5) cooling and filtering to obtain the glabridin nanocomposite.

5. The glabridin nanocomposition according to claim 4, wherein the stirring speed in step (1), step (2) and step (3) is 30 rpm.

6. The glabridin nanocomposition according to claim 4, wherein the temperature is heated to 80°C in step (1) and step (2), and the oil phase is added at 80°C with stirring in step (3).

7. The glabridin nanocomposition according to claim 4, wherein the emulsification and homogenization in step (3) is performed for 8 minutes.

8. Use of the glabridin nanocomposition according to any one of claims 1 to 3 in the preparation of cosmetics.

9. The use according to claim 8, wherein the cosmetic is a cosmetic having whitening, anti-oxidation and / or anti-aging effects.

10. The use according to claim 8, wherein the cosmetic is a facial cream or an essence.

Images