Thermo-sensitive retinol lipid carrier as well as preparation method and application thereof

Abstract

The invention provides a temperature-sensitive retinol lipid carrier as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The thermo-sensitive retinol lipid carrier provided by the invention is prepared from the following components in percentage by mass: 0.1 to 15 percent of retinol active matter, 1 to 20 percent of grease, 4 to 15 percent of lecithin, 0.05 to 5 percent of antioxidant, 0.1 to 25 percent of poloxamer, 0 to 5 percent of preservative and the balance of deionized water, and the pH is 6 to 8. The temperature-sensitive retinol lipid carrier is high in high-temperature acceleration stability, the monthly retention rate is greater than 85%, the temperature-sensitive retinol lipid carrier is not easy to discolor, and demulsification and oil floating are avoided. Besides, the temperature-sensitive retinol lipid carrier has a temperature-sensitive slow release characteristic, so that slow release of the retinol lipid carrier in cosmetic skin care application is facilitated, and irritation of retinol active matters in cosmetic skin care application can be reduced.

Description

[0001] The present invention is a divisional application of a Chinese patent application filed on October 21, 2024, with application number 2024114652786 and invention name “A thermosensitive retinol lipid carrier and its preparation method and application”, all contents of which are incorporated by reference in the application. Technical Field

[0002] The present invention relates to the field of biomedicine technology, and in particular to a thermosensitive retinol liposome and a preparation method and application thereof. Background Art

[0003] Retinol, also known as vitamin A or retinol, is a fat-soluble vitamin with multiple biological activities. It participates in a variety of biological processes in the human body, such as cell growth, differentiation and development. In the field of cosmetics, retinol is highly praised for its significant anti-aging, anti-wrinkle, anti-acne and skin tone regulating effects.

[0004] However, retinol has encountered challenges in cosmetic applications. First, retinol is easily degraded under conditions such as light, oxygen, and high temperature, resulting in reduced activity, resulting in negligible retinol content during the shelf life. Secondly, retinol is a fat-soluble active substance with a very low water solubility. In the early stage of cosmetic configuration, it is usually dissolved in the oil phase, and then emulsified to form the desired product, or the intermediate is encapsulated by retinol and directly added to the product in the later stage of cosmetic configuration. It is difficult to achieve the ideal concentration in the cosmetic formula, which limits its efficacy. Due to the nature of retinol itself, the skin bioavailability of retinol is often relatively low. Finally, due to the tolerance problems of some consumers, retinol products may cause these consumers to experience adverse reactions such as dry skin, erythema, and desquamation when using cosmetics containing retinol, which affects the product experience and consumer acceptance.

[0005] Therefore, the main technical solution to the above problems in the cosmetics industry is the inclusion carrier technology. Encapsulating retinol with a carrier can not only delay the chemical stability of retinol, but also enhance the skin bioavailability of retinol. At the same time, due to the sustained release effect of the carrier, the irritation of retinol is reduced. The inventors conducted high-temperature accelerated tests on retinol inclusion products used in cosmetics on the market. The weekly degradation rate of retinol is relatively high. For example, the inclusion product retinol nanoemulsion showed demulsification and oil floating after 2 weeks of accelerated testing at 45°C, and the weekly degradation rate was greater than 10%. Retinol powder is insoluble in water and oil. After a 2-week accelerated test at 45°C, there was no change in appearance, but the weekly degradation rate was greater than 10%. Therefore, the current lack of highly stable retinol inclusion products in the cosmetics industry has greatly limited the widespread application of retinol.

[0006] Liposome is a lipid carrier system composed of a bilayer of lecithin, which has good biocompatibility and stability. The main component of liposome is lecithin, which is also the main component of human cell membrane. Lecithin has good biocompatibility and has become the mainstream as a membrane material for wrapping carriers in carrier systems used in the biological, pharmaceutical and cosmetic industries.

[0007] Poloxamer 407 is a thermosensitive block copolymer with a molecular weight between 9840 and 14600. It has the functions of emulsification, solubilization and wetting. One of the unique properties of Poloxamer 407 aqueous solution is its temperature sensitivity, that is, it is in a liquid state when it is below body temperature (37°C), and turns into a gel state when it is above body temperature (40°C). This temperature-sensitive property makes Poloxamer 407 have potential application value in the medical field.

