A ceramide ethosome and its preparation method and application

Abstract

The present invention provides a ceramide ethosome and a preparation method and application thereof. The ceramide ethosome comprises the following components: in terms of mass percentage concentration, 0.1-10% of a ceramide mixture, 5-30% of a surfactant, 0.5-10% of a phospholipid, 4-24% of a penetration enhancer, and 50-80% of a polyol. The ceramide ethosome prepared by using a specific proportion of polyol, surfactant, and phospholipid as basic components of the ethosome has high ceramide content, high water-soluble transparency, and good stability; by making ceramide into an ethosome form and using a combination of medium- and long-chain pentanediol, hexanediol, and dipropylene glycol, the penetration-enhancing effect of ceramide is further improved, and transdermal absorption is good; the obtained product is safe and non-irritating, can be directly added to a cosmetic formula for use, exerts anti-aging, repairing, and soothing effects, and meets the needs of consumers for treating or caring for the skin; the preparation method is simple and has good industrial prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of ceramides, and in particular relates to a ceramide ethosome and a preparation method and application thereof. Background Art

[0002] Ceramide is a class of amide compounds formed by dehydration of long-chain fatty acids and the amino group of sphingosine. 40% to 50% of sebum in the stratum corneum is composed of ceramide. Ceramide is the main part of the intercellular matrix. Ceramide also has a strong ability to associate water molecules. It maintains skin moisture by forming a reticular structure in the stratum corneum and plays an important role in maintaining the balance of moisture in the stratum corneum. At the same time, ceramide can increase the thickness of the epidermal stratum corneum, reduce wrinkles, enhance skin elasticity, and delay skin aging. And experimental studies have shown that ceramide has the functions of regulating cell growth and variation and inducing cell apoptosis. However, with the increase of age, the secretion of ceramide in the skin will gradually decrease. By supplementing ceramide from the outside to make up for the lack of self-secretion, it is beneficial to delay aging, so cosmetics containing ceramide have gradually attracted widespread attention. However, due to its own high melting point, poor water solubility, and easy crystallization, ceramide is difficult to be directly added to cosmetics for use.

[0003] Ethosomes are a new type of transdermal delivery carrier. They are multi-layer vesicle structures with loose lipid bilayers. They have good deformability and fluidity. They can directly penetrate the stratum corneum, assist drugs or active ingredients to penetrate into all layers of the skin, and increase the accumulation of drugs or active ingredients in the skin. Compared with ordinary liposomes, they have small particle size, high encapsulation rate, stable structure, high drug loading, good skin tolerance, better flexibility, easy deformation into the deep layer of the skin, and can assist drugs or active ingredients to penetrate, thereby significantly improving the transdermal rate and skin retention of drugs or active ingredients. In addition, the addition of alcohol enables the system Zeta potential to be optimized, further improving the stability of ethosomes, and greatly increasing the storage time compared to traditional liposomes. These characteristics of ethosomes have attracted widespread attention in the field of transdermal drug delivery, and have become a research hotspot in transdermal absorption preparations in recent years.

[0004] However, traditional ethosomes generally use high-concentration ethanol as the main component, and the presence of high-concentration ethanol is more irritating, and there are shortcomings such as ethanol volatility and easy leakage of drugs. After that, other low-chain alcohols are used to replace ethanol as the main component to prepare ethosomes. Although the problems of large irritation, volatility and easy leakage of drugs in the ethosomes prepared by ethanol are overcome, the system stability is poor and it is difficult to play a role efficiently. Therefore, in view of the problems existing in the prior art, it is of great significance to select suitable alcohol substances as the main component of ethosomes, and develop a ceramide ethosome with good stability, high encapsulation efficiency, good transdermal absorption, safety and no stimulation, which can be directly added to the cosmetic formula and used and is easy to prepare. Summary of the invention

[0005] In order to overcome the defects of the prior art, the inventors use a specific ratio of polyols, surfactants, and phospholipids as the basic components of the alcohol body, and use medium and long chain polyols instead of traditional alcohol substances, which solves the problems of traditional alcohol bodies being highly irritating, volatile, and easy to leak drugs. Due to the presence of high concentrations of alcohol in the phospholipid layer, it has better flexibility and membrane fluidity, making the active substance more stable in nature, deeper in penetration depth, and better in transdermal effect. In addition, the prepared ceramide alcohol body has a high ceramide content, is soluble in water, and has high transparency, and can be directly added to cosmetic formulas for use. After testing, the ceramide alcohol body was diluted 20 times with deionized water, and the average particle size was measured to be 80-150nm. After 4000r / min, 30min centrifugal test, it can still remain stable and not stratified, and the average particle size is still 80-150nm, thus completing the present invention.

