Ceramide and allantoin co-loaded liposome as well as composition and application of ceramide and allantoin co-loaded liposome

Abstract

The invention belongs to the technical field of cosmetics, and particularly relates to a ceramide and allantoin co-loaded liposome as well as a composition and application of the ceramide and allantoin co-loaded liposome. The invention firstly provides the composition for preparing the ceramide and allantoin co-carrier liposome, and the composition comprises ceramide, allantoin and an auxiliary material for preparing the liposome according to the mass ratio of (1 to 8): (0.5 to 1.5): (90.5 to 98.5), the auxiliary materials comprise hydrogenated phosphatidylcholine, cholesterol, Tween 80, an ionic surfactant, an organic solvent, a stabilizer, a water-phase medium, an antioxidant, a preservative and a chelating agent. According to the invention, two skin repairing components, namely ceramide and allantoin, are compatible and prepared into the co-loaded liposome, and the co-loaded liposome is found to have excellent solubility and skin permeability under the specific formula and proportion, so that the residence time of the two components in the skin is successfully prolonged, and the repairing and moisturizing effects can be exerted for a longer time.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and specifically relates to a ceramide-allantoin co-loaded liposome and a composition and application thereof. Background Art

[0002] The skin is the first barrier covering the human body. It can protect various parts of the human body from physical and chemical damage caused by harmful external factors, and prevent the loss of nutrients, water and electrolytes in the body. It plays a very important role in maintaining the stability of the human body's internal environment. The stratum corneum and sebum membrane together constitute the skin barrier, protecting the skin from damage by the external environment. When the skin barrier is damaged, the skin will lose its normal protective function, and symptoms such as dryness, dehydration, inflammation, itching, erythema, etc. will appear. It will also cause a series of skin diseases, which seriously endangers the physical and mental health of the human body.

[0003] Ceramide is a sphingolipid composed of sphingosine long-chain bases and fatty acids. It is the main component (>50%) of the intercellular lipids in the outermost stratum corneum of human skin. It plays an important role in maintaining the integrity of the epidermal structure and has the functions of maintaining the skin barrier, moisturizing, anti-aging and disease treatment. Allantoin is an amphoteric compound that can directly act on keratin, increase and promote the hydration capacity of the stratum corneum, reduce water loss, and relieve and treat dry skin. At the same time, allantoin also has the functions of promoting cell growth and accelerating wound healing. It is a good repair agent and anti-inflammatory agent for skin trauma. Ceramide and allantoin are often used in combination in cosmetic products to provide moisturizing, repairing and protecting the skin barrier. However, ceramide and allantoin have the disadvantages of poor solubility, easy crystallization, and low skin permeability, which greatly limit the application of the two ingredients in cosmetics. Therefore, in order to make ceramide and allantoin better play their own functions, it is necessary to overcome the defects of ceramide and allantoin.

[0004] Liposomes are microscopic spherical carriers formed by encapsulating active ingredients in lipid bilayers. Water-soluble ingredients can be encapsulated in the inner water phase of phospholipids, and fat-soluble ingredients can be encapsulated between phospholipid bilayers. Since the components of liposomes (lipids) are highly similar to the stratum corneum of the skin, liposomes encapsulating drugs can pass smoothly through the gaps between lipid particles, which can increase the local accumulation of active ingredients, continuously release active ingredients, and also improve the stability and bioavailability of active ingredients.

[0005] In the prior art, some technicians use liposome technology to improve the solubility and stability of ceramide. For example, 1) The invention patent with publication number CN111346025A discloses a liposome that can improve the skin delivery effect of water-soluble ingredients, which is composed of phospholipids and ceramide; 2) The invention patent with publication number CN113368005A discloses a ceramide liposome with deep intradermal delivery effect, which is composed of soybean lecithin, cholesterol and ceramide 3; 3) The invention patent with publication number CN115429713A discloses a moisturizing, repairing and anti-aging composition containing ceramide and its preparation method. Using phospholipid liposome encapsulation technology, ceramide NP, which is poorly soluble in oil and water, is encapsulated in liposomes with phospholipids as carriers, and the phospholipid ceramide liposomes are made into liposome transparent microemulsions with nanometer particle size; 4) The invention patent with publication number CN107028810A discloses a transdermal moisturizing combination and its application in the preparation of cosmetics. The invention prepares ceramide into liposomes, and then compoundes it with betaine, allantoin, amino acids and chitosan oligosaccharides. The formed composition has a good effect of increasing skin moisture content and reducing skin moisture loss.

[0006] When ceramide and allantoin are used in combination, the amount of allantoin added and the skin permeability are still limited. The above prior art only discloses the use of liposome technology to improve the solubility and permeability of a single component, ceramide. How to improve the solubility and permeability of allantoin, especially how to improve the solubility and permeability of both ceramide and allantoin at the same time, has not been reported in the prior art. Summary of the invention

[0007] In view of this, the present invention provides a ceramide-allantoin co-loaded liposome and its composition and application. The present invention uses liposome technology to simultaneously encapsulate two insoluble skin barrier repairing ingredients, ceramide and allantoin, in liposome vesicles. By optimizing the liposome components and ratios, the solubility of ceramide and allantoin is successfully improved, and the drug loading and permeability are increased. The present invention has found that the co-loaded liposomes prepared under specific components and ratios have excellent sustained-release effects, can exert repair and moisturizing effects to a greater extent, and are helpful for the research and development of skin barrier repair cosmetics.

[0008] One of the purposes of the present invention is to provide a composition for preparing ceramide-allantoin co-loaded liposomes.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] A composition for preparing ceramide-allantoin co-loaded liposomes, comprising ceramide, allantoin and auxiliary materials for preparing liposomes, wherein the mass ratio thereof is 1-8:0.5-1.5:90.5-98.5.

[0011] Furthermore, the auxiliary materials include hydrogenated phosphatidylcholine and cholesterol, and the ratio of the total amount of hydrogenated phosphatidylcholine and ceramide to cholesterol is in the range of 3:1 to 5:1.

