A self-assembled inclusion of glabridin with ultra-small particle size and its preparation method and application

Abstract

The present invention relates to a self-assembled inclusion of glabridin with an ultra-small particle size, a preparation method, and an application thereof, and belongs to the field of cosmetic technology. The composition of the present invention comprises the following components in parts by weight: 0.5-5 parts of glabridin, 10-30 parts of polyol, 0.4-6.5 parts of a licorice carrier component, 1.5-3 parts of a nonionic emulsifier A, 0.45-1.8 parts of a nonionic emulsifier B, and 53.7-87.15 parts of water; the licorice carrier component comprises at least one of glycyrrhizic acid, ammonium glycyrrhizate, and glycyrrhetinic acid; the nonionic emulsifier A is a nonionic emulsifier with a hydrophilic-lipophilic balance value (HLB) greater than 9; the nonionic emulsifier B is a nonionic emulsifier with a hydrophilic-lipophilic balance value (HLB) of 2-4. The self-assembled inclusion of glabridin of the present invention has a smaller particle size, good encapsulation performance, and good targeting; it has good stability, the glabridin encapsulation does not precipitate, and the transdermal absorption rate is higher.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to a self-assembled inclusion of glabridin with ultra-small particle size, a preparation method and an application thereof. Background Art

[0002] Glabridin is a natural flavonoid compound extracted from the root of Glycyrrhiza glabra. It can reduce melanin production by inhibiting tyrosinase activity, thus having a whitening effect. It also scavenges free radicals, protecting the skin from oxidative damage, and has antioxidant and anti-inflammatory effects.

[0003] Glabridin is not easily soluble in water, but stratum corneum cells are hydrophilic, thus creating a barrier effect on the absorption and utilization of glabridin. Therefore, glabridin needs to be encapsulated to promote transdermal absorption of glabridin and improve its bioavailability. Conventional cyclodextrin encapsulation systems have two drawbacks. First, cyclodextrin itself feels very sticky on the skin, which can cause consumers to experience an unpleasant sticky feeling during use. Second, cyclodextrin encapsulation systems are prone to crystallization in the formula. Literature has shown that polyols such as pentanediol and hexanediol can affect the encapsulation stability of cyclodextrin, causing formulators to face difficulties in developing cosmetic formulas. Most other inclusions require the use of complex equipment such as high-pressure homogenizers and high-pressure microfluidizers for emulsification and homogenization in the preparation method to obtain small and uniform glabridin inclusions; or they require the addition of some organic solvents to improve the solubility of glabridin. Methods that involve high energy and specialized equipment inevitably consume significant energy during production, while dissolution methods using organic solvents can result in residual organic solvents in the final product. For example, Chinese patent CN119837779A discloses glycyrrhizic acid-encapsulated glabridin nanovesicles, their preparation method, and their use in the preparation of whitening skincare cosmetics. While glycyrrhizic acid is used as a carrier for glabridin, the solubility of glabridin is increased, boosting its skin permeability. However, ultrasonic hydration and other treatments are still required to obtain the nanovesicles.

[0004] Therefore, there is still a need to optimize the formula of encapsulated glabridin to improve the transdermal absorption and bioavailability of glabridin and simplify the preparation method. Summary of the Invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a self-assembled inclusion of glabridin with ultra-small particle size and a preparation method and application thereof.

[0006] To achieve the above object, the technical solution adopted by the present invention is:

[0007] In a first aspect, the present invention provides a composition comprising the following components in parts by weight: 0.5 to 5 parts of glabridin, 10 to 30 parts of a polyol, 0.4 to 6.5 parts of a licorice carrier component, 1.5 to 3 parts of a nonionic emulsifier A, 0.45 to 1.8 parts and 53.7 to 87.15 parts of a nonionic emulsifier B;

[0008] The licorice carrier component includes at least one of glycyrrhizic acid, ammonium glycyrrhizate and glycyrrhetinic acid;

[0009] The nonionic emulsifier A is a nonionic emulsifier with a hydrophilic-lipophilic balance value HLB>9;

[0010] The nonionic emulsifier B is a nonionic emulsifier with a hydrophilic-lipophilic balance value HLB=2~4.

