Supramolecule of γ-aminobutyric acid and a substance with cinnamic acid structure, preparation method thereof and application thereof

Abstract

The present application discloses a supramolecule of γ-aminobutyric acid-a substance having a phenylacrylic acid structure, a crystal form, a preparation method, and applications thereof. The supramolecule connects γ-aminobutyric acid and a substance having a phenylacrylic acid structure through a non-covalent bond. When the supramolecule is added to cosmetics, it can not only significantly enhance the efficacy and activity of the substance having a phenylacrylic acid structure, but also achieve synergistic enhancement of GABA and the substance having a phenylacrylic acid structure.

Description

Technical Field

[0001] The present application relates to the field of cosmetic technology, and in particular to a supramolecule of a γ-aminobutyric acid-substance having a phenylacrylic acid structure, a preparation method, and applications thereof. Background Art

[0002] Substances with a phenylacrylic acid structure, including phenylacrylic acid and its derivatives, are a class of organic acid compounds, typically including cinnamic acid, ferulic acid, p-hydroxycinnamic acid, and sinapinic acid. Ferulic acid is used in cosmetics to reduce the activity of the matrix metalloproteinase (MMP-1), which causes collagen degradation, by upregulating the expression of TIMP-1 mRNA, a matrix metalloproteinase inhibitor, thereby increasing collagen content. Cinnamic acid, when used in cosmetics, not only increases skin protein content, achieving anti-aging effects, but also inhibits tyrosinase activity, reducing melanin formation and achieving a whitening effect.

[0003] However, although substances with a phenylacrylic acid structure have a certain effect on increasing the content of collagen and elastin in the skin, the effect is weak. Elastin and collagen, as the main protein components in the skin, determine the degree of skin aging, which shows that the use of substances with a phenylacrylic acid structure cannot effectively achieve anti-aging. Summary of the Invention

[0004] In response to the above problems, the present application forms a supramolecule by combining GABA with a substance having a phenylacrylic acid structure, which not only significantly improves the efficacy and activity of the substance having a phenylacrylic acid structure, but also achieves synergistic enhancement of GABA and the substance having a phenylacrylic acid structure.

[0005] The specific technical solutions of this application are as follows:

[0006] A supramolecule of γ-aminobutyric acid and a substance having a phenylacrylic acid structure, wherein the supramolecule links γ-aminobutyric acid and a substance having a phenylacrylic acid structure via a non-covalent bond.

[0007] 2. The supramolecule according to item 1, wherein the substance having a phenylacrylic acid structure comprises one of ferulic acid, cinnamic acid, hydroxycinnamic acid, and sinapinic acid.

[0008] 3. The supramolecule according to item 1 or 2, wherein the molar ratio of the γ-aminobutyric acid to the substance having a phenylacrylic acid structure is 1:1.

[0009] 4. The supramolecule according to any one of items 1 to 3, wherein the supramolecule has a wavelength of 2920±10 cm -1 There is an absorption peak at

[0010] Preferably, also at 1640±10cm-1 、1500±10cm -1 One or two of them have absorption peaks,

[0011] More preferably, at 1400±10cm -1 、1310±10cm -1 One or two of them have absorption peaks.

[0012] 5. The supramolecule according to any one of items 1 to 4, wherein the supramolecule is a γ-aminobutyric acid-ferulic acid supramolecule, and when the supramolecule is analyzed using nuclear magnetic resonance, the nuclear magnetic characteristics are: 1 HNMR: (CD3OD, 400MHz, ppm), δ3.00-2.98ppm(t,2H), 2.39-2.37ppm(t,2H), 1.93-1.88ppm(m,2H), δ7.54-7.52pp m(d,1H), 7.17ppm(d,1H), 7.06-7.04ppm(dd,1H), 6.83-6.82ppm(d,1H), 6.35-6.33ppm(d,1H), 3.90ppm(s,3H).

[0013] 6. The supramolecule according to any one of items 1 to 4, wherein the supramolecule is a γ-aminobutyric acid-cinnamic acid supramolecule, and when the supramolecule is analyzed using nuclear magnetic resonance, the nuclear magnetic characteristics are: 1 HNMR: (CD3OD, 400MHz, ppm), δ2.98-2.96ppm(t,2H),2.37-2.35ppm(t,2H),1.91-1. 86ppm(m,2H), δ7.58-7.55ppm(m,3H), 7.37-7.35ppm(m,3H), 6.50-6.48ppm(d,1H).