[0012] Furthermore, the mass ratio of ceramide, allantoin, hydrogenated phosphatidylcholine and cholesterol is 1-8:0.5-1.5:5-10:2-5.

[0013] Furthermore, the ceramide is contained in the phospholipid bilayer of the liposome, and the allantoin is contained in the inner water phase of the liposome.

[0014] Furthermore, the auxiliary materials also include Tween 80, ionic surfactant, organic solvent, stabilizer, aqueous medium, antioxidant, preservative and chelating agent, and the mass ratio thereof is 1-3: 0.4-1.5: 9-20: 0.5-2: 46.9-79.99: 0.1-1.0: 0.5-1.0: 0.01-0.1; the ionic surfactant includes any one of behenamidopropyl dimethylamine and sodium stearoyl glutamate; the organic solvent includes any one or both of ethanol and propylene glycol; the stabilizer is polyvinyl alcohol; the aqueous medium is phosphate buffer; the antioxidant is tocopherol acetate; the preservative includes any one or both of a compound preservative of phenoxyethanol and ethylhexylglycerin and a compound preservative of o-cymene-5-ol and isopentyl glycol; and the chelating agent is disodium edetate.

[0015] Furthermore, the behenamidopropyl dimethylamine is a cationic surfactant, and the sodium stearoyl glutamate is an anionic surfactant.

[0016] Preferably, the organic solvent is propylene glycol.

[0017] Furthermore, the composition is composed of the following components in parts by weight: 5 to 10 parts of hydrogenated phosphatidylcholine, 2 to 5 parts of cholesterol, 1 to 8 parts of ceramide, 0.5 to 1.5 parts of allantoin, 1 to 3 parts of Tween 80, 0.4 to 1.5 parts of ionic surfactants, 9 to 20 parts of organic solvents, 0.5 to 2 parts of stabilizers, 0.1 to 1.0 parts of antioxidants, 0.5 to 1.0 parts of preservatives, 0.01 to 0.1 parts of chelating agents, and the aqueous phase medium is supplemented to 100 parts.

[0018] Furthermore, the composition is composed of the following components in parts by weight: 5 to 9 parts of hydrogenated phosphatidylcholine, 2.3 to 5 parts of cholesterol, 2 to 5 parts of ceramide, 0.6 to 1 part of allantoin, 1 to 3 parts of Tween 80, 0.4 to 1 part of ionic surfactant, 9 to 18 parts of organic solvent, 0.5 to 2 parts of stabilizer, 0.5 parts of antioxidant, 0.5 to 0.7 parts of preservative, 0.02 parts of chelating agent, and the aqueous phase medium is supplemented to 100 parts.

[0019] Furthermore, the composition is composed of the following components in parts by weight: 5 to 9 parts of hydrogenated phosphatidylcholine, 2.3 to 5 parts of cholesterol, 2 to 5 parts of ceramide, 0.6 to 1 part of allantoin, 1 to 3 parts of Tween 80, 0.4 to 1 part of an ionic surfactant, 9 to 18 parts of propylene glycol, 0.5 to 2 parts of polyvinyl alcohol, 0.5 part of tocopherol acetate, 0.5 to 0.7 parts of a preservative, 0.02 parts of disodium edetate, and phosphate buffer is supplemented to 100 parts.

[0020] Furthermore, the composition is composed of the following components in parts by weight: 5 to 8 parts of hydrogenated phosphatidylcholine, 1 to 3 parts of ceramide, 2 to 4 parts of cholesterol, 0.4 to 0.6 parts of sodium stearoyl glutamate, 0.4 to 0.6 parts of tocopherol acetate, 8 to 10 parts of propylene glycol, 2 to 4 parts of Tween 80, 0.6 to 0.8 parts of allantoin, 1 to 3 parts of polyvinyl alcohol, 0.01 to 0.03 parts of disodium edetate, 0.6 to 0.8 parts of phenoxyethanol / ethylhexylglycerin, and 70 to 75 parts of phosphate buffered saline.

[0021] Furthermore, the composition is composed of the following components in parts by weight: 5 to 7 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 2.3 to 3 parts of cholesterol, 0.5 parts of sodium stearoyl glutamate, 0.5 parts of tocopherol acetate, 9 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 2 parts of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of phenoxyethanol / ethylhexylglycerin, and 71.58 to 74.28 parts of phosphate buffered saline.

[0022] Furthermore, the composition is composed of the following components in parts by weight: 5 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 2.3 parts of cholesterol, 0.5 parts of sodium stearoyl glutamate, 0.5 parts of tocopherol acetate, 9 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 2 parts of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of phenoxyethanol / ethylhexylglycerin, and 74.28 parts of phosphate buffered saline.

[0023] Furthermore, the composition is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 3 parts of cholesterol, 0.5 parts of sodium stearoyl glutamate, 0.5 parts of tocopherol acetate, 9 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 2 parts of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of phenoxyethanol / ethylhexylglycerin, and 71.58 parts of phosphate buffered saline.

[0024] A second object of the present invention is to provide a method for improving the solubility and permeability of ceramide and allantoin.

[0025] To achieve the above object, the present invention adopts the following technical solutions:

[0026] The method for improving the solubility and permeability of ceramide and allantoin is to prepare co-loaded liposomes of ceramide and allantoin by an organic solvent injection method, wherein the organic solvent injection method comprises the following steps:

[0027] (1) mixing phospholipids, ceramide, cholesterol, antioxidants and an organic solvent to obtain an organic phase;

[0028] (2) mixing Tween 80, a chelating agent, a stabilizer, allantoin and an aqueous phase medium to obtain an aqueous phase;

[0029] (3) injecting the organic phase obtained in step (1) into the aqueous phase obtained in step (2) for hydration to obtain a suspension;

[0030] (4) adding a preservative to the suspension obtained in step (3), and homogenizing under high pressure to obtain ceramide and allantoin co-loaded liposomes;

[0031] In step (1) or step (2), an ionic surfactant is added; if the ionic surfactant is a cationic surfactant, it is added to the organic phase; if the ionic surfactant is an anionic surfactant, it is added to the aqueous phase.

