阅读说明：本技术 一种水溶性神经酰胺np组合物及其制备工艺和应用 (Water-soluble ceramide NP composition and preparation process and application thereof ) 是由 沈罟 方紫 陈晓颖 于 2021-08-05 设计创作，主要内容包括：本发明涉及IPC A61K8/68领域,尤其涉及一种水溶性神经酰胺NP组合物及其制备工艺和应用。水溶性神经酰胺NP组合物的原料包括神经酰胺NP,磷脂质,表面活性剂,端羟基化合物,溶剂；所述神经酰胺NP和磷脂质的重量为1：(2-15)。本发明水溶性神经酰胺的平均粒径可低至70nm,成功解决了神经酰胺熔点高,水溶性差,难乳化的应用问题,大大提升神经酰胺配方的应用便利性。应用于化妆品中能够修复屏障,延缓衰老,即时修复皮肤屏障功能；还能够提高皮肤角质层水分含量,激活老化成纤维细胞,减少皱纹,提升皮肤柔软性；同时还能有效清除自由基,协同皮肤美白,改善皮肤光泽度。(The invention relates to the field of IPC A61K8/68, in particular to a water-soluble ceramide NP composition and a preparation process and application thereof. The raw materials of the water-soluble ceramide NP composition comprise ceramide NP, phospholipid, a surfactant, a hydroxyl-terminated compound and a solvent; the weight of the ceramide NP and the phospholipid is 1: (2-15). The average particle size of the water-soluble ceramide can be as low as 70nm, so that the application problems of high melting point, poor water solubility and difficult emulsification of the ceramide are successfully solved, and the application convenience of the ceramide formula is greatly improved. Can repair the barrier, delay aging and immediately repair the skin barrier function when being applied to cosmetics; the water content of the skin cuticle can be increased, aged fibroblasts are activated, wrinkles are reduced, and the skin softness is improved; meanwhile, the skin whitening cream can effectively remove free radicals, and is used for whitening the skin and improving the skin glossiness.)

1. A water-soluble ceramide NP composition is characterized in that raw materials of the composition comprise ceramide NP, phospholipid, a surfactant, a hydroxyl-terminated compound and a solvent; the weight of the ceramide NP and the phospholipid is 1: (2-15).

2. The water-soluble ceramide NP composition of claim 1, wherein the phospholipids comprise a combination of one or more of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, diphosphatidylglycerol, sphingomyelin, and plasmalogen.

3. The water-soluble ceramide NP composition of claim 2, wherein the phospholipid is phosphatidylcholine.

4. The water-soluble ceramide NP composition of any one of claims 1-3, wherein the surfactant comprises a combination of one or more of an anionic surfactant, a cationic surfactant, a nonionic surfactant, and an amphoteric surfactant.

5. The water-soluble ceramide NP composition of claim 4, wherein the anionic surfactant comprises a combination of one or more of a carboxylic acid compound, a sulfate ester compound, a sulfonic acid compound, a phosphate ester compound, an amino acid compound, a phenolate salt compound, a ketosulfonamide salt compound.

6. The water-soluble ceramide NP composition of claim 5, wherein the amino acid compounds comprise a combination of one or more of sodium stearoyl glutamate, sodium myristoyl glutamate, potassium coconut oil fatty acid acyl glycinate, triethanolamine coconut oil fatty acid acyl glutamate, disodium coconut oil fatty acid acyl glutamate, and sodium N-lauroyl sarcosinate.

7. The water-soluble ceramide NP composition of any one of claims 1-6, wherein the hydroxyl-terminated compound comprises one or more combinations of 1, 2-propanediol, 2-methyl-1, 3-propanediol, dipropylene glycol, glycerol, 1, 2-butanediol, 1, 3-butanediol, 1, 4-butanediol, 2, 2-dimethyl-1, 3-propanediol, 1, 2-hexanediol.

8. A process for preparing a water-soluble ceramide NP composition according to any one of claims 1 to 7, comprising the steps of:

s1, mixing ceramide NP and phospholipid and carrying out pretreatment to obtain a mixture I;

s2, sequentially adding a solvent, a surfactant and a hydroxyl-terminated compound into the first mixture, and homogenizing to obtain a second mixture;

s3, performing high-pressure micro-jet treatment on the mixture II to obtain a coarse material;

and S4, filtering the coarse material, discharging and packaging to obtain a finished product.

