A kind of glabridin nano-scale bimolecular layer inclusion and its preparation method and application

Abstract

The invention discloses a glabridin nano-scale bilayer inclusion and a preparation method and application thereof, belonging to the field of cosmetics. The glabridin nano-inclusion composition comprises phase A, phase B and phase C, wherein phase A encapsulates phase B, and phase B encapsulates phase C; the phase C is water; the phase B comprises glabridin, polyol, liquid oil and emulsifier I; the phase A comprises water, targeting polypeptide and emulsifier II; the liquid oil is squalane; the polyol is 1,2-hexanediol and 1,3-butanediol; the emulsifier I is diphosphatidylglycerol; the emulsifier II is polyglycerol 10 oleate and lecithin. The glabridin nano-inclusion composition is a nano-scale bilayer inclusion structure. The glabridin nano-inclusion composition has good stability, good whitening effect, and unexpected technical effects.

Description

Technical Field

[0001] The invention relates to the field of whitening skin care products, and in particular to a glabridin nano-scale double-molecular layer inclusion body and a preparation method and application thereof. Background Art

[0002] Glabridin (flavonoids) is a natural plant extract extracted from polyphenols in wild African licorice. Glabridin has multiple effects such as antioxidant, immunomodulatory, anti-inflammatory, and anti-depression. Studies have shown that glabridin has anti-free radical activity and can effectively inhibit the damage of free radicals to cells.

[0003] The targets of glabridin and some other common whitening agents are located in the nucleus of melanocytes. When the α-MSH targeting peptide binds to the MC1-R receptor on the melanocyte membrane, it causes intracellular reactions such as upregulation of protein kinase A expression, and the activated tyrosinase catalyzes tyrosine to eventually form melanin. When inflammation such as allergies, acne or sunburn occurs, it will also induce the binding of α-MSH and MC1-R receptors, upregulating the expression of inflammatory factors such as IL-1, IL-6, IL-8 and TNF-α, and ultimately leading to pigmentation after inflammation heals. Therefore, the formation of melanin is caused by a series of complex reactions in melanocytes. To achieve a good whitening effect, in addition to inhibiting tyrosinase activity, it is also necessary to consider it from different angles.

[0004] Existing technical solutions: ① CN108451837A also compounded and encapsulated functional ingredients for different whitening mechanisms to achieve multi-target whitening and convenient formulation application. ② CN114796008A encapsulates glabridin and polypeptide at the same time. ③ CN115778886A discloses a glabridin plant-derived microcapsule inclusion and a preparation method thereof.

[0005] However, the inventors of the present invention have found that the products obtained by the above-mentioned technical solutions of the prior art or other technical solutions of the prior art have problems such as poor stability (for example, problems such as large changes in appearance after being placed at high temperature or room temperature for 30 days, stratification after centrifugation, and poor stability at high temperature, room temperature or low temperature after being prepared as a preparation product), poor permeability and poor whitening effect.

[0006] Therefore, there is still an urgent need for a whitening product with good stability, good permeability and good whitening effect. Summary of the invention

[0007] In order to solve the aforementioned technical problems, the present invention provides the following technical solutions.

[0008] In a first aspect, the present invention provides a glabridin nano-inclusion composition.

[0009] A glabridin nano inclusion composition, characterized in that the glabridin nano inclusion composition comprises a phase A, a phase B and a phase C, wherein the phase A encapsulates the phase B, and the phase B further encapsulates the phase C;

[0010] The phase C is water; the phase B includes glabridin, polyol, liquid oil and emulsifier I; the phase A includes water, targeting polypeptide and emulsifier II;

[0011] The liquid oil is squalane;

[0012] The polyols are 1,2-hexanediol and 1,3-butanediol;

[0013] The emulsifier I is at least one of diphosphatidylglycerol, phosphatidylinositol, and phosphatidylethanolamine;

[0014] The emulsifier II is polyglycerol 10 oleate and phospholipids;

[0015] The phospholipid in the emulsifier II is at least one of lecithin, hydrogenated lecithin, and sphingomyelin;

[0016] The preparation method of the glabridin nano inclusion composition comprises the following steps:

[0017] (1) mixing and dissolving glabridin and polyol to obtain a mixed solution 1;

[0018] (2) Mixing the liquid oil and emulsifier I, heating to dissolve, and cooling to 30°C-40°C to obtain a mixed solution 2, which is then mixed with the mixed solution 1 to obtain phase B;

[0019] (3) While stirring phase B, add phase C to phase B to obtain mixed solution 3;

[0020] (4) Mixing water, targeting polypeptide and emulsifier II, heating and dissolving to obtain phase A;

[0021] (5) While stirring phase A, the mixed solution 3 is added dropwise into phase A and sheared under high pressure to obtain the glabridin nano-inclusion composition.

[0022] In some embodiments, the glabridin nano-inclusion composition is a nanoscale double-layer inclusion structure.

[0023] In some preferred embodiments, the emulsifier I is diphosphatidylglycerol.

[0024] In some preferred embodiments, the phospholipid in the emulsifier II is lecithin.

[0025] In some embodiments, the targeting polypeptide is palmitoyl tripeptide-8.