[0032] Furthermore, in step (1) and step (2), the components are mixed and dissolved in a water bath at 60°C-80°C, more preferably in a water bath at 70°C.

[0033] Furthermore, in step (3), the reaction conditions include: 60°C-80°C hot water bath, 400rpm-500rpm rotation speed, and hydration reaction time of 0.5-2h.

[0034] Preferably, in step (3), the reaction conditions are: 70°C hot water bath, 450 rpm rotation speed, and hydration reaction for 1 hour.

[0035] Furthermore, the suspension obtained in step (3) is cooled to 30°C-40°C in an ice-water bath, and then a preservative is added; more preferably, the suspension is cooled to 30°C.

[0036] Furthermore, in step (4), the high-pressure homogenization is to circulate the crude liposome suspension through a high-pressure homogenizer at a pressure of 400 bar to 1000 bar for 3 to 6 times.

[0037] Preferably, in step (4), the high-pressure homogenization is to circulate the crude liposome suspension through a high-pressure homogenizer at a pressure of 800 bar for 3 times.

[0038] Furthermore, the method specifically comprises the following steps:

[0039] (1) mixing phospholipids, ceramide, cholesterol, behenamidopropyl dimethylamine, an antioxidant and an organic solvent, stirring and dissolving them in a 70° C. water bath to obtain an organic phase;

[0040] (2) mixing Tween 80, a chelating agent, allantoin, a stabilizer, and an aqueous medium, stirring and dissolving in a 70° C. water bath to obtain an aqueous phase;

[0041] (3) Injecting the organic phase obtained in step (1) into the aqueous phase obtained in step (2) in a hot water bath at 70° C. and a rotation speed of 450 rpm for hydration for 1 h to obtain a suspension;

[0042] (4) cooling the suspension obtained in step (3) to 30° C. in an ice water bath, adding a preservative and mixing well to obtain a crude liposome suspension;

[0043] (5) The crude liposome suspension obtained in step (4) is circulated three times by a high-pressure homogenizer at a pressure of 800 bar to obtain the ceramide and allantoin co-loaded liposomes.

[0044] Or the method comprises the following specific steps:

[0045] (1) mixing phospholipids, ceramide, cholesterol, antioxidants and organic solvents, stirring and dissolving in a 70° C. water bath to obtain an organic phase;

[0046] (2) mixing Tween 80, a chelating agent, allantoin, a stabilizer, sodium stearoyl glutamate and an aqueous phase medium, stirring and dissolving them in a 70° C. water bath to obtain an aqueous phase;

[0047] (3) Injecting the organic phase obtained in step (1) into the aqueous phase obtained in step (2) in a hot water bath at 70° C. and a rotation speed of 450 rpm for hydration for 1 h to obtain a suspension;

[0048] (4) cooling the suspension obtained in step (3) to 30° C. in an ice water bath, adding a preservative and mixing well to obtain a crude liposome suspension;

[0049] (5) The crude liposome suspension obtained in step (4) is circulated three times by a high-pressure homogenizer at a pressure of 800 bar to obtain the ceramide and allantoin co-loaded liposomes.

[0050] The third object of the present invention is to provide a ceramide-allantoin co-loaded liposome prepared by the above method.

[0051] Furthermore, in the co-loaded liposome, ceramide is encapsulated in the phospholipid bilayer, and allantoin is encapsulated in the inner water phase.

[0052] The fourth object of the present invention is to provide a use of the aforementioned pharmaceutical preparation composition and / or the aforementioned ceramide allantoin co-loaded liposomes in the preparation of moisturizing and repairing cosmetics with sustained release effects.

[0053] To achieve the above object, the present invention adopts the following technical solutions:

[0054] Use of the aforementioned pharmaceutical preparation composition and / or the aforementioned ceramide-allantoin co-loaded liposomes in the preparation of moisturizing and repairing cosmetics with sustained-release effects.

[0055] Furthermore, the pharmaceutical preparation composition and / or the co-loaded liposomes are used in preparing cosmetics for repairing skin barrier.

[0056] Furthermore, the pharmaceutical preparation composition and / or the co-loaded liposomes are used in the preparation of products that promote the expression of hyaluronic acid in human keratinocytes, the expression of filaggrin and / or the migration of human fibroblasts.

[0057] The beneficial effects of the present invention are:

[0058] 1. The present invention utilizes liposome encapsulation technology to encapsulate ceramide and allantoin in the phospholipid bilayer and the inner water phase, respectively. By optimizing the ratio of each component, the drug loading of ceramide and allantoin is increased, the skin permeability of the two ingredients is improved, and the problems of poor solubility, easy crystallization and poor permeability of ceramide and allantoin are solved.

[0059] 2. The ceramide and allantoin co-loaded liposomes prepared by the present invention have a small particle size, a high ceramide and allantoin encapsulation rate, good stability, and are safe and non-irritating.

[0060] 3. The ceramide and allantoin co-loaded liposomes of the present invention have an excellent sustained-release effect, which can reduce the exposure risk of ceramide and allantoin, while increasing the retention amount of the two components on the skin and prolonging the retention time of the two components in the skin, thereby exerting the efficacy for a long time.

[0061] 4. The ceramide and allantoin co-loaded liposomes of the present invention can promote the increase of hyaluronic acid expression in human keratinocytes, filaggrin expression, and migration rate of human fibroblasts in a dose-dependent manner, and have excellent moisturizing and repairing effects.

