Multi-ceramide and phytosphingosine compound as well as preparation method and application thereof

Abstract

The invention discloses a multi-ceramide and phytosphingosine compound as well as a preparation method and application thereof, and belongs to the technical field of cosmetics. The preparation method comprises the following steps: combining multiple ceramides, compound phospholipid and cholesterol to form ceramide liposome with a double-layer membrane structure, and further embedding phytosphingosine into the membrane structure of the ceramide liposome to obtain a first phase; and the first phase is mixed with a second phase consisting of glycerol, hydrogenated phosphatidylcholine and purified water to obtain the multiple ceramide and phytosphingosine compound, so that the stability and bioavailability of ceramide are greatly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to a multi-ceramide and phytosphingosine complex and a preparation method and application thereof. Background Art

[0002] Ceramide is an important class of skin lipid components that plays an important role in maintaining skin barrier function and moisturizing properties. However, due to the characteristics of its chemical structure, ceramide has poor solubility in aqueous environments, which limits its widespread application in cosmetics. In traditional cosmetic formulations, in order to improve the solubility of ceramide, organic solvents or surfactants are often required, but these methods may cause irritation to the skin or affect the safety of the product.

[0003] In the cosmetics industry, in order to overcome this problem, researchers have been exploring new formulation technologies to improve the solubility and stability of ceramides. For example, by using specific liposome encapsulation technology or nanoemulsification technology, the dispersibility of ceramides in aqueous formulations can be significantly improved, thereby enhancing its applicability in cosmetics. In addition, some new carrier systems, such as solid lipid nanoparticles (SLNs) and porous silicon nanoparticles, have also been developed to improve the solubility and bioavailability of ceramides. Despite certain progress, how to balance the solubility, stability and skin absorbability of ceramides remains a major challenge in cosmetic research and development. Future research may focus on developing more efficient formulation technologies and exploring the synergistic effects of ceramides with other active ingredients to achieve better skin care effects. Summary of the invention

[0004] The main purpose of the present invention is to provide a multiple ceramide and phytosphingosine complex and a preparation method and application thereof, so as to solve the technical problem that ceramide has poor solubility and is difficult to improve its bioavailability.

[0005] To achieve the above object, the present invention provides a method for preparing a multi-ceramide phytosphingosine complex, comprising the following steps:

[0006] S10, dissolving ceramide, complex phospholipids, and cholesterol in an organic solvent to obtain a liposome solution;

[0007] S20, placing the liposome solution in a sealed container, heating to evaporate the organic solvent and vacuum suction to obtain a liposome film, then continuing to heat until the liposome film falls off, and performing ultrasonic dispersion to form a ceramide liposome solution;

[0008] S30, dissolving phytosphingosine in a solvent to form a phytosphingosine solution, extruding the ceramide liposome solution in step S20 to form ceramide liposome droplets and dispersing the droplets into the phytosphingosine solution to obtain a first phase;

[0009] S40, adding glycerol and hydrogenated phosphatidylcholine into purified water respectively, heating and stirring to dissolve and mix them evenly to obtain a second phase;

[0010] S50, adding the first phase into the second phase in a thin stream, and stirring in the same direction to obtain a multi-ceramide phytosphingosine complex;

[0011] The ceramide includes at least two of ceramide NP, ceramide AS, ceramide NS, ceramide EOS, ceramide AP, ceramide NDS, ceramide EOP, glucosylceramide and omega hydroxyceramide.

[0012] In some embodiments of the present invention, the complex lecithin comprises a mixture of soybean lecithin and hydrogenated soybean lecithin.

[0013] In some embodiments of the present invention, the weight ratio of ceramide, complex phospholipid and cholesterol is 5:(10-20):(10-20).

[0014] In some embodiments of the present invention, the heating temperature in step S20 is 75°C to 85°C.

[0015] In some embodiments of the present invention, in the step S30, ceramide liposome droplets are formed by extrusion through a filter membrane and dispersed into the phytosphingosine solution to obtain a first phase, and the filter membrane comprises a polycarbonate filter membrane.

[0016] In some embodiments of the present invention, the pore size of the filter membrane ranges from 30 nm to 80 nm.

[0017] In some embodiments of the present invention, the weight ratio of the glycerol, hydrogenated phosphatidylcholine and purified water is 10:(2-5):(50-80).

[0018] In some embodiments of the present invention, the mass ratio of the first phase to the second phase is 1:(50-80).

[0019] The present invention also provides a method for preparing a multiple ceramide phytosphingosine complex and the multiple ceramide phytosphingosine complex prepared therefrom.