[0026] In some embodiments, the particle size D50 of the glabridin nano inclusions in the glabridin nano inclusion composition is 20nm-50nm; and the polydispersity index PDI is less than 0.3. In some embodiments, the particle size D50 of the glabridin nano inclusions in the glabridin nano inclusion composition is 20nm, 25 nm, 26 nm, 27 nm, 28 nm, 29 nm, 30 nm, 31nm, 32 nm, 33 nm, 34 nm, 35 nm, 36 nm, 37 nm, 38 nm, 39 nm, 40 nm, 45 nm or 50nm; and the polydispersity index PDI is less than 0.3. In some embodiments, the particle size D50 of the glabridin nano inclusions in the glabridin nano inclusion composition is 28nm; and the polydispersity index PDI is less than 0.3.

[0027] In some embodiments, the polydispersity index PDI is less than or equal to 0.25. In some embodiments, the polydispersity index PDI is less than or equal to 0.20. In some embodiments, the polydispersity index PDI is less than or equal to 0.15.

[0028] In some embodiments, the content of glabridin is 1.00wt%-3.00wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of glabridin is 1.00wt%, 1.5wt%, 2.0wt%, 2.5wt% or 3.00wt% based on the total mass of the glabridin nano inclusion composition.

[0029] In some embodiments, the content of the polyol is 10.00wt%-50.00wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the polyol is 10.00wt%, 15.00wt%, 20.00wt%, 25.00wt%, 30.00wt%, 35.00wt%, 40.00wt%, 45.00wt% or 50.00wt% based on the total mass of the glabridin nano inclusion composition.

[0030] In some embodiments, the content of the emulsifier I is 0.30wt%-1.50wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the emulsifier I is 0.30wt%, 0.40wt%, 0.50wt%, 0.60wt%, 0.70wt%, 0.80wt%, 0.90wt%, 1.00wt%, 1.10wt%, 1.20wt%, 1.30wt%, 1.40wt% or 1.50wt% based on the total mass of the glabridin nano inclusion composition.

[0031] In some embodiments, the content of the liquid oil is 1.00wt%-5.00wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the liquid oil is 1.00wt%, 1.50wt%, 2.00wt%, 2.50wt%, 3.00wt%, 3.50wt%, 4.00wt%, 4.50wt% or 5.00wt% based on the total mass of the glabridin nano inclusion composition.

[0032] In some embodiments, the content of the C phase is 0.001wt%-5.000wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the C phase is 0.01wt%-5.00wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the C phase is 0.1wt%-5.000wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the C phase is 1.00wt%-5.00wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the C phase is 1.00wt%, 2.00wt%, 3.00 wt%, 4.00 wt% or 5.00wt% based on the total mass of the glabridin nano inclusion composition.

[0033] In some embodiments, the water content in the phase A is 27.00 wt%-84.69wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the water content in the phase A is 27.00 wt%, 30.00 wt%, 35.00 wt%, 40.00 wt%, 45.00wt%, 50.00 wt%, 55.00 wt%, 60.00 wt%, 65.00 wt%, 66.80 wt%, 70.00 wt%, 75.00 wt%, 80.00 wt% or 84.69wt% based on the total mass of the glabridin nano inclusion composition.

[0034] In some embodiments, the content of the emulsifier II is 3.00wt%-8.00wt% based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the emulsifier II is 3.00wt%, 3.50wt%, 4.00wt%, 4.50wt%, 5.00wt%, 5.50wt%, 6.00wt%, 6.50wt%, 7.00wt%, 7.50wt% or 8.00wt% based on the total mass of the glabridin nano inclusion composition.

[0035] In some embodiments, the content of the targeting polypeptide is 0.01wt%-0.50wt% calculated based on the total mass of the glabridin nano inclusion composition. In some embodiments, the content of the targeting polypeptide is 0.01wt%, 0.05wt%, 0.10wt%, 0.15wt%, 0.20wt%, 0.25wt%, 0.30wt%, 0.35wt%, 0.40wt%, 0.45wt% or 0.50wt% calculated based on the total mass of the glabridin nano inclusion composition.

[0036] In some embodiments, the mass ratio of polyglycerol 10 oleate to lecithin in the emulsifier II is 1:1-1:5. In some embodiments, the mass ratio of polyglycerol 10 oleate to lecithin in the emulsifier II is 1:1, 1:2, 1:3, 1:4 or 1:5.

[0037] In some embodiments, the mass ratio of 1,2-hexanediol to 1,3-butanediol in the polyol is 1:15-1:30. In some embodiments, the mass ratio of 1,2-hexanediol to 1,3-butanediol in the polyol is 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29 or 1:30.

[0038] In some embodiments, based on the total mass of the glabridin nano-inclusion composition, the content of glabridin is 1.00wt%, the content of the polyol is 10.00wt%, the content of the emulsifier I is 0.30wt%, the content of the liquid oil is 1.00wt%, the content of the C phase is 1.00wt%, the content of water in the A phase is 83.69wt%, the content of the emulsifier II is 3.00wt%, and the content of the targeting polypeptide is 0.01wt%; the mass ratio of polyglycerol 10 oleate and lecithin in the emulsifier II is 1:1; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:15.