[0008] Therefore, overcoming the application problem of poor stability of retinol in the prior art and providing a highly stable, low-irritation retinol lipid carrier system with slow release is a current research hotspot. Summary of the invention

[0009] In view of the above-mentioned deficiencies, the present invention aims to provide a thermosensitive retinol lipid carrier and its preparation method and application. The thermosensitive retinol lipid carrier provided by the present invention comprises, by mass percentage: 0.1%-15% retinol active substances, 1%-20% oil, 4%-15% lecithin, 0.05%-5% antioxidant, 0.1%-25% poloxamer, 0%-5% preservative, the balance is deionized water, and the pH is 6-8. The thermosensitive retinol lipid carrier has high high temperature accelerated stability, a monthly retention rate of more than 85%, is not easy to change color, and does not break emulsions or float oil. In addition, the improved thermosensitive retinol lipid carrier has a temperature-sensitive slow release characteristic, which is conducive to the slow release of retinol lipid carriers in cosmetic skin care applications, and can reduce the irritation of retinol active substances in cosmetic skin care applications.

[0010] To achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0011] In the first aspect, the present invention provides a thermosensitive retinol lipid carrier, characterized in that the thermosensitive retinol lipid carrier comprises, by mass percentage: 0.1%-15% retinol active ingredient, 1%-20% oil, 4%-15% lecithin, 0.05%-5% antioxidant, 0.1%-25% poloxamer, 0%-5% preservative, and the balance is deionized water; the pH of the thermosensitive retinol lipid carrier is 6-8.

[0012] Specifically, the thermosensitive retinol lipid carrier includes, by mass percentage, 0.1%-0.5%, 0.5%-1%, 1%-2%, 2%-3%, 3%-4%, 4%-5%, 5%-6%, 6%-7%, 7%-8%, 8%-9%, 9%-10%, 10%-11%, 11%-12%, 12%-13%, 13%-14% or 14%-15% retinol active ingredient.

[0013] Specifically, the thermosensitive retinol lipid carrier includes, by mass percentage, 1%-2%, 2%-3%, 3%-4%, 4%-5%, 5%-6%, 6%-7%, 7%-8%, 8%-9%, 9%-10%, 10%-11%, 11%-12%, 12%-13%, 13%-14%, 14%-15%, 15%-16, 16%-17%, 17%-18%, 18%-19% or 19%-20% oil.

[0014] Specifically, the thermosensitive retinol lipid carrier includes, by mass percentage, 4%-5%, 5%-6%, 6%-7%, 7%-8%, 8%-9%, 9%-10%, 10%-11%, 11%-12%, 12%-13%, 13%-14% or 14%-15% lecithin.

[0015] Specifically, the thermosensitive retinol lipid carrier includes, by mass percentage, 0.05%-0.1%, 0.1%-0.5%, 0.5%-1%, 1%-2%, 2%-3%, 3%-4% or 4%-5% antioxidant.

[0016] Preferably, the thermosensitive retinol lipid carrier comprises, by mass percentage, 0.1%-2.5% antioxidant.

[0017] Specifically, the thermosensitive retinol lipid carrier includes, by mass percentage, 0.1%-1%, 1%-2%, 2%-3%, 4%-5%, 5%-6%, 6%-7%, 7%-8%, 8%-9%, 9%-10%, 10%-11%, 11%-12%, 12%-13%, 13%-14%, 14%-15%, 15%-16, 16%-17%, 17%-18%, 18%-19%, 19%-20%, 20%-21%, 21%-22%, 22%-23% or 24%-25% poloxamer.

[0018] Specifically, the temperature-sensitive retinol lipid carrier includes, by mass percentage, 0%-0.1%, 0.1%-0.5%, 0.5%-1%, 1%-2%, 2%-3%, 3%-4% or 4%-5% preservatives.

[0019] Specifically, the retinol active ingredients include, but are not limited to: one or more of retinol, retinol propionate, retinol palmitate, retinol acetate, retinal, hydroxypinacolone retinoic acid ester, tocopherol retinoic acid ester, and retinol retinoic acid ester.

[0020] Preferably, the retinol active ingredient includes: one or more of retinol, retinol propionate, and hydroxypinacolone retinoic acid ester.

[0021] Specifically, the oils include but are not limited to: one or more of soybean oil, olive oil, corn germ oil, macadamia oil, sunflower oil, caprylic / capric triglyceride, oleic triglyceride, linoleic triglyceride, linolenic triglyceride, lauric triglyceride, coconut oil caprylic / capric ester, jojoba oil, squalene, and squalane.

[0022] More specifically, the oil also includes: one or more of natural animal and plant oils, triglyceride oils, diglyceride oils, and wax oils.

[0023] Preferably, the oil comprises: one or more of soybean oil, caprylic / capric triglyceride, coconut oil caprylic / capric ester, corn germ oil, and olive oil.

[0024] Specifically, the lecithin includes, but is not limited to, one or more of soybean lecithin, egg yolk lecithin, and sunflower lecithin.

[0025] Specifically, the phosphatidylcholine content of the lecithin is ≥45%.

