Branched-chain ceramide with excellent dissolving property as well as preparation method and application of branched-chain ceramide
By introducing branched-chain ceramides with a branched structure, a green synthesis process was used to solve the problem of poor solubility of traditional ceramides, achieving high concentration addition and long-term stability, thereby improving the production efficiency and user experience of cosmetics.
Patent Information
- Application Number
- CN202511581513.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-31
- Publication Date
- 2026-01-23
AI Technical Summary
Most existing ceramide raw materials have a traditional linear structure, which has poor solubility, resulting in limited addition amounts in cosmetics. The production process is complex and unstable, making it difficult to achieve optimal efficacy, and they are prone to precipitation and turbidity during storage.
By introducing branched-chain ceramides with branched structures, and using green synthesis processes such as chemical condensation or lipase catalysis, the melting point is lowered and the solubility is improved, making them suitable for a variety of cosmetic formulation systems.
It achieves high concentrations and long-term stability of branched-chain ceramides in various cosmetics, simplifies the production process, avoids precipitation and turbidity problems, and enhances skin barrier repair and moisturizing effects.
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Figure CN121378034A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of skin science and formulation engineering, in particular to a branched ceramide with excellent solubility, a preparation method and application thereof, mainly including molecular design, green synthesis of branched ceramide and its application in skin care and hair care products. BACKGROUND
[0002] As the main component of the intercellular lipid in the stratum corneum of human skin, ceramide accounts for about 40% to 50% of the total mass, and plays a crucial role in maintaining the integrity and function of the skin barrier and preventing excessive water loss. When the ceramide content in the skin decreases due to internal or external factors, it will lead to impaired skin barrier function, and even cause dryness, sensitivity and a series of skin diseases. Therefore, supplementing exogenous ceramide in skin care products has become one of the core strategies to repair and strengthen the skin barrier.
[0003] At present, the ceramide raw materials widely used in the cosmetic industry are mainly traditional straight-chain structures. However, these molecules generally exhibit dense crystal form and high melting point due to their regular structure and strong interchain interaction. This characteristic leads to their poor solubility in conventional cosmetic solvents such as polyols and various polar and non-polar oil esters. In order to incorporate them into the formulation system, high-temperature melting, high-shear dispersion or complex carrier encapsulation technology is often required in the production process, which not only greatly increases the process difficulty and energy consumption, but also may challenge the stability of other heat-sensitive active ingredients in the formulation. More importantly, the limitations of solubility and dispersibility make the effective addition amount of ceramide in actual products often suppressed at a low level, making it difficult to reach the optimal efficacy concentration in theory, and prone to precipitation, turbidity and other problems during product storage, affecting the stability and use experience of the final product.
[0004] In order to break through the above application bottleneck, structural modification of ceramide molecules, such as introducing branched structures at the alpha position or adjacent position of the fatty acyl chain, is considered as a promising solution. From the perspective of molecular design, the introduction of branched chains can effectively disrupt the regular arrangement of the molecule, reduce its crystallization tendency and melting point, and thus is expected to significantly improve its solubility and compatibility in various matrices. This improvement will enable ceramide to be more conveniently and stably integrated into a variety of dosage forms such as serums, emulsions, creams and transparent formulations with higher addition amount.
[0005] Although the theoretical advantages of branched ceramides are obvious, the technology still faces significant obstacles from concept to industrialization. Existing research is limited to a few specific branched structures, and there is a lack of systematic exploration and regular summary of the influence of factors such as branched position, length and number on the key performance of the product. In addition, the reported synthesis routes are often tedious, harsh conditions or high cost, and there is a lack of a green, efficient and economically viable preparation process that can meet the needs of large-scale industrial production. At the same time, the application data on the long-term stability of this new type of ceramide in complex formula systems, compatibility with other ingredients, and final sensory evaluation are still severely lacking, which greatly limits the confidence of formulators in its development and application.
[0006] Therefore, there is an urgent need in the art for a branched ceramide based on rational molecular design, which can be scaled up by green and environmentally friendly processes, and has excellent solubility and wide formula applicability, to solve the core problems in the process from basic research to market product conversion. SUMMARY
[0007] In view of the above technical deficiencies, the present application provides a branched ceramide with excellent solubility, which is obtained by acylating branched saturated fatty acids such as isostearic acid, isopalmitic acid and 2-hexyldecanoic acid with sphingosine, phytosphingosine and dihydrosphingosine amide. The branched ceramide has low melting point, high solubility and good formula adaptability, and can achieve high loading and long-term stability in multiple systems.