[0039] In some embodiments, based on the total mass of the glabridin nano-inclusion composition, the content of glabridin is 2.00wt%, the content of the polyol is 20.00wt%, the content of the emulsifier I is 1.00wt%, the content of the liquid oil is 2.00wt%, the content of the C phase is 2.00wt%, the content of water in the A phase is 66.80wt%, the content of the emulsifier II is 6.00wt%, and the content of the targeting polypeptide is 0.20wt%; the mass ratio of polyglycerol 10 oleate and lecithin in the emulsifier II is 1:3; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:20.

[0040] In some embodiments, based on the total mass of the glabridin nano-inclusion composition, the content of glabridin is 3.00wt%, the content of the polyol is 50.00wt%, the content of the emulsifier I is 1.50wt%, the content of the liquid oil is 5.00wt%, the content of the C phase is 5.00wt%, the content of water in the A phase is 27.00wt%, the content of the emulsifier II is 8.00wt%, and the content of the targeting polypeptide is 0.50wt%; the mass ratio of polyglycerol 10 oleate and lecithin in the emulsifier II is 1:5; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:30.

[0041] In some embodiments, calculated based on the total mass of the glabridin nano-inclusion composition, the content of glabridin is 1.00wt%-3.00wt%; the content of the polyol is 10.00wt%-50.00wt%; the content of the emulsifier I is 0.30wt%-1.50wt%; the content of the liquid oil is 1.00wt%-5.00wt%; the content of the C phase is 1.00wt%-5.00wt%; the content of water in the A phase is 27.00 wt%-84.69wt%; the content of the emulsifier II is 3.00wt%-8.00wt%; and the content of the targeting polypeptide is 0.01wt%-0.50wt%.

[0042] In some embodiments, based on the total mass of the glabridin nano inclusion composition, the content of glabridin is 1.00wt%-3.00wt%; the content of the polyol is 10.00wt%-50.00wt%; the content of the emulsifier I is 0.30wt%-1.50wt%; the content of the liquid oil is 1.00wt%-5.00wt%; the content of the C phase is 1.00wt%-5.00wt%; the content of water in the A phase is 27.00 wt%-84.69wt%; the content of the emulsifier II is 3.00wt%-8.00wt%; the content of the targeting polypeptide is 0.01wt%-0.50wt%; the emulsifier II is polyglycerol 10 oleate and lecithin; the mass ratio of polyglycerol 10 oleate and lecithin in the emulsifier II is 1:1-1:5 ; The mass ratio of 1,2-hexanediol to 1,3-butanediol in the polyol is 1:15-1:30.

[0043] In some embodiments, calculated based on the total mass of the glabridin nano-inclusion composition, the content of glabridin is 1.00wt%-3.00wt%; the content of the polyol is 10.00wt%-50.00wt%; the content of the emulsifier I is 0.30wt%-1.50wt%; the content of the liquid oil is 1.00wt%-5.00wt%; the content of the C phase is 0.001wt%-5.000wt%; the content of the emulsifier II is 3.00wt%-8.00wt%; the content of the targeting polypeptide is 0.01wt%-0.50wt%; and the remainder is water in phase A.

[0044] In some embodiments, based on the total mass of the glabridin nano inclusion composition, the content of the glabridin is 1.00wt%-3.00wt%; the content of the polyol is 10.00wt%-50.00wt%; the content of the emulsifier I is 0.30wt%-1.50wt%; the content of the liquid oil is 1.00wt%-5.00wt%; the content of the C phase is 0.001wt%-5.000wt%; the content of the emulsifier II is 3.00wt%-8.00wt%; the content of the targeting polypeptide is 0.01wt%-0.50wt%; the remainder is water in phase A; the mass ratio of polyglycerol 10 oleate and lecithin in the emulsifier II is 1:1-1:5; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:15-1:30.

[0045] In some embodiments, the dissolving in step (1) is performed at 40°C-45°C, and then the temperature is reduced to 20°C-40°C. In some embodiments, the heating dissolving in step (1) is performed at 40°C, 41°C, 42°C, 43°C, 44°C or 45°C, and then the temperature is reduced to 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C or 40°C.

[0046] In some embodiments, the heating and dissolving in step (2) is heating to 60°C-70°C for dissolving. In some embodiments, the heating and dissolving in step (2) is heating to 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C or 70°C for dissolving.

[0047] In some embodiments, the heating and dissolving in step (4) is heating to 60°C-70°C for dissolving. In some embodiments, the heating and dissolving in step (4) is heating to 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C or 70°C for dissolving.

[0048] In some embodiments, the temperature of phase A during the dropwise addition in step (5) is 55° C.-65° C. In some embodiments, the temperature of phase A during the dropwise addition in step (5) is 55° C., 56° C., 57° C., 58° C., 59° C., 60° C., 61° C., 62° C., 63° C., 64° C., or 65° C.

[0049] In some embodiments, the drop-by-drop acceleration in step (5) is 1 ml / min-5 ml / min. In some embodiments, the drop-by-drop acceleration in step (5) is 1 ml / min, 2 ml / min, 2.5 ml / min, 3 ml / min, 3.5 ml / min, 4 ml / min or 5 ml / min. In some embodiments, the drop-by-drop acceleration in step (5) is 3 ml / min.

