Pterostilbene flexible liposome as well as preparation method and application thereof

Abstract

The invention relates to pterostilbene flexible liposome as well as a preparation method and application thereof. The pterostilbene flexible liposome is mainly prepared from the following components in percentage by mass: 0.5%-1.25% of pterostilbene, 2%-4% of phospholipid, 0.06%-0.2% of cholesterol, 1%-2.5% of an emulsifying agent, 0.1%-0.6% of a membrane softening agent, 5.08%-12.1% of an auxiliary agent and 79.35%-91.26% of water, the emulsifier is a single-chain surfactant; the membrane softener is dipotassium glycyrrhizinate. The pterostilbene flexible liposome has good solubility in water, is mild to a human body, has good skin physiological effects of oxidation resistance, whitening, aging resistance and inflammation resistance, has good stability and good transdermal property, can penetrate through a skin surface layer to reach a deep layer and slowly release pterostilbene to play a role, improves the dose-effect relationship and bioavailability of pterostilbene, and has a good application prospect. The composition can be well used in the field of cosmetics.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, and particularly relates to a pterostilbene flexible liposome and its preparation method and application. Background Art

[0002] Pterostilbene (Pt), with the chemical name of (E)-3,5-dimethoxy-4'-hydroxystilbene, is naturally derived from plants such as Pterocarpus santalinus, blueberries, and Ormosia henryi. It is a compound in which two hydroxyl groups of resveratrol are replaced by methoxy groups, and it is also one of the metabolites of resveratrol in the human body. Its liposolubility and chemical properties are better than those of resveratrol. Compared with the 20% bioavailability of resveratrol, the bioavailability of pterostilbene can reach 80%, so it is called the second-generation "resveratrol". Pterostilbene has good skin physiological effects of antioxidant, whitening, anti-aging, and anti-inflammatory, but its water solubility is poor and it is almost insoluble in water, so its application in cosmetics is less.

[0003] To address the problem of the application limitations of pterostilbene in cosmetics, traditional methods mainly involve preparing pterostilbene into forms such as liposomes, nanoemulsions, or submicrons. These products contain a large amount of emulsifiers, co-emulsifiers, and polyols, which may cause irritation to the skin after long-term use. Moreover, the particle sizes of the prepared liposomes, nanoemulsions, or submicron products are much larger than the skin pores, and they have no deformation ability and are difficult to penetrate the skin to reach the deep layer, making it difficult to play a role. Summary of the Invention

[0004] Based on this, the purpose of the present invention is to provide a pterostilbene flexible liposome with good water solubility, good transdermal permeability, good stability, and mildness to the human body, which can be applied to cosmetics.

[0005] The technical solution is as follows:

[0006] A pterostilbene flexible liposome is mainly made of the following components in mass percentage:

[0007]

[0008] The emulsifier is a single-chain surfactant;

[0009] The film softener is dipotassium glycyrrhizinate.

[0010] In one embodiment, the emulsifier is selected from one or a combination of several of cetearyl glucoside, methyl glucoside sesquistearate, ceteth-20, steareth-21, cetearyl alcohol polyether-25, oleth-20, and behenyl alcohol polyether-25.

[0011] In one embodiment, the phospholipid is selected from one or a combination of several of injection-grade soybean phospholipid PC90, phospholipid PC50, phospholipid PC90G, phospholipid S45, and large phospholipid S75.

[0012] In one embodiment, the auxiliary agents include one or a combination of several of a stabilizer, an antioxidant, and a preservative.

[0013] In one embodiment, the pterostilbene flexible liposome is mainly made of the following components by mass percentage:

[0014]

[0015] In one embodiment, the stabilizer is glycerol.

[0016] In one embodiment, the antioxidant is pentaerythritol tetra(bis-tert-butylhydroxyhydrocinnamate).

[0017] In one embodiment, the preservative is selected from one or a combination of two of p-hydroxyacetophenone and pentanediol.

[0018] In one embodiment, the pterostilbene flexible liposome is a light blue transparent liquid, with a particle size of 20 nm to 200 nm, a PDI of 0.1 to 0.5, and an encapsulation efficiency of more than 90%.

[0019] The present invention also provides a preparation method of the pterostilbene flexible liposome as described above, and the technical solution is as follows:

[0020] A preparation method of a pterostilbene flexible liposome includes the following steps:

[0021] Mix the components used to prepare the pterostilbene flexible liposome.

[0022] In one embodiment, the preparation method of the pterostilbene flexible liposome includes the following steps:

[0023] Mix the phospholipid, cholesterol, emulsifier, and part of the auxiliary agents in an alcohol solvent to prepare an oil-phase mixture;

[0024] Mix the film softener and part of the auxiliary agents in water to prepare an aqueous-phase mixture;

[0025] Mix the oil-phase mixture and the aqueous-phase mixture, and perform a first homogenization treatment to prepare a primary emulsion;

[0026] Perform a second homogenization treatment on the primary emulsion.

[0027] In one embodiment, the alcohol solvent is ethanol.

[0028] In one embodiment, when preparing the oil-phase mixture, the temperature of the system is 40°C to 70°C.

[0029] In one embodiment, the first homogenization treatment is homogenization treatment by a homogenizer, or stirring treatment by a stirrer or magnetic stirring treatment.

[0030] In one embodiment, the first homogenization treatment is homogenization treatment by a homogenizer, and the rotation speed of the homogenization treatment by the homogenizer is 3000 rpm to 6000 rpm, and the time is 20 min to 1 h.

[0031] In one embodiment, the first homogenization treatment is stirring treatment by a stirrer, and the rotation speed of the stirring treatment by the stirrer is 300 rpm to 600 rpm, and the time is 20 min to 1 h.

[0032] In one embodiment, the first homogenization treatment is magnetic stirring treatment, and the rotation speed of the magnetic stirring treatment is 300 rpm to 600 rpm, and the time is 20 min to 1 h.

[0033] In one embodiment, the second homogenization treatment of the colostrum includes the following steps:

[0034] Prepare pterostilbene flexible liposomes with an alcohol solvent mass content ≤ 5%;

[0035] Perform at least one of multiple high-pressure homogenization treatments, atmospheric pressure homogenization treatments, stirring treatments by a stirrer, and magnetic stirring treatments on the pterostilbene flexible liposomes with an alcohol solvent mass content ≤ 5%.

[0036] In one embodiment, the preparation of pterostilbene flexible liposomes with an alcohol solvent mass content ≤ 5% includes the following steps:

[0037] Perform decompression concentration treatment on the colostrum to prepare pterostilbene flexible liposomes with an alcohol solvent mass content ≤ 5%.

[0038] In one embodiment, the temperature of the decompression concentration treatment is 40°C to 70°C.

[0039] In one embodiment, the pressure of the high-pressure homogenization treatment is 400 bar to 700 bar, and the number of homogenization times is 3 to 5 times.

[0040] The present invention also provides the application of the pterostilbene flexible liposomes as described above. The technical solution is as follows:

[0041] A cosmetic, characterized in that it includes the pterostilbene flexible liposomes as described above.

[0042] In one of the embodiments, the cosmetic product is selected from at least one of a facial mask, eye cream, facial cream, primer, essence, lotion and skin softener.

