Pterostilbene liposome as well as preparation method and application thereof

Abstract

The invention relates to the technical field of cosmetics, in particular to pterostilbene lipidosome and a preparation method and application thereof.The pterostilbene lipidosome is at least prepared from, by mass, 40%-60% of glycerinum, 5%-15% of caprylic acid-capric triglyceride, 2%-4% of hydrogenated lecithin, 4%-7% of pterostilbene, 0.5%-1.5% of ascorbyl tetraisopalmitate, 0.6%-2.5% of alcohol solvent and the balance water. According to the pterostilbene lipidosome provided by the invention, by optimizing a lipidosome formula and a preparation process thereof, the stability of pterostilbene is effectively improved, the bioavailability is improved, the whitening effect is further improved, and the biological effect of the raw materials reaches the highest efficiency.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, in particular to a pterostilbene liposome and a preparation method and application thereof. Background Art

[0002] Pterostilbene is a structural homologue of resveratrol and a commonly used whitening ingredient with excellent antioxidant activity. However, pterostilbene still faces problems in cosmetic applications. It is unstable in light and air, and its phenolic hydroxyl groups are easily oxidized, thus losing its efficacy. Pterostilbene is highly lipid-soluble but very poorly water-soluble, with relatively low bioavailability. Moreover, excessive addition can cause skin irritation. Prior art methods address these issues with pterostilbene by preparing it into nanoformulations such as liposomes, nanoemulsions, lipid nanocapsules, or lipid nanoparticles. A Chinese patent application (publication number CN115040420A) discloses a method for preparing pterostilbene liposomes. The resulting pterostilbene liposomes have excellent water dispersibility, expanding their scope of application. However, the liposomes have a relatively high average particle size, and their stability needs to be further improved. A Chinese patent application (publication number CN116549303A) discloses a method for preparing and applying supramolecular pterostilbene microcapsules for whitening and anti-aging. The method mainly uses a product formulation system to prepare high-content pterostilbene liposomes. However, ionic liquids need to be added to ensure low particle size and uniform distribution. Furthermore, the higher the ionic liquid content, the smaller the particle size and the more uniform the distribution, making it difficult to promote and apply the microcapsules on a large scale industrially. Summary of the Invention

[0003] In order to solve the above problems, the present invention provides a pterostilbene liposome, which effectively improves the stability of pterostilbene and increases its bioavailability by optimizing the liposome formula and its preparation process, thereby improving the whitening effect and achieving the highest efficiency of the raw material biological effect.

[0004] On one hand, the present invention provides a pterostilbene liposome, which comprises at least the following components by mass percentage: 40-60% glycerol, 5-15% caprylic-capric triglyceride, 2-4% hydrogenated lecithin, 4-7% pterostilbene, 0.5-1.5% ascorbyl tetraisopalmitate, 0.6-2.5% alcohol solvent, and the balance made up of water.

[0005] In one embodiment, the pterostilbene liposomes comprise at least the following components, calculated by mass percentage: 45-50% glycerol, 10-14% caprylic-capric triglyceride, 2.5-3.5% hydrogenated lecithin, 4.5-6% pterostilbene, 0.8-2% ascorbyl tetraisopalmitate, 1-1.8% alcohol solvent, and the balance made up of water.

[0006] In one embodiment, the alcohol solvent includes at least 1,2-hexanediol and 1,2-pentanediol.

[0007] In one embodiment, the mass ratio of the 1,2-hexanediol to the 1,2-pentanediol is (0.1-1): (0.5-1.5).

[0008] In one embodiment, the mass ratio of the 1,2-hexanediol to the 1,2-pentanediol is (0.3-0.8): (0.7-1).

[0009] The present invention uses glycerol, caprylic-capric triglyceride, and hydrogenated lecithin as oils to encapsulate pterostilbene and ascorbyl tetraisopalmitate in liposomes. The resulting liposomes have a small average particle size, uniform distribution, and a high encapsulation efficiency, effectively overcoming the large particle size and insufficient stability of existing pterostilbene raw materials. Furthermore, by controlling the pterostilbene content in the system to 4-7%, the present invention further reduces the average particle size of the liposomes, improves the liposome encapsulation efficiency, and prevents precipitation of the product during storage.

