A method for preparing a ceramide

Abstract

This invention relates to the field of cosmetics, and in particular to a method for preparing ceramides. The preparation method includes the following steps: mixing a fatty acyl halide, a sphingosine compound, a reaction solvent, and an acid-binding agent; reacting the mixture to obtain a ceramide mixture; and hydrolyzing the ceramide mixture under alkaline conditions to obtain ceramides. This invention utilizes the acyl halide method to prepare ceramides, significantly reducing the addition of other reaction reagents. Furthermore, after the reaction is complete, an alkali is used to hydrolyze the byproduct esterification to convert it into ceramide products. This not only improves the reaction yield but also reduces the residue of byproducts in the final ceramide product. The ceramide synthesis process of this invention eliminates the need for complex and lengthy post-processing operations, requiring only separation, concentration, and crystallization. This not only improves the quality of ceramides but also significantly shortens the production cycle and reduces production costs, giving it a clear competitive advantage in the market.

Description

Technical Field

[0001] This invention relates to the field of cosmetics, and in particular to a method for preparing ceramides. Background Technology

[0002] Ceramides are natural lipid components composed of sphingosine and long-chain fatty acids linked by amide bonds. They are widely found in the stratum corneum of human skin and play an important role in maintaining skin barrier function, moisturizing and locking in moisture, and delaying aging. With the increasing demand for repair products in the cosmetics industry, the application of ceramides is becoming increasingly widespread.

[0003] Currently, the main methods for obtaining ceramides fall into two categories: natural extraction and chemical synthesis. Natural extraction uses plants and animals as sources, but it is limited by factors such as low ceramide content in raw materials, high extraction costs, and inconsistent product quality, making it difficult to meet the needs of large-scale commercial production. Furthermore, ceramides extracted from animal tissues may be contaminated with pathogens, which restricts their application in cosmetics and other applications where human safety is paramount. In contrast, chemical synthesis uses sphingosine compounds as substrates, preparing ceramides through an amidation reaction between fatty acids and sphingosine. This method yields products with a single component and a defined structure, and allows for the rapid construction of functionally similar ceramide derivatives, expanding their application range. Therefore, it has become the mainstream preparation method.

[0004] In chemical synthesis, the carbodiimide condensing agent method is one of the more common synthetic strategies. This method uses carbodiimide compounds such as dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) as condensing agents, and simultaneously adds condensation activators such as 4-N,N-dimethylpyridine (DMAP) and 1-hydroxy-benzotriazole (HOBT) to carry out the amidation reaction. The reaction formula is as follows:

[0005] Carbodiimide condensing agents activate carboxylic acids to form reactive intermediates, which then react with amino groups to form amide bonds. However, this method requires both the condensing agent and the activator to be added in stoichiometric quantities, resulting in a complex reaction system, high byproduct content, and increased difficulty in product quality control.

[0006] The mixed anhydride method is another commonly used amidation strategy. In this method, a carboxylic acid reacts with a sulfonyl chloride to generate a mixed anhydride of carboxylic acid and sulfonic acid, which then reacts with an amine to give the corresponding amide. Commonly used sulfonyl chlorides include methanesulfonyl chloride (MsCl), p-toluenesulfonyl chloride (TsCl), and p-nitrobenzenesulfonyl chloride (NsCl). The reaction formula is as follows:

[0007]

[0008] However, the sulfonyl chloride reagents and their derivatives (such as methanesulfonic acid, p-toluenesulfonic acid, p-nitrobenzoic acid, etc.) introduced by this method may undergo side reactions with lower alcohols in subsequent reactions to generate sulfonate esters. Sulfonate esters are a class of potentially genotoxic impurities, posing a safety risk to the subsequent formulation and application of ceramides.

[0009] Therefore, there is an urgent need to develop a method for preparing ceramides that has mild reaction conditions, is easy to operate, produces controllable byproducts, uses readily available raw materials, and is suitable for industrial production. Summary of the Invention

[0010] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a method for preparing ceramides, which solves the problems of uncontrollable byproducts, complex operation, and uncontrollable quality of the obtained ceramides in the prior art during the synthesis process.