[0008] To achieve the above-mentioned purposes, the specific technical solutions of the present application are as follows: The present application provides a branched ceramide with excellent solubility, and the raw material composition is: branched saturated fatty acids such as isostearic acid, isopalmitic acid and 2-hexyldecanoic acid and sphingosine base.
[0009] Further, the branched fatty acid is one or more of isopalmitic acid, isostearic acid and 2-hexyldecanoic acid, and the GC purity is more than 98%.
[0010] Further, the sphingosine base (Sph) is one or more of sphingosine, phytosphingosine and dihydrosphingosine, and the HPLC purity is more than 90%.
[0011] Further, the condensing agent is one or more of 1-propyl phosphonic anhydride (T3P) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI).
[0012] Further, the catalyst is 4-dimethylaminopyridine (DMAP).
[0013] Further, the organic base is one or more of N,N-diisopropylethylamine (DIPEA), triethylamine (TEA) and N-methylmorpholine (NMM) for neutralizing the acid produced in the reaction and promoting the reaction.
[0014] Further, anhydrous tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-Me THF), dichloromethane (DCM) and acetonitrile are the organic solvents.
[0015] The application also provides a branched ceramide with excellent solubility, which is obtained by condensation of branched saturated fatty acid and sphingosine base using T3P / EDCI and other green condensing or lipase catalysis process, and the specific preparation method comprises the following steps: S1: under an inert atmosphere, mixing the branched fatty acid and the solvent, and activating the branched fatty acid with T3P, DIPEA or EDCI, DMAP or DIC, DMAP; S2: adding sphingosine base and reacting at 0-30℃ for 1-24 h; S3: post-treatment and purification to obtain the product branched ceramide.
[0016] Further, the solvent in step S2 is selected from one or more of anhydrous THF, dichloromethane and acetonitrile.
[0017] Further, the fatty acid:sphingosine base:condensing agent = (1.0-1.5):1:(1.1-2.0).
[0018] In addition, the application also provides a branched ceramide with excellent solubility, which can also be obtained by condensation of branched fatty acid (or its ester) and Sph under the catalysis of lipase (Novozym 435) in 2-MeTHF or solvent-free conditions at 40-65℃, and the obtained product is filtered to remove the enzyme and purified.
[0019] The application provides a branched ceramide with excellent solubility, which is characterized by the molecular structure that is obtained by condensation of specific branched saturated fatty acid and sphingosine base through an amide bond. The branched saturated fatty acid is preferably selected from one or more of isostearic acid, isopalmitic acid and 2-hexyldecanoic acid, which carries a methyl group or a short alkyl chain at the alpha position or near the alpha position, and the GC purity is not less than 98% to ensure the high efficiency of the reaction and the uniformity of the product structure. The sphingosine base (Sph) is preferably selected from one or more of sphingosine, phytosphingosine and dihydrosphingosine, and the HPLC purity is not less than 90% to ensure the biological activity of the final product.
[0020] The present application introduces a branched structure with significant steric hindrance effect on the fatty acyl chain of ceramide through ingenious molecular design. This structural modification fundamentally breaks the regular arrangement of the molecular chain and effectively suppresses its tendency to form a dense crystal structure, thereby endowing the product with a series of outstanding physical and chemical properties. Compared with traditional straight-chain ceramides (such as ceramide NP, AP), the branched ceramide provided by the present application exhibits a significantly reduced melting point (usually below 70°C, even lower), which is the basis for its excellent solubility.
[0021] Benefiting from the reduction of melting point and the loosening of crystal structure, the branched ceramide of the present application exhibits a revolutionary high solubility in a variety of polar and non-polar solvents. Experiments show that its solubility in common cosmetic oil esters such as caprylic / capric triglyceride, isononyl isononanoate, and polyols such as butanediol, pentanediol, etc. can be increased by tens of times compared with traditional straight-chain ceramides. This excellent solubility directly translates into significant formulation advantages, enabling the branched ceramide to be easily and stably integrated into a variety of complex formulation systems with high addition amount (e.g., up to 2% or higher), including but not limited to O / W emulsion, W / O emulsion, anhydrous cream, transparent oil gel, serum, and cleansing products containing surfactants. During long-term storage of the product, it can effectively avoid stability problems such as precipitation and turbidity caused by recrystallization of raw materials, ensuring the clear appearance and smooth skin feel of the final product.