[0050] In some embodiments, the temperature of the high pressure shearing in step (5) is 30° C.-40° C. In some embodiments, the temperature of the high pressure shearing in step (5) is 30° C., 35° C. or 40° C.

[0051] In some embodiments, the pressure of the high-pressure shearing in step (5) is 400 bar-1200 bar, and the number of high-pressure shearing cycles is 2-5 times (eg, 2 times, 3 times, 4 times or 5 times).

[0052] In some embodiments, the pressure of the high pressure shear in step (5) is 400 bar, 500 bar, 600 bar, 700 bar, 800 bar, 900 bar, 1000 bar, 1100 bar or 1200 bar.

[0053] In a second aspect, the present invention provides a cosmetic.

[0054] A cosmetic comprising the glabridin nano inclusion composition of the first aspect and at least one cosmetic auxiliary material.

[0055] In some embodiments, the cosmetic is in the form of an aqueous solution, essence, lotion or cream.

[0056] In a third aspect, the present invention provides an application of the glabridin nano-inclusion composition described in the first aspect.

[0057] A use of the glabridin nano-inclusion composition of the first aspect in the preparation of cosmetics.

[0058] Beneficial Effects

[0059] Compared with the prior art, a certain technical solution of the present invention has at least one of the following beneficial effects:

[0060] (1) Compared with other polyols, the polyol provided by the present invention is more conducive to improving the stability of the obtained glabridin nano inclusion composition and the product containing the glabridin nano inclusion composition in terms of particle size, polydispersity coefficient, appearance, acid value (pH value), odor and glabridin encapsulation rate under the conditions of light, high temperature, low temperature and variable temperature test cycles, as well as mechanical test stability, and has unexpected technical effects.

[0061] (2) Compared with other emulsifiers, the use of the emulsifier I provided by the present invention in phase B is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the product containing the glabridin nano-inclusion composition under the conditions of light, high temperature, low temperature, and variable temperature test cycles, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor, and glabridin encapsulation rate, and mechanical test stability, and has unexpected technical effects.

[0062] (3) Compared with other emulsifiers, the use of the emulsifier II provided by the present invention in phase A is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the product containing the glabridin nano-inclusion composition under the conditions of light, high temperature, low temperature, and variable temperature test cycles, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor, and glabridin encapsulation rate, and mechanical test stability, and has unexpected technical effects.

[0063] (4) Compared with other emulsifier II ratios, the emulsifier II ratio provided by the present invention is more conducive to improving the stability of the obtained glabridin nano inclusion composition and the product containing the glabridin nano inclusion composition under the conditions of light, high temperature, low temperature, and variable temperature test cycles, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor, and glabridin encapsulation rate, and mechanical test stability, and has unexpected technical effects.

[0064] (5) Compared with other liquid oils, the use of the liquid oil provided by the present invention in phase B is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the product containing the glabridin nano-inclusion composition under the conditions of light, high temperature, low temperature, and variable temperature test cycles, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor, and glabridin encapsulation rate, and mechanical test stability, and has unexpected technical effects.

[0065] (6) Compared with the glabridin nano-inclusion composition and the products containing the glabridin nano-inclusion composition obtained by other technical solutions, the liquid oil provided by the present invention is more conducive to improving the stability of the particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate of the obtained glabridin nano-inclusion composition and the products containing the glabridin nano-inclusion composition under the conditions of light, high temperature, low temperature and variable temperature test cycles, and mechanical test stability, and has unexpected technical effects.

[0066] (7) Compared with the case where no phase C is added, the glabridin nano inclusion composition obtained by adding phase C (water) to the glabridin nano inclusion composition and the product comprising the glabridin nano inclusion composition have unexpected technical effects in terms of stability of particle size, polydispersity coefficient, appearance, acid value (pH value), odor and glabridin encapsulation rate under the conditions of illumination, high temperature, low temperature and variable temperature test cycles, as well as mechanical test stability.

[0067] (8) The glabridin nano-inclusion composition provided by the present invention has excellent technical effects of reducing skin melanin content and improving skin chroma, which has unexpected technical effects.

[0068] Terminology

[0069] In the above text of the present invention, regardless of whether the words "about" or "approximately" are used, all the numbers disclosed herein are approximate values. Based on the disclosed numbers, the value of each number may vary by less than ±10% or reasonable differences considered by those skilled in the art, such as ±1%, ±2%, ±3%, ±4% or ±5%.

[0070] The terms "optional", "optional" or "optionally" mean that the subsequently described event or circumstance may but need not occur.

[0071] The term "and / or" should be understood to mean any one of the optional items or a combination of any two or more of the optional items.

[0072] The term "wt%" means percent by mass.

[0073] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction. DETAILED DESCRIPTION

[0074] In order to enable those skilled in the art to better understand the technical solution of the present invention, some non-limiting embodiments are further disclosed below to further illustrate the present invention in detail.

[0075] The reagents used in the present invention can be purchased from the market or prepared by the method described in the present invention.