[0011] To achieve the above and other related objectives, the present invention is obtained through the following technical solution.

[0012] The first aspect of this invention is to provide a method for preparing ceramides, the method comprising the following steps:

[0013] (1) Mix fatty acyl halides, sphingosine compounds, reaction solvents and acid-binding agents, and react to obtain a ceramide mixture;

[0014] (2) The ceramide mixture is hydrolyzed under alkaline conditions to obtain ceramide.

[0015] A second aspect of the present invention is to provide a ceramide prepared by the preparation method described above.

[0016] A third aspect of the present invention is to provide ceramides prepared by the preparation method described above, and / or the use of the ceramides described above in the preparation of cosmetics.

[0017] A fourth aspect of the present invention is to provide a cosmetic product comprising the ceramide prepared by the method described above.

[0018] As described above, the method for preparing ceramide according to the present invention has the following beneficial effects:

[0019] 1. The present invention provides a method for preparing ceramides, using fatty acyl halides and sphingosine compounds as reaction substrates, with mild reaction conditions and simple operation;

[0020] 2. Through the study of the reaction mechanism, this invention, after the reaction is completed, adds a small amount of alkaline solution to hydrolyze the reaction byproducts into the target product, thereby improving the reaction yield, reducing reaction byproducts, and ensuring the quality of the ceramide product.

[0021] 3. Fatty acid acyl halides, especially fatty acyl chlorides, are already chemicals produced on a large scale in industry. Therefore, the fatty acyl halides selected in this invention are very readily available raw materials, which have an industrial cost advantage.

[0022] 4. Compared with previously reported methods, this invention has relative advantages in terms of ceramide quality control, production scale-up feasibility, and cost control, and is a highly innovative and novel method. Attached Figure Description

[0023] Figure 1 The image shown is an HPLC chromatogram of ceramide NP obtained in Example 1 of this invention.

[0024] Figure 2 The image shown is an HPLC chromatogram of the ceramide NDS prepared in Example 2 of this invention.

[0025] Figure 3 The image shown is an HPLC chromatogram of ceramide NS obtained in Example 3 of this invention.

[0026] Figure 4 The image shown is an HPLC chromatogram of the mixed ceramides prepared in Example 4 of this invention.

[0027] Figure 5 The figure shown is the HPLC chromatogram of ceramide NP prepared in Comparative Example 1 of this invention.

[0028] Figure 6 The figure shown is the HPLC chromatogram of ceramide NP prepared in Comparative Example 2 of this invention. Detailed Implementation

[0029] To make the inventive objectives, technical solutions, and beneficial effects of this invention clearer, the invention will be further described in detail below with reference to embodiments. Those skilled in the art can easily understand other advantages and effects of this invention from the content disclosed in this specification.

[0030] Generally, the nomenclature used herein (e.g., IUPAC nomenclature) and the laboratory procedures described below (including those for cell culture, organic chemistry, analytical chemistry, and pharmacology) are those well-known and commonly used in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0031] In this invention, "at least one" means one or more, such as one, two, or more. "Multiple" or "several" means at least two, such as two, three, etc., and "multi-layered" means at least two layers, such as two layers, three layers, etc., unless otherwise explicitly specified. In the description of this invention, "several" means at least one, such as one, two, etc., unless otherwise explicitly specified.

[0032] When a numerical range is disclosed herein, the range is considered continuous and includes the minimum and maximum values ​​of the range, as well as every value between the minimum and maximum values. Furthermore, when the range refers to integers, it includes every integer between the minimum and maximum values ​​of the range. Additionally, when multiple ranges are provided to describe a feature or characteristic, the ranges may be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges to which they are incorporated.

[0033] This invention provides a method for preparing ceramides, which uses fatty acyl halides and sphingosine compounds as reaction substrates, and carries out a condensation reaction under mild reaction conditions. This method is simple to operate and easy to control. After the reaction is complete, a small amount of alkaline solution is added to the reaction system. Based on in-depth research into the reaction mechanism, the inventors discovered that byproducts generated during the reaction (such as byproducts of esterification with sphingosine compounds) are usually removed as impurities in conventional processing. However, this invention, through alkaline treatment, can hydrolyze these byproducts in situ, directly converting them into the target product, ceramide. This "turning waste into treasure" strategy not only significantly improves the overall reaction yield but also reduces byproduct residues at the source, thereby effectively ensuring the chemical purity and quality consistency of the finished ceramide product.

