A multiple protection glabrene carrier, a preparation method and application thereof

Abstract

The application discloses a kind of multiple protection glabridin carriers and preparation method and application thereof, belong to cosmetic technical field;The multiple protection glabridin carrier provided by the application includes the following mass percentages of components: glabridin 2-3%, polyol 20-40%, liquid emulsifier 1-10%, liquid oil 0.5-5%, antioxidant 0.01-0.5%, phospholipid 1-15%, water balance.The multiple protection glabridin carrier provided by the application is amphiphilic vesicle structure, with small and uniform particle size, high stability, high solubility and high transdermal absorption, and the product provided by the application does not contain organic solvent, with good safety;Meanwhile, the preparation method provided by the application is simple to operate, without special equipment, conducive to practical production application.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of cosmetics, and particularly relates to a multiple-protected glabridin carrier and a preparation method and application thereof. BACKGROUND

[0002] Glabridin has potential application value as an efficacy raw material in cosmetics, and its structure is shown in Formula I; however, glabridin has the defects of poor water solubility, poor light stability and high-temperature stability, and poor transdermal absorption; therefore, it is difficult to be applied to products.

[0003]

[0004] The prior art provides different technical solutions to solve the above defects of glabridin. For example, CN106619148A prepares a water-soluble microcapsule to increase transdermal absorption in view of the poor transdermal absorption and solubility of glabridin; although the patent provides data of transdermal absorption, it does not explore the stability of the product, and the technical solution provided in the patent contains glutaraldehyde solvent, which inevitably causes irritation to the skin during use. Patent CN108815012A prepares an alpha-cyclodextrin microcapsule in view of the poor solubility of glabridin, and increases the solubility of glabridin by using alpha-cyclodextrin microcapsule wrapping; although the patent explores the solubility, it does not explore the stability, and the technical solution uses acetone as a solvent, which is difficult to completely remove during preparation, and thus causes irritation to the skin during subsequent use. Patent CN110169928A prepares a cyclodextrin multiple-wrapped product in view of the solubility, stability and transdermal absorption of glabridin, so as to increase the solubility, stability and transdermal absorption of glabridin; however, the technical solution uses anhydrous ethanol, which may have solvent residues, thus causing certain irritation to the skin during use, and the method uses cyclodextrin wrapping, which has certain limitations in transdermal absorption because cyclodextrin is a cyclic oligosaccharide and no lipophilic group is exposed in the structure, and the technical solution does not explore the light stability of the product. Patent CN105581911A improves the stability of glabridin and promotes penetration by using a solid lipid carrier; however, the technical solution does not study the stability, and in addition, the technical solution adopts an ultrasonic emulsification process, which is difficult to realize mass production. SUMMARY

[0005] The present application aims to overcome the deficiencies of the prior art, and provides a multiple-protected glabridin carrier which does not require an organic solvent, is easy to realize mass production, and has excellent stability, solubility, transdermal absorption and safety, and a preparation method and application thereof.

[0006] To achieve the above object, in a first aspect of the present application, a multiple-protected glabridin carrier is provided, which comprises the following components in mass parts:

[0007] Glabridin 2-3%, polyhydric alcohol 20-40%, liquid emulsifier 1-10%, liquid oil 0.5-5%, antioxidant 0.01-0.5%, phospholipid 1-15%, water balance;

[0008] The polyhydric alcohol has a carbon atom number of 3-5;

[0009] The antioxidant is a phenolic antioxidant.

[0010] The multiple-protected glabridin carrier provided by the present application can realize high stability, high solubility and excellent transdermal absorption by selecting appropriate mass percentages of components and specific polyhydric alcohol and antioxidant. Specifically, the multiple-protected glabridin carrier provided by the present application is a bilayer vesicular amphiphilic carrier, in which the phospholipid is the main wall material, the polyhydric alcohol and glabridin are the main components in the bilayer, and the liquid oil and antioxidant are the main components in the vesicular center. Therefore, the formed amphiphilic vesicular structure can well increase the solubility of glabridin in water, and the structure is similar to the skin lipid structure, so that the transdermal absorption is good. At the same time, the structure formed can better increase the stability of the product by wrapping glabridin and antioxidant in the wall material.

[0011] The phenolic antioxidant in the present application refers to an antioxidant containing a phenolic hydroxyl group.

[0012] The liquid oil in the present application refers to oil that is in a liquid state at room temperature (25°C).