[0062] 5. The present invention adopts an organic solvent injection method to prepare ceramide and allantoin co-loaded liposomes, the preparation process is simple, the prepared product has high stability, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] Figure 1 This is the blank control cell scratch image;

[0064] Figure 2 This is the scratch repair picture of the blank control group;

[0065] Figure 3 This is the cell scratch image of the sample diluted 80 times in Example 6;

[0066] Figure 4 This is the scratch repair image of the sample diluted 80 times in Example 6;

[0067] Figure 5 This is the cell scratch image of the sample diluted 40 times in Example 6;

[0068] Figure 6 This is the scratch repair image of the sample diluted 40 times in Example 6;

[0069] Figure 7 This is the cell scratch image of the sample diluted 20 times in Example 6;

[0070] Figure 8 This is the scratch repair image of the sample diluted 20 times in Example 6. DETAILED DESCRIPTION

[0071] The technical solution of the present invention will be further described clearly and completely in conjunction with specific embodiments below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Therefore, based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work belong to the protection scope of the present invention.

[0072] In the examples of the present invention, the mass percentages of the components in the ceramide and allantoin co-loaded liposomes of Examples 1 to 8 are shown in Table 1.

[0073] Table 1. Summary of prescriptions for Examples 1 to 8

[0074]

[0075] In the embodiments of the present invention, the mass percentages of the components in the ceramide and allantoin co-loaded liposomes of Comparative Examples 1 to 9 are shown in Table 2 below.

[0076] Table 2. Summary of prescriptions for comparative examples 1 to 9

[0077]

[0078]

[0079] Example 1

[0080] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 5 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 2.3 parts of cholesterol, 0.5 parts of sodium stearoyl glutamate, 0.5 parts of tocopherol acetate, 9 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 2 parts of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of phenoxyethanol / ethylhexylglycerin, and 74.28 parts of phosphate buffered saline.

[0081] The ceramide and allantoin co-loaded liposomes were prepared by an organic solvent (propylene glycol) injection method, and the specific steps are as follows:

[0082] (1) Weigh hydrogenated phosphatidylcholine, ceramide, cholesterol, tocopherol acetate, and propylene glycol in proportion, and stir and dissolve them in a 70° C. water bath to obtain an organic phase;

[0083] (2) Tween 80, an ionic surfactant (sodium stearoyl glutamate in this embodiment), disodium edetate, allantoin, polyvinyl alcohol, and a phosphate buffer solution are weighed in proportion, and the mixture is stirred and dissolved in a 70° C. water bath to obtain an aqueous phase;

[0084] (3) Inject the organic phase into the aqueous phase for hydration at 70° C. and 450 rpm for 1 h in a hot water bath. After the resulting suspension is cooled to 30° C. in an ice water bath, add a prescribed amount of preservative (a composite preservative of phenoxyethanol + ethylhexylglycerin is used in this embodiment) and mix well to obtain a crude liposome suspension;

[0085] (4) The crude liposome suspension was passed through a high-pressure homogenizer at a pressure of 800 bar for 3 cycles to obtain the final sample.

[0086] Example 2

[0087] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 3 parts of cholesterol, 0.5 parts of sodium stearoyl glutamate, 0.5 parts of tocopherol acetate, 9 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 2 parts of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of phenoxyethanol / ethylhexylglycerol, and 71.58 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0088] Example 3

[0089] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 9 parts of hydrogenated phosphatidylcholine, 4 parts of ceramide, 5 parts of cholesterol, 0.5 parts of tocopherol acetate, 18 parts of propylene glycol, 3 parts of Tween 80, 1 part of allantoin, 0.5 parts of polyvinyl alcohol, 0.5 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 57.78 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0090] Example 4

[0091] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 9 parts of hydrogenated phosphatidylcholine, 4 parts of ceramide, 5 parts of cholesterol, 0.5 parts of behenamidopropyl dimethylamine, 0.5 parts of tocopherol acetate, 18 parts of propylene glycol, 3 parts of Tween 80, 1 part of allantoin, 0.5 parts of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 57.78 parts of phosphate buffered saline. The preparation method is compared with that of Example 1, except that the addition method of the ionic surfactant is changed: in step (1), a cationic surfactant (behenamidopropyl dimethylamine) is added in the preparation of the organic phase, in step (2), no ionic surfactant is added in the preparation of the aqueous phase, and steps (3) and (4) are the same.

[0092] Example 5

[0093] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 6 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 2.7 parts of cholesterol, 0.5 parts of tocopherol acetate, 10 parts of propylene glycol, 2 parts of Tween 80, 0.6 parts of allantoin, 2 parts of polyvinyl alcohol, 0.4 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.5 parts of phenoxyethanol / ethylhexylglycerol, and 73.28 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0094] Example 6

[0095] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 6 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 2.7 parts of cholesterol, 0.5 parts of tocopherol acetate, 10 parts of propylene glycol, 1 part of Tween 80, 0.6 parts of allantoin, 2 parts of polyvinyl alcohol, 0.4 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.5 parts of phenoxyethanol / ethylhexylglycerol, and 74.28 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0096] Example 7

[0097] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 5 parts of ceramide, 4 parts of cholesterol, 1 part of behenamidopropyl dimethylamine, 0.5 parts of tocopherol acetate, 16 parts of propylene glycol, 1 part of Tween 80, 0.7 parts of allantoin, 1 part of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 63.08 parts of phosphate buffered saline. The preparation method thereof is compared with that of Example 1, except that the addition method of the ionic surfactant is changed: in step (1), a cationic surfactant (behenamidopropyl dimethylamine) is added in the preparation of the organic phase, in step (2), no ionic surfactant is added in the preparation of the aqueous phase, and steps (3) and (4) are the same.

[0098] Example 8

[0099] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 5 parts of ceramide, 2.4 parts of cholesterol, 1 part of behenamidopropyl dimethylamine, 0.5 parts of tocopherol acetate, 16 parts of propylene glycol, 1 part of Tween 80, 0.7 parts of allantoin, 1 part of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 64.68 parts of phosphate buffered saline. The preparation method thereof is compared with that of Example 1, except that the addition method of the ionic surfactant is changed: in step (1), a cationic surfactant (behenamidopropyl dimethylamine) is added in the preparation of the organic phase, in step (2), no ionic surfactant is added in the preparation of the aqueous phase, and steps (3) and (4) are the same.