[0006] Therefore, the present invention aims to provide a ceramide alcohol body with good stability, high ceramide content, high water solubility transparency, good transdermal absorption, safety and non-irritation, which can be directly added into cosmetic formulas as a cosmetic additive to exert anti-aging, repairing and soothing effects, meet consumers' needs for skin treatment or care, and the preparation method is simple and has good industrial prospects.

[0007] The ceramide ethosome of the present invention comprises the following components: calculated by mass percentage, 0.1-10% of ceramide mixture, 5-30% of surfactant, 0.5-10% of phospholipid, 4-24% of penetration enhancer and 50-80% of polyol.

[0008] Optionally, the following components are included: calculated by mass percentage, 0.5-8% of ceramide mixture, 8-25% of surfactant, 2-8% of phospholipid, 8-16% of penetration enhancer, and 55-70% of polyol.

[0009] Optionally, the following components are included: calculated by mass percentage, 3-5% of ceramide mixture, 10-20% of surfactant, 4-6% of phospholipid, 10-15% of penetration enhancer, and 60-65% of polyol.

[0010] Optionally, the ceramide mixture consists of ceramide NP, ceramide AP and phytosphingosine, wherein the mass ratio of ceramide NP, ceramide AP and phytosphingosine is 1:(0.04-1):(0.04-1).

[0011] In the embodiments of the present invention, the mass ratio of ceramide NP, ceramide AP and phytosphingosine is preferably 1:0.16:0.16, 1:0.04:0.04, 1:0.08:0.08 or 1:0.4:0.6.

[0012] Optionally, the surfactant is selected from one or more of sodium di(laurylamide glutamine) lysine, disodium cocoyl glutamate, glyceryl polyoxyethylene ether, lanolin alcohol ether, cetyl alcohol polyether or lauryl alcohol polyether;

[0013] The phospholipid is lecithin and / or phosphatidylcholine;

[0014] The penetration enhancer is selected from one or more of octyl dodecanol, azone, ethanol, fatty alcohol, pyrrolidone or fatty acid;

[0015] The polyol is a medium-chain polyol selected from pentanediol, hexanediol and dipropylene glycol, and the mass ratio of pentanediol, hexanediol and dipropylene glycol is 12: (5-10): (45-50).

[0016] In the embodiment of the present invention, the surfactant is preferably 5% of sodium di(laurylamide glutamine) lysine and 5% of disodium cocoyl glutamate in terms of mass percentage; and the penetration enhancer is preferably 16% of octyldodecanol.

[0017] Optionally, an antioxidant and / or a pH adjuster are also included.

[0018] Optionally, the antioxidant is selected from one or more of tocopherol acetate, butylated hydroxytoluene or butylated hydroxyanisole;

[0019] The pH regulator is selected from one or more of citric acid, lactic acid, acetic acid, phosphoric acid, tartaric acid, malic acid or glycolic acid.

[0020] In the embodiment of the present invention, in terms of mass percentage, the antioxidant is preferably 1.5% tocopherol acetate; and the pH adjuster is preferably 0.3% lactic acid or 0.3% acetic acid.

[0021] In another aspect, the present invention provides a method for preparing the ceramide ethosomes described above, comprising the following steps:

[0022] (1) Weighing a prescribed amount of phospholipids and polyols, heating and dissolving the phospholipids in the polyols at a specified temperature to obtain a mixed solution;

[0023] (2) Weigh the prescribed amount of the surfactant and ceramide mixture, optionally add an antioxidant, add the mixture to the mixed solution obtained in step (1), dissolve under specified conditions, and perform ultrasonic treatment to obtain a crude ethosome:

[0024] (3) selectively adding a pH regulator to the crude ethosome obtained in step (2), mixing evenly, and homogenizing under high pressure to obtain the ceramide ethosome.

[0025] Optionally, the specified temperature in step (1) is 30-45°C;

[0026] The specified conditions in step (2) are a temperature of 40 to 60° C. and a stirring speed of 400 to 600 r / min;

[0027] The ultrasonic conditions in step (2) are as follows: power 200 W, ultrasonic treatment for 5 seconds, intermittent stop for 5 seconds, and ultrasonic treatment for 8 to 12 minutes;

[0028] The parameters of the high pressure homogenization in step (4) are 400-800 bar, and the homogenization is performed 2-6 times.