[0010] Another aspect of the present invention provides a method for preparing pterostilbene liposomes, comprising at least the following steps:

[0011] (1) Premix glycerol, caprylic-capric triglyceride, and hydrogenated lecithin at 70-90° C. to obtain phase A;

[0012] (2) Cooling phase A to 40-45° C., adding pterostilbene, ascorbyl tetraisopalmitate, and an alcohol solvent, and stirring to obtain a mixed liquid;

[0013] (3) adding water to the mixed liquid, stirring at a low speed of 800-1500 r / min for 10-20 min, and dispersing at a high speed of 5000-8000 r / min for 10-20 min to obtain colostrum;

[0014] (4) Colostrum is treated with a high-pressure microfluidic nanocollider to obtain pterostilbene liposomes.

[0015] In one embodiment, the premixing is performed at a rotation speed of 1000-2000 r / min and for a time of 10-40 min.

[0016] In one embodiment, the premixing is performed at a rotation speed of 1500 r / min and for a time of 20-25 min.

[0017] In one embodiment, the stirring and mixing is performed at a rotation speed of 500-1000 r / min and for a time of 20-60 min.

[0018] In one embodiment, the stirring and mixing is performed at a rotation speed of 800 r / min and for a time of 35-40 min.

[0019] In an embodiment, the rotation speed of the high-speed dispersion is 6000-7000 r / min, and the time is 10-15 min.

[0020] In an embodiment, the parameters of the high-pressure microfluidic nanocollision instrument are set as follows: 20000-35000 psi, 2-5 cycles of collision.

[0021] In an embodiment, the parameters of the high-pressure microfluidic nanocollision instrument are set as follows: 25000-30000 psi, 3-4 cycles of collision.

[0022] Further, the present application prepares low-particle-size stable pterostilbene liposomes by sequentially preparing an A phase, mixing a liquid and colostrum, and then treating with a high-pressure microfluidic nanocollision instrument, especially by controlling the high-speed dispersion conditions and the parameters of the high-pressure microfluidic nanocollision instrument to obtain pterostilbene liposomes with an average particle size of less than 100 nm, an encapsulation efficiency of >95%, no precipitation after storage at 25°C for 30 days, and a particle size change of <5%.

[0023] The third aspect of the present application provides a use of pterostilbene liposomes in the preparation of a whitening composition.

[0024] In an embodiment, the whitening composition at least comprises pterostilbene liposomes, tremella extract, dendrobium stem extract, and bellis perennis L extract.

[0025] In an embodiment, the mass ratio of the pterostilbene liposomes, tremella (Tremella fuciformis) extract, dendrobium loddigesii Rolfe extract, and bellis perennis L extract is (15-25):(1-5):(2-4):(5-8).

[0026] In an embodiment, the preparation method of the whitening composition is as follows: the pterostilbene liposomes, tremella extract, dendrobium stem extract, and bellis perennis L extract are stirred and mixed.

[0027] The pterostilbene liposomes provided by the present application, when mixed with tremella extract, dendrobium stem extract, and bellis perennis L extract, have excellent anti-aging performance, long-term stability, and light stability, and the composition can be widely added to various cosmetic systems, and has high market promotion value.

[0028] Advantages

[0029] 1. The present application provides a pterostilbene liposome, which effectively improves the stability of pterostilbene, improves the bioavailability, and further improves the whitening effect, so that the raw material biological effect reaches the highest efficiency by optimizing the liposome formula and the preparation process.

[0030] 2. The present invention uses glycerol, caprylic-capric triglyceride and hydrogenated lecithin as oils to encapsulate pterostilbene and ascorbyl tetraisopalmitate in liposomes. The obtained liposomes have a small average particle size, uniform distribution and high encapsulation efficiency, effectively overcoming the problems of large particle size and insufficient stability of existing pterostilbene raw materials.

