Nanostructure lipid carrier containing hydroxyresveratrol

Abstract

The invention relates to a nano-structure lipid carrier containing hydroxyresveratrol, which can effectively coat hydroxyresveratrol by virtue of the nano-structure lipid carrier composed of specific components and proportions, so that hydroxyresveratrol can be effectively transferred to the deep layer of skin so as to enhance the whitening effect.

Description

Technical Field

[0001] The present invention relates to a nanostructured lipid carrier containing hydroxy-resveratrol, in particular to a nanostructured lipid carrier containing hydroxy-resveratrol which can effectively deliver hydroxy-resveratrol to the deep layer of the skin. Background Art

[0002] In recent years, with the rapid development of science and technology, the modern cosmetics industry has also ushered in an unprecedented transformation. With the unremitting efforts of many beauty brands, beauty care is no longer just about concealing blemishes, but is gradually moving towards bringing health and translucence to the skin. In particular, the whitening and brightening function has become one of the focuses of attention in the current market.

[0003] Market analysis data from the past five years show that the demand for whitening and brightening products has been growing continuously; consumers’ demand for skin tone optimization is constantly increasing, which also reflects modern people’s pursuit of healthy and beautiful skin and the importance they place on self-confidence.

[0004] Studies have shown that about two-thirds of the world's plants have medicinal value, and many plant extracts are used in health research. Among them, white mulberry (Morus alba) is a small to medium-sized deciduous tree of the genus Morus, widely distributed in China. Its trunk mainly contains hydroxyresveratrol (Hydroxyresveratrol), resveratrol (Resveratrol) and other ingredients. Hydroxyresveratrol can be separated and purified through extraction and purification. Wild jackfruit (Artocarpus lakoocha, also known as monkey fruit) is also one of the plants of the Moraceae family. It is produced in Southeast Asian countries. It has biological properties such as antiviral, antibacterial, wound healing, anti-inflammatory, and anti-cancer. It also contains active compounds such as artocarpin, polyphenols and flavonoids. Hydroxyresveratrol can also be separated and purified through extraction.

[0005] As a gift from nature, the extracts of mulberry plants are mild in nature and suitable for all skin types. They reduce irritation to the skin, making them the first choice for whitening in the minds of many people. White mulberry extract is rich in antioxidants, especially hydroxy-resveratrol, which can effectively inhibit the production of melanin and slow down the formation of skin spots. Baobab is rich in polyphenols and flavonoids, and also has whitening, antioxidant and anti-inflammatory effects, keeping the skin even and translucent. It also has excellent soothing and repairing effects, which can effectively relieve skin discomfort caused by environmental pressure and daily resistance to external aggression, and enhance the overall radiance of the skin.

[0006] However, although Moraceae plant extracts have excellent whitening effects, they are often difficult to penetrate into the deep layers of the skin, even to the dermis, thereby greatly reducing the whitening effect. Therefore, it is necessary to find a method that can make Moraceae plant extracts more easily penetrate into the deep layers of the skin and improve the whitening effect. Summary of the invention

[0007] In order to solve the problem that the whitening plant extract of the Moraceae family cannot easily penetrate into the deep layer of the skin, resulting in poor whitening effect, the inventor has finally developed a nanostructured lipid carrier after unremitting research and development and experiments. The nanostructured lipid carrier can be used to improve the delivery effect of the Moraceae plant extract.

[0008] Nanocarrier technology has attracted much attention in the fields of drug delivery and cosmetics in recent years. By encapsulating the extract of Moraceae plants in a nanostructured lipid carrier (NLC), the extract of Moraceae plants can be efficiently delivered to the deep layers of the skin. This carrier technology not only takes advantage of the mild nature of Moraceae plant extracts and their ability to inhibit melanin production, but also makes their whitening effect more efficient, providing more possibilities for those who pursue translucent and bright skin.

[0009] On the other hand, hydroxy-resveratrol in the extract of Moraceae plants has the disadvantages of being easily oxidized, unstable, having low water solubility and low bioavailability, so many current studies have used nanocarriers to encapsulate it for use; however, in the prior art, although nanostructured lipid carriers (NLCs) can be used to encapsulate hydroxy-resveratrol, their stability is poor and they can only be stored at 4°C for a maximum of 12 months. In addition, the particle size of the carrier will gradually increase over time and cannot be stored at room temperature for a long time.