[0011] Compared with the instability and poor compatibility of cyclodextrin systems with formulations, as well as other methods that require the introduction of high energy and special equipment, resulting in increased energy consumption during the production process or the addition of organic solvents, which can cause residual organic solvents in the final cosmetic product, the present invention utilizes glycyrrhizic acid, ammonium glycyrrhizate, and glycyrrhetinic acid, which have self-assembly properties, derived from licorice, and encapsulates glabridin by adding a certain proportion of co-emulsifiers. The preparation method is simple and feasible, and the preparation process does not require the introduction of high-energy equipment, greatly reducing the equipment and energy consumption requirements required for large-scale production. No organic solvents are required during the preparation process, making it safer. The resulting glabridin self-assembled inclusions have better stability, smaller particle size, and higher transdermal absorption rate.

[0012] Preferably, the weight ratio of the glabridin to the licorice carrier component is glabridin: licorice carrier component = 1: (0.8-1.3).

[0013] Preferably, the weight ratio of the nonionic emulsifier A to the nonionic emulsifier B is nonionic emulsifier A:nonionic emulsifier B=1:(0.3~0.6).

[0014] Further, the nonionic emulsifier A includes at least one of polyglyceryl-10 oleate, polyglyceryl-10 myristate, polyglyceryl-10 isostearate, polyglyceryl-10 diisostearate, polyglyceryl-10 laurate, sucrose stearate and sucrose palmitate;

[0015] And / or, the nonionic emulsifier B includes at least one of polyglycerol-2 oleate, polyglycerol-2 silicate, sucrose polystearate, sorbitan monostearate, sorbitan monooleate, glyceryl monostearate and propylene glycol monostearate;

[0016] And / or, the polyol includes at least one of glycerol, 1,2-propylene glycol, dipropylene glycol, 1,3-butylene glycol, hexylene glycol, pentylene glycol and hexyldecanol.

[0017] As a preferred embodiment of the present invention, the nonionic emulsifier A is sucrose stearate, and the nonionic emulsifier B is sucrose polystearate.

[0018] Preferably, the polyol comprises glycerol, dipropylene glycol or 1,3-butylene glycol.

[0019] As a preferred embodiment of the present invention, the composition comprises the following components in parts by weight: 3 parts glabridin, 25 parts polyol, 3-4 parts licorice carrier component, 2 parts nonionic emulsifier A, 1 part nonionic emulsifier B, and 65-66 parts water. The resulting glabridin self-assembled inclusions have a smaller particle size and polydispersity coefficient, and a higher glabridin encapsulation efficiency.

[0020] Furthermore, when the licorice carrier components are glycyrrhizic acid and glycyrrhizinium, the mass ratio of glycyrrhizic acid to glycyrrhizinium is: glycyrrhizic acid: glycyrrhizinium = 1: (0.5~1); preferably, glycyrrhizic acid: glycyrrhizinium = 1:1.

[0021] Furthermore, when the licorice carrier components are glycyrrhetinic acid and glycyrrhizin ammonium, the mass ratio of glycyrrhetinic acid to glycyrrhizin ammonium is: glycyrrhetinic acid: glycyrrhizin ammonium = 1: (0.5~1); preferably, glycyrrhetinic acid: glycyrrhizin ammonium = 1:1.

[0022] Furthermore, when the licorice carrier components are glycyrrhizic acid and glycyrrhetinic acid, the mass ratio of glycyrrhizic acid to glycyrrhetinic acid is: glycyrrhizic acid: glycyrrhetinic acid = 1: (0.8~1); preferably, glycyrrhizic acid: glycyrrhetinic acid = 1:1.

[0023] Furthermore, when the licorice carrier components are glycyrrhizic acid, glycyrrhetinic acid and glycyrrhizin ammonium, the mass ratio of glycyrrhizic acid, glycyrrhetinic acid and glycyrrhizin ammonium is: glycyrrhizic acid: glycyrrhetinic acid: glycyrrhizin ammonium = 1: (0.5~1): (0.8~1); preferably, glycyrrhizic acid: glycyrrhetinic acid: glycyrrhizin ammonium = 1:1:1.

