Nano-emulsion wrapped with tocopheryl acetate and preparation method of nano-emulsion

Abstract

The invention discloses a nano-emulsion coated with tocopheryl acetate and a preparation method thereof, and the nano-emulsion coated with tocopheryl acetate is prepared from the following components in percentage by mass: 2-6% of polyglycerol-10 diisostearate, 0.2-3% of tocopheryl acetate, 10-20% of camellia seed oil, 1-5% of sodium dodecyl benzene sulfonate and the balance of water. The mass percent of the distilled water is 2-5%, the mass percent of the glycerol is 65-85%, and the sum of the mass percent of all the components is 100%. According to the invention, plant-derived camellia seed oil is selected as an oil phase of a nano-emulsion system, so that the fluidity of lipid can be increased, and the efficacy can be improved.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and particularly to a method for preparing nanoemulsion encapsulating tocopheryl acetate. Background Art

[0002] Tocopheryl acetate, which is the acetate form of vitamin E, is a commonly used active substance in cosmetics as a potent antioxidant. It can scavenge free radicals in the body, reduce the damage of ultraviolet rays to the skin, restore the proliferative activity of cells, delay skin photoaging, and achieve the effect of anti-aging. Tocopheryl acetate is also an effective emollient, which helps to moisten and soften the skin, improve the texture and appearance of the skin, and provide multiple benefits for the skin and formulations.

[0003] Since tocopheryl acetate is a fat-soluble vitamin, it is prone to oxidation in light and air, resulting in a decrease in its biological activity. To maintain its stability, esterification modification is usually required, but this will increase the production cost. Secondly, although tocopheryl acetate has excellent efficacy, due to its own solubility problem, it cannot be added in aqueous solution non-emulsified systems (such as water, essence, mask and other products), and it is difficult to penetrate the skin through transdermal absorption to exert its efficacy. Therefore, its application in the cosmetics field still faces great limitations.

[0004] Nanoemulsion is a colloidal system composed of two immiscible liquids. The average particle size of the dispersed phase is generally between 10 and 200 nm. The emulsion droplets are spherical, uniform in size, and the overall appearance is a light blue transparent emulsion, and it will not stratify when heated or centrifuged. Nanoemulsion not only has the advantages of simple preparation process, good solubilization effect, slow release, high bioavailability, etc., but also can increase the solubility of the oil phase in water, improve the oil loading capacity, and show great application potential in various fields such as biology, food, and medicine.

[0005] Nanoemulsion is a kinetically stable system, but it is prone to stratification after long-term storage, resulting in poor stability. To solve this problem, a long-chain oil phase can be added to the nanoemulsion to reduce its solubility in water, but this method still has problems such as high interfacial tension and difficult emulsification; and in a low-temperature environment, the nanoemulsion is prone to solidification and cannot flow, resulting in poor stability.

[0006] Currently, there have been studies on tocopheryl acetate emulsion. For example, a microemulsion system of tocopheryl acetate is formed by adding a large amount of emulsifier and co-emulsifier, but the large addition of emulsifier is not friendly to the skin and may even cause certain irritation, resulting in skin allergy. Therefore, usually, on the premise of ensuring the stability of the emulsion, the lower the content of the emulsifier added to the system, the better. So the application of this kind of system in the cosmetics field has great limitations and is not easily accepted by consumers. Summary of the Invention

[0007] The object of the present invention is to solve the application limitations of tocopheryl acetate in the field of cosmetics, and provide a preparation method of nanoemulsion encapsulating tocopheryl acetate with simple process, small particle size, good water solubility, good stability and good transdermal effect.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows: The nanoemulsion encapsulating tocopheryl acetate comprises polyglyceryl-10 diisostearate at a mass percentage of 2-6%, tocopheryl acetate at a mass percentage of 0.2-3%, camellia seed oil at a mass percentage of 10-20%, distilled water at a mass percentage of 2-5% and glycerol at a mass percentage of 65-85%, and the sum of each component is 100%.

[0009] In one embodiment, the polyglyceryl-10 diisostearate can specifically be selected from any one value of 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6% or any range formed by them.

[0010] In one embodiment, the camellia seed oil can specifically be selected from any one value of 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, 15%, 15.5%, 16%, 16.5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20% or any range formed by them.

[0011] In one embodiment, the preferred mass percentage of glycerol is 68-83%, and can specifically be selected from any one value of 68%, 68.5%, 69%, 69.5%, 70%, 70.5%, 71%, 71.5%, 72%, 72.5%, 73%, 73.5%, 74%, 74.5%, 75%, 75.5%, 76%, 76.5%, 77%, 77.5%, 78%, 78.5%, 79%, 79.5%, 80%, 80.5%, 81%, 81.5%, 82%, 82.5%, 83% or any range formed by them.

