Transparent ceramide liposome as well as preparation method and application thereof

Abstract

The invention relates to the technical field of cosmetics, in particular to transparent ceramide liposome as well as a preparation method and application thereof, and the transparent ceramide liposome comprises the following components in percentage by mass: 0.1-3% of an active matter, 0.2-10% of an emulsifier, 0.05-3% of a co-emulsifier A, 0.05-3% of a co-emulsifier B, 0.2-20% of a cosolvent and 62-98.4% of a water-phase matrix, the transparent ceramide liposome provided by the invention has good water dispersibility, can be mutually dissolved with an aqueous solution in any proportion, is in a completely transparent state, has good long-time storage stability, does not precipitate crystals, is small in particle size, and improves the bioavailability of ceramide.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a transparent ceramide liposome, its preparation method, and its application. Background Technology

[0002] Ceramides are composed of long-chain sphingosine bases and fatty acids linked by amide bonds. Ceramide raw materials are widely used in cosmetics, offering benefits such as barrier repair, moisturizing, water retention, and soothing. While ceramides have numerous benefits, their hydrophilic head and hydrophobic tail give them high lipophilicity, high molecular weight, and polymorphic properties, making them difficult to dissolve in oil and water. Although they can dissolve in oil at high temperatures, they easily recrystallize during cooling, causing difficulties in cosmetic applications. Undissolved ceramides can form needle-like crystals, affecting product efficacy and, in severe cases, even leading to product flocculation or stratification.

[0003] While traditional ceramide encapsulation technology can improve the stability of ceramide formulations at the application stage, it cannot be applied to transparent aqueous solutions. Furthermore, most ceramide formulations have large particle sizes and low dispersibility, affecting transdermal absorption and bioavailability. CN119367229A provides a liquid crystal emulsification technology for encapsulating stable ceramides, applicable to creams and lotions to improve their stability, but it cannot be used in aqueous solutions. CN118948666A and CN120267559A provide a ceramide liposome encapsulation technology, which significantly improves the water dispersibility of ceramides, resulting in high water dispersion transparency. However, the actual aqueous dispersion is bluish-green and semi-transparent, not completely transparent, and long-term stability studies have not been conducted, making it difficult to meet the requirements for application and stable storage in completely transparent aqueous solutions.

[0004] To address the above pain points, there is an urgent need to develop a highly stable, transparent ceramide liposome formulation that dissolves completely in water, is completely transparent, and is stable without precipitation, thus meeting the requirements for transparent aqueous formulations. Summary of the Invention

[0005] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a transparent ceramide liposome, its preparation method and application, to solve the problems of ceramide being poorly soluble in oil and water, difficult to apply in formulations, and prone to crystallization during storage, as well as the problems of ceramide having large particle size, easy crystallization, difficulty in realizing bioavailability and efficacy, and difficulty in adding it to formulations at high concentrations.

[0006] To achieve the above and other related objectives, the present invention provides a transparent ceramide liposome comprising the following components by weight percentage: Active ingredient 0.1-3%, emulsifier 0.2-10%, co-emulsifier A 0.05-3%, co-emulsifier B 0.05-3%, co-solvent 0.2-20%, aqueous matrix 62-98.4%; The active ingredient is selected from one or more of ceramides and ceramide-like substances, phytosphingosine, and sterols; The emulsifier is selected from one or more of the following: soybean lecithin, phosphatidylcholine, lysophosphatidylcholine, hydrogenated lecithin, hydrogenated lysophosphatidylcholine, egg yolk lecithin, hydroxylated lecithin, distearyl phosphatidylcholine, dilauryl phosphatidylcholine, dipalmitoyl phosphatidylcholine, and dimyristoyl phosphatidylcholine. The co-emulsifier A is an amino acid-type anionic surfactant; the amino acid-type anionic surfactant is selected from one or more of sodium stearoyl glutamate, sodium palmitoyl glutamate, sodium myristoyl glutamate, sodium lauroyl glutamate, potassium cocoyl glutamate, and sodium bis(lauramide glutamine) lysine. The co-emulsifier B is a PEG-based surfactant; The co-solvent is selected from one or more of 1,3-butanediol, 1,2-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, propylene glycol, 1,3-propanediol, dipropylene glycol, etc. The aqueous matrix includes water, a humectant, and a preservative.