[0100] Comparative Example 1

[0101] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 3 parts of hydrogenated phosphatidylcholine, 3 parts of ceramide, 2 parts of cholesterol, 0.5 parts of tocopherol acetate, 20 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 1 part of polyvinyl alcohol, 0.5 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.5 parts of phenoxyethanol / ethylhexylglycerol, and 65.78 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0102] Comparative Example 2

[0103] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 12 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 4.7 parts of cholesterol, 0.5 parts of tocopherol acetate, 18 parts of propylene glycol, 3 parts of Tween 80, 0.7 parts of allantoin, 1 part of polyvinyl alcohol, 0.5 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.5 parts of phenoxyethanol / ethylhexylglycerol, and 57.08 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0104] Comparative Example 3

[0105] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 5 parts of hydrogenated phosphatidylcholine, 3 parts of ceramide, 4 parts of cholesterol, 0.5 parts of tocopherol acetate, 10 parts of propylene glycol, 2 parts of Tween 80, 0.6 parts of allantoin, 2 parts of polyvinyl alcohol, 0.5 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 71.68 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0106] Comparative Example 4

[0107] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 2 parts of ceramide, 1 part of cholesterol, 0.5 parts of tocopherol acetate, 9 parts of propylene glycol, 2 parts of Tween 80, 0.7 parts of allantoin, 2 parts of polyvinyl alcohol, 0.5 parts of sodium stearoyl glutamate, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 74.58 parts of phosphate buffered saline. The preparation method is the same as that of Example 1.

[0108] Comparative Example 5

[0109] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 3 parts of ceramide, 3.3 parts of cholesterol, 1 part of behenamidopropyl dimethylamine, 0.5 parts of tocopherol acetate, 15 parts of propylene glycol, 0.5 parts of Tween 80, 0.8 parts of allantoin, 1 part of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.5 parts of phenoxyethanol / ethylhexylglycerol, and 67.38 parts of phosphate buffered saline. The preparation method thereof is compared with that of Example 1, except that the addition method of the ionic surfactant is changed: in step (1), a cationic surfactant (behenamidopropyl dimethylamine) is added in the preparation of the organic phase, in step (2), no ionic surfactant is added in the preparation of the aqueous phase, and steps (3) and (4) are the same.

[0110] Comparative Example 6

[0111] A ceramide and allantoin co-loaded liposome is composed of the following components in parts by weight: 7 parts of hydrogenated phosphatidylcholine, 3 parts of ceramide, 3.3 parts of cholesterol, 1 part of behenamidopropyl dimethylamine, 0.5 parts of tocopherol acetate, 15 parts of propylene glycol, 4 parts of Tween 80, 0.8 parts of allantoin, 1 part of polyvinyl alcohol, 0.02 parts of disodium edetate, 0.7 parts of o-cymene-5-ol / isopentyldiol, and 63.68 parts of phosphate buffered saline. The preparation method is compared with that of Example 1, except that the addition method of the ionic surfactant is changed: in step (1), a cationic surfactant (behenamidopropyl dimethylamine) is added in the preparation of the organic phase, in step (2), no ionic surfactant is added in the preparation of the aqueous phase, and steps (3) and (4) are the same.

[0112] Comparative Example 7

[0113] The ceramide-allantoin mixed solution is composed of the following components in parts by weight: 2 parts of ceramide, 20 parts of propylene glycol, 0.6 parts of allantoin, and 77.4 parts of purified water.

[0114] The preparation method of ceramide allantoin mixed solution is as follows:

[0115] (1) Weighing a prescribed amount of ceramide, adding it to propylene glycol, stirring and dissolving in a 70° C. water bath to obtain a ceramide solution;

[0116] (2) Weighing a prescribed amount of allantoin, adding it to purified water, stirring and dissolving it in a 70° C. water bath to obtain an allantoin solution;

[0117] (3) adding the ceramide solution obtained in step (1) to the allantoin solution obtained in step (2), stirring and mixing, and cooling to 30° C. to obtain a ceramide-allantoin mixed solution.

[0118] Comparative Example 8

[0119] Ceramide allantoin emulsion is composed of the following components in parts by weight: 2 parts of ceramide, 12 parts of medium chain triglycerides, 6 parts of candelilla wax, 4 parts of polyglyceryl-6 distearate (and) jojoba esters (and) polyglyceryl-3 beeswax ester (and) cetyl alcohol, 0.6 parts of allantoin, 0.5 parts of phenoxyethanol / ethylhexylglycerin, and 74.9 parts of purified water.

[0120] The preparation method of ceramide allantoin emulsion is as follows:

[0121] (1) Weigh the prescribed amount of medium chain triglycerides, candelilla wax, polyglyceryl-6 distearate (and) jojoba esters (and) polyglyceryl-3 beeswax ester (and) cetyl alcohol, and ceramide, heat to 80°C to completely melt the oils and fats, stir evenly, and keep the temperature at 80±2°C for later use;

[0122] (2) Weigh the prescribed amount of allantoin and purified water, stir and dissolve in an 80°C water bath, keep warm to 80±2°C, and set aside; add water to the prescribed amount before use;

[0123] (3) In a hot water bath at 80° C., the solution obtained in step (1) was added to the allantoin solution obtained in step (2), and the mixture was stirred at 300 rpm for 20 min; the mixture was then cooled to 30° C. at room temperature and 100 rpm, and phenoxyethanol / ethylhexylglycerol was added and stirred to mix well. The mixture was then homogenized and emulsified at 6000 rpm for 5 min to obtain a ceramide allantoin emulsion.

[0124] Comparative Example 9

[0125] The ceramide allantoin suspension is composed of the following components in parts by weight: 2 parts of ceramide, 3 parts of docusate sodium, 9 parts of propylene glycol, 0.7 parts of allantoin, and 85.3 parts of phosphate buffered saline.