[0012] In one embodiment, the preferred mass percentage of distilled water is 3-5%, and can specifically be selected from any one value of 3%, 3.5%, 4%, 4.5%, 5% or any range formed by them.

[0013] In one embodiment, the mass percentage of tocopheryl acetate is 0.5-3%, and can specifically be selected from any one value of 0.5%, 1%, 1.5%, 2%, 2.5%, 3% or any range formed by them.

[0014] The present invention also provides a preparation method of nanoemulsion encapsulating tocopheryl acetate, which is carried out according to the following steps:

[0015] (1) At room temperature, stir and mix the formula amounts of glycerol, polyglyceryl-10 diisostearate, and water until homogeneous, and label it as Liquid A;

[0016] (2) At room temperature, stir and mix the formula amounts of tocopheryl acetate and camellia seed oil until homogeneous, and label it as Liquid B;

[0017] (3) Stir and mix the prepared Liquid A and Liquid B until homogeneous. Subsequently, homogenize them in a high-pressure homogenizer to obtain a crude tocopheryl acetate emulsion;

[0018] (4) Homogenize the above-mentioned crude tocopheryl acetate emulsion with a high-pressure microfluidic homogenizer to obtain a clear and transparent nanoemulsion encapsulating tocopheryl acetate.

[0019] In one embodiment, in step (3) of the method, the high-pressure homogenizer is homogenized at 7,000 - 12,000 rpm, preferably 8,000 rpm, and the homogenization time is 2 - 4 min, preferably 3 min.

[0020] In one embodiment, in step (4) of the method, the high-pressure microfluidic homogenizer is homogenized at 18,000 psi - 22,000 psi and homogenized 2 - 5 times; more preferably, in step (4), the high-pressure microfluidic homogenizer is homogenized at 20,000 psi and homogenized 3 times.

[0021] The present invention also provides the application of the nanoemulsion encapsulating tocopheryl acetate in the preparation of skin care products or cosmetics.

[0022] Advantages of the present invention:

[0023] (1) The present invention selects plant-derived camellia seed oil as the oil phase of the nanoemulsion system, which can increase the fluidity of lipids and improve the penetration of the anti-aging, whitening, repair, and antioxidant and other efficacy activities of tocopheryl acetate.

[0024] (2) The present invention solves the problems of the antioxidant active substance tocopheryl acetate being difficult to dissolve, having poor stability, and lacking application prospects in the emulsion system, and at the same time improves the moisturizing performance of the product.

[0025] (3) The present invention provides a preparation method of a supramolecular nanoemulsion, which has simple process, mild conditions, and has the advantages of simple and controllable operation, good repeatability, and time-saving. It solves the problems of poor fluidity, easy stratification, and poor stability of the nanoemulsion. The prepared nanoemulsion product of tocopheryl acetate has a clear and transparent appearance, good water solubility, is easy to disperse in the water phase, the particle size distribution range is between 100 - 200 nm, and it is stable at high temperature for 1 month and stable at low temperature for 3 months. It conforms to the basic characteristics of nanoscale materials and has strong application potential. Description of the Drawings

[0026] Figure 1 are nano - emulsion samples prepared from different oil phases and their dispersion effects after being diluted to 1% (1 g emulsion + 99 g water mixed uniformly) in the aqueous phase.

[0027] Figure 2 are different reactions of water and the sample of Example 3 under light.

[0028] Figure 3 is the appearance comparison of the sample of Example 3 after being placed at different temperatures for 1 month.

[0029] Figure 4 are the particle size detection results of the sample of Example 3 after being placed at different temperatures for 1 month. Detailed Description of the Invention

[0030] The following examples facilitate a better understanding of the present invention, but do not limit the present invention. The experimental methods in the following examples are all conventional methods unless otherwise specified. The test materials used in the following examples are all obtained from regular biochemical reagent stores unless otherwise specified.

[0031] Examples 1 - 5

[0032] (1) Under room - temperature conditions, add the formulated amounts of glycerol, polyglyceryl - 10 diisostearate, and water to a beaker, and stir and mix until homogeneous, marked as Solution A;

[0033] (2) Under room - temperature conditions, add the formulated amounts of tocopheryl acetate and camellia seed oil to another beaker, and stir and mix in a certain proportion until homogeneous, marked as Solution B;

[0034] (3) Stir and mix the prepared Solution A and Solution B until homogeneous, and then place them in a high - pressure homogenizer and homogenize at 8000 rpm for 3 min to obtain a crude tocopheryl acetate emulsion. A crude emulsion can be obtained by homogenizing at 7,000 - 12,000 rpm.