[0020] The present invention also provides an application of the multi-ceramide phytosphingosine complex in the field of cosmetics.

[0021] The beneficial effects that can be achieved by the present invention are:

[0022] The present invention combines multiple ceramides, complex phospholipids and cholesterol to form ceramide liposomes with a double-layer membrane structure. The double-layer membrane structure of the liposome is similar to that of a biological cell membrane and has high biocompatibility. When applied to cosmetics, it is beneficial to promote skin absorption and exert the bioavailability of ceramide.

[0023] The present invention further embeds phytosphingosine into the membrane structure of the ceramide liposome to obtain the first phase, which can limit the swing of the fatty acid acyl chain in the double-layer membrane, reduce the fluidity of the membrane, improve the membrane structure stability of the ceramide liposome, prevent the precipitation and gelation of ceramide, and maintain the integrity of the membrane.

[0024] Furthermore, the present invention utilizes the hydrophilic groups exposed by phytosphingosine to form a densely arranged continuous water phase on the periphery of the ceramide liposome, which greatly enhances the water solubility of the ceramide liposome, allowing it to be widely used in various cosmetics. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0026] Figure 1 The present invention is a schematic diagram of the preparation process of a multi-ceramide phytosphingosine complex.

[0027] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0028] It should be understood that the specific embodiments described herein are only used to explain the present invention, and are not used to limit the present invention.

[0029] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] In the present invention, descriptions such as "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In addition, the technical solutions between the various embodiments can be combined with each other, but they must be based on the ability of ordinary technicians in the field to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0031] Ceramide is an important class of skin lipid components that plays an important role in maintaining skin barrier function and moisturizing properties. However, due to the characteristics of its chemical structure, ceramide has poor solubility in aqueous environments, which limits its widespread application in cosmetics.

[0032] In view of this, refer to Figure 1 The present invention provides a method for preparing a multi-ceramide phytosphingosine complex, comprising the following steps:

[0033] S10, dissolving ceramide, complex phospholipids, and cholesterol in an organic solvent to obtain a liposome solution;

[0034] S20, placing the liposome solution in a sealed container, heating to evaporate the organic solvent and vacuum suction to obtain a liposome film, then continuing to heat until the liposome film falls off, and performing ultrasonic dispersion to form a ceramide liposome solution;

[0035] S30, dissolving phytosphingosine in a solvent to form a phytosphingosine solution, extruding the ceramide liposome solution in step S20 to form ceramide liposome droplets and dispersing the droplets into the phytosphingosine solution to obtain a first phase;

[0036] S40, adding glycerol and hydrogenated phosphatidylcholine into purified water respectively, heating and stirring to dissolve and mix them evenly to obtain a second phase;

[0037] S50, adding the first phase into the second phase in a thin stream, and stirring in the same direction to obtain a multi-ceramide phytosphingosine complex.

[0038] The ceramide of the present invention includes at least two of ceramide NP, ceramide AS, ceramide NS, ceramide EOS, ceramide AP, ceramide NDS, ceramide EOP, glucosylceramide and omega hydroxyceramide. There are abundant varieties of ceramides, and multiple ceramide phytosphingosine complexes can be prepared from them. When applied to the skin, they can greatly enhance the skin barrier, improve the moisturizing effect, anti-inflammatory effect, promote skin repair and anti-aging effects. Multiple ceramides are co-loaded, reasonably matched, and synergistically enhanced, thereby improving the skin absorption capacity of ceramides in the formula.

[0039] In some embodiments, ceramides include ceramide NP, ceramide AS, ceramide NS, ceramide EOS, ceramide AP, ceramide NDS, ceramide EOP, glucosylceramide and omega hydroxyceramide. This embodiment does not limit the weight ratio of the above types of ceramides.

[0040] The present invention prepares a liposome solution through step S10. The liposome solution contains multiple ceramides and has a double-layer membrane structure. The double-layer membrane structure is similar to a biological cell membrane and has high biocompatibility. When applied to cosmetics, it is beneficial to promote skin absorption and improve the utilization effect of ceramide.

[0041] In some embodiments, the organic solvent in step S10 includes anhydrous ethanol, which can promote the dissolution of ceramide, complex phospholipids, and cholesterol.

[0042] In some embodiments, after ceramide, complex phospholipids and cholesterol are dispersed in an organic solvent, they are further subjected to ultrasonic dispersion treatment, which is beneficial to promote the uniform dispersion of ceramide, complex phospholipids and cholesterol, obtain a uniform liposome solution, and prevent the aggregation and precipitation of ceramide.