9. The process of claim 8, wherein the step S3, the pressure of the high pressure micro-jet treatment is 100-300 MPa.

10. Use of the water-soluble ceramide NP composition of any one of claims 1-7 in a skin care product.

Technical Field

The invention relates to the field of IPC A61K8/68, in particular to a water-soluble ceramide NP composition and a preparation process and application thereof.

Background

Ceramide (Ceramide) is an important physiological lipid component, and is important for maintaining the barrier function of skin, strengthening the adhesion between keratinocytes and balancing the hydration of epidermal layers. With the aging, the ceramide content in the skin is reduced, and the addition of ceramide in cosmetics has become a popular means for improving the skin care effect. However, the traditional ceramide raw material is a fat-soluble substance, has extremely low solubility in water and is difficult to be absorbed by a human body; meanwhile, after the ceramide is directly added into a cosmetic formula, the ceramide is easy to crystallize and separate out in the standing process, and the system stability is reduced.

Chinese patent CN201810215403.6 discloses a ceramide liposome and a preparation method and application thereof, wherein glycerol, ethoxy diglycol, ceramide, phospholipid and water are mixed to prepare a faint yellow ceramide liposome with high stability and good dispersibility in water. Chinese patent CN202011577818.1 discloses a composition with repairing function and a preparation method and application thereof, wherein a product with the effect of repairing and treating damaged skin is obtained by the combined action of ceramide3, tocopherol or tocopherol derivatives, alpha-bisabolol and a repairing compound. In the prior art, the solubility of ceramide is improved by liposome, but the problems of higher product particle size and poor color still exist, so that a clear and transparent ceramide composition with low particle size cannot be prepared, and the effect of the ceramide composition in the field of cosmetics is limited.

Under the background, the research of a ceramide product which has low particle size and high transparency, can effectively repair skin barriers, maintain stability, resist aging, replenish water and moisturize the skin becomes a problem to be solved in the field.

Disclosure of Invention

The invention provides the water-soluble ceramide NP composition, solves the problems of low ceramide solubility and poor stability in the prior art, and realizes the water-soluble ceramide NP composition which has low particle size and high transparency, can effectively repair skin barriers, maintain stability, resist aging and moisturize.

The invention provides a water-soluble ceramide NP composition, which comprises raw materials of ceramide NP, phospholipid, a surfactant, a hydroxyl-terminated compound and a solvent; the weight ratio of the ceramide NP to the phospholipid is (1-4): (2-10); preferably 2.5: 7.

the invention discloses a Ceramide, which comprises Ceramide1, Ceramide2, Ceramide3, Ceramide5, Ceramide6 II and the like, and the Ceramide NP (namely Ceramide3) can be effectively combined with phospholipid and can effectively act on skin tissues after acting on skin, so that the skin barrier can be repaired immediately, the water locking capacity of the skin stratum corneum is improved, the water-deficient state of the skin is improved, the skin peeling and desquamation are reduced, the water content of the skin is improved, and the smooth operation of substance circulation in the skin tissues is further ensured.

In some preferred embodiments, the phospholipid comprises a combination of one or more of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, diphosphatidylglycerol, sphingomyelin, and plasmalogen.

In order to improve the coating effect on ceramide and the stability of the water-soluble ceramide NP composition, it is further preferable that the phospholipid is phosphatidylcholine. The invention discovers that the phospholipid and the ceramide NP are mixed, and the bilayer structure of the phospholipid can effectively encapsulate the ceramide NP; further, the inventors found that when the phospholipid is phosphatidylcholine, the formed coating can maintain a strong adsorption effect in the composition, inhibit the precipitation tendency of ceramide, and further improve the stability.

In some preferred embodiments, the surfactant comprises a combination of one or more of an anionic surfactant, a cationic surfactant, a nonionic surfactant, and an amphoteric surfactant. In some of the preferred embodiments of the present invention,

the anionic surfactant comprises one or more of carboxylic acid compound, sulfate compound, sulfonic acid compound, phosphate compound, amino acid compound, phenolate compound and keto-sulfonamide compound.

In some preferred embodiments, the amino acid compound comprises a combination of one or more of sodium stearoyl glutamate, sodium myristoyl glutamate, potassium coconut oil fatty acid acyl glycinate, triethanolamine coconut oil fatty acid acyl glutamate, disodium coconut oil fatty acid acyl glutamate, and sodium N-lauroyl sarcosinate.