[0034] Furthermore, the fatty acyl halides (especially fatty acyl chlorides) used in this invention are mature chemicals produced on a large industrial scale, with ample market supply and low cost. This contrasts sharply with existing technologies that rely on expensive or difficult-to-obtain acylation reagents, giving this invention significant advantages in terms of raw material accessibility and production cost control. Therefore, this invention is superior to previously reported methods in terms of reaction yield, product quality, feasibility of production scale-up, and overall cost control.

[0035] This invention addresses the problem of difficulty in suppressing esterification byproducts during the preparation of ceramides via the fatty acyl halide process. It proposes a synergistic control method combining process inhibition and post-treatment conversion. On one hand, by precisely controlling the dropping rate of the fatty acyl halide, the amount of esterification byproducts generated is significantly reduced at the source. On the other hand, after the reaction is complete, alkali is added for hydrolysis, converting the small amount of esterification byproducts already generated into the target ceramide. This method extends conventional single-stage process control to a two-stage linkage of "inhibition-conversion," effectively reducing the accumulation of byproducts, improving the purity of the reaction solution, and yielding high-purity ceramides after post-treatment.

[0036] The first aspect of this invention is to provide a method for preparing ceramides, the method comprising the following steps:

[0037] (1) Mix fatty acyl halides, sphingosine compounds, reaction solvents and acid-binding agents, and react to obtain a ceramide mixture;

[0038] (2) The ceramide mixture is hydrolyzed under alkaline conditions to obtain ceramide.

[0039] This invention provides a simple, easy-to-operate, and high-quality-control method for preparing ceramides. This invention utilizes the acyl halide method to prepare ceramides, significantly reducing the need for other reaction reagents. Furthermore, after the reaction, an alkali is used to hydrolyze the byproduct esterification, converting it into ceramide products. This not only improves the reaction yield but also reduces the residue of byproducts in the final ceramide product. The ceramide synthesis process of this invention eliminates the need for complex and lengthy post-processing after the reaction; only separation, concentration, and crystallization are required. This not only improves the quality of ceramides but also significantly shortens the production cycle and reduces production costs, giving it a clear competitive advantage in the market.

[0040] In some embodiments of the present invention, in step (1), the molar ratio of the fatty acyl halide and the sphingosine compound is 1-1.5:1; for example, 1-1.2:1 or 1.2-1.5:1.

[0041] In some embodiments of the present invention, in step (1), the acid-binding agent is selected from one or more of organic or inorganic bases; the organic base is selected from one or more of triethylamine, pyridine, or diisopropylethylamine; and the inorganic base is selected from one or more of Na2CO3, NaHCO3, K2CO3, NaOH, or KOH.

[0042] In some embodiments of the present invention, in step (1), the reaction solvent is selected from one or more of tetrahydrofuran, dimethyltetrahydrofuran, or 1,4-dioxane;

[0043] In some embodiments of the present invention, in step (1), the reaction temperature is 0-30°C; for example, 0-8°C, 8-15°C, 15-23°C, 23-30°C; and the reaction time is 6-12h; for example, 6-7.5h, 7.5-9h, 9-10.5h, 10.5-12h.

[0044] In some embodiments of the present invention, in step (1), the molar ratio of the acid-binding agent to the sphingosine compound is 1-1.5:1; for example, 1-1.2:1 or 1.2-1.5:1.

[0045] In some embodiments of the present invention, in step (1), the mass ratio of the sphingosine compound to the reaction solvent is 1:5-12. For example, it is 1:5-8 or 1:8-12.

[0046] In some embodiments of the present invention, in step (1), the fatty acyl halide is a C10-C30 fatty acyl halide; preferably, the fatty acyl halide is selected from one or more of myristoyl chloride, stearoyl chloride, palmitoyl chloride, oleoyl chloride, linoleoyl chloride, linolenic acid chloride, myristoyl bromide, stearoyl bromide, palmitoyl bromide, oleoyl bromide, linolenic acid bromide or linolenic acid bromide.