[0035] (3) Homogenize the above - mentioned crude tocopheryl acetate emulsion 3 times at 20,000 psi with a high - pressure microfluidizer to obtain a clear and transparent nano - emulsion encapsulating tocopheryl acetate.

[0036] The percentages of each component in steps (1) and (2) are as shown in Table 1:

[0037] Table 1

[0038]

[0039] Investigate the relevant properties of the tocopheryl acetate nano - emulsions prepared in Examples 1 - 5 and Comparative Examples 1 - 2.

[0040] 1. Appearance properties of tocopheryl acetate nanoemulsion:

[0041] Observed with the naked eye, the final products of the nanoemulsions encapsulating tocopheryl acetate prepared in Examples 1 - 5 all presented as transparent / semi - transparent liquids with a slightly blue light. The samples could form a light path through the light, producing the Tyndall effect, which proved the formation of the nanoemulsion structure, as Figure 2 ; The final products of the nanoemulsions encapsulating tocopheryl acetate prepared in Comparative Examples 1 - 2 all presented as opaque or layered liquids, and no nanoemulsion was formed.

[0042] 2. Particle size detection of tocopheryl acetate nanoemulsion:

[0043] In this invention, a particle size analyzer was used to measure the particle size of the tocopheryl acetate nanoemulsion prepared in Examples 1 - 5. The detection results showed that the particle size distribution range was between 150 - 180 nm, which met the basic characteristics of nanoscale materials.

[0044] 3. Water solubility test of tocopheryl acetate nanoemulsion:

[0045] The tocopheryl acetate nanoemulsion prepared by the methods of Examples 1 - 5 could quickly dissolve in water in any proportion. The solution was clear and transparent without impurities, indicating that the nanoemulsion had good water solubility.

[0046] 4. Stability investigation of tocopheryl acetate nanoemulsion:

[0047] According to the requirements of the appendix of the 2000 edition of the Pharmacopoeia of the People's Republic of China, the tocopheryl acetate nanoemulsion prepared by the methods of Examples 1 - 5 was centrifuged at 4,000 r / min for 15 minutes, and no layering phenomenon was observed, which proved that the stability of the tocopheryl acetate nanoemulsion prepared by the methods of Examples 1 - 5 met the requirements.

[0048] The tocopheryl acetate nanoemulsion prepared by the method of Example 3 was placed at 4°C, 25°C, and 45°C for 1 month respectively, and its appearance was observed as Figure 3 shown. It could still maintain the initial state without precipitation or separation; its particle size was analyzed, and the results are shown in Figure 4 , and the particle sizes at different temperatures were basically the same, which proved that it had good storage stability.

[0049] Comparative Examples 3 - 4

[0050] The differences between Comparative Examples 3 - 4 and Example 3 were that in Comparative Example 3, the camellia seed oil in Example 3 was replaced by squalane; in Comparative Example 4, the camellia seed oil in Example 3 was replaced by glyceryl caprylate / caprate (GTCC), and the others were the same as in Example 3.

[0051] It was found that when squalane and glyceryl caprylate / caprate (GTCC) were used as the oil phase, the prepared emulsion had a relatively large particle size, which was not conducive to product stability and transdermal effect. Moreover, the appearance was opaque and turbid, and the dispersibility in the aqueous solution was poor. See Figure 1 , and the results showed that for the commonly used oil components in the market, such as squalane and glyceryl caprylate / caprate (GTCC), etc., the prepared emulsion had a relatively high particle size, and the samples were opaque, with poor dispersibility in the aqueous phase. Therefore, the camellia seed oil selected in the present invention has certain advantages in the microemulsion system.

[0052] Comparative Examples 5-7

[0053] The differences from Example 3 were that in Comparative Example 5, the high-pressure microfluidic homogenizer at 20,000 psi in Example 3 was replaced with a high-pressure microfluidic homogenizer at 10,000 psi; in Comparative Example 6, the high-pressure microfluidic homogenizer at 20,000 psi in Example 3 was replaced with a high-pressure microfluidic homogenizer at 15,000 psi, and in Comparative Example 7, the high-pressure microfluidic homogenizer at 20,000 psi in Example 3 was replaced with a high-pressure microfluidic homogenizer at 25,000 psi. Other conditions were the same as those in Example 3.

[0054] It was found that the sample could obtain a clear and transparent nanoemulsion after being treated at 20,000 psi in Example 3. When the pressure was lower than this value, the particle size was larger. Although the sample was clear and transparent, it could not form the Tyndall effect and could not meet the requirements. When the pressure was higher than this value, the nano-droplets were damaged, the particle size of the sample would increase instead, and the appearance transparency decreased.