[0043] The present invention has at least the following beneficial effects:

[0044] The pterostilbene flexible liposome provided by the present invention comprises phospholipids, cholesterol, an emulsifier, pterostilbene, a membrane softener, an auxiliary agent and water in specific mass percentages. The emulsifier is a single-chain surfactant, and the membrane softener is dipotassium glycyrrhizinate. The present invention mainly realizes the purpose of regulating the deformation ability and fluidity of the flexible liposome through the combined action of dipotassium glycyrrhizinate and the single-chain surfactant. Among them, while regulating the deformation ability of the flexible liposome, the single-chain surfactant greatly reduces the particle size and PDI of the liposome, improves its transdermal absorption, can easily penetrate through the skin to reach the deep layer and effectively play a role; while increasing the deformation ability and fluidity of the flexible liposome, dipotassium glycyrrhizinate can also be used as an anti-inflammatory substance, making up for the possible irritation caused by only using the single-chain surfactant to increase the deformation ability of the flexible liposome. Moreover, the pterostilbene flexible liposome of the present invention does not need to use a large amount of emulsifier, co-emulsifier and polyol, and can avoid the problem of irritating the skin after long-term use.

[0045] It has been confirmed that the pterostilbene flexible liposome provided by the present invention has good solubility in water, is mild to the human body, has good skin physiological effects of antioxidant, whitening, anti-aging and anti-inflammatory, has good stability, is relatively stable under the condition of 4°C, and there are no obvious changes in the particle size, PDI and Zeta potential measured at 0 day, 7 days, 14 days, 30 days and 60 days. It has good transdermal property, and has obvious better transdermal advantages compared with ordinary liposomes and free pterostilbene solutions with the same concentration. It can penetrate through the skin surface layer to reach the deep layer and slowly release pterostilbene to play a role, improving the dose-effect relationship and bioavailability of pterostilbene. In view of the above-mentioned many advantages of the pterostilbene flexible liposome, it can be well used in the cosmetic field.

[0046] In addition, the preparation method of the pterostilbene flexible liposome of the present invention is simple, easy for industrial production, and at the same time the reaction conditions are mild, and the degree of mechanization of the whole process is high, so that the product quality and process have good reproducibility and stability. Description of the Drawings

[0047] Figure 1 is a preparation method of a pterostilbene flexible liposome of the present invention;

[0048] Figure 2 is a particle size distribution diagram of the pterostilbene flexible liposome prepared in Example 8;

[0049] Figure 3The percutaneous absorption curves of pterostilbene flexible liposomes prepared in Example 12, pterostilbene conventional liposomes in Comparative Example 2, and 1% pterostilbene GTCC solution;

[0050] Figure 4 Comparison of skin retention amounts of pterostilbene flexible liposomes prepared in Example 12, pterostilbene conventional liposomes in Comparative Example 2, and 1% pterostilbene GTCC solution. Detailed implementation manners

[0051] The present invention will be further described in detail below in conjunction with specific embodiments. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, these embodiments are provided to make the understanding of the disclosed content of the present invention more thorough and comprehensive.

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention herein are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0053] In the present invention, "above" and "below" both include the number itself. For example, below 1 means ≥1.

[0054] In the present invention, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are considered continuous and include the minimum and maximum values of the range, as well as each value between such minimum and maximum values. Further, when the range refers to an integer, it includes each integer between the minimum and maximum values of the range. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed in the present invention should be understood to include any and all sub-ranges subsumed therein.

[0055] In the present invention, for the units of data ranges, if the unit is only attached after the right endpoint, it means that the units of the left endpoint and the right endpoint are the same. For example, 800~850nm means that the units of the left endpoint "800" and the right endpoint "850" are both nm (nanometers).

[0056] In the present invention, for temperature parameters, unless otherwise specified, both constant temperature treatment and treatment within a certain temperature range are allowed. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument.

[0057] In the present invention, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one such feature. In the description of the invention, the meaning of "at least one" is one, two, or more than two, the meaning of "several" and "multiple" is at least two, such as two, three, etc., unless otherwise specifically defined. In the description of the present application, the meaning of "several" is at least one, such as one, two, etc., unless otherwise specifically defined.

[0058] If there is no special instruction, all steps of the present invention can be carried out in sequence or randomly, and preferably in sequence. For example, the method includes steps (a) and (b), which means that the method may include steps (a) and (b) carried out in sequence, or may also include steps (b) and (a) carried out in sequence. For example, it is mentioned that the method may further include step (c), which means that step (c) can be added to the method in any order. For example, the method may include steps (a), (b), and (c), or may also include steps (a), (c), and (b), or may also include steps (c), (a), and (b), etc.

[0059] In the present invention, unless otherwise mentioned, terms in the singular form may include the plural form and should not be construed as having a quantity of one.

[0060] In addition, the drawings of the present invention are not drawn to a scale of 1:1, and the relative sizes of the components are only drawn by way of example in the drawings for the convenience of understanding the present invention, but are not necessarily drawn to the actual scale. The scale in the drawings does not constitute a limitation to the present invention.

[0061] Pterostilbene (Pt), with the chemical name of (E)-3,5-dimethoxy-4'-hydroxystilbene, is naturally derived from plants such as Pterocarpus indicus, blueberries, and Ormosia henryi. It is a compound in which two hydroxyl groups of resveratrol are replaced by methoxy groups, and its bioavailability can reach 80%. Pterostilbene has good skin physiological effects of antioxidant, whitening, anti-aging, and anti-inflammatory, but its water solubility is poor and it is almost insoluble in water, so its application in cosmetics is less.

[0062] In view of the limitations of pterostilbene in the application of cosmetics, carrier technologies such as liposomes have begun to be applied to cosmetics, significantly improving the water solubility, stability, and transdermal ability of substances. Traditional methods mainly involve preparing pterostilbene in the form of liposomes, nanoemulsions, or submicrons. For example, it has been reported that pterostilbene is encapsulated in the form of submicron lipid particles, which mainly consist of pterostilbene, lipids, emulsifiers, co-emulsifiers, stabilizers, and water, with a particle size of about 100 - 500 nm. Or a liposome that dissolves pterostilbene in liquid oil, using 1 - 8 parts of hydrogenated lecithin as the emulsifier, 30 - 80 parts of polyol as the co-emulsifier and stabilizer, which is essentially still closer to a nanoemulsion. Or a pterostilbene nanoemulsion, with a composition of 0.1 - 25 parts of pterostilbene, 1 - 10 parts of liquid oil, 5 - 35 parts of emulsifier, and 3 - 20 parts of polyol, with a particle size of about 200 - 400 nm. These products contain a large amount of emulsifiers, co-emulsifiers, and polyols, which may cause irritation to the skin after long-term use. Moreover, the particle sizes of the prepared liposomes, nanoemulsions, or submicron products are much larger than the skin pores, and they have no deformation ability and are difficult to penetrate the skin to reach the deep layer, making it difficult to play a role.

[0063] In addition, pterostilbene has poor photo-stability. Under ultraviolet irradiation, its trans configuration is easily converted into a cis configuration without obvious biological activity, which may be the result of the phenolic hydroxyl group of pterostilbene being easily oxidized.

