Liposome precursor composition as well as preparation method and application thereof

Abstract

The invention discloses a liposome precursor composition, which is prepared from the following ingredients in percentage by mass: 40 to 53 percent of polyhydric alcohol, 35 to 45 percent of panthenol, 10 to 15 percent of lecithin and 2 to 4 percent of ceramide NP. According to the liposome precursor composition disclosed by the invention, the problem that ceramide is not matched with a common formula system is effectively improved by adding panthenol with a specific content and combining the combined action of lecithin and polyhydric alcohol, and the stability, the water solubility and the permeability on the skin surface of a ceramide system are remarkably enhanced; the ceramide can play a better role in the epidermal layer and the corium layer of the skin. The invention also discloses a preparation method of the liposome precursor composition, in the method, chemical penetration enhancers which are not welcomed by cosmetics such as azone and the like are not used, and any unwelcomed solubilizers or surfactants are not introduced, so that the safe and effective application of the ceramide NP is realized.

Description

Technical Field

[0001] The present invention relates to a raw material for skin products, in particular to a liposome precursor composition and a preparation method thereof and application thereof in skin products. Background Art

[0002] The epidermal barrier mainly refers to the stratum corneum, which is the first line of defense against countless potentially harmful invaders. Ceramide, as the core of the structure and function of the permeability barrier, constitutes the extracellular lipid matrix of the epidermal barrier in a nearly equimolar ratio with fatty acids and cholesterol. In skin care, ceramide is particularly important because it has a large number of hydrophilic groups, which makes ceramide have a strong ability to associate with water molecules. Ceramide forms a mesh structure in the stratum corneum to maintain moisture, adhere to keratinocytes, repair the barrier, and resist the invasion of the external environment, such as bacteria and chemicals. At present, ceramide has significant effects in moisturizing, anti-aging, anti-inflammatory and protection.

[0003] Ceramide itself has poor permeability in the skin and low skin retention, making it difficult to exert its efficacy and thus having low bioavailability. In addition, ceramide has a high melting point, poor water solubility, is difficult to emulsify, and is easy to crystallize or flocculate from the cosmetic formula system, which not only affects the stability of the formula, but also reduces the utilization rate of ceramide, greatly limiting its application in the cosmetic field, and cannot be widely used in conventional topical preparations such as lotions, emulsions, creams, essences, and masks.

[0004] Patent CN112190574B discloses a method for preparing a ceramide phospholipid complex, which uses phospholipid complex technology to improve the water solubility of ceramide, but in the preparation process, a highly volatile, neurotoxic aliphatic hydrocarbon solvent is used. Although there is a subsequent drying and removal process, there may still be problems with subsequent waste liquid treatment and environmental pollution risks. Patent CN113616544A discloses a preparation process for a water-soluble ceramide NP composition, which uses emulsification homogenization combined with high-pressure microjetting to prepare ceramide liposomes, improve the water solubility and stability of ceramide, but the preparation process is relatively complicated and involves the use of surfactants, which may be unpopular in the field of cosmetics. Most of the existing ceramide liposomes or phospholipid complexes are mainly composed of polyols, phospholipids, and ceramides. Although they can improve the stability and bioavailability of ceramide NPs to a certain extent, they involve the use of chloroform, toluene, dichloromethane, acetone or neurotoxic aliphatic hydrocarbon solvents, and there are risks such as solvent residues, which are not conducive to the application of ceramide in the field of cosmetics. Summary of the invention

[0005] The purpose of the present invention is to overcome the above-mentioned problems of the prior art and provide a liposome precursor composition that has good solubility in an oil phase system, can spontaneously form liposomes in an aqueous system, has strong permeability of ceramide NP, and has high bioavailability; at the same time, the present invention also provides a simple, environmentally friendly method for preparing a liposome precursor composition that can effectively avoid solvent residues, as well as the use of the liposome precursor composition in skin products.

[0006] In the first aspect, the present invention provides a liposome precursor composition with good solubility and permeability, high bioavailability and can be conveniently added to various topical preparations. To achieve this purpose, the technical solution adopted by the present invention is: a liposome precursor composition, which contains the following components in percentage by weight: 40-53% of polyol, 35-45% of panthenol, 10-15% of lecithin, and 2-4% of ceramide NP.

[0007] The inventors of the present application found in the study that when preparing a liposome precursor composition, a certain amount of panthenol is used to cooperate with polyols, lecithin and ceramide NP. Panthenol has the same amide bond as ceramide, and the part connected to the amide bond has a similar structure. The two are highly compatible, and the units formed by the covalent bonds of the nitrogen and oxygen atoms of the amide bond have a high degree of commonality, which allows them to form hydrogen bonds. At a suitable ratio, the addition of panthenol helps prevent ceramide crystallization, thereby ensuring the stability of the liposome precursor complex and the smooth formation of the liposome structure during use. Therefore, the addition of the specific content of panthenol can have a synergistic effect in promoting penetration, improve the stability, permeability and sustained release effect of the prepared liposome precursor composition, and significantly increase the skin retention and bioavailability of ceramide. In addition, the addition of panthenol also further enhances the moisturizing and water-locking effect of the system, strengthens the skin barrier, softens the skin, and improves roughness and peeling conditions. In addition, ceramide is composed of fatty acids and sphingosine bases, and the phosphatidylcholine molecules contained in lecithin have a similar structure to them. The structure of the ceramide NP and the specific content of lecithin can effectively act on the skin tissue after acting on the skin, instantly repair the skin barrier, while enhancing the skin's stratum corneum's ability to lock in water, improving the skin's dehydration, reducing skin peeling and desquamation, and increasing the skin's water content, further ensuring the smooth circulation of substances inside the skin tissue.