[0024] In a second aspect, the present invention provides a method for preparing glabridin self-assembled inclusions, comprising the following steps:

[0025] S1: mixing glabridin, polyol, licorice carrier component, nonionic emulsifier A and nonionic emulsifier B in the composition, adjusting the temperature to 60-65° C. with stirring, and dissolving in a water bath to obtain phase A;

[0026] S2: Phase B is water in the composition, and the temperatures of phase A and phase B are adjusted to 60-65° C. to obtain heated phase A and heated phase B;

[0027] S3: Mix the heated phase A and the heated phase B while stirring at 400-500 rpm, keep the mixture at 60-65° C. for 30-40 min, and slowly cool the mixture to room temperature to obtain glabridin self-assembled inclusions.

[0028] Preferably, in step S1, the temperature is adjusted to 60°C.

[0029] Preferably, in step S1, the water bath is 8 to 12 minutes, preferably 10 minutes.

[0030] Preferably, in steps S2 and S3, the temperature is 65°C.

[0031] Preferably, in step S3, the stirring speed is 500 rpm.

[0032] Preferably, in step S3, the holding time is 30 minutes.

[0033] In a third aspect, the present invention further seeks to protect a glabridin self-assembled inclusion body prepared by the preparation method.

[0034] In a fourth aspect, the present invention also seeks to protect the use of the glabridin self-assembled inclusions in the preparation of whitening and freckle-removing products.

[0035] In a fifth aspect, the present invention provides a cosmetic comprising the glabridin self-assembled inclusions.

[0036] Furthermore, the cosmetics also contain cosmetic accessories.

[0037] Compared with the prior art, the present invention has the following beneficial effects:

[0038] (1) The particle size of glabridin self-assembled inclusions is smaller and their transdermal absorption rate is higher than that of free glabridin.

[0039] (2) Licorice is used as the wrapping shell, which has good wrapping performance, good targeting, and stronger efficacy.

[0040] (3) The preparation method is simple by using licorice carrier components in conjunction with a specific proportion of emulsifiers. No special equipment is required. Only simple heating, stirring and mixing are required. It has low energy consumption and does not require the introduction of organic solvents during the preparation process, which is safer.

[0041] (4) The licorice carrier component is used in conjunction with a specific proportion of emulsifiers to achieve good stability and prevent the glabridin from precipitating. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 are the particle size and polydispersity coefficient of Example 1.

[0043] Figure 2This is a competitive binding assay, where α-MSH is α-melanocyte stimulating hormone.

[0044] Figure 3 This is the human body whitening efficacy test data, where ITA° is the individual skin type angle. DETAILED DESCRIPTION

[0045] To better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below with reference to specific examples. Other materials, reagents, etc. used in the examples, unless otherwise specified, can be obtained from commercial sources.

[0046] Examples 1-10, Comparative Examples 1-12

[0047] The formulas of the glabridin self-assembled inclusions of Examples 1 to 10 and Comparative Examples 1 to 12 are shown in Table 1 and Table 2, respectively. HLB is the hydrophile-lipophile balance. The preparation methods are as follows:

[0048] (1) Mix glabridin, polyol, licorice carrier component and two emulsifiers, adjust the temperature to 60°C, stir, and dissolve in a water bath for 10 minutes to obtain phase A;

[0049] (2) heating phase A and phase B to 65°C respectively to obtain heated phase A and heated phase B;

[0050] (3) Pour the heated phase B directly into the heated phase A while stirring at 500 rpm, keep the temperature at 65°C for 30 min, and then slowly cool it down to room temperature to obtain glycyrrhizin self-assembled inclusions.

[0051] Table 1 Formula of Glabridin Self-Assembly Inclusions in Examples 1 to 10

[0052]

[0053] Table 2 Comparative Examples 1 to 12 Glabridin Self-Assembly Inclusion Formulas

[0054]

[0055] Test Example 1

[0056] The properties of the samples of the glabridin self-assembled inclusions prepared in Examples 1 to 10 and Comparative Examples 1 to 12 were detected, and the average particle size (nm) and the polydispersity index (PDI) were measured using a nanoparticle size potentiometer.

