A deep eutectic solvent for improving solubility of ceramide ⅢB, and a preparation method and application thereof

Abstract

The application belongs to the field of solvent chemistry, and discloses a preparation method of a eutectic solvent for improving the solubility of ceramide III B. The preparation method of the eutectic solvent comprises the following steps: (1) drying a hydrogen bond acceptor and a hydrogen bond donor respectively; (2) mixing the hydrogen bond acceptor and the hydrogen bond donor, heating, and stirring to obtain the eutectic solvent; (3) adding the eutectic solvent obtained in step (2) into a test tube, heating, opening a laser emitter and a laser receiver, so that the former two are on the same horizontal line with the test tube, and recording the initial laser intensity; (4) adding ceramide III B into the test tube, and recording the laser intensity when the ceramide III B is dissolved; (5) continuously adding the ceramide III B, and repeatedly operating until the laser intensity remains unchanged within 3 hours and cannot be restored to the maximum intensity, and then calculating the solubility at this time by using a formula. The eutectic solvent provided by the application has the advantages of simple preparation process, low cost, and being an environmentally friendly solvent system.

Description

Technical Field

[0001] The present invention belongs to the field of solvent chemistry, and particularly relates to a method for preparing a deep eutectic solvent for improving the solubility of ceramide IIIB. Background Art

[0002] Ceramide is a lipid substance composed of different long chains of sphingosine and fatty acids of various saturations. It accounts for 40%-50% of human skin and is an important component of the stratum corneum. It not only participates in the construction of the stratum corneum epidermis, but also has the effects of moisturizing, repairing the barrier and delaying aging. However, ceramide has a special structure. Its polar head, amide bond and hydroxyl group form a tridentate donor / acceptor center, which allows ceramide molecules to directly form a tight and orderly network structure through hydrogen bonding. This results in high crystallinity of ceramide, making it difficult to dissolve, which greatly limits its application.

[0003] Currently, the application of ceramides relies primarily on encapsulation technology and solubility in high-polarity oils. Encapsulation technology requires relatively high costs for the excipients and equipment, and the preparation process is complex, with uncertain encapsulation efficiency. High-polarity oils require high temperatures to dissolve ceramides, and their use in formulations can lead to ceramide precipitation, necessitating consideration of compatibility with other ingredients in the formulation. Currently, finding solvents capable of dissolving ceramides under mild conditions remains a challenge, significantly hindering their application.

[0004] Deep eutectic solvents (DES) are a class of room-temperature molten salts formed by the interaction of two or more hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs). Their melting points are lower than those of their constituent components. DESs are dominated by intermolecular interactions such as hydrogen bonds. The interactions between hydrogen bond donors and acceptors cause charge delocalization, resulting in physicochemical properties that differ from those of their constituent compounds. These solvents offer advantages such as low preparation cost, easy degradation, high solubility, low irritation, and sustainable development, making them promising green solvents.

[0005] As disclosed in Chinese patent CN117883939A, a kind of eutectic solvent and its application and the method for absorbing V0Cs using eutectic solvent, characterized in that, the eutectic solvent contains at least one pair of hydrogen bond acceptor-hydrogen bond donor;Wherein, in the eutectic solvent, the total amount of hydrogen bond acceptor and the total amount of hydrogen bond donor are 1:0.1-10 in the molar ratio;Hydrogen bond acceptor is selected from one or more than two of choline chloride, tetrabutylammonium bromide, tetraoctylammonium chloride, menthol and thymol;Hydrogen bond donor is selected from organic acid.The eutectic solvent disclosed in the application can achieve deep emission reduction of V0Cs when used for absorbing V0Cs.However, the hydrogen bond donor and acceptor part selected by the application has irritancy and toxicity, which is not suitable for application in cosmetics.

[0006] For example, Chinese patent CN112569632B discloses a kind of eutectic solvent composition and its preparation and application for separating aromatic hydrocarbon.The eutectic solvent composition comprises eutectic solvent and ionic solvent;The amount of ionic solvent is 0.1% to 80% of the mass of eutectic solvent;The eutectic solvent comprises hydrogen bond acceptor, hydrogen bond donor and Lewis acid salt, wherein the molar ratio of hydrogen bond donor and hydrogen bond acceptor is 0.4:1 to 24:1;The amount of Lewis acid salt added is 0 to 20% of the total mass of eutectic solvent.The technical solution of the application reduces the content of ionic solvent without reducing the separation effect of aromatic hydrocarbon, supplements eutectic solvent as an effective extraction solvent component, increases the efficiency of the combined solvent in extracting aromatic hydrocarbon, and solves the problems of relatively complex synthesis process, high cost and environmental unfriendliness of ionic solvent.The application also has the above problems.