[0008] Preferably, the lecithin contains phosphatidylcholine, and the mass percentage of the phosphatidylcholine in the lecithin is ≥75%. Phosphatidylcholine is a natural emulsifier and moisturizer. Since the molecular structure of phosphatidylcholine is similar to that of ceramide, it is composed of hydrophobic fatty acids with a hydrophilic head and a lipophilic tail, and phosphatidylcholine is the main component of eukaryotic membranes and plays an important role in maintaining the integrity of the membrane; due to the similar structure, ceramide and phosphatidylcholine molecules interact with each other, so that the tail chains can be hinged to each other to form a stable and tight micro-domain structure. Lecithin with a high content of phosphatidylcholine is more likely to combine with ceramide, promote the stability of the system, and further facilitate the formation of liposome structure during use, promoting product efficacy.

[0009] More preferably, the lecithin is soybean lecithin or hydrogenated lecithin, the mass percentage of phosphatidylcholine in the soybean lecithin is ≥80%, and the content of hydrogenated phosphatidylcholine in the hydrogenated lecithin is ≥95%. The content of phosphatidylcholine in common soybean lecithin is generally 20-40%, and the soybean lecithin with a mass percentage of phosphatidylcholine ≥80% is selected in the present invention, especially soybean lecithin with a phosphatidylcholine content ≥95% (for example, purchased from LIPOID), or hydrogenated lecithin with a phosphatidylcholine content ≥75%, especially hydrogenated lecithin with a hydrogenated phosphatidylcholine content ≥95% (for example, purchased from LIPOID), the selected lecithin can not only significantly improve the stability of the system, but also has better affinity to the skin, can better combine with ceramide NP molecules, is conducive to the stability of the system, and makes it easy to promote ceramide NP to penetrate into the deep layer of the skin, give full play to its beneficial effects, not only more conducive to the formation of liposome structure during use, but also can promote product efficacy.

[0010] Preferably, the polyol is a short-medium carbon chain polyol with 5-6 carbon atoms. The polyol used in the present invention is preferably a short-medium carbon chain polyol with 5-6 carbon atoms, and more preferably, the polyol is at least one of 1,2-pentanediol and 1,2-hexanediol. The 1,2-pentanediol can be purchased from Shanghai Qianyi Chemical Co., Ltd., and the 1,2-hexanediol can be purchased from COSBON CO., LTD. The higher content of polyol in the present invention can provide moisturizing effect. When the polyol selects a short-medium carbon chain polyol with 5-6 carbon atoms, it can also provide an antiseptic function for the system, and has a good antiseptic effect without adding a preservative, thereby improving the safety during use. In addition, the presence of polyols allows the liposome precursor complex to participate in the formation of liposomes when forming liposomes under hydration in the aqueous phase system, providing higher stability and elasticity for the liposome membrane structure, and helping to improve the penetration ability of the active substance.

[0011] Preferably, the panthenol is D-panthenol. The panthenol used in the liposome precursor composition of the present invention is limited to D-panthenol, and the D-panthenol can be purchased from Anhui Huaheng Biotechnology Co., Ltd., for example. Panthenol has good moisturizing properties and can repair skin damage. It can be divided into three types: racemic isomer (DL-type), dextrorotatory isomer (D-type) and levorotatory isomer (L-type), among which D-panthenol has better biological activity. D-panthenol contains three hydroxyl structures and has high physiological activity. It can be converted into pantothenic acid when entering the human body, and then synthesize coenzyme A, promote the metabolism of human protein, fat, and carbohydrates, protect the skin surface mucosa, strengthen the skin barrier, and has good moisturizing ability. In addition, the molecular structure of D-panthenol enables it to form intermolecular interactions with ceramide and phosphatidylcholine, which is beneficial to the stability of the system. Moreover, D-panthenol has a small molecular weight and is easy to penetrate the stratum corneum of the skin, which can play a positive role in the penetration ability of the system.

[0012] Preferably, the mass ratio of ceramide NP to lecithin is 1:(2.5-5).

[0013] Preferably, the mass ratio of ceramide NP to panthenol is 1:(10-20).

[0014] The inventors of the present application have found that the mass ratios of ceramide NP to lecithin, and ceramide NP to panthenol have a direct impact on the performance of the liposome precursor composition prepared, especially on the permeability, stability, etc. of the liposome precursor composition. Specifically, the mass ratio of ceramide NP to lecithin can be any value of 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, or values ​​therebetween; the mass ratio of ceramide NP to panthenol can be any value of 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or values ​​therebetween.