[0014] 7. A supramolecule crystal form according to any one of items 1 to 4, wherein the crystal form is a crystal form of γ-aminobutyric acid-ferulic acid, and the X-ray powder diffraction pattern of the crystal form has characteristic peaks at 27.1°±0.2°, 30.8°±0.2°, and 24.3°±0.2° in 2θ expressed in degrees;

[0015] Preferably, there are characteristic peaks at one, two or three of 10.5°±0.2°, 20.6°±0.2° and 34.5°±0.2°.

[0016] 8. A supramolecule crystal form according to any one of items 1 to 4, wherein the crystal form is a crystal form of γ-aminobutyric acid-ferulic acid, and the differential scanning calorimetry diagram of the crystal form produces a heat absorption peak between 120-130°C.

[0017] 9. A crystal form of the supramolecule according to any one of items 1 to 4, wherein the crystal form is a crystal form of γ-aminobutyric acid-ferulic acid, the crystal form is a monoclinic system, the space group is C2 / c, and the unit cell parameters are α=90°, β=93.2540(10)°, γ=90°,

[0018] Preferably, the number of molecules in the unit cell is Z=4, and the unit cell volume is

[0019] 10. A crystal form of the supramolecule according to any one of items 1 to 4, wherein the crystal form is a crystal form of γ-aminobutyric acid-cinnamic acid, the crystal form is a monoclinic system, the space group is P21 / c, and the unit cell parameters are β=97.847(16)°, γ=90°;

[0020] Preferably, the number of molecules in the unit cell is Z=4, and the unit cell volume is

[0021] 11. A supramolecule crystal form according to any one of items 1 to 4, wherein the crystal form is a crystal form of γ-aminobutyric acid-cinnamic acid, and the differential scanning calorimetry diagram of the crystal form produces a heat absorption peak between 110-130°C.

[0022] 12. A method for preparing the supramolecule according to any one of items 1 to 11, comprising:

[0023] Dissolving a substance having a phenyl acrylic acid structure in a solvent I to obtain a solution I;

[0024] dissolving γ-aminobutyric acid in solvent II to obtain solution II;

[0025] Solution II is added to solution I to carry out supramolecular modification reaction;

[0026] After the reaction is completed, the obtained material is crystallized to obtain supramolecules.

[0027] 13. The preparation method according to item 12, wherein the solvent I and solvent II are polar solvents, which may be the same or different, and preferably include water, methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran or N,N-dimethylformamide.

[0028] 14. The preparation method according to item 12 or 13, wherein the reaction temperature is 40-100°C, preferably 50-90°C;

[0029] 15. The preparation method according to any one of items 12 to 14, wherein the temperature during the crystallization is -1°C to -20°C, preferably -5°C to -10°C.

[0030] 16. The preparation method according to any one of items 12 to 15, wherein the molar ratio of γ-aminobutyric acid to the substance having a phenylacrylic acid structure is 1:0.1-10, preferably 1:1-5.

[0031] 17. Use of the supramolecule according to any one of items 1 to 11 or the supramolecule prepared by the preparation method according to any one of items 12 to 16 in the preparation of cosmetics.

[0032] 18. The use according to item 17, wherein the supramolecule is used in anti-aging.

[0033] 19. Application of γ-aminobutyric acid and substances with phenylacrylic acid structure in the preparation of supramolecules.

[0034] 20. A cosmetic composition comprising the supramolecule according to any one of items 1 to 11 or the supramolecule prepared by the preparation method according to any one of items 12 to 16.

[0035] 21. The composition according to item 20, wherein the supramolecule accounts for 0.1-30% by mass in the composition, preferably 0.5-5%.

[0036] 22. The composition according to item 20 or 21, wherein the composition further comprises excipients and / or other effective ingredients.

[0037] Effects of the Invention

[0038] In the present application, GABA is pre-conjugated with a phenylacrylic acid structure into a supramolecule, which is then added to cosmetics. This can significantly increase the production of collagen and elastin by substances with a phenylacrylic acid structure, thereby achieving effective anti-aging effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 Schematic diagram of powder diffraction of the supramolecule of Example 1.

[0040] Figure 2 This is a schematic diagram of the single crystal diffraction of the supramolecule of Example 1.

[0041] Figure 3 Schematic diagram of differential scanning calorimetry analysis of the supramolecule of Example 1.