[0043] In some embodiments, step S20 is heated to 75° C. to 85° C., while ensuring the activity of ceramide, promoting the volatilization of organic solvents such as anhydrous ethanol. It is understood that heating to 75° C. to 85° C. includes the heating temperature at which the organic solvent is heated to evaporate and vacuum suction is performed to obtain a liposome film, and also includes the subsequent heating to a temperature at which the liposome film falls off.

[0044] In some embodiments, the complex lecithin comprises a mixture of soybean lecithin and hydrogenated soybean lecithin, and the weight ratio of soybean lecithin to hydrogenated soybean lecithin is 1:(1-2).

[0045] In some embodiments, the weight ratio of ceramide, complex phospholipid, and cholesterol is 5:(10-20):(10-20).

[0046] The multiple ceramide phytosphingosine complex of the present invention contains too many types of ceramides and too high a content, which may cause the ceramide liposomes to rupture and the ceramides to easily precipitate and crystallize. The liposome structure is unstable, which is not conducive to long-term storage or application in the preparation of cosmetics.

[0047] Therefore, the present invention further extrude the ceramide liposome solution into the phytosphingosine solution in step S30 to prepare the first phase. In the first phase, the phytosphingosine molecule contains a hydrophobic long-chain alkyl group and a hydrophilic polar head. The ceramide liposome is extruded and dispersed into the phytosphingosine solution. The hydrophobic long-chain alkyl group of the phytosphingosine can be embedded in the membrane structure of the ceramide liposome and parallel to the fatty acid chain, while the other end of the chain exposes the hydrophilic group. In this way, on the one hand, the swing of the fatty acid acyl chain can be restricted, the fluidity of the membrane can be reduced, the structural stability of the ceramide liposome can be improved, the precipitation of ceramide and the gelation of the liposome can be prevented, and the integrity of the membrane can be maintained. On the other hand, it also has good permeability and adsorption to skin tissue, and can form a firm and breathable protective film on the skin surface, effectively maintaining the moisture on the skin surface and promoting skin metabolism.

[0048] In some embodiments, the extrusion pressure is 40 MPa to 60 MPa. Under the above extrusion pressure, it is beneficial to extrude complete ceramide liposome droplets.

[0049] In some embodiments, ceramide liposomes are obtained by extrusion through a filter membrane.

[0050] In some embodiments, the filter membrane comprises a polycarbonate filter membrane.

[0051] In some embodiments, the pore size range of the filter membrane is 30nm to 80nm, for example, 30nm, 50nm, 70nm, 80nm, etc., any value in the range of 30nm to 80nm, thereby squeezing out ceramide liposome droplets with smaller particle sizes, increasing the specific surface area of ​​ceramide liposomes, and facilitating the embedding of phytosphingosine. The embedding of a large amount of phytosphingosine can greatly improve the stability of ceramide liposomes and prevent gelation. At the same time, a large number of hydrophilic groups are exposed on the periphery of ceramide liposomes, thereby improving the hydrophilic effect.

[0052] In some embodiments, phytosphingosine is dissolved in a solvent to form a phytosphingosine solution, and the solvent includes caprylic / capric triglyceride. Caprylic / capric triglyceride can easily disperse the phytosphingosine evenly, making it easy for the phytosphingosine to be embedded in the membrane structure of the ceramide liposome. Caprylic / capric triglyceride has good moisturizing and softening effects on the skin, and also has an emulsifying effect. After the ceramide liposome is dropped into the phytosphingosine solution, it is beneficial to obtain a uniform system.

[0053] The present invention connects phytosphingosine molecules to the membrane structure of the ceramide liposome and exposes the hydrophilic groups of the ceramide liposome, thereby obtaining good dispersibility and solubilization effects and having good emulsification properties. Even if the ceramide liposome contains different varieties and the ceramide content is too high, the ceramide liposome is not prone to precipitating ceramide outwards, thereby greatly reducing the risk of ceramide liposome gelation and improving its stability.

[0054] In some embodiments, after the ceramide liposomes are extruded and dispersed into a phytosphingosine solution by extrusion, ultrasonic treatment is further performed to further promote the dispersion of the ceramide liposomes, so that the phytosphingosine and the membrane structure of the ceramide liposomes are fully in contact, and a large amount of phytosphingosine is embedded in the membrane structure of the ceramide liposomes.

[0055] In some embodiments, the weight ratio of phytosphingosine to caprylic / capric triglyceride is 1:(5-10), which is conducive to obtaining a phytosphingosine solution with moderate consistency.

[0056] The first phase obtained in step S30 contains ceramide liposomes embedded with phytosphingosine, thereby improving the stability of the ceramide liposomes, and the exposed hydrophilic end of the phytosphingosine also gives it a certain hydrophilicity.

