A ceramide liposome for skin care and a method for preparing the same

Abstract

The application relates to the field of skin care products and discloses a ceramide liposome for skin care products and a preparation method thereof, the ceramide liposome comprising the following components in parts by weight: 5-10 parts of hydrogenated lecithin, 0.5-2 parts of modified cholesterols, 0.5-2 parts of ceramides, 0.1-2.5 parts of sucrose stearate, 0.1-1 part of polyglyceryl-10 stearate and 15-30 parts of an organic solvent; the modified cholesterols are prepared by grafting glycine cholesterols and carboxymethyl chitosan through chemical reactions, the glycine cholesterols are prepared by taking cholesterols, N-tert-butoxycarbonylglycine and trifluoroacetic acid as raw materials, and the carboxymethyl chitosan is prepared by grafting chloroacetic acid and chitosan; the ceramide liposome with good stability and good skin barrier repair and moisturizing and water-locking effects is prepared by taking the hydrogenated lecithin, the modified cholesterols, the ceramides, the sucrose stearate and the polyglyceryl-10 stearate as raw materials.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of skin care products, and particularly relates to a ceramide liposome for skin care products and a preparation method thereof. BACKGROUND

[0002] Ceramide is also known as cerebroside, N-acylsphingosine, and is a common structural unit of sphingolipids. Ceramide is an important lipid naturally existing in the stratum corneum of the skin, and has physiological functions such as moisturizing, maintaining skin barrier, anti-aging, anti-allergy, and inducing cell apoptosis. Studies have shown that ceramide can induce skin lesion cells, cancer cells and the like to undergo apoptosis, and has potential medical application value. With the development of nanotechnology, nanocarrier delivery technology mainly based on liposomes has become an important means to promote the transdermal absorption of drugs, and is also a hot spot in the field of cosmetic technology. Conventional liposomes are composed of soybean lecithin and cholesterol, can effectively encapsulate water-soluble and fat-soluble active ingredients, and have advantages such as targeting, sustained release, penetration promotion, and good cell affinity, and have been widely used in the fields of daily chemicals, agriculture, biological medicine and the like.

[0003] In recent years, with the in-depth research of ceramide, more and more scientific research institutions and brand companies have launched a large number of ceramide-containing cosmetics, which have attracted widespread attention and become best-selling products. However, an important prerequisite for realizing the skin care effect is that the active ingredients can effectively penetrate the skin surface and be concentrated and retained in the skin tissue for a long time, that is, the skin-targeted delivery of skin care active ingredients is realized. However, natural ceramide has high melting point and low solubility, and direct addition of ceramide may cause crystallization, poor transdermal performance, and instability due to the influence of the surrounding environment, which not only affects the stability of the formula, but also reduces the utilization rate of ceramide, and limits the application of ceramide in the field of skin care products and the like. SUMMARY

[0004] To solve the problems mentioned in the background, the present application provides a ceramide liposome for skin care products and a preparation method thereof. The ceramide liposome has good stability, good skin barrier repair property, and good moisturizing and water-locking effects, and is prepared from hydrogenated lecithin, modified cholesterol, ceramide, sucrose stearate, and polyglycerol-10 stearate as raw materials.

[0005] The object of the present application can be achieved by the following technical solutions.

[0006] A ceramide liposome for skin care products comprises the following components in parts by weight: hydrogenated lecithin 5-10 parts, modified cholesterol 0.5-2 parts, ceramide 0.5-2 parts, sucrose stearate 0.1-2.5 parts, polyglycerol-10 stearate 0.1-1 part, and organic solvent 15-30 parts.

[0007] The modified cholesterol is prepared by grafting glycine cholesteryl ester and carboxymethyl chitosan through chemical reaction, wherein the glycine cholesteryl ester is prepared by using cholesterol, N-tert-butyloxycarbonyl glycine and trifluoroacetic acid as raw materials, and the carboxymethyl chitosan is prepared by grafting chloroacetic acid and chitosan.

[0008] Preferably, the ceramide is one or more of ceramide NP, ceramide NH, ceramide AH, ceramide NDS, ceramide AS, ceramide AP, ceramide NS, ceramide EOS, ceramide EOH, ceramide ADS, ceramide EOP in combination.