[0010] The object of the present invention is to provide a nanostructured lipid carrier containing hydroxy-resveratrol. The nanostructured lipid carrier composed of specific components and proportions can effectively encapsulate the moraceae plant extract containing hydroxy-resveratrol and has excellent stability. At the same time, it can effectively deliver the moraceae plant extract to the deep layers of the skin to improve the whitening effect.

[0011] The present invention will be further described in detail below in conjunction with specific embodiments and drawings to provide a better understanding of the purpose, technical content, features and technical effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The present invention will be further described below in conjunction with the accompanying drawings:

[0013] Figure 1 A schematic diagram of the ratio of hydroxy-resveratrol content in the stable formulation groups of the nanostructured lipid carrier containing hydroxy-resveratrol after being placed at different temperatures for 50 days; Figure 2 A schematic diagram of the ratio of hydroxy-resveratrol content between hydroxy-resveratrol encapsulated by nanostructured lipid carriers and hydroxy-resveratrol not encapsulated by nanostructured lipid carriers after being placed at different temperatures for 90 days; Figure 3 FIG. 1 is a schematic diagram of the coverage rate of the raw material encapsulated by the nanostructured lipid carrier in the stable formulation group of the nanostructured lipid carrier containing hydroxy-resveratrol; Figure 4 FIG. 1 is a schematic diagram of particle size distribution of nanostructured lipid carriers in a stable formulation group of nanostructured lipid carriers containing hydroxyresveratrol; Figure 5 Schematic diagram of the percutaneous absorption test results. DETAILED DESCRIPTION

[0014] In order to better understand the technical features, contents and advantages of the present invention and the technical effects achieved by the present invention, the present invention will now be described in detail in the form of embodiments in conjunction with the accompanying drawings. The drawings used in the present invention are only for illustration and auxiliary explanation, and may not be the actual proportions and precise configurations after the implementation of the present invention. Therefore, the scope of rights of the present invention in actual implementation is not limited to the proportions and configuration relationships of the drawings.

[0015] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the meanings commonly understood by those of ordinary skill in the art to which the invention belongs. It will be further understood that, for example, those terms defined in commonly used dictionaries should be interpreted as having meanings consistent with their meanings in the context of the relevant technology and the present invention, and will not be interpreted as idealized or overly formal meanings, unless explicitly defined as such herein.

[0016] Example 1 Preparation of Nanostructured Lipid Carriers Containing Hydroxyresveratrol

[0017] Common methods for preparing NLC include high (low) shear homogenization, ultrasonic vibration, thin film contact technology, emulsification solvent evaporation and high pressure homogenization. The present invention combines high shear homogenization, high pressure homogenization and low shear homogenization to prepare the desired nanostructured lipid carrier.

[0018] 0.1-0.5 wt % of a Moraceae plant extract (white mulberry extract or monkey fruit extract) containing hydroxy-resveratrol is dissolved in an oil phase solution, wherein the oil phase solution comprises: 2.5-8 wt % of cetylpalmitate, 2-5 wt % of caprylic / capric triglycerides, and then 0-4.5 wt % of sorbitan monolaurate (SPAN20) or 0-1.875 wt % of lecithin or 0-3 wt % of decyl glucoside are added to the oil phase solution respectively; and the aqueous phase solution comprises: 0-6 wt % of polysorbate 80 (Tween80) and 79.5-89.075 wt % of water.

[0019] The oil phase solution and the water phase solution are heated to 60° C., 70° C., 80° C., and 90° C., respectively, and subjected to high shear homogenization; the oil phase solution is added to the water phase solution for pre-emulsification, and emulsified for 3 to 10 minutes at a rotation speed of 4000 to 12000 RPM using a high-speed homogenizer to obtain a pre-emulsified mixture; wherein, through quality screening, the most suitable pre-emulsification conditions are 70° C., a rotation speed of 8000 RPM, and pre-emulsification for 3 minutes.

[0020] Next, a high-pressure homogenization method is performed, and each group of pre-emulsified mixtures mentioned above is transferred to a high-pressure homogenizer (model SPXAPV2000), and the homogenization pressure is set to 100-1000 bar. 4-10 cycles of homogenization are performed, and the temperature is maintained at 60-90°C to obtain a high-pressure treated mixture; among them, through quality screening, the most suitable high-pressure homogenization conditions are 65°C, a pressure of 500 bar, and 5-6 cycles.