[0057] Therefore, in the present invention, in steps S40 and S50, the ceramide liposomes are further allowed to react with the second phase to form a tightly arranged continuous aqueous phase at the outermost periphery. The continuous aqueous phase coats the ceramide liposomes, thereby greatly enhancing the water solubility of the ceramide liposomes.

[0058] In some embodiments, the weight ratio of glycerol, hydrogenated phosphatidylcholine and purified water in the second phase is 5:(10-20):(10-20).

[0059] In some embodiments, the mass ratio of the first phase to the second phase is 1:(50-80), which can be 1:50, 1:60, 1:70, or 1:80, which is beneficial to improving the dispersibility of the first phase, so that each drop of ceramide liposome is coated by the second phase to form a continuous aqueous phase, thereby improving the water solubility and stability of the multi-ceramide phytosphingosine complex, so that it can be widely used in cosmetics, and greatly exerting the biological effects of ceramide.

[0060] In some embodiments, the present invention further adds a water-soluble penetration enhancer in the second phase, and the penetration enhancer includes one or more of inositol, dimethyl isosorbide, and bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate, preferably one or two of inositol and bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate. The addition of the penetration enhancer is conducive to the effective penetration of the active substance into the skin and long-term retention, sustained release, controlled release of the active substance, significantly increasing the skin retention of the active substance, and improving its transdermal penetration bioavailability.

[0061] The multiple ceramide phytosphingosine complex of the present invention has good stability and water solubility, and can be added to cosmetics as an additive. The cosmetics include the above multiple ceramide phytosphingosine complex and have at least all the beneficial effects of the multiple ceramide phytosphingosine complex.

[0062] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments. It should be understood that the following specific embodiments are only used to explain the present invention, and are not used to limit the present invention.

[0063] Example 1

[0064] Example 1 The preparation method of the multi-ceramide phytosphingosine complex is as follows:

[0065] S10. Dissolve ceramide, complex phospholipid and cholesterol in an organic solvent at a mass ratio of 5:10:10 to obtain a liposome solution, wherein the complex phospholipid is a mixture of soybean lecithin and hydrogenated soybean lecithin, and the weight ratio of soybean lecithin to hydrogenated soybean lecithin is 1:(1-2).

[0066] S20, placing the liposome solution in a sealed container, evaporating the organic solvent at 85° C., and vacuum-sucking to obtain a liposome film, and then continuing to heat until the liposome film falls off, and performing ultrasonic dispersion to form a ceramide liposome solution.

[0067] S30, dissolving phytosphingosine into caprylic / capric triglyceride at a weight ratio of 1:10 to form a phytosphingosine solution, extruding the ceramide liposome solution in step S20 to form ceramide liposome droplets and dispersing them into the phytosphingosine solution to obtain a first phase, wherein the film used for extrusion is a polycarbonate resin filter membrane with a pore size of 30 nm to 80 nm, and the extrusion pressure is 40 MPa to 60 MPa;

[0068] S40. Add glycerol and hydrogenated phosphatidylcholine into purified water at a weight ratio of 10:2:60, respectively, heat and stir to dissolve them, and mix them evenly to obtain a second phase.

[0069] S50. Add the first phase into the second phase in a thin stream at a weight ratio of 1:50, and stir in the same direction to obtain a multi-ceramide phytosphingosine complex.

[0070] The ceramide of this embodiment includes ceramides including ceramide NP, ceramide AS, ceramide NS, ceramide EOS, ceramide AP, ceramide NDS, ceramide EOP, glucosylceramide and omega hydroxyceramide, and the masses of various ceramides are the same.

[0071] Example 2

[0072] Example 2 was prepared by referring to the preparation method of Example 1, but the difference was that in Example 2, the first phase was added to the second phase in a thin stream at a weight ratio of 1:80, and stirred in the same direction to obtain a multi-ceramide phytosphingosine complex.

[0073] Example 3

[0074] Example 3 was prepared by referring to the preparation method of Example 1, but the difference was that in step S10, ceramide, complex phospholipid and cholesterol were dissolved in an organic solvent at a mass ratio of 5:10:20 to obtain a liposome solution.

[0075] Comparative Example 1

[0076] Comparative Example 1 was prepared by referring to the preparation method of Example 1, but the difference was that Comparative Example 1 did not perform subsequent steps S30 to S50.

[0077] Comparative Example 2

[0078] Comparative Example 2 was prepared by referring to the preparation method of Example 1, but the difference was that step S30 was not performed in Comparative Example 2, and the ceramide liposome solution obtained in step S10 was directly extruded to form ceramide liposome droplets which were dispersed in the second phase.