[0007] Therefore, there is an urgent need to develop a kind of eutectic solvent, so that ceramide III B can be quickly dissolved at room temperature, showing a stable state of clear and transparent and not precipitating. SUMMARY

[0008] Based on the problems existing in the prior art, the present application provides a preparation method of eutectic solvent, so that ceramide III B can be quickly dissolved at room temperature, showing a stable state of clear and transparent and not precipitating.The preparation method adopted by the present application is simple, low in cost, and is an environmentally friendly solvent system.

[0009] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows:

[0010] The present application provides a preparation method of eutectic solvent for improving the solubility of ceramide III B, comprising the following steps:

[0011] (1) Dry the hydrogen bond acceptor and the hydrogen bond donor respectively;

[0012] (2) mixing the hydrogen bond acceptor and the hydrogen bond donor, heating, stirring to obtain a eutectic solvent;

[0013] (3) adding the eutectic solvent obtained in step (2) into a test tube, heating; using a laser dynamic method, turning on a laser emitter and a laser receiver, so that the former two are in the same horizontal line with the test tube, recording the initial laser intensity;

[0014] (4) adding ceramide III B into the test tube, recording the laser intensity at this time after the dissolution is completed;

[0015] (5) continuing to add ceramide III B, repeating the operation until the laser intensity remains unchanged within 3h and cannot be restored to the maximum intensity, recording the sum of the added ceramide III B at this time, and bringing it into the formula to calculate the solubility at this time.

[0016] Preferably, the hydrogen bond acceptor in step (1) is selected from one or more of choline chloride, L-arginine, L-lysine, L-proline, betaine, decanoic acid, lauric acid, myristic acid, and DL-menthol.

[0017] More preferably, the hydrogen bond acceptor in step (1) is a mixture of DL-menthol, decanoic acid, lauric acid, and myristic acid.

[0018] Preferably, the hydrogen bond donor in step (1) is selected from one or more of urea, malic acid, citric acid, ethylene glycol, glycerol, caprylic acid, decanoic acid, lauric acid, and myristic acid.

[0019] More preferably, the hydrogen bond donor in step (1) is a mixture of caprylic acid, decanoic acid, lauric acid, and myristic acid.

[0020] Preferably, the molar ratio of the mixture of the hydrogen bond acceptor and the hydrogen bond donor in step (2) ranges from 1-2:1-4.

[0021] Preferably, the heating in step (2) is water bath heating, and the heating temperature is 333.15K.

[0022] Preferably, the stirring in step (2) is performed by a magnetic stirrer.

[0023] Preferably, the components of the eutectic solvent obtained in step (2) include but are not limited to DL-menthol, caprylic acid, decanoic acid, lauric acid, and myristic acid.

[0024] More preferably, in the components of the eutectic solvent in step (2), the molar ratio of caprylic acid to decanoic acid, lauric acid, and myristic acid is 1:3; the molar ratio of DL-menthol to caprylic acid and decanoic acid is 1:2; and the molar ratio of DL-menthol to lauric acid is 2:1.

[0025] Preferably, the eutectic solvent is added in step (3) in an amount of 1 g.

[0026] Preferably, the heating temperature in step (3) is 298.15K-318.15K.

[0027] Preferably, the ceramide III B is added in step (4) in an amount of 40-60 mg.

[0028] More preferably, the ceramide III B is added in step (4) in an amount of 50 mg.

[0029] Preferably, the ceramide III B is added in step (5) in an amount of 10-30 mg.

[0030] Preferably, the formula in step (5) is:

[0031]

[0032] In the formula, x is the solubility of ceramide III B, m is the mass of the solute, M is the relative molecular mass of the solute; m1 and m2 are the mass of the hydrogen bond acceptor and the hydrogen bond donor, respectively, and M1 and M2 are the relative molecular mass of the hydrogen bond acceptor and the hydrogen bond donor, respectively.

[0033] The application also provides the eutectic solvent prepared by the above method.

[0034] The application also provides the use of the eutectic solvent prepared by the above method in the preparation of a ceramide III B solution.

[0035] Compared with the prior art, the application has the following beneficial effects:

[0036] (1) The eutectic solvent provided by the application can make ceramide reach a higher solubility under mild conditions compared with ordinary oil and fat, and no crystallization occurs at room temperature.

[0037] (2) The raw materials of the eutectic solvent provided by the application are DL-menthol and fatty acid, which are inexpensive, easy to obtain, and non-toxic and harmless.

[0038] (3) The eutectic solvent provided by the application has a simple operation process, low cost, and does not damage the structure of ceramide itself. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 Figure 1 is a diagram of a laser dynamic emission experimental device.

[0040] Reference signs: 1. Laser emitter; 2. Magnetic stirrer; 3. Thermometer; 4. Test tube; 5. Beaker; 6. Laser receiver; 7. Automatic recorder; 8. Rotor.

