A nano-liposome protective agent with anti-ultraviolet and anti-oxidation functions, a preparation method, a preparation and applications thereof

Abstract

The application provides a kind of nano-liposome protective agent with anti-ultraviolet and antioxidant function, preparation method, preparation and application, it is related to cosmetic technical field.The nano-liposome protective agent includes the following components: benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sulfonic acid sodium, tris (tetramethylhydroxy piperidol) citrate, troxerutin / rutin and pentaerythritol tetra (bis-tert-butyl hydroxyl hydrogenated cinnamic acid) ester / tocopheryl acetate.The nano-liposome protective agent has anti-ultraviolet and antioxidant activity at the same time, when it is added to nano-liposome, it can effectively reduce the loss of active ingredient activity and nano-liposome phospholipid membrane material caused by ultraviolet and oxygen during storage and shelf life, achieve the effect of prolonging shelf life, improving curative effect and promoting the percutaneous penetration of nano-liposome.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of cosmetic technology, and particularly relates to a nano-liposome protective agent with anti-ultraviolet and anti-oxidation functions, a preparation method, a preparation and application thereof. BACKGROUND

[0002] The role of nano-liposomes in the field of cosmetics can be summarized as follows: improving the solubility of active ingredients, protecting active ingredients that are susceptible to change, improving transdermal effects, controlling the penetration rate of active substances to reduce irritation, and improving the permeability, application synergies and landing production effectiveness of active ingredients.

[0003] However, the structure layer of nano-liposomes is mainly composed of phospholipids or phosphatidylcholine, which can be oxidized by air and dissolved oxygen in solution when air is isolated, and phospholipids or phosphatidylcholine do not have the function of isolating the influence of ultraviolet light on the photodegradation of active ingredients and the influence of excited state intensity on the system. Chinese Invention Patent Application CN112006924A discloses a chitosan-modified composite vitamin nano-liposome, a preparation method thereof and application thereof in cosmetics. In order to overcome the shortcomings and deficiencies of the existing technology of the composite vitamin nano-liposome, a double-layer wrapping method is adopted, that is, a layer of chitosan coating is wrapped outside the liposome, which maximally solves the problems of oxidation and acidification of the liposome and the burst release of the composite vitamin, further improves the stability of the product, and non-patent document "Modification and Stability of Mulberry Anthocyanin Nano-liposomes [J]" (Chang Ying, Yang Xiaoxue, Jiao Yan, et al. Food Science and Technology, 2020, 45 (12): 251-257. DOI: 10.13684 / j.cnki.spkj.2020.12.038.) compared with unmodified liposomes, chitosan-modified anthocyanin nano-liposomes can reduce the degradation and loss of anthocyanins under the conditions of light, heat and metal ions, which helps to enhance the structural stability of mulberry anthocyanins and further play their effective biological activity, but the anti-ultraviolet and anti-oxidation functions of the nano-liposome wrapping system need to be further improved.

[0004] There are nearly thirty chemical UV absorbers allowed to be used in the Cosmetic Safety Technical Specifications (2015 Edition), and more inorganic UV absorbers, but the light stability of some UV absorbers is relatively poor, and isomerization is an important factor for the instability of some UV absorbers, and photo-induced degradation not only reduces the expected UV protection efficacy of some UV absorbers, but also may produce harmful photolysis products. And preventing the oxidation of active ingredients and preventing the oxidation of phospholipids are the basic requirements for building an antioxidant system, and antioxidants are the most effective form for the system to play an antioxidant role. From the efficacy and safety, it is necessary to require that the UV absorbers and antioxidants have high stability and significant efficacy. Therefore, it is necessary to develop a kind of protective agent with anti-ultraviolet and antioxidant functions for the nanoliposome encapsulation system. SUMMARY

[0005] The present application provides a kind of nanoliposome protective agent with anti-ultraviolet and antioxidant functions, preparation method, preparation and its application, to solve the problems existing in the prior art. The components of the nanoliposome protective agent include benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sodium sulfonate, tris (tetramethylhydroxy piperidol) citrate, troxerutin / rutin and pentaerythritol tetra (bis-tert-butyl hydroxy cinnamic acid) ester / tocopheryl acetate. The nanoliposome protective agent is added to the nanoliposome, which can effectively reduce the loss of active ingredients and nanoliposome phospholipid membrane material during storage and shelf life, prolong the shelf life, improve the effect and promote the transdermal penetration of nanoliposome.