[0064] In summary, pterostilbene, as a cosmetic efficacy raw material with good antioxidant, whitening, anti-aging and other skin physiological effects, has limitations such as poor water solubility, instability, and easy isomerization. In order to enable good application of pterostilbene, the present invention prepares it into flexible liposomes, which can not only improve the solubility and stability of pterostilbene in water, but also increase the transdermal absorption performance of pterostilbene, be able to penetrate through the skin surface to reach the deep layer and slowly release pterostilbene to play a role, and improve the dose-effect relationship and bioavailability of pterostilbene.

[0065] The technical solution is as follows:

[0066] A pterostilbene flexible liposome is mainly made of the following components by mass percentage:

[0067]

[0068] The emulsifier is a single-chain surfactant;

[0069] The film softener is dipotassium glycyrrhizinate.

[0070] The present invention mainly realizes the purpose of regulating the deformation ability and fluidity of flexible liposomes through the combined action of dipotassium glycyrrhizinate and single-chain surfactants. Among them, while regulating the deformation ability of flexible liposomes, the single-chain surfactant greatly reduces the particle size and PDI of liposomes, improves their transdermal absorption, and can easily penetrate the skin to reach the deep layer and effectively play a role; dipotassium glycyrrhizinate can increase the deformation ability and fluidity of flexible liposomes and can also act as an anti-inflammatory substance, making up for the possible irritation caused by only using a single-chain surfactant to increase the deformation ability of flexible liposomes. Moreover, the pterostilbene flexible liposomes of the present invention do not need to use a large amount of emulsifiers, co-emulsifiers, and polyols, and can avoid the problem of skin irritation caused by long-term use.

[0071] The present invention uses flexible liposomes to encapsulate pterostilbene, which not only effectively improves the poor water solubility and light-induced isomerization instability of pterostilbene itself, but also greatly increases the transdermal absorption performance of pterostilbene, enabling it to penetrate through the skin surface to reach the deep layer and form a drug reservoir, slowly releasing pterostilbene to continuously play a role and improving the dose-effect relationship and bioavailability of pterostilbene.

[0072] In the present invention, calculated by mass percentage, the pterostilbene flexible liposomes contain 0.5% - 1.25% of pterostilbene, including but not limited to 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2% or 1.25%.

[0073] In the present invention, calculated by mass percentage, the pterostilbene flexible liposomes also contain 2% - 4% of phospholipids, including but not limited to 2%, 2.5%, 3%, 3.5% or 4%, and preferably 3%.

[0074] In one of the embodiments, the phospholipid is selected from one or a combination of several of injection-grade soybean phospholipid PC90, phospholipid PC50, phospholipid PC90G, phospholipid S45, and large phospholipid S75.

[0075] In the present invention, calculated by mass percentage, the pterostilbene flexible liposomes also contain 0.06% - 0.2% of cholesterol, including but not limited to 0.06%, 0.07%, 0.075%, 0.08%, 0.09%, 0.1%, 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19% or 0.2%.

[0076] In the present invention, calculated by mass percentage, the pterostilbene flexible liposomes also contain 1% - 2.5% of emulsifier, including but not limited to 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4% or 2.5%.

[0077] In the present invention, the emulsifier is a single-chain surfactant, preferably a single-chain surfactant with an HLB value of 14 to 15, and the length of its hydrophobic carbon chain is comparable to that of its hydrophilic carbon chain, both being about 16 to 25 carbons. Further, the emulsifier is selected from one or a combination of several of cetearyl glucoside, methyl glucoside sesquistearate, ceteth-20, steareth-21, cetearyl alcohol polyether-25, oleth-20, and behenyl alcohol polyether-25. Even more preferably, the emulsifier is behenyl alcohol polyether-25, because when at least one of cetearyl glucoside, methyl glucoside sesquistearate, ceteth-20, steareth-21, cetearyl alcohol polyether-25, and oleth-20 is used as the emulsifier, the stability of the pterostilbene flexible liposome is poor, and soluble flocs may appear at high temperatures. However, when behenyl alcohol polyether-25 is used as the emulsifier, there is no such problem, and the pterostilbene flexible liposome is very stable under both high and low temperature conditions.

[0078] In the present invention, in terms of mass percentage, the pterostilbene flexible liposome further contains 0.1% to 0.6% of dipotassium glycyrrhizinate film softener, including but not limited to 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, or 0.6%. Preferably, in terms of mass percentage, the pterostilbene flexible liposome further contains 0.4% to 0.6% of dipotassium glycyrrhizinate film softener, which will have the effect of significantly increasing the deformation ability of the flexible liposome.

[0079] In the present invention, in terms of mass percentage, the pterostilbene flexible liposome further contains 5.08% to 12.1% of an auxiliary agent, including but not limited to 5.08%, 5.1%, 5.18%, 5.2%, 5.28%, 6%, 6.1%, 6.18%, 6.2%, 6.28%, 7%, 7.1%, 7.18%, 7.2%, 7.28%, 8%, 8.1%, 8.18%, 8.2%, 8.28%, 9%, 9.1%, 9.18%, 9.2%, 9.28%, 10%, 10.1%, 10.18%, 10.2%, 10.28%, 11%, 11.1%, 11.18%, 11.2%, 11.28%, 12%, 12.06%, 12.08%, or 12.1%.

[0080] In one embodiment, the auxiliary agent includes one or a combination of several of a stabilizer, an antioxidant, and a preservative. Further, the auxiliary agent includes a stabilizer, an antioxidant, and a preservative.

[0081] In one embodiment, the pterostilbene flexible liposome is mainly made of the following components in terms of mass percentage:

[0082]

[0083] Understandably, calculated by mass percentage, the pterostilbene flexible liposome contains 5% to 10% of a stabilizer, including but not limited to 5%, 6%, 7%, 8%, 9% or 10%.

[0084] In one embodiment, the stabilizer is glycerol. Glycerol can not only improve the freeze-thaw properties of the flexible liposome and be used as a stabilizer or protective agent, but also play a moisturizing effect and enhance the moisturizing property of the pterostilbene flexible liposome.

[0085] Understandably, calculated by mass percentage, the pterostilbene flexible liposome contains 0.03% to 0.05% of an antioxidant, including but not limited to 0.03%, 0.035%, 0.04%, 0.045% or 0.05%.

[0086] In one embodiment, the antioxidant is pentaerythrityl tetrakis (di-tert-butyl hydroxyhydrocinnamate).

[0087] Understandably, calculated by mass percentage, the pterostilbene flexible liposome contains 0.05% to 2.05% of a preservative, including but not limited to 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 1.1%, 1.18%, 1.2%, 1.28%, 1.3%, 1.31%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.03% or 2.05%.

[0088] In one embodiment, the preservative is selected from one or a combination of two of hydroxyacetophenone and pentylene glycol. Further, the preservative is a mixture of hydroxyacetophenone and pentylene glycol. Preferably, calculated by mass percentage, the pterostilbene flexible liposome contains 0.03% of hydroxyacetophenone and 2% of pentylene glycol.

[0089] In the present invention, calculated by mass percentage, the pterostilbene flexible liposome further contains 79.35% to 91.26% of water, including but not limited to 79.35%, 80%, 82%, 84%, 86%, 86.26%, 87.65%, 88%, 89%, 90% or 91.26%.

[0090] In one embodiment, the pterostilbene flexible liposome is a light blue transparent liquid, with a particle size of 20 nm to 200 nm, a PDI of 0.1 to 0.5, and an encapsulation efficiency of more than 90%. Further, the particle size of the pterostilbene flexible liposome is 40 nm to 70 nm.