[0022] In terms of preparation method, the present application provides two green, efficient and suitable for industrial amplification synthesis paths. The first path is based on advanced chemical condensation reagents, using 1-propyl phosphonic anhydride (T3P) or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as the condensation core, in the presence of 4-dimethylaminopyridine (DMAP) catalyst and organic base (such as N,N-diisopropylethylamine, DIPEA), the amidation reaction is completed in solvents such as anhydrous tetrahydrofuran, dichloromethane, etc. under mild conditions (0-30°C). This route has the advantages of mild reaction conditions, easy removal of by-products, and high atom economy. The second path uses biological catalysis method, using immobilized lipase (such as Novozym 435) to catalyze the condensation of branched fatty acid (or its active ester) and sphingosine base in green solvent 2-methyltetrahydrofuran or solvent-free system at 40-65°C. This route has the remarkable characteristics of extremely mild conditions, good stereoselectivity, and environmental friendliness. Both routes are simple to operate and easy to handle, and the product can be accurately structurally confirmed by nuclear magnetic resonance hydrogen spectrum (¹H NMR) and carbon spectrum (¹³C NMR) after purification.
[0023] In summary, the branched ceramide with high application value is successfully developed by the ingenious structure design, the innovative synthesis process and the comprehensive performance evaluation. The excellent solubility, the outstanding formula compatibility and the stable chemical property indicate the huge application potential in the high-end skin care, the scalp care and the color cosmetic products, and can provide the core raw material support for developing the next generation of efficient skin barrier repair and moisturizing products.
[0024] The beneficial effects of the present application are: 1. Excellent solubility and wide application: by introducing the branch in the molecule, the melting point of the product is significantly reduced, the solubility in various oil esters and polyols is greatly improved, high concentration addition can be realized, and the product can be applied to transparent essence, anhydrous cream and the like.
[0025] 2. Simple formula and high stability: the excellent solubility enables the raw material to be conveniently added at room temperature, without harsh processes such as high temperature and high shear, simplifying the production and fundamentally solving the stability problems of precipitation and turbidity in product storage.
[0026] 3. Green synthesis and suitable for scale-up: the present application provides two synthesis paths of chemical method and enzyme catalysis, which have the characteristics of mild conditions, simple steps and environmental friendliness, the by-products are easy to handle, and are suitable for large-scale industrial production.
[0027] 4. Significant effect and great potential: the product retains the core biological activity of ceramide, and the addition amount can be greatly improved, which can more efficiently play the excellent effect of repairing skin barrier and persistent moisturizing, and has broad market application prospect. BRIEF DESCRIPTION OF DRAWINGS
[0028] Figure 1 The nuclear magnetic hydrogen spectrum of 2-hexyl decanoic acid-phytosphingosine ceramide of example 3.
[0029] Figure 2 The nuclear magnetic hydrogen spectrum of 2-hexyl decanoic acid-sphingosine ceramide of example 4.
[0030] Figure 3 The nuclear magnetic hydrogen spectrum of 2-hexyl decanoic acid-dihydro sphingosine ceramide of example 5. DETAILED DESCRIPTION
[0031] The application will be further described in conjunction with the following examples without thereby limiting the application. The experimental methods in the following examples are all conventional methods, and the reagents used are analytical pure or above, unless otherwise specified, and the reactions are carried out in an inert atmosphere. The examples are used for illustration but not limitation. NMR spectra are characterized by using a Bruker DPX 400 nuclear magnetic resonance instrument, 1H NMR is 400 MHz, the solvent is deuterated chloroform, deuterated methanol, or deuterated DMSO, and tetramethylsilane (TMS) is used as an internal standard. The unit of chemical shift is ppm, and the unit of coupling constant is Hz. In 1H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, and m represents multiplet.
[0032] Example 1 Preparation of isostearic acid-phytosphingosine ceramide, the structural formula of isostearic acid-phytosphingosine ceramide is as follows: , which is composed of the following raw materials by weight: isostearic acid 1.2 eq, T3P 1.5 eq, DMAP 0.1 eq, DIPEA 2.0 eq, phytosphingosine 1.0 eq, THF.