In order to improve the moisturizing and repairing effects of the water-soluble ceramide NP composition, it is further preferable that the amino acid compound is sodium stearyl glutamate. The invention discovers that the combined action of sodium stearyl glutamate and a ceramide NP-phosphatidylcholine composite active factor can improve the water content of the skin, repair the skin barrier and improve the bonding force of the skin cuticle through a large number of attempts. It was further found that when the weight ratio of amino acid compound to ceramide was 1: (3-6), a transparent water-soluble ceramide NP composition can be obtained, and the problems that most of the existing ceramide compositions are milky white and low in transparency are solved; the water-soluble ceramide NP composition has the particle size of less than 100nm, can be completely transparent when dissolved in water, has an excellent skin care effect, and simultaneously has an attractive appearance.

In some preferred embodiments, the hydroxyl terminated compound comprises a combination of one or more of 1, 2-propanediol, 2-methyl-1, 3-propanediol, dipropylene glycol, glycerol, 1, 2-butanediol, 1, 3-butanediol, 1, 4-butanediol, 2, 2-dimethyl-1, 3-propanediol, 1, 2-hexanediol.

In order to further improve the water holding capacity of the skin, the hydroxyl-terminated compound is preferably 1, 3-butanediol and 1, 2-hexanediol; the weight ratio of the 1, 3-butanediol to the 1, 2-hexanediol is (10-40): 1. the invention finds that the water solubility of the ceramide can be improved by adopting the specific hydroxyl-terminated compound, the ceramide is promoted to be effectively absorbed by the skin, the water holding capacity of the skin is further improved, and the water content of the skin can still be kept more than 20% after the water-soluble ceramide NP composition is continuously used for 7 days and then is stopped to be used for 6 days.

Preferably, the weight ratio of the hydroxyl-terminated compound to ceramide is (0.5-6): 1.

in some preferred embodiments, the solvent is water; preferably deionized water; the weight ratio of the solvent to the ceramide is (40-70): (0.4-5).

In a second aspect, the present invention provides a process for preparing a water-soluble ceramide NP composition, comprising the steps of:

s1, mixing ceramide NP and phospholipid and carrying out pretreatment to obtain a mixture I;

s2, sequentially adding a solvent, a surfactant and a hydroxyl-terminated compound into the first mixture, and homogenizing to obtain a second mixture;

s3, performing high-pressure micro-jet treatment on the mixture II to obtain a coarse material;

and S4, filtering the coarse material, discharging and packaging to obtain a finished product.

In some preferred embodiments, the step S1 is specifically to dissolve ceramide and phospholipid in organic solvent, homogenize for 1-5min, and then transfer to a rotary evaporator to remove the organic solvent, so as to obtain a first mixture. The homogenizing operation enables the ceramide-phospholipid to be fully micronized and homogenized in the organic solvent, effectively reduces the particle size of the water-soluble ceramide NP, and improves the compatibility of the ceramide-phospholipid with the surfactant and the hydroxyl-terminated compound.

In some preferred embodiments, the organic solvent comprises a combination of one or more of methanol, ethanol, chloroform, ethyl acetate, n-hexane, petroleum ether.

In some preferred embodiments, the step S2 is specifically, adding the solvent, the surfactant and the hydroxyl-terminated compound into the first mixture in sequence, performing ultrasonic treatment for 1-5min, and homogenizing for 1-5min under the conditions of 1000-;

in some preferred embodiments, in the step S3, the operating pressure of the high-pressure micro-jet treatment is 100-300 MPa.

Further preferably, the step S3 is specifically to perform high-pressure microjet treatment of 240-300MPa on the mixture II, collect the coarse material I, and perform high-pressure microjet treatment of 100-180MPa on the coarse material I to obtain the coarse material II. According to the invention, a large number of researches show that the ceramide NP-phosphatidylcholine can be effectively promoted to form an interactive cavity in a solvent by adopting high-pressure microjet operation, and the ceramide NP-phosphatidylcholine can be further uniformly dispersed in a composition system, and can be rapidly permeated into the interior of the skin to mediate the physiological activity of cells after contacting the skin, so that the skin condition is improved, and the skin barrier is repaired.

In some preferred embodiments, the step S4 is specifically to filter the coarse material two by using a double-layer filter cloth of 50-600 meshes, so as to obtain the product.

The invention discovers through a great deal of experimental researches that the water-soluble ceramide NP composition with low particle size and high transparency can be obtained by firstly combining the ceramide NP with phospholipid, then mixing the ceramide NP with a solvent, a surfactant and a hydroxyl-terminated compound, homogenizing the mixture and then carrying out high-pressure micro-jet treatment. The prior ceramide improved product is mostly milky white with the average particle size of more than 200nm, while the particle size of the product prepared by the specific process can be as low as 70nm, and the product is transparent in color.