[0091] Understandably, in one embodiment, the pterostilbene flexible liposome provided by the present invention can be written in the following form:

[0092] Phase A:

[0093]

[0094]

[0095] Phase B:

[0096] Glycerol 5% - 10%, Film softener 0.1% - 0.6%,

[0097] Deionized water 80.35% - 88.26%;

[0098] Phase C:

[0099] p - Hydroxyacetophenone 0.05%,

[0100] Pentylene glycol 2%.

[0101] In one embodiment, the pterostilbene flexible liposome is composed of the following components by mass percentage: Phase A:

[0102]

[0103] Phase B:

[0104] Glycerol 10%,

[0105] Dipotassium glycyrrhizinate 0.6%,

[0106] Deionized water the balance;

[0107] Phase C:

[0108] p - Hydroxyacetophenone 0.05%,

[0109] Pentylene glycol 2%.

[0110] The present invention also provides a preparation method of the pterostilbene flexible liposome as described above, and the technical solution is as follows:

[0111] A preparation method of a pterostilbene flexible liposome, comprising the following steps:

[0112] Mix the components for preparing the pterostilbene flexible liposome.

[0113] In one embodiment, the preparation method of the pterostilbene flexible liposome comprises the following steps: Mix the phospholipid, cholesterol, emulsifier and part of the auxiliaries in an alcohol solvent to prepare an oil - phase mixture; Mix the film softener and part of the auxiliaries in water to prepare an aqueous - phase mixture;

[0114] Mix the oil-phase mixture with the water-phase mixture and perform a first homogenization treatment to prepare a primary emulsion; perform a second homogenization treatment on the primary emulsion.

[0115] In one embodiment, the alcohol solvent is ethanol.

[0116] In the present invention, by mass percentage, the addition amount of the alcohol solvent accounts for 5% - 23.7% of pterostilbene flexible liposomes, including but not limited to 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23% or 23.7%.

[0117] In one embodiment, when preparing the oil-phase mixture, the temperature of the system is 40°C - 70°C.

[0118] In one embodiment, the first homogenization treatment is homogenization treatment by a homogenizer, or stirring treatment by a stirrer or magnetic stirring treatment.

[0119] In one embodiment, the first homogenization treatment is homogenization treatment by a homogenizer. Further, the rotation speed of the homogenization treatment by the homogenizer is 3000 rpm - 6000 rpm, and the time is 20 min - 1 h. It can be understood that the rotation speed of the homogenization treatment by the homogenizer includes but not limited to 3000 rpm, 4000 rpm, 5000 rpm or 6000 rpm; the time includes but not limited to 20 min, 30 min, 40 min, 50 min or 1 h.

[0120] In one embodiment, the first homogenization treatment is stirring treatment by a stirrer. Further, for the first homogenization treatment, the rotation speed of the stirring treatment by the stirrer is 300 rpm - 600 rpm, and the time is 20 min - 1 h. It can be understood that for the first homogenization treatment, the rotation speed of the stirring treatment by the stirrer includes but not limited to 300 rpm, 400 rpm, 500 rpm or 600 rpm; the time includes but not limited to 20 min, 30 min, 40 min, 50 min or 1 h.

[0121] In one embodiment, the first homogenization treatment is magnetic stirring treatment. Further, for the first homogenization treatment, the rotation speed of the magnetic stirring treatment is 300 rpm - 600 rpm, and the time is 20 min - 1 h. It can be understood that for the first homogenization treatment, the rotation speed of the magnetic stirring treatment includes but not limited to 300 rpm, 400 rpm, 500 rpm or 600 rpm; the time includes but not limited to 20 min, 30 min, 40 min, 50 min or 1 h.

[0122] In one embodiment, the second homogenization treatment of the colostrum comprises the following steps:

[0123] Prepare pterostilbene flexible liposomes with an alcohol solvent mass content of ≤5%;

[0124] Perform at least one of multiple high-pressure homogenization treatments, atmospheric pressure homogenization treatments, stirrer stirring treatments, and magnetic stirring treatments on the pterostilbene flexible liposomes with an alcohol solvent mass content of ≤5%.

[0125] In one embodiment, the preparation of pterostilbene flexible liposomes with an alcohol solvent mass content of ≤5% comprises the following steps:

[0126] Perform decompression concentration treatment on the colostrum to prepare pterostilbene flexible liposomes with an alcohol solvent mass content of ≤5%.

[0127] In one embodiment, the temperature of the decompression concentration treatment is 40°C to 70°C. Further, the decompression concentration treatment is rotary evaporation treatment.

[0128] In one embodiment, the second homogenization treatment is high-pressure homogenization treatment, which is beneficial to reducing the particle size of pterostilbene flexible liposomes. Further, the pressure of the high-pressure homogenization treatment is 400 bar to 700 bar, and the number of homogenization times is 3 to 5 times. It can be understood that the pressure of the high-pressure homogenization treatment includes but is not limited to 400 bar, 500 bar, 600 bar, or 700 bar; the number of homogenization times includes but is not limited to 3 times, 4 times, or 5 times.

[0129] It has been found through research that (1) for the scheme of selecting a high ethanol content (>5%, such as 23.7%) when preparing pterostilbene flexible liposomes in the present invention, ethanol can be removed by rotary evaporation first, and then homogenization treatment is carried out. At least one of high-pressure homogenization, atmospheric pressure homogenization, stirrer stirring, and magnetic stirring is used as the homogenization means. If high-pressure homogenization is not carried out, the particle size of the prepared pterostilbene flexible liposomes is 100 nm to 200 nm. At this time, the rotation speed and duration of the first homogenization treatment are the main factors determining the particle size of pterostilbene flexible liposomes. (2) For the scheme of selecting a low ethanol content (such as 5%) when preparing pterostilbene flexible liposomes in the present invention, rotary evaporation can be omitted, and the first and second homogenization treatments are directly carried out on the colostrum. At least two of high-pressure homogenization, atmospheric pressure homogenization, stirrer stirring, and magnetic stirring are used as the homogenization means. At this time, the parameters of the second homogenization treatment are the main factors determining the particle size of pterostilbene flexible liposomes. Preferably, the second homogenization treatment is multiple high-pressure homogenization treatments, which is the key step determining the particle size of pterostilbene flexible liposomes. Generally speaking, the second homogenization treatment being high-pressure homogenization treatment is more beneficial to reducing the particle size of pterostilbene flexible liposomes.

[0130] Understandably, after the step of homogenizing the colostrum, the alcohol solvent is removed, and water needs to be added to make up for the amount of the alcohol solvent so that the sum of the mass percentages of the added components is 100%.

[0131] Preferably, the pterostilbene flexible liposomes of the present invention are prepared by the ethanol injection method combined with the high-pressure homogenization method. The preparation method is simple, rapid, and the process is simple, which is suitable for large-scale industrial production.