[0006] To achieve the above object, the technical scheme adopted by the present application is as follows:

[0007] The first aspect of the present application is to provide a kind of nanoliposome protective agent with anti-ultraviolet and antioxidant functions, the nanoliposome protective agent includes the following components: benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sodium sulfonate, tris (tetramethylhydroxy piperidol) citrate, troxerutin / rutin and pentaerythritol tetra (bis-tert-butyl hydroxy cinnamic acid) ester / tocopheryl acetate.

[0008] Preferably, the components consist of benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sodium sulfonate 0.05-0.2 parts, tris (tetramethylhydroxy piperidol) citrate 0.05-0.2 parts, troxerutin / rutin 0.15-0.6 parts and pentaerythritol tetra (bis-tert-butyl hydroxy cinnamic acid) ester / tocopheryl acetate 0.05-0.2 parts by weight.

[0009] Further preferably, the components are composed of the following parts by weight: benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sodium sulfonate 0.1 parts, tri (tetramethylhydroxy piperidinol) citrate 0.15 parts, troxerutin / rutin 0.3 parts, and pentaerythritol tetra (bis-tert-butyl hydroxy hydrocinnamic acid) ester / tocopheryl acetate 0.1 parts.

[0010] The second aspect of the present application is to provide a preparation method of the above-mentioned nanoliposome protective agent, which comprises dissolving benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sodium sulfonate, tri (tetramethylhydroxy piperidinol) citrate, troxerutin / rutin and pentaerythritol tetra (bis-tert-butyl hydroxy hydrocinnamic acid) ester / tocopheryl acetate in propylene glycol solvent, and homogenizing to obtain the nanoliposome protective agent.

[0011] Preferably, the homogenization is mixing shear homogenization and / or microfluidizer homogenization.

[0012] Further preferably, the mixing shear pressure is 12000 rpm-16000 rpm, and the mixing shear homogenization time is 5-15 min.

[0013] Further preferably, the microfluidizer homogenization pressure is 12000 psi-20000 psi, and the homogenization times is 1-3 times.

[0014] The third aspect of the present application is to provide a nanoliposome preparation containing the above-mentioned nanoliposome protective agent.

[0015] Preferably, the nanoliposome preparation comprises the following preparation steps:

[0016] (1) dissolving benzotriazolyl dodecyl p-cresol / benzotriazolyl butylphenol sodium sulfonate, tri (tetramethylhydroxy piperidinol) citrate, troxerutin / rutin and pentaerythritol tetra (bis-tert-butyl hydroxy hydrocinnamic acid) ester / tocopheryl acetate in propylene glycol solvent, and homogenizing to obtain an alcohol phase;

[0017] (2) performing shear homogenization on the oil phase and the water phase of the liposome and the alcohol phase of step (1) to obtain a mixture initial milk;

[0018] (3) performing single homogenization treatment on the mixture initial milk by a microfluidizer homogenizer to obtain the nanoliposome preparation.

[0019] Further preferably, the weight percentage of the alcohol phase in the nanoliposome preparation in step (2) is 0.1-0.5%.

[0020] Further preferably, the homogenization time in step (2) is 5-15 min, and more specifically 10 min.

[0021] Further preferably, the microfluidization pressure in step (3) is 12000-20000 psi, and the microfluidization times is 1-3 times. More specifically, the microfluidization pressure is 16000 psi, and the microfluidization times is 3 times.

[0022] The fourth aspect of the present application provides the use of the above-mentioned nanoliposome protective agent or the nanoliposome protective agent prepared by the above-mentioned preparation method or the nanoliposome preparation containing the above-mentioned nanoliposome protective agent in the preparation of a cosmetic product with anti-ultraviolet and antioxidant functions.