[0031] 3. The present invention further reduces the average particle size of the liposomes by controlling the content of pterostilbene in the system to 4-7%, thereby increasing the encapsulation efficiency of the liposomes and avoiding precipitation of the product during storage.

[0032] 4. The present invention sequentially prepares phase A, mixes a liquid and colostrum, and then uses a high-pressure microfluidic nanocollider to prepare stable pterostilbene liposomes with low particle size. In particular, the high-speed dispersion conditions and high-pressure microfluidic nanocollider parameters are controlled to obtain an average particle size of less than 100 nm, an encapsulation efficiency of >95%, no precipitation after storage at 25°C for 30 days, and a particle size change of <5%.

[0033] 5. The whitening composition of the pterostilbene liposomes provided by the present invention, mixed with Tremella fuciformis extract, Dendrobium officinale stem extract, and Bellis perennis flower extract, has excellent aging resistance, long-term stability, and light stability. The composition can be widely added and applied to various cosmetic systems and has high market promotion value. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a comparison chart of the room temperature stability test results of pterostilbene liposomes provided in Example 1 and Comparative Example 1, with Example 1 on the left and Comparative Example 1 on the right. DETAILED DESCRIPTION

[0035] The sources of the raw materials in the embodiments, comparative examples, application examples and application comparative examples are as follows:

[0036] Glycerol: KLKEPONG OLEOMASSDN.BHD.20002670440;

[0037] Caprylic-capric triglyceride: STERARINERIE DUBOIS14012;

[0038] Hydrogenated lecithin: Shanghai Hongjiu Enterprise Development Co., Ltd. T2112288;

[0039] Pterostilbene: Zhuhai Bairui Pharmaceutical Technology Co., Ltd. C062240801;

[0040] Ascorbyl tetraisopalmitate: Zhuhai Bairui Pharmaceutical Technology Co., Ltd. C031230701;

[0041] 1,2-Hexanediol: THOR SPECIALTY CHEMICAL (ZHENJIANG) CO., LTD CZ2G1162407;

[0042] 1,2-Pentanediol: THOR SPECIALTY CHEMICAL (ZHENJIANG) CO., LTD RP00992900012511;

[0043] Tremella fuciformis fruiting body extract: Shanghai Huiwen Biotechnology Co., Ltd.;

[0044] Dendrobium officinale stem extract: SUPERCARE II Suzhou Plantel Skin Cell Technology Co., Ltd. Daisy flower extract: Shaanxi Weimi Biotechnology Co., Ltd. 240415.

[0045] Examples 1-3, Comparative Examples 1-4

[0046] On the one hand, Examples 1-3 and Comparative Examples 1-4 of the present invention provide a pterostilbene liposome, and the formula thereof is shown in Table 1 in terms of mass percentage.

[0047] Table 1

[0048]

[0049]

[0050] On the other hand, Example 1 of the present invention provides a method for preparing pterostilbene liposomes, comprising the following steps: (1) premixing glycerol, caprylic-capric triglyceride, and hydrogenated lecithin at 80° C. to obtain phase A;

[0051] (2) Cooling phase A to 45° C., adding pterostilbene, ascorbyl tetraisopalmitate, 1,2-hexanediol, and 1,2-pentanediol, and stirring to obtain a mixed liquid;

[0052] (3) adding water to the mixed liquid, stirring at a low speed of 1000 r / min for 15 min, and dispersing at a high speed of 6000 r / min for 15 min to obtain colostrum;

[0053] (4) Colostrum is treated with a high-pressure microfluidic nanocollider to obtain pterostilbene liposomes.

[0054] The rotation speed of the premixing is 1500 r / min and the time is 20 min.

[0055] The stirring and mixing was performed at a rotation speed of 800 r / min and for 40 min.

[0056] The parameter settings of the high-pressure microfluidic nanocollision instrument are: 25000 psi, 3 cycles of collision.

[0057] Embodiment 2 of the present application provides, in another aspect, a preparation method of pterostilbene liposomes, the specific implementation of which is the same as that of embodiment 1, except that the parameter settings of the high-pressure microfluidic nanocollision instrument are: 30000 psi, 4 cycles of collision.