[0026] Preferably, the phosphatidylcholine content of the lecithin comprises 45%-50%, 50%-55%, 55%-60%, 60%-65%, 65%-70%, 70%-75%, 75%-80%, 80%-85%, 85%-90%, 90%-95% or 95%-100%.

[0027] More preferably, the phosphatidylcholine content of the lecithin is ≥ 70%.

[0028] Still more preferably, the phosphatidylcholine content of the lecithin is ≥ 90%.

[0029] Specifically, the antioxidant includes but is not limited to: one or more of tocopherol, tocopherol acetate, butylated hydroxyanisole, butylated hydroxytoluene, 2,6-di-tert-butyl-p-cresol, phytosterols, idebenone, coenzyme Q10, astaxanthin, ferulic acid, pentaerythritol tetraester or dimethylmethoxybenzodihydropyranol.

[0030] Preferably, the antioxidant comprises: one or more of tocopherol, coenzyme Q10, 2,6-di-tert-butyl-p-cresol, butylated hydroxyanisole, and ferulic acid.

[0031] Preferably, the poloxamer is: poloxamer 407 and / or poloxamer 188.

[0032] Specifically, the preservatives include, but are not limited to, one or more of 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, ethylhexylglycerin, phenoxyethanol, p-hydroxyacetophenone, and caprylhydroxamic acid.

[0033] Preferably, the preservative is 1,2-pentanediol and / or 1,2-hexanediol.

[0034] Specifically, the pH of the thermosensitive retinol lipid carrier is 6.5-7.5.

[0035] Preferably, the pH of the thermosensitive retinol lipid carrier is 6.5-6.6, 6.6-6.7, 6.7-6.8, 6.8-6.9, 6.9-7.0, 7.0-7.1, 7.1-7.2, 7.2-7.3, 7.3-7.4 or 7.4-7.5.

[0036] Specifically, the pH regulator of the thermosensitive retinol lipid carrier includes, but is not limited to, one or more of sodium hydroxide, potassium hydroxide, tromethamine, triethanolamine, citric acid, sodium citrate, sodium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, 4-hydroxyethylpiperazineethanesulfonic acid, 2-(N-morpholino)ethanesulfonic acid, 2-(N-morpholino)propanesulfonic acid or 2-(N-morpholino)propanesulfonic acid.

[0037] Preferably, the pH regulator of the thermosensitive retinol lipid carrier includes one or more of sodium hydroxide, potassium hydroxide, citric acid, sodium citrate, sodium dihydrogen phosphate / disodium hydrogen phosphate, and 4-hydroxyethylpiperazineethanesulfonic acid.

[0038] Specifically, the particle size of the thermosensitive retinol lipid carrier is ≤500nm.

[0039] Preferably, the particle size of the thermosensitive retinol lipid carrier is ≤350 nm.

[0040] More preferably, the particle size of the thermosensitive retinol lipid carrier is 40-320 nm.

[0041] In a second aspect, the present invention provides a method for preparing the above-mentioned temperature-sensitive retinol lipid carrier, the preparation method comprising the following steps:

[0042] S1, oil, lecithin, antioxidant are mixed, stirred and dissolved to form lecithin oil solution;

[0043] S2, adding the retinol active substance to the lecithin oil solution formed in step S1, stirring and dissolving, to form a retinol lecithin oil solution;

[0044] S3, adding poloxamer and preservative into deionized water, stirring and dissolving, to form a poloxamer aqueous solution;

[0045] S4, mixing the retinol lecithin oil solution formed in step S2 and the poloxamer aqueous solution formed in step S3, and emulsifying them to form a retinol lipid carrier precursor;

[0046] S5. Adjust the pH of the retinol lipid carrier precursor to 6-8, and homogenize to obtain a retinol lipid carrier.

[0047] Specifically, the temperature for stirring and dissolving in step S1 is 50-75°C.

[0048] Preferably, the temperature for stirring and dissolving in step S1 is 50-60°C.

[0049] More preferably, the temperature of the stirring and dissolving in step S1 is 60°C.

[0050] Specifically, the stirring and dissolving conditions described in step S1 are stirring at 50-400 rpm for 10-120 min;

[0051] Preferably, the stirring and dissolving condition in step S1 is stirring at 200-400 rpm for 15-30 min.

[0052] Specifically, the stirring and dissolving conditions in step S2 are: introducing nitrogen, stirring at 45-60° C. and 50-400 rpm for 10-30 min.

[0053] Preferably, the stirring and dissolving conditions in step S2 are: introducing nitrogen, stirring at 55° C. and 200-400 rpm for 10-15 min.

[0054] Preferably, the concentration of the nitrogen gas introduced in step S2 is 99.99%.

