Eutectic solvent for improving solubility of ceramide IIIB as well as preparation method and application of eutectic solvent

Abstract

The invention belongs to the field of solvent chemistry, and discloses a preparation method of a eutectic solvent for improving the solubility of ceramide IIIB. The preparation method of the eutectic solvent comprises the following steps: (1) respectively drying a hydrogen bond acceptor and a hydrogen bond donor; (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 the step (2) into a test tube, and heating; starting the laser transmitter and the laser receiver to enable the two to be on the same horizontal line with the test tube, and recording initial laser intensity; (4) adding ceramide IIIB into the test tube, and recording the laser intensity at the moment after the ceramide IIIB is completely dissolved; and (5) continuing to add ceramide IIIB, repeating the operation until the laser intensity remains unchanged within 3 hours and cannot be recovered to the maximum intensity, and substituting the laser intensity into a formula to calculate the solubility at the moment. The eutectic solvent provided by the invention is simple in preparation process and low in cost, and is an environment-friendly solvent system.

Description

Technical Field

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

[0002] Ceramide is a lipid substance composed of different sphingosine long chains 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 barriers 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, resulting in high crystallinity of ceramide, making ceramide difficult to dissolve, greatly limiting its application.

[0003] At present, the application of ceramide mainly relies on encapsulation technology and high-polarity oil dissolution. The cost of auxiliary materials and equipment required for encapsulation technology is relatively high, and the preparation process is complicated, and the encapsulation rate effect cannot be guaranteed; high-polarity oils need high temperatures to dissolve ceramide and ceramide will precipitate when used in the formula, and compatibility with other raw materials in the formula needs to be considered. At present, it is still difficult to dissolve ceramide solvents under mild conditions, which seriously hinders the application of ceramide.

[0004] Deep Eutectic Solvents (DES) are a class of room temperature molten salts formed by the interaction of two or more hydrogen bond donors (HBD) and hydrogen bond acceptors (HBAs), and their melting points are all lower than the melting points of the components. DES is dominated by intermolecular interactions such as hydrogen bonds. The interaction between hydrogen bond donors and acceptors can cause charge delocalization, resulting in physical and chemical properties that are different from those of their constituent compounds. This solvent has the advantages of low preparation cost, easy degradation, high solubility, low irritation, and sustainable development. It is a green solvent with great development prospects.

[0005] For example, Chinese patent CN117883939A discloses a low eutectic solvent and its application and a method for absorbing VOCs using the low eutectic solvent, characterized in that the low eutectic solvent contains at least one pair of hydrogen bond acceptor-hydrogen bond donor; wherein, in the low eutectic solvent, the total amount of hydrogen bond acceptor and the total amount of hydrogen bond donor are in a ratio of 1:0.1-10; the hydrogen bond acceptor is selected from one or more of choline chloride, tetrabutylammonium bromide, tetraoctylammonium chloride, menthol and thymol; the hydrogen bond donor is selected from organic acid. The low eutectic solvent described in the invention can achieve deep emission reduction of VOCs when used to absorb VOCs. However, the donor acceptor part of the hydrogen bond selected by the invention is irritating and toxic, and is not suitable for application in cosmetics.

[0006] For another example, Chinese patent CN112569632B discloses a low eutectic solvent composition, its preparation method and its application for separating aromatic hydrocarbons. The low eutectic solvent composition comprises a low eutectic solvent and an ionic solvent; the amount of the ionic solvent is 0.1%-80% of the mass of the low eutectic solvent; the low eutectic solvent comprises a hydrogen bond acceptor, a hydrogen bond donor, and a Lewis acid salt, wherein the molar ratio of the hydrogen bond donor to the hydrogen bond acceptor is 0.4:1-24:1; the amount of the Lewis acid salt added is 0-20% of the total mass of the low eutectic solvent. The technical solution of this invention reduces the content of the ionic solvent without reducing the separation effect of aromatic hydrocarbons, supplements the low eutectic solvent as a component of the effective extraction solvent, increases the efficiency of the combined solvent in extracting aromatic hydrocarbons, and solves the problem that the synthesis process of the ionic solvent is relatively complex, the cost is high, and it is not environmentally friendly. This invention also has the above-mentioned problems.

[0007] Therefore, it is urgent to develop a low eutectic solvent that allows ceramide IIIB to dissolve quickly at room temperature and present a clear, transparent and stable state without precipitation. Summary of the invention

[0008] Based on the problems existing in the prior art, the present invention provides a method for preparing a low eutectic solvent, which enables ceramide IIIB to be quickly dissolved at room temperature, presenting a clear, transparent and stable state without precipitation. The preparation method adopted by the present invention has a simple process and low cost, and is an environmentally friendly solvent system.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] The present invention provides a method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB, comprising the following steps:

[0011] (1) drying the hydrogen bond acceptor and the hydrogen bond donor separately;

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

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

[0014] (4) Add ceramide IIIB to the test tube and record the laser intensity after the dissolution is complete;

[0015] (5) Continue to add ceramide III B and repeat the operation until the laser intensity remains unchanged within 3 h and cannot be restored to the maximum intensity. Record the total amount of ceramide III B added at this time and substitute it into the formula to calculate the solubility at this time.

[0016] Preferably, the hydrogen bond acceptor in step (1) is selected from the group consisting of: choline chloride, L-arginine, L-lysine, L-proline, betaine, capric acid, lauric acid, myristic acid, and DL-menthol;

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

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

[0020] Preferably, the molar ratio of the hydrogen bond acceptor and the donor in step (2) is in the range of 1-2:1-4;

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

[0022] Preferably, the stirring in step (2) is carried out using a magnetic stirrer.