[0047] In some embodiments of the present invention, in step (1), the sphingosine compound is selected from one or more of phytosphingosine, neurosphingosine, dihydrosphingosine, or 6-hydroxysphingosine;

[0048] In some embodiments of the present invention, in step (2), the alkali used for the alkaline conditions is selected from one or more of sodium hydroxide or potassium hydroxide; the weight ratio of the alkali to the sphingosine compound is 0.2-0.6:1; for example, 0.2-0.4:1 or 0.4-0.6:1.

[0049] In some embodiments of the present invention, in step (2), the temperature of the hydrolysis reaction is 40-50°C, for example, 40-42°C, 42-44°C, 44-46°C, or 46-50°C; and the reaction time is 3-6 hours, for example, 3-4 hours, 4-5 hours, or 5-6 hours.

[0050] In some embodiments of the present invention, in step (2), the hydrolysis reaction is followed by post-treatment to obtain ceramide. The post-treatment operation is as follows: the reactants obtained from the hydrolysis reaction are allowed to stand and separated to obtain organic phase one. Organic phase one is acid washed and separated to obtain organic phase two. Organic phase two is concentrated, a crystallization solvent is added, the temperature is raised, and then the temperature is lowered to crystallize. The mixture is filtered, washed, and a filter cake is obtained. The obtained filter cake is then slurried with methanol once and dried to obtain ceramide.

[0051] In some embodiments of the present invention, the crystallization solvent is an alcohol solvent; preferably, the alcohol solvent is a C1-C10 alcohol; more preferably, the crystallization solvent is selected from one or more of methanol, ethanol, isopropanol or n-butanol.

[0052] In some embodiments of the present invention, the drying temperature is 40-65°C; for example, 40-46°C, 46-52°C, 52-58°C, or 58-65°C; and the drying time is 5-12 hours; for example, 5-7 hours, 7-9 hours, 9-11 hours, or 11-12 hours.

[0053] A second aspect of the present invention is to provide a ceramide prepared by the preparation method described above.

[0054] In this invention, the above preparation method can be used to prepare various ceramides with different structures, including but not limited to the following structural formulas:

[0055] .

[0056] In some embodiments of the present invention, the above-mentioned ceramides play a role in promoting skin hydration, repairing skin, and soothing skin.

[0057] A third aspect of the present invention is to provide ceramides prepared by the preparation method described above, and / or the use of the ceramides described above in the preparation of cosmetics.

[0058] A fourth aspect of the present invention is to provide a cosmetic product comprising the ceramide prepared by the method described above.

[0059] In some embodiments of the present invention, the cosmetics include at least daily chemical industrial products that are applied to any part of the human body surface (skin, hair, nails, lips, etc.) by rubbing, spraying or similar methods to achieve the purposes of cleaning, removing unpleasant odors, skin care, beauty and decoration. Specifically, they may include, but are not limited to, lotions and creams, such as hand cream, face cream, skin lotion, etc.

[0060] In some embodiments of the present invention, the cosmetic may further include other ingredients, such as thickeners, emulsifiers, preservatives, moisturizers (e.g., hyaluronic acid, sodium hyaluronate, propylene glycol, butylene glycol, panthenol, etc.), antioxidants (e.g., vitamin E, vitamin C), preservatives such as parabens, active ingredients (e.g., retinol, nicotinamide), occlusive agents (e.g., petrolatum, lanolin, cetyl alcohol, mineral oil, siloxane derivatives, etc.), soothing agents (e.g., allantoin, urea), various plant extracts (centella asiatica extract, purslane extract, bisabolol, dipotassium glycyrrhizate), whitening ingredients (e.g., niacinamide, arbutin, vitamin C, phenylethyl resorcinol, tranexamic acid, glutathione, kojic acid, etc.), anti-aging ingredients (e.g., retinol), and acne-fighting ingredients (e.g., azelaic acid, salicylic acid, fruit acids, etc.). Those skilled in the art can select appropriate ingredients according to actual needs.