[0023] Compared with the prior art, the present application has the following beneficial effects: (1) the nanoliposome protective agent provided by the present application has both anti-ultraviolet and antioxidant activities, and during the shelf life, the nanoliposome preparation has a good appearance, no rancidity or collapse, and the retention rate of active ingredients is higher; (2) the system transdermal performance is maintained and enhanced, and the effect of the system is enhanced. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 : Transmission electron microscope morphology observation chart of nanoliposome preparation 1 sample on the first day and after being placed at 45℃ for 28 days;

[0025] Figure 2 : Particle size detection results of nanoliposome preparation 1 sample on the first day and after being placed at 45℃ for 28 days;

[0026] Figure 3 : Zeta potential chart of nanoliposome preparation 1 sample on the first day and after being placed at 45℃ for 28 days;

[0027] Figure 4 : Stability detection results of nanoliposome preparation 1 sample. DETAILED DESCRIPTION

[0028] The following non-limiting examples can enable those skilled in the art to have a more comprehensive understanding of the present application, but do not limit the present application in any way. The following content is only an exemplary description of the scope of the present application, and those skilled in the art can make various changes and modifications to the present application according to the disclosed content, and it should also belong to the scope of the present application.

[0029] Example 1:

[0030] The component composition of the nanoliposome protective agents numbered 1-6 is shown in Table 1.

[0031] Table 1: Component composition of nanoliposome protective agent (unit: part)

[0032]

[0033] Example 2:

[0034] (1) Nanoliposome preparation 1-7

[0035] Oil phase composition: 15 parts of octyldodecanol, 6 parts of phospholipid, 3 parts of polysorbate-80

[0036] Water phase composition: 10 parts of glycerol, the balance of water

[0037] Alcohol phase: 1 part of nanoliposome protective agent numbered 1-6 or no nanoliposome protective agent

[0038] Active ingredient: 5 parts of 4-butylresorcinol

[0039] Note: The total amount of nanoliposome preparation 1-7 is 100 parts, and the balance is made up with water.

[0040] (2) Nanoliposome preparation 8-14

[0041] Oil phase composition: 8 parts of phospholipid, 40 parts of caprylic / capric triglyceride, 3 parts of polysorbate-80

[0042] Water phase composition: the balance of water

[0043] Alcohol phase: 1 part of nanoliposome protective agent numbered 1-6 or no nanoliposome protective agent

[0044] Active ingredient: 0.5 parts of astaxanthin

[0045] Note: The total amount of nanoliposome preparation 8-14 is 100 parts, and the balance is made up with water.

[0046] Test Example 1: Property detection of nanoliposome preparation 1

[0047] 1. Transmission electron microscope morphology observation

[0048] Test method: Hitachi HT7800 high-contrast transmission electron microscope was used to observe the surface morphology of the sample. The nanoliposome preparation 1 samples prepared on the 1st day and the 28th day were diluted to an appropriate concentration with ultrapure water at pH 7.0 before analysis. 10 μL of the diluted sample was dropped on the copper mesh, and after standing for 2 min, the excess sample around the copper mesh was absorbed. Then the copper mesh was negatively stained with 2.0 wt% uranyl acetate solution for 5 min. The excess staining solution was removed with filter paper, and an appropriate amount of sample was dropped on the copper mesh plate at room temperature, and then recorded data were taken, and the results are shown in Figure 1 wherein Figure 1 A in the above formula is the transmission electron microscope morphology observation result of the nanoliposome preparation 1 sample on the 1st day, Figure 1 B in the above formula is the transmission electron microscope morphology observation result of the nanoliposome preparation 1 sample on the 28th day.

[0049] 2. Particle size, PDI and Zeta potential

[0050] The average particle size, PDI, and Zeta potential of the samples were determined using a Zetasizer Nano ZSE nanoparticle size analyzer. First, the nanoliposome formulation 1 samples prepared on day 1 and day 28 were diluted 100-fold with ultrapure water. The test temperature was set at 25 °C, and the scattering angle at 90°. Each sample was scanned three times, and the average value was used as the measured value. The results are shown in the figure. Figure 2 ,in Figure 2 In the figure, A represents the average particle size of sample 1 of the nanoliposome formulation on day 1. Figure 2 In the table, B represents the average particle size of sample 1 of nanoliposome formulation on day 28. The specific values ​​are shown in Table 2.