[0007] The present invention also provides a method for preparing the transparent ceramide liposomes as described above, comprising the following steps: S1. Weigh the active ingredient, emulsifier, co-emulsifier B and co-solvent according to the proportion, heat and mix them evenly until completely dissolved to obtain phase A, and set aside. S2. Weigh the co-emulsifier A and the aqueous matrix according to the proportion, heat and mix them evenly until completely dissolved to obtain phase B, and set aside. S3. Under homogeneous conditions, the A phase obtained in step S1 is injected into the B phase obtained in step S2, and the homogenization is continuously sheared to obtain the C phase. S4. Homogenize the C phase obtained in step S3 to obtain highly stable transparent ceramide liposomes.

[0008] The present invention also provides an application of the transparent ceramide liposomes described above in the field of cosmetics.

[0009] As described above, the transparent ceramide liposomes, their preparation method, and their applications of the present invention have the following beneficial effects: (1) The transparent ceramide liposomes of the present invention have the advantages of good water solubility, complete transparency, high stability and significant efficacy. They are also completely transparent when added in any proportion in aqueous formulations.

[0010] (2) The ceramide liposomes of the present invention solve the problem that ceramides are difficult to dissolve in water and oil and are difficult to apply in formulations. They have good water dispersibility, can be miscible with water in any proportion, and are completely transparent. They have good long-term storage stability and no crystallization. They can also be added to formulations at high concentrations.

[0011] (3) The ceramide liposomes provided by the present invention have small particle size, are stable and not easily crystallized and precipitated, thus improving the bioavailability of ceramide.

[0012] (4) The ceramide liposomes provided by the present invention have the effect of repairing lipid barrier. The product is mild and non-irritating, and the 2%-5% concentration patch is non-irritating. Attached Figure Description

[0013] Figure 1 The images show a comparison of the appearance of samples from Example 1, Comparative Example 1, and Comparative Example 6.

[0014] Figure 2 The images show a comparison of the appearance of samples from Example 1, Comparative Example 1, and Comparative Example 6 when dispersed in 2% water.

[0015] Figure 3 The particle size distributions are for samples from Example 1, Comparative Example 1, and Comparative Example 6.

[0016] Figure 4 The images show the appearance of samples from Example 1 at 10%, 20%, 50%, and 80% water dispersion. Detailed Implementation

[0017] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0018] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention; in the specification and claims of the present invention, unless otherwise expressly stated in the text, the singular forms "a", "an" and "this" include the plural forms.

[0019] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0020] Furthermore, it should be understood that one or more method steps mentioned in this invention do not preclude the existence of other method steps before or after the combined steps, or the insertion of other method steps between these expressly mentioned steps, unless otherwise stated.

[0021] The first aspect of this invention provides a transparent ceramide liposome comprising the following components by weight percentage: Active ingredient 0.1-3%, emulsifier 0.2-10%, co-emulsifier A 0.05-3%, co-emulsifier B 0.05-3%, co-solvent 0.2-20%, aqueous matrix 62-98.4%.

[0022] The active ingredient may be 0.1-0.4%, 0.4-0.8%, 0.8-1.2%, 1.2-1.6%, 1.6-2%, 2-2.4%, 2.4-2.8%, or 2.8-3%. The active ingredient is selected from one or more of ceramides and ceramide-like substances, phytosphingosine, and sterols.