[0029] In an embodiment of the present invention, the specified temperature in step (I) is preferably 30°C, 40°C or 45°C; the temperature of the specified conditions in step (2) is preferably 40°C, 45°C, 50°C or 60°C, and the stirring speed is preferably 400r / min, 500r / min or 600r / min; the ultrasonic treatment in step (2) is preferably 8min, 10min or 12min; the parameters of the high-pressure homogenization in step (4) are preferably 400bar, 600bar or 800bar, and the homogenization is performed 2 times, 4 times or 6 times.

[0030] Another aspect of the present invention provides a use of ceramide ethosomes in cosmetics, wherein the ceramide ethosomes are used as cosmetic additives.

[0031] When used as a cosmetic additive, the ceramide alcohol body has better flexibility and membrane fluidity due to the presence of high concentrations of alcohol in the phospholipid layer, making the active substance more stable, penetrating deeper, and having better transdermal effect, and can be directly added to cosmetic formulas for use. According to the test, the ceramide alcohol body was diluted 20 times with deionized water, and the average particle size was measured to be 80-150nm. After the centrifugal test at 4000r and 30min, it can still remain stable and not stratified, and the average particle size is still 80-150nm.

[0032] The beneficial effects achieved by the present invention include:

[0033] 1. The reagents and raw materials used in the present invention are all commercially available products and are easily available. The ceramide ethosomes prepared by using a specific ratio of polyols, surfactants, and phospholipids as basic components of the ethosomes have high ceramide content, high water solubility, high transparency, and good stability. The preparation method is simple and has good industrial prospects. By using medium- and long-chain polyols instead of traditional alcohol substances, the problems of traditional ethosomes such as high irritation, easy volatility, and easy drug leakage are solved.

[0034] 2. The present invention prepares ceramide in alcohol form, selects medium- and long-chain pentanediol, hexanediol and dipropylene glycol in combination, and the mass ratio of pentanediol, hexanediol and dipropylene glycol is 12: (5-10): (45-50), thereby further improving the penetration-enhancing effect of ceramide and achieving good transdermal absorption; the obtained product is safe and non-irritating, and can be directly added to cosmetic formulas for use, exerting anti-aging, repairing and soothing effects, and meeting consumers' needs for treating or caring for the skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a particle size distribution diagram of the ceramide ethosomes prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0036] In order to better understand the present invention, the invention is described in detail below in conjunction with embodiments and drawings. However, it should be understood that these embodiments and drawings are only used for illustrative purposes and are not intended to limit the scope of the present invention.

[0037] The particle size and potential size of the ceramide ethosomes obtained in the example were tested by OMEC NS-90Z nanoparticle size and potential analyzer.

[0038] Example 1

[0039] Weigh 2g of lecithin, 12g of pentanediol, 7g of hexylene glycol, and 48.3g of dipropylene glycol, and heat and stir at 40°C to form a uniform transparent solution; add 2.5g of ceramide NP, 0.2g of ceramide AP, 0.2g of phytosphingosine, 16g of octyldodecanol, 5g of sodium di(laurylamide glutamine) lysine, 5g of disodium cocoyl glutamate, and 1.5g of tocopherol acetate in a container, heat to 50°C, turn on the stirrer, stir at a rate of 500r / min for 3min, stop stirring, and then ultrasonically treat for 10min at 200W, ultrasonically treat for 5s, and stop for 5s; then add 0.3g of lactic acid, stir and mix well, and then high-pressure homogenize at 600bar for 4 times to obtain. The particle size distribution diagram of the obtained ceramide alcohol body is as follows: Figure 1 , and its average particle size is 102.6nm.

[0040] Example 2

[0041] Weigh 2g of lecithin, 12g of pentanediol, 8g of hexanediol, and 47.5g of dipropylene glycol, and heat and stir at 40°C to form a uniform transparent solution; add 2.5g of ceramide NP, 0.1g of ceramide AP, 0.1g of phytosphingosine, 16g of octyldodecanol, 5g of sodium di(laurylamide glutamine) lysine, 5g of disodium cocoyl glutamate, and 1.5g of tocopherol acetate in a container, heat to 50°C, turn on the stirrer, stir at a rate of 500r / min for 3min, stop stirring, and then ultrasonically treat for 10min at 200W, ultrasonically treat for 5s, and stop for 5s; then add 0.3g of lactic acid, stir and mix well, and then high-pressure homogenize at 600bar for 4 times to obtain the obtained ceramide alcohol body with an average particle size of 99.02nm.