[0051] Table 2: Average particle size detection results of sample 1 of nanoliposome formulation on day 1 and day 28

[0052]

[0053] The sample was not diluted before measuring the Zeta potential; it was directly added to the Zeta potential cell. The results are shown in [Figure number missing]. Figure 3 ,in Figure 3 In the figure, A represents the Zeta potential detection result of sample 1 of the nanoliposome formulation on day 1. Figure 3 In the table, B represents the zeta potential detection result of sample 1 of the nanoliposome formulation on day 28. Specific values ​​are shown in Table 3.

[0054] Table 3: Zeta potential detection results of sample 1 of nanoliposome formulation on day 1 and day 28.

[0055]

[0056] 3. Stability testing

[0057] The physical stability of 5% PT-NLPs was evaluated by the method of quantifying the change of the concentration of the localized dispersed particles by recording the light transmission trajectory through the whole sample and the amount of detectable incident light attenuation using LUMiSizer® 651 stability analyzer. About 15 mL of the sample of nanoliposome preparation 1 prepared on day 1 was injected into the bottom of the nanocolloidal stability test tube. The temperature setting for the high temperature six-month system stability test group (hereinafter referred to as the high temperature short-term group) was predicted to be 45 °C, the accelerated centrifugal rotation speed was 4000 rpm / min, and the sample transmission light characteristics were recorded every 30 s, with a total measurement time of 2 h. The temperature setting for the normal temperature two-year system stability test group (hereinafter referred to as the normal temperature long-term group) was predicted to be 25 °C, the accelerated centrifugal rotation speed was 4000 rpm / min, and the sample transmission light characteristics were recorded every 30 s, with a total measurement time of 8 h. The curve of the instability coefficient changing with time was drawn by software to represent the instability state of the sample during high-speed centrifugation. The greater the instability coefficient, the more dramatic the change, indicating that the physical stability of the sample during the storage period is poorer. The results are shown in Figure 4 wherein Figure 4 A in the formula (I) is the Lumisizer stability detection result of the nanoliposome preparation 1 sample in the high temperature short-term group, Figure 4 B in the formula (I) is the Lumisizer stability detection result of the nanoliposome preparation 1 sample in the normal temperature long-term group.

[0058] Test Example 2: Determination of 4-butylresorcinol content in nanoliposome preparations 1-7

[0059] Curve establishment: The content of 4-butylresorcinol was determined by high performance liquid chromatography (HPLC). 18Column (4.6 mm x 250 mm, 5 µm); column temperature: 30 ℃, detection wavelength: 280 nm, mobile phase: 50% acetonitrile-50% standard sodium phosphate buffer solution, flow rate: 1.0 mL / min; injection volume: 5 µL; program: isocratic elution; accurately weigh 4-butylresorcinol 0.1 g (accurate to 0.00001 g) into a 10 mL volumetric flask, and make up with acetonitrile to prepare a 10 g / L stock solution I for standby. Take 10 g / L 4-butylresorcinol standard solution 0.05 mL, 0.10 mL, 0.2 mL, 0.3 mL, 0.5 mL into a 10 mL volumetric flask, and make up with acetonitrile to prepare a standard series solution of 50 µg / mL, 100 µg / mL, 200 µg / mL, 300 µg / mL, 500 µg / mL, shake well, and standby. Analyze according to the chromatographic conditions to obtain the standard substance chromatogram, and take the peak area and the mass concentration of the sample as the vertical and horizontal coordinates to obtain the standard curve equation by linear regression, and the linear range is 10-500 g / mL. In this patent, the encapsulation efficiency is calculated according to the following formula: drug encapsulation efficiency (%) = amount of 4-butylresorcinol encapsulated / total amount of 4-butylresorcinol x 100%.