[0126] The preparation method of the ceramide allantoin suspension is as follows: weigh the prescribed amount of sodium docusate, propylene glycol, and phosphate buffered saline solution, stir and dissolve; then, add the prescribed amount of ceramide and allantoin under stirring, and homogenize at 5000 rpm for 5 minutes to evenly disperse the ceramide and allantoin to obtain the ceramide allantoin suspension.

[0127] Example 9. Appearance, particle size and encapsulation efficiency detection experiment

[0128] The appearance, particle size, and encapsulation efficiency of ceramide and allantoin of the products of Examples 1-8 and Comparative Examples 1-8 were investigated, and the test results are shown in Table 3. The results show that the sample particle size prepared by Examples 1-8 is small, and the encapsulation efficiency of ceramide and allantoin is high. The particle size of the products of Comparative Examples 1, 4, 5, and 6 is close to that of the example samples, but the encapsulation efficiency of ceramide and allantoin is low. The properties of Comparative Example 2 are unqualified. Comparative Example 3 is layered after being placed, and the stability is poor. The products of Comparative Examples 7 and 8 have ceramide and allantoin crystals precipitated after cooling, and no crystals were precipitated in Examples 5 and 6 with the same content of the two components, indicating that ceramide and allantoin have poor solubility in Comparative Examples 7 and 8 systems. Ceramide and allantoin can be dissolved in conventional solvents, but are related to temperature. The present invention encapsulates ceramide in the lipid bilayer through liposome encapsulation technology, and allantoin is encapsulated in the inner water phase, and the two components no longer change in solubility with temperature. The invention significantly improves the solubility of ceramide and allantoin and has outstanding characteristics.

[0129] Table 3. Appearance, particle size and encapsulation efficiency inspection results

[0130]

[0131] Example 10. Stability Study

[0132] The products of Examples 1 to 8 and Comparative Examples 1, 4, 5 and 6 were subjected to stability tests at 40°C for 30 days, 2-8°C for 40 days and 25°C for 40 days, with liposome appearance, particle size, and ceramide and allantoin encapsulation rates as the test indicators.

[0133] The results of the investigation are shown in Table 4. The data show that the sample appearance, particle size, ceramide and allantoin encapsulation rate of the liposome sample in the embodiment did not change significantly after being placed at 2-8°C for 40 days, 25°C for 40 days, and 40°C for 30 days. Comparative Examples 5 and 6 have poor stability under the above investigation conditions. Comparative Examples 1 and 4 have good stability under the above investigation conditions, but the ceramide and allantoin encapsulation rates are low. This shows that the sample obtained by the prescription and preparation process disclosed in the present invention has a smaller particle size, a higher ceramide and allantoin encapsulation rate, and better stability.

[0134] Table 4. Stability test results

[0135]

[0136] Example 11. Skin irritation test

[0137] According to the test method in Chapter 6 of the "Technical Specification for Safety of Cosmetics" (2015 edition), skin irritation tests were performed on the samples of Example 2, Example 4, Example 6 and Example 8.

[0138] (1) Animals

[0139] Healthy ordinary New Zealand rabbits, male or female, weighing 2.2-2.5 kg. Provided by Guizhou Yikeda Biotechnology Co., Ltd. (Production License No.: SCXK(Guizhou)2021-0001). The experimental animals will be kept in an ordinary environment, and the breeding facilities meet the requirements for the breeding of ordinary experimental animals (Use License: SYXK(Yu)2020-0007).

[0140] (2) Test methods

[0141] The samples of Example 2, Example 4, Example 6, and Example 8 were used as experimental groups, and 0.9% sodium chloride injection (manufacturer: Sichuan Kelun Pharmaceutical Co., Ltd., batch number: G123010605) was used as a negative control group. 24 hours before the experiment, the hair on both sides of the animal's back spine was removed, the hair removal range was 3cm×3cm each, and the application area was 2.5cm×2.5cm. 0.5ml of the test substance was applied directly to the left skin, and then covered with two layers of gauze (2.5cm×2.5cm) and a layer of cellophane or the like, and then fixed with non-irritating adhesive tape and bandages. 0.5ml of physiological saline was applied to the right side as a control. The closed application was applied for 4 hours, once a day, and the administration was continued for 14 days. Starting from the second day, the hair was cut before each application. After the application, the residual test substance was removed with water. The results were observed 1 hour after the drug was removed every day, and 24, 48 and 72 hours after the last application, and the skin irritation reaction was scored according to Table 5.

[0142] Table 5. Skin irritation response scoring table

[0143]

[0144] (3) Result evaluation

[0145] Calculate the average score for each animal per day according to the following formula and determine the skin irritation intensity according to Table 6.

[0146]

[0147] Table 6. Skin irritation intensity evaluation standard table

[0148]

[0149]

[0150] The results are shown in Table 7. The samples of Examples 2, 4, 6, and 8 are all non-irritating. The Tween 80 that may be irritating in the co-loaded liposomes provided by the present method is the maximum value of the patent scope in Example 2. Therefore, when the sample of Example 2 is non-irritating, the samples of other examples with lower Tween 80 content are also non-irritating. That is, the prescription of the present invention is safe and non-irritating.

[0151] Table 7. Skin irritation test results

[0152] Sample No. Integral mean Irritating results Example 2 0 Non-irritating Example 4 0 Non-irritating Example 6 0 Non-irritating Example 8 0 Non-irritating Control group 0 Non-irritating

[0153] Example 12. In vitro skin permeation experiment

[0154] The samples of Example 1, Example 2, Comparative Example 4 and Comparative Example 9 were subjected to in vitro skin permeation tests. The test method is as follows:

[0155] (1) In vitro skin cumulative permeation measurement

[0156] In vitro transdermal diffusion test (IVPT) was carried out using a vertical Franz transdermal diffusion system. Equal amounts of samples of Example 1, Example 2, Comparative Example 4 and Comparative Example 9 were taken and injected at 15 mg / cm 2 The drug was administered to the ex vivo skin of Bama miniature pigs, and a mixture of physiological saline and ethanol (4:1) was used as the receiving solution. The receiving solution was sampled 12 h after administration (1 sampling point in total), 0.65 mL of the sample was taken, and 0.65 mL of the solution was replenished at the same time. The contents of ceramide and allantoin in the receiving solution were determined, and the cumulative skin penetration of ceramide and allantoin of each sample after 12 h was calculated.

