A photothermal stable nano-lipid carrier system, a preparation method and application thereof

Abstract

The application provides a photothermal stability nanometer lipid carrier system, a preparation method and application, and relates to the technical field of nanometer preparations.The lipid carrier comprises the following components: an active substance, hydrogenated lecithin, jojoba seed oil, SpectrastatTM HCP, an emulsifying agent and a chelating agent, and the active substance is resveratrol.The lipid carrier has good stability, is stable under conditions such as dilution and centrifugation, and can be stored for a long time in a harsh environment.By wrapping resveratrol and other poorly soluble substances with the lipid carrier, the water solubility of such substances can be significantly improved, and the problem of poor solubility is improved.In addition, the wrapping of the lipid carrier can effectively isolate the influence of environmental factors such as oxygen and light, can improve the stability of the active substance, and can effectively improve the discoloration problem.When applied to preparations, the nanometer lipid carrier is more easily penetrated into the skin barrier, penetrates into the deep layer of the skin, and is more conducive to the delivery of the efficacy of the active substance.

Description

Technical Field

[0001] This invention relates to the field of nanoparticle technology, specifically to a photothermally stable nanolipid carrier system, its preparation method, and its application. Background Technology

[0002] Lipid carriers are substances containing active ingredients encapsulated in lipid materials to prevent the active substances from being destroyed by the environment (temperature, oxygen, pH, enzymes, etc.), thereby improving the bioactivity and utilization rate of the active substances. Lipid carriers have a structure similar to cell membranes, consisting of concentric vesicles composed of a phospholipid bilayer, capable of simultaneously loading water-soluble, lipid-soluble, and oil-poorly soluble active ingredients. Water-soluble components are encapsulated within the aqueous cavities, while lipophilic components are encapsulated between the lipid bilayers. Furthermore, lipid carriers possess advantages such as high bioavailability, convenient absorption, and high stability, and are widely used in pharmaceuticals, cosmetics, food, and genetic engineering.

[0003] Lipid carriers possess the following unique properties: ① Amphiphilicity: Lipid carriers can encapsulate both lipid-soluble and water-soluble substances; ② Sustained-release effect: Active substances encapsulated by lipid carriers are released slowly and continuously, improving their utilization; ③ Protective effect: Many bioactive substances can be deactivated by temperature, light, etc. Lipid carriers act like clothing, protecting active substances and preventing their denaturation and deactivation; ④ In skincare products, lipid carriers have a moisturizing effect, providing excellent hydration to the skin; ⑤ Skincare effect: The unsaturated phospholipids in lipid carriers can repair damaged skin cells and significantly improve rough skin. Especially in recent years, with the development of functional skincare products and the increased demand for effectiveness and utility, the good compatibility of lipid carriers with skin cell structure has given them broad application prospects in the skincare field.

[0004] Studies have confirmed that many poorly soluble plant active ingredients possess significant health benefits. For example, pterostilbene exerts whitening and anticancer effects through potent antioxidant, anti-inflammatory, and anti-tumor mechanisms; diosgenin has estrogen-like regulatory functions; and resveratrol exhibits anti-aging, cardiovascular protective, and neuroprotective effects. However, these ingredients generally suffer from poor water solubility and easy oxidative degradation, resulting in low oral bioavailability. Traditional controlled-release technologies are limited by high costs and insufficient adaptability to gastrointestinal pH fluctuations, severely restricting their clinical translation and application. Therefore, developing novel nanodelivery systems with both high stability and high bioavailability is crucial for overcoming the bottlenecks in the application of poorly soluble active substances.

[0005] Taking resveratrol as an example, resveratrol, also known as stilbene triol, is a phytoalexin produced by plants to resist external stimuli such as ultraviolet radiation, fungal infections, viral infections, or mechanical damage. Resveratrol has free radical scavenging effects, antioxidant regulatory effects, and can reduce inflammation by regulating cytokines. It also has good whitening effects. In addition, it has various physiological functions such as anti-cancer, cardiovascular protection, estrogen regulation, nerve and liver protection, anti-radiation, antitussive and antiasthmatic effects, blood pressure reduction, microcirculation improvement, and treatment of AIDS and shock. However, due to its unstable chemical properties, resveratrol is easily decomposed by light and heat, and has poor water solubility, making its application in cosmetics difficult. For example, its poor oil and water solubility makes formulation application difficult, and it is easily inactivated under light and oxygen, resulting in discoloration. Based on this, researchers in this field are attempting to develop a lipid carrier to encapsulate the poorly soluble and unstable active ingredients like resveratrol, allowing them to exert better efficacy.

[0006] However, existing studies have many problems, such as: ① The low content of resveratrol in the lipid carrier makes it difficult to add sufficient amounts (resveratrol content 0.0397%, "Preparation of resveratrol nanolipid carriers by high pressure microfluidic method", Chen Qiongling, Liu Hongzhi; Journal of Nuclear Agricultural Sciences 2015, 29(5):0916-0924), and many studies have not clearly stated the encapsulation ratio of resveratrol in the lipid carrier; ② The lipid carrier generally has poor stability, especially under extreme conditions, such as high temperature and light, and the long-term stability test time is limited. Insufficient information ("Preparation and Characterization of Resveratrol Flexible Nanoliposome Carriers", Wang Chunxiao, Xia Qiang; Daily Chemicals Science, Vol. 36, No. 1, January 2013), or insufficient dimensions, leads to potential quality risks in product application; ③ Most reports use traditional preparation methods for lipid carriers, such as thin-film hydration, reverse evaporation, and solvent injection. These operations often introduce toxic organic reagents, which can easily lead to potential skin irritation risks if not handled properly. At the same time, these traditional preparation methods have application problems such as poor process repeatability and difficulty in scaling up production. For example, Chinese patent application CN101874763A discloses a resveratrol flexible lipid carrier, which contains the following components by weight percentage: resveratrol 0.1-10%, phospholipids 0.5-10%, and a flexible agent 0.1-30%. However, its preparation process uses organic solvents such as dichloromethane, trichloromethane, diethyl ether, and methanol, which pose potential skin irritation risks.