[0042] Figure 4 This is the NMR spectrum of the supramolecule of Example 1.

[0043] Figure 5 This is the infrared spectrum of monomeric GABA.

[0044] Figure 6 This is the infrared spectrum of monomer ferulic acid.

[0045] Figure 7 This is the infrared spectrum of the supramolecule of Example 1.

[0046] Figure 8 This is a schematic diagram of the single crystal diffraction of the supramolecule of Example 13.

[0047] Figure 9 Schematic diagram of differential scanning calorimetry analysis of the supramolecule of Example 13.

[0048] Figure 10 This is the NMR spectrum of the supramolecule of Example 13.

[0049] Figure 11 This is the infrared spectrum of monomeric cinnamic acid.

[0050] Figure 12 This is the infrared spectrum of the supramolecule of Example 13.

[0051] Figure 13 Schematic diagram of the differences among GABA-ferulic acid supramolecule, monomeric ferulic acid, and monomeric GABA in regulating MMP-1 content.

[0052] Figure 14 Schematic diagram showing the differences among GABA-cinnamic acid supramolecular, monomeric cinnamic acid, and monomeric GABA in regulating MMP-1 content.

[0053] Figure 15 Schematic diagram showing the differences among GABA-cinnamic acid supramolecule, monomeric cinnamic acid, and monomeric GABA in regulating elastin content. DETAILED DESCRIPTION

[0054] The present application is described in detail below in conjunction with the described embodiments. Although specific embodiments of the present application are shown, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art.

[0055] It should be noted that certain words are used in the specification and claims to refer to specific components. Those skilled in the art should understand that technicians may use different nouns to refer to the same component. This specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of the components as the criterion for distinction. As mentioned throughout the specification and claims, "including" or "comprising" are open-ended terms and should be interpreted as "including but not limited to". The subsequent description of the specification is a preferred embodiment of the present application, but the description is based on the general principles of the specification and is not intended to limit the scope of the present application. The scope of protection of this application shall be as defined by the attached claims.

[0056] The present application provides a supramolecule of γ-aminobutyric acid-a substance having a phenylacrylic acid structure, wherein the supramolecule connects the γ-aminobutyric acid and the substance having a phenylacrylic acid structure through a non-covalent bond.

[0057] In the present application, the substance having a phenylacrylic acid structure refers to a substance containing a phenylacrylic acid structure, for example, ferulic acid, cinnamic acid, hydroxycinnamic acid or sinapinic acid.

[0058] In some embodiments, in the supramolecule, the molar ratio of γ-aminobutyric acid to the substance having a phenylacrylic acid structure is 1:1.

[0059] In the present application, there is no limitation on the method for determining the molar ratio of γ-aminobutyric acid and the substance having a phenylacrylic acid structure in the supramolecular structure. The molar ratio of γ-aminobutyric acid and the substance having a phenylacrylic acid structure in the supramolecular structure can be determined by conventional methods in the art, for example, by using nuclear magnetic resonance to determine the molar ratio of the substance having a phenylacrylic acid structure in the supramolecular structure.

[0060] A supramolecule is a complex, organized aggregate composed of two or more molecules bound together by intermolecular interactions, maintaining a certain degree of integrity that results in a well-defined microstructure and macroscopic properties. In this application, the supramolecule is a structure formed by γ-aminobutyric acid and a substance having a phenylacrylic acid structure, wherein the γ-aminobutyric acid is linked to the substance having a phenylacrylic acid structure via a non-covalent bond.

[0061] In some embodiments, the amino group of the γ-aminobutyric acid is connected to the carboxyl group of the substance with an α-phenylacrylic acid structure through a non-covalent bond.

[0062] In some embodiments, the non-covalent bonds include hydrogen bonds, van der Waals forces, π-π stacking, and electrostatic interactions.

[0063] In some embodiments, when the supramolecule is analyzed using infrared spectroscopy, the wavelength of the supramolecule is 2920±10 cm -1There is an absorption peak at 1640±10cm -1 、1500±10cm -1 One or two of the absorption peaks have an absorption peak, and more preferably, an absorption peak at 1400±10cm -1 、1310±10cm -1 One or two of them have absorption peaks.

[0064] In some embodiments, the supramolecule is analyzed by infrared spectroscopy at approximately 2920±2 cm -1 There is an absorption peak at 1640±2cm -1 、1500±2cm -1 One or two of the absorption peaks have an absorption peak, and more preferably, at 1400±2cm -1 、1310±2cm -1 One or two of them have absorption peaks.