[0009] Preferably, the organic solvent is anhydrous ethanol.

[0010] Preferably, the preparation method of the modified cholesterol comprises the following steps:

[0011] A. Cholesterol and N-tert-butyloxycarbonyl glycine are dissolved in anhydrous dichloromethane, 4-dimethylaminopyridine and N, N'-dicyclohexyl carbodiimide are added, and ice bath reaction is carried out for 20-24 hours. After the reaction is completed, filtration is carried out, and the solvent is removed by distillation under reduced pressure. The reaction product is dissolved in acetone and placed at 0-4°C for 8-12 hours. After the precipitate is removed by filtration, the solvent is evaporated to obtain N-tert-butyloxycarbonyl glycine-cholesterol ester.

[0012] B. The obtained N-tert-butyloxycarbonyl glycine-cholesterol ester is dissolved in anhydrous dichloromethane, and trifluoroacetic acid is added under ice bath stirring. After being placed at 0-4°C for 2-3 hours, the solvent is removed by distillation under reduced pressure. The reaction product is dissolved in sodium chloride solution, and the pH value is adjusted to 4-5 after filtration. The filtrate is extracted with chloroform, and the organic phase is dried with anhydrous sodium sulfate for 8-12 hours. Finally, the solvent is evaporated to obtain glycine cholesteryl ester.

[0013] C. Chitosan powder is taken in a reactor, isopropanol is added and reacted for 3-4 hours, then sodium hydroxide solution is added, and the temperature is raised to 55-70°C. Chloroacetic acid is dissolved in isopropanol and added to the reactor for stirring reaction for 1-2 hours. After the reaction is completed, the temperature is cooled to room temperature, the upper solution is removed, and the remaining product is added to deionized water for stirring and mixing. Hydrochloric acid solution is used to adjust the pH value to neutral, and then centrifugation is carried out to remove the insoluble matter. The supernatant is fully precipitated with methanol, and then centrifugation is carried out. The precipitate is washed with anhydrous ethanol, and finally centrifugation and drying are carried out to obtain carboxymethyl chitosan.

[0014] D, carboxymethyl chitosan is dissolved in dimethyl sulfoxide, N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl) carbonyl diimide hydrochloride are added and reacted for 20-30 min, then glycine cholesteryl ester is dissolved in N, N-dimethylformamide and added to the reaction system, and the reaction is carried out under nitrogen protection for 20-24 h, after the reaction is completed, the reaction liquid is poured into acetone for precipitation, filtration, then the precipitate is washed with tetrahydrofuran, the final product is dialyzed and freeze-dried to prepare the modified cholesterols.

[0015] Preferably, the mass ratio of cholesterols and N-tert-butoxycarbonylglycine in step A is 1:0.45-0.6.

[0016] Preferably, the mass ratio of chitosan and chloroacetic acid in step C is 1:0.5-1.

[0017] Preferably, the mass ratio of carboxymethyl chitosan and glycine cholesteryl ester in step D is 0.17-0.35:1.

[0018] The preparation method of the ceramide liposome for skin care products as described above comprises the following steps: weighing each weight part of raw materials, taking hydrogenated lecithin, modified cholesterols and ceramides into a reactor, adding an organic solvent to dissolve ultrasonically, placing in a 40-50℃ reduced pressure rotary evaporator to remove the organic solvent, adding sucrose stearate and polyglyceryl-10 stearate, rotating for 1-2 h, and then ultrasonic treatment under a power of 60-100 W to prepare the ceramide liposome for skin care products.

[0019] Preferably, the hydration temperature is 40-50℃.