[0007] In summary, developing a process technology that can improve the solubility of poorly soluble and unstable substances and solve their problems of poor stability, easy discoloration, and application difficulties in cosmetic formulations is a key research focus for researchers in this field. Summary of the Invention

[0008] This invention addresses the aforementioned problems by providing a photothermally stable nanolipid carrier system. Through optimized components and preparation methods, this system exhibits superior stability, remaining stable under dilution and centrifugation conditions and allowing for long-term storage even in harsh environments. Furthermore, unlike other preparation processes that introduce toxic organic solvents, this invention's nanolipid carrier does not use organic solvents during preparation, making the production process green, non-toxic, and environmentally friendly, avoiding toxic residues and minimizing skin irritation. In research cases, lipid carrier encapsulation improves resveratrol solubility and solves the application challenges of resveratrol in cosmetic formulations. Moreover, lipid carrier encapsulation effectively isolates resveratrol from environmental factors such as oxygen and light, enhancing its stability and addressing the issue of resveratrol's tendency to discolor under light while maintaining its activity. When applied to cosmetic formulations, the nano-sized resveratrol lipid carrier more easily penetrates the skin barrier and reaches deeper layers of the skin, demonstrating enhanced whitening and moisturizing effects.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] In a first aspect, the present invention provides a photothermally stable nanolipid carrier system comprising the following components: an active substance, hydrogenated lecithin, jojoba seed oil, Spectrastat™ HCP, an emulsifier, and a chelating agent, wherein the active substance is resveratrol.

[0011] Preferably, the hydrogenated lecithin is PHOSPHOLIPON 80H.

[0012] Preferably, the emulsifier is selected from at least one of polysorbate-80, decaglycerol monolaurate, sodium stearoyl glutamate, PEG-8 stearate, or PEG-2 hexadecyl alcohol ether.

[0013] More preferably, the emulsifier is polysorbate-80.

[0014] Preferably, the chelating agent is selected from at least one of disodium ethylenediaminetetraacetate, butylated hydroxyanisole, vitamin E, sodium metabisulfite, or 2,6-di-tert-butyl-p-cresol.

[0015] More preferably, the chelating agent is disodium ethylenediaminetetraacetate.

[0016] Preferably, the product comprises, by weight percentage: 0.1%-8% resveratrol, 0.5%-5% hydrogenated lecithin, 5%-15% jojoba seed oil, 0.1%-2% Spectrastat™ HCP, 1%-20% emulsifier and 0.005%-0.5% chelating agent, with water to make up to 100%.

[0017] More preferably, the product comprises, by weight percentage: 0.1%-5% resveratrol, 0.5%-3% hydrogenated lecithin, 5%-12% jojoba seed oil, 0.1%-1.5% Spectrastat™ HCP, 1%-10% emulsifier and 0.01%-0.1% chelating agent, with water to make up to 100%.

[0018] More preferably, by weight percentage, it comprises the following ingredients: 0.1%-1% resveratrol, 0.5%-2% hydrogenated lecithin, 5%-10% jojoba seed oil, 0.5%-1.5% Spectrastat™ HCP, 1%-5% emulsifier and 0.01%-0.09% chelating agent, with water made up to 100%.

[0019] Secondly, the present invention provides a method for preparing the lipid carrier described above, comprising the following steps:

[0020] S1: Emulsifier, chelating agent and water are mixed to obtain an aqueous phase;

[0021] S2: Hydrogenated lecithin, jojoba seed oil and active ingredients are mixed to obtain the oil phase;

[0022] S3: Mix the aqueous and oil phases, homogenize, and then add Spectrastat™ HCP.

[0023] Preferably, in step S1, the mixing temperature is 60-80°C; more preferably, in step S1, the mixing temperature is 60-70°C.

[0024] Preferably, in step S2, the mixing temperature is 60-80℃; more preferably, in step S2, the mixing temperature is 60-70℃.

[0025] Preferably, in step S3, the mixing parameters are: shear rate of 8000-9500 rpm and time of 1-3 min; more preferably, in step S3, the mixing parameters are: shear rate of 8000-9000 rpm and time of 1-2 min.

[0026] Preferably, in step S3, the homogenization parameters are: pressure of 200-1000 bar, temperature of 10-80℃, and number of cycles of 5-10.

[0027] More preferably, in step S3, the homogenization parameters are: pressure of 450-500 bar, temperature of 60-70°C, and number of cycles of 5-8.

[0028] Thirdly, the present invention provides the application of the lipid carrier described above in the preparation of cosmetics.

[0029] Preferably, the effects of the cosmetic include, but are not limited to, moisturizing, skin barrier repair, skin brightening, spot removal, whitening, and anti-aging.

[0030] Preferably, the cosmetic product can be a lotion, serum, toner, cream, mask, or powder product.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. By optimizing the components and ratios, this invention, especially by using the combination of hydrogenated lecithin, disodium EDTA, Spectrastat™ HCP and jojoba seed oil, produces a lipid carrier with good stability. It is stable under dilution, centrifugation and other conditions, and can be stored for a long time under various conditions.