[0023] The emulsifier may be 0.2-0.5%, 0.5-1%, 1-2%, 2-4%, 4-6%, 6-8%, or 8-10%. The emulsifier is selected from one or more of soybean lecithin, phosphatidylcholine, lysophosphatidylcholine, hydrogenated lecithin, hydrogenated lysophosphatidylcholine, egg yolk lecithin, hydroxylated lecithin, distearylphosphatidylcholine, dilauroylphosphatidylcholine, dipalmitoylphosphatidylcholine, and dimyristoylphosphatidylcholine.

[0024] The co-emulsifier A can be 0.05-0.1%, 0.1-0.5%, 0.5-1%, 1-1.5%, 1.5-2%, 2-2.5%, or 2.5-3%. The co-emulsifier A is an amino acid-type anionic surfactant. The amino acid-type anionic surfactant is selected from one or more of sodium stearoyl glutamate, sodium palmitoyl glutamate, sodium myristoyl glutamate, sodium lauroyl glutamate, potassium cocoyl glutamate, and sodium bis(lauramide-glutamine)lysine.

[0025] The co-emulsifier B can be 0.05-0.1%, 0.1-0.5%, 0.5-1%, 1-1.5%, 1.5-2%, 2-2.5%, or 2.5-3%. The co-emulsifier B is a PEG-based surfactant.

[0026] The co-solvent can be 0.2-0.5%, 0.5-1%, 1-5%, 5-10%, 10-15%, or 15-20%. The co-solvent is selected from one or more of 1,3-butanediol, 1,2-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, propylene glycol, 1,3-propanediol, and dipropylene glycol.

[0027] The aqueous phase matrix can be 62-65%, 65-70%, 70-75%, 75-80%, 80-85%, 85-90%, 90-95%, or 95-98.4%. The aqueous phase matrix includes water, humectants, and preservatives.

[0028] In some embodiments of the present invention, the ceramide is selected from 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, and ceramide EODS.

[0029] In some embodiments of the present invention, the ceramide is selected from one or more of cetyl-PG hydroxyethyl palmitamide, 2-oleamido-1,3-octadecanediol, N-palmitoylhydroxyproline cetyl ester, dihydroxyisopropylpalmitoyl palmitamide, bis-octanoyloxypalmitamide isopropanol, hydroxypropylbispalmitamide MEA, arachidamide MEA, hydroxypropyl bisstearamide MEA, and hydroxypropyl bislaurate MEA.

[0030] In some embodiments of the present invention, the phytosphingosine is selected from one or more of phytosphingosine, dihydrosphingosine, salicylphytosphingosine, and tetraacetylphytosphingosine.

[0031] In some embodiments of the present invention, the sterol is selected from one or more of cholesterol and phytosterols. In a preferred embodiment of the present invention, the cholesterol is selected from one or more of cholesterol, dehydrocholesterol, and hydroxycholesterol. In a preferred embodiment of the present invention, the phytosterol is selected from one or more of β-sitosterol, stigmasterol, and campesterol.

[0032] In some embodiments of the present invention, the amino acid-type anionic surfactant is selected from one or more of sodium stearoyl glutamate, sodium palmitoyl glutamate, sodium myristoyl glutamate, sodium lauroyl glutamate, potassium cocoyl glutamate, and sodium di(lauramide glutamine)lysine, but is not limited thereto.

[0033] In some embodiments of the present invention, the PEG surfactant is selected from one or more of toxol (vitamin E polyethylene glycol succinate), PEG-40 hydrogenated castor oil, Tween 20, Tween 80, PEG-20 glyceryl cocoate, and lauryl ether-23, but is not limited thereto.

[0034] In some embodiments of the present invention, the moisturizer is selected from one or more of glycerin, butylene glycol, sugar alcohol, etc.

[0035] In this invention, the preservative is not limited to one or more of phenoxyethanol, p-hydroxyacetophenone, ethylhexylglycerin, and 1,2-hexanediol.