[0033] The preparation method of isostearic acid-phytosphingosine ceramide specifically includes the following steps: S1: under an inert atmosphere, isostearic acid (60 mmol), T3P (55-100 mmol, preferably 75 mmol), DMAP (5-10 mmol, preferably 5 mmol), and DIPEA (100-120 mmol, preferably 100 mmol) are placed in a 250 mL round-bottom flask, 150 mL of tetrahydrofuran is added, and activation is carried out at 0-5°C (preferably 0°C) for 40 min; S2: add a tetrahydrofuran solution of phytosphingosine (50 mmol), and stir at 25°C for 12 h until the phytosphingosine raw material is completely consumed; S3: the reaction system is quenched with water, washed with saturated sodium bicarbonate solution, washed with saturated brine, dried, filtered, and rotary evaporated to obtain a crude product, which is purified by column chromatography to obtain a pure product 21.9 g with a yield of 75%.
[0034] The nuclear magnetic resonance data of the obtained isostearic acid-phytosphingosine ceramide pure product are as follows: 1 H NMR (400 MHz, DMSO- d 6) δ 7.51 (d, J = 8.9 Hz, 1H), 4.56 (d, J = 5.3 Hz, 1H), 4.50 (t, J= 5.4 Hz, 1H), 4.23 (d, J = 6.7 Hz, 1H), 3.81 (d, J = 7.4 Hz, 1H), 3.49 (h, J =5.5 Hz, 4H), 2.17 (t, J = 6.9 Hz, 2H), 1.62 – 1.57 (m, 1H), 1.52 – 1.34 (m,3H), 1.23 – 1.17 (m, 49H), 1.05 (d, J = 6.9 Hz, 6H), 0.90 – 0.74 (m, 3H). Example 2 Preparation of isopalmitic acid-phytosphingosine ceramide, the structural formula of which is as follows: consists of the following raw materials by weight: isopalmitic acid 1.1 eq, T3P 1.5 eq, DMAP 0.2 eq, DIPEA 2.0 eq, phytosphingosine 1.0 eq, THF.
[0035] The preparation method of isopalmitic acid-phytosphingosine ceramide specifically comprises the following steps: S1: under an inert atmosphere, isopalmitic acid (55 mmol), T3P (60-75 mmol, preferably 75 mmol), DMAP (5-10 mmol, preferably 10 mmol), DIPEA (100-120 mmol, preferably 100 mmol) are placed in a 250 mL round-bottom flask, 150 mL of tetrahydrofuran is added, and activated at 0-5°C (preferably 0°C) for 40 min; S2: add a tetrahydrofuran solution of phytosphingosine (50 mmol), stir at 25°C for 16 h until the phytosphingosine raw material is completely consumed; S3: quench the reaction system with water, wash with saturated sodium bicarbonate solution, wash with saturated brine, dry, filter, and rotary evaporate to obtain a crude product, which is purified by column chromatography to obtain a pure product 20.0 g with a yield of 72%.
[0036] The nuclear magnetic resonance data of the obtained pure isopalmitic acid-phytosphingosine ceramide are as follows: 1 H NMR (400 MHz, DMSO- d 6) δ 7.48 (d, J = 8.6 Hz, 1H), 4.59 (d, J = 5.2 Hz, 1H), 4.45 (t,J = 5.4 Hz, 1H), 4.33 (d, J = 6.5 Hz, 1H), 3.71 (d, J = 7.2 Hz, 1H), 3.57 – 3.41(m, 4H), 2.13 (t, J = 6.7 Hz, 2H), 1.52 – 1.44 (m, 1H), 1.42 – 1.31 (m, 2H),1.18 – 1.07 (m, 46H), 0.96 (d, J = 7.2 Hz, 6H), 0.89 – 0.77 (m, 3H). Example 3 2-hexyldecanoic acid-phytosphingosine ceramide was prepared, and its structural formula is as follows: It is composed of the following raw materials by weight: 2-hexyldecanoic acid 1.2 eq, EDCI 1.2 eq, DMAP 0.1 eq, DIPEA 2.0 eq, phytosphingosine 1.0 eq, THF.