[0041] Figure 2 For Examples 1-8 and Comparative Examples 1-4, the solubility of ceramide III B in the eutectic solvent at temperature 298.15 K.

[0042] Figure 3 For Examples 9-16, the solubility of ceramide III B in the eutectic solvent at temperature 298.15 K-318.15 K. DETAILED DESCRIPTION

[0043] The technical solutions of the present application will be described in detail below with specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application. The materials, reagents, etc. used, if not specifically stated, are commercially available reagents and materials.

[0044] Example 1 A method for preparing a eutectic solvent for improving the solubility of ceramide III B

[0045] comprising the following steps:

[0046] (1) Dry octanoic acid and decanoic acid;

[0047] (2) Mix octanoic acid and decanoic acid according to the molar ratio of 1:3, heat to 333.15 K, and stir to obtain a eutectic solvent;

[0048] (3) Add 1 g of the eutectic solvent obtained in step (2) to a test tube, heat to 298.15 K; use a laser dynamic method, such as Figure 1 , turn on the laser emitter and the laser receiver so that the former two are on the same horizontal line as the test tube, and record the initial laser intensity;

[0049] (4) Add 50 mg of ceramide III B to the test tube, and record the laser intensity when it is completely dissolved;

[0050] (5) Continue to add 10 mg of ceramide III B, repeat the operation until the laser intensity remains unchanged within 3 h and cannot be restored to the maximum intensity, record the sum of ceramide III B added at this time, and bring it into the formula to calculate the solubility at this time.

[0051] Example 2 A method for preparing a eutectic solvent for improving the solubility of ceramide III B

[0052] The difference from Example 1 is only that decanoic acid is replaced by lauric acid, and the other steps are the same as Example 1.

[0053] Example 3 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0054] The difference from Example 1 is only that capric acid is replaced by myristic acid, and other steps are the same as Example 1.

[0055] Example 4 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0056] The difference from Example 1 is only that capric acid is replaced by DL-menthol, and the molar ratio of DL-menthol to caprylic acid is 1:2, and other steps are the same as Example 1.

[0057] Example 5 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0058] The difference from Example 1 is only that caprylic acid is replaced by DL-menthol, and the molar ratio of DL-menthol to capric acid is 1:2, and other steps are the same as Example 1.

[0059] Example 6 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0060] The difference from Example 1 is only that caprylic acid and capric acid are replaced by DL-menthol and lauric acid, and the molar ratio of DL-menthol to lauric acid is 2:1, and other steps are the same as Example 1.

[0061] Example 7 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0062] The difference from Example 1 is only that the molar ratio of caprylic acid to capric acid is 1:1, and other steps are the same as Example 1.

[0063] Example 8 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0064] The difference from Example 1 is only that the molar ratio of caprylic acid to capric acid is 1:4, and other steps are the same as Example 1.

[0065] Example 9 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0066] The difference from Example 1 is only that the heating temperature in step (3) is 303.15 K, and other steps are the same as Example 1.

[0067] Example 10 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0068] The difference from Example 4 is only that the heating temperature in step (3) is 303.15 K, and other steps are the same as Example 4.

[0069] Example 11 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0070] The difference from Example 1 is only that the heating temperature in step (3) is 308.15 K, and other steps are the same as Example 1.

[0071] Example 12 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0072] The difference from Example 4 is only that the heating temperature in step (3) is 308.15 K, and other steps are the same as Example 4.

[0073] Example 13 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0074] The difference from Example 1 is only that the heating temperature in step (3) is 313.15 K, and other steps are the same as Example 1.

[0075] Example 14 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0076] The difference from Example 4 is only that the heating temperature in step (3) is 313.15 K, and other steps are the same as Example 4.

[0077] Example 15 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0078] The difference from Example 1 is only that the heating temperature in step (3) is 318.15 K, and other steps are the same as Example 1.

[0079] Example 16 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0080] The difference from Example 4 is only that the heating temperature in step (3) is 318.15 K, and other steps are the same as Example 4.

[0081] Comparative Example 1 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0082] The difference from Example 1 is only that caprylic capric acid is replaced by ordinary oil and fat (GTCC), and other steps are the same as Example 1.

[0083] Comparative Example 2 A method for preparing a deep eutectic solvent for improving solubility of ceramide III B

[0084] The difference from Example 1 is that the heating temperature in step (3) is 343.15 K, and other steps are the same as Example 1.

[0085] Preparation method of a eutectic solvent for improving solubility of ceramide III B

[0086] The difference from Example 1 is that the heating temperature in step (3) is 283.15 K, and other steps are the same as Example 1.

[0087] Preparation method of a eutectic solvent for improving solubility of ceramide III B

[0088] The difference from Example 1 is that the molar ratio of caprylic acid and capric acid is 1:6, and other steps are the same as Example 1.