[0060] wherein the amount of 4-butylresorcinol encapsulated is determined: weigh 80 mg of 4-butylresorcinol liposome solution into a 10 mL centrifuge tube, add 6 mL of ultrapure water, and shake to disperse uniformly at room temperature. Place the centrifuge tube in the centrifuge, centrifuge at 3000 r / min for 5 min, take 5 mL of supernatant, pre-freeze in a-40 ℃ refrigerator for 3 h, and then freeze-dry in a freeze-dryer. Take the freeze-dried powder, weigh it using a weighing bottle, and then add it to 2 mL of acetonitrile and vortex for 1 min to dissolve the membrane material, and then add 4 mL of acetonitrile and vortex for 1 min to extract 4-butylresorcinol. Take 2 mL of n-hexane and dilute it with an equal amount of anhydrous ethanol, and then centrifuge 1 mL of the diluted solution at 5000 r / min for 10 min. Finally, take 800 µL of the centrifuged supernatant and inject it into the sample bottle of the automatic HPLC for 4-butylresorcinol content detection. After conversion, the 4-butylresorcinol content encapsulated by the liposome per unit mass (M1) is calculated, and the amount of 4-butylresorcinol encapsulated is M1 x the design formulation amount of lecithin blank material. Store at room temperature for 12 months, and the 4-butylresorcinol content determination results of the nano-liposome preparations 1-7 are shown in Table 4.

[0061] Table 4: Stability test results of nano-liposome preparations 1-7

[0062]

[0063] From the experimental results, it can be seen that the content of 4-butylresorcinol in preparation 1 and preparation 6 is stable, the destruction of 4-butylresorcinol in preparation 7 is the most serious, and the content of 4-butylresorcinol in preparations 2-5 decreases more obviously than that in preparations 1 and 6. At the same time, according to the shape observation of the nano-liposome preparation, the appearance of preparation 7 collapses seriously, and the appearance of preparations 1 and 6 has no obvious change after being placed at room temperature for 12 months, and there is no particle feeling and stratification phenomenon, and the particle size has no obvious change. The appearance of preparations 2-5 has different degrees of collapse. Preparations 1 and 6 have good stability, so the liposome protective agent of the application can obviously increase the stability of the nano-liposome, and well protect the active ingredients wrapped in the nano-liposome.

[0064] Test example 3: determination of astaxanthin content in nano-liposome 8-14

[0065] The content of astaxanthin was determined by high performance liquid chromatography (HPLC). 18 Column (4.6mmx250mm, 5µm); column temperature: 30℃, detection wavelength: 280nm, mobile phase: 50% acetonitrile-50% buffer solution, flow rate: 1.0mL / min; injection volume: 5µL; program: isocratic elution; accurately weigh 0.1g of astaxanthin (accurate to 0.00001g) into a 10mL volumetric flask, and make up with acetonitrile to prepare a 10g / L stock solution I for standby. Take 0.05mL, 0.10mL, 0.2mL, 0.3mL and 0.5mL of 10g / L astaxanthin standard solution into a 10mL volumetric flask, and make up with acetonitrile to prepare 50µg / mL, 100µg / mL, 200µg / mL, 300µg / mL and 500µg / mL standard series solutions, and shake well for standby. Analyze according to the chromatographic conditions to obtain the chromatogram of the standard substance, and take the peak area and the mass concentration of the sample as the vertical and horizontal coordinates to obtain the standard curve equation by linear regression. In this patent, the encapsulation efficiency is calculated according to the following formula: drug encapsulation efficiency (%) = amount of encapsulated astaxanthin / total amount of astaxanthin x 100%.

[0066] Determination of the amount of encapsulated astaxanthin: 80 mg of astaxanthin liposome solution was weighed into a 10 mL centrifuge tube, 6 mL of ultrapure water was added, and the mixture was shaken and dispersed uniformly at room temperature. The centrifuge tube was placed in a centrifuge and centrifuged at 3000 r / min for 5 min. 5 mL of supernatant was taken and pre-frozen in a refrigerator at -40°C for 3 h, and then dried in a freeze dryer. The freeze-dried powder was weighed and recorded, and then the powder was added to 2 mL of acetonitrile and vortexed for 1 min to dissolve the membrane material. 4 mL of acetonitrile was added and vortexed for 1 min to extract astaxanthin. 2 mL of n-hexane was added to dilute the same amount of anhydrous ethanol, and 1 mL of the diluted solution was centrifuged at 5000 r / min for 10 min. Finally, 800 μL of the centrifugal supernatant was injected into the sample bottle of the automatic HPLC for astaxanthin content detection. After conversion, the amount of astaxanthin encapsulated by the liposome per unit mass (M1) was calculated. The amount of encapsulated astaxanthin was M1x the design formula amount of phospholipid blank material. After 12 months of storage at room temperature, the astaxanthin content of the nano-liposome preparation 8-14 was determined, and the results are shown in Table 5.