[0013] As a preferred embodiment of the multiple-protected glabridin carrier of the present application, the multiple-protected glabridin carrier comprises the following components in mass parts: polyhydric alcohol 25-35%, liquid emulsifier 2-5%, liquid oil 3-4%, antioxidant 0.1-0.3%, phospholipid 5-10%.

[0014] The inventors have found that the selection of the mass percentage of the components can affect the performance of the product. When the mass percentage of the components is further selected within the above range, the comprehensive performance of the obtained product is more excellent.

[0015] As a preferred embodiment of the multiple-protected glabridin carrier of the present application, the polyhydric alcohol is at least one of glycerol and 1,3-butanediol.

[0016] The polyol and glabridin mainly exist in the bilayer of the amphiphilic vesicle structure, and when the number of carbon atoms in the selected polyol is 3-5, and especially when the polyol is further selected as glycerol or 1,3-butylene glycol, glabridin can be better stabilized, and the comprehensive performance of the multiple-protected glabridin carrier can be improved.

[0017] As a preferred embodiment of the multiple-protected glabridin carrier, the antioxidant is at least one of tocopherol, pentaerythritol tetra (bis-tert-butyl hydroxyl hydrogenated cinnamic acid) ester, and tert-butyl hydroquinone.

[0018] Preferably, the antioxidant is tocopherol.

[0019] The antioxidant and the liquid oil mainly exist in the center of the amphiphilic vesicle, and the inventors have found that when the selected antioxidant is a phenolic antioxidant, especially at least one of tocopherol, pentaerythritol tetra (bis-tert-butyl hydroxyl hydrogenated cinnamic acid) ester, and tert-butyl hydroquinone, the stability of the product can be significantly improved; when the selected antioxidant is tocopherol, the comprehensive performance of the obtained product is better.

[0020] As a preferred embodiment of the multiple-protected glabridin carrier, the liquid emulsifier is at least one of a polysorbate emulsifier and a polyglycerol emulsifier.

[0021] As a preferred embodiment of the multiple-protected glabridin carrier, the polysorbate emulsifier is at least one of polysorbate-60 and polysorbate-80.

[0022] And / or, the polyglycerol emulsifier is at least one of polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 oleate, and polyglyceryl-4 oleate.

[0023] Preferably, the liquid emulsifier is polysorbate-80.

[0024] As a preferred embodiment of the multiple-protected glabridin carrier, the liquid oil is at least one of caprylic / capric triglyceride, squalane, dicaprylyl carbonate, glyceryl tri (ethylhexanoate), hydrogenated polydecene, and isononyl isononanoate.

[0025] Preferably, the liquid oil is caprylic / capric triglyceride.

[0026] As a preferred embodiment of the multiple-protected glabridin carrier, the phospholipid is at least one of hydrogenated lecithin, soybean lecithin, and soybean phosphatidylcholine.

[0027] Preferably, the phospholipid is soybean lecithin.

[0028] The inventors have found that the types of the liquid emulsifier, the liquid oil and the phospholipid also affect the comprehensive performance of the product, and when the liquid emulsifier, the liquid oil and the phospholipid are further selected, the comprehensive performance of the obtained product is more excellent.

[0029] In the second aspect of the present application, the present application provides a preparation method of the multiple-protected glabridin carrier, and the preparation method comprises the following steps:

[0030] (1) dissolving glabridin and polyol to obtain phase A;

[0031] (2) dissolving the liquid emulsifier, the liquid oil, the antioxidant and the phospholipid to obtain phase B;

[0032] (3) heating water to obtain phase C;

[0033] (4) mixing phase A and phase B, then adding phase C to homogenize and circularly shear to obtain the multiple-protected glabridin carrier.

[0034] As a preferred embodiment of the preparation method of the present application, in the step (1), the temperature for dissolving is 60-70℃.

[0035] As a preferred embodiment of the preparation method of the present application, in the step (2), the temperature for dissolving is 65-75℃.

[0036] As a preferred embodiment of the preparation method of the present application, in the step (3), the temperature for heating is 65-75℃.

[0037] As a preferred embodiment of the preparation method of the present application, in the step (4), the rotation speed for homogenizing is 2000-3000 rpm, and the time is 3-5 min.

[0038] As a preferred embodiment of the preparation method of the present application, in the step (4), the temperature for circularly shearing is 30-50℃, the pressure is 550-650 bar, and the number of times is 5-7.

[0039] The inventors have found that under the preparation method provided by the present application, the product prepared can be ensured to be a two-pole vesicle structure, and the product obtained has small particle size, high transparency and small particle size distribution coefficient; so as to ensure that the product obtained has excellent stability.