[0021] Finally, a low shear homogenization method was performed, and the mixtures treated with high pressure in each group were placed in an ice bath at 4°C for cooling, and then moved to a high-speed homogenizer for re-emulsification at a speed of 1000-12000RPM, and the temperature was detected to drop from 65-70°C to 15-20°C, thereby obtaining a nanostructured lipid carrier containing hydroxy-resveratrol; wherein, through quality screening, the most suitable emulsification conditions were cooling in an ice bath at 4°C, a speed of 4000RPM, and emulsification for at least 5 minutes until the temperature reached 15-20°C. The raw material formulas of each group and the state of the prepared nanostructured lipid carrier containing hydroxy-resveratrol are shown in Table 1.

[0022] Table 1

[0023] As shown in Table 1, the nanostructured lipid carriers containing hydroxy-resveratrol in the E1 and E2 groups precipitated after preparation, while the E3, E4, E5, E8, E9, E10, E11, and E12 groups showed stratification after preparation. Only the E6 and E7 groups showed a uniform and stable state. Therefore, after screening, the stable formula groups were E6 and E7, and various experiments were subsequently carried out using these two groups.

[0024] Example 2 Stability screening experiment

[0025] The stable formula groups E6 and E7 obtained in Example 1 were screened for stability. The nanostructured lipid carriers containing hydroxy-resveratrol in groups E6 and E7 were placed at 5°C, 25°C and 45°C for 50 days, respectively, and the content of hydroxy-resveratrol was determined by HPLC. The results are as follows: Figure 1 As shown in the figure, it can be seen that the stable formula groups E6 and E7 were stored at 45°C for 50 days, and the relative contents of hydroxy-resveratrol were 83.8% and 65.4% respectively compared with those on day 0. The hydroxy-resveratrol content in the E6 group was significantly higher than that in the E7 group, and the reduction in the E7 group was about 2.1 times that of the E6 group ((100-65.4) / (100-83.8)=2.1), so the E6 group was finally selected for subsequent testing.

[0026] Next, the stability of hydroxy-resveratrol dissolved in glycerol was compared between the group without nanostructured lipid carrier encapsulation and the group with E6 encapsulated by nanostructured lipid carrier. After the two groups were placed at 5°C, 25°C and 45°C for 90 days, the content of hydroxy-resveratrol was determined by HPLC. The results are as follows: Figure 2 As shown in the figure, it can be seen that the E6 group coated with the nanostructured lipid carrier can effectively protect hydroxy-resveratrol from high temperature and oxidation, and its relative content of hydroxy-resveratrol is higher than that of the uncoated group. Compared with the uncoated group, the content of hydroxy-resveratrol in the E6 group coated with the nanostructured lipid carrier increased by about 13.4% (83.0-69.6=13.4), which proves that the nanostructured lipid carrier formula of the E6 group has the ability to protect the active ingredients it encapsulates.

[0027] Example 3 Coverage and Particle Size Distribution Experiment

[0028] The E6 group was tested for encapsulation efficiency. 100 μL of the E6 group was placed in a high-speed centrifuge tube feed tank (model Vivaspin 500) and centrifuged at 12,000 RPM for 60 minutes using a refrigerated high-speed centrifuge (model Hitachi CF16RN). The lower layer of liquid was then extracted and the content of the Moraceae plant extract containing hydroxyresveratrol (i.e., the encapsulated raw material) was detected using HPLC. The calculation formula is as follows:

[0029] like Figure 3 As shown, the encapsulation rate of the Moraceae plant extract containing hydroxy-resveratrol encapsulated in the E6 group is as high as 99.9999%, which can be regarded as basically complete encapsulation.

[0030] Next, 100 μL of the E6 group was taken and added to 900 μL of secondary water (ddH2O), mixed evenly, and transferred to the sample tank. The particle size distribution experiment was performed using a nanoparticle size and interface potential measurement instrument (MalvernNano ZS).

[0031] like Figure 4 As shown, the average particle size of the nanostructured lipid carriers in group E6 was 181.8 nm, and the particle size distribution quality was assessed as good.

[0032] Example 4 Percutaneous absorption experiment

[0033] The E6 group was applied to cosmetics such as creams and essences, and compared with the active ingredients that were not encapsulated by nanostructured lipid carriers (i.e., unencapsulated Moraceae plant extract containing hydroxy-resveratrol).