[0033] 2. The lipid carrier prepared in this invention improves the solubility of resveratrol by encapsulating it, thus overcoming the challenges of its application in cosmetic formulations. Furthermore, the lipid carrier effectively isolates resveratrol from oxygen and light, enhancing its stability and mitigating discoloration while maintaining its activity. Simultaneously, the nano-sized resveratrol lipid carrier more easily penetrates the skin barrier, reaching deeper layers of the skin and enhancing its whitening and moisturizing effects.

[0034] 3. The resveratrol lipid carrier prepared by this invention is mild and non-irritating. When used in a formulation, it does not affect the original system's viscosity, pH, or other physicochemical properties, skin feel, or formulation stability.

[0035] 4. The preparation method of the present invention is green and pollution-free, avoids the use of organic solvents or toxic reagents, and can be industrialized. Attached Figure Description

[0036] Figure 1 The appearance and Tyndall effect of the resveratrol lipid carrier prepared in Example 1.

[0037] Figure 2 The particle size distribution of the resveratrol lipid carrier prepared in Example 1 is shown in the diagram.

[0038] Figure 3 Transmission electron microscopy (TEM) image of the resveratrol lipid carrier prepared in Example 1.

[0039] Figure 4 The images show the color change of the resveratrol lipid carrier prepared in Example 1, where (a) is the appearance after 0 days of storage at room temperature in the dark, and (b) is the appearance after 1 month of storage at room temperature in the dark.

[0040] Figure 5 The image shows the long-lasting skin moisture content evaluation of the resveratrol lipid carrier prepared in Example 1.

[0041] Figure 6 This is an evaluation diagram of long-term transdermal water loss in the skin of the resveratrol lipid carrier prepared in Example 1.

[0042] Figure 7 The image shows the long-lasting skin color ITA° value evaluation of the resveratrol lipid carrier prepared in Example 1.

[0043] Figure 8 The evaluation diagram shows the area ratio of long-acting VISIA-CR surface spots of the resveratrol lipid carrier prepared in Example 1.

[0044] Figure 9 This is a picture of the serum's appearance.

[0045] Figure 10 This is a picture of the cream's appearance.

[0046] Figure 11 The image shows the results of the serum's discrimination test.

[0047] Figure 12 The image shows the results of the cream discrimination test. Detailed Implementation

[0048] To make the technical means, creative features, achieved objectives, and effects of this invention readily understandable, the invention is further illustrated below with specific embodiments. However, these embodiments are merely preferred embodiments and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the scope of protection of this invention. It is worth noting that the raw materials used in this invention are all common commercially available products, and their sources are not specifically limited. The technical and scientific terms used in the embodiments have the meanings commonly understood by those skilled in the art to which this invention pertains.

[0049] raw material:

[0050] Table 1. Raw Material Manufacturers

[0051]

[0052] Example 1

[0053] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 2.

[0054] Table 2. Raw materials and proportions (mass percentage / %)

[0055]

[0056] The preparation method is as follows:

[0057] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0058] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 70°C until completely dissolved to obtain the oil phase;

[0059] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 70℃;

[0060] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0061] Example 2

[0062] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 3.

[0063] Table 3. Raw materials and proportions (mass percentage / %)

[0064]

[0065] The preparation method is as follows:

[0066] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 60°C to obtain an aqueous phase, and keep warm at 60°C.

[0067] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 80°C until completely dissolved to obtain the oil phase;

[0068] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 8000 rpm for 3 min; High-pressure homogenization: 10 cycles at 1000 bar and 10℃;

[0069] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0070] Example 3

[0071] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 3.

[0072] The preparation method is as follows:

[0073] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 80°C to obtain an aqueous phase, and keep warm at 80°C.

[0074] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 60°C until completely dissolved to obtain the oil phase;

[0075] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9500 rpm for 1 min; High-pressure homogenization: 5 cycles at 200 bar and 80℃;

[0076] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0077] Example 4

[0078] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 4.

[0079] Table 4. Raw materials and proportions (mass percentage / %)

[0080]

[0081] The preparation method is as follows:

[0082] S1. Mix water, sodium stearoyl glutamate and sodium metabisulfite, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0083] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 70°C until completely dissolved to obtain the oil phase;

[0084] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 50℃;

[0085] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0086] Comparative Example 1

[0087] A resveratrol lipid carrier, compared with Example 1, only changed the mass percentage of the raw materials, as shown in Table 5.

[0088] Table 5. Raw materials and proportions (mass percentage / %)

[0089]

[0090] The preparation method is the same as in Example 1.

[0091] Comparative Example 2

[0092] A resveratrol lipid carrier, compared with Example 1, uses only soybean lecithin instead of hydrogenated lecithin, as shown in Table 6.

[0093] Table 6. Raw materials and proportions (mass percentage / %)

[0094]

[0095] The preparation method is as follows:

[0096] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0097] S2. Mix soybean lecithin, jojoba seed oil and resveratrol, heat to 70°C until completely dissolved to obtain the oil phase;

[0098] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 70℃;

[0099] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0100] Comparative Example 3

[0101] A resveratrol lipid carrier, compared to Example 1, uses only ethyl p-hydroxybenzoate instead of Spectrastat™ HCP, as shown in Table 7.

[0102] Table 7. Raw materials and proportions (mass percentage / %)

[0103]

[0104] The preparation method is as follows:

[0105] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0106] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 70°C until completely dissolved to obtain the oil phase;

[0107] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 70℃;

[0108] S4. Add ethyl p-hydroxybenzoate while stirring to obtain resveratrol lipid carrier.

[0109] Comparative Example 4

[0110] A resveratrol lipid carrier, compared to Example 1, uses only sweet almond oil instead of jojoba seed oil, as shown in Table 8.