[0076] Palmitoyl Tripeptide-8: purchased from Guangzhou Qingnang Biotechnology Co., Ltd. The basic information of the raw materials is as follows:

[0077] CAS No.: 936544-53-5;

[0078] Molecular formula: C 37 H 61 N9O4;

[0079] Molecular weight: 695.94.

[0080] Example 1-Example 3: Preparation of glabridin nano-inclusion composition

[0081] Recipe: See Table 1.

[0082] Table 1: Formula of glabridin nano inclusion composition

[0083]

[0084] Preparation method:

[0085] (1) mixing glabridin and polyol, heating to 40° C. to dissolve, and cooling to 30° C. to obtain a mixed solution 1;

[0086] (2) Mixing the liquid oil and emulsifier I, heating to 65°C to dissolve, and cooling to 30°C to obtain a mixed solution 2, which is then mixed with the mixed solution 1 to obtain a phase B;

[0087] (3) While stirring phase B, add phase C to phase B to obtain mixed solution 3;

[0088] (4) Mix water, targeting peptide and emulsifier II, heat to 65° C. to dissolve, and obtain phase A;

[0089] (5) While stirring phase A and keeping the temperature of phase A at 60° C., the mixed solution 3 was added dropwise into phase A (the dropping speed of the mixed solution 3 was 3 ml / min, i.e., about 1 drop / second) at a dropping speed of 3 ml / min, and high-pressure shearing was performed at 800 bar. The high-pressure shearing cycle number was 5, and the glabridin nano-inclusion composition was obtained.

[0090] The glabridin nano-inclusion compositions obtained in the above examples were respectively observed by transmission electron microscopy, and the results showed that the glabridin nano-inclusion compositions obtained in the above examples 1 to 3 were nanoscale double-molecular-layer inclusion structures.

[0091] Comparative Examples 1-4: Investigation of Polyols

[0092] Formulation: Polyols were investigated based on the formulation of Example 2. The detailed formulation is shown in Table 2.

[0093] Table 2: Polyol Investigation

[0094]

[0095] Preparation method: Refer to the preparation method of Example 2. Except for the different types of polyols, the remaining operations are the same as the preparation method of Example 2.

[0096] Comparative Examples 5-7: Investigation of Emulsifier I

[0097] Formula: Emulsifier I was investigated based on the formula of Example 2. The detailed formula is shown in Table 3.

[0098] Table 3: Investigation of Emulsifier I

[0099]

[0100] Preparation method: refer to the preparation method of Example 2. Except for the different types of emulsifier I, the remaining operations are the same as the preparation method of Example 2.

[0101] Comparative Examples 8-11: Investigation of Emulsifier II

[0102] Formula: Emulsifier II was investigated based on the formula of Example 2. The detailed formula is shown in Table 4.

[0103] Table 4: Investigation of Emulsifier II

[0104]

[0105] Preparation method: refer to the preparation method of Example 2. Except for the different types of emulsifier II, the remaining operations are the same as the preparation method of Example 2.

[0106] Comparative Example 12-Comparative Example 14: Investigation of the ratio of emulsifier II

[0107] Formula: The proportion of emulsifier II was investigated based on the formula of Example 2. The detailed formula is shown in Table 5.

[0108] Table 5: Investigation of the ratio of emulsifier II

[0109]

[0110] Preparation method: refer to the preparation method of Example 2. Except for the different proportion of emulsifier II, the other operations are the same as the preparation method of Example 2.

[0111] Comparative Example 15-Comparative Example 17: Investigation of Liquid Grease

[0112] Formulation: Liquid oil was investigated based on the formulation of Example 2. The detailed formulation is shown in Table 6.

[0113] Table 6: Investigation of liquid grease

[0114]

[0115] Preparation method: refer to the preparation method of Example 2. Except for the different types of liquid oils, the remaining operations are the same as the preparation method of Example 2.

[0116] Comparative Example 18: Investigation of the prior art technical solution (CN116270355A Example 3)

[0117] (1) Mix 1 wt % glabridin and 20 wt % butanediol in a 65° C. water bath and stir until dissolved to obtain phase A.

[0118] (2) Mix 2 wt% polyglycerol-10 laurate, 1.5 wt% peony seed oil, 5 wt% soybean lecithin, and 0.15 wt% palmitoyl tripeptide-8 in a 70°C water bath and stir until dissolved to obtain phase B.

[0119] (3) 1 wt% glutathione and 3 wt% 3-o-ethyl ascorbic acid were dissolved in 66.35 wt% water and heated to 65 °C to obtain phase C.

[0120] (4) After mixing phase A and phase B, add phase C to emulsify and obtain a crude inclusion emulsion.

[0121] (5) The crude emulsion is treated to nanoscale by high-pressure shearing, and the circulating water bath is controlled at 30-40° C. and 800 bar pressure for 6 times to obtain a whitening composition inclusion solution.

[0122] Comparative Example 19: Investigation of different preparation processes (without phase C)

[0123] Recipe: See Table 7.