[0079] Comparative Example 3

[0080] Comparative Example 3 was prepared by referring to the preparation method of Example 1, but the difference is that the second phase was not prepared in Comparative Example 3, and the first phase obtained in step S30 was used as the final product.

[0081] Performance Testing

[0082] 1. Place the multi-amide phytosphingosine complex at 25°C in a room and observe its stability on day 0, day 7, and day 14. This test record is Group A.

[0083] 2. The products prepared in Examples 1 to 3 and Comparative Examples 1 to 3 and the aqueous solution were uniformly mixed in a mass ratio of 1:10, allowed to stand at 25°C indoors, and their stability was observed on the 0th, 7th and 14th days, and recorded as Group B.

[0084] Table 1

[0085]

[0086] It can be seen from Table 1 that the multi-ceramide phytosphingosine complexes prepared in Examples 1 to 3 have good stability both by themselves and after being added to the aqueous solution.

[0087] The main components of the ceramide liposomes in Comparative Example 1 only contained ceramide, complex phospholipids and cholesterol. Group A precipitated crystals on the 7th day and became turbid, while Group B became turbid immediately after the addition of the aqueous solution.

[0088] In Comparative Example 2, phytosphingosine was not embedded in the membrane structure of ceramide liposomes. The stability of Group A and Group B was relatively poor. Crystals precipitated on the 14th day and the mixture became turbid.

[0089] In Comparative Example 3, no second phase was prepared and no continuous aqueous phase was used for coating. Group A had better stability and only slight turbidity was observed on the 14th day. However, after the aqueous solution was added to Group B, crystals precipitated on the 14th day and the mixture became turbid.

[0090] The above are only preferred embodiments of the present invention, and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A method for preparing a multi-ceramide phytosphingosine complex, comprising the following steps: S10, dissolving ceramide, complex phospholipids, and cholesterol in an organic solvent to obtain a liposome solution; S20, placing the liposome solution in a sealed container, heating to evaporate the organic solvent and vacuum suction to obtain a liposome film, then continuing to heat until the liposome film falls off, and performing ultrasonic dispersion to form a ceramide liposome solution; S30, dissolving phytosphingosine in a solvent to form a phytosphingosine solution, extruding the ceramide liposome solution in step S20 to form ceramide liposome droplets and dispersing the droplets into the phytosphingosine solution to obtain a first phase; S40, adding glycerol and hydrogenated phosphatidylcholine into purified water respectively, heating and stirring to dissolve and mix them evenly to obtain a second phase; S50, adding the first phase into the second phase in a thin stream, and stirring in the same direction to obtain a multi-ceramide phytosphingosine complex; The ceramide includes at least two of ceramide NP, ceramide AS, ceramide NS, ceramide EOS, ceramide AP, ceramide NDS, ceramide EOP, glucosylceramide and omega hydroxyceramide.

2. The method for preparing the multi-ceramide phytosphingosine complex according to claim 1, characterized in that: The complex lecithin comprises a mixture of soybean lecithin and hydrogenated soybean lecithin.

3. The method for preparing the multiple ceramide phytosphingosine complex according to claim 1, characterized in that: The weight ratio of ceramide, complex phospholipid and cholesterol is 5:(10-20):(10-20).

4. The method for preparing the multiple ceramide phytosphingosine complex according to claim 1, characterized in that: The heating temperature in step S20 is 75°C to 85°C.

5. The method for preparing the multi-ceramide phytosphingosine complex according to claim 1, characterized in that: In the step S30, ceramide liposome droplets are formed by extrusion through a filter membrane and dispersed into the phytosphingosine solution to obtain a first phase, and the filter membrane includes a polycarbonate filter membrane.

6. The method for preparing the multiple ceramide phytosphingosine complex according to claim 5, characterized in that: The pore size of the filter membrane ranges from 30 nm to 80 nm.

7. The method for preparing the multiple ceramide phytosphingosine complex according to claim 1, characterized in that: The weight ratio of the glycerol, hydrogenated phosphatidylcholine and purified water is 10:(2-5):(50-80).

8. The method for preparing the multi-ceramide phytosphingosine complex according to claim 1, characterized in that: The mass ratio of the first phase to the second phase is 1:(50-80).

9. The multiple ceramide phytosphingosine complex prepared according to the method for preparing the multiple ceramide phytosphingosine complex according to any one of claims 1 to 8.

10. Use of the multi-ceramide phytosphingosine complex according to claim 9 in the field of cosmetics.

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