[0037] The preparation method of 2-hexyldecanoic acid-phytosphingosine ceramide specifically comprises the following steps: S1: Under an inert atmosphere, 2-hexyldecanoic acid (60 mmol), EDCI (55-65 mmol, preferably 60 mmol), DMAP (5-10 mmol, preferably 5 mmol), and DIPEA (100-120 mmol, preferably 100 mmol) are placed in a 250 mL round-bottom flask, 120 mL of tetrahydrofuran is added, and activated at 0-5°C (preferably 0°C) for 30 min; S2: Add a tetrahydrofuran solution of phytosphingosine (50 mmol), and stir at 25°C for 20 h until the phytosphingosine raw material is completely consumed; S3: The reaction system is quenched with water, washed with saturated sodium bicarbonate solution, washed with saturated brine, dried, filtered, and rotary evaporated to obtain a crude product, which is purified by column chromatography to obtain a pure product 20.4 g with a yield of 70%.
[0038] The nuclear magnetic resonance data of the obtained 2-hexyldecanoic acid-phytosphingosine ceramide pure product are as follows: 1 H NMR (400 MHz, Methanol- d 4) δ 4.10 (dt, J = 6.7, 4.8 Hz, 1H), 3.74 (d, J= 4.8 Hz, 2H), 3.67– 3.61 (m, 1H), 3.58 (ddd, J = 7.6, 5.4, 2.2 Hz, 1H), 2.24 (tt, J = 9.7, 4.8Hz, 1H), 1.60 (td, J = 15.2, 14.4, 8.8 Hz, 4H), 1.33 – 1.29 (m, 48H), 0.92(td, J = 6.8, 2.0 Hz, 9H). Example 4 2-Hexyldecanoic acid-sphingosine ceramide was prepared, the structural formula of which is as follows: It is composed of the following raw materials by weight: 2-hexyldecanoic acid 1.2 eq, sphingosine 1.0 eq, Novozym 435 (10 wt%), 2-MeTHF.
[0039] The preparation method of 2-hexyldecanoic acid-sphingosine ceramide specifically comprises the following steps: 2-hexyldecanoic acid (60 mmol) and sphingosine (50 mmol) were dissolved in 120 mL of 2-MeTHF, Novozym 435 (10 wt%) was added, the reaction system was heated to 50-60°C (preferably 60°C), and the reaction was carried out for 8-24 h (preferably 24 h); the enzyme was recovered by filtration, the filtrate was rotary evaporated to obtain a crude product, and the crude product was purified by column chromatography to obtain a pure product 23.4 g with a yield of 80%.
[0040] The nuclear magnetic resonance data of the obtained 2-hexyldecanoic acid-sphingosine ceramide (enzyme catalysis) pure product are as follows: 1 H NMR (400MHz, Chloroform- d ) δ 6.23 (d, J = 7.2 Hz, 1H), 5.79 (dt, J = 14.2, 6.7 Hz,1H), 5.53 (dd, J = 15.4, 6.5 Hz, 1H), 4.31 (d, J = 6.5 Hz, 1H), 3.93 (td, J =9.0, 7.8, 3.9 Hz, 2H), 3.74 – 3.63 (m, 1H), 2.90 (s, 2H), 2.06 (td, J= 9.2, 4.8 Hz, 3H), 1.71 (s, 2H), 1.58 (ddd, J = 14.0, 8.9, 4.9 Hz, 2H), 1.50 - 1.34 (m, 4H), 1.26 (s, 42H), 0.93 - 0.78 (m, 9H). Example 5 2-hexyldecanoic acid-dihydrosphingosine ceramide was prepared, and its structure is as follows: It is composed of the following weight parts of raw materials: 2-hexyldecanoic acid 1.2 eq, EDCI 1.2 eq, DMAP 1.0 eq, dihydrosphingosine 1.0 eq, THF.
[0041] The preparation method of 2-hexyldecanoic acid-dihydrosphingosine ceramide specifically includes the following steps: S1: Under an inert atmosphere, 2-hexyldecanoic acid (60 mmol), EDCI (55-65 mmol, preferably 60 mmol), and DMAP (50-60 mmol, preferably 50 mmol) were placed in a 250 mL round-bottom flask, 120 mL of tetrahydrofuran was added, and activated at 0-5°C (preferably 0°C) for 30 min; S2: Add a tetrahydrofuran solution of dihydrosphingosine (50 mmol), and stir at 40°C for 10 h until the dihydrosphingosine raw material is completely consumed; S3: The reaction system was quenched with water, washed with saturated sodium bicarbonate solution, washed with saturated brine, dried, filtered, and rotary evaporated to obtain a crude product, which was purified by column chromatography to obtain a pure product 20.4 g; yield: 84%.