[0111] Table 8. Raw materials and proportions (mass percentage / %)

[0112]

[0113] The preparation method is as follows:

[0114] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0115] S2. Mix PHOSPHOLIPON 80H, sweet almond oil and resveratrol, heat to 70°C until completely dissolved to obtain the oil phase;

[0116] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 70℃;

[0117] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0118] Comparative Example 5

[0119] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 9.

[0120] Table 9. Raw materials and proportions (mass percentage / %)

[0121]

[0122] The preparation method is as follows:

[0123] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0124] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 70°C until completely dissolved to obtain the oil phase;

[0125] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 70℃;

[0126] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0127] Comparative Example 6

[0128] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 10.

[0129] Table 10. Raw materials and proportions (mass percentage / %)

[0130]

[0131] The preparation method is as follows:

[0132] S1. Mix water and polysorbate-80, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0133] S2. Mix PHOSPHOLIPON 80H and resveratrol, heat to 70°C until completely dissolved, and obtain the oil phase;

[0134] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 9000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 500 bar and 70℃ to obtain resveratrol lipid carrier.

[0135] Comparative Example 7

[0136] A resveratrol lipid carrier, with the same raw materials and proportions as in Example 1, but a different preparation method.

[0137] Table 11. Raw materials and proportions (mass percentage / %)

[0138]

[0139] The preparation method is as follows:

[0140] S1. Mix water, polysorbate-80 and disodium EDTA, heat to 50°C to obtain an aqueous phase, and keep warm at 50°C.

[0141] S2. Mix PHOSPHOLIPON 80H, jojoba seed oil and resveratrol, heat to 90°C until completely dissolved to obtain the oil phase;

[0142] S3. Mix the aqueous phase and oil phase, and process under high-speed shear at 7000 rpm for 2 min; high-pressure homogenization: cycle 8 times at 100 bar and 90℃;

[0143] S4. Add Spectrastat™ HCP while stirring to obtain resveratrol lipid carrier.

[0144] Comparative Example 8

[0145] A resveratrol lipid carrier, the raw materials and formulation are shown in Table 12.

[0146] Table 12. Raw materials and proportions (mass percentage / %)

[0147]

[0148] The preparation method is as follows:

[0149] S1. Mix water and polysorbate-80, heat to 70°C to obtain an aqueous phase, and keep warm at 70°C.

[0150] S2. Mix jojoba seed oil and resveratrol, heat to 70°C until completely dissolved, and obtain the oil phase;

[0151] S3. The aqueous and oil phases were mixed and treated at a high speed of 9000 rpm for 2 minutes. The system separated into layers and could not form a homogeneous phase, so no further tests were conducted.

[0152] Test Example 1

[0153] 1) Appearance

[0154] Photographs were taken of the resveratrol lipid carriers prepared in the examples to observe their appearance. The appearance of Example 1 is shown in the figure below. Figure 1 As shown, the resveratrol lipid carrier is milky white in appearance and exhibits the Tyndall effect after dispersion in water.

[0155] 2) Particle size

[0156] Test method: Add the sample dropwise to the Malvern Mastersizer 3000 wet sampler until the light-blocking range is reached. Take the average value of the three tests to obtain the average particle size of the lipid carrier.

[0157] The particle size of the resveratrol lipid carriers prepared in Examples 1-4 and Comparative Examples 1-7 was measured. The average particle sizes were 133 nm, 105 nm, 152 nm, 118 nm, 477 nm, 146 nm, 138 nm, 125 nm, 150 nm, 140 nm, and 220 nm, respectively.

[0158] The particle size distribution diagram of Example 1 is as follows: Figure 2 As shown, the resveratrol lipid carrier prepared in Example 1 has an average particle size of 133 nm, a narrow particle size distribution, and uniform size.

[0159] 3) Transmission electron microscopy characterization images

[0160] The resveratrol lipid carrier prepared in Example 1 was characterized by transmission electron microscopy.

[0161] The transmission electron microscopy (TEM) characterization image of Example 1 is shown below. Figure 3 As shown, the hollow cavity and vesicle wall are visible, indicating that it is a lipid carrier with a particle size of about 100 nm. The particles are round and uniform in size.

[0162] Test Example 2

[0163] stability:

[0164] 1) Long-term storage particle size stability

[0165] The resveratrol lipid carriers prepared in Examples 1-4 and Comparative Examples 1-7 were stored under light, at 45°C and 5°C for a long period of time, and particle size was measured on day 0, day 2, day 7, day 14, day 30, day 60 and day 90, respectively; the results are shown in Tables 13, 14.1 and 14.2.

[0166] Table 13. Long-term storage particle size stability (particle size / nm) of Examples 1-4

[0167]

[0168] Table 14.1 Long-term storage particle size stability (particle size / nm) of Comparative Examples 1-2

[0169]

[0170] Table 14.2 Long-term storage particle size stability (particle size / nm) of Comparative Examples 3-7

[0171]

[0172] Note: The " / " in Tables 14.1 and 14.2 indicates data for which this effect does not exist.

[0173] in conclusion:

[0174] The resveratrol lipid carrier prepared in Example 1 exhibited stable particle size for 3 months under light exposure, 45°C, and 5°C conditions, with a particle size variation of <5 nm, indicating long-term particle size stability. The resveratrol lipid carriers prepared in Examples 2-4 showed slightly lower particle size stability than those in Example 1, but were still significantly better than Comparative Examples 1-7. The resveratrol lipid carriers prepared in Comparative Examples 1-7 had unstable particle sizes and could not achieve long-term storage under various conditions.

[0175] 2) Dilution stability

[0176] The resveratrol lipid carriers prepared in Examples 1-4 and Comparative Examples 1-7 were diluted 2, 5, 10, 20, 50, 100, and 200 times, respectively, and allowed to stand. The particle size was tested on day 0, day 1, day 2, and day 7. The results are shown in Tables 15, 16.1, and 16.2.