[0061] In some embodiments of the present invention, the cosmetic can be prepared by mixing the ceramide provided by the present invention with other ingredients in the cosmetic.

[0062] The present invention will be further illustrated by the following examples, but these examples do not limit the scope of the invention.

[0063] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments whose manufacturers are not specified are conventional products that can be purchased commercially. In addition to the specific methods, equipment, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, equipment, and materials similar to or equivalent to those described, used, and materials in the embodiments of this invention may be used to implement this invention.

[0064] The CAS number of the plant sphingosine of this invention is 554-62-1; the manufacturer is Chongqing Zhihe Biomedical Co., Ltd.

[0065] The CAS number of the dihydrosphingosine of this invention is 764-22-7; the manufacturer is Chongqing Zhihe Biomedical Co., Ltd.

[0066] The CAS number of the sphingosine of this invention is 123-78-4; the manufacturer is Chongqing Zhihe Biomedical Co., Ltd.

[0067] The CAS number of the 6-hydroxysphingosine of this invention is 566203-07-4; the manufacturer is Chongqing Zhihe Biomedical Co., Ltd.

[0068] The manufacturer of the fatty acyl halide of this invention is Chongqing Zhihe Biomedical Co., Ltd.

[0069] Example

[0070] Example 1 (Ceramide NP)

[0071]

[0072] This embodiment provides a method for preparing ceramide, including the following steps:

[0073] 50.0 g of phytosphoprotein, 300 g of tetrahydrofuran, and 16 g of triethylamine were added to a reactor. The temperature was lowered to 0-3°C, and 52.2 g of oleoyl chloride was slowly added dropwise over 5 hours. After 2 hours of addition, 100.0 g of water and 50 g of 40% sodium hydroxide were added to the reaction solution, and the temperature was raised to 40-43°C and stirred for 5 hours. The mixture was allowed to stand and separated. The organic phase was washed with 100 g of 20% citric acid and then separated again. After concentrating the organic phase, 400.0 g of methanol was added, and the temperature was raised to 55°C. The mixture was then cooled to crystallize, filtered, and washed with 100 g of methanol. The resulting filter cake was then slurried once more with methanol and dried at 55°C for 6 hours to obtain 74.3 g of a white solid with a purity of 96.0% (HPLC chromatogram shown). Figure 1 The yield was 81.1%.

[0074] Example 2 (Ceramide NDS)

[0075]

[0076] This embodiment provides a method for preparing ceramide, including the following steps:

[0077] 50.0 g of dihydrosphingosine, 300 g of tetrahydrofuran, and 27.5 g of potassium carbonate were added to a reactor. The temperature was lowered to 5-8 °C, and 52.8 g of stearoyl chloride was slowly added dropwise over 7 hours. After the addition was complete, the reaction was allowed to proceed for 1.5 hours. Then, 100.0 g of water and 50 g of 40% potassium hydroxide were added to the reaction mixture, and the temperature was raised to 42-45 °C with stirring for 3 hours. The mixture was allowed to stand and separated. The organic phase was washed with 100 g of 20% citric acid and then separated again. After concentrating the organic phase, 500.0 g of ethanol was added, and the temperature was raised to 55 °C. The mixture was then cooled to crystallize, filtered, and washed with 100 g of ethanol. The resulting filter cake was then slurried once more with ethanol and dried at 50 °C for 8 hours to obtain 84.3 g of a white solid with a purity of 97.0% (HPLC chromatogram shown). Figure 2 The yield was 89.4%.