[0042] The nuclear magnetic resonance data of the obtained 2-hexyldecanoic acid-dihydrosphingosine ceramide pure product are as follows: 1 H NMR (400 MHz, Chloroform- d ) δ 6.33 (d, J = 7.8 Hz, 1H), 4.01 (dt, J = 11.4, 3.8 Hz, 1H), 3.83 (dt, J = 7.5, 3.7 Hz, 1H), 3.75 (ddd, J = 10.3, 8.0, 4.5 Hz, 2H), 2.87 (dd, J = 6.6, 4.1 Hz, 1H), 2.72 (dd, J= 6.1, 1.5 Hz, 1H), 2.05 (tq, J = 8.8,4.4, 3.7 Hz, 1H), 1.69 (s, 2H), 1.65 – 1.47 (m, 5H), 1.43 (dq, J = 11.5, 5.9Hz, 2H), 1.26 (s, 47H), 0.88 (td, J = 6.8, 2.2 Hz, 9H). Example 6 The melting point data comparison results are shown in Table 1: Comparing the melting point data of the traditional straight-chain ceramide and branched-chain ceramide, it can be found that the melting point of phytosphingosine ceramide isopentadecanoate and phytosphingosine ceramide isopalmitate is reduced by more than ten degrees compared with the corresponding straight-chain compound, indicating that the introduction of branched-chain fatty acid can significantly reduce the melting point of ceramide sample. When the length of the branched chain increases (from methyl to hexyl), the melting point of the product is significantly reduced, and the melting point of 2-hexyl decanoic acid-phytosphingosine ceramide and 2-hexyl decanoic acid-sphingosine ceramide is reduced to about seventy-two degrees and eighty degrees respectively. The melting point temperature can be widely used in different dosage form compound systems.
[0043] Table 1 Melting point of straight-chain ceramide and branched-chain ceramide Example 7 The solubility data comparison results are shown in Table 2.
[0044] The solubility of straight-chain ceramide and branched-chain ceramide in different polar solvents at 40°C was compared respectively. Different solvents 5g were heated to 40°C, and then different amounts of ceramide were added respectively, and stirred until fully dissolved. The solubility data of different ceramides in three different solvents were calculated. The results show that the solubility of branched-chain ceramide in different polar solvents is higher than that of straight-chain ceramide. The results show that the application of branched-chain ceramide in different polar formula systems is better than that of straight-chain ceramide.
[0045] Table 2 Solubility comparison of straight-chain ceramide and branched-chain ceramide Example 8 The application in oil-soluble system is shown in Table 3.
[0046] Select the samples of examples 1-4 and straight-chain ceramide, and prepare the oil-soluble samples according to the following steps: (1) Mix the components of phase A, heat to 95°C, and homogenize to mix well; (2) When the system temperature drops to 50°C, add the components of phase B, homogenize well, and then discharge. Observe the stability of the sample at different temperatures. The results are shown in Table 4.
[0047] Table 3 Sample formulation table Observe the stability of the oil-soluble sample, as shown in Table 4, and the results show that the branched ceramide oil-soluble sample at the same concentration has better stability at different temperatures than the straight-chain ceramide oil-soluble sample. The higher the degree of branching of the sample, the more excellent the stability.
[0048] Table 4 Stability "√" indicates clear, "X" indicates turbidity or precipitation Example 9 Application of branched ceramide in O / W emulsion (ceramide content: 0.5 wt%) Formulation composition: Aqueous phase: deionized water to 100%, glycerol 5.0%, butanediol 3.0%, xanthan gum 0.2%, disodium EDTA 0.05% Oil phase: branched ceramide (Example 3) 0.5%, caprylic / capric triglyceride 5.0%, squalane 3.0%, cetylstearyl alcohol 2.0%, tocopheryl acetate 0.5% Emulsifier: PEG-100 stearate & glyceryl stearate 2.5% Preservative: octisalate & ethylhexylglycerin 0.8% Preparation process: heat the aqueous phase and oil phase to 70-80°C respectively. Slowly add the oil phase to the aqueous phase under stirring, homogenize (5000-8000 rpm) emulsify for 5 minutes. Continue to stir and cool to 45°C, add the preservative, and cool to room temperature before collecting the material.