[0036] A second aspect of the present invention provides a method for preparing the transparent ceramide liposomes as described above, comprising the following steps: S1. Weigh the active ingredient, emulsifier, co-emulsifier B and co-solvent according to the proportion, heat and mix them evenly until completely dissolved to obtain phase A, and set aside. S2. Weigh the co-emulsifier A and the aqueous matrix according to the proportion, heat and mix them evenly until completely dissolved to obtain phase B, and set aside. S3. Under homogeneous conditions, the A phase obtained in step S1 is injected into the B phase obtained in step S2, and the homogenization is continuously sheared to obtain the C phase. S4. Homogenize the C phase obtained in step S3 to obtain highly stable transparent ceramide liposomes.

[0037] In some embodiments of the present invention, the heating temperature in step S1 is 75~95°C. For example, it is 75~80°C, 80~85°C, 85~90°C, or 90~95°C.

[0038] In some embodiments of the present invention, the heating temperature in step S2 is 75~95°C. For example, it is 75~80°C, 80~85°C, 85~90°C, or 90~95°C.

[0039] In some embodiments of the present invention, the rotational speed for homogenization in step S3 is 4000~7000 rpm. For example, it is 4000~5000 rpm, 5000~6000 rpm, or 6000~7000 rpm. The homogenization is performed using a homogenizing disperser.

[0040] In some embodiments of the present invention, the duration of continuous shearing and homogenization in step S3 is 5 to 20 minutes. For example, it is 5 to 10 minutes, 10 to 15 minutes, or 15 to 20 minutes.

[0041] In some embodiments of the present invention, the homogenization in step S4 is performed using a high-pressure microjet homogenizer, and the homogenization pressure is 10,000 to 30,000 psi, for example, 10,000 to 15,000 psi, 15,000 to 20,000 psi, 20,000 to 25,000 psi or 25,000 to 30,000 psi; the number of homogenization cycles is 1 to 5, for example, 1 to 2, 2 to 4 or 4 to 5.

[0042] A third aspect of this invention provides an application of the transparent ceramide liposomes described above in the cosmetics field. The cosmetics include, but are not limited to, toners, serums, lotions, creams, and other similar formulations.

[0043] For experimental methods in the following examples where specific conditions are not specified, follow conventional methods and conditions, or select according to the product instructions.

[0044] Example Table 1. Raw material composition ratios of Examples 1-4 and Comparative Examples 1-6

[0045] Example 1 Preparation of transparent ceramide liposomes: S1. Weigh out the following ingredients in proportion: ceramide NP, ceramide AP, ceramide EOP, phytosphoprotein, phytosterol, phosphatidylcholine, toxoxellen, and butylene glycol. Heat and stir at 85°C until completely dissolved to obtain phase A for later use. S2. Weigh out sodium stearoyl glutamate and aqueous matrix in proportion, heat and stir at 85°C until completely dissolved to obtain phase B for later use. S3. Under homogenization conditions of 6000 rpm, the A phase of step S1 is injected into the B phase of step S2, and the phase is continuously sheared and homogenized for 5 min to obtain the C phase for later use. S4. The C phase obtained in step S3 is processed using a high-pressure microfluidic homogenizer. The homogenization pressure is 20,000 psi and the homogenization is performed 3 times to obtain highly stable transparent ceramide liposomes.

[0046] The specific components added to the sample in Example 1 and their contents are shown in Table 1.

[0047] Example 2 The preparation steps and conditions are the same as in Example 1. The difference between the components in Example 2 and those in Example 1 is that the proportions of active ingredients such as ceramides and emulsifiers are different. The specific components added to the sample in Example 2 and their contents are shown in Table 1.

[0048] Example 3 The preparation steps and conditions are the same as in Example 2. The types of components selected are the same as in Example 2, but the content of the components is different. The specific components added to the sample in Example 3 and their contents are shown in Table 1.