[0042] Example 3

[0043] Weigh 2g of lecithin, 12g of pentanediol, 8g of hexanediol, and 47g of dipropylene glycol, and heat and stir at 40°C to form a uniform transparent solution; add 2.5g of ceramide NP, 0.4g of ceramide AP, 0.4g of phytosphingosine, 16g of octyldodecanol, 5g of sodium di(laurylamide glutamine) lysine, 5g of disodium cocoyl glutamate, and 1.5g of tocopherol acetate in a container, heat to 50°C, turn on the stirrer, stir at a rate of 500r / min for 3min, stop stirring, and then ultrasonically treat for 10min at 200W, ultrasonically treat for 5s, and stop for 5s; then add 0.4g of lactic acid, stir and mix well, and then high-pressure homogenize at 600bar for 4 times to obtain the obtained ceramide ethosome with an average particle size of 103.2nm.

[0044] Example 4

[0045] Weigh 2g of phosphatidylcholine, 12g of pentanediol, 10g of hexanediol, and 45g of dipropylene glycol, and heat and stir at 45°C to form a uniform transparent solution; add 2.5g of ceramide NP, 1g of ceramide AP, 1.5g of phytosphingosine, 16g of octyldodecanol, 5g of disodium cocoyl glutamate, 3g of glycerol polyoxyethylene ether, and 1.5g of tocopherol acetate in a container, heat to 60°C, turn on the stirrer, stir at a rate of 400r / min for 3min, stop stirring, then ultrasonically treat for 8min at 200W, ultrasonically treat for 5s, and stop for 5s, then add 0.5g of glycolic acid, stir and mix well, and then high-pressure homogenize at 800bar for 2 times to obtain the obtained ceramide ethosome with an average particle size of 106.5nm.

[0046] Example 5

[0047] Weigh 2g of lecithin, 12g of pentanediol, 5g of hexanediol, and 50g of dipropylene glycol, and heat and stir at 40°C to form a uniform transparent solution; add 2.5g of ceramide NP, 0.2g of ceramide AP, 0.2g of phytosphingosine, 16g of octyldodecanol, 5g of sodium di(laurylamide glutamine) lysine, 5g of disodium cocoyl glutamate, and 1.8g of tocopherol acetate in a container, heat to 50°C, turn on the stirrer, stir at a rate of 500r / min for 3min, stop stirring, and then ultrasonically treat for 10min at 200W, ultrasonically treat for 5s, and stop for 5s; then add 0.3g of lactic acid, stir and mix well, and then high-pressure homogenize at 600bar for 4 times to obtain the obtained alcohol body. The average particle size of the obtained alcohol body is 98.46nm.

[0048] Example 6 Preparation of an emulsion containing ceramide ethosomes

[0049]

[0050]

[0051] Preparation method: Mix all materials of phase A, heat in a water bath at 85°C, and stir to disperse evenly until there are no particles; at the same time, mix all materials of phase B, heat to 70-75°C to dissolve; then slowly pour phase B into phase A and homogenize for 5 minutes, continue stirring and keep warm for 20 minutes; when stirring and cooling to 45°C, add all materials of phase C one by one, stir evenly.

[0052] Example 7 Preparation of Toner Containing Ceramide Ethanoids

[0053]

[0054] Preparation method: Mix all materials of phase A, place in a water bath at 85°C, heat, stir for 20 minutes, and disperse evenly; when the temperature drops to 45°C, add all materials of phase B one by one, stir evenly, and the mixture is obtained.

[0055] Example 8 Preparation of cream containing ceramide ethosomes

[0056]

[0057] Preparation method: Heat the materials of phase A to 60-70°C in a suitable container and stir until dissolved, and set aside; add the materials of phase B in a batching pot one after another, mix and place in a water bath at 85°C and heat to 80-85°C; at the same time, mix the materials of phase C and heat to 70-75°C until completely dissolved; then slowly pour phase C into phase B, homogenize for 5 minutes, continue stirring, and maintain the temperature at 80-85°C for 20 minutes; then stir and cool to 55-60°C, add phase A, continue stirring and cool to 45°C, add the materials of phase D one after another, stir evenly, and obtain.

[0058] Comparative Example 1

[0059] Weigh 2 g of lecithin and 67.3 g of ethanol, heat and stir at 40° C. to form a uniform transparent solution; add 2.5 g of ceramide NP, 0.2 g of ceramide AP, 0.2 g of phytosphingosine, 16 g of octyldodecanol, 5 g of sodium di(laurylamide glutamine) lysine, 5 g of disodium cocoyl glutamate, and 1.5 g of tocopherol acetate in a container, heat to 50° C., turn on the stirrer, stir at a rate of 500 r / min for 3 min, stop stirring, and then ultrasonically treat for 10 min at 200 W, ultrasonically treat for 5 s, and stop for 5 s; then add 0.3 g of lactic acid, stir and mix well, and then high-pressure homogenize at 600 bar for 4 times to obtain the product.