[0034] First, the formulas of the cream and the essence are shown in Tables 2 and 3, wherein the base formulation of the cream group comprises oil, emulsifier, water, moisturizer and preservative, wherein the oil is selected from at least one of isotridecyl isononanoate, pentaerythrityltetraethylhexanoate and camellia oleifera seed oil, the emulsifier is selected from at least one of polyacrylate-13, polyisobutylene, polysorbate-20, sodium arcylates copolymer, lecithin and sorbitanisostearate, and the moisturizer is selected from at least one of 1,3-propanediol, glycerol, 1,2-propylene glycol and 1,3-propanediol. The preservative is selected from at least one of 1,2-hexanediol, caprylhydroxamic acid, hydroxyacetophenone, dipropylene glycol and caprylyl glycol;The base formulation of the essence group includes water, a skin conditioner, a thickener, a preservative and a moisturizer, wherein the skin conditioner is selected from at least two of niacinamide, dipotassium glycyrrhizate, propanediol and ascorbyl glucoside, the thickener is selected from at least two of sodium arcylate copolymer, lecithin, xanthan gum and sodium hyaluronate, the preservative is selected from at least two of propylene glycol, 1,2-hexanediol and caprylhydroxamic acid, the moisturizer is selected from at least two of propylene glycol, glycerol, propylene glycol and glycerin. glycol), polyethylene glycol-400 (PEG-400), polyacrylate-13 (polyacrylate-13) and polyisobutylene (polyisobutylene).

[0035] Table 2

[0036] Table 3

[0037] Next, we adopted Bionic skin is used as a simulation model. Through the Franz Cell vertical diffusion tank system, the whitening ingredients are simulated to penetrate the skin. This system is specially used to perform drug absorption and release tests. It is also suitable for various types of samples, including liquids, lotions, gels, ointments and creams. According to the OECD429 guidelines, we added 30 mg of the test substance (i.e., E29, E32, ES1 and ES2 groups) to the upper supply tank. After 6 hours of simulated penetration, the experimental conditions were 37.5°C and 600RPM, and the following contents were collected respectively. All samples were analyzed by high-performance liquid chromatography to measure their contents: 1. Data from the bionic skin (indicates that ingredients with whitening effects penetrate and accumulate in the surface layer of the skin). 2. Data of the lower buffer solution (representing that the whitening ingredients penetrated the dermis and reached the lower skin tissue). All samples were analyzed by high performance liquid chromatography to measure their content.

[0038] The above experimental results are as follows Figure 5 As shown in the figure, it can be seen that in the E29 group, which is a general cream, about 35% of the whitening ingredients enter the epidermis, but fail to penetrate effectively. Bionic skin, reaching the lower buffer solution; in contrast, the total penetration rate (total absorption amount) of the E32 group containing NLC-encapsulated whitening ingredients in the cream is about 36.6%, of which the content in the membrane is about 31.2% and the content in the lower buffer solution is about 5.4%.

[0039] On the other hand, it can be seen from the figure that in the ES1 group, which is a general essence, about 36.8% of the whitening ingredients entered the epidermis and also failed to penetrate effectively. Bionic skin, reaching the lower buffer solution; however, the ES2 group containing whitening functional ingredients encapsulated by NLC in the essence has a total penetration rate (total absorption amount) of about 36.7%, of which the content in the membrane is about 32.3% and the content in the lower buffer solution is about 4.4%.

[0040] The above experimental results show that the E29 and ES1 groups without NLC-encapsulated whitening ingredients cannot effectively penetrate Bionic skin; and the E33 and ES2 groups with whitening ingredients coated with NLC can penetrate The whitening ingredients that penetrate from the surface of the bionic skin to the lower skin tissue are about 4.4-5.4%, which is converted into a relative penetration of 11.98% (4.4 / 36.7*100) to 14.75% (5.4 / 36.6*100), which can effectively penetrate into the lower liquid. It can be seen that the whitening ingredients are coated with NLC, so that the whitening ingredients can effectively penetrate into the lower skin tissue, so that the whitening ingredients act on the dermis of the skin, achieve percutaneous absorption, and enhance the whitening effect.