[0157] (2) Determination of skin retention

[0158] After 12 hours of in vitro transdermal experiment, the excised skin was removed, the inner and outer surfaces of the skin were rinsed with physiological saline, the moisture on the skin surface was absorbed, and the skin was cut into pieces to prepare skin homogenate. An appropriate amount of methanol was added and vortexed for 5 minutes, and then ultrasonically treated for 30 minutes; after centrifugation at 5000rpm for 5 minutes, it was filtered and the filtrate was taken to determine the contents of ceramide and allantoin, and the skin retention of ceramide and allantoin in each sample was calculated.

[0159] (3) Test results

[0160] The results of the in vitro transdermal test are shown in Table 8. Compared with the ceramide allantoin suspension (Comparative Example 9), the ceramide allantoin co-loaded liposome has a lower cumulative permeation amount and a higher skin retention amount, indicating that the ceramide allantoin liposome has a sustained release effect, which can reduce the exposure risk of the two components, while increasing the retention of the two components on the skin, prolonging the retention time of the two components in the skin, and is conducive to the two components to play a better and longer role. The cumulative permeation amount of the two components in Comparative Example 4 is higher than that of Examples 1 and 2, and the skin retention amount is lower than that of Examples 1 and 2, indicating that the encapsulation rate of the two components is negatively correlated with the cumulative permeation amount of the skin and positively correlated with the skin retention amount. Compared with non-liposomal preparations, the ceramide allantoin co-loaded liposomes of the present invention have obvious advantages in transdermal performance.

[0161] Table 8. In vitro skin permeation test results

[0162]

[0163] Note: Cumulative permeation represents exposure risk. The lower the cumulative permeation, the lower the exposure risk. Skin retention represents sustained-release effect. The higher the skin retention, the better the sustained-release effect.

[0164] Example 13. In vitro efficacy evaluation

[0165] The present invention selected Example 6 with the lowest sample content to evaluate the moisturizing and repairing effects, and the experimental method is as follows:

[0166] (1) Evaluation of moisturizing efficacy (human keratinocyte hyaluronic acid (HA) expression experiment)

[0167] Add 1 × 10 4 Individual keratinocytes were plated and placed in an incubator (37°C, 5% CO2) for 24 hours. Samples were given when the cell plating rate in the 96-well plate reached 40% to 60%. The blank control group was inoculated with KcGrowth culture medium without any treatment, and the sample groups were inoculated with KcGrowth culture medium of each diluted sample concentration (200 μL each). After the sampling was completed, the 96-well plate was placed in an incubator (37°C, 5% CO2) for 24 hours. After the culture was completed, the cell culture medium was collected in a 1.5 mL Eppendorf tube, centrifuged at 4°C and 1000×g, and the supernatant was taken for quantitative detection of hyaluronic acid.

[0168] (2) Evaluation of repair efficacy

[0169] a. Expression experiment of FLG in human keratinocytes

[0170] Add 1 × 10 4 Individual keratinocytes were plated and placed in an incubator (37°C, 5% CO2) for 24 hours. Samples were added when the cell plating rate in the 96-well plate reached 40% to 60%. The blank control group was inoculated with KcGrowth culture medium without any treatment, and the sample groups were inoculated with KcGrowth culture medium of each diluted sample concentration (200 μL each). After the sampling was completed, the 96-well plate was placed in an incubator (37°C, 5% CO2) for 24 hours. After the culture was completed, the cell culture medium was collected in a 1.5 mL Eppendorf tube, centrifuged at 4°C and 1000×g, and the supernatant was taken for quantitative detection of filaggrin.

[0171] b. Human fibroblast migration (scratch) assay

[0172] Add 2 × 10 5Individual fibroblasts were plated, and a straight line was drawn horizontally on the back with a marker pen to mark, and then placed in an incubator (37°C, 5% CO2) for 24 hours. When the cell plating rate in the 6-well plate reached 80% to 90%, a 1mL pipette tip was used to scratch. During the scratching process, the tip was slightly tilted to the plane, perpendicular to the marker mark, and the bottom of the plate was evenly scratched. The observation point was located above or below the intersection of the scratch and the marker mark, and 4 observation points were set for each well. After the scratching was completed, a photo was taken immediately at 0h to record the original scratch size and the observation point sequence number. Four photos were taken for each well, and then PBS was used to gently wash 2-3 times to remove floating cells, and the sample was processed. The blank control group was inoculated with cells in FbGrowth culture medium (serum-free), and the sample groups were inoculated with cells in FbGrowth culture medium (serum-free) with each concentration of diluted samples (2mL each). After the sampling was completed, the 6-well plate was placed in an incubator (37°C, 5% CO2) for 24 hours. After the incubation, take photos at the same observation point as the one taken at 0h using an objective lens of the same magnification for 24h to record the scratch repair status.

[0173] The test results are shown in Tables 9-11. Figure 1-Figure 8 As shown, when the sample concentration of Example 6 is 1.25% to 5%, it can promote the increase of hyaluronic acid expression in human keratinocytes, filaggrin expression, and migration rate of human fibroblasts in a dose-dependent manner, and there are significant differences compared with the negative control (P < 0.01). This shows that the prescription disclosed in the present invention has moisturizing and repairing effects. The present invention selects the sample with the lowest content in the embodiment for efficacy evaluation. When the sample with the lowest content has moisturizing and repairing effects, then other embodiments with higher contents will also have moisturizing and repairing effects.