[0132] In one embodiment, the preparation method of the pterostilbene flexible liposomes includes the following steps:

[0133] (1) Weigh phospholipids, cholesterol, and emulsifier and place them in a beaker. Add anhydrous ethanol and heat to dissolve. After dissolution, add pterostilbene, and after dissolution, add an antioxidant and continue to dissolve. After the solution is clear and transparent, it is used as the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in deionized water as the water phase;

[0134] (2) Slowly drop the dissolved oil phase into the water phase while homogenizing with a homogenizer at 5000 rpm for 20 min to 1 h to obtain the primary emulsion; if the mass content of the added ethanol > 5%, for example, 23.7 g, then the ethanol needs to be removed by rotary evaporation first. If the ethanol content added ≤ 5%, for example, 5 g, then directly pour the primary emulsion into a high-pressure homogenizer for homogenization;

[0135] (3) After the pterostilbene flexible liposomes are cooled to room temperature, add the previously dissolved phase C.

[0136] Figure 1 This is a preparation method of the pterostilbene flexible liposomes of the present invention.

[0137] The present invention also provides the application of the pterostilbene flexible liposomes as described above. The technical solution is as follows:

[0138] A cosmetic, characterized in that it includes the pterostilbene flexible liposomes as described above.

[0139] In one embodiment, the cosmetic is selected from at least one of a facial mask, eye cream, facial cream, primer, essence, lotion, and skin softener.

[0140] The following is the specific embodiment part.

[0141] Unless otherwise specified, all raw materials are commercially available products.

[0142] In the following examples and comparative examples, the weights of all raw materials are weighed in g.

[0143] In the following examples and comparative examples, the particle size is measured using a Malvern laser particle size analyzer, the 45-degree Celsius environment is an oven, and whether the drug leaks is observed with the naked eye.

[0144] Example 1

[0145] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0146] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0147] Phase A:

[0148]

[0149] Phase B:

[0150] Glycerol 8.5%,

[0151] Dipotassium glycyrrhizinate 0.4%,

[0152] Deionized water q.s.;

[0153] Phase C:

[0154] p-Hydroxyacetophenone 0.05%,

[0155] Pentylene glycol 2%.

[0156] (2) Preparation of the pterostilbene flexible liposome:

[0157] 1) Weigh S45 phospholipid, cholesterol, and polyoxyethylene 25 behenyl ether and place them in a beaker. Add 5 g of absolute ethanol, heat and dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the water phase;

[0158] 2) Slowly drip the dissolved oil phase into the water phase while homogenizing at a speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 3 times under a pressure of 500 bar;

[0159] 3) Add the pre-dissolved Phase C and stir well;

[0160] The particle size of the pterostilbene flexible liposome prepared in this example is (61.05 ± 0.49) nm, the PDI is (0.2421 ± 0.02), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a dark environment for 60 days. However, drug leakage occurs after storing at 45 °C for 60 days.

[0161] Example 2

[0162] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0163] (1) The pterostilbene flexible liposome is composed of the following components by mass percentage:

[0164] Phase A:

[0165]

[0166] Phase B:

[0167] Glycerol 10%,

[0168] Dipotassium glycyrrhizinate 0.1%,

[0169] Deionized water q.s.;

[0170] Phase C:

[0171] p-Hydroxyacetophenone 0.05%,

[0172] Pentylene glycol 2%.

[0173] (2) Preparation of pterostilbene flexible liposome:

[0174] 1) Weigh PC90G phospholipid, cholesterol, and steareth-21 and place them in a beaker. Add 23.7 g of absolute ethanol, heat and dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate), and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the water phase;

[0175] 2) Slowly drip the dissolved oil phase into the water phase while homogenizing at a speed of 5000 rpm for 20 min to obtain the primary emulsion. After rotary evaporation to remove ethanol at 50 °C, add 23.7 mL of water to make up for the amount of ethanol; pour it into a high-pressure homogenizer and homogenize 5 times at a pressure of 600 bar;

[0176] 3) Add the pre-dissolved Phase C and stir well;

[0177] The particle size of the pterostilbene flexible liposome prepared in this example is (27.93 ± 0.17) nm, the PDI is (0.1997 ± 0.01), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storage at 4 °C, room temperature, or -15 °C for 60 days, freeze-thawing (one day at -15 °C, one day at 45 °C) for 16 times, light storage for 60 days, and storage in a dark environment for 60 days. Flocculation occurs after being placed at 45 °C for about 3 days.

[0178] Example 3

[0179] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0180] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0181] Phase A:

[0182]

[0183]

[0184] Phase B:

[0185] Glycerol 10%,

[0186] Dipotassium glycyrrhizinate 0.1%,

[0187] Deionized water q.s.;

[0188] Phase C:

[0189] p-Hydroxyacetophenone 0.05%,

[0190] Pentylene glycol 2%.

[0191] (2) Preparation of the pterostilbene flexible liposome:

[0192] 1) Weigh PC90 G phospholipid, cholesterol, and cetostearyl polyether-25 and place them in a beaker. Add 23.7 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythritol tetra(bis-tert-butyl hydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the water phase;

[0193] 2) Slowly drip the dissolved oil phase into the water phase at a constant speed and homogenize at a speed of 5000 rpm for 20 min to obtain the primary emulsion. After rotary evaporation to remove ethanol at 50 °C, add 23.7 mL of water to make up for the amount of ethanol; pour the primary emulsion into a high-pressure homogenizer and homogenize 5 times at a pressure of 600 bar;

[0194] 3) Add the pre-dissolved Phase C and stir well;

[0195] The particle size of the pterostilbene flexible liposome prepared in this example is (26.6 ± 0.49) nm, the PDI is (0.370 ± 0.02), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storage at 4 °C, room temperature, or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, light storage for 60 days, and storage in a dark environment for 60 days. Soluble flocculants appear after being placed at 45 °C for about 3 days.

[0196] Example 4

[0197] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0198] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0199] Phase A:

[0200]

[0201] Phase B:

[0202] Glycerol 10%,

[0203] Dipotassium glycyrrhizinate 0.1%,

[0204] Deionized water in the balance;

[0205] Phase C:

[0206] p-Hydroxyacetophenone 0.05%,

[0207] Pentylene glycol 2%.

[0208] (2) Preparation of the pterostilbene flexible liposome:

[0209] 1) Weigh PC90 G phospholipid, cholesterol, and ceteth-20 and place them in a beaker. Add 23.7 g of absolute ethanol, heat and dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the water phase;

[0210] 2) Slowly drip the dissolved oil phase into the water phase while homogenizing at a speed of 5000 rpm for 20 min to obtain the primary emulsion. After rotary evaporation to remove ethanol at 50 °C, add 23.7 mL of water to make up for the amount of ethanol after homogenization; pour the primary emulsion into a high-pressure homogenizer and homogenize 5 times at a pressure of 600 bar,

[0211] 3) Add the pre-dissolved Phase C and stir well;

[0212] The particle size of the pterostilbene flexible liposome prepared in this example is (22.23 ± 0.047) nm, the PDI is (0.2007 ± 0.007), and the stability is good. There is no drug leakage, demulsification, flocculent substances, etc. after storing at 4 °C, room temperature, or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a light-proof environment for 60 days. Soluble flocculent substances appear after placing at 45 °C for about 3 days.

[0213] Example 5

[0214] This example provides a pterostilbene flexible liposome and its preparation method, specifically as follows:

[0215] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0216] Phase A:

[0217]

[0218] Phase B:

[0219] Glycerol 10%,

[0220] Dipotassium glycyrrhizinate 0.1%,

[0221] Deionized water in the balance;

[0222] Phase C:

[0223] p-Hydroxyacetophenone 0.05%,

[0224] Pentylene glycol 2%.