[0065] In some embodiments, the infrared spectrum of the γ-aminobutyric acid-ferulic acid supramolecule is at 2200±10 cm -1 、3440±10cm -1 The absorption peak at disappears.

[0066] In some embodiments, the infrared spectrum of the supramolecule of γ-aminobutyric acid-ferulic acid is as follows: Figure 7 shown.

[0067] In some embodiments, the infrared spectrum of the γ-aminobutyric acid-cinnamic acid supramolecule is also at 2200±10 cm -1 There is an absorption peak at.

[0068] In some embodiments, the infrared spectrum of the supramolecule of γ-aminobutyric acid-cinnamic acid is as follows: Figure 12 shown.

[0069] In some embodiments, the NMR characteristics of the γ-aminobutyric acid-ferulic acid supramolecule are: 1 HNMR: (CD3OD, 400MHz, ppm), δ3.00-2.98ppm(t,2H), 2.39-2.37ppm(t,2H), 1.93-1.88ppm(m,2H), δ7.54-7.52pp m(d,1H), 7.17ppm(d,1H), 7.06-7.04ppm(dd,1H), 6.83-6.82ppm(d,1H), 6.35-6.33ppm(d,1H), 3.90ppm(s,3H).

[0070] In some embodiments, the NMR characteristics of the γ-aminobutyric acid-cinnamic acid supramolecule are:1 HNMR: (CD3OD, 400MHz, ppm), δ2.98-2.96ppm(t,2H),2.37-2.35ppm(t,2H),1.91-1. 86ppm(m,2H), δ7.58-7.55ppm(m,3H), 7.37-7.35ppm(m,3H), 6.50-6.48ppm(d,1H).

[0071] The present application provides a crystal form of the above supramolecule.

[0072] In some embodiments, the crystal form is a crystal form of γ-aminobutyric acid-ferulic acid, and the X-ray powder diffraction pattern of the crystal form has characteristic peaks at 27.1°±0.2°, 30.8°±0.2°, and 24.3°±0.2° in 2θ expressed in degrees.

[0073] In some embodiments, the X-ray powder diffraction pattern of the crystalline form has characteristic peaks at one, two or three of 10.5°±0.2°, 20.6°±0.2° and 34.5°±0.2° in 2θ expressed in degrees.

[0074] In some embodiments, the differential scanning calorimetry diagram of the crystalline form produces a heat absorption peak between 120-130°C.

[0075] For example, the differential scanning calorimetry diagram of the crystal form can produce heat absorption peaks between 120°C, 121°C, 122°C, 123°C, 124°C, 125°C, 126°C, 127°C, 128°C, 129°C, 130°C, etc.

[0076] In some embodiments, the crystal form is monoclinic, the space group is C2 / c, and the unit cell parameters are α=90°, β=93.2540(10)°, γ=90°,

[0077] In some embodiments, the number of molecules in the unit cell is Z=4, and the unit cell volume is

[0078] In some embodiments, the crystal form is a crystal form of γ-aminobutyric acid-cinnamic acid, the crystal form is a monoclinic system, the space group is P21 / c, and the unit cell parameters are α=90°, β=97.847(16)°, γ=90°.

[0079] In some embodiments, the number of molecules in the unit cell is Z=4, and the unit cell volume is

[0080] In some embodiments, the differential scanning calorimetry diagram of the crystalline form produces a heat absorption peak between 110-130°C.

[0081] For example, the differential scanning calorimetry diagram of the crystal form can produce heat absorption peaks between 110°C, 111°C, 112°C, 113°C, 114°C, 115°C, 116°C, 117°C, 118°C, 119°C, 120°C, 121°C, 122°C, 123°C, 124°C, 125°C, 126°C, 127°C, 128°C, 129°C, 130°C, etc.

[0082] In some embodiments, when the substance having a phenylacrylic acid structure is ferulic acid, the supramolecular structure is as follows:

[0083]

[0084] In some embodiments, when the substance having a phenylacrylic acid structure is cinnamic acid, the supramolecular structure is as follows:

[0085]

[0086] In some embodiments, the non-covalent bond is a non-covalent bond formed between a carboxyl group of a substance having a phenylacrylic acid structure and an amino group of γ-aminobutyric acid.

[0087] In some embodiments, the supramolecular structure is a single crystal.