[0177] Table 15. Dilution stability (particle size / nm) of Examples 1-4

[0178]

[0179] Table 16.1 Dilution stability (particle size / nm) of Comparative Examples 1-4

[0180]

[0181] Table 16.2 Dilution stability (particle size / nm) of Comparative Examples 5-7

[0182]

[0183] in conclusion:

[0184] The resveratrol lipid carriers prepared in Example 1, after dilution at concentrations of 2, 5, 10, 20, 50, 100, and 200, showed stable particle size on days 0, 1, 2, and 7 after standing, with a particle size variation of <5 nm, indicating good dilution stability. The resveratrol lipid carriers prepared in Examples 2-4 showed slightly lower dilution stability than those in Example 1, but significantly better than those in Comparative Examples 1-7. The resveratrol lipid carriers prepared in Comparative Examples 1-7 showed unstable particle size after dilution.

[0185] 3) Centrifugal stability

[0186] The resveratrol lipid carriers prepared in Examples 1-4 and Comparative Examples 1-7 were centrifuged at 3000 rpm for 30 min, and the sample state and particle size changes were observed. The results are shown in Table 17.

[0187] Table 17. Centrifugal stability (particle size / nm)

[0188]

[0189] in conclusion:

[0190] The resveratrol lipid carrier prepared in Example 1 had an average particle size of 133 nm before centrifugation and an average particle size of 134 nm after centrifugation, indicating good centrifugal stability. The resveratrol lipid carriers prepared in Examples 2-4 showed an increase in particle size of 7-11 nm after centrifugation, indicating lower centrifugal stability than Example 1. The resveratrol lipid carriers prepared in Comparative Examples 1-7 showed a significant increase in particle size or stratification after centrifugation, indicating poor centrifugal stability.

[0191] 4) Color change

[0192] The resveratrol lipid carrier and resveratrol dispersion (0.2% resveratrol dispersed in 1,3-butanediol) prepared in Example 1 were stored at room temperature in the dark for one month, and their colors were observed. The results are as follows. Figure 4 As shown, the resveratrol lipid carrier remained largely unchanged in color, while the resveratrol dispersion turned yellow. This indicates that lipid carrier encapsulation can delay the discoloration of resveratrol.

[0193] Test Example 3

[0194] Microbiological testing

[0195] Microbiological tests were conducted on the resveratrol lipid carriers prepared in Examples 1-4 and Comparative Examples 1-7. The tests were conducted according to the microbiological testing methods in the "Cosmetic Safety Technical Specifications (2015 Edition)" to examine the total number of colonies, thermotolerant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, molds and yeasts. The testing standards are shown in Table 18 below.

[0196] Table 18. Microbiological Testing Standards

[0197]

[0198] Results: Microbiological test results showed that the total number of colonies, molds and yeasts in the resveratrol lipid carriers of Examples 1-4 and Comparative Examples 1-7 met the requirements, and no thermotolerant Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were detected. The microbiological test was qualified.

[0199] Test Example 4

[0200] Safety assessment

[0201] Human skin patch tests were conducted on the resveratrol lipid carriers prepared in Examples 1-4 and Comparative Examples 1-7. The method for closed patch testing of the skin was followed according to the "Cosmetic Safety Technical Specifications (2015 Edition)". Specifically, qualified patch testing equipment was selected, and 0.020 mL of the test substance was placed in the patch testing device using the closed patch testing method. The patch was then applied to the inside of the subject's arm with a hypoallergenic adhesive tape. The test substance was removed after 24 hours, and the skin reaction was observed at 0.5 h, 24 h, and 48 h after removal. The results were recorded according to the skin reaction grading standards in the "Cosmetic Safety Technical Specifications (2015 Edition)".

[0202] Participants: A total of 16 participants, 2 males and 14 females, aged 23 to 54 years, who met the criteria for voluntary participation. Each participant's arm was divided into 11 areas, and different products were tested in each area.

[0203] Table 19. Skin Reaction Rating Table

[0204]

[0205] Table 20. Summary Results of Human Skin Patch Tests

[0206]

[0207] Results: Human skin patch test results showed that the resveratrol lipid carriers prepared in the examples and comparative examples had good safety.

[0208] Test Example 5

[0209] Efficacy test

[0210] Test method:

[0211] Thirty healthy Chinese male and female subjects, aged 18-60 years, with facial dryness, dehydration, peeling, redness, and dullness were selected and divided into two groups of 15. A before-and-after control method was used. Skin moisture content, transepidermal water loss, skin color ITA° value, and VISIA-CR surface spot area percentage were measured before and after 21 days of continuous product use. Evaluation results before and after product use were compared using statistical tests to determine if there were statistically significant differences.

[0212] A control group (hereinafter referred to as the control group) of resveratrol essence and an experimental group (hereinafter referred to as the experimental group) of resveratrol lipid carrier essence were prepared, and the content of resveratrol and other ingredients in the two groups were kept consistent.

[0213] Table 21. Control group formula

[0214]

[0215] Table 22. Experimental Group Formula

[0216]

[0217] Preparation process: Phase A and Phase B are heated to 80℃ respectively, mixed and homogenized at 13000rpm for 2min; the mixture is stirred and cooled to 40℃, and Phases C, D (and E) are added in sequence, mixed evenly, and then discharged.

[0218] 1) Evaluation of long-lasting skin moisture content

[0219] Experimental design: The control group and the experimental group were respectively applied to the left and right cheeks, and the skin moisture content was tested at 0d, 7d, 14d and 21d.