[0225] (2) Preparation of the pterostilbene flexible liposome:

[0226] 1) Weigh PC90G phospholipid, cholesterol, and polyoxyethylene oleyl ether - 20 and place them in a beaker. Add 23.7 g of absolute ethanol, heat and dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis - tert - butylhydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the water phase;

[0227] 2) Slowly drip the dissolved oil phase into the water phase at a constant speed, homogenize at a speed of 5000 rpm for 20 min to obtain the primary emulsion. After rotary evaporation to remove ethanol at 50 °C, add 23.7 mL of water to make up for the amount of ethanol; pour the primary emulsion into a high - pressure homogenizer and homogenize 5 times at a pressure of 600 bar;

[0228] 3) Add the pre - dissolved Phase C and stir well;

[0229] The particle size of the pterostilbene flexible liposome prepared in this example is (22.27 ± 0.17) nm, the PDI is (0.331 ± 0.012), and the stability is good. When stored at 4 °C, room temperature, or - 15 °C for 60 days, frozen and thawed (one day at - 15 °C and one day at 45 °C) 16 times, stored under light for 60 days, and stored in a dark environment for 60 days, there are no cases of drug leakage, demulsification, floccules, etc. Soluble floccules appear after being placed at 45 °C for about 3 days.

[0230] Example 6

[0231] This example provides a pterostilbene flexible liposome and its preparation method, specifically as follows:

[0232] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0233] Phase A:

[0234]

[0235] Phase B:

[0236] Glycerol 8.5%,

[0237] Dipotassium glycyrrhizinate 0.1%,

[0238] Deionized water q.s.;

[0239] Phase C:

[0240] p-Hydroxyacetophenone 0.05%,

[0241] Pentylene glycol 2%.

[0242] (2) Preparation of pterostilbene flexible liposomes:

[0243] 1) Weigh PC90G phospholipid, cholesterol, and polyoxyethylene 25 behenyl ether, place them in a beaker, add 5 g of absolute ethanol, heat and dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate), and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate in water to obtain the aqueous phase;

[0244] 2) Slowly drop the dissolved oil phase into the aqueous phase at a constant speed, and homogenize at a speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 3 times at a pressure of 600 bar;

[0245] 3) Add glycerol and the previously dissolved Phase C and stir well;

[0246] The particle size of the pterostilbene flexible liposomes prepared in this example is (70.7 ± 0.72) nm, the PDI is (0.4245 ± 0.008), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a dark environment for 60 days.

[0247] Example 7

[0248] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0249] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0250] Phase A:

[0251]

[0252] Phase B:

[0253] Glycerol 10%,

[0254] Dipotassium glycyrrhizinate 0.1%,

[0255] Deionized water q.s.;

[0256] Phase C:

[0257] p-Hydroxyacetophenone 0.05%,

[0258] Pentylene glycol 2%.

[0259] (2) Preparation of pterostilbene flexible liposomes:

[0260] 1) Weigh PC90G phospholipids, cholesterol, and beheneth-25 and place them in a beaker. Add 5 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase;

[0261] 2) Slowly drop the dissolved oil phase into the aqueous phase while homogenizing at a speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 3 times at a pressure of 600 bar;

[0262] 3) Add the pre-dissolved Phase C and stir well;

[0263] The particle size of the pterostilbene flexible liposomes prepared in this example is (51.15 ± 0.44) nm, the PDI is (0.2341 ± 0.003), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C, or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a light-proof environment for 60 days.

[0264] Example 8

[0265] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0266] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0267] Phase A:

[0268]

[0269] Phase B:

[0270] Glycerol 10%,

[0271] Dipotassium glycyrrhizinate 0.4%,

[0272] Deionized water q.s.;

[0273] Phase C:

[0274] p-Hydroxyacetophenone 0.05%,

[0275] Pentylene glycol 2%.

[0276] (2) Preparation of pterostilbene flexible liposomes:

[0277] 1) Weigh PC90G phospholipid, cholesterol, and beheneth-25 and place them in a beaker. Add 5 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene. After dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase;

[0278] 2) Slowly drip the dissolved oil phase into the aqueous phase while homogenizing at a rotation speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 3 times under a pressure of 400 bar.

[0279] 3) Add the pre-dissolved Phase C and stir well;

[0280] The particle size of the pterostilbene flexible liposomes prepared in this example is (58.92 ± 0.50) nm, the PDI is (0.1994 ± 0.0087), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C, or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a light-proof environment for 60 days.

[0281] Figure 2 It is the particle size distribution diagram of the pterostilbene flexible liposomes prepared in Example 8. It can be seen that the distribution is very narrow.

[0282] Example 9

[0283] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0284] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0285] Phase A:

[0286]

[0287] Phase B:

[0288] Glycerol 10%,

[0289] Dipotassium glycyrrhizinate 0.4%,

[0290] Deionized water q.s.;

[0291] Phase C:

[0292] p-Hydroxyacetophenone 0.05%,

[0293] Pentylene glycol 2%.

[0294] (2) Preparation of pterostilbene flexible liposomes:

[0295] 1) Weigh PC90 G phospholipid, cholesterol, and polyoxyethylene 25 behenyl ether and place them in a beaker. Add 5 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene. After dissolution, add pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase;

[0296] 2) Slowly drip the dissolved oil phase into the aqueous phase while homogenizing at a speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 5 times at a pressure of 700 bar;

[0297] 3) Add the pre-dissolved Phase C and stir well;

[0298] The particle size of the pterostilbene flexible liposomes prepared in this example is (45.44 ± 0.271) nm, the PDI is (0.1459 ± 0.0102), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a dark environment for 60 days.

[0299] Example 10

[0300] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0301] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0302] Phase A:

[0303]

[0304] Phase B:

[0305] Glycerol 10%,

[0306] Dipotassium glycyrrhizinate 0.6%,

[0307] Deionized water q.s.;

[0308] Phase C:

[0309] 4-Hydroxyacetophenone 0.05%,

[0310] Pentylene glycol 2%.

[0311] (2) Preparation of pterostilbene flexible liposomes:

[0312] 1) Weigh PC90G phospholipid, cholesterol, and beheneth-25 and place them in a beaker. Add 5 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butyl hydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase;

[0313] 2) Slowly drip the dissolved oil phase into the aqueous phase at a constant speed and homogenize at a rotation speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 4 times at a pressure of 500 bar;

[0314] 3) Add the pre-dissolved phase C and stir well;

[0315] The particle size of the pterostilbene flexible liposomes prepared in this example is (53.45 ± 0.105) nm, the PDI is (0.2397 ± 0.002), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a light-proof environment for 60 days.

[0316] Example 11

[0317] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0318] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0319] Phase A:

[0320]

[0321]

[0322] Phase B:

[0323] Glycerol 10%,

[0324] Dipotassium glycyrrhizinate 0.4%,

[0325] Deionized water q.s.;

[0326] Phase C:

[0327] 4-Hydroxyacetophenone 0.05%,

[0328] 2% pentylene glycol

[0329] (2) Preparation of pterostilbene flexible liposomes:

[0330] 1) Weigh PC90G phospholipid, cholesterol, and polyoxyethylene 25 behenyl ether, place them in a beaker, add 5 g of absolute ethanol, heat and dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butyl hydroxyhydrocinnamate), and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase.