In a third aspect, the invention provides the use of a water-soluble ceramide NP composition for application in a skin care product.

The skin care product is a product commonly used in the field of cosmetics, and comprises, but is not limited to, smoothing toner, essence, lotion, cream, facial cleanser and shower gel.

Has the advantages that:

the water-soluble ceramide NP composition provided by the invention has the following advantages:

(1) the average particle size of the water-soluble ceramide can be as low as 100nm (even can reach 70nm), the application problems of high melting point, poor water solubility and difficult emulsification of the ceramide are successfully solved, and the ceramide can be made into a transparent system, so that the application convenience of a ceramide formula is greatly improved.

(2) The water-soluble ceramide of the invention can repair barriers, delay aging and repair skin barrier functions in time when being applied to cosmetics; the moisture content of the skin cuticle can be improved, the skin can be kept moisture for a long time, the dryness of the skin can be improved, and the desquamation phenomenon of the skin can be reduced; meanwhile, the activity of collagenase and elastase can be inhibited, aged fibroblasts are activated, wrinkles are reduced, and the skin softness is improved; meanwhile, the skin whitening cream can effectively remove free radicals, and is used for whitening the skin and improving the skin glossiness.

(3) The invention has easily obtained raw materials, mild and safe formula, less than 10ppm of heavy metal content, less than 100CFU/mL of total bacteria number, no stimulation to human body and accordance with industrial standard; the invention has strong process practicability, can achieve obvious skin care effect under extremely low consumption, and has wide application prospect in the field of cosmetics.

Drawings

FIG. 1 shows the results of stratum corneum cohesion test of sample A;

FIG. 2 shows the results of the stratum corneum cohesion test of sample C to be tested;

FIG. 3 is a comparison of the water-soluble ceramide NP composition of example 1 with the commercial ceramide product (degussa) (left for the degussa ceramide product and right for the final product of example 1 of the present invention);

fig. 4 is a comparison graph of the water-soluble ceramide NP composition of example 1 and a commercial ceramide product (degussa) dissolved in water (both at 1% by mass) (left is an aqueous solution of the degussa ceramide product, and right is an aqueous solution of the finished product of example 1 of the present invention).

Detailed Description

Example 1.

This example provides a water-soluble ceramide NP composition, which comprises ceramide, phospholipid, surfactant, hydroxyl-terminated compound, solvent; the weight ratio of the ceramide, the phospholipid, the surfactant, the hydroxyl-terminated compound and the solvent is 2.5:7:0.5:31: 59.

The ceramide is ceramide NP, the INCI name is CERAMIDE NP, and the ceramide is sourced from Germany winning.

The phospholipid is PHOSPHATIDYLCHOLINE, and the INCI is PHOSPHATIDYLCHOLINE, and is from Sigma-Aldrich company.

The surfactant is SODIUM stearyl glutamate, INCI is SODIUM stearylolglutamate, and CAS number is 38517-23-6.

The hydroxyl-terminated compound is 1, 3-butanediol and 1, 2-hexanediol; the weight ratio of the 1, 3-butanediol to the 1, 2-hexanediol is 30: 1.

the solvent is deionized water.

The preparation process of the water-soluble ceramide NP composition comprises the following steps:

s1, mixing ceramide NP and phospholipid and carrying out pretreatment to obtain a mixture I;

s2, sequentially adding a solvent, a surfactant and a hydroxyl-terminated compound into the first mixture, and homogenizing to obtain a second mixture;

s3, performing high-pressure micro-jet treatment on the mixture II to obtain a coarse material;

and S4, filtering the coarse material, discharging and packaging to obtain a finished product.

The S1 step is specifically that dissolving ceramide NP and phospholipid in an organic solvent, homogenizing for 2min at 1000r/min, and then transferring to a rotary evaporator to remove the organic solvent to obtain a mixture I.

The organic solvent is trichloromethane; the weight ratio of the organic solvent to the ceramide is 20: 1.

The step S2 is specifically that a solvent, a surfactant and a hydroxyl-terminated compound are sequentially added into the mixture I, ultrasonic treatment is carried out for 3min, and homogenization is carried out for 3min under the condition of 1800r/min to obtain a mixture II;

and the step S3 is specifically to perform 260MPa high-pressure micro-jet treatment on the mixture II, collect the coarse material I, and perform 120MPa high-pressure micro-jet treatment on the coarse material I to obtain the coarse material II.