[0049] Example 4 The preparation steps and conditions are the same as in Example 1. The difference between the components in Example 4 and those in Example 1 is that the types and contents of active substances such as ceramides are different, as are the contents of emulsifiers. The specific components added to the sample in Example 4 and their contents are shown in Table 1.

[0050] Comparative Example 1 The preparation steps and conditions are the same as in Example 1. The difference between the components in Example 1 and Example 1 is that only phosphatidylcholine is added as an emulsifier, and sodium stearoyl glutamate and toxolene are not added. The specific components added to the sample of Comparative Example 1 and their contents are shown in Table 1.

[0051] Comparative Example 2 The preparation steps and conditions are the same as in Example 1. The difference between Example 1 and Example 2 is that only phosphatidylcholine and sodium stearoyl glutamate are added as emulsifiers, and toxolene is not added. The specific components added to the sample of Comparative Example 2 and their contents are shown in Table 1.

[0052] Comparative Example 3 The preparation steps and conditions are the same as in Example 1. The difference between the components in Example 1 and Example 3 is that the emulsifier is different. Phosphatidylcholine, sodium stearoyl glutamate and hydroxyethylidene are added. The specific components added to the sample of Comparative Example 3 and their contents are shown in Table 1.

[0053] Comparative Example 4 The preparation steps and conditions are the same as in Example 1. The difference between the components in Example 1 and Example 4 is that the emulsifier is different. Phosphatidylcholine, sodium stearoyl glutamate and polyglycerol-6 octanoate are added. The specific components added to the sample of Comparative Example 4 and their contents are shown in Table 1.

[0054] Comparative Example 5 The preparation steps and conditions are the same as in Example 1. The difference between the components in Example 1 and Example 5 is that the emulsifier is different. Phosphatidylcholine, sodium stearoyl glutamate and polyglycerol-10 laurate are added. The specific components added to the sample of Comparative Example 5 and their contents are shown in Table 1.

[0055] Comparative Example 6 The formulation is the same as that of Example 1, except that the high-pressure homogenization process in step S4 was not performed. The specific components and their contents added to the sample of Comparative Example 6 are shown in Table 1.

[0056] Performance Test I: Particle Size and Appearance of Samples After preparation, the samples of Examples 1-4 and Comparative Examples 1-6 were placed at room temperature (25°C) for 24 hours, and their initial appearance was observed. The initial particle size was then tested using dynamic light scattering. After storage at room temperature for 6 months, the appearance and particle size were observed and tested. The average particle size and appearance of the transparent ceramide liposome samples of Examples 1-4 and Comparative Examples 1-5 were measured, and the test results are detailed in Table 2.

[0057] Table 2

[0058]

[0059] The samples in Examples 1-4 were initially transparent liquids with small particle sizes, approximately 30 nm. In contrast, the samples in Comparative Examples 1 and 6 initially had poor transparency, appearing as semi-transparent, slightly hazy liquids and milky, viscous liquids, respectively, with larger particle sizes of 129 nm and 186.2 nm. Comparative Examples 2-5 initially appeared as transparent liquids with particle sizes of over 40 nm, slightly larger than those in Examples 1-4. After 6 months of storage at room temperature, the samples in Examples 1-4 remained transparent liquids with a slight increase in particle size to approximately 50 nm. The samples in Comparative Examples 2-5 became semi-transparent liquids with particle sizes increasing to 60-70 nm. Comparative Examples 1 and 6 became semi-transparent, slightly hazy liquids and milky, solidified, non-flowing liquids, respectively, with further increases in particle size to 176.1 nm and 256.6 nm, respectively. This indicates a problem with the stability of the comparative examples, with significant changes in appearance and particle size after 6 months at room temperature.

[0060] Performance Test II: Stability The samples of Examples 1-4 and Comparative Examples 1-6 were stored at room temperature and 4°C for 6 months. The product appearance stability is detailed in Table 3.