[0015] In a second aspect, the present invention provides a method for preparing a liposome precursor composition which is simple and environmentally friendly and has no solvent residue in the product. To achieve this purpose, the technical solution adopted by the present invention is: a method for preparing a liposome precursor composition, the preparation method comprising the following steps:

[0016] (1) Weighing polyol, panthenol, lecithin and ceramide NP into a container, immersing and dissolving them in ethanol, and continuously stirring at 60-80° C. under a sealed condition to fully dissolve and disperse the components to obtain a clear and transparent liquid;

[0017] (2) placing the clear transparent liquid obtained in step (1) in a flask, and performing rotary evaporation in a water bath at 40-70° C. under vacuum conditions until the ethanol is completely evaporated, and then continuing the rotary evaporation at room temperature until a uniform liquid film is formed on the inner wall of the flask, thereby obtaining a liposome precursor composition.

[0018] Preferably, the amount of ethanol added in step (1) is an appropriate amount that can immerse and dissolve the raw materials. The stirring time in step (1) can be 0.5-2 hours.

[0019] Preferably, the vacuum degree of the vacuum condition in step (2) is ≤-0.05Mpa. In step (2), rotary evaporation can be performed in a rotary evaporator, and the rotary evaporation time is preferably 1-3 hours until the ethanol is completely evaporated.

[0020] Preferably, the rotary evaporation at room temperature in step (2) is continued for 1-3 hours until a uniform liquid film is formed on the inner wall of the flask, and then the contents are taken out to obtain the liposome precursor composition.

[0021] In a third aspect, the present invention provides a skin product having strong skin permeability of ceramide, high bioavailability and stable formula. To achieve this purpose, the technical solution adopted by the present invention is: a skin product, wherein the skin product contains the liposome precursor composition as described above.

[0022] The skin care product of the present invention contains the liposome precursor composition composed of the above-mentioned specific structure and ingredients. Ceramide can not only exist stably in the skin care product, but also the ceramide NP in the skin care product can penetrate well into the deep layer of the skin, so that ceramide can play a better role in the epidermis and dermis of the skin, and has good effects such as moisturizing, locking water, and repairing the barrier.

[0023] Preferably, the content of the liposome precursor composition in the skin product is 0.5-10%. The content of the liposome precursor composition in the skin product is preferably but not limited to 0.5-10%, for example, it can be any value of 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or an intermediate value therebetween.

[0024] Preferably, the skin product is skin care lotion, skin care lotion, skin care cream, essence or facial mask liquid.

[0025] Finally, the present invention provides the use of the liposome precursor composition described above in skin products. Ceramide is difficult to be directly applied to cosmetic formulations due to its poor biocompatibility. The present invention provides the use of the above-mentioned liposome precursor composition in skin products. The liposome precursor composition can be added to a moisturizing lotion system in any proportion under normal temperature conditions to form a uniform and stable system. The system is cold-resistant, heat-resistant, and has no flocculation, stratification, etc. in a one-month normal temperature stability test, which widely improves the application of ceramide in skin products.

[0026] Preferably, when the liposome precursor composition is used in skin products, the skin products may be skin care lotion, skin care lotion, skin care cream, essence or facial mask.

[0027] Preferably, when the liposome precursor composition is used in skin products, the liposome precursor composition can be conveniently added thereto in a suitable ratio. The amount of the liposome precursor composition added includes but is not limited to 0.5-10%, and it can remain stable under various conditions.

[0028] The liposome precursor composition of the present invention, by adding a specific amount of panthenol and combining the lecithin and polyol, effectively improves the problem of incompatibility between ceramide and common formula systems, significantly enhances the stability of the ceramide system, and significantly enhances water solubility, and can spontaneously form a liposome encapsulation structure in water, has a sustained release effect, and achieves a long-lasting skin care benefit effect. It can also enhance the penetration of ceramide on the skin surface, so that ceramide can better play a role in the epidermis and dermis of the skin.

[0029] The method for preparing the liposome precursor composition of the present invention does not use chemical penetration enhancers such as azone that are not welcome in cosmetics, nor does it introduce any unwelcome solubilizers or surfactants. It can not only quickly and conveniently prepare the liposome precursor composition of the specific structure, but also realizes the safe and effective application of ceramide NP.