[0220] The experimental results are shown in Table 23 below. Figure 5 As shown:

[0221] Table 23. Results of Skin Moisture Content Test

[0222]

[0223] Note: The data in the table are homogeneous ± standard error.

[0224] result:

[0225] ① After 21 consecutive days of use of the control group, the skin moisture content in the tested area increased compared to the baseline value, with an increase rate of 16.13%.

[0226] ②After 21 consecutive days of use in the experimental group, the skin moisture content in the tested area increased compared to the baseline value, with an increase rate of 24.57%.

[0227] Note: Measurement value: The higher the skin moisture content value, the more hydrated the skin.

[0228] Conclusion: Compared with unencapsulated resveratrol, the resveratrol lipid carrier prepared in Example 1 of this invention has better skin moisturizing effect.

[0229] 2) Evaluation of long-term transepidermal water loss

[0230] Experimental design: The control group and the experimental group were respectively applied to the left and right cheeks, and the transepidermal water loss of the skin was tested at 0d, 7d, 14d and 21d.

[0231] The results are shown in Table 24 and Figure 6 As shown.

[0232] Table 24. Results of transepidermal water loss detection

[0233]

[0234] Note: The data in the table are homogeneous ± standard error.

[0235] Results: ① After 21 days of continuous use of the control group, the transdermal water loss in the tested area increased compared with the baseline value, with an increase rate of 4.40%.

[0236] ②After 21 consecutive days of use in the experimental group, the transdermal water loss in the tested area decreased compared to the baseline value, with a decrease rate of 16.04%.

[0237] Note: Measurement value: The lower the transepidermal water loss value, the better the skin barrier function.

[0238] Conclusion: Compared with unencapsulated resveratrol, the resveratrol lipid carrier prepared in Example 1 of this invention has better skin barrier repair efficacy.

[0239] 3) Long-lasting skin color ITA° value evaluation

[0240] Experimental design: The skin color ITA° value was tested on the left and right cheeks of the control group and the experimental group respectively at 0d, 7d, 14d and 21d.

[0241] The experimental results are shown in Table 25 and Figure 7 As shown:

[0242] Table 25. Results of ITA° value test for skin color

[0243]

[0244] Note: The data in the table are homogeneous ± standard error.

[0245] result:

[0246] ① After 21 consecutive days of use of the control group, the skin color ITA° value in the tested area increased compared with the baseline value, with an increase rate of 2.92%;

[0247] ② After 21 days of continuous use in the experimental group, the skin color ITA° value in the tested area increased compared with the baseline value, with an increase rate of 5.06%;

[0248] Note: Measurement value: The higher the ITA° value of skin color, the lighter the skin color.

[0249] Conclusion: Compared with unencapsulated resveratrol, the resveratrol lipid carrier prepared in Example 1 of this invention has a better skin brightening effect.

[0250] 4) Evaluation of the proportion of surface spot area on long-lasting VISIA-CR

[0251] Experimental design: VISIA-CR surface spot area percentage was measured on the left and right cheeks of the control group and experimental group respectively at 0d, 7d, 14d and 21d.

[0252] The experimental results are shown in Table 26 and Figure 8 As shown:

[0253] Table 26. Results of VISIA-CR surface spot area ratio detection

[0254]

[0255] Note: The data in the table are homogeneous ± standard error.

[0256] Results: ① After 21 days of continuous use of the control group, the proportion of surface spots in the tested area increased compared with the baseline value, with an increase rate of 3.24%.

[0257] ②After 21 consecutive days of use in the experimental group, the proportion of VISIA-CR surface spots in the tested area decreased compared with the baseline value, with a decrease rate of 8.01%.

[0258] Conclusion: Compared with unencapsulated resveratrol, the resveratrol lipid carrier prepared in Example 1 of this invention has better spot-removing effects.

[0259] Test Example 6

[0260] application:

[0261] 1) Formula information:

[0262] Resveratrol lipocarriers at concentrations of 0.5%, 1%, 1.5%, and 2% were added to creams and serums, with a control group (0%) containing no resveratrol lipocarrier. The formulations of the resveratrol lipocarrier creams and serums are shown in Tables 27-28 below. The consistency and pH of the formulations were tested, and the results are shown in Table 29 below. Twenty volunteers were recruited to conduct discrimination tests on the creams and serums.

[0263] Table 27. Formula

[0264]

[0265] Preparation process: Phase A and Phase B are heated to 80℃ respectively, mixed and homogenized at 13000rpm for 2min; the mixture is stirred and cooled to 40℃, and Phases C, D and E are added in sequence, mixed evenly, and then discharged.

[0266] Table 28. Formula

[0267]

[0268] Preparation process: Phase A is heated to 80℃ and homogenized at 13000rpm for 2min; then cooled to 40℃ with stirring, and phases B, C, D and E are added in sequence, mixed evenly, and discharged.

[0269] Its appearance is shown in the figure. Figure 9-10 As shown.

[0270] Conclusion: ① Figure 10 As shown, compared with the blank group, adding 0.5%, 1%, 1.5% and 2% resveratrol lipocarriers to the cream did not change the original appearance.

[0271] ②For example Figure 9 As shown, the serum containing 0.5%, 1%, 1.5% and 2% resveratrol lipid carriers is white and semi-transparent in appearance.

[0272] 2) Viscosity and pH

[0273] Operating instructions:

[0274] Viscosity test: Place the rotor in the sample, submerging it above the rotor scale line, start the test and record the results;

[0275] pH test: Dilute the sample with deionized water (10 times), stir to disperse evenly, test with a pH meter, and record the results.

[0276] The results are shown in Table 29.