[0020] The beneficial effects of the present application are:

[0021] The application utilizes the reaction of cholesterol and N-tert-butoxycarbonyl protected glycine to prepare N-tert-butoxycarbonyl glycine-cholesterol ester, then deprotects by adding trifluoroacetic acid to prepare glycine-cholesterol ester, and modifies the glycine-cholesterol ester into carboxymethyl chitosan by using chitosan, and further utilizes the reaction of carboxymethyl chitosan and glycine-cholesterol ester to prepare modified cholesterol, so that the carboxymethyl chitosan is grafted onto the molecular chain of cholesterol through a firm chemical bond, so that the carboxymethyl chitosan grafted with cholesterol has amphiphilicity, wherein the chitosan is a natural amino basic polysaccharide widely existing in nature, which is renewable, non-toxic, has good biocompatibility and degradability, and has the effects of bacteriostasis and moisturizing, and the carboxymethyl chitosan has good solubilizing property, thickening property and dispersing property, and can increase the stability of liposomes. The application utilizes hydrogenated lecithin, modified cholesterol and ceramide as raw materials, adds sucrose stearate and polyglycerol-10 stearate as emulsifiers and surfactants to form ceramide liposomes, can efficiently transdermally deliver active ingredients encapsulated therein, has excellent stability and skin tolerance, can also renew the natural protective layer of skin and form an effective barrier to prevent water loss, and the prepared ceramide liposomes applied to skin care products can promote the penetration of ceramide through the epidermis and produce sufficient accumulation in the corresponding parts, so that the effects of efficient moisturizing and water locking, skin repair, antioxidation and anti-aging are achieved. DETAILED DESCRIPTION

[0022] The technical solutions in the embodiments of the application will be clearly and completely described below with reference to the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0023] The preparation method of the modified cholesterol in the embodiment 1 comprises the following steps:

[0024] A, 5.7g of cholesterol and 2.9g of N-tert-butoxycarbonyl glycine are dissolved in 100mL of anhydrous dichloromethane, 0.3g of 4-dimethylaminopyridine and 2.3g of N,N'-dicyclohexyl carbodiimide are added, ice bath reaction is carried out for 24h, after the reaction is completed, filtration is carried out, the solvent is removed by reduced pressure distillation, the reaction product is dissolved in 20mL of acetone and then placed at 4℃ for 10h, the precipitate is removed by filtration, and the solvent is evaporated to obtain N-tert-butoxycarbonyl glycine-cholesterol ester;

[0025] B, the obtained N-tert-butoxycarbonyl glycine-cholesterol ester is dissolved in 50 mL of anhydrous dichloromethane, 50 mL of trifluoroacetic acid is added under ice bath stirring, and the reaction is carried out at 0°C for 2 h, then the solvent is removed by reduced pressure distillation, the reaction product is dissolved in 15% sodium chloride solution, the pH value is adjusted to 5, then filtered, the filtrate is extracted with chloroform, the organic phase is dried with anhydrous sodium sulfate for 12 h, and finally evaporated to obtain glycine-cholesterol ester;

[0026] C, 5 g of chitosan powder is taken in a reactor, 20 mL of isopropyl alcohol is added and reacted for 4 h, then 30% sodium hydroxide solution is added, the temperature is raised to 65°C, 3 g of chloroacetic acid is dissolved in 20 mL of isopropyl alcohol and added to the reactor, stirred and reacted for 2 h, then cooled to room temperature, the upper solution is removed, the remaining product is added to 50 mL of deionized water and stirred, 10% hydrochloric acid solution is used to adjust the pH value to neutral, then centrifuged to remove the insoluble matter, the supernatant is precipitated with methanol, then centrifuged, the precipitate is washed with anhydrous ethanol, and finally centrifuged and dried to obtain carboxymethyl chitosan;

[0027] D, 2.2 g of carboxymethyl chitosan is dissolved in 100 mL of dimethyl sulfoxide, 0.6 g of N-hydroxysuccinimide and 2.1 g of 1-ethyl-(3-dimethylaminopropyl) carbonyldiimidazole hydrochloride are added and reacted for 30 min, then 10 g of glycine-cholesterol ester is dissolved in 100 mL of N,N-dimethylformamide and added to the reaction system, and the reaction is carried out under nitrogen protection for 24 h, then the reaction solution is poured into acetone to precipitate and filter, the precipitate is washed with tetrahydrofuran, the final product is dialyzed and freeze-dried to obtain modified cholesterol.