[0055] Specifically, the temperature of the stirring and dissolving in step S3 is 0-15°C.

[0056] Specifically, the stirring and dissolving conditions in step S3 are stirring at 50-400 rpm for 10-30 min.

[0057] Preferably, the stirring and dissolving condition in step S3 is stirring at 100-200 rpm for 10-30 min.

[0058] Specifically, the poloxamer aqueous solution described in step S3 needs to be kept at a constant temperature;

[0059] Preferably, the poloxamer aqueous solution in step S3 needs to be kept at a constant temperature of 45-60°C.

[0060] More preferably, the poloxamer aqueous solution in step S3 needs to be kept at a constant temperature of 50-60°C.

[0061] Specifically, the emulsification conditions in step S4 are 45-60° C., 1000-8000 rpm, and emulsification for 5-30 min.

[0062] Preferably, the emulsification conditions in step S4 are 50-60° C., 3000-8000 rpm, and emulsification for 5-15 min.

[0063] Specifically, the pH in step S5 is 6.5-7.5.

[0064] Preferably, the pH in step S5 is 6.5-6.6, 6.6-6.7, 6.7-6.8, 6.8-6.9, 6.9-7.0, 7.0-7.1, 7.1-7.2, 7.2-7.3, 7.3-7.4 or 7.4-7.5.

[0065] Specifically, the homogenization method described in step S5 is to use a high-pressure homogenizer or a microfluidizer.

[0066] Preferably, the homogenization condition in step S5 is 700-1500 bar homogenization cycle 3-8 times.

[0067] In a third aspect, the present invention provides use of the above-mentioned temperature-sensitive retinol lipid carrier in the preparation of cosmetics containing retinol active ingredients.

[0068] In a fourth aspect, the present invention provides cosmetics comprising the above-mentioned temperature-sensitive retinol lipid carrier.

[0069] Preferably, the cosmetics include: face cream, face mask, eye cream, neck cream, hand cream, body lotion, moisturizing lotion, essence, toner, shampoo, conditioner, shower gel or cleanser.

[0070] The beneficial effects of the present invention are:

[0071] (1) The retinol lipid carrier provided by the present invention has high high temperature accelerated stability, a monthly retention rate of more than 85%, is not easy to change color, and does not break the emulsion or emit oil.

[0072] (2) The retinol lipid carrier provided by the present invention has a temperature-sensitive slow release property, which is conducive to the slow release of the retinol lipid carrier in cosmetic skin care applications.

[0073] (3) The retinol lipid carrier provided by the present invention has the effect of reducing the irritation of retinol in cosmetic skin care applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0074] Figure 1 The release rate of retinol was measured. DETAILED DESCRIPTION

[0075] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0076] The present invention

[0077] Soybean lecithin (PC content greater than 90%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd. with the product number SY-SO-231208.

[0078] Soybean lecithin (PC content greater than 70%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd. with the product number SD-240501.

[0079] Egg yolk lecithin (PC content greater than 80%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd. with the product number SY-EI80-240301.

[0080] Sunflower lecithin (PC content greater than 70%) was purchased from Shenyang Tianfeng Biopharmaceutical Co., Ltd. with the product number SK-240301.

[0081] The PC content is the phosphatidylcholine content.

[0082] Example 1-Example 10

[0083] The composition formula table of Example 1 to Example 10 is shown in Table 1. The unit of raw material content in the formula table is g, and the total weight is 100g.

[0084] Table 1 Composition formula table of embodiment 1-embodiment 10 (g)

[0085]

[0086]

[0087] The components in Table 1 are used to obtain a retinol lipid carrier according to the following steps:

[0088] S1, dissolving oil, lecithin and antioxidant at 60°C and 200 rpm for 30 min to form a transparent lecithin oil solution;

[0089] S2, adding the retinol active substance to the lecithin oil solution formed in step S1, passing 99.99% nitrogen gas for protection, stirring at 200 rpm for 15 min at 55° C. to dissolve to form a retinol lecithin oil solution;

[0090] S3, adding poloxamer and preservative into deionized water, stirring at 100 rpm for 30 min at 5°C to dissolve to form a poloxamer aqueous solution, and maintaining the temperature at 50°C;

[0091] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer aqueous solution formed in step S3 to obtain a mixed solution (100 g in total), and shearing and emulsifying at 4000 rpm for 5 min at 50° C. to form a retinol lipid carrier precursor;

[0092] S5. The retinol lipid carrier precursor prepared in step S4 is adjusted to pH 7.5 by using a 10 M sodium hydroxide aqueous solution, and homogenized by a high-pressure homogenizer at 1000 bar for 5 cycles to obtain a retinol lipid carrier.