[0061] Table 3

[0062] Compared to Comparative Examples 1-6, the samples in Examples 1-4 remained stable and transparent at room temperature and 4°C after a long storage period of 6 months, demonstrating good overall stability. This indicates that the emulsifiers phosphatidylcholine + sodium stearoyl glutamate + toxolene can achieve long-term stable encapsulation of ceramide transparent formulations.

[0063] The initial appearance of the sample in Comparative Example 1 was opaque, showing a semi-transparent and slightly hazy state, indicating that emulsifiers containing only phosphatidylcholine cannot prepare transparent formulations. The initial appearance of the sample in Comparative Example 6 was opaque, showing a milky white and viscous liquid, indicating that the process conditions must meet the requirements (i.e., high-pressure homogenization is required) to prepare stable transparent formulations.

[0064] Comparative Examples 2-5 showed good initial appearance and remained relatively good for 1-2 months. However, Comparative Examples 2-4 showed significant precipitation after 3 months of storage at 4℃, and the transparency also decreased at room temperature. Comparative Example 5 showed significant precipitation after 6 months of storage at 4℃, indicating that the long-term storage stability of the comparative examples was poor. This suggests that the emulsifier phosphatidylcholine + sodium stearoyl glutamate cannot achieve long-term stable encapsulation of ceramide transparent formulations, and neither can phosphatidylcholine + sodium stearoyl glutamate + hydroxyethylidene or polyglycerol-6 octanoate or polyglycerol-10 laurate achieve long-term stable encapsulation of ceramide transparent formulations.

[0065] Performance Test III The samples prepared in Example 1, Comparative Example 1, and Comparative Example 6 were compared, and their appearance was observed. See details below. Figure 1 Observe the appearance of the 2% aqueous dispersion, see details below. Figure 2 .

[0066] Depend on Figure 1 As can be seen, the sample in Example 1 was a transparent aqueous solution with no crystals or solid particles precipitated, indicating that the ceramide was completely encapsulated. Its transparent appearance indicates that it has reached the nanoscale particle size, resulting in higher bioavailability and facilitating transdermal absorption, thus enabling the application of ceramide in transparent aqueous solutions. In contrast, Comparative Examples 1 and 6 both exhibited opaque appearances. Comparative Example 1 was a semi-transparent, slightly foggy liquid, and upon close inspection, flocculent particles could be observed precipitating out. Comparative Example 6 was a milky white, viscous liquid, and its opacity also indicated a larger particle size. The presence of particles in Comparative Example 1 also suggests potential stability issues, making it unsuitable for use in transparent aqueous solutions.

[0067] Depend on Figure 2 It can be seen that the 1-2% aqueous dispersion of Example 1 is a transparent liquid with no particle precipitation. The 1-2% aqueous dispersion of Comparative Example 1 is relatively transparent, but upon closer inspection, fine particles are observed to precipitate in the liquid, with obvious flocculent particles in the middle. Both the sample and the aqueous dispersion are unstable. The 6-2% aqueous dispersion of Comparative Example 6 has decreased transparency and presents a semi-transparent, slightly hazy appearance, which does not meet the requirements for the application of transparent aqueous agents.

[0068] Performance Test IV The samples prepared in Example 1, Comparative Example 1, and Comparative Example 6 were measured using dynamic light scattering (DLS) technology. The particle size distribution of the samples is shown in the figure. Figure 3 The horizontal axis represents the particle diameter (in nanometers), while the vertical axis represents the proportion or intensity of particles of each size. (a), (b), and (c) represent samples from Example 1, Comparative Example 1, and Comparative Example 6, respectively.

[0069] Depend on Figure 3(a) It can be seen that the particle size of the sample in Example 1 has two obvious peaks, peak1 is 26.7nm and peak2 is 63.28nm. The peaks are relatively concentrated and the peak width is narrow, indicating that the particle size is relatively consistent and the stability is high. The Z-average particle size is 30.32nm, which is small and therefore presents a transparent appearance.