And S4, specifically, filtering the coarse material II by using 200-mesh double-layer filter cloth, discharging and packaging to obtain a finished product.

Performance test method

Mixing the water-soluble ceramide NP composition provided in example 1 with 2 wt% of Tween 80 aqueous solution respectively to obtain a sample A to be detected and a sample B to be detected; wherein the mass concentration of the water-soluble ceramide NP composition in the sample A to be tested is 5 percent, and the mass concentration of the water-soluble ceramide NP composition in the sample B to be tested is 0.5 percent; meanwhile, a commercial ceramide product (derived from Degussa) aqueous solution (with the concentration of 5 wt%) is taken as a sample C to be detected. 1. The moisturizing effect is as follows:

screening 60 volunteers, dividing the volunteers into 3 groups, respectively using a sample to be tested on the front side of one arm of each group, and taking the front side of the other arm as a blank control; the using method comprises the following steps: is administered 1 time each day in the morning and evening, and the single dose is 2mg/cm²。

Continuously using for 7 days, measuring the moisture content of the skin on the 1 st, 3 rd and 7 th days in the using process, continuously measuring the moisture content of the skin on the 8 th, 10 th and 13 th days (note: the sample to be measured is not used on the 8 th to 13 th days in the experiment process), averaging the measurement results of each group, calculating the increase of the moisture content of the skin after the treatment of each group of the sample to be measured relative to a blank control (calculated by the average value of each group), and recording the increase in the moisture content of the skin after the treatment of each group of the sample to be measured in the table 1.

2. The repairing effect is as follows:

referring to the method of use of the moisturizing effect test, the test specimen was continuously used for 7 days, and then hot-compressed at the test site (including the blank site) for 2 hours at 45 ℃ using SDS (5% aqueous sodium dodecyl sulfate solution), and the epidermal moisture loss rate TEWL (%) of the test site was measured using a skin moisture loss (TEWL) test probe of the german CK company, see table 2.

The TEWL (%) of the blank control is the average of the epidermal water loss rate at the blank control sites of all subjects.

3. Testing the skin stratum corneum bonding force:

screening 2 subjects, and using the sample A to be tested and the sample C to be tested on the front side of the left arm respectively for 18 days, wherein the using method is the same as that of the above; the stratum corneum condition of the skin was observed after 18 days of use, as shown in fig. 1.

4. Average particle size:

the water-soluble ceramide NP composition of example 1 was measured using a high performance laser particle sizer and the average particle size of the sample was measured to be 70.2 nm.

Performance test data

Table 1.

Measuring time	Sample A to be tested	Sample B to be tested	Sample C to be tested
				Day 1	35.8％	24.6％	15.1％
Day 3	37.2％	26.1％	21.9％
				Day 7	39.1％	30.5％	29.3％
Day 8	35.3％	23.5％	5.0％
				Day 10	29.4％	9.9％	＜0
Day 13	15.3％	＜0	＜0

Table 2.

	Sample A to be tested	Sample B to be tested	Sample C to be tested	Blank control
					TEWL/％	500	275	890	1005

Compared with the experimental results, the water-soluble ceramide NP composition provided by the invention can keep the skin hydration degree longer, does not disturb the normal physiological function of the skin after use, does not block the skin, and has less TEWL% increase after SDS hot compress in an area treated by the product, thereby embodying the excellent protection effect of the water-soluble ceramide NP composition on the skin, effectively preventing the skin from being damaged due to the influence of irritants, and remarkably regulating the skin barrier function and preventing the skin from being inflamed and damaged. As can be seen from a combination of FIGS. 1 and 2, the skin treated with the test sample A of the present invention had only a small amount of debris left on the adhesive tape, while the control adhesive tape had a large amount of cell material. The longitudinal binding force and the whole binding force of the skin are obviously improved after 18 days of using the product of the invention, the water-soluble ceramide NP composition is suitable for improving the conditions of skin scurf, dullness, roughness, sensitivity and the like, and can greatly reduce skin fragments after being used, so that the skin is more youthful and bright. As is apparent from fig. 3 and 4, the present invention has superior characteristics of high transparency and water solubility, compared to the milky-white, water-insoluble ceramide on the market. According to the invention, the ceramide NP is made into a transparent system, so that the application convenience of the ceramide formula is greatly improved.