[0093] Embodiment 11

[0094] S1. Dissolve 5 g corn germ oil, 5 g soybean lecithin (PC content greater than 90%), and 2 g tocopherol at 60° C. and 400 rpm for 15 min to form a transparent lecithin oil solution;

[0095] S2, adding 10 g of retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 400 rpm for 10 min at 55° C. to dissolve the retinol lecithin oil solution;

[0096] S3, adding 3 g of poloxamer 407 to 75 g of deionized water, stirring at 100 rpm for 15 min at 5 ° C to dissolve to form a poloxamer 407 aqueous solution, and keeping the temperature at 50 ° C;

[0097] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 8000 rpm for 5 min at 50°C to form a retinol lipid carrier precursor;

[0098] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to pH 6.8 by a 2M citric acid / sodium citrate aqueous solution at pH 6.8, and homogenized by a high-pressure homogenizer at 700 bar for 8 cycles to obtain a retinol lipid carrier.

[0099] Example 12

[0100] S1. Dissolve 5 g olive oil, 5 g egg yolk lecithin (PC content greater than 80%), and 1 g tocopherol at 60° C. and 400 rpm for 15 min to form a transparent lecithin oil solution;

[0101] S2, adding 10 g of retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 400 rpm for 10 min at 55° C. to dissolve the retinol lecithin oil solution;

[0102] S3, adding 4 g of poloxamer 407 to 75 g of deionized water, stirring at 100 rpm for 15 min at 5°C to dissolve the solution to form a poloxamer 407 aqueous solution, and maintaining the temperature at 50°C;

[0103] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 3000 rpm for 10 min at 50°C to form a retinol lipid carrier precursor;

[0104] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to pH 7.3 by using a 2M sodium dihydrogen phosphate / disodium hydrogen phosphate aqueous solution at pH 7.5, and homogenized by a high-pressure homogenizer at 1000 bar for 5 cycles to obtain a retinol lipid carrier.

[0105] Example 13

[0106] S1. Dissolve 5 g of caprylic / capric triglyceride, 5 g of sunflower lecithin (PC content greater than 70%), and 0.5 g of butylated hydroxyanisole at 60° C. and 400 rpm for 15 min to form a transparent lecithin oil solution;

[0107] S2, adding 10 g of retinol propionate to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 10 min at 60° C. to dissolve to form a retinol propionate lecithin oil solution;

[0108] S3, adding 3 g of poloxamer 407 to 76.5 g of deionized water, stirring at 200 rpm for 15 min at 0°C to dissolve the solution to form a poloxamer 407 aqueous solution, and maintaining the temperature at 60°C;

[0109] S4, adding the retinol propionate lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 3000 rpm for 15 min at 60°C to form a retinol propionate lipid carrier precursor;

[0110] S5. The retinol propionate lipid carrier precursor obtained in step S4 is adjusted to pH 8 by using a 10 M potassium hydroxide aqueous solution, and homogenized by a high-pressure homogenizer at 1500 bar for 3 cycles to obtain a retinol propionate lipid carrier.

[0111] Embodiment 14

[0112] S1. Dissolve 5 g of caprylic / capric triglyceride, 5 g of soybean lecithin (PC content greater than 90%), and 0.5 g of tocopherol at 60° C. and 400 rpm for 15 min to form a transparent lecithin oil solution;

[0113] S2, adding 10 g of hydroxypinacolone retinoic acid ester to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 10 min at 60° C. to dissolve to form a hydroxypinacolone retinoic acid ester lecithin oil solution;

[0114] S3, add 5 g of poloxamer 407 to 74.5 g of deionized water, stir at 200 rpm for 10 min at 15°C to dissolve to form a poloxamer 407 aqueous solution, and keep the temperature at 60°C;

[0115] S4, adding the hydroxypinacolone retinoic acid ester lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 4000 rpm for 10 min at 60°C to form a hydroxypinacolone retinoic acid ester lipid carrier precursor;

[0116] S5. The hydroxypinacolone retinoic acid ester lipid carrier precursor obtained in step S4 is adjusted to pH 6.8 by 2M 4-hydroxyethylpiperazineethanesulfonic acid / sodium hydroxide aqueous solution, and homogenized by a high-pressure homogenizer at 1000 bar for 5 cycles to obtain a hydroxypinacolone retinoic acid ester lipid carrier.