[0030] The skin care product of the present invention contains the ceramide liposome precursor with the specific structure and composition, which not only has good system stability, but also has a long-lasting sustained release effect of the ceramide NP therein, and can achieve skin care effects such as long-lasting moisturizing and water locking, and repairing the skin barrier. The application of the ceramide liposome in the skin care product of the present invention provides a new option for the stable use of ceramide in skin care products. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is a diagram showing the appearance changes of the liposome precursor composition described in Example 1 of the present invention after being stored at different temperatures for 24 hours, 30 days and 3 months;

[0032] Figure 2 This is a diagram showing the appearance changes of the liposome precursor composition described in Example 3 of the present invention after being stored at different temperatures for 24 hours, 30 days and 3 months;

[0033] Figure 3 This is a graph showing the cumulative release of ceramide NPs of Example 1 of the present invention and Comparative Example 1 at 32° C. for 48 hours;

[0034] Figure 4 This is a comparison chart of the skin retention amounts of Example 1 of the present invention and Comparative Examples 2 and 3 at different addition amounts;

[0035] Figure 5 Comparison chart of skin moisture content after the subjects used the treatment group cream and the control group cream for 7 days and 14 days;

[0036] Figure 6 The test results of skin redness area after the subjects used the treatment group cream and the control group cream for 7 days and 14 days;

[0037] Figure 7 Facial test images of the subjects after using the treatment group cream on days 0, 7, and 14. DETAILED DESCRIPTION

[0038] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.

[0039] Unless otherwise specified, the substances used in the following examples can be directly purchased from commercial sources or prepared by conventional methods in the art. Examples of the purchase sources of some substances are as follows:

[0040] Soy lecithin, purchased from LIPOID, phosphatidylcholine content ≥ 95%;

[0041] Hydrogenated lecithin, purchased from LIPOID, phosphatidylcholine content ≥ 95%;

[0042] 1,2-Pentanediol was purchased from Shanghai Qianyi Chemical Co., Ltd.;

[0043] 1,2-Hexanediol was purchased from COSBON CO., LTD.

[0044] The above purchase sources are for illustrative purposes only and should not be construed as limiting the scope of protection of this application.

[0045] Example 1

[0046] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0047] 1,2-Hexanediol 45%, D-Panthenol 40%, Soy Lecithin 12%, Ceramide NP 3%.

[0048] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0049] (1) Weigh each component according to the mass ratio and place it in a container, immerse it in an appropriate amount of ethanol to dissolve it, and keep stirring for 0.5 h at 80°C under sealed conditions to allow each component to fully dissolve and disperse to obtain a clear and transparent liquid;

[0050] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 40°C water bath under vacuum conditions (vacuum degree ≤ -0.05 MPa) for 3 h until the ethanol is completely evaporated, and then the rotary evaporation is continued for 1.5 h at room temperature until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0051] Example 2

[0052] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0053] 1,2-Pentanediol 45%, D-Panthenol 40%, Soy Lecithin 12%, Ceramide NP 3%.

[0054] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0055] (1) Weigh each component according to the mass ratio and place it in a container, immerse it in an appropriate amount of ethanol to dissolve it, and stir it continuously for 1 hour under a sealed condition at 70°C to allow each component to be fully dissolved and dispersed to obtain a clear and transparent liquid;

[0056] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 50°C water bath under vacuum conditions (vacuum degree ≤ -0.05 MPa) for 2 h until the ethanol is completely evaporated, and then the rotary evaporation is continued for 1.5 h at room temperature until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0057] Example 3

[0058] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0059] 1,2-Hexanediol 47%, D-Panthenol 40%, Hydrogenated Lecithin 10%, Ceramide NP 3%.

[0060] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0061] (1) Weigh each component according to the mass ratio and place it in a container, immerse it in an appropriate amount of ethanol to dissolve it, and stir it continuously for 2 h under a sealed condition at 60°C to allow each component to fully dissolve and disperse to obtain a clear and transparent liquid;

[0062] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 60° C. water bath under vacuum conditions (vacuum degree ≤ −0.05 MPa) for 2 h until the ethanol is completely evaporated, and then the rotary evaporation is continued for 2 h at room temperature until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0063] Example 4

[0064] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0065] 1,2-Pentanediol 47%, D-Panthenol 40%, Hydrogenated Lecithin 10%, Ceramide NP 3%.

[0066] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0067] (1) Weigh each component according to the mass ratio and place it in a container. Use an appropriate amount of ethanol to immerse and dissolve it. Stir continuously for 1.5 h at 70°C in a sealed condition to allow each component to fully dissolve and disperse to obtain a clear and transparent liquid.

[0068] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 55°C water bath under vacuum conditions (vacuum degree ≤ -0.05 MPa) for 2 h until the ethanol is completely evaporated, and then the rotary evaporation is continued at room temperature for 1 h until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0069] Example 5

[0070] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0071] 1,2-Hexanediol 53%, D-Panthenol 35%, Soy Lecithin 10%, Ceramide NP 2%.

[0072] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0073] (1) Weigh the components according to the mass ratio and place them in a container. Use an appropriate amount of ethanol to immerse and dissolve them. Stir continuously for 2 h at 65°C in a sealed condition to allow the components to fully dissolve and disperse to obtain a clear and transparent liquid.

[0074] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 45°C water bath under vacuum conditions (vacuum degree ≤ -0.05 MPa) for 3 h until the ethanol is completely evaporated, and then the rotary evaporation is continued at room temperature for 2 h until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0075] Example 6

[0076] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0077] 1,2-Pentanediol 40%, D-Panthenol 45%, Soy Lecithin 11%, Ceramide NP 4%.