[0088] The present application provides a method for preparing the supramolecule, comprising:

[0089] Dissolving a substance having a phenyl acrylic acid structure in a solvent I to obtain a solution I;

[0090] dissolving γ-aminobutyric acid in solvent II to obtain solution II;

[0091] Solution II is added to solution I to carry out supramolecular modification reaction;

[0092] After the reaction is completed, the obtained material is crystallized to obtain supramolecules.

[0093] In some embodiments, solvent I and solvent II may be the same or different.

[0094] In some embodiments, the solvent is a polar solvent, such as water, methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran and N,N-dimethylformamide, preferably water, methanol and isopropanol.

[0095] In some embodiments, in the presence of an inert gas, a substance having a phenylacrylic acid structure is dissolved in a solvent I to obtain a solution I. Preferably, the inert gas is nitrogen, argon and / or helium.

[0096] In some embodiments, the substance having a phenylacrylic acid structure is completely dissolved by stirring and dissolving to obtain solution I; preferably, the stirring speed is 200-400 rpm, preferably 250-350 rpm; preferably, the stirring temperature is 40-100°C, preferably 50-90°C.

[0097] For example, the stirring speed is 200rpm, 210rpm, 220rpm, 230rpm, 240rpm, 250rpm, 260rpm, 270rpm, 280rpm, 290rpm, 300rpm, 310rpm, 320rpm, 330rpm, 340rpm, 350rpm, 360rpm, 370rpm, 380rpm, 390rpm, 400rpm, etc.;

[0098] The stirring temperature is 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, etc.

[0099] In some embodiments, a substance having a phenylacrylic acid structure is mixed with solvent I, and an inert gas is introduced to completely replace the air in the reaction container. The substance having a phenylacrylic acid structure is completely dissolved under stirring to obtain solution I.

[0100] In some embodiments, the molar ratio of γ-aminobutyric acid to the substance having a phenylacrylic acid structure (n γ-氨基丁酸 :n 苯丙烯酸结构的物质 ) is 1:0.1-10, preferably 1:1-5.

[0101] For example, the molar ratio of γ-aminobutyric acid to the substance having a phenylacrylic acid structure (n γ-氨基丁酸 :n 苯丙烯酸结构的物质 ) can be 1:0.1, 1:0.5, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, etc.

[0102] In the present application, the molar ratio of γ-aminobutyric acid and the substance having a phenylacrylic acid structure refers to the molar ratio of the materials fed during the reaction.

[0103] In some embodiments, the temperature for adding solution II to solution I for the supramolecular modification reaction is 40-100°C, preferably 50-90°C. For example, the reaction temperature is 40°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, etc.

[0104] Preferably, the reaction time is 6-48 hours, preferably 8-24 hours, and the reaction time is 6 hours, 8 hours, 10 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, 26 hours, 28 hours, 30 hours, 32 hours, 34 hours, 36 hours, 38 hours, 40 hours, 42 hours, 44 hours, 46 hours, 48 hours, etc.

[0105] In some embodiments, solution II is added to solution I for a supramolecular modification reaction, preferably under stirring, and the stirring speed is 200-400 rpm, preferably 250-350 rpm; for example, the stirring speed is 200 rpm, 210 rpm, 220 rpm, 230 rpm, 240 rpm, 250 rpm, 260 rpm, 270 rpm, 280 rpm, 290 rpm, 300 rpm, 310 rpm, 320 rpm, 330 rpm, 340 rpm, 350 rpm, 360 rpm, 370 rpm, 380 rpm, 390 rpm, 400 rpm, etc.

[0106] In some embodiments, the rate of adding Solution II to Solution I is 0.5-20.0 mL / min, preferably 1.5-2.0 mL / min. For example, the rate can be 0.5 mL / min, 1.0 mL / min, 1.5 mL / min, 2.0 mL / min, 2.5 mL / min, 3.0 mL / min, 4.0 mL / min, 5.0 mL / min, 6.0 mL / min, 7.0 mL / min, 8.0 mL / min, 9.0 mL / min, 10.0 mL / min, 11.0 mL / min, 12.0 mL / min, 13.0 mL / min, 14.0 mL / min, 15.0 mL / min, etc.

[0107] In some embodiments, after the reaction is completed, the obtained material is cooled and dried. For example, the obtained material is slowly cooled to room temperature, vacuum dried, and then crystallized to obtain supramolecules.

[0108] In some embodiments, the vacuum drying is performed using a rotary evaporator; preferably, the rotary evaporation time of the rotary evaporator is 1-20 hours, preferably 2-8 hours.