[0040] In the third aspect of the present application, the present application provides the application of the multiple-protected glabridin carrier in the preparation of cosmetics.

[0041] The multiple-protected glabridin carrier prepared by the present application has high stability, high solubility and transdermal absorption, so as to be applied to the preparation of cosmetics.

[0042] Compared with the prior art, the present application has the following advantages:

[0043] The multiple-protected glabridin carrier provided by the present application can be prepared by selecting appropriate mass percentages of specific components and using appropriate preparation methods, so that the multiple-protected glabridin carrier with an amphiphilic vesicular structure can be prepared. The product obtained has small and uniform particle size, high stability, high solubility and high transdermal absorption, and does not contain organic solvents, so it has good safety. Meanwhile, the preparation method provided by the present application is simple to operate and does not require special equipment, which is conducive to practical production and application. DETAILED DESCRIPTION

[0044] For the purpose of better illustrating the object, technical scheme and advantages of the present application, the present application will be further described in combination with specific examples.

[0045] Unless otherwise specified, the raw materials used in the present application are conventional commercially available raw materials, and the raw materials used in the parallel examples or comparative examples in the present application are consistent.

[0046] Examples 1-9 and Comparative Examples 1-16

[0047] The multiple-protected glabridin carrier provided by Examples 1-9 and Comparative Examples 1-16 of the present application has the component content (mass percentage, %) as shown in Tables 1-2.

[0048] Table 1

[0049]

[0050]

[0051] Table 2

[0052]

[0053] The preparation method of the multiple-protected glabridin carrier provided by Example 1 comprises the following steps:

[0054] (1) Dissolve glabridin and polyols at 65℃ in a water bath to obtain phase A;

[0055] (2) Dissolve liquid emulsifiers, liquid oils, antioxidants and phospholipids at 70℃ in a water bath to obtain phase B;

[0056] (3) Heat water to 70℃ to obtain phase C;

[0057] (4) Mix phase A and phase B, then add phase C, homogenize at a speed of 2500 rpm for 4 min, and then perform cyclic shearing at a pressure of 600 bar and a temperature of 40℃ for 6 times to obtain the multiple-protected glabridin carrier.

[0058] The preparation process of examples 2-9 and comparative examples 1-13 and the preparation method of example 1 remain unchanged, and the relevant components are directly used without addition.

[0059] Comparative example 14

[0060] The comparative example of the present application provides a multiple-protected glabridin carrier. The difference between the comparative example and example 1 is not only the difference in components in table 2, but also the difference in preparation methods. The comparative example uses a solubilized method as a carrier. The preparation method of the comparative example is as follows:

[0061] (1) glabridin and polyol are mixed and dissolved in a 65°C water bath to obtain phase A;

[0062] (2) liquid emulsifier and antioxidant are mixed and dissolved in a 70°C water bath to obtain phase B;

[0063] (3) water is heated to 70°C to obtain phase C;

[0064] (4) phase A and phase B are mixed and then added to phase C, and homogenized at a speed of 1000 rpm for 30 min to obtain a multiple-protected glabridin carrier.

[0065] Comparative example 15

[0066] The comparative example of the present application provides a multiple-protected glabridin carrier. The only difference between the comparative example and example 1 is the difference in preparation processes. The preparation method of the comparative example is as follows:

[0067] (1) glabridin and polyol are mixed and dissolved in a 65°C water bath to obtain phase A;

[0068] (2) liquid emulsifier, liquid oil, antioxidant, and phospholipid are mixed and dissolved in a 70°C water bath to obtain phase B;

[0069] (3) water is heated to 70°C to obtain phase C;

[0070] (4) phase A and phase B are mixed and then added to phase C, and homogenized at a speed of 2500 rpm for 4 min to obtain a multiple-protected glabridin carrier.

[0071] Comparative example 16

[0072] The comparative example of the present application provides a multiple-protected glabridin carrier. The difference between the comparative example and example 1 is not only the difference in components in table 2, but also the difference in preparation methods. The comparative example uses a solubilized method as a carrier. The preparation method of the comparative example is as follows:

[0073] (1) glabridin and polyol are mixed and dissolved in a 65°C water bath to obtain phase A;

[0074] (2) mixed the cyclodextrin derivative and the balance of water at 70°C water bath to dissolve, obtained phase B;

[0075] (3) slowly added phase A to phase B, stirred at 1000 rpm for 30 min, obtained multiple-protected glabridin carrier.