[0117] Embodiment 15

[0118] S1, dissolving 5 g of caprylic / capric triglyceride, 5 g of soybean lecithin (PC content greater than 70%), and 0.5 g of tocopherol at 60° C. and 200 rpm for 30 min to form a transparent lecithin oil solution;

[0119] S2, adding 10 g of retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 15 min at 60° C. to dissolve to form a retinol lecithin oil solution;

[0120] S3, adding 0.1 g of poloxamer 407, 0.5 g of 1,2-hexanediol and 2 g of 1,2-pentanediol to 76.9 g of deionized water, stirring at 100 rpm for 30 min at 15° C. to dissolve to form a poloxamer 407 aqueous solution, and maintaining the temperature at 60° C.;

[0121] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 4000 rpm for 10 min at 60°C to form a retinol lipid carrier precursor;

[0122] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to pH 7.0 by using a 2M sodium dihydrogen phosphate / disodium hydrogen phosphate aqueous solution at pH 7.5, and homogenized by a high-pressure homogenizer at 900 bar for 6 cycles to obtain a retinol lipid carrier.

[0123] Example 16

[0124] S1, dissolving 5 g of caprylic / capric triglyceride, 5 g of soybean lecithin (PC content greater than 70%), and 0.5 g of tocopherol at 60° C. and 200 rpm for 30 min to form a transparent lecithin oil solution;

[0125] S2, adding 10 g of retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 15 min at 60° C. to dissolve to form a retinol lecithin oil solution;

[0126] S3, adding 1 g of poloxamer 407, 2 g of 1,2-hexanediol and 2 g of 1,2-pentanediol to 74.5 g of deionized water, stirring at 100 rpm for 30 min at 15° C. to dissolve to form a poloxamer 407 aqueous solution, and maintaining the temperature at 60° C.;

[0127] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 4000 rpm for 10 min at 60°C to form a retinol lipid carrier precursor;

[0128] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to pH 7.0 by using a 2M sodium dihydrogen phosphate / disodium hydrogen phosphate aqueous solution at pH 7.5, and homogenized by a high-pressure homogenizer at 900 bar for 6 cycles to obtain a retinol lipid carrier.

[0129] Embodiment 17

[0130] S1, dissolving 5 g of caprylic / capric triglyceride, 5 g of soybean lecithin (PC content greater than 70%), and 0.5 g of tocopherol at 60° C. and 200 rpm for 30 min to form a transparent lecithin oil solution;

[0131] S2, adding 10 g of retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 15 min at 60° C. to dissolve to form a retinol lecithin oil solution;

[0132] S3, adding 3 g of poloxamer 407, 0.5 g of 1,2-hexanediol and 2 g of 1,2-pentanediol to 74 g of deionized water, stirring at 100 rpm for 30 min at 15° C. to dissolve to form a poloxamer 407 aqueous solution, and maintaining the temperature at 60° C.;

[0133] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution. Shear emulsification was performed at 4000 rpm for 10 min at 60°C to form a retinol lipid carrier precursor;

[0134] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to pH 7.0 by using a 2M sodium dihydrogen phosphate / disodium hydrogen phosphate aqueous solution at pH 7.5, and homogenized by a high-pressure homogenizer at 900 bar for 6 cycles to obtain a retinol lipid carrier.

[0135] Comparative Example 1-Comparative Example 7

[0136] The composition formula table of Comparative Examples 1 to 7 is shown in Table 2. The raw material content in the formula table is in g, and the total weight is 100 g.

[0137] Table 2 Composition formula table of comparative example 1-comparative example 7 (g)

[0138]

[0139] The components in Table 2 are used to obtain a retinol lipid carrier according to the following steps:

[0140] S1, dissolving soybean lecithin (PC content greater than 90%), caprylic / capric triglyceride, and tocopherol at 60° C. and 200 rpm for 30 min to form a transparent lecithin oil solution (no soybean lecithin was added in Comparative Examples 2, 5, and 6);

[0141] S2, adding retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 15 min at 60° C. to dissolve to form a retinol lecithin oil solution;

[0142] S3, adding emulsifier, 1,2-hexanediol and 1,2-pentanediol into deionized water, stirring at 100 rpm for 30 min at 15°C to dissolve into an emulsifier aqueous solution, and maintaining the temperature at 60°C;

[0143] S4, adding the retinol lecithin oil solution formed in step S2 to the emulsifier aqueous solution formed in step S3 to obtain a mixed solution (100 g in total). Shear emulsification at 4000 rpm for 10 min at 60°C to form a retinol lipid carrier precursor;

[0144] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to pH 7.0 by using a 2M sodium dihydrogen phosphate / disodium hydrogen phosphate aqueous solution at pH 7.5, and homogenized by a high-pressure homogenizer at 900 bar for 6 cycles to obtain a retinol lipid carrier.

[0145] Experimental Example 1 Particle size, appearance stability, and retention rate determination

[0146] 1.1 Particle size determination

[0147] The retinol lipid carriers prepared in Examples 1 to 17 and Comparative Examples 1 to 7 were diluted 100 times with deionized water, and their particle sizes were measured by a laser particle size analyzer.