[0078] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0079] (1) Weigh each component according to the mass ratio and place it in a container. Use an appropriate amount of ethanol to immerse and dissolve it. Stir continuously for 0.5 h at 75°C in a sealed condition to allow each component to fully dissolve and disperse to obtain a clear and transparent liquid.

[0080] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 55°C water bath under vacuum conditions (vacuum degree ≤ -0.05 MPa) for 2 h until the ethanol is completely evaporated, and then the rotary evaporation is continued for 3 h at room temperature until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0081] Example 7

[0082] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0083] 1,2-Hexanediol 40%, D-Panthenol 43%, Hydrogenated Lecithin 15%, Ceramide NP 2%.

[0084] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0085] (1) Weigh each component according to the mass ratio and place it in a container, immerse it in an appropriate amount of ethanol to dissolve it, and stir it continuously for 1 hour under a sealed condition at 70°C to allow each component to be fully dissolved and dispersed to obtain a clear and transparent liquid;

[0086] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 65° C. water bath under vacuum conditions (vacuum degree ≤ −0.05 MPa) for 2.5 h until the ethanol is completely evaporated, and then the rotary evaporation is continued at room temperature for 2 h until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0087] Example 8

[0088] An embodiment of the liposome precursor composition of the present invention, the liposome precursor composition of this embodiment contains the following components in percentage by weight:

[0089] 1,2-Pentanediol 50%, D-Panthenol 35%, Hydrogenated Lecithin 11%, Ceramide NP 4%.

[0090] The method for preparing the liposome precursor composition described in this embodiment comprises the following steps:

[0091] (1) Weigh each component according to the mass ratio and place it in a container, immerse it in an appropriate amount of ethanol to dissolve it, and stir it continuously for 1 hour under a sealed condition at 80°C to allow each component to be fully dissolved and dispersed to obtain a clear and transparent liquid;

[0092] (2) The clear transparent liquid obtained in step (1) is placed in a flask, and rotary evaporated in a rotary evaporator in a 70°C water bath under vacuum conditions (vacuum degree ≤ -0.05 MPa) for 1 hour until the ethanol is completely evaporated, and then the rotary evaporation is continued for 2 hours at room temperature until a uniform liquid film is formed on the inner wall of the flask, and the contents are taken out to obtain the liposome precursor composition described in this example.

[0093] Comparative Example 1

[0094] A comparative example of the liposome precursor composition of the present invention, the liposome precursor composition of this comparative example contains the following components in percentage by weight:

[0095] 1,2-Hexanediol 85%, Soy Lecithin 12%, Ceramide NP 3%.

[0096] The preparation method of the liposome precursor composition in this comparative example is the same as that in Example 1.

[0097] Comparative Example 2

[0098] A comparative example of the liposome precursor composition of the present invention, the liposome precursor composition of this comparative example contains the following components in percentage by weight:

[0099] 1,2-Hexanediol 65%, D-Panthenol 20%, Soy Lecithin 12%, Ceramide NP 3%.

[0100] The preparation method of the liposome precursor composition in this comparative example is the same as that in Example 1.

[0101] Comparative Example 3

[0102] A comparative example of the liposome precursor composition of the present invention, the liposome precursor composition of this comparative example contains the following components in percentage by weight:

[0103] 1,2-Hexanediol 25%, D-Panthenol 60%, Soy Lecithin 12%, Ceramide NP 3%.

[0104] The preparation method of the liposome precursor composition in this comparative example is the same as that in Example 1.

[0105] Effect Example 1

[0106] This effect example tests the stability, in vitro release and permeability of the liposome precursor composition of the present invention.

[0107] 1. Stability test

[0108] 1. Temperature stability test

[0109] Test method: The liposome precursor compositions prepared in Examples 1 to 8 and Comparative Examples 1 to 3 were tested. An equal amount of the liposome precursor composition was taken in a sample bottle in each group, and then placed under four conditions of room temperature, -20°C, 45°C, and 4°C for observation for 24 hours, 30 days, and 3 months. The appearance changes of the products were visually observed at room temperature without direct sunlight when the products were placed for 24 hours, 30 days, and 3 months, as well as the changes in the pH value and ceramide NP content of the test products.

[0110] The liposome precursor compositions described in Examples 1 to 8 were placed at room temperature, -20°C, 45°C, and 4°C for 24 hours, 30 days, and 3 months, and all had a light yellow transparent liquid appearance. The appearance did not change significantly with the extension of the placement time, and all had a characteristic odor. The appearance pictures of the liposome precursor compositions described in Examples 1 and 3 after being placed at room temperature, -20°C, 45°C, and 4°C for 24 hours, 30 days, and 3 months are shown in the attached figure. Figure 1 and 2 shown.

[0111] Attached Figure 1-2 The figure shows the appearance changes of the liposome precursor compositions prepared in Example 1 and Example 3 after storage at four different temperature conditions: room temperature, -20°C, 45°C, and 4°C for 0 month, 1 month, and 3 months. It can be seen from the figure that the liposome precursor compositions prepared by the present invention do not show significant appearance changes under various conditions.