[0076] Effect example

[0077] The effect example verifies the performance of the multiple-protected glabridin carrier prepared by examples 1-9 and comparative examples 1-16, specifically including the following aspects:

[0078] 1. Particle size, particle size distribution coefficient (PDI) determination: tested by nanoparticle size potential analyzer; the obtained results are shown in table 3;

[0079] Table 3

[0080] Particle size / nm PDI Particle size / nm PDI Particle size / nm PDI Example 1 58 0.652 Comparative Example 1 / / Comparative Example 10 / / Example 2 63 0.687 Comparative Example 2 / / Comparative Example 11 / / Example 3 98 0.832 Comparative Example 3 / / Comparative Example 12 156 0.732 Example 4 96 0.785 Comparative Example 4 / / Comparative Example 13 74 0.671 Example 5 73 0.705 Comparative Example 5 / / Comparative Example 14 / / Example 6 68 0.713 Comparative Example 6 / / Comparative Example 15 12000 0.813 Example 7 69 0.812 Comparative Example 7 / / Comparative Example 16 46 0.928 Example 8 75 0.698 Comparative Example 8 53 0.832 Example 9 70 0.802 Comparative Example 9 / /

[0081] In table 3, " / " indicates that the amphiphilic nanovesicle system of the multiple-protected glabridin carrier is not formed, so no corresponding particle size value and PDI value are given; specifically, comparative examples 1-7, 9-11 occur in the observation of austenitic ripening, and the stable nanovesicle carrier structure is not formed; in comparative example 14, the antioxidant and glabridin are solubilized in water by using solubilization, and the nanovesicle carrier structure is not formed, and occurs in the observation of austenitic ripening;

[0082] As can be seen from Table 3, the technical solutions of the present application can all obtain stable amphiphilic nanovesicle systems, the particle size of the obtained products is below 98 nm, and the PDI is below 0.832, that is, the particle size of the obtained products is small, and the particle size distribution is uniform; as can be seen from Examples 1-4 and Comparative Examples 1-5, when the mass parts of the components are changed, it is difficult to form a nanovesicle structure with small and uniform particle size and stability, and Austen aging is prone to occur; as can be seen from Examples 1 and Comparative Examples 6-10, when one of the components is not added, part of the obtained products undergoes Austen aging, and in Comparative Example 8, the addition of an antioxidant can form a stable nanovesicle structure, but the uniformity of the particle size distribution of the obtained nanovesicle structure shows a certain downward trend, and compared with Example 1, the PDI value increases by 27.61%; as can be seen from Examples 1, Examples 5-9 and Comparative Examples 11-13, the type of the components can also affect the performance of the products, when the type of the selected components is not in the present application, it is difficult to form a nanovesicle structure with small and uniform particle size and stability, and even in Comparative Example 10, when the type of the polyhydric alcohol is not selected in the present application, a stable nanovesicle structure cannot be formed; as can be seen from Examples 1 and Comparative Examples 14-16, the preparation method and carrier method of the products can also affect the performance of the products.

[0083] 2. Stability: The prepared multiple-protected glabridin carriers were respectively placed in normal temperature (25±0.5℃), high temperature (45±0.5℃), freezing (-15±0.5℃) and light (daylight) environments for 39 weeks, and after the placement was completed, the appearance and whether it was layered were observed, and the content of glabridin after 39 weeks of placement was detected by HPLC. Specifically, the glabridin HPLC content detection used an Agilent high-performance liquid chromatograph model 1100, and the obtained data was detected by QB / T 4951-2016 “Cosmetic raw materials: glabridin root extract”; the obtained data is shown in Table 4.

[0084] Table 4

[0085]

[0086]

[0087] As can be seen from Table 4, the product obtained by using the technical scheme of the present application has excellent stability, and no delamination and discoloration occurs after being placed for 39 weeks under normal temperature, high temperature, freezing or light, and the content of glabridin in the product is almost not reduced; as can be seen from Examples 1-4 and Comparative Examples 1-5, when the mass fraction of the components is changed, the comprehensive performance of the obtained product is also obviously reduced, and in Comparative Example 1-5, when the polyol, emulsifier, liquid oil, phospholipid or antioxidant is too much, discoloration or unstable phenomenon of austenitic ripening occurs, and the content of glabridin in the product is obviously reduced; as can be seen from Example 1 and Comparative Examples 6-10, when one of the components is not added, the comprehensive performance of the obtained product is also obviously reduced, and in Comparative Examples 6, 7, 9 and 10, when the emulsifier, liquid oil, polyol or phospholipid is not added, austenitic ripening is more likely to occur, and in Comparative Example 8, when the antioxidant is not added, discoloration is more likely to occur in the product, and the content of glabridin in the product is poor, especially under high temperature and light, the content of glabridin is significantly reduced; as can be seen from Example 1, Examples 5-9 and Comparative Examples 11-13, the type of the components also affects the performance of the product, and when the type of the selected components is replaced by other types of polyol, antioxidant or liquid oil, the stability performance or glabridin content performance of the obtained product is not good; as can be seen from Example 1 and Comparative Examples 14-16, the preparation method and carrier type of the product also affect the performance of the product.