[0148] 1.2 Appearance

[0149] The appearance of Examples 1 to 17 and Comparative Examples 1 to 7 was observed with naked eyes, which is the initial state of preparation.

[0150] 1.3 Stability determination

[0151] HPLC test method for retinol active substances: Take the retinol carrier sample and shake it evenly, take 0.2g of the sample and dilute it to 100ml, as the sample diluent for the test, and determine the content of retinol active substances by HPLC. HPLC test conditions: the chromatographic column is ShimNex CS C18 chromatographic column (4.6mm×150mm×5μm); the mobile phase is methanol; the column temperature is 35℃; the flow rate is 1.0mL / min; the injection volume is 10μL; the detection wavelength varies depending on the active substance (retinol 325nm, hydroxypinacolone retinoic acid ester 360nm, retinol propionate 325nm).

[0152] The retinol lipid carriers prepared in Examples 1 to 17 and Comparative Examples 1 to 7 were placed at 45° C. for accelerated stability testing, and taken out after one month to observe their appearance stability. The retention rate of retinol was determined by HPLC.

[0153] Retention rate of retinol active substances (%) = content of retinol active substances in the sample after acceleration at 45° C. for 1 month / content of retinol active substances in the sample before acceleration×100%.

[0154] 1.4 Measurement results

[0155] The results of the particle size, appearance stability and retention rate of Examples 1-17 and Comparative Examples 1-7 are shown in Table 3.

[0156] Table 3 Particle size, appearance stability, retention rate measurement results

[0157]

[0158] From the high temperature accelerated test experiment in Table 3, it can be seen that the retinol lipid carriers prepared in Examples 1 to 17 of the present invention are uniform emulsions without demulsification and stratification, showing very good stability. After one month of high temperature acceleration, the retention rate of retinol active substances reaches more than 85%.

[0159] The retinol lipid carriers prepared in Comparative Examples 1 to 7 showed demulsification and stratification. After accelerated treatment at high temperature for one month, the retinol content retention rate was between 46.2% and 78.2%.

[0160] Experimental Example 2 Effect of pH

[0161] The preparation methods of test examples 1-6 are as follows:

[0162] S1. Dissolve 5 g soybean lecithin (PC content greater than 90%), 5 g caprylic / capric triglyceride, and 0.3 g tocopherol at 60° C. and 200 rpm for 30 min to form a transparent lecithin oil solution;

[0163] S2, adding 10 g of retinol to the lecithin oil solution formed in step S1, introducing 99.99% nitrogen gas for protection, stirring at 200 rpm for 15 min at 60° C. to dissolve to form a retinol lecithin oil solution;

[0164] S3, add 3g of poloxamer 407, 0.5g of 1,2-hexanediol and 2g of 1,2-pentanediol to 74.2g of deionized water, stir at 100 rpm for 30min at 15°C to dissolve to form a poloxamer 407 aqueous solution, and keep the temperature at 60°C;

[0165] S4, adding the retinol lecithin oil solution formed in step S2 to the poloxamer 407 aqueous solution formed in step S3 to obtain a mixed solution, and shearing and emulsifying at 4000 rpm for 10 min at 60° C. to form a retinol lipid carrier precursor;

[0166] S5. The retinol lipid carrier precursor obtained in step S4 is adjusted to the target pH value (see Table 4) by using a 2M sodium dihydrogen phosphate / disodium hydrogen phosphate aqueous solution at pH 7.5, and homogenized by a high-pressure homogenizer at 1000 bar for 5 cycles to obtain a retinol lipid carrier.

[0167] Table 4 pH target values ​​of test examples 1-6

[0168] project Test Example 1 Test Example 2 Test Example 3 Test Example 4 Test Example 5 Test Example 6 pH 5.5 6 6.5 7 7.5 8

[0169] The retinol lipid carrier prepared in Test Example 1-6 was placed at 45°C for accelerated stability test, and taken out after 1 month to observe its appearance stability, and the retention rate of retinol was measured by HPLC. The results are shown in Table 5.

[0170] Table 5 Retinol retention rate of test examples 1-6

[0171] project Test Example 1 Test Example 2 Test Example 3 Test Example 4 Test Example 5 Test Example 6 Retention Rate % 59.6 85.4 92.8 97.1 96.9 88.7

[0172] As shown in Table 5, when the pH is less than 6, retinol degrades rapidly in the high temperature accelerated stability test of the retinol lipid carrier. The retinol retention rate of the sample with pH 5.5 after one month is only 59.6%. When the pH is greater than 6, the high temperature accelerated retinol degradation slows down, and the retinol retention rate is greater than 85%. When the pH is greater than 6.5, the retinol retention rate is greater than 90%, indicating that retinol degradation is slowest when the pH is close to neutral.