[0070] Depend on Figure 3 (b) It can be seen that the particle size of the Comparative Example 1 sample has three obvious peaks: peak1 is 2.745 nm, peak2 is 75.2 nm, and peak3 is 2291 nm. The peak width is very wide, indicating that the particle size difference is large and the subsequent stability is poor. The Z-average particle size is 129 nm, which is relatively large, so it presents an opaque appearance.

[0071] Depend on Figure 3 (c) It can be seen that the particle size of the Comparative Example 6 sample has two obvious peaks, peak1 is 105.9 nm and peak2 is 1745 nm, indicating that the difference in particle size is relatively large and there will be stability issues in the future. The Z-average particle size is 186.2 nm, which is large and therefore presents an opaque appearance.

[0072] Performance Test V Example 1 was prepared by dissolving water in different proportions to form 10%, 20%, 50%, and 80% aqueous dispersions, respectively. The appearance was then observed. (See details below.) Figure 4 .Depend on Figure 4 It can be seen that the sample in Example 1 and water are well miscible at different ratios and present a transparent and clear state, thus enabling the addition of high content in the finished aqueous solution.

[0073] Performance Test VI The samples prepared in Example 1 were subjected to human skin patch tests according to the "Cosmetic Safety Technical Specifications" (2015 edition). The results of the human skin patch tests are shown in Table 4. As shown in Table 4, the human skin patch test results indicate that no adverse reactions occurred in any of the 30 individuals in both Sample Group 1 (2% ceramide transparent aqueous solution 2.0-YL5922) and Sample Group 2 (5% ceramide transparent aqueous solution 2.0-YL5922). This demonstrates that the samples prepared in Example 1, at concentrations of 2-5%, showed no irritation in the human skin patch test.

[0074] 1. Materials and Methods (1) Test substance: Sample group 1 (2% ceramide transparent water agent 2.0-YL5922).

[0075] (2) Test substance: Sample group 2 (5% ceramide transparent water agent 2.0-YL5922).

[0076] (3) Negative control: blank control and distilled water control.

[0077] (4) Subjects: A total of 30 subjects, including 6 males and 24 females, aged 23 to 59 years, with an average age of 42 ± 13 years. All of them met the criteria for voluntary inclusion of subjects.

[0078] (5) Patch test method: Select qualified patch test equipment and use the closed patch test method. Place 0.020mL-0.025mL of the test substance into the patch tester respectively, and apply it to the flexor of the forearm of the subject with low-allergenic adhesive tape. Remove the test substance after 24 hours. Observe the skin reaction at 0.5, 24 and 48 hours after removal. Record the results according to the skin reaction grading standard of the Cosmetic Safety Technical Specification (2015 edition).

[0079] 2. Test Results Table 4 Results of Cosmetic Human Skin Patch Test

[0080] In summary, this invention effectively overcomes the various shortcomings of the prior art and has high industrial application value.

[0081] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A transparent ceramide liposome, characterized in that, The components include the following mass percentages: Active ingredient 0.1-3%, emulsifier 0.2-10%, co-emulsifier A 0.05-3%, co-emulsifier B 0.05-3%, co-solvent 0.2-20%, aqueous matrix 62-98.4%; The active ingredient is selected from one or more of ceramides and ceramide-like substances, phytosphingosine, and alcohols; The emulsifier is selected from one or more of the following: soybean lecithin, phosphatidylcholine, lysophosphatidylcholine, hydrogenated lecithin, hydrogenated lysophosphatidylcholine, egg yolk lecithin, hydroxylated lecithin, distearyl phosphatidylcholine, dilauryl phosphatidylcholine, dipalmitoyl phosphatidylcholine, and dimyristoyl phosphatidylcholine. The co-emulsifier A is an amino acid-type anionic surfactant; the amino acid-type anionic surfactant is selected from one or more of sodium stearoyl glutamate, sodium palmitoyl glutamate, sodium myristoyl glutamate, sodium lauroyl glutamate, potassium cocoyl glutamate, and sodium bis(lauramide glutamine) lysine. The co-emulsifier B is a PEG-based surfactant; The co-solvent is selected from one or more of 1,3-butanediol, 1,2-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, propylene glycol, 1,3-propanediol, dipropylene glycol, etc. The aqueous matrix includes water, a humectant, and a preservative.