[0041] In summary, the nanostructured lipid carrier containing hydroxy-resveratrol of the present invention has good stability, coverage rate and particle size distribution, and is applied to cosmetics such as creams and essences, which can indeed allow the coated functional ingredients to penetrate deeply into the underlying skin tissue, so that the functional ingredients can play their role more efficiently.

[0042] A person of ordinary skill in the art to which the present invention belongs can understand from the foregoing that the present invention can be exemplified by other specific forms without changing the technical concepts or essential features of the content of the present invention. In this regard, the embodiments disclosed herein are only for illustration and should not be interpreted as limiting the scope of the content of the present invention. On the contrary, the content of the present invention not only includes the embodiments, but also includes the technical solutions obtained by making various changes, modifications or equivalent substitutions to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A nanostructured lipid carrier containing hydroxyresveratrol, characterized in that: The nanostructured lipid carrier containing hydroxy-resveratrol comprises the following components: 0.1-0.5 wt% of a Moraceae plant extract containing hydroxyresveratrol; 2.5-8wt% of cetyl palmitate; 2-5 wt% caprylic / capric triglyceride; 0-4.5wt% sorbitol monolaurate; 0-1.875wt% lecithin; 0-3 wt% of decyl glucoside; 0-6 wt% of polysorbate 80; and 79.5 to 89.075 wt% water, of which Based on the total weight of the nanostructured lipid carrier containing hydroxy-resveratrol, the sum of the above components is 100wt%; and When the content of any one or more of the above components is 0 wt %, it means that the nanostructured lipid carrier containing hydroxy-resveratrol does not contain any one or more of the above components, and the sum of the above components still maintains 100 wt %.

2. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 1, characterized in that: The Moraceae plant extract is selected from white mulberry extract or monkey fruit extract.

3. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 1, characterized in that: The nanostructured lipid carrier containing hydroxy-resveratrol comprises the following components: 0.3 wt% of a Moraceae plant extract containing hydroxyresveratrol; 5wt% cetyl palmitate; 5wt% caprylic / capric triglyceride; 4.5wt% sorbitan monolaurate; 3.5 wt% polysorbate 80; and 81.7 wt% water.

4. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 1, characterized in that: The preparation method of the nanostructured lipid carrier containing hydroxy-resveratrol is as follows: The moraceae plant extract containing hydroxy-resveratrol, the cetyl palmitate, the caprylic / capric triglyceride, the sorbitan monolaurate, the lecithin, the decyl glucoside, the polysorbate 80 and the water are mixed to obtain a mixture, and the mixture is subjected to a high shear homogenization step by a high-speed homogenizer to perform pre-emulsification to obtain a pre-emulsified mixture; transferring the pre-emulsified mixture to a high-pressure homogenizer for a high-pressure homogenization step to obtain a high-pressure treated mixture; and The high-pressure treated mixture is cooled in an ice bath and simultaneously transferred to the high-speed homogenizer for a low-shear homogenization step to obtain the nanostructured lipid carrier containing hydroxy-resveratrol.

5. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 4, characterized in that: In the high shear homogenization step, the preparation conditions of the nanostructured lipid carrier containing hydroxy-resveratrol are 70° C., rotation speed 8000 RPM, and pre-emulsification for 3 minutes.

6. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 4, characterized in that: In the high-pressure homogenization step, the preparation conditions of the nanostructured lipid carrier containing hydroxy-resveratrol are 65° C., 500 bar, and 5 to 6 cycles.

7. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 4, characterized in that: In the low shear homogenization step, the preparation conditions of the nanostructured lipid carrier containing hydroxy-resveratrol are cooling in an ice bath at 4° C., rotating at 4000 RPM, and emulsifying for at least 5 minutes until the temperature reaches 15-20° C.

8. The nanostructured lipid carrier containing hydroxy-resveratrol according to any one of claims 1 to 7, characterized in that: The nanostructured lipid carrier containing hydroxy-resveratrol is applied in cream or essence.

9. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 8, characterized in that: Based on the total weight of the cream or the essence, the nanostructured lipid carrier containing hydroxy-resveratrol accounts for 50 wt%.

10. The nanostructured lipid carrier containing hydroxy-resveratrol according to claim 8, characterized in that: When the nanostructured lipid carrier containing hydroxy-resveratrol is applied to the cream or the essence, the relative penetration amount of the nanostructured lipid carrier containing hydroxy-resveratrol into the underlying skin tissue is 11.98-14.75% based on the total absorption amount of the skin.

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