[0088] 3. Transdermal penetration test: the pigskin is washed with distilled water, then washed with physiological saline, and dried with filter paper for standby; a Franz diffusion cell is used for transdermal experiment, the diffusion cell is kept at constant temperature (37℃) by a circulating water jacket, the skin is fixed between the supply chamber and the receiving cell, the surface of the skin faces the supply chamber, the effective penetration area S is 2.8 cm 2 , the receiving cell has a volume of 7.0 mL, the receiving liquid is physiological saline, 1.0 g of the multiple-protected glabridin carrier is uniformly applied to the surface of the skin in the supply chamber, and a magnetic stirrer is started to stir at a speed of 300 r / min; 0.5 mL of the receiving liquid is taken out at 1, 2, 3, 4, 5 and 6 h (after each sampling, an equal amount of physiological saline is added), the sample is centrifuged to obtain the supernatant, the content of glabridin is determined, and the cumulative transdermal drug release amount Q per unit area is calculated; the results are shown in Table 5;

[0089] Table 5

[0090]

[0091]

[0092] As can be seen from Table 5, the product obtained by using the technical scheme of the present application has excellent transdermal permeability, and the cumulative transdermal drug release amount at 6h is 28.21μg / cm 2 As can be seen from Examples 1-4 and Comparative Examples 1-5, when the mass parts of the components are changed, the transdermal drug release amount of the obtained product at each time node is reduced, and compared with Example 1, the cumulative transdermal drug release amount at 6h is greatly reduced; as can be seen from Example 1 and Comparative Examples 6-10, when one of the components is not added, specifically, when polyhydric alcohol, emulsifier, liquid oil, antioxidant or phospholipid is not added, the content of glabridin is reduced due to the instability of the product, thereby affecting the transdermal permeability, and compared with Example 1, the cumulative transdermal drug release amount at 6h is greatly reduced; as can be seen from Example 1 and Comparative Examples 11-13, the type of the components can also affect the performance of the product, when the type of the selected component is not in the present application, specifically, when other polyhydric alcohol, antioxidant or other solid oil is selected, the transdermal drug release amount of the obtained product is poor, and compared with Example 1, the cumulative transdermal drug release amount at 6h is greatly reduced; as can be seen from Example 1 and Comparative Examples 14-16, the preparation process and carrier mode of the product can also affect the performance of the product, when there is no subsequent step of cyclic shearing in Comparative Example 15, compared with Example 1, the cumulative transdermal drug release amount at 6h is reduced by 80.75%; when the common cyclodextrin derivative is used as the raw material in Comparative Example 16, compared with Example 1, the cumulative transdermal drug release amount at 6h is reduced by 77.63%.

[0093] Finally, it should be noted that the above examples are used to illustrate the technical scheme of the present application, but not to limit the protection scope of the present application, although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical scheme of the present application can be modified or replaced equivalently without departing from the essence and scope of the technical scheme of the present application.

Claims

1. A multiple protected glabrene carrier, characterized by, The multiple-protected glabridin carrier is composed of the following components in mass percentage: Glabridin 2-3%, polyhydric alcohol 30-35%, liquid emulsifier 2-5%, liquid oil 3-4%, antioxidant 0.2-0.3%, phospholipid 5-10%, water balance; The polyhydric alcohol is 1,3-butanediol; The antioxidant is tocopherol; The phospholipid is soybean lecithin; The liquid emulsifier is polysorbate-80; The liquid oil is caprylic / capric triglyceride; The preparation method of the multiple-protected glabridin carrier comprises the following steps: (1) mixing and dissolving glabridin and polyhydric alcohol to obtain phase A; (2) mixing and dissolving liquid emulsifier, liquid oil, antioxidant and phospholipid to obtain phase B; (3) heating water to obtain phase C; (4) mixing phase A and phase B, then adding phase C, homogenizing and circulating shearing to obtain the multiple-protected glabridin carrier; In step (4), the temperature of circulating shearing is 30-50℃, the pressure is 550-650 bar, and the number of times is 5-7.

2. Use of the multiple-protected glabridin carrier in claim 1 in the preparation of cosmetics.

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