[0331] 2) Slowly drip the dissolved oil phase into the aqueous phase at a constant speed, and homogenize at a speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 4 times under a pressure of 500 bar.

[0332] 3) Add the pre-dissolved phase C and stir well.

[0333] The particle size of the pterostilbene flexible liposomes prepared in this example is (54.36 ± 0.142) nm, the PDI is (0.2394 ± 0.010), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a light-proof environment for 60 days.

[0334] Example 12

[0335] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0336] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0337] Phase A:

[0338]

[0339] Phase B:

[0340] 10% glycerol

[0341] 0.6% dipotassium glycyrrhizinate

[0342] The balance is deionized water;

[0343] Phase C:

[0344] 0.05% p-hydroxyacetophenone

[0345] 2% pentylene glycol

[0346] (2) Preparation of pterostilbene flexible liposomes:

[0347] 1) Weigh PC90G phospholipid, cholesterol, and behenyl alcohol polyether-25 and place them in a beaker. Add 5 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butyl hydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase;

[0348] 2) Slowly drip the dissolved oil phase into the aqueous phase while homogenizing at a speed of 5000 rpm for 20 min to obtain the primary emulsion. Pour the primary emulsion into a high-pressure homogenizer and homogenize it 4 times at a pressure of 500 bar;

[0349] 3) Add the pre-dissolved Phase C and stir well;

[0350] The particle size of the pterostilbene flexible liposomes prepared in this example is (60.11 ± 0.54) nm, and the PDI is (0.2366 ± 0.003), with good stability.

[0351] Example 13

[0352] This example provides a pterostilbene flexible liposome and its preparation method, which are as follows:

[0353] (1) The pterostilbene flexible liposome is composed of the following components in mass percentage:

[0354] Phase A:

[0355]

[0356] Phase B:

[0357] Glycerol 10%,

[0358] Dipotassium glycyrrhizinate 0.4%,

[0359] Deionized water q.s.;

[0360] Phase C:

[0361] p-Hydroxyacetophenone 0.05%,

[0362] Pentylene glycol 2%.

[0363] (2) Prepare the pterostilbene flexible liposome:

[0364] 1) Weigh PC90G phospholipid, cholesterol, and behenyl alcohol polyether-25 and place them in a beaker. Add 5 g of absolute ethanol and heat to dissolve at 45 °C. After dissolution, add pterostilbene, and after dissolution, add pentaerythrityl tetra(bis-tert-butyl hydroxyhydrocinnamate) and continue to dissolve to obtain the oil phase; dissolve dipotassium glycyrrhizinate and glycerol in water to obtain the aqueous phase;

[0365] 2) Slowly and evenly add the dissolved oil phase dropwise to the aqueous phase, homogenize at a rotation speed of 5000 rpm for 20 min to obtain the primary emulsion, pour the primary emulsion into a high-pressure homogenizer, and perform high-pressure homogenization 4 times at a pressure of 500 bar;

[0366] 3) Add the pre-dissolved Phase C and stir well;

[0367] The particle size of the pterostilbene flexible liposomes prepared in this example is (50.03 ± 0.299) nm, the PDI is (0.2286 ± 0.0089), and the stability is good. There is no drug leakage, demulsification, flocculation, etc. after storing at 4 °C, room temperature, 45 °C or -15 °C for 60 days, freeze-thawing (one day at -15 °C and one day at 45 °C) 16 times, storing under light for 60 days, and storing in a light-proof environment for 60 days.

[0368] Comparative Example 1

[0369] This comparative example provides a pterostilbene flexible liposome and its preparation method. Compared with Example 13, the difference is only that Tween-80 is used to replace dipotassium glycyrrhizinate in Example 13, as shown in Table 1 below:

[0370] Table 1

[0371]

[0372] As can be seen from Table 1, the particle size of the pterostilbene flexible liposomes prepared using Tween-80 as the membrane softening agent is larger than that using dipotassium glycyrrhizinate as the membrane softening agent. Since the flexible liposomes pass through a 20-nm membrane under external force when testing the deformation ability by the thin film extrusion method, the smaller the particle size, the smaller the degree of deformation required, and the easier it is to pass through the membrane. Therefore, a smaller particle size has more advantages. If the particle size is large, in order to pursue high deformation ability, a high content of single-chain surfactant needs to be added, which may cause certain irritation to the skin. While using dipotassium glycyrrhizinate has a soothing effect, so dipotassium glycyrrhizinate is selected as the membrane softening agent.

[0373] Comparative Example 2, Comparative Example 3

[0374] Comparative Example 2 and Comparative Example 3 provide two pterostilbene flexible liposomes and their preparation methods. Compared with Example 13, the difference is only that Comparative Example 2 does not add dipotassium glycyrrhizinate in Example 13, and Comparative Example 3 adds an excessive amount of dipotassium glycyrrhizinate, as shown in Table 2 below:

[0375] Table 2

[0376]

[0377] Since the addition amount of dipotassium glycyrrhizinate is directly related to the deformation ability of flexible liposomes, instead of simply using particle size and PDI to characterize flexible liposomes, an index characterizing the deformation ability of flexible liposomes is added for screening. The film extrusion method is used to determine the flexibility of the lipid bilayer membrane of nano-liposomes. A 5 ml syringe is used to draw about 5 g of flexible liposomes respectively, and an external force of about 1.25 kg is applied to extrude the liposomes through a microporous membrane with a pore size of 20 nm, and the pressure is applied for 5 min. Finally, the deformation ability of the lipid membrane is evaluated by indicators such as particle size, polydispersity coefficient, the percentage of the mass of the original solution filtered through a single filter to the mass of the drawn filtrate, and the content of pterostilbene in the obtained filtrate. The pterostilbene flexible liposomes added with 0.4% dipotassium glycyrrhizinate have better deformation ability, and the dipotassium glycyrrhizinate with 0% addition amount also has a certain degree of deformation ability. This may be because beheneth-25 is a single-chain surfactant with a high radius of curvature, which also endows the flexible liposomes with a certain deformation ability. However, compared with the pterostilbene flexible liposomes with 0.4% dipotassium glycyrrhizinate, the deformation ability of the pterostilbene flexible liposomes without dipotassium glycyrrhizinate is much worse. An excessive addition amount of dipotassium glycyrrhizinate not only has no obvious promotion effect on the deformation ability of flexible liposomes after increasing the deformation ability to a certain extent, but will greatly reduce the stability of flexible liposomes. For example, the stop filtration time of the pterostilbene flexible liposomes prepared in Comparative Example 3 becomes 5 min, and the percentage of the filtrate mass to the inhaled liquid mass is not as high as that in Example 13. Moreover, the particle size of the flexible liposomes in Comparative Example 3 increases to about 200 nm after one freeze-thaw cycle, and the freeze-thaw stability is significantly deteriorated.

[0378] Comparative Example 4

[0379] This comparative example provides a pterostilbene flexible liposome and its preparation method. Compared with Example 13, the difference is only the addition amount of beheneth-25, as shown in Table 3 below:

[0380] Table 3

[0381]

[0382] Test

[0383] (1) Investigate the stability of liposomes:

[0384] The pterostilbene flexible liposomes prepared in Example 12 are stored at 4 °C in the refrigerator and at 25 °C at room temperature. The particle size, PDI and Zeta potential are measured on the 0th day, 7th day, 14th day, 30th day, 60th day, and 90th day respectively, and the appearance is observed to determine the stability. The results are shown in Table 4 and Table 5.