[0078] Example 3 (Ceramide NS)

[0079]

[0080] This embodiment provides a method for preparing ceramide, including the following steps:

[0081] 50.0 g of sphingosine, 400 g of 1,4-dioxane, and 18.6 g of triethylamine were added to a reactor. The temperature was lowered to 0-3°C, and 55.7 g of stearoyl chloride was slowly added dropwise over 6 hours. After the addition was complete, the reaction was allowed to proceed for 2 hours. Then, 100.0 g of water and 50 g of 40% sodium hydroxide were added to the reaction solution, and the temperature was raised to 45-48°C with stirring for 4 hours. The mixture was allowed to stand and separated. The organic phase was washed with 100 g of 20% citric acid and then separated again. After concentrating the organic phase, 400.0 g of ethanol was added, and the temperature was raised to 60°C. The mixture was then cooled to crystallize, filtered, and washed with 100 g of ethanol. The resulting filter cake was then slurried once more with ethanol and dried at 55°C for 7 hours to obtain 75.5 g of a white solid with a purity of 95.7% (HPLC chromatogram shown). Figure 3 The yield was 79.8%.

[0082] Example 4 Mixed Ceramides

[0083]

[0084] This embodiment provides a method for preparing ceramide, including the following steps:

[0085] Add 50.0g of phytosphohydrin, 400g of tetrahydrofuran, and 16.3g of triethylamine to a reactor. Cool the mixture to 5-8℃ and slowly add 56.8g of low-purity fatty acyl halide (of which oleoyl chloride >80%) dropwise over 6 hours. After the dropwise addition is complete, react for 3 hours. Add 100.0g of water and 50g of 40% potassium hydroxide to the reaction mixture, heat to 40-43℃, and stir for 3 hours. Allow the mixture to stand and separate the liquids. Wash the organic phase with 100g of 20% citric acid, then separate the liquids again. After concentrating the organic phase, add 500.0g of methanol, heat to 60℃, cool to crystallize, filter, and wash with 100g of methanol. The resulting filter cake was then slurried once more with methanol and dried at 55°C for 8 hours to obtain 76.2 g of a mixed ceramide white solid. The total purity of the mixed ceramides was 96.1%; the purity of oleic acid ceramide was 89.5%, linoleic acid ceramide was 4.4%, stearic acid ceramide was 0.5%, and palmitic acid ceramide was 1.7%, with a yield of 83.2%. HPLC chromatograms are shown below. Figure 4 .

[0086] Comparative Example

[0087] Comparative Example 1 (Ceramide NP)

[0088]

[0089] This comparative example provides a method for preparing ceramide, comprising the following steps:

[0090] 10g of phytosphoprotein, 10.2g of oleic acid, 4.5g of HOBT, and 60g of tetrahydrofuran were dissolved at room temperature with stirring. 4.8g of DIC was added, and the mixture was heated to 30-33℃ and reacted for 4 hours. After 4 hours, the reaction was stopped, and the mixture was washed twice with 100g of 5% sodium chloride solution each time. The organic phase was concentrated, and 80g of methanol was added. The mixture was heated to 55℃, cooled to crystallize, filtered, and washed with 2g of methanol. The resulting filter cake was then slurried once more with methanol and dried at 55℃ for 6 hours to obtain 11.3g of a white solid with a purity of 89.3% (HPLC chromatogram shown). Figure 5 The yield was 61.7%. The above experiments show that the method using carbodiimide condensing agents suffers from reduced product purity and yield because the large amount of HOBT and DIC added cannot be completely removed during post-processing, and this method also produces many reaction byproducts.

[0091] Comparative Example 2 (Ceramide NP)

[0092]

[0093] This comparative example provides a method for preparing ceramide, comprising the following steps:

[0094] 50.0 g of phytosphingosine, 300 g of tetrahydrofuran, and 16 g of triethylamine were added to a reactor. The temperature was lowered to 0-3°C, and 52.2 g of oleoyl chloride was slowly added dropwise over 5 hours. After 2 hours of addition, 100.0 g of water was added to the reaction solution, and the temperature was raised to 40-43°C and stirred for 5 hours. The mixture was allowed to stand and separated. The organic phase was washed with 100 g of 20% citric acid and then separated again. After concentrating the organic phase, 400.0 g of methanol was added, and the temperature was raised to 55°C. The mixture was then cooled to crystallize, filtered, and washed with 100 g of methanol. The resulting filter cake was then slurried once more with methanol and dried at 55°C for 6 hours to obtain 61.8 g of a white solid with a purity of 91.9% (HPLC chromatogram shown). Figure 6 The yield was 67.5%.