[0112] After the liposome precursor compositions described in Comparative Examples 1 to 3 were placed under four conditions of room temperature, -20°C, 45°C, and 4°C for 24 hours, 30 days, and 3 months, crystals or flocculation appeared in appearance. As the placement time increased, the crystals or flocculation gradually increased, especially in the liposome precursor composition described in Comparative Example 1, there were more crystals and flocculations.

[0113] The pH value refers to the pH of a 10% dispersion prepared from a liposome precursor composition. The test method is: take a certain mass of sample and disperse it with laboratory pure water to obtain a 10% sample pure water dispersion, and then The pH value of the sample was tested by ATARTER3100 pH meter. The test results are shown in Table 1.

[0114] The ceramide NP content refers to the content of ceramide NP in the liposome precursor composition, and the test method is: accurately weigh 250.00 mg of the sample into a 10 ml volumetric flask, dilute to the scale with methanol:tetrahydrofuran (70:30), and ultrasonicate for 10 minutes to obtain the sample solution to be tested; accurately weigh 45.5 mg of the ceramide NP reference substance into a 10 ml volumetric flask, dilute to the scale with a diluent, and ultrasonicate for 5 minutes to obtain a ceramide NP reference substance mother solution, accurately transfer 1 ml of the NP reference substance mother solution into a 10 ml volumetric flask, dilute to the scale with a diluent, and shake well to obtain a ceramide NP reference substance solution. Chromatographic column: Waters XBridge BEH C8 (4.6*150mm, 5μm); mobile phase A: water-methanol-trifluoroacetic acid (600:400:0.6), mobile phase B: acetonitrile; mobile phase A: mobile phase B = 15%:85%; flow rate: 1mL / min; column temperature: 40°C; injection volume: 10L; running time: 12min; detection wavelength: ceramide NP detection wavelength is 202nm. The test results are shown in Table 2.

[0115] Table 1 pH test results of each group of liposome precursor compositions at different temperatures

[0116]

[0117]

[0118] Table 2 The content of ceramide NP in each group of liposome precursor compositions at different temperatures

[0119]

[0120]

[0121] As can be seen from Table 1, Table 2 and the product appearance pictures, the content of ceramide NP in the liposome precursor compositions prepared in the examples of the present invention remains stable, indicating that the liposome precursor compositions prepared in the present invention enhance the stability of ceramide NP, which helps to ensure the quality stability and efficacy of the product during the normal shelf life. Although the liposome precursor compositions of Comparative Examples 1-3 have no significant difference in the content of ceramide NP at different pH and temperatures compared with Example 1, the liposome precursor compositions of Comparative Examples 1-3 have more crystals and flocculation as the storage time increases.

[0122] 2. Light stability test

[0123] Take equal amounts of the liposome precursor compositions of Examples 1 to 8 and Comparative Examples 1 to 3 in sample bottles and place them at 25°C and 1.2 W / m 2 After 48 h of illumination under the same conditions, the changes in ceramide NP content and encapsulation efficiency in each group were tested.

[0124] The test method for ceramide NP content is the same as the temperature stability test above, and the test results are shown in Table 3.

[0125] The encapsulation efficiency test method is as follows: take 1 ml of the sample to be tested into a 10 ml volume, dilute to the mark with deionized water, mix well and take 1 ml of the diluent into a centrifuge tube, centrifuge at 5000 rpm / min for 60 min, take 0.5 ml of the supernatant into a 5 ml volumetric flask, dilute to the mark with a diluent (methanol: tetrahydrofuran = 70:30), take the diluent and filter through a 0.22 μm filter head and analyze by HPLC. The ceramide III in the liquid after centrifugation is the encapsulated ceramide III. The test results are shown in Table 4.

[0126] Table 3 Changes in ceramide NP content in each group before and after illumination

[0127]

[0128]

[0129] It can be seen from the results in Table 3 that, compared with Comparative Example 1 in which panthenol is not added, the liposome precursor composition prepared in Example can improve the photostability of ceramide NP in the system and effectively prevent the rapid photodegradation of ceramide NP.

[0130] Table 4 Changes in encapsulation efficiency of each group before and after illumination

[0131] Group Encapsulation rate before illumination (%) Encapsulation rate after illumination (%) Example 1 95.96 95.53 Example 2 94.67 94.21 Example 3 96.52 96.10 Example 4 94.44 93.89 Example 5 94.87 94.42 Example 6 95.32 94.9 Example 7 91.35 90.12 Example 8 90.87 89.58 Comparative Example 1 78.52 75.21 Comparative Example 2 85.47 80.79 Comparative Example 3 80.11 76.15

[0132] As shown in Table 4, the encapsulation efficiency of the liposome precursor compositions prepared in Examples 1-8 did not change significantly, indicating that the encapsulation efficiency of the liposome precursor compositions of the present invention was stable under illumination conditions. However, the encapsulation efficiency of Comparative Examples 1-3 was relatively low, and the encapsulation efficiency decreased significantly under the influence of illumination conditions.