[0109] For example, the rotary evaporation time of the rotary evaporator can be 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, etc.

[0110] In some embodiments, the temperature is adjusted to -1 to -20°C to allow the obtained material to be crystallized. Preferably, the temperature is adjusted to -5 to -10°C.

[0111] For example, the temperature can be adjusted to -1°C, -2°C, -3°C, -4°C, -5°C, -6°C, -7°C, -8°C, -9°C, -10°C, -11°C, -12°C, -13°C, -14°C, -15°C, -16°C, -17°C, -18°C, -19°C, -20°C, etc.

[0112] In some embodiments, the supramolecules obtained by crystallization are placed in a drying oven for vacuum drying, preferably at a drying temperature of 40-65° C., more preferably 45-60° C.;

[0113] Preferably, the drying time is 5-20 hours, preferably 10-15 hours.

[0114] The present application provides the use of gamma-aminobutyric acid and a substance having a phenylacrylic acid structure in the preparation of supramolecules.

[0115] The supramolecule prepared by the method described in the present application is a spatial structure formed by the non-covalent interaction between GABA and a substance having a phenylacrylic acid structure, which significantly improves the efficacy and activity of the substance having a phenylacrylic acid structure and GABA, and achieves synergistic enhancement between the substance having a phenylacrylic acid structure and GABA.

[0116] In the present application, the method for determining synergistic enhancement can be verified by comparing the efficacy of the supramolecule with the efficacy of the free mixture with the same content, and the King's formula can also be used to qualitatively determine whether the clinical combination of drugs has synergistic properties. King's formula: q = E(a+b) / (Ea+Eb-Ea×Eb).

[0117] When used to evaluate the synergistic effect of the supramolecule on MMP-1, E(a+b) is the MMP-1 inhibition rate of the combined drug treatment group, and Ea and Eb are the MMP-1 inhibition rates after drug a and drug b are treated alone, respectively. If q>1.15, it indicates a synergistic effect; 0.85≤q≤1.15 indicates a simple additive effect when the two drugs are used together; and q<0.85 indicates an antagonistic effect.

[0118] Similarly, when used to evaluate the synergistic effect of the supramolecule on elastin, E(a+b) is the rate of increase in elastin in the combined drug treatment group, Ea and Eb are the rates of increase in elastin after drug a and drug b treatment alone, respectively. If q>1.15, it indicates a synergistic effect; 0.85≤q≤1.15 indicates a simple additive effect when the two drugs are used together; q<0.85 indicates an antagonistic effect.

[0119] The present application provides the use of the supramolecule described above or the supramolecule prepared by the preparation method described above in the preparation of products. Preferably, the product includes cosmetics.

[0120] Preferably, the amount of the supramolecule added to the product is 0.1-30 wt%, preferably 0.5-5 wt%. For example, the amount of the supramolecule added can be 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, etc.

[0121] Preferably, the cosmetics include but are not limited to lotions, emulsions or creams.

[0122] The present application provides a cosmetic composition comprising the supramolecule described above or the supramolecule prepared by the preparation method described above.

[0123] In some embodiments, the supramolecule accounts for 0.1-30% by mass in the cosmetic composition, preferably 0.5-5%.

[0124] In some embodiments, the cosmetic composition includes but is not limited to lotions, emulsions, or creams.

[0125] Preferably, the cosmetic composition further comprises excipients and / or other functional ingredients.

[0126] In the present application, the auxiliary materials are commonly used in the art, for example, surfactants, moisturizers, oils, preservatives, alcohols, flavors, dyes, pigments, etc.

[0127] In the present application, the other functional ingredients include oil-soluble active ingredients and / or water-soluble active ingredients.

[0128] Example

[0129] This application provides general and / or specific descriptions of the materials and experimental methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used without manufacturer indication are commercially available conventional reagents. The raw materials and equipment used in the examples and comparative examples are shown in Table 1.