[0089] Effect experiment

[0090] According to formula (1) (In the formula, x is the solubility of ceramide III B, m is the mass of the solute, M is the relative molecular mass of the solute; m1 and m2 are the masses of the hydrogen bond acceptor and the hydrogen bond donor, respectively, and M1 and M2 are the relative molecular masses of the hydrogen bond acceptor and the hydrogen bond donor, respectively.) The results of calculating the solubility of ceramide III B in Examples 1-16 and Comparative Examples 1-4 are shown in Table 1.

[0091] Table 1

[0092] Solubility Example 1 4.003 Example 2 2.910 Example 3 1.530 Example 4 4.450 Example 5 3.632 Example 6 1.927 Example 7 1.221 Example 8 2.935 Example 9 5.888 Example 10 7.209 Example 11 8.031 Example 12 10.009 Example 13 10.080 Example 14 12.585 Example 15 12.738 Example 16 16.080 Comparative Example 1 0.223 Comparative Example 2 1.117 Comparative Example 3 0.783 Comparative Example 4 1.072

[0093] From the data in Table 1 and Figure 2 , 3 It can be seen that the solubility of ceramide III B in Examples 1-16 is higher than that in Comparative Examples 1-4. From Examples 1-8, it can be seen that at a temperature of 293.15 K, the solubility of ceramide III B in the eutectic system of capric acid-caprylic acid and DL-menthol-caprylic acid is the highest. From Examples 9-16, it can be seen that as the temperature increases, the solubility of ceramide III B in the eutectic system gradually increases. From Comparative Example 1, it can be seen that when the eutectic system is replaced by ordinary oil, the solubility of ceramide III B is very low. From Comparative Example 2, it can be seen that when the temperature exceeds 318.15 K, the solubility of ceramide III B in the eutectic system does not increase but decreases; from Comparative Example 3, it can be seen that when the temperature is lower than 298.15 K, the solubility of ceramide III B in the eutectic system is also not ideal. From Comparative Example 4, it can be seen that changing the molar ratio of caprylic acid and capric acid, the solubility of ceramide III B is not as good as that in Example 1.

[0094] In summary, only by using the ratio range, temperature range and eutectic system disclosed in the present application can the optimal effect be achieved.

Claims

1. A method for preparing a deep eutectic solvent for increasing solubility of ceramide III B, characterized by, It comprises the following steps: (1) drying the hydrogen bond acceptor and the hydrogen bond donor respectively; (2) mixing the hydrogen bond acceptor and the hydrogen bond donor, heating, and stirring to obtain a eutectic solvent; (3) adding the eutectic solvent obtained in step (2) into a test tube and heating; using a laser dynamic method, turning on a laser emitter and a laser receiver so that the former two are in the same horizontal line with the test tube, and recording the initial laser intensity; (4) adding ceramide III B into the test tube and recording the laser intensity after the ceramide III B is dissolved; (5) continuously adding ceramide III B and repeating the operation until the laser intensity remains unchanged within 3 hours and cannot be restored to the maximum intensity, recording the sum of the added ceramide III B at this time, and bringing it into a formula to calculate the solubility at this time.

2. The method of claim 1, wherein: The hydrogen bond acceptor in step (1) is selected from one or more of choline chloride, L-arginine, L-lysine, L-proline, betaine, decanoic acid, lauric acid, myristic acid, and DL-menthol.

3. The method of claim 2, wherein: The hydrogen bond acceptor in step (1) is a mixture of DL-menthol, decanoic acid, lauric acid, and myristic acid.

4. The method of claim 1, wherein: The hydrogen bond donor in step (1) is selected from one or more of urea, malic acid, citric acid, ethylene glycol, glycerol, caprylic acid, decanoic acid, lauric acid, and myristic acid.

5. The method of claim 4, wherein: The hydrogen bond donor in step (1) is a mixture of caprylic acid, decanoic acid, lauric acid, and myristic acid.

6. The method of claim 1, wherein: The molar ratio of the hydrogen bond acceptor to the hydrogen bond donor in step (2) is 1-2:1-4.

7. The method of claim 1, wherein: The heating temperature in step (3) is 298.15K-318.15K.

8. The method of claim 1, wherein: The formula in step (5) is: In the formula, x is the solubility of ceramide III B, m is the mass of the solute, M is the relative molecular mass of the solute; m1 and m2 are the masses of the hydrogen bond acceptor and the hydrogen bond donor, respectively, and M1 and M2 are the relative molecular masses of the hydrogen bond acceptor and the hydrogen bond donor, respectively.

9. The eutectic solvent prepared by the preparation method of any one of claims 1-8.

10. The use of the eutectic solvent according to claim 9 in the preparation of a ceramide III B solution.

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