[0060] Comparative Example 2

[0061] Weigh 2 g of lecithin and 67.3 g of pentanediol, heat and stir at 40° C. to form a uniform transparent solution; add 2.5 g of ceramide NP, 0.2 g of ceramide AP, 0.2 g of phytosphingosine, 16 g of octyldodecanol, 5 g of sodium di(laurylamide glutamine) lysine, 5 g of disodium cocoyl glutamate, and 1.5 g of tocopherol acetate in a container, heat to 50° C., turn on the stirrer, stir at a rate of 500 r / min for 3 min, stop stirring, and then ultrasonically treat for 10 min at 200 W, ultrasonically treat for 5 s, and stop for 5 s; then add 0.3 g of lactic acid, stir and mix well, and then high-pressure homogenize at 600 bar for 4 times to obtain the product.

[0062] Comparative Example 3

[0063] Weigh 2 g of lecithin and 67.5 g of hexylene glycol, heat and stir at 40° C. to form a uniform transparent solution; add 2.5 g of ceramide NP, 0.1 g of ceramide AP, 0.1 g of phytosphingosine, 16 g of octyldodecanol, 5 g of sodium di(laurylamide glutamine) lysine, 5 g of disodium cocoyl glutamate, and 1.5 g of succinic acid in a container, heat to 50° C., turn on the stirrer, stir at a rate of 500 r / min for 3 min, stop stirring, and then ultrasonically treat for 10 min at 200 W, ultrasonically treat for 5 s, and stop for 5 s; then add 0.3 g of lactic acid, stir and mix well, and then high-pressure homogenize at 600 bar for 4 times to obtain the product.

[0064] Comparative Example 4

[0065] Weigh 2 g of lecithin and 67 g of dipropylene glycol, heat and stir at 40° C. to form a uniform transparent solution; add 2.5 g of ceramide NP, 0.4 g of ceramide AP, 0.4 g of phytosphingosine, 16 g of octyldodecanol, 5 g of sodium di(laurylamide glutamine) lysine, 5 g of disodium cocoyl glutamate, and 1.5 g of tocopherol acetate in a container, heat to 50° C., turn on the stirrer, stir at a rate of 500 r / min for 3 min, stop stirring, and then ultrasonically treat for 10 min at 200 W, ultrasonically treat for 5 s, and stop for 5 s; then add 0.4 g of lactic acid, stir and mix well, and then high-pressure homogenize at 600 bar for 4 times to obtain the product.

[0066] Comparative Example 5

[0067] Weigh 2 g of phosphatidylcholine, 12 g of pentylene glycol, and 55 g of dipropylene glycol, heat and stir at 45° C. to form a uniform transparent solution; add 2.5 g of ceramide NP, 1 g of ceramide AP, 1.5 g of phytosphingosine, 16 g of octyldodecanol, 5 g of disodium cocoyl glutamate, 3 g of glyceryl polyoxyethylene ether, and 1.5 g of tocopherol acetate in a container, heat to 60° C., turn on the stirrer, stir at a rate of 400 r / min for 3 min, stop stirring, then ultrasonically treat for 8 min at 200 W, ultrasonically treat for 5 s, and stop for 5 s, then add 0.5 g of glycolic acid, stir and mix well, and then high-pressure homogenize at 800 bar for 2 times to obtain the product.

[0068] Comparative Example 6

[0069] Weigh 2 g of lecithin, 5 g of hexylene glycol, and 62 g of dipropylene glycol, heat and stir at 40° C. to form a uniform transparent solution; add 2.5 g of ceramide NP, 0.2 g of ceramide AP, 0.2 g of phytosphingosine, 16 g of octyldodecanol, 5 g of sodium di(laurylamide glutamine) lysine, 5 g of disodium cocoyl glutamate, and 1.8 g of tocopherol acetate in a container, heat to 50° C., turn on the stirrer, stir at a rate of 500 r / min for 3 min, stop stirring, and then ultrasonically treat for 10 min at 200 W, ultrasonically treat for 5 s, and stop for 5 s; then add 0.3 g of lactic acid, stir and mix well, and then high-pressure homogenize at 600 bar for 4 times to obtain the product.

[0070] Test Example 1 Dispersibility and stability test in water

[0071] 1.1 Instrument

[0072] Constant temperature and humidity chamber, thermometer, pH meter, OMEC NS-90Z nanoparticle size and potential analyzer.