[0385] Table 4 Stability results of pterostilbene flexible liposomes at 4 °C

[0386]

[0387]

[0388] As can be seen from Table 4, the pterostilbene flexible liposomes are relatively stable at 4°C. There are no significant changes in the measured particle size, PDI, and Zeta potential at 0 day, 7 days, 14 days, 30 days, 60 days, and 90 days, indicating that the pterostilbene flexible liposomes have good stability.

[0389] Table 5 Stability results of pterostilbene flexible liposomes at 25°C

[0390] Time Particle size (nm) PDI Potential (mV) Day 0 60.11±0.542 0.2365±0.003 -10.16±0.536 Day 7 63.59±0.211 0.2342±0.005 -15.88±0.205 Day 14 56.67±0.260 0.1755±0.003 -8.020±0.649 Day 30 59.43±0.094 0.1938±0.007 -10.24±1.07 Day 60 62.11±0.265 0.2101±0.002 -12.46±0.970 Day 90 59.10±0.557 0.1588±0.010 -14.16±0.399

[0391] As can be seen from Table 5, the pterostilbene flexible liposomes are relatively stable at 4°C and 25°C. There are no significant changes in the measured particle size, PDI, and Zeta potential at 0 day, 7 days, 14 days, 30 days, 60 days, and 90 days, indicating that the pterostilbene flexible liposomes have good stability.

[0392] (2) Test the in vitro transdermal absorption performance of pterostilbene flexible liposomes:

[0393] Use a modified Franz diffusion cell. The upper chamber is the supply chamber, and the lower chamber is the receiving chamber. The volume of the receiving chamber is 12 mL, the inner diameter of the supply chamber is 1.5 cm, and the effective diffusion area is 1.767 cm 2 , with a constant temperature water bath at 37°C and magnetic stirring at a constant speed of 600 r / min. Fill the receiving chamber with the receiving solution (30% ethanol - physiological sodium chloride solution), fix the pig skin between the two chambers with the stratum corneum facing up, and make the dermis layer fully contact with the receiving solution to remove air bubbles. Add pterostilbene flexible liposomes with a high encapsulation efficiency to the supply chamber. Precisely withdraw 1 mL of the receiving sample from the sampling tube at 2, 4, 6, 8, 12, and 24 h respectively, and immediately replenish the corresponding amount of blank receiving solution to start removing air bubbles. The drug content of the sampled sample solution is determined by ultraviolet analysis, and the cumulative permeation amount per unit volume (Q n ) is calculated according to the following formula:

[0394]

[0395] In the formula: C n represents the drug concentration in the receiving solution at the nth time point, V represents the volume of the receiving chamber (12 mL), Ci represents the drug concentration in the corresponding receiving solution at the ith time point, Vi is the sampling volume corresponding to the ith time point, and A is the effective contact area (1.767 cm 2 .

[0396] After the transdermal experiment, the pig skin was taken out and repeatedly rinsed with saline to remove the residual drug and receptor solution. The surface liquid was dried with filter paper. The excess pig skin was removed and the pig skin at the effective contact area was cut into pieces with surgical scissors. 5 ml of anhydrous ethanol was added. After water bath ultrasound for 10 minutes, the skin was centrifuged at 10000 r / min for 10 minutes to calculate the skin retention amount Q s .

[0397] Figure 3 The percutaneous permeation and absorption curves of the pterostilbene flexible liposomes prepared in Example 12, Comparative Example 2 (pterostilbene ordinary liposomes), and 1% pterostilbene GTCC solution are shown. Figure 4 The skin retention amount of the pterostilbene flexible liposomes prepared in Example 12 is compared with that of Comparative Example 2 (pterostilbene ordinary liposomes) and 1% pterostilbene GTCC solution.

[0398] from Figure 3 , Figure 4 It can be seen that the transdermal permeability of the pterostilbene flexible liposome is stronger than that of the pterostilbene liposome and the pterostilbene GTCC solution. At 24 hours, the cumulative permeation amount of Example 12 is 2.57 times that of Example 2 and 6.22 times that of the pterostilbene GTCC solution. The skin retention amount of Example 12 is 2.99 times that of the skin retention amount of Example 2 and 16.52 times that of the skin retention amount of the pterostilbene GTCC solution. This is mainly because the flexible liposome increases the fluidity and deformation ability of the liposome membrane, thereby greatly increasing the transdermal absorption capacity of the liposome, which is conducive to the better function of the active ingredients.

[0399] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0400] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A pterostilbene flexible liposome, characterized in that, It is mainly made of the following components by mass percentage: The emulsifier is a single-chain surfactant; The film softener is dipotassium glycyrrhizinate.

2. The pterostilbene flexible liposome according to claim 1, wherein The emulsifier is selected from one or a combination of several of cetearyl glucoside, methyl glucoside sesquistearate, ceteth-20, steareth-21, cetearyl alcohol polyether-25, oleth-20, and beheneth-25.

3. The pterostilbene flexible liposome according to claim 1, wherein The phospholipid is selected from one or a combination of several of injection-grade soy phospholipid PC90, phospholipid PC50, phospholipid PC90 G, phospholipid S45, and large phospholipid S75.

4. The pterostilbene flexible liposome according to any one of claims 1 to 3, characterized in that The auxiliary agents include one or a combination of several of stabilizers, antioxidants, and preservatives.

5. The pterostilbene flexible liposome according to claim 4, wherein, It is mainly made of the following components by mass percentage:

6. The pterostilbene flexible liposome according to claim 5, wherein Meet at least one of the following (1) to (3): (1) The stabilizer is glycerol; (2) The antioxidant is pentaerythrityl tetra(bis-tert-butylhydroxyhydrocinnamate); (3) The preservative is selected from one or a combination of two of p-hydroxyacetophenone and pentylene glycol.

7. The pterostilbene flexible liposome according to any one of claims 1 to 3, characterized in that, The pterostilbene flexible liposome is a light blue transparent liquid, with a particle size of 20 nm to 200 nm, a PDI of 0.1 to 0.5, and an encapsulation efficiency of more than 90%.

8. A method for preparing the pterostilbene flexible liposome according to any one of claims 1 to 7, characterized in that, It includes the following steps: Mix the components used to prepare the pterostilbene flexible liposome.

9. The preparation method of pterostilbene flexible liposome according to claim 8, characterized in that, It includes the following steps: Mix the phospholipid, cholesterol, emulsifier, and part of the auxiliary agents in an alcohol solvent to prepare an oil-phase mixture; Mix the film softener and part of the auxiliary agents in water to prepare an aqueous-phase mixture; Mix the oil-phase mixture with the aqueous-phase mixture and perform the first homogenization treatment to prepare a primary emulsion; Perform a second homogenization treatment on the primary emulsion.

10. A cosmetic, characterized in that, It includes the pterostilbene flexible liposome according to any one of claims 1 to 7.

11. The cosmetic according to claim 10, characterized in that, The cosmetic is selected from at least one of facial masks, eye creams, face creams, primer, essence, lotions, and skin toners.

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