[0173] Experimental Example 3 Determination of the release rate of retinol

[0174] The retinol lipid carriers prepared in Example 15 and Example 17 were subjected to in vitro release investigation at 25°C and 37.5°C using reverse dialysis. The release medium was 33% ethanol aqueous solution. 0.2-0.3 g of retinol liposomes were weighed and added to a 500 mL high-foot beaker containing 290 mL of the release medium. A dialysis bag (13KD) containing 10 mL of the release medium was placed in the beaker and stirred at 500 rpm constant temperature magnetic stirring (all light-proof). 0.5 mL of the release medium in the dialysis bag was taken out at 1, 2, 3, 4, 5, 6, 7, and 8 h, respectively, and 0.5 mL of fresh release medium was added. The retinol content in the release solution was determined by HPLC. The release rate (Q) of retinol at different time points was calculated according to the formula:

[0175]

[0176] Wherein, Q is the release rate; c is the concentration of retinol in the dialysis bag; and m is the mass of retinol in the retinol liposomes.

[0177] The results of the test are as follows Figure 1 As shown, the results show that Example 15 and Example 17 can slowly release retinol at 25°C and 37.5°C, indicating that the retinol lipid carrier provided by the present invention has a temperature-sensitive slow release property, which is beneficial to the slow release of retinol lipid carriers in cosmetic skin care applications.

[0178] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A thermosensitive retinol lipid carrier, characterized in that: The thermosensitive retinol lipid carrier is composed of 0.1%-15% retinol active substance, 1%-20% oil, 4%-15% lecithin, 0.05%-5% antioxidant, 0.1%-25% poloxamer, 0%-5% preservative, and the balance is deionized water in terms of mass percentage; the pH of the thermosensitive retinol lipid carrier is 6-8; The retinol active ingredient is one or more of retinol, retinol propionate, hydroxypinacolone retinoic acid ester; the oil is one or more of soybean oil, caprylic / capric triglyceride, coconut oil caprylic / capric ester, corn germ oil, and olive oil; the lecithin is one or more of soybean lecithin, egg yolk lecithin, and sunflower lecithin.

2. The thermosensitive retinol lipid carrier according to claim 1, characterized in that The phosphatidylcholine content of the lecithin is ≥45%; preferably, the phosphatidylcholine content of the lecithin is ≥70%.

3. The thermosensitive retinol lipid carrier according to claim 1, characterized in that The antioxidant comprises one or more of tocopherol, tocopherol acetate, butylated hydroxyanisole, butylated hydroxytoluene, 2,6-di-tert-butyl-p-cresol, phytosterol, idebenone, coenzyme Q10, astaxanthin, ferulic acid, pentaerythritol tetraester or dimethylmethoxybenzodihydropyranol.

4. The thermosensitive retinol lipid carrier according to claim 1, characterized in that The preservatives include: one or more of 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, ethylhexylglycerin, phenoxyethanol, p-hydroxyacetophenone, and caprylhydroxamic acid.

5. The thermosensitive retinol lipid carrier according to claim 1, characterized in that The poloxamer is: poloxamer 407 and / or poloxamer 188.

6. The thermosensitive retinol lipid carrier according to claim 1, characterized in that: The pH of the temperature-sensitive retinol lipid carrier is 6.5-7.

5.

7. The method for preparing the thermosensitive retinol lipid carrier according to any one of claims 1 to 6, characterized in that: The preparation method comprises the following steps: S1, oil, lecithin, antioxidant are mixed, stirred and dissolved to form lecithin oil solution; S2, adding the retinol active substance to the lecithin oil solution formed in step S1, stirring and dissolving, to form a retinol lecithin oil solution; S3, adding poloxamer and preservative into deionized water, stirring and dissolving, to form a poloxamer aqueous solution; S4, mixing the retinol lecithin oil solution formed in step S2 and the poloxamer aqueous solution formed in step S3, and emulsifying them to form a retinol lipid carrier precursor; S5. Adjust the pH of the retinol lipid carrier precursor to 6-8, and homogenize to obtain a retinol lipid carrier.

8. Use of the thermosensitive retinol lipid carrier according to any one of claims 1 to 6 in the preparation of cosmetics containing retinol active ingredients.

9. A cosmetic comprising the temperature-sensitive retinol lipid carrier according to any one of claims 1 to 6.

10. The cosmetic according to claim 9, characterized in that: The cosmetics include: face cream, face mask, eye cream, neck cream, hand cream, body lotion, moisturizing lotion, essence, toner, shampoo, conditioner, shower gel or cleanser.

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