[0095] The above experiments show that by simply omitting the hydrolysis step with the addition of alkali, while keeping all other steps unchanged according to the present invention, the purity of the prepared ceramide is significantly reduced. This is because without the addition of alkali for hydrolysis, there are relatively more byproducts in the post-processing, thus reducing the purity and yield of the prepared ceramide.

[0096] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A method for preparing ceramide, characterized in that, The preparation method includes the following steps: (1) Mix fatty acyl halides, sphingosine compounds, reaction solvents and acid-binding agents, and react to obtain a ceramide mixture; (2) The ceramide mixture is hydrolyzed under alkaline conditions to obtain ceramide.

2. The method for preparing ceramide according to claim 1, characterized in that: It also includes one or more of the following features: 11) In step (1), the molar ratio of the fatty acyl halide and the sphingosine compound is 1-1.5:1; 12) In step (1), the acid-binding agent is selected from one or more organic or inorganic bases; 13) In step (1), the reaction solvent is selected from one or more of tetrahydrofuran, dimethyltetrahydrofuran, or 1,4-dioxane; 14) In step (1), the reaction temperature is 0-30℃; the reaction time is 6-12h; 15) In step (1), the molar ratio of the acid-binding agent to the sphingosine compound is 1-1.5:1; 16) In step (1), the mass ratio of the sphingosine compound to the reaction solvent is 1:5-12.

3. The method for preparing ceramide according to claim 2, characterized in that: It also includes one or more of the following features: 111) In feature 11), the fatty acyl halide is a C10-C30 fatty acyl halide; 112) In feature 11), the sphingosine compound is selected from one or more of phytosphingosine, neurosphingosine, dihydrosphingosine, or 6-hydroxysphingosine; 121) In feature 12), the organic base is selected from one or more of triethylamine, pyridine, or diisopropylethylamine; 122) In feature 12), the inorganic base is selected from one or more of Na2CO3, NaHCO3, K2CO3, NaOH or KOH.

4. The method for preparing ceramide according to claim 3, characterized in that: In feature 111), the fatty acyl halide is selected from one or more of myristoyl chloride, stearoyl chloride, palmitoyl chloride, oleoyl chloride, linoleoyl chloride, linolenic acid chloride, myristoyl bromide, stearoyl bromide, palmitoyl bromide, oleoyl bromide, linolenic acid bromide or linolenic acid bromide.

5. The method for preparing ceramide according to claim 1, characterized in that: It also includes one or more of the following features: 21) In step (2), the alkali used for the alkaline conditions is selected from one or more of sodium hydroxide or potassium hydroxide; 22) In step (2), the temperature of the hydrolysis reaction is 40-50℃ and the reaction time is 3-6h; 23) In step (2), after the hydrolysis reaction, ceramide is obtained through post-treatment. The post-treatment operation is as follows: the reactants obtained from the hydrolysis reaction are allowed to stand and separated to obtain organic phase one. Organic phase one is acid washed and separated to obtain organic phase two. Organic phase two is concentrated, crystallization solvent is added, the temperature is raised, and then the temperature is lowered to crystallize. The mixture is filtered, washed, and a filter cake is obtained. The obtained filter cake is then slurried with methanol once and dried to obtain ceramide.

6. The method for preparing ceramide according to claim 5, characterized in that: It also includes one or more of the following features: 211) In feature 21), the weight ratio of the base to the sphingosine compound is 0.2-0.6:1; 231) In feature 23), the crystallization solvent is an alcohol solvent; preferably, the alcohol solvent is a C1-C10 alcohol; 232) In feature 23), the drying temperature is 40-65℃; the drying time is 5-12h.

7. The method for preparing ceramide according to claim 6, characterized in that: In feature 231), the crystallization solvent is selected from one or more of methanol, ethanol, isopropanol or n-butanol.

8. A ceramide, characterized in that: It is prepared by the preparation method described in any one of claims 1-7.

9. The ceramide prepared by the method according to any one of claims 1-7, and / or the ceramide according to claim 8, in the preparation of cosmetics.

10. A cosmetic product, characterized in that: Including ceramides prepared by the method according to any one of claims 1-7.

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