[0124] Table 7: Investigation of different preparation processes (without phase C)

[0125]

[0126] Preparation method:

[0127] (1) mixing glabridin and polyol, heating to 40° C. to dissolve, and cooling to 30° C. to obtain a mixed solution 1;

[0128] (2) Mixing the liquid oil and emulsifier I, heating to 65°C to dissolve, and cooling to 30°C to obtain a mixed solution 2, which is then mixed with the mixed solution 1 to obtain a phase B;

[0129] (3) Mix water, targeting peptide and emulsifier II, heat to 65° C. to dissolve, and obtain phase A;

[0130] (4) While stirring phase A at a temperature of 60° C., phase B was added dropwise into phase A at a dropping speed of 3 ml / min, and high-pressure shearing was performed at 800 bar. The high-pressure shearing cycle number was 5, and the glabridin nano-inclusion composition was obtained.

[0131] Example 4: Preparation of aqueous solution

[0132] The above examples and comparative examples were respectively prepared into aqueous solutions according to the following formulas and preparation processes.

[0133] An aqueous solution comprising the following components in mass:

[0134] Phase S1: 86.95 parts by weight of water; 5 parts by weight of glycerol; 0.05 parts by weight of disodium EDTA;

[0135] S2 phase: 3 parts by weight of butanediol; 0.5 parts by weight of p-hydroxyacetophenone;

[0136] S3 phase: 4 parts by weight of the glabridin nano-inclusion composition prepared in the above-mentioned embodiment or comparative example; and 0.5 parts by weight of hexylene glycol.

[0137] Preparation method: respectively mix the S1 phase raw materials into one container, and mix the S2 phase raw materials into another container, then heat to 65°C, pour the S1 phase raw materials into the mixture after the S2 phase is completely dissolved, stir evenly, and obtain the aqueous preparation of each embodiment or comparative example.

[0138] Test Example 1: Stability Test

[0139] Refer to T / GDCQMA 002-2023 "Cosmetic Stability Test Specification" for stability testing.

[0140] High temperature stability test: The glabridin nano-inclusion composition or its aqueous solution (Example 4) obtained in the above-mentioned examples or comparative examples was placed in a sealed container and then placed under high temperature conditions (50°C ± 2°C) for a 30-day stability test. The particle size, polydispersity coefficient, appearance, acid value (pH value), odor and glabridin encapsulation rate of each example or comparative example after 0 day and 30 days under high temperature conditions (50°C ± 2°C) were tested. The results are shown in Tables 8 to 10 and 13.

[0141] Cold resistance test: The aqueous solution prepared by using the glabridin nano-inclusion composition obtained in each of the above embodiments or comparative examples in Example 4 was placed at -20°C for 30 days, and the particle size, polydispersity coefficient, acid value (pH value), appearance, odor and glabridin encapsulation rate of the aqueous solution of each embodiment or comparative example after 0 day and -20°C for 30 days were tested. The results are shown in Tables 10-11.

[0142] Strong light irradiation test: The aqueous solution prepared by using the glabridin nano-inclusion composition obtained in the above embodiments or comparative examples in Example 4 was placed in a transparent container and placed in a light box. The glabridin nano-inclusion composition was stored for 10 days at an illumination of 4500 lx±500 lx. Samples were taken on the 5th and 10th days to detect the particle size, polydispersity coefficient, appearance, acid value (pH value), odor and glabridin encapsulation rate. The results were compared with those on day 0. The results are shown in Table 12.

[0143] Table 8: 0-day results of stability test of glabridin nano inclusion composition

[0144]

[0145]

[0146]

[0147] Table 9: Results of stability test of glabridin nano inclusion composition at 50°C ± 2°C for 30 days

[0148]

[0149]

[0150] Table 10: Results of aqueous solution stability test at day 0

[0151]

[0152]

[0153]

[0154] Table 11: Aqueous solution stability test - 20°C 30 days results

[0155]

[0156]

[0157] Table 12: Results of strong light irradiation of aqueous solution

[0158]

[0159]

[0160] Table 13: Results of aqueous solution stability test at 50℃±2℃ for 30 days

[0161]

[0162]

[0163] in conclusion:

[0164] (1) Compared with other polyols, the polyol provided by the present invention is more conducive to improving the stability of the obtained glabridin nano inclusion composition and the product containing the glabridin nano inclusion composition under high temperature, low temperature and light conditions, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate, and has unexpected technical effects.

[0165] (2) Compared with other emulsifiers, the use of the emulsifier I provided by the present invention in phase B is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the product containing the glabridin nano-inclusion composition under high temperature, low temperature and light conditions, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate, and has unexpected technical effects.

[0166] (3) Compared with other emulsifiers, the use of the emulsifier II provided by the present invention in phase A is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the product containing the glabridin nano-inclusion composition under high temperature, low temperature and light conditions, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate, and has unexpected technical effects.

[0167] (4) Compared with other emulsifier II ratios, the emulsifier II ratio provided by the present invention is more conducive to improving the stability of the obtained glabridin nano inclusion composition and the product containing the glabridin nano inclusion composition under high temperature, low temperature and light conditions, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate, and has unexpected technical effects.

[0168] (5) Compared with other liquid oils, the use of the liquid oil provided by the present invention in phase B is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the product containing the glabridin nano-inclusion composition under high temperature, low temperature and light conditions, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate, and has unexpected technical effects.