[0028] Example 2 A kind of ceramide liposome for skin care products, including the following weight parts components: hydrogenated lecithin 5 parts, modified cholesterol prepared in example 1 0.7 parts, ceramide NP 0.8 parts, sucrose stearate 0.3 parts, polyglycerol-10 stearate 0.2 parts, anhydrous ethanol 17 parts.

[0029] The preparation method of the above-mentioned ceramide liposome for skin care products includes the following steps: weighing each weight part of raw materials, taking hydrogenated lecithin, modified cholesterol and ceramide NP in a reactor, adding anhydrous ethanol and ultrasonic dissolving, dissolving uniformly, then placing in 45°C under reduced pressure rotary evaporation to remove organic solvent, adding sucrose stearate and polyglycerol-10 stearate, rotating hydration for 1 h, the hydration temperature is 40°C, then ultrasonic treatment under 80W power, to prepare ceramide liposome for skin care products.

[0030] Example 3 A ceramide liposome for skin care products, comprising the following components by weight: hydrogenated lecithin 7 parts, modified cholesterol prepared in Example 1 1.2 parts, ceramide NP 1.4 parts, sucrose stearate 1.7 parts, polyglyceryl-10 stearate 0.5 parts, anhydrous ethanol 24 parts.

[0031] The preparation method of the above ceramide liposome for skin care products is the same as that of Example 2.

[0032] Example 4 A ceramide liposome for skin care products, comprising the following components by weight: hydrogenated lecithin 10 parts, modified cholesterol prepared in Example 1 1.8 parts, ceramide NP 2 parts, sucrose stearate 2.2 parts, polyglyceryl-10 stearate 1 part, anhydrous ethanol 28 parts.

[0033] The preparation method of the above ceramide liposome for skin care products is the same as that of Example 2.

[0034] Comparative Example 1 A ceramide liposome for skin care products, comprising the following components by weight: hydrogenated lecithin 10 parts, modified cholesterol prepared in Example 1 1.8 parts, ceramide NP 2 parts, Tween 80 3.2 parts, anhydrous ethanol 28 parts.

[0035] The preparation method of the above ceramide liposome for skin care products comprises the following steps: weighing each component by weight, taking hydrogenated lecithin, modified cholesterol and ceramide NP into a reactor, adding anhydrous ethanol and dissolving under ultrasonic, placing in a 45℃ environment for rotary evaporation under reduced pressure to remove organic solvents, adding Tween 80, rotating for 1h at a hydration temperature of 40℃, and then treating under ultrasonic at a power of 80W to obtain the ceramide liposome for skin care products.

[0036] Comparative Example 2 A ceramide liposome for skin care products, comprising the following components by weight: hydrogenated lecithin 10 parts, cholesterol 1.8 parts, ceramide NP 2 parts, sucrose stearate 2.2 parts, polyglyceryl-10 stearate 1 part, anhydrous ethanol 28 parts.

[0037] The preparation method of the above ceramide liposome for skin care products comprises the following steps: weighing each component by weight, taking hydrogenated lecithin, cholesterol and ceramide NP into a reactor, adding anhydrous ethanol and dissolving under ultrasonic, placing in a 45℃ environment for rotary evaporation under reduced pressure to remove organic solvents, adding sucrose stearate and polyglyceryl-10 stearate, rotating for 1h at a hydration temperature of 40℃, and then treating under ultrasonic at a power of 80W to obtain the ceramide liposome for skin care products.

[0038] Performance detection

[0039] The ceramide liposome prepared in Example 2-4 and Comparative Example 1-2 was formulated into a gel:

[0040] (1) Deionized water, erythritol, butylene glycol, glycereth-26, acryloyldimethyltaurine ammonium / VP copolymer, xanthan gum, carbomer, p-hydroxyacetophenone, 1,2-hexanediol were heated to 78°C, and stirred to obtain mixture A;

[0041] (2) The polydimethylsiloxane, cyclopentasiloxane, cyclohexylsiloxane, peony seed oil, red mandarin oil were added to mixture A, and subjected to a first homogenization treatment to obtain homogenized mixture B, under the following conditions: homogenization temperature 82°C, homogenization speed 7500 rpm, and homogenization time about 3 min;

[0042] (3) Arginine, ceramide liposome, panthenol, and compound sensate were added to mixture B, and stirred to obtain a gel containing ceramide liposome.