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

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

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

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

[0027] Preferably, the amount of ceramide IIIB added in step (4) is 40-60 mg;

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

[0029] Preferably, the amount of ceramide IIIB added again in step (5) is 10-30 mg;

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

[0031]

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

[0033] The present invention also provides a low eutectic solvent prepared by the above method.

[0034] The present invention also provides the use of the low eutectic solvent prepared by the above method in preparing a ceramide III B solution.

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

[0036] (1) Compared with common oils and fats, the low eutectic solvent provided by the present invention can make ceramide reach a higher solubility under mild conditions, and no precipitation and crystallization occur at room temperature.

[0037] (2) The raw materials of the low eutectic solvent provided by the present invention are DL-menthol and fatty acids, which have the advantages of being cheap, readily available, non-toxic and harmless;

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

[0039] Figure 1 This is a diagram of the laser dynamic emission experimental setup.

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

[0041] Figure 2 The solubility of ceramide IIIB in a deep eutectic solvent at a temperature of 298.15K for Examples 1-8 and Comparative Examples 1-4.

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

[0043] The technical scheme of the present invention is clearly and completely described below with specific implementation methods. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention. The materials, reagents, etc. used, if not otherwise specified, are reagents and materials available from commercial sources.

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

[0045] The steps include:

[0046] (1) drying caprylic acid and capric acid;

[0047] (2) caprylic acid and capric acid are mixed in a molar ratio of 1:3, heated to 333.15 K, and stirred to obtain a deep eutectic solvent;

[0048] (3) Add 1 g of the low eutectic solvent obtained in step (2) to a test tube and heat to 298.15 K; use a laser dynamic method, such as Figure 1 , turn on the laser transmitter and laser receiver so that the former two are at the same level 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 after the solution is complete;

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

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

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

[0053] Example 3 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0055] Example 4 Preparation method of a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0057] Example 5 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0059] Example 6 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

[0060] The only difference from Example 1 is 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. The other steps are the same as Example 1.

[0061] Example 7 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0063] Example 8 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0065] Example 9 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0067] Example 10 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0069] Example 11 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0071] Example 12 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0073] Example 13 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0075] Example 14 Preparation method of a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0077] Example 15 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0079] Example 16 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0081] Comparative Example 1 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0083] Comparative Example 2 A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0085] Comparative Example 3 Preparation method of a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0087] Comparative Example 4: A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB

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

[0089] Effect Experiment

[0090] According to formula (1) (Wherein, x is the solubility of ceramide IIIB, m is the solute mass, and 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 IIIB of 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 Embodiment 11 8.031 Example 12 10.009 Example 13 10.080 Embodiment 14 12.585 Embodiment 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] Through Table 1 and Figure 2 , 3 It can be seen from the data that the solubility of ceramide IIIB in Examples 1-16 is higher than that in Comparative Examples 1-4. It can be seen from Examples 1-8 that at a temperature of 293.15K, the solubility of ceramide IIIB in the eutectic system of capric acid-octanoic acid and DL-menthol-octanoic acid is the highest. It can be seen from Examples 9-16 that as the temperature increases, the solubility of ceramide IIIB in the eutectic system gradually increases. It can be seen from Comparative Example 1 that when the eutectic system is replaced with ordinary oils and fats, the solubility of ceramide IIIB is extremely low. It can be seen from Comparative Example 2 that when the temperature exceeds 318.15K, the solubility of ceramide IIIB in the eutectic system does not increase but decreases; it can be seen from Comparative Example 3 that when the temperature is lower than 298.15K, the solubility of ceramide IIIB in the eutectic system is not ideal. It can be seen from Comparative Example 4 that the solubility of ceramide IIIB is not as good as that in Example 1 when the molar ratio of caprylic acid and capric acid is changed.

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

Claims

1. A method for preparing a low eutectic solvent for improving the solubility of ceramide IIIB, characterized in that: The steps include: (1) Drying the hydrogen bond acceptor and the hydrogen bond donor separately; (2) mixing the hydrogen bond acceptor and the hydrogen bond donor, heating, and stirring to obtain a deep eutectic solvent; (3) adding the low eutectic solvent obtained in step (2) into the test tube and heating it; using the laser dynamic method, turning on the laser transmitter and the laser receiver so that the former two are at the same horizontal line with the test tube, and recording the initial laser intensity; (4) Add ceramide IIIB to the test tube and record the laser intensity after dissolution is complete; (5) Continue to add ceramide III B and repeat the operation until the laser intensity remains unchanged within 3 h and cannot be restored to the maximum intensity. Record the total amount of ceramide III B added at this time and substitute it into the formula to calculate the solubility at this time.

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

3. The preparation method according to claim 2, characterized in that: The hydrogen bond acceptor in step (1) is a mixture of DL-menthol, capric acid, lauric acid and myristic acid.

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

5. The preparation method according to claim 4, characterized in that: The hydrogen bond donor in step (1) is a mixture of caprylic acid, capric acid, lauric acid and myristic acid.

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

7. The preparation method according to claim 1, characterized in that: The heating temperature in step (3) is 298.15K-318.15K.

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

9. A deep eutectic solvent prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the deep eutectic solvent according to claim 9 in preparing a ceramide IIIB solution.

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