2. The transparent ceramide liposome according to claim 1, characterized in that, It also includes one or more of the following features: A1) The ceramide is selected from one or more of the following: ceramide NP, ceramide NH, ceramide AH, ceramide NDS, ceramide AS, ceramide AP, ceramide NS, ceramide EOS, ceramide EOH, ceramide ADS, ceramide EOP, and ceramide EODS; A2) The ceramide-like substance is selected from one or more of cetyl-PG hydroxyethyl palmitamide, 2-oleamido-1,3-octadecanediol, N-palmitoylhydroxyproline cetyl ester, dihydroxyisopropylpalmitoyl palmitamide, bis-octanoyloxypalmitamidoisopropanol, hydroxypropylbispalmitamide MEA, arachidamide MEA, hydroxypropyl bisstearamide MEA, and hydroxypropyl bislaurate MEA; A3) The phytosphingosine mentioned is selected from one or more of phytosphingosine, dihydro(neurosphingosine), salicylphytosphingosine, and tetraacetylphytosphingosine; A4) The sterols mentioned are selected from one or more of cholesterol and phytosterols.

3. The transparent ceramide liposome according to claim 2, characterized in that, It also includes one or more of the following features: A41) The cholesterol is selected from one or more of cholesterol, dehydrocholesterol and hydroxycholesterol; (A42) The phytosterols mentioned are selected from one or more of β-sitosterol, stigmasterol and campesterol.

4. The transparent ceramide liposome according to claim 1, characterized in that, It also includes one or more of the following features: B1) The PEG surfactant is selected from one or more of toxolene, PEG-40 hydrogenated castor oil, Tween 20, Tween 80, PEG-20 glyceryl cocoate, and lauryl ether-23; B2) The moisturizer is selected from one or more of glycerin, butylene glycol, sugar alcohol, etc.

5. A method for preparing transparent ceramide liposomes according to any one of claims 1 to 4, characterized in that, Includes the following steps: S1. Weigh the active ingredient, emulsifier, co-emulsifier B and co-solvent according to the proportion, heat and mix them evenly until completely dissolved to obtain phase A, and set aside. S2. Weigh the co-emulsifier A and the aqueous matrix according to the proportion, heat and mix them evenly until completely dissolved to obtain phase B, and set aside. S3. Under homogeneous conditions, the A phase obtained in step S1 is injected into the B phase obtained in step S2, and the homogenization is continuously sheared to obtain the C phase. S4. Homogenize the C phase obtained in step S3 to obtain highly stable transparent ceramide liposomes.

6. The method for preparing transparent ceramide liposomes according to claim 5, characterized in that, The heating temperature in step S1 is 75~95℃.

7. The method for preparing transparent ceramide liposomes according to claim 5, characterized in that, The heating temperature in step S2 is 75~95℃.

8. The method for preparing transparent ceramide liposomes according to claim 5, characterized in that, It also includes one or more of the following features: C1) The rotational speed for homogenization in step S3 is 4000~7000 rpm; C2) The duration of continuous shearing and homogenization in step S3 is 5~20 min.

9. The method for preparing transparent ceramide liposomes according to claim 5, characterized in that, The homogenization in step S4 is performed using a high-pressure microjet homogenizer, with a homogenization pressure of 10,000 to 30,000 psi and a homogenization frequency of 1 to 5 times.

10. The application of a transparent ceramide liposome according to any one of claims 1 to 4 in the field of cosmetics.

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