[0277] Table 29. Formulation viscosity and pH test results

[0278]

[0279] Results: Compared with the control group, the creams and serums with added resveratrol lipid carriers showed less change in consistency and pH, indicating that the addition of resveratrol lipid carriers had little impact on the physicochemical properties of the formulation.

[0280] 3) Formulation stability

[0281] ① Stability test of resveratrol lipid carrier essence formula:

[0282] Reference standards: "Technical Guidelines for Stability Testing and Evaluation of Cosmetics", "QB / T 2660-2004 Toners"

[0283] The stability of the resveratrol lipid carrier essence was tested under the following conditions: high and low temperature cycling, -15℃, 45℃ and light exposure, for 3 months.

[0284] Results: No significant quality changes were observed under high and low temperature cycling, -15℃, 45℃, and light exposure conditions, indicating that the sample stability test was satisfactory. This demonstrates that the application of resveratrol lipid carriers does not affect the stability of the formulation.

[0285] ②Stability test of resveratrol lipid carrier cream formulation

[0286] Reference standards: "Technical Guidelines for Stability Testing and Evaluation of Cosmetics", "QB / T 1857-2013 Moisturizing Creams"

[0287] The stability of the resveratrol lipid carrier cream was tested under the following conditions: high and low temperature cycling, -15℃, 45℃ and light exposure, for 3 months.

[0288] Results: No significant quality changes were observed under high and low temperature cycling, -15℃, 45℃, and light exposure conditions, indicating that the sample stability test was satisfactory. This demonstrates that the application of resveratrol lipid carriers does not affect the stability of the formulation.

[0289] 4) Discrimination test

[0290] Evaluator information: There are 20 evaluators, aged 23-54, 7 males and 13 females, who meet the selection criteria for evaluators.

[0291] Scoring criteria: 1 point is extremely weak sensory intensity, 7 points is extremely strong sensory intensity, Prob refers to significant difference, with 0.5 as the smallest unit, as shown in Table 30.

[0292] Table 30. Sensory Evaluation Scoring Sheet

[0293]

[0294] 1. Serum Discrimination Test

[0295] Methodological reference: GB / T39625-2020 Guidelines for Establishing Sensory Profiles in Sensory Analysis Methodology

[0296] Test indicators: ① Product appearance: product consistency; ② Product application: wateriness, skin stickiness, amount of product residue;

[0297] Test method: The serums containing 0.5%, 1%, 1.5%, and 2% resveratrol lipid carrier were compared with the serums without resveratrol lipid carrier.

[0298] ① Product consistency (visual): Observe the product's flow rate.

[0299] Squeeze 2 mL of product onto a smooth plate. Tilt the plate at a constant speed of 45° for 3 seconds to observe the flow rate of the product. If there is no flow after 2 seconds, increase the tilt angle to 90°. After 2 seconds, place the plate flat and observe the flow length. (If the product does not flow on its own, you can also tilt it at 45° and tap the table twice to observe the degree of flow (collapse).

[0300] ② Watery feel (tactile sensation + other): The sensation of how much water the product contains when applying it.

[0301] During the first 30 circles of application, feel the moisture content of the product. If you feel a watery sensation on your arm, the product has a strong water-retaining effect; conversely, if you don't feel any water on your arm, the product has a weak water-retaining effect.

[0302] ③ Skin stickiness (tactile sensation): Use your index finger to feel the stickiness of the skin when your finger touches it. The more force you apply when you lift your index finger away from your skin, the stickier the product is, and vice versa.

[0303] ④ Amount of product residue (tactile sensation): Use your index finger to feel how much product remains on the skin surface after application. The more product remains on the skin surface, the more residue there is (after use), and vice versa.

[0304] The results are shown in Tables 31.1-31.5 and Figure 11 As shown: there was no significant difference, indicating that adding ≤2% resveratrol lipid carrier has no effect on the skin feel of the serum.

[0305] Table 31.1 Results of the discrimination test for resveratrol lipid carrier essence (0%)

[0306]

[0307] Table 31.2 Results of the discrimination test for resveratrol lipid carrier essence (0.5%)

[0308]

[0309] Table 31.3 Results of the discrimination test for resveratrol lipid carrier essence (1%)

[0310]

[0311] Table 31.4 Results of the discrimination test for resveratrol lipid carrier essence (1.5%)

[0312]

[0313] Table 31.5 Results of the discrimination test for resveratrol lipid carrier essence (2%)

[0314]

[0315] 2. Cream Discrimination Test

[0316] Evaluators: 20 evaluators, aged 23-54, 7 males and 13 females, who meet the evaluator selection criteria.

[0317] Scoring criteria: 1 point indicates extremely weak sensory intensity, 7 points indicates extremely strong sensory intensity, Prob refers to significant difference, with 0.5 as the smallest unit, as shown in Table 32.

[0318] Table 32. Sensory Evaluation Scoring Sheet

[0319]

[0320] Methodological reference: GB / BT39625-2020 Guidelines for Establishing Sensory Profiles in Sensory Analysis Methodology

[0321] Test indicators: Product appearance: fineness of product texture, gloss of product, consistency of product; First contact: softness or hardness of cream; When applying product: oily feel.

[0322] Test method: Creams containing 0.5%, 1%, 1.5%, and 2% resveratrol lipid carriers were compared with creams without resveratrol lipid carriers.

[0323] ① Product texture fineness (visual): The amount of particles and bubbles on the product surface

[0324] Use the back of a small spoon to push aside the surface of the product and observe the amount of particles and bubbles on the surface to judge the texture of the product. If there are almost no particles and bubbles on the surface of the product, it means that the texture of the product is very fine; if there are obvious particles and bubbles on the surface of the product, it means that the texture of the product is not fine at all.