[0057] Table 3 Properties of glabridin self-assembled inclusions

[0058]

[0059] Figure 1The average particle size (nm) and polydispersity index (PDI) of the glabridin self-assembled inclusions prepared in Example 1 were measured by a nanoparticle size potential analyzer. As can be seen from Table 3, the glabridin self-assembled inclusions prepared in Examples 1 to 10 are light yellow transparent solutions with an average particle size of 10 to 15 nm and a polydispersity index of 0.11 to 0.20. However, in Comparative Examples 1 to 3, precipitation occurred and they could not be completely encapsulated. This may be because the ratio of glabridin to the licorice encapsulation component exceeded the range, thus affecting the encapsulation properties, so the next step of testing was not performed. The average particle size of Comparative Examples 4 to 12 is larger than that of the examples, ranging from 22 to 114 nm, and the polydispersity index is 0.12 to 0.70. It can be seen that changing the ratio of glabridin to the licorice encapsulation component, and changing the type or ratio of the emulsifier, have an impact on the particle size of the self-assembled inclusions.

[0060] Test Example 2

[0061] The glabridin self-assembled inclusions prepared in Examples 1 to 10 and Comparative Examples 4 to 12 were placed under room temperature (25±0.5°C), high temperature (50±0.5°C), frozen (-15±0.5°C), and light (sunlight) conditions for 53 weeks. After the placement, their appearance and presence of stratification were observed. HPLC was used to detect the glabridin content after 53 weeks. Specifically, the glabridin HPLC content was determined using an Agilent 1100 high performance liquid chromatograph according to the QB / T 4951-2016 "Cosmetic Raw Materials: Glycyrrhiza glabra Root Extract" method. The data obtained are shown in Table 4.

[0062] Table 4 Stability of glabridin self-assembled inclusions

[0063]

[0064] The results showed that after 53 weeks of storage under high temperature, room temperature, freezing, and light conditions, the appearance of Examples 1 to 10 did not change significantly, and the glabridin content remained at 2.96% to 2.99%, indicating good stability. The appearance of Comparative Examples 4 and 5 became darker, and the glabridin content of Comparative Example 4 decreased significantly. Comparative Examples 6, 10, and 12 all showed precipitation in appearance, and the glabridin content of Comparative Examples 6 and 7 decreased significantly. Therefore, Comparative Examples 4 to 7, 10, and 12 were not tested further.

[0065] Test Example 3

[0066] Transdermal permeation test: Pig skin was washed with distilled water, then with physiological saline, and dried with filter paper for later use. Transdermal permeation experiments were performed using a modified Franz diffusion cell (static vertical transdermal diffusion cell). The diffusion cell was insulated with a constant temperature (37°C) circulating water jacket. The skin was fixed between the supply chamber and the receiving chamber, with the skin surface facing the supply chamber. The effective permeation area S was 2.8 cm. 2The volume of the receiving tank is 7.0 mL, and the receiving liquid is normal saline. 1.0 g of glabridin self-assembled inclusions are evenly applied to the skin surface of the donor chamber, and the magnetic stirrer is turned on and stirred at a speed of 300 r / min; 0.5 mL of the receiving liquid is taken out after 8 hours (an equal amount of normal saline is added after each sampling), and the sample is centrifuged and the supernatant is taken to determine the content of glabridin; and the cumulative transdermal drug release per unit area Q is calculated.

[0067] Table 5 Transdermal penetration test results of glabridin self-assembled inclusions

[0068]

[0069] The results are shown in Table 5. The self-assembled inclusions of glabridin prepared in Examples 1 to 10 of the present invention have excellent transdermal permeability, with a cumulative transdermal drug release of 75.20 μg / cm at 6 h. 2 The above; comparative examples 8, 9, 11 in 8h cumulative transdermal drug release decreased significantly.

[0070] Test Example 4

[0071] The competitive binding assay method is as follows:

[0072] HEK 293 cells (human embryonic kidney 293) were transfected with the human MCIR gene (melanocortin receptor 1). 48 hours prior to the assay, HEK 293 cells were seeded in 96-well plates and grown to 100,000 cells per well. During the assay, the culture medium was removed. The cells were then incubated with varying concentrations of unlabeled test compounds and NDP-α-MSH (a synthetic derivative of α-melanocyte-stimulating hormone) at 37°C for 40 minutes and washed twice with binding buffer.