[0058] Embodiment 3 of the present application provides, in another aspect, a preparation method of pterostilbene liposomes, the specific implementation of which is the same as that of embodiment 1, except that the rotation speed of the high-speed dispersion is 8000 r / min, and the time is 20 min.

[0059] Comparative Example 1 of the present application provides, in another aspect, a preparation method of pterostilbene liposomes, which comprises the following steps: dissolving pterostilbene in 1,2-hexanediol and 1,2-pentanediol by stirring to obtain a mixed solution, adding the mixed solution into water, and stirring at a low speed of 1000 r / min for 20 min, and high-speed dispersion at 6000 r / min for 15 min.

[0060] Comparative Examples 2 and 3 of the present application provide, in another aspect, a preparation method of pterostilbene liposomes, the specific implementation of which is the same as that of embodiment 1.

[0061] Comparative Example 4 of the present application provides, in another aspect, a preparation method of pterostilbene liposomes, the specific implementation of which is the same as that of embodiment 1, except that step (4) is not performed.

[0062] Application Examples 1-5 and Comparative Examples 1-4

[0063] Application Examples 1-5 and Comparative Examples 1-4 of the present application provide a whitening composition, the formulation of which is shown in Table 2 in terms of weight parts.

[0064] Table 2

[0065]

[0066] Performance Test

[0067] 1. Average particle size: the average particle size of the pterostilbene liposomes provided in the embodiments and comparative examples was tested using the instrument Litesizer 500, and the results are shown in Table 3.

[0068] 2. Encapsulation efficiency: the encapsulation efficiency of the pterostilbene liposomes provided in the embodiments and comparative examples was tested and calculated based on the formula, and the results are shown in Table 3.

[0069] The test method is as follows: the sample is placed in an ultracentrifuge tube; the instrument is set to centrifuge parameters of 100,000 × g, 1 hour, and 4°C; after centrifugation, a precipitate (encapsulated particles) and a supernatant (unencapsulated pterostilbene) are formed; the supernatant is analyzed to determine the pterostilbene content (i.e., the unencapsulated amount)

[0070] Encapsulation efficiency formula:

[0071]

[0072] W total :Total dosage (mg or μg)

[0073] W frree : Amount of unencapsulated drug (measured in the supernatant).

[0074] 3. Stability at room temperature: The pterostilbene liposomes provided in the examples and comparative examples were placed at 25°C for 30 days, and the appearance was observed and the changes in particle size were recorded. The results are shown in Table 3 and Figure 1 .

[0075] Table 3

[0076]

[0077] pass Figure 1 As shown in Table 3, the pterostilbene liposomes of the example have a smaller average particle size, a higher encapsulation efficiency and better stability than those of the comparative example.

[0078] 4. After the whitening compositions provided in the application examples and comparative examples were placed at a temperature of 40°C and a humidity of 75°C for 3 months (accelerated stability test), the pterostilbene content in the whitening compositions was tested and the pterostilbene retention rate was calculated (pterostilbene retention rate = pterostilbene content in the whitening composition before the accelerated stability test - pterostilbene content in the whitening composition after the accelerated stability test / pterostilbene content in the whitening composition before the accelerated stability test × 100%). The physical state of the whitening compositions was observed and microbial testing was performed. The results are shown in Table 4.

[0079] Table 4

[0080]

[0081]

[0082] It can be seen from the data in Table 4 that the whitening composition containing the pterostilbene liposomes provided in the examples has excellent accelerated stability.

[0083] 5. After the whitening compositions provided in the application examples and comparative examples were placed at a temperature of 25°C and a humidity of 60°C for 12 months (long-term stability test), the pterostilbene content in the whitening compositions was tested and the pterostilbene retention rate was calculated (pterostilbene retention rate = pterostilbene content in the whitening composition before long-term stability test - pterostilbene content in the whitening composition after long-term stability test / pterostilbene content in the whitening composition before long-term stability test × 100%). Changes in the appearance of the whitening compositions were observed. The results are shown in Table 5.