[0325] ② Product brightness (visual): The degree of reflectivity of the product under white light.

[0326] Flatten the product surface with the back of a small spoon and place it under a white light. The tester observes the product's reflectivity under the white light from a 45-degree downward angle. High reflectivity, which feels very glaring, indicates that the product is very shiny; conversely, low reflectivity, which does not feel glaring at all, indicates that the product has low shine.

[0327] ③ Product consistency (visual): Observe the product's flow rate.

[0328] Squeeze 2 mL of product onto a smooth plate. After 3 seconds, tilt the plate at a constant speed of 45° and observe the flow rate of the product. If there is no flow after 2 seconds, increase the tilt angle to 90°. After 2 seconds, flatten the plate and observe the flow length. (If the product does not flow on its own, you can also tilt it at 45° and tap the table twice to observe the degree of flow (collapse).

[0329] ④ The softness or hardness of the cream (tactile sensation): Under the same force, the amount of resistance encountered when pressing the product with the index finger.

[0330] Press the product down three times at a 45° angle with your index finger, filling the container to half its depth. Feel the resistance your index finger encounters during this process. Greater resistance indicates a firmer product, while less resistance indicates a softer product.

[0331] ⑤ Oiliness (tactile sensation + other): The amount of oil the product feels like when applying it.

[0332] During the first 30 circles of application, feel the amount of oil in the product. If you feel an oily sensation on your arm, the product is oily; conversely, if you feel almost no oil on your arm, the product is not oily.

[0333] The results are shown in Tables 33.1-33.5 and Figure 12 As shown: there was no significant difference, indicating that adding ≤2% resveratrol lipid carrier has no effect on the skin feel of the cream.

[0334] Table 33.1 Results of the discrimination test for resveratrol lipid carrier cream (0%)

[0335] Table 33.2 Results of the discrimination test for resveratrol lipid carrier cream (0.5%)

[0336]

[0337] Table 33.3 Results of the discrimination test for resveratrol lipid carrier cream (1%)

[0338]

[0339] Table 33.4 Results of the discrimination test for resveratrol lipid carrier cream (1.5%)

[0340]

[0341] Table 33.5 Results of the discrimination test for resveratrol lipid carrier cream (2%)

[0342]

[0343] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A photothermally stable nanolipid carrier system, characterized in that, It is composed of the following ingredients: 0.1%-8% resveratrol, 0.5%-5% hydrogenated lecithin, 5%-15% jojoba seed oil, 0.1%-2% Spectrastat™ HCP, 1%-20% emulsifier and 0.005%-0.5% chelating agent, with water to make up to 100%; the hydrogenated lecithin is PHOSPHOLIPON 80H; The preparation method of the photothermally stable nanolipid carrier system includes the following steps: S1: Emulsifier, chelating agent and water are mixed to obtain an aqueous phase; the mixing temperature is 60-80℃. S2: Hydrogenated lecithin, jojoba seed oil and resveratrol are mixed to obtain the oil phase; the mixing temperature is 60-80℃. S3: Mix the aqueous phase and oil phase, homogenize, and then add Spectrastat™ HCP; the mixing parameters are: shear rate of 8000-9500 rpm, time of 1-3 min; the homogenization parameters are: pressure of 200-1000 bar, temperature of 10-80℃, and number of cycles of 5-10.

2. The photothermally stable nanolipid carrier system according to claim 1, characterized in that, The emulsifier is selected from at least one of polysorbate-80, decaglycerol monolaurate, sodium stearoyl glutamate, PEG-8 stearate, or PEG-2 hexadecyl ether.

3. The photothermally stable nanolipid carrier system according to claim 2, characterized in that, The emulsifier is polysorbate-80.

4. The photothermally stable nanolipid carrier system according to claim 1, characterized in that, The chelating agent is selected from at least one of disodium ethylenediaminetetraacetate, butylated hydroxyanisole, vitamin E, sodium metabisulfite, or 2,6-di-tert-butyl-p-cresol.

5. The photothermally stable nanolipid carrier system according to claim 4, characterized in that, The chelating agent is disodium ethylenediaminetetraacetate.

6. The photothermally stable nanolipid carrier system according to claim 1, characterized in that, The product is composed of the following ingredients by weight percentage: 0.1%-5% resveratrol, 0.5%-3% hydrogenated lecithin, 5%-12% jojoba seed oil, 0.1%-1.5% Spectrastat™ HCP, 1%-10% emulsifier and 0.01%-0.1% chelating agent, with water to make up to 100%.

7. A method for preparing the photothermally stable nanolipid carrier system according to any one of claims 1-6, characterized in that, Includes the following steps: S1: Emulsifier, chelating agent and water are mixed to obtain an aqueous phase; the mixing temperature is 60-80℃. S2: Hydrogenated lecithin, jojoba seed oil and resveratrol are mixed to obtain the oil phase; the mixing temperature is 60-80℃. S3: Mix the aqueous phase and oil phase, homogenize, and then add Spectrastat™ HCP; the mixing parameters are: shear rate of 8000-9500 rpm, time of 1-3 min; the homogenization parameters are: pressure of 200-1000 bar, temperature of 10-80℃, and number of cycles of 5-10.

8. The preparation method according to claim 7, characterized in that, In steps S1 and S2, the mixing temperature is 60-80℃; In step S3, the mixing parameters are: shear rate of 8000-9500 rpm and time of 1-3 min; the homogenization parameters are: pressure of 200-1000 bar, temperature of 10-80℃ and number of cycles of 5-10.

9. The use of the photothermally stable nanolipid carrier system according to any one of claims 1-6 in the preparation of cosmetics.

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