[0067] Table 5: Results of stability experiment of nano-liposome preparation 8-14

[0068]

[0069] From the experimental results, it can be seen that the astaxanthin content of preparation 8 and preparation 13 is stable, the astaxanthin in preparation 14 is destroyed the most seriously, and the astaxanthin content in preparation 9-12 decreases more obviously than that in preparation 8 and preparation 13. At the same time, according to the observation of the shape of the nano-liposome preparation, the appearance of preparation 14 collapses seriously, and the appearance of preparation 8 and preparation 13 does not change obviously after 12 months of storage at room temperature, without particle feeling and stratification phenomenon, and the particle size does not change obviously. The appearance of preparation 9-12 collapses to different degrees. Preparation 8 and 13 have good stability, so the liposome protective agent of the present application can significantly increase the stability of the nano-liposome and well protect the active ingredients encapsulated in the nano-liposome.

[0070] Test Example 4: Transdermal experiment

[0071] The treated pigskin was fixed on a Frank diffusion cell, PBS buffer (PH = 7.4) was added to the receiving cell, and preparation 1-7 was added to the supply chamber, and the water bath was kept at 37°C, and the stirring speed was 300 r / min -1 At 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h, and 48 h, the receiving liquid was taken and an equal amount of PBS was added. The receiving liquid was diluted 10 times with the mobile phase, and the content of 4-butylresorcinol was determined by the high performance liquid chromatography method in Test Example 1, and the cumulative transdermal penetration amount was calculated. The results are shown in Table 6.

[0072] Table 6: Transdermal experiment results of preparation 1-7

[0073]

[0074] From the experimental results, it can be seen that the cumulative permeation amount of 4-butylresorcinol in preparation 1 and preparation 6 is obviously higher than that in preparations 2-5, and more obviously higher than that in preparation 7. Therefore, the liposome protective agent of the present application can enhance the transdermal performance of the nano-liposome system.

Claims

1. A nano-liposome formulation containing a nano-liposome protective agent having an anti-UV and anti-oxidation function, characterized in that, The nanoliposome protective agent is composed of the following components by weight: benzotriazolyl dodecyl p-cresol 0.05-0.2 parts, tris (tetramethylhydroxy piperidol) citrate 0.05-0.2 parts, troxerutin 0.15-0.6 parts and pentaerythritol tetra (bis-tert-butyl hydroxy cinnamic acid) ester 0.05-0.2 parts; The nanoliposome preparation includes the following preparation steps: (1) Dissolve benzotriazolyl dodecyl p-cresol, tris (tetramethylhydroxy piperidol) citrate, troxerutin and pentaerythritol tetra (bis-tert-butyl hydroxy cinnamic acid) ester in propylene glycol solvent, homogenize to obtain an alcohol phase; (2) Shearing homogenization of the oil phase and the water phase of the liposome and the alcohol phase of step (1) to obtain a mixture of initial milk; (3) The mixture of initial milk is subjected to single homogenization treatment by a microfluidic homogenizer, and the nanoliposome preparation is obtained.

2. The nanoliposome formulation of claim 1, wherein, The nanoliposome protective agent is composed of the following components by weight: benzotriazolyl dodecyl p-cresol 0.1 parts, tris (tetramethylhydroxy piperidol) citrate 0.15 parts, troxerutin 0.3 parts and pentaerythritol tetra (bis-tert-butyl hydroxy cinnamic acid) ester 0.1 parts.

3. The nanoliposome formulation of claim 1, wherein, Step (1) The homogenization is mixed shearing homogenization and homogenization by a microfluidic homogenizer.

4. The nanoliposome formulation of claim 3, wherein, The mixed shearing pressure is 12000 rpm-16000 rpm, and the mixed shearing homogenization time is 5-15 min; the microfluidic homogenization pressure is 12000 psi-20000 psi, and the homogenization frequency is 1-3 times.

5. Use of the nanoliposome preparation according to any one of claims 1-4 in the preparation of cosmetics with anti-ultraviolet and antioxidant functions.

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