[0073] 1.2 Test samples

[0074] Ceramide ethosomes prepared in Example 1 and ceramide ethosomes prepared in Comparative Example 1.

[0075] 1.3 Test methods

[0076] Under the conditions of light, -10℃, 4℃, 25℃ and 40℃, the appearance and color of the samples were observed before the test, on the 7th day, 14th day, 1 month, 2 months and 3 months respectively. The pH value, average particle size and Zeta potential of the samples were tested, and the encapsulation efficiency of the products was calculated.

[0077] 1.4 Test results

[0078] The dispersibility and stability data of the test samples in water are shown in Table 1 below:

[0079] Table 1 Dispersibility and stability data of test samples in water

[0080]

[0081]

[0082]

[0083] From the results in the above table, it can be seen that the appearance and color, pH, particle size, Zeta potential, and encapsulation efficiency of the ceramide ethosomes prepared in Comparative Example 1 all showed significant changes after being placed for 3 months, among which the encapsulation efficiency was greatly reduced; while the appearance and color, pH, particle size, Zeta potential, and encapsulation efficiency of the ceramide ethosomes prepared in Example 1 of the present invention did not show significant changes after being placed for 3 months, and were still within the quality standard range, meeting the actual application requirements. Therefore, compared with the traditional ceramide ethosomes prepared by single ethanol, the present invention uses a specific ratio of polyols, surfactants, and phospholipids as the basic components of the ethosomes, and the prepared ceramide ethosomes have high stability, good dispersion effect in water, and high transparency when dissolved in water.

[0084] Test Example 2 Irritation Test

[0085] 2.1 Reagents and Materials

[0086] Chicken embryos of 10-11 days old, normal saline, and Teflon ring.

[0087] 2.2 Instruments

[0088] Egg candling machine, constant temperature and humidity chamber.

[0089] 2.3 Test samples

[0090] Ceramide ethosomes prepared in Example 1 and ceramide ethosomes prepared in Comparative Example 1.

[0091] 2.4 Test methods

[0092] Select 12 chicken embryos of 10-11d embryonic age, mark them, number 1-12, look after the marked air chamber position with an egg light, peel off the eggshell part on the upper layer of the air chamber with tweezers, expose the white eggshell membrane, and drip an appropriate amount of physiological saline to moisten the eggshell membrane. Carefully remove the eggshell membrane with tweezers to ensure that the vascular membrane is not damaged. Place a Teflon ring at a dense blood vessel, take 40 μL of the ceramide alcohol body sample prepared by embodiment 1 to the chicken embryo numbered 1-6, then take 40 μL of the ceramide alcohol body sample prepared by comparative example 1 to the chicken embryo numbered 7-12, and after cultivating 30min in a constant temperature and humidity chamber, evaluate and record the vascular damage in the Teflon ring. Make a score according to the vascular response of the chicken embryo chorioallantoic membrane (CAM), and record the irritation score of the sample.

[0093] The chicken embryo irritation test reaction grading standard is as follows: 0-no reaction; 1-ghost blood vessels; 2-capillary damage; 3-very slight bleeding; 4-mild bleeding; 5-very slight bleeding; 6-mild bleeding; 7-moderate bleeding; 8-severe bleeding.

[0094] 2.5 Test results

[0095] The results of the test samples' irritation to chicken embryos are shown in Table 2 below:

[0096] Table 2 Test results of the irritation of the test samples to chicken embryos

[0097]

[0098]

[0099] From the results in the above table, it can be seen that the ceramide ethosomes prepared in Example 1 of the present invention are basically non-irritating to chicken embryos, safe and reliable, and can be used in daily chemical products; while the ceramide ethosomes prepared by single ethanol in Comparative Example 1 are obviously irritating to chicken embryos. Therefore, the ceramide ethosomes of the present invention can be used as cosmetic additives and directly added to cosmetic formulas for use.

[0100] Test Example 3 Transdermal Delivery Effect Test

[0101] 3.1 Reagents and Materials

[0102] Ceramide caprylic / capric triglyceride solution (containing 2.5% ceramide NP).

[0103] 3.2 Instruments

[0104] Intelligent drug transdermal diffusion tester.

[0105] 3.3 Test samples

[0106] Administration group: ceramide ethosomes prepared in Examples 1-5, ceramide ethosomes prepared in Comparative Examples 2-6;

[0107] Control group: ceramide caprylic / capric triglyceride solution;

[0108] Blank group: no treatment.

[0109] 3.4 Test methods

[0110] The sample was used in the skin model for 6 hours and then the permeation amount of ceramide NP in the model was measured. The test was repeated 3 times and the average permeation concentration was calculated.