[0169] (6) Compared with the glabridin nano-inclusion composition obtained by other technical solutions and the products containing the glabridin nano-inclusion composition, the liquid oil provided by the present invention is more conducive to improving the stability of the obtained glabridin nano-inclusion composition and the products containing the glabridin nano-inclusion composition under high temperature, low temperature and light conditions, such as particle size, polydispersity coefficient, appearance state, acid value (pH value), odor and glabridin encapsulation rate, and has unexpected technical effects.

[0170] (7) Compared with the case where no phase C is added, the glycyrrhizin nano inclusion composition obtained by adding phase C (water) to the glycyrrhizin nano inclusion composition and the product containing the glycyrrhizin nano inclusion composition have unexpected technical effects in terms of stability of particle size, polydispersity coefficient, appearance, acid value (pH value), odor and glycyrrhizin encapsulation rate under high temperature, low temperature and light conditions.

[0171] Test Example 2: Mechanical Test

[0172] The samples of the glabridin nano-inclusion composition obtained in the above-mentioned embodiments or comparative examples at 0 days and after being placed under high temperature stability test conditions (50°C) for 30 days, and the samples obtained after 7 cycles of variable temperature test (placed at 50°C for 24 hours and then moved to -5°C for 24 hours, and cycled 7 times) were centrifuged at 4000 rpm for 30 minutes; then the stability was compared with that observed under static conditions. The results are shown in Table 14.

[0173] Table 14: Mechanical test stability results

[0174]

[0175]

[0176] in conclusion:

[0177] (1) Compared with other polyols, the polyol provided by the present invention is more conducive to improving the mechanical test stability of the obtained glabridin nano inclusion composition and the products containing the glabridin nano inclusion composition under high temperature conditions, low temperature conditions, and variable temperature test cycle conditions, and has unexpected technical effects.

[0178] (2) Compared with other emulsifiers, the use of the emulsifier I provided by the present invention in phase B is more conducive to improving the mechanical test stability of the obtained glabridin nano-inclusion composition and the products containing the glabridin nano-inclusion composition under high temperature conditions, low temperature conditions, and variable temperature test cycle conditions, and has unexpected technical effects.

[0179] (3) Compared with other emulsifiers, the use of the emulsifier II provided by the present invention in phase A is more conducive to improving the mechanical test stability of the obtained glabridin nano-inclusion composition and the products containing the glabridin nano-inclusion composition under high temperature conditions, low temperature conditions, and variable temperature test cycle conditions, and has unexpected technical effects.

[0180] (4) Compared with other emulsifier II ratios, the emulsifier II ratio provided by the present invention is more conducive to improving the mechanical test stability of the obtained glabridin nano inclusion composition and the products containing the glabridin nano inclusion composition under high temperature conditions, low temperature conditions, and variable temperature test cycle conditions, and has unexpected technical effects.

[0181] (5) Compared with other liquid oils, the use of the liquid oil provided by the present invention in phase B is more conducive to improving the mechanical test stability of the obtained glabridin nano-inclusion composition and the products containing the glabridin nano-inclusion composition under high temperature conditions, low temperature conditions, and variable temperature test cycle conditions, and has unexpected technical effects.

[0182] (6) Compared with the glabridin nano-inclusion composition obtained by other technical solutions and the products containing the glabridin nano-inclusion composition, the liquid oil provided by the present invention is more conducive to improving the mechanical test stability of the glabridin nano-inclusion composition obtained and the products containing the glabridin nano-inclusion composition under high temperature conditions, low temperature conditions, and variable temperature test cycle conditions, and has unexpected technical effects.

[0183] (7) Compared with not adding phase C, the mechanical test stability of the glabridin nano inclusion composition obtained by adding phase C (water) to the glabridin nano inclusion composition and the product containing the glabridin nano inclusion composition under high temperature conditions, low temperature conditions and variable temperature test cycle conditions has unexpected technical effects.

[0184] Test Example 3: Whitening Effect Investigation

[0185] In order to compare the whitening effects of the embodiments, the skin analyzers Demalab Combo and VISIA were used to test the samples for efficacy, and the test standard was "Test Method for Cosmetic Whitening and Anti-freckle Efficacy" T / ZHCA 001-2018. 4wt% of Example 1, 2wt% of Example 2 or 1.33wt% of Example 3 were added to the blank essence to obtain essences containing the glabridin nano inclusion compositions of different embodiments. The MI value and ITA° value of qualified volunteers before and after skin application were tested and compared according to the test standard "Test Method for Cosmetic Whitening and Anti-freckle Efficacy" T / ZHCA001-2018. The results are shown in Tables 15 and 16.

[0186] The lower the MI value, the less melanin in the skin, and the whiter the skin looks. The higher the ITA° value, the whiter and brighter the skin.

[0187] Table 15: MI value comparison table

[0188]

[0189] Table 16: ITA° value comparison table

[0190]

[0191] Conclusion: The glabridin nano-inclusion composition provided by the present invention has excellent technical effects of reducing skin melanin content and improving skin chroma, and has unexpected technical effects.

[0192] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any slight modification, equivalent substitution and improvement made to the above embodiment based on the technical essence of the present invention should be included in the protection scope of the technical solution of the present invention.