[0133] 2. In vitro release test

[0134] Based on the Franz cell diffusion pool system, a Franz diffusion pool release experiment was carried out on different samples using a PTFE membrane. The release capacity of ceramide NP in Example 1 and Comparative Example 1 was investigated by measuring the content of ceramide NP in the diffusion pool at different times.

[0135] The specific operation method is: fix the PTFE membrane between the diffusion chamber and the receiving chamber of the Franz cell diffusion pool. After fixing the PTFE membrane, add 8mL of receiving liquid (60% isopropanol) to the receiving chamber to make the PTFE membrane in close contact with the receiving liquid. Fix the Franz diffusion cell in the transdermal diffuser, set the temperature to 32°C, and the speed of the magnetic stirring rotor to 600rpm. After the water bath temperature of the diffuser is constant, the sample is loaded. The sample addition amount is 0.1g. The sample is added to the surface of the PTFE membrane and spread evenly. When released for 2h, 4h, 8h, 12h, and 24h, the receiving liquids of Example 1 and Comparative Example 1 are collected, and the ceramide NP in the receiving liquid is quantitatively analyzed by high performance liquid chromatography. The cumulative in vitro release of the liposome precursor composition described in Example 1 and Comparative Example 1 for 24h is shown in the attached. Figure 3 shown.

[0136] Attached Figure 3 The cumulative release of ceramide NPs of Example 1 and Comparative Example 1 at 32°C for 48 hours is shown. From the analysis of the results, it can be seen that the ceramide NPs of Comparative Example 1 have been completely released at 4 hours of release, and Example 1 achieves continuous slow release within 12 hours, indicating that the liposome precursor composition of the present invention has a sustained release effect, which helps to achieve a sustained release of ceramide NPs in the skin, allowing it to reside in the skin for a long time and exert its efficacy.

[0137] 3. Penetration Testing

[0138] (1) Sample preparation: Take the products prepared in Example 1 (0.03% deuterated ceramide NP is added as a marker during the preparation process), Comparative Example 2 and Comparative Example 3 (0.03% deuterated ceramide NP is added as a marker during the preparation process), add them to the essence base, stir evenly, and obtain the samples to be tested, wherein the content of ceramide NP is 0.03%, and the content of the marker deuterated ceramide NP is 0.003%. All the samples to be tested are prepared using a unified essence gel base, and the formula is: 3% propylene glycol, 3% glycerin, 0.8% thickener SIMULGEL FL (hydroxyethyl acrylate & sodium dimethyl taurate copolymer & isohexadecane & polysorbate 60), and the rest is water.

[0139] (2) Test process: The transdermal test was verified according to the in vitro transdermal test guidelines stipulated by the OECD / OCDE "European OECD Chemical Testing Guidelines". The specific operation method is as follows: During the experiment, the Strat-M artificial membrane was first placed in a phosphate buffer solution (pH 7.4) for 30 minutes. After hydration, the surface moisture of the artificial membrane was wiped dry and the artificial membrane was placed between the receiving pool and the supply pool of the Franz diffusion cell, with the smooth side facing the supply pool; the receiving pool contained phosphate buffer solution (pH 7.4); 0.1g of sample was added to the supply pool; the assembled Franz diffusion cell was placed in the transdermal diffusion instrument, and the experimental conditions were set as follows: temperature of 32°C, stirring speed of 600rpm, and penetration time of 12h. The receiving solution after sample penetration was taken, and in order to eliminate the interference of ceramide NP originally present in the skin, the skin retention amount of deuterated ceramide NP was quantified by LC-MS, thereby extrapolating the skin retention amount of ceramide NP in the sample. The specific data are shown in the attached Figure 4 shown.

[0140] Attached Figure 4 The comparison of the skin retention at different addition amounts of Example 1, Comparative Example 2 and Comparative Example 3 is shown. From the test results, it can be seen that after 12 hours of penetration, the skin retention of ceramide NP in Example 1 is 3.32ug / cm 2 , which is 2.27 times the retention amount of ceramide NP in comparative example 2 and 1.46 times the retention amount of ceramide NP in comparative example 3, indicating that the liposome precursor composition of the present invention significantly enhances the skin retention amount of ceramide NP in the skin, indicating that the preparation process of the liposome precursor composition of the present invention improves the transdermal absorption capacity of ceramide NP, helps ceramide NP to better repair the skin barrier in the skin and effectively exert its efficacy.

[0141] Effect Example 2

[0142] Human efficacy experiment of the liposome precursor composition of the present invention

[0143] The specific method of this experiment is as follows:

[0144] (1) Sample preparation: Prepare the facial creams for the treatment group and the control group of the human efficacy test according to the components and proportions in Table 5.