[0174] Table 9. Experimental results of hyaluronic acid expression in human keratinocytes

[0175] Group HA content (ng / mL) HA relative expression (%) Blank control 65.81±3.14 —— Example 6 (sample dilution concentration 1.25%) <![CDATA[85.44±3.49 ** ]]> 129.82±5.30 Example 6 (sample dilution concentration 2.5%) <![CDATA[89.62±2.63 ** ]]> 136.18±3.99 Example 6 (sample dilution concentration 5%) <![CDATA[105.08±3.63 ** ]]> 159.68±5.51

[0176] Note: "**" indicates significant difference compared with the blank control group (P<0.01).

[0177] Table 10. Experimental results of human keratinocyte filaggrin expression

[0178] Group FLG content (ng / mL) FLG relative expression (%) Blank control 4.37±0.13 —— Example 6 (sample dilution concentration 1.25%) <![CDATA[5.65±0.15 ** ]]> 129.36±3.44 Example 6 (sample dilution concentration 2.5%) <![CDATA[6.35±0.16 ** ]]> 145.27±3.55 Example 6 (sample dilution concentration 5%) <![CDATA[7.33±0.11 ** ]]> 167.64±2.45

[0179] Note: "**" indicates significant difference compared with the blank control group (P<0.01).

[0180] Table 11. Results of human fibroblast migration assay

[0181] Group Cell migration rate (%) Relative cell migration rate (%) Blank control 9.69±0.88 —— Example 6 (sample dilution concentration 1.25%) <![CDATA[22.99±1.08 ** ]]> 137.26±1.23 Example 6 (sample dilution concentration 2.5%) <![CDATA[28.33±1.34 ** ]]> 192.35±1.66 Example 6 (sample dilution concentration 5%) <![CDATA[40.98±1.93 ** ]]> 322.94±1.88

[0182] Note: "**" indicates significant difference compared with the blank control group (P<0.01).

Claims

1. A composition for preparing ceramide-allantoin co-loaded liposomes, characterized in that: The composition comprises ceramide, allantoin and auxiliary materials for preparing liposomes, and the mass ratio thereof is 1-8:0.5-1.5:90.5-98.

5.

2. The composition according to claim 1, characterized in that The auxiliary materials include hydrogenated phosphatidylcholine and cholesterol, and the ratio of the total amount of hydrogenated phosphatidylcholine and ceramide to cholesterol is in the range of 3:1 to 5:

1.

3. The composition according to claim 1, characterized in that The ceramide is contained in the phospholipid bilayer, and the allantoin is contained in the inner water phase.

4. The composition according to claim 1, characterized in that The auxiliary materials also include Tween 80, ionic surfactant, organic solvent, stabilizer, aqueous medium, antioxidant, preservative and chelating agent, and the mass ratio thereof is 1-3: 0.4-1.5: 9-20: 0.5-2: 46.9-79.99: 0.1-1.0: 0.5-1.0: 0.01-0.1; the ionic surfactant includes any one of behenamidopropyl dimethylamine and sodium stearoyl glutamate; the organic solvent includes any one or both of ethanol and propylene glycol; the stabilizer is polyvinyl alcohol; the aqueous medium is phosphate buffer; the antioxidant is tocopherol acetate; the preservative includes any one or both of a compound preservative of phenoxyethanol and ethylhexylglycerin and a compound preservative of o-cymene-5-ol and isopentyl glycol; and the chelating agent is disodium edetate.

5. The composition according to claim 1, characterized in that The composition is composed of the following components in parts by weight: 5 to 10 parts of hydrogenated phosphatidylcholine, 2 to 5 parts of cholesterol, 1 to 8 parts of ceramide, 0.5 to 1.5 parts of allantoin, 1 to 3 parts of Tween 80, 0.4 to 1.5 parts of ionic surfactant, 9 to 20 parts of organic solvent, 0.5 to 2 parts of stabilizer, 0.1 to 1.0 parts of antioxidant, 0.5 to 1.0 parts of preservative, 0.01 to 0.1 parts of chelating agent, and the aqueous phase medium is supplemented to 100 parts.

6. The composition according to claim 1, characterized in that The composition consists of the following components in parts by weight: 5 to 8 parts of hydrogenated phosphatidylcholine, 1 to 3 parts of ceramide, 2 to 4 parts of cholesterol, 0.4 to 0.6 parts of sodium stearoyl glutamate, 0.4 to 0.6 parts of tocopherol acetate, 8 to 10 parts of propylene glycol, 2 to 4 parts of Tween 80, 0.6 to 0.8 parts of allantoin, 1 to 3 parts of polyvinyl alcohol, 0.01 to 0.03 parts of disodium edetate, 0.6 to 0.8 parts of phenoxyethanol / ethylhexylglycerin, and 70 to 75 parts of phosphate buffered saline.

7. A method for improving the solubility and permeability of ceramide and allantoin, characterized in that: The ceramide and allantoin are prepared into co-loaded liposomes by an organic solvent injection method, wherein the organic solvent injection method comprises the following steps: (1) mixing phospholipids, ceramide, cholesterol, antioxidants and an organic solvent to obtain an organic phase; (2) mixing Tween 80, a stabilizer, a chelating agent, allantoin and an aqueous phase medium to obtain an aqueous phase; (3) injecting the organic phase obtained in step (1) into the aqueous phase obtained in step (2) for hydration to obtain a suspension; (4) adding a preservative to the suspension obtained in step (3), and homogenizing under high pressure to obtain ceramide-allantoin co-loaded liposomes; In step (1) or step (2), an ionic surfactant is added; if the ionic surfactant is a cationic surfactant, it is added to the organic phase; if the ionic surfactant is an anionic surfactant, it is added to the aqueous phase.

8. The method according to claim 7, characterized in that In step (3), the reaction conditions include: 60°C-80°C hot water bath, 400rpm-500rpm rotation speed, and hydration reaction time of 0.5-2h.

9. Ceramide-allantoin co-loaded liposomes prepared by the method according to any one of claims 7-8.

10. Use of the composition according to any one of claims 1 to 6 and / or the ceramide and allantoin co-loaded liposomes according to claim 9 in the preparation of moisturizing and repairing cosmetics with sustained release effects.

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