[0043] A. Stability test: The prepared gel containing ceramide liposome was placed under high temperature (45°C), low temperature (-15°C), and high temperature (45°C, 48 h), normal temperature (25°C, 12 h), and low temperature (-15°C, 48 h) cyclic temperature conditions for 90 days, and whether the sample had delamination, particle precipitation, panthol, transparency change, crystallization, and other phenomena was observed. The sample was continuously placed under natural light for 90 days, and whether the sample had discoloration, off-flavor, and other phenomena was observed, and the data results are shown in Table 1.

[0044] B. Skin irritation test: The test was performed according to the patch test method in the Cosmetic Safety Technical Specification (2015 edition), 32 subjects meeting the standard were selected, about 0.020-0.025 mL of sample was applied to the patch chamber, and a special adhesive tape was applied to the back or forearm of the subject, and after 24 h, the patch was removed, and if there was remaining product, it was gently wiped off with a wet paper towel. The skin reaction was observed at 0.5 h, 24 h, and 48 h, respectively, and the data results are shown in Table 1.

[0045] Table 1 Test sample stability and skin irritation test results

[0046]

[0047]

[0048] As can be seen from the data in Table 1, the skin care products prepared in Examples 2-4 of the present application have good stability, and no stratification, particle precipitation, roughness, transparency change, crystallization phenomenon occurs after being placed for 90 days under high temperature, low temperature and cross conditions. The samples do not change color and taste after being placed for 90 days under natural light conditions, and have no skin irritation. In Comparative Example 1, sucrose stearate and polyglyceryl-10 stearate are replaced with an equal amount of Tween 80, and in Comparative Example 2, cholesterol is not modified, and the sample is stratified under high temperature and cyclic temperature conditions, indicating that the addition of sucrose stearate and polyglyceryl-10 stearate and the grafting of carboxymethyl chitosan can improve the stability of the sample.

[0049] C. Moisturizing function and skin barrier function test: 40 subjects aged 25-45 years old were selected, including 20 females and 20 males, who were randomly divided into 5 groups, 8 in each group. The subjects had healthy skin and met the inclusion criteria. The test area of 5 cm x 5 cm was drawn on the inner side of the right forearm of the subjects at room temperature 20℃ and relative humidity 35%, and the skin was stabilized for at least half an hour. After 10 times of skin tearing with adhesive tape, the experimental sample was applied, and the sample usage was 1 mL. The moisturizing function and skin barrier function test was carried out:

[0050] C 1。 Moisturizing function test: The skin water content tester Corneometer CM825 was used to test the skin water content before and after skin damage, and 4 hours after applying the sample. The average value was obtained by repeating 3 times, and the skin moisture content growth rate was calculated according to the following formula: skin moisture content growth rate = (M1-M2) / M2 x 100%, wherein M2 is the skin water content before use, and M1 is the skin water content after use. The data results are shown in Table 2.

[0051] C2. Skin barrier function test: TewameterTM300 was used to test the skin water loss before and after skin damage, and 6 hours after applying the sample. The average value was obtained by repeating 3 times, and the change rate of TEWL value was calculated, wherein TEWL value is an important parameter for describing skin barrier and is closely related to skin stratum corneum water content. The higher the TEWL value, the more water is lost through the skin, and the poorer the barrier function of the stratum corneum. The data results are shown in Table 2.

[0052] Table 2 Test results of moisturizing function and skin barrier function of samples

[0053]

[0054] As can be seen from the data in Table 2, the skin care products prepared in Examples 2-4 have good skin barrier repair and moisturizing and water-locking effects. The moisture content increase rate measured for Comparative Examples 1-2 is lower than that of Examples 2-4, and the transdermal water loss is significantly higher than that of Examples 2-4, indicating that the addition of sucrose stearate and polyglyceryl-10 stearate and the grafting of carboxymethyl chitosan can prolong the moisturizing and water-locking effect of the sample and reduce the transdermal water loss.