[0145] (2) Sample source: 10 Asian healthy adult subjects aged 18-50 years old used the treatment group cream (liposome precursor composition cream prepared in Example 1) and the control group cream (liposome precursor composition cream prepared in Control Group 2) on both sides of their cheeks, after cleansing their faces in the morning and evening every day, for 14 consecutive days. On the 0th day (T0), the 7th day (T1) and the 14th day (T2) of the test, the skin condition of the subjects was comprehensively tested using the facial image analyzer Antera 3D and the skin moisture tester Cutometer dual MPA580.

[0146] (3) Test results: Paired sample T test was used to analyze the changes in skin physiological indicators of the treatment group and the control group, with the test level α = 0.05. The results are shown in the attached Figure 5-7 shown.

[0147] Table 5 Cream ingredients and contents in treatment group and control group

[0148]

[0149]

[0150] Attached Figure 5 The test results of the subjects' skin moisture content improvement after using the treatment group cream and the control group cream for 7 and 14 days are shown. As can be seen from the figure, the subjects' skin moisture content is significantly improved after using the treatment group cream (liposome precursor composition cream) (p<0.05). After 7 days of use, the skin moisture content is increased by 24% compared with the initial value, which is 1.4 times the degree of improvement of the skin moisture content using the control group cream; after 14 days of use, the skin moisture content is increased by 64% compared with the initial value, which is 2.2 times the degree of improvement of the skin moisture content using the control group cream. The results show that the liposome precursor composition of the present invention can better moisturize the skin, exert its efficacy, and have a good moisturizing effect compared with the liposome precursor composition prepared by other formulas.

[0151] Attached Figure 6The test results of the skin reddening area of ​​the subjects after using the treatment group cream and the control group cream for 7 days and 14 days are shown. It can be seen from the figure that the reddening area of ​​the skin of the subjects decreased significantly after using the treatment group cream (liposome precursor composition cream) (p<0.05). After 7 days of use, the reddening area of ​​the skin decreased by 6% compared with the initial value of the reddening area of ​​the skin, which is 2.5 times the decrease in the reddening area of ​​the control group cream; after 14 days of use, the reddening area of ​​the skin decreased by 10% compared with the initial value of the reddening area of ​​the skin, which is 3.1 times the decrease in the reddening area of ​​the control group cream. The results show that the liposome precursor composition of the present invention can better relieve the symptoms of skin redness and play a soothing and repairing effect compared with the liposome precursor composition prepared by other formulas.

[0152] Attached Figure 7 The figure shows the facial test images of the subjects after using the treatment group cream added with Example 1 for 0 days, 7 days and 14 days. It can be seen from the figure that after the subjects used the treatment group cream (liposome precursor composition cream), the area of ​​skin redness decreased and the number of red blood streaks decreased, indicating that the liposome precursor composition of the present invention is suitable for improving skin redness and sensitivity, regulating skin barrier function, and alleviating symptoms of skin inflammation and damage.

[0153] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A liposome precursor composition, characterized in that: The liposome precursor composition comprises the following components in percentage by weight: 40-53% of polyol, 35-45% of panthenol, 10-15% of lecithin, and 2-4% of ceramide NP.

2. The liposome precursor composition according to claim 1, characterized in that The lecithin contains phosphatidylcholine, and the mass percentage of the phosphatidylcholine in the lecithin is ≥75%.

3. The liposome precursor composition according to claim 1 or 2, characterized in that The polyol is a short- to medium-chain polyol having 5 to 6 carbon atoms; and / or, the panthenol is D-panthenol; The lecithin is soybean lecithin or hydrogenated lecithin.

4. The liposome precursor composition according to claim 3, characterized in that The mass percentage of phosphatidylcholine in the soybean lecithin is ≥80%; And / or, the content of hydrogenated phosphatidylcholine in the hydrogenated lecithin is ≥95%.

5. The liposome precursor composition according to claim 3, characterized in that The polyol is at least one of 1,2-pentanediol and 1,2-hexanediol.

6. The liposome precursor composition according to claim 1, characterized in that The mass ratio of ceramide NP to lecithin is 1:(2.5-5); And / or, the mass ratio of the ceramide NP to panthenol is 1:(10-20).

7. A method for preparing the liposome precursor composition according to any one of claims 1 to 6, characterized in that: The preparation method comprises the following steps: (1) Weighing polyol, panthenol, lecithin and ceramide NP into a container, immersing and dissolving them in ethanol, and continuously stirring at 60-80° C. under a sealed condition to fully dissolve and disperse the components to obtain a clear and transparent liquid; (2) placing the clear transparent liquid obtained in step (1) in a flask, and performing rotary evaporation in a water bath at 40-70° C. under vacuum conditions until the ethanol is completely evaporated, and then continuing the rotary evaporation at room temperature until a uniform liquid film is formed on the inner wall of the flask, thereby obtaining a liposome precursor composition.

8. A skin care product, characterized in that: The skin product comprises the liposome precursor composition according to any one of claims 1 to 6.

9. The skin care product according to claim 8, wherein: The content of the liposome precursor composition in the skin product is 0.5-10%; And / or, the skin product is skin care lotion, skin care lotion, skin care cream, essence or facial mask liquid.

10. Use of the liposome precursor composition according to any one of claims 1 to 6 in skin products.

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