[0055] Performance Test of Example 6

[0056] Group 1 was the basic essence without adding the microemulsion sample, Group 2 was adding the microemulsion sample prepared in Example 1 to the basic essence; Group 3 was adding the microemulsion sample prepared in Example 3 to the basic essence. The percentages of each component in Groups 1-3 are shown in Table 2 as follows:

[0057] Table 2

[0058]

[0059]

[0060] The finished essence products prepared from Groups 1-3 were subjected to performance tests, and the test indexes and test methods are as follows:

[0061] (1) Skin irritation: Fifteen volunteers aged 18 to 60 years old were selected. Referring to the "Technical Specifications for Cosmetics Safety (2015 Edition)" - Human Skin Patch Test for irritation testing, Comparative Examples 8 - 10 were respectively added into the patch test devices. Then, the patch test devices were attached to the inner side of the volunteers' arms with non-irritating tape, and gently pressed with the palm to make it evenly attached to the skin. After 24 hours, the test substance patch test devices were removed, and the residual test substance at the test site was gently wiped off with a moistened absorbent cotton ball. After 0.5 hour, when the indentation disappeared, the skin reaction was observed. If the result was negative, it was observed again 24 hours after removing the patch.

[0062] The test results are shown in Table 3. It can be seen from the test results that adding the microemulsion prepared by the present invention to the essence has no adverse reactions to human skin and has less irritation to the skin.

[0063] Table 3

[0064]

[0065] (2) Moisturizing property: Fifteen volunteers aged 18 to 60 years old were selected. Three different areas were located on the inner side of the arm, and the initial skin moisture content was measured respectively using a Real Bubee skin moisture tester. Subsequently, Comparative Examples 8 - 10 were quantitatively applied to the above three different areas, and gently kneaded with the palm to make the application uniform. After the sample was fully absorbed, the skin moisture content was measured again. The moisture was measured at 10 minutes and 60 minutes respectively. After 3 measurements in each area, the average value was calculated.

[0066] The test results are shown in Table 4. Adding the microemulsion prepared by the present invention to the essence, the immediate moisturizing performance of the products in Group 2 and Group 3 has been significantly improved and still has good moisturizing performance after one hour, and the improvement is significant compared with other groups.

[0067] Table 4

[0068]

[0069] Note: The values in the table are the average values calculated from the tests of 15 volunteers at different time points.

Claims

1. A nanoemulsion encapsulating tocopherol acetate, characterized in that: The invention comprises 2-6% by mass of polyglycerol-10 diisostearate, 0.2-3% by mass of tocopherol acetate, 10-20% by mass of camellia seed oil, 2-5% by mass of distilled water and 65-85% by mass of glycerol, the sum of all components is 100%, wherein the preferred mass percentage of the glycerol is 68-83%.

2. The nanoemulsion encapsulating tocopherol acetate according to claim 1, characterized in that: The mass percentage of distilled water is 3-5%.

3. The nanoemulsion encapsulating tocopherol acetate according to claim 1, characterized in that: The mass percentage of tocopherol acetate is 0.5-3%.

4. The method for preparing a nanoemulsion containing tocopherol acetate according to claim 1, wherein: Follow these steps: (1) At room temperature, stir and mix the formulated amounts of glycerol, polyglyceryl-10 diisostearate and water until they are uniform, which is labeled as liquid A; (2) At room temperature, stir and mix the formulated amount of tocopherol acetate and camellia seed oil until they are uniform, which is labeled as liquid B; (3) stirring and mixing the prepared liquid A and liquid B until they are uniform, and then homogenizing them in a high-pressure homogenizer at 7,000 to 12,000 rpm to obtain a crude emulsion of tocopherol acetate; (4) homogenizing the tocopherol acetate crude emulsion by a high-pressure microfluidizer to obtain a clear and transparent nanoemulsion encapsulating tocopherol acetate.

5. The preparation method according to claim 4, characterized in that: The mass percentage of distilled water is 3-5%.

6. The preparation method according to claim 4, characterized in that: The mass percentage of tocopherol acetate is 0.5-3%.

7. The preparation method according to claim 4, characterized in that: The homogenization time in step (3) is 3 minutes.

8. The preparation method according to claim 4, characterized in that: In step (4), the mixture is homogenized by a high pressure microfluidizer at 18,000 psi to 22,000 psi for 2 to 5 times.

9. The preparation method according to claim 8, characterized in that: In step (4), the mixture was homogenized with a high pressure microfluidizer at 20,000 psi for 3 times.

10. Use of the nanoemulsion encapsulating tocopherol acetate according to any one of claims 1 to 3 in the preparation of skin care products or cosmetics.

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