Claims

1. A glabridin nano-inclusion composition, characterized in that: The glabridin nano inclusion composition consists of phase A, phase B and phase C, wherein phase A encapsulates phase B, and phase B encapsulates phase C; the particle size D50 of the glabridin nano inclusion in the glabridin nano inclusion composition is 20nm-50nm; and the polydispersity index PDI is less than 0.3; The C phase is water; the B phase is composed of glabridin, polyol, liquid oil and emulsifier I; the A phase is composed of water, targeting polypeptide and emulsifier II; The liquid oil is squalane; The polyols are 1,2-hexanediol and 1,3-butanediol; The emulsifier I is diphosphatidylglycerol; The emulsifier II is polyglycerol-10 oleate and lecithin; The targeting polypeptide is palmitoyl tripeptide-8; Calculated based on the total mass of the glabridin nano inclusion composition, the content of the glabridin is 1.00wt%-3.00wt%; the content of the polyol is 10.00wt%-50.00wt%; the content of the emulsifier I is 0.30wt%-1.50wt%; the content of the liquid oil is 1.00wt%-5.00wt%; the content of the C phase is 1.00wt%-5.00wt%; the content of water in the A phase is 27.00 wt%-83.69wt%; the content of the emulsifier II is 3.00wt%-8.00wt%; the content of the targeting polypeptide is 0.01wt%-0.50wt%; The mass ratio of polyglycerol-10 oleate to lecithin in the emulsifier II is 1:1-1:5; the mass ratio of 1,2-hexanediol to 1,3-butanediol in the polyol is 1:15-1:30; The preparation method of the glabridin nano inclusion composition comprises the following steps: (1) mixing and dissolving glabridin and polyol to obtain a mixed solution 1; (2) Mixing the liquid oil and emulsifier I, heating to dissolve, and cooling to 30°C-40°C to obtain a mixed solution 2, which is then mixed with the mixed solution 1 to obtain phase B; (3) While stirring phase B, add phase C to phase B to obtain mixed solution 3; (4) Mixing water, targeting polypeptide and emulsifier II, heating and dissolving to obtain phase A; (5) While stirring phase A, the mixed solution 3 is added dropwise into phase A and sheared under high pressure to obtain the glabridin nano-inclusion composition. 2 . The glabridin nano-inclusion composition according to claim 1 , wherein the particle size D50 of the glabridin nano-inclusions in the glabridin nano-inclusion composition is 28 nm, and the polydispersity index PDI is less than 0.

3.

3. The glabridin nano inclusion composition according to any one of claims 1-2, wherein, calculated based on the total mass of the glabridin nano inclusion composition, the content of glabridin is 1.00wt%, the content of the polyol is 10.00wt%, the content of the emulsifier I is 0.30wt%, the content of the liquid oil is 1.00wt%, the content of the C phase is 1.00wt%, the content of water in the A phase is 83.69wt%, the content of the emulsifier II is 3.00wt%, and the content of the targeting polypeptide is 0.01wt%; the mass ratio of polyglycerol-10 oleate and lecithin in the emulsifier II is 1:1; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:15; or Calculated based on the total mass of the glabridin nano inclusion composition, the content of glabridin is 2.00wt%, the content of the polyol is 20.00wt%, the content of the emulsifier I is 1.00wt%, the content of the liquid oil is 2.00wt%, the content of the C phase is 2.00wt%, the content of water in the A phase is 66.80wt%, the content of the emulsifier II is 6.00wt%, and the content of the targeting polypeptide is 0.20wt%; the mass ratio of polyglycerol-10 oleate and lecithin in the emulsifier II is 1:3; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:20; or Calculated based on the total mass of the glabridin nano inclusion composition, the content of the glabridin is 3.00wt%, the content of the polyol is 50.00wt%, the content of the emulsifier I is 1.50wt%, the content of the liquid oil is 5.00wt%, the content of the C phase is 5.00wt%, the content of water in the A phase is 27.00wt%, the content of the emulsifier II is 8.00wt%, and the content of the targeting polypeptide is 0.50wt%; the mass ratio of polyglycerol-10 oleate and lecithin in the emulsifier II is 1:5; the mass ratio of 1,2-hexanediol and 1,3-butanediol in the polyol is 1:

30.

4. The glabridin nano-inclusion composition according to any one of claims 1 to 2, wherein the dissolving in step (1) is carried out at 40°C-45°C and then the temperature is lowered to 20°C-40°C; The heating and dissolving in step (2) is heating to 60°C-70°C for dissolving; The heating and dissolving in step (4) is to heat to 60°C-70°C for dissolving; the temperature of phase A during dropwise addition in step (5) is 55°C-65°C; The dropwise addition acceleration in step (5) is 1 ml / min-5 ml / min; The temperature of the high pressure shearing in step (5) is 30°C-40°C; The pressure of the high-pressure shearing in step (5) is 400 bar-1200 bar, and the number of high-pressure shearing cycles is 2-5 times.

5. A cosmetic, characterized in that: The invention comprises the glabridin nano inclusion composition according to any one of claims 1 to 4 and at least one cosmetic auxiliary material.

6. Use of the glabridin nano-inclusion composition according to any one of claims 1 to 4 in the preparation of cosmetics.

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