[0049] Example 10 Corneometer value test of skin horny layer water content of Example 9 sample emulsion and control group Control group*: refers to the branched ceramide (Example 3) in the sample emulsion of Example 9, and the insufficient amount is supplemented by deionized water, and the number of subjects is 5.
[0050] The test results show that after the test product sample emulsion of Example 9 is continuously used for 4 weeks, the corneometer value of the skin corneous layer moisture content of the subjects has a very significant increase on the 28th day of product use. Among them, the higher the measured value: corneometer value, the higher the skin corneous layer moisture content. After using the control group emulsion for 4 weeks, the corneometer value of the skin corneous layer moisture content of the subjects has a slight increase. It shows that the branched ceramide of Example 3 plays a very important role in the moisturizing effect of the skin.
[0051] The above is only an example and a description of the concept of the present application. Those skilled in the art can make various modifications or supplements to the described specific embodiments or use similar ways to replace them, as long as they do not deviate from the concept of the present application or exceed the scope defined by the present claims.
Claims
1. A branched ceramide having excellent solubility, characterized by, having the general formula I or its stereoisomers, the structural formula of which is as follows:
2. The branched ceramide of claim 1, wherein The general formula I is abbreviated as Rb-CO-NH-Sph, wherein Sph is selected from the group consisting of sphingosine, dihydrosphingosine or phytosphingosine, Rb is a saturated C14-C20 fatty acyl group having an alpha or near alpha branching; the Rb is selected from one or more of iso-palmitoyl (iso-C16:0), iso-stearoyl (iso-C18:0) and 2-hexyldecanoyl.
3. The branched ceramide of claim 2, wherein Sph is phytosphingosine, to obtain one of the following compounds: isostearic acid- phytosphingosine ceramide, isopalmitic acid-phytosphingosine ceramide, 2-hexyldecanoic acid- phytosphingosine ceramide, whose structural formulas are as follows: , , ; Sph is sphingosine, to obtain 2-hexyldecanoic acid-sphingosine ceramide, whose structural formula is as follows: ; Sph is dihydrosphingosine, to obtain 2-hexyldecanoic acid-dihydrosphingosine ceramide, whose structural formula is as follows: .
4. The branched ceramide with excellent solubility according to any one of claims 1-3, a preparation method thereof comprising the following steps: S1: under an inert atmosphere, mixing branched fatty acid and solvent, and activating the branched fatty acid with T3P, DIPEA or EDCI, DMAP or DIC, DMAP; S2: adding sphingosine base and reacting at 0-30°C for 1-24 h; S3: post-treatment and purification to obtain the product branched ceramide.
5. The branched ceramide excellent in solubility according to claim 4, characterized by The solvent is selected from one or more of anhydrous THF, dichloromethane and acetonitrile, and the fatty acid:sphingosine base:condensing agent = 1.0-1.5:1:1.1-2.
0.
6. The branched ceramide excellent in solubility according to claim 1, characterized by The branched ceramide is condensed with Sph catalyzed by lipase (Novozym 435) under 2-MeTHF or solvent-free conditions at 40-65°C, and the obtained product is filtered to remove the enzyme and purified.
7. The branched ceramide excellent in solubility according to any one of claims 1 to 6, characterized by The physical and chemical characteristics thereof satisfy: the melting point is lower than that of the corresponding straight-chain ceramide by >10°C; the solubility at 40°C in squalane, 1,2-pentanediol and caprylic / capric acid triglyceride is 3-10 times higher than that of the straight-chain ceramide.
8. The branched ceramide excellent in solubility according to any one of claims 1 to 6, characterized by A method for improving the load and clarity of ceramide formulations, so that the formulations remain clear or low turbidity and stable at 4°C, 25°C and 45°C for at least 1 week.
9. An external use composition comprising 0.05-5.0 wt% of the branched ceramide with excellent solubility according to any one of claims 1-6, the composition being an O / W emulsion, a W / O cream, an anhydrous oil gel, a transparent oil phase essence, a microemulsion, a shampoo / hair or bath product.
10. The branched ceramide excellent in solubility according to any one of claims 1 to 6, characterized by Use of the branched ceramide in the preparation of an external use product for improving skin barrier, improving moisturizing property, soothing sensitive skin and enhancing hair toughness.