[0084] Table 5

[0085] sample Pterostilbene retention rate (%) Appearance changes Application Example 1 88.2±1.0 No change Application Example 2 87.5±0.7 No change Application Example 3 85.4±1.2 No change Application Example 4 87.3±0.8 No change Application Example 5 86.9±1.0 No change Comparative Application Example 1 52.1±2.5 Severe yellowing Application Comparative Example 2 60.3±1.8 Sedimentation and stratification Application Comparative Example 3 40.2±3.1 Turbidity and lumps Comparative Application Example 4 73.6±1.5 Creaming, particle coarsening

[0086] It can be seen from the data in Table 5 that the whitening composition containing the pterostilbene liposomes provided in the examples has excellent long-term stability.

[0087] 6. After the whitening compositions provided in the application examples and comparative examples were placed under 4500 Lux illumination for 14 hours (light stability test), the pterostilbene content in the whitening compositions was tested and the pterostilbene retention rate was calculated (pterostilbene retention rate = pterostilbene content in the whitening composition before light stability test - pterostilbene content in the whitening composition after light stability test / pterostilbene content in the whitening composition before light stability test × 100%). The results are shown in Table 6.

[0088] Table 6

[0089]

[0090]

[0091] It can be seen from the data in Table 6 that the whitening composition containing the pterostilbene liposomes provided in the examples has excellent light stability.

Claims

1. A pterostilbene liposome, characterized in that: Calculated by mass percentage, the invention comprises at least the following components: 40-60% glycerol, 5-15% caprylic acid-capric acid triglyceride, 2-4% hydrogenated lecithin, 4-7% pterostilbene, 0.5-1.5% ascorbyl tetraisopalmitate, 0.6-2.5% alcohol solvent, and the balance is made up of water.

2. The pterostilbene liposome according to claim 1, wherein The pterostilbene liposomes comprise at least the following components by mass percentage: 45-50% glycerol, 10-14% caprylic-capric triglyceride, 2.5-3.5% hydrogenated lecithin, 4.5-6% pterostilbene, 0.8-2% ascorbic acid tetraisopalmitate, 1-1.8% alcohol solvent, and the balance made up of water.

3. A method for preparing the pterostilbene liposome according to any one of claims 1 to 2, characterized in that: At least the following steps: (1) Premix glycerol, caprylic-capric triglyceride, and hydrogenated lecithin at 70-90° C. to obtain phase A; (2) Cooling phase A to 40-45° C., adding pterostilbene, ascorbyl tetraisopalmitate, and an alcohol solvent, and stirring to obtain a mixed liquid; (3) adding water to the mixed liquid, stirring at a low speed of 800-1500 r / min for 10-20 min, and dispersing at a high speed of 5000-8000 r / min for 10-20 min to obtain colostrum; (4) Colostrum is treated with a high-pressure microfluidic nanocollider to obtain pterostilbene liposomes.

4. The method for preparing pterostilbene liposomes according to claim 3, wherein The rotation speed of the premixing is 1000-2000 r / min, and the time is 10-40 min.

5. The method for preparing pterostilbene liposomes according to claim 3, wherein The stirring and mixing is performed at a rotation speed of 500-1000 r / min and for a time of 20-60 min.

6. The method for preparing pterostilbene liposomes according to claim 3, wherein The high-speed dispersion has a rotation speed of 6000-7000 r / min and a time of 10-15 min.

7. The method for preparing pterostilbene liposomes according to claim 3, wherein The parameters of the high-pressure microfluidic nanocollider are set as: 20,000-35,000 psi, 2-5 cyclic collisions.

8. A use of the pterostilbene liposome according to any one of claims 1 to 2, characterized in that: The invention is used for preparing whitening compositions.

9. The use of the pterostilbene liposome according to claim 8, characterized in that The whitening composition at least comprises pterostilbene liposomes, tremella extract, dendrobium officinale stem extract and daisy flower extract.

10. The use of the pterostilbene liposome according to claim 9, characterized in that: The mass ratio of the pterostilbene liposome, the tremella extract, the dendrobium officinale stem extract and the daisy flower extract is (15-25): (1-5): (2-4): (5-8).

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