[0111] 3.5 Test results

[0112] The results of the permeation concentration of the test samples are shown in Table 3 below:

[0113] Table 3 Permeation concentration results of test samples

[0114]

[0115]

[0116] As can be seen from the results in the above table, compared with the ceramide solution in the control group, the permeation amount of ceramide prepared in the form of ethosomes is significantly increased, indicating that the vesicle structure formed by the ethosomes in the ceramide ethosome preparation can directly penetrate the stratum corneum with active substances, and its flexibility and membrane fluidity increase the fluidity and permeability of the active substances in the epidermal tissue. By comparing the average permeation concentration of the ceramide ethosomes prepared in Examples 1-5 and Comparative Examples 2-6, it can be seen that the average permeation concentration of the ceramide ethosomes prepared in Examples 1-5 using a combination of pentanediol, hexanediol and dipropylene glycol is higher, and the technical effect is better. Therefore, the present invention prepares ceramide into ethosomes, uses pentanediol, hexanediol and dipropylene glycol in combination, and the mass ratio of pentanediol, hexanediol and dipropylene glycol is 12: (5-10): (45-50), thereby further improving the penetration-promoting effect of ceramide, good transdermal absorption, and can be matched with the required skin care product preparation at room temperature, so that the preparation of cosmetics containing ceramide is simple and convenient, thereby being widely used in the field of cosmetics.

[0117] Test Example 4 Patch Test

[0118] 4.1 Reagents and Materials

[0119] Hypoallergenic tape, spot testing equipment.

[0120] 4.2 Test samples

[0121] Administration group: the emulsion containing ceramide ethosomes prepared in Example 4;

[0122] Negative control group: blank + filter disc.

[0123] 4.3 Test methods

[0124] Select qualified patch test equipment and use the closed patch test method. Place 0.020-0.025g of the sample to be tested in the patch test equipment and apply it to the curved side of the subject's forearm with a low-allergenic tape. Remove the sample to be tested after 24 hours and observe the skin reaction at 0.5h, 24h, and 48h after removal. Record the results according to the skin reaction grading standard.

[0125] Skin reaction grading standard for occlusive patch test: 0-negative reaction; 1-questionable reaction, only slight erythema; 2-weak positive reaction (erythema reaction); erythema, infiltration, edema, and papules may be present; 3-strong positive reaction (herpes reaction); erythema, infiltration, edema, papules, and herpes; the reaction may extend beyond the tested area; 4-strong positive reaction (herpes reaction); erythema, infiltration, edema, papules, and herpes; the reaction may extend beyond the tested area.

[0126] 4.4 Test results

[0127] The present invention conducts a human patch test on cosmetics containing ceramide alcohol bodies to evaluate the irritation of the ceramide alcohol bodies of the present invention to human skin when used in cosmetics. The patch test results of the test samples are shown in Table 4 below:

[0128] Table 4 Patch test results of test samples

[0129]

[0130] From the results in the above table, it can be seen that among the 32 subjects, no adverse reactions occurred, indicating that the application of ceramide ethosomes in cosmetics according to the present invention is safe and non-irritating, will not cause allergic reactions, and can be directly added to cosmetic formulas for use.

[0131] Test Example 5 Performance test of cosmetics containing ceramide ethosomes

[0132] 5.1 Instrument

[0133] Skin elasticity tester, multifunctional skin imaging and analysis system.

[0134] 5.2 Test samples

[0135] Example 4: The ceramide ethosome-containing emulsion prepared in Example 4.

[0136] 5.3 Test methods

[0137] Thirty healthy women aged 27-42 years were selected and treated with a lotion containing ceramide ethosomes.

[0138] During the test, the subjects first cleaned their faces with the same cleanser, and then applied the corresponding lotion products on their faces, about 0.8g each time, once in the morning and once in the evening, for 2 consecutive months. During the test period, the subjects maintained a regular life and avoided outdoor exposure. During the test period, no cosmetics, medicines, or health products that may affect the results were used.

[0139] After two months, the specific degree of improvement in the subjects' facial skin elasticity, skin gloss, and skin smoothness was evaluated.

[0140] 5.4 Test Results

[0141] The improvement of the test samples on various facial indicators is shown in Table 5 below:

[0142] Table 5 Improvement of facial indicators by test samples

[0143] Test samples Skin elasticity % Skin Gloss % Skin smoothness % Example 4 Emulsion containing ceramide ethosomes prepared 76.3 89.9 67.1

[0144] From the results in the above table, it can be seen that the emulsion containing ceramide alcohol body can improve the elasticity, glossiness and smoothness of the skin, and has a good anti-aging and repairing effect. Therefore, the ceramide alcohol body of the present invention can be used as a cosmetic additive and directly added to the cosmetic formula for use, to exert the anti-aging, repairing and soothing effects, and meet the needs of consumers for treating or caring for the skin.