[0055] In the description of the present specification, the description referring to the terms "one embodiment", "an example", "a specific example" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0056] The above shows and describes the basic principles, main features and advantages of the present application. It should be understood by those skilled in the art that the present application is not limited by the above examples, and the above examples and descriptions in the specification are only illustrative of the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the present application.

Claims

1. A ceramide liposome for a skin care product, characterized by, The preparation method of the ceramide liposome for skin care products comprises the following steps: weighing raw materials, taking hydrogenated lecithin, modified cholesterol and ceramide in a reactor, adding an organic solvent and dissolving under ultrasonic, placing in a 40-50℃ environment to remove the organic solvent under reduced pressure by rotary evaporation, adding sucrose stearate and polyglyceryl-10 stearate, rotating hydration for 1-2h, and then ultrasonic treatment under a power of 60-100W to prepare the ceramide liposome for skin care products. The preparation method of the modified cholesterol comprises the following steps: A, taking cholesterol and N-tert-butoxycarbonylglycine in anhydrous dichloromethane, adding 4-dimethylaminopyridine and N,N'-dicyclohexyl carbodiimide, ice bath reaction for 20-24h, filtering after the reaction is completed, removing the solvent under reduced pressure, dissolving the reaction product in acetone and placing in a 0-4℃ environment for 8-12h, filtering to remove the precipitate, and evaporating the solvent to prepare N-tert-butoxycarbonylglycine-cholesterol ester; B, dissolving the obtained N-tert-butoxycarbonylglycine-cholesterol ester in anhydrous dichloromethane, stirring under ice bath to add trifluoroacetic acid, placing in a 0-4℃ environment for 2-3h, removing the solvent under reduced pressure, dissolving the reaction product in sodium chloride solution, adjusting the pH value to 4-5, filtering, extracting the filtrate with chloroform, drying the organic phase with anhydrous sodium sulfate for 8-12h, and finally evaporating to prepare glycine cholesterate; C, taking chitosan powder in a reactor, adding isopropyl alcohol and reacting for 3-4h, then adding sodium hydroxide solution, heating to 55-70℃, dissolving chloroacetic acid in isopropyl alcohol and adding to the reactor, stirring and reacting for 1-2h, cooling to room temperature after the reaction is completed, removing the upper solution, adding deionized water to the remaining product and stirring, adjusting the pH value to neutral with hydrochloric acid solution, then centrifuging to remove insoluble substances, precipitating the supernatant with methanol, centrifuging, washing the precipitate with anhydrous ethanol, and finally centrifuging and drying to prepare carboxymethyl chitosan; D, dissolving carboxymethyl chitosan in dimethyl sulfoxide, adding N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl) carbonyldiimidazole hydrochloride and reacting for 20-30min, then dissolving glycine cholesterate in N,N-dimethylformamide and adding to the reaction system, reacting for 20-24h under nitrogen protection, precipitating the reaction liquid in acetone after the reaction is completed, filtering, washing the precipitate with tetrahydrofuran, and finally dialyzing and freeze-drying the product to prepare modified cholesterol. The ceramide is one or a combination of ceramide NP, ceramide NH, ceramide AH, ceramide NDS, ceramide AS, ceramide AP, ceramide NS, ceramide EOS, ceramide EOH, ceramide ADS and ceramide EOP.

2. The ceramide liposome for a skin care product according to claim 1, characterized by, The organic solvent is anhydrous ethanol.

3. The ceramide liposome for a skin care product according to claim 1, wherein ​ 4. The ceramide liposome for a skin care product according to claim 1, wherein The mass ratio of the cholesterol and N-tert-butoxycarbonyl glycine in the step A is 1:0.45-0.

6.

5. The ceramide liposome for a skin care product according to claim 1, wherein The mass ratio of the chitosan and chloroacetic acid in the step C is 1:0.5-1.

6. The ceramide liposome for a skin care product according to claim 1, wherein The mass ratio of the carboxymethyl chitosan and the glycine cholesteryl ester in the step D is 0.17-0.35:

1.

7. The ceramide liposome for a skin care product according to claim 1, wherein The hydration temperature is 40-50℃.

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