[0073] The cells were lysed with 50 μL of 0.1 mM sodium hydroxide and 50 μL of 1% (v / v) Triton X-100, dried overnight in a fume hood, and then 50 μL of scintillation fluid was added to each well.

[0074] Radioactivity was measured and data analyzed using a MicroBeta2 microwell counter. In each well, the mass concentration of undecylenylphenylalanine in the undecylenylphenylalanine group was 0.05%, and in the glycyrrhizic acid group, the mass concentration of glycyrrhizic acid was 0.05%. In the experimental groups, the addition amount of the glabridin self-assembled inclusions prepared in Examples 1-10, Comparative Examples 8, 9, and 11 was 1.7%, respectively (calculated concentration of the glycyrrhizic acid carrier component in each well of Examples 1-7 was 0.05%, mass concentration).

[0075] The results are as follows Figure 2As shown, the ability of glycyrrhizic acid to compete for binding to α-MSH (α-melanocyte stimulating hormone) is comparable to that of the positive group undecylenoylphenylalanine. The glabridin self-assembled inclusions prepared by Examples 1 to 10 of the present invention have excellent competitive binding inhibition rates for α-MSH compared to Comparative Examples 8, 9 and 11, and improve the targeting to MC1R.

[0076] Test Example 5

[0077] Human efficacy test: 2% of the self-assembled inclusions were added to the aqueous base formula (as shown in Table 6) to obtain the test product. The change rate of the individual skin type angle (ITA°) of different test products was measured according to T / ZHCA 001-2018 "Test Method for the Whitening and Anti-Blemish Efficacy of Cosmetics".

[0078] Table 6 Basic formula of aqueous solution

[0079]

[0080] The results are as follows Figure 3 As shown, the tested products obtained by using the glabridin self-assembled inclusions prepared by Examples 1 to 10 of the present invention have excellent transdermal permeability and targeting, and better whitening efficacy, while the whitening efficacy of Comparative Examples 8, 9, and 11 is poorer than that of Examples 1 to 10.

[0081] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A glabridin self-assembly inclusion composition, characterized in that: The invention is composed of the following components in parts by weight: 3 parts of glabridin, 25 parts of polyol, 3-3.9 parts of licorice carrier component, 2 parts of nonionic emulsifier A, 1 part of nonionic emulsifier B and 65.1-66 parts of water; The licorice carrier component is at least one of glycyrrhizic acid, ammonium glycyrrhizate and glycyrrhetinic acid; The nonionic emulsifier A has a hydrophilic-lipophilic balance (HLB) value greater than 9 and is sucrose stearate; The nonionic emulsifier B has a hydrophilic-lipophilic balance (HLB) of 2-4 and is sucrose polystearate.

2. The glabridin self-assembled inclusion composition according to claim 1, characterized in that: The polyol includes at least one of glycerol, 1,2-propylene glycol, dipropylene glycol, 1,3-butylene glycol, hexylene glycol, pentylene glycol, and hexyldecanol.

3. A method for preparing glabridin self-assembled inclusions, characterized in that: The following steps are involved: S1: Mix the glabridin, polyol, licorice carrier component, nonionic emulsifier A and nonionic emulsifier B in the glabridin self-assembled inclusion composition of claim 1 or 2, adjust the temperature to 60-65° C., stir, and dissolve in a water bath to obtain phase A; S2: Phase B is the water in the glabridin self-assembled inclusion composition according to claim 1 or 2, and the temperatures of phase A and phase B are adjusted to 60-65° C. respectively to obtain heated phase A and heated phase B; S3: Mix the heated phase A and the heated phase B while stirring at 400-500 rpm, keep the mixture at 60-65° C. for 30-40 min, and slowly cool the mixture to room temperature to obtain glabridin self-assembled inclusions.

4. A glabridin self-assembled inclusion body, characterized in that: The product is prepared by the preparation method according to claim 3.

5. Use of the glabridin self-assembled inclusions according to claim 4 in the preparation of whitening and freckle-removing products.

6. A cosmetic, characterized in that: The cosmetic contains the glabridin self-assembled inclusions according to claim 4.

7. The cosmetic according to claim 6, wherein The cosmetics also contain cosmetic accessories.

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