[0145] Although the preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the embodiments of the present invention.

[0146] Finally, it should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or terminal device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or terminal device. In the absence of further restrictions, the elements defined by the sentence "including a..." do not exclude the presence of other identical elements in the process, method, article or terminal device including the elements.

[0147] The above is a detailed introduction to a ceramide ethosome provided by the present invention, and its preparation method and application. Specific examples are used herein to illustrate the principle and implementation mode of the present invention. The description of the above embodiments is only used to help understand the method of the present invention and its core idea. At the same time, for those skilled in the art, according to the idea of ​​the present invention, there will be changes in the specific implementation mode and application scope. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A ceramide ethosome, It is characterized in that The invention comprises the following components: in terms of mass percentage, 0.1-10% of a ceramide mixture, 5-30% of a surfactant, 0.5-10% of a phospholipid, 4-24% of a penetration enhancer and 50-80% of a polyol; the polyol is a combination of pentylene glycol, hexylene glycol and dipropylene glycol, and the mass ratio of pentylene glycol, hexylene glycol and dipropylene glycol is 12:(5-10):(45-50).

2. The ceramide ethosome according to claim 1, It is characterized in that The invention comprises the following components: calculated by mass percentage, 0.5-8% of ceramide mixture, 8-25% of surfactant, 2-8% of phospholipid, 8-16% of penetration enhancer and 55-70% of polyol.

3. The ceramide ethosome according to claim 1, It is characterized in that The invention comprises the following components: calculated by mass percentage, ceramide mixture 3-5%, surfactant 10-20%, phospholipid 4-6%, penetration enhancer 10-15% and polyol 60-65%.

4. The ceramide ethosome according to any one of claims 1 to 3, It is characterized in that The ceramide mixture consists of ceramide NP, ceramide AP and phytosphingosine, wherein the mass ratio of ceramide NP, ceramide AP and phytosphingosine is 1:(0.04-1):(0.04-1).

5. The ceramide ethosome according to any one of claims 1 to 3, It is characterized in that The surfactant is selected from one or more of sodium di(laurylamide glutamine) lysine, disodium cocoyl glutamate, glyceryl polyoxyethylene ether, lanolin alcohol ether, cetyl alcohol polyether or lauryl alcohol polyether; The phospholipid is lecithin and / or phosphatidylcholine; The penetration enhancer is selected from one or more of octyl dodecanol, azone, ethanol, fatty alcohol, pyrrolidone or fatty acid.

6. The ceramide ethosome according to any one of claims 1 to 3, It is characterized in that Antioxidants and / or pH adjusters may also be included.

7. The ceramide ethosome according to claim 6, It is characterized in that The antioxidant is selected from one or more of tocopherol acetate, butylated hydroxytoluene or butylated hydroxyanisole; The pH regulator is selected from one or more of citric acid, lactic acid, acetic acid, phosphoric acid, tartaric acid, malic acid or glycolic acid.

8. The method for preparing ceramide ethosomes according to any one of claims 1 to 7, It is characterized in that The following steps are involved: (1) Weighing the prescribed amount of phospholipids and polyols, heating and dissolving the phospholipids in the polyols at a specified temperature to obtain a mixed solution; (2) weighing a prescribed amount of a surfactant and a ceramide mixture, optionally adding an antioxidant, adding the mixture to the mixed solution obtained in step (1), dissolving the mixture under specified conditions, and ultrasonically treating the mixture to obtain a crude ethosome; (3) A pH regulator is selectively added to the crude ethosome obtained in step (2), mixed evenly, and homogenized under high pressure to obtain the ceramide ethosome.

9. The method for preparing ceramide ethosomes according to claim 8, It is characterized in that The specified temperature in step (1) is 30-45°C; The specified conditions in step (2) are a temperature of 40-60° C. and a stirring speed of 400-600 r / min; The ultrasonic conditions in step (2) are as follows: power 200 W, ultrasonic treatment for 5 seconds, intermittent stop for 5 seconds, and ultrasonic treatment for 8 to 12 minutes; The parameters of the high pressure homogenization in step (3) are 400-800 bar, and the homogenization is performed 2-6 times.

10. Use of the ceramide ethosome according to any one of claims 1 to 7 in cosmetics, wherein the ceramide ethosome is used as a cosmetic additive.

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