[0130] Table 1 Raw materials and equipment used in the examples

[0131] name factory GABA Bloomage Bio Ferulic acid Shaanxi Bolin Biological, purity 98% Cinnamic acid Adamas, 98% purity Methanol Adamas, 99% pure ethanol Adamas, 99% pure Isopropyl alcohol Adamas, 99% pure acetone Adamas, 99% pure Acetonitrile Adamas, 99% pure Tetrahydrofuran Adamas, 99.9% purity N,N-Dimethylformamide Greagent, 99.9% purity Reactor Shanghai Sinovac Rotary evaporator Zhengzhou Great Wall Science, Industry and Trade Pump-push syringe Keli Jianyuan

[0132] Example 1 Preparation of supramolecular GABA-ferulic acid

[0133] (1) 19.4 g (0.1 mol) of ferulic acid was weighed and added to a reaction kettle, followed by the addition of 200 mL of methanol solvent. Inert nitrogen was introduced into the reaction kettle and replaced 3 to 5 times until the air in the reaction kettle was completely replaced. Stirring and heating were started at a stirring speed of 300 rpm and a temperature of 70° C. until the ferulic acid was completely dissolved to obtain a clear and transparent solution.

[0134] (2) In another container, weigh 10.3 g of GABA (0.1 mol), add 30 mL of deionized water, and stir until the GABA is completely dissolved to obtain a colorless, clear, and transparent solution.

[0135] (3) Maintaining the stirring speed and stirring temperature in the reactor of step (1), the GABA solution was added dropwise to the reactor at a rate of 1.8 mL / min via a pump-driven syringe, so that GABA and ferulic acid under these reaction conditions underwent supramolecular modification reaction, and the reaction time was 10 h. After the reaction, the material was slowly cooled to room temperature and transferred to a rotary evaporator, the temperature was set to 50° C., the vacuum was set to 0.09 MPa, and the rotary evaporation was performed for 1 h to remove most of the solvent. The rotary evaporator temperature was then adjusted to -7° C. and stirring was continued for 3 h until the supramolecular GABA-ferulic acid precipitated. After the supramolecular GABA-ferulic acid precipitated, it was filtered, the filtrate was discarded, the solid was collected, and it was placed in a 55° C. vacuum oven for 12 h to obtain a final crystal sample with a purity of 99.68% and a yield of 86.68%.

[0136] The structural formula of the supramolecule obtained in Example 1 is shown below:

[0137]

[0138] Its structure was identified by the following method:

[0139] A. Powder Diffraction

[0140] Powder diffraction is a technical means of using X-ray, neutron or electron diffraction to characterize the structure of powder or microcrystalline samples. When verifying the supramolecular structure by X-ray powder diffractometer, first, the sample is evenly sprinkled into the sample cell, solidified, and a wide-angle diffraction-Co target (5-85°) is set, the scanning speed is 8° / min, the scanning time is set to 10 minutes, and data is collected after the scanning is completed. The product obtained in Example 1 is subjected to powder diffraction, and the results are shown as follows. Figure 1 shown.

[0141] from Figure 1 It can be seen that the powder diffraction spectrum of the supramolecular GABA-ferulic acid shows characteristic peaks at 2θ=27.1°±0.2°, 30.8°±0.2°, 24.3°±0.2°, 10.5°±0.2°, 20.6°±0.2°, and 34.5°±0.2°. Compared with the diffraction spectrum of GABA and ferulic acid monomers, the characteristic peaks of ferulic acid monomer at 2θ=22.1°±0.2° and 25.6°±0.2° disappear, and a new characteristic peak appears at 2θ=27.1°±0.2°, proving that a new phase is generated, indicating that GABA and ferulic acid form a new crystal structure.

[0142] B. Single crystal diffraction

[0143] The eutectic structure is formed by the assembly of different types of molecules through intermolecular forces (hydrogen bonds, van der Waals forces, π-π stacking and electrostatic interactions, etc.), and belongs to the category of supramolecular compounds. Single crystal diffraction is an experimental method that uses the diffraction effect of single crystals on X-rays to determine the crystal structure. A Bruker X-ray single crystal diffractometer is used to identify the supramolecular single crystal structure. A suitable single crystal is selected and mounted on a crystal stage. The test environment is controlled with liquid nitrogen, and data is then collected. The product obtained in Example 1 is subjected to single crystal diffraction, and the results are shown below. Figure 2 shown.

[0144] from Figure 2 It can be seen that the supramolecular cocrystal parameters are monoclinic, C2 / c space group, and the unit cell parameters are α=90°,β=93.2540(10)°,γ=90°,Z=4,the unit cell volume is The molecular formula is C 14 H 19 N2O6.

[0145] C. Differential Scanning Calorimetry

[0146] Differential Scanning Calorimetry (DSC) uses the heat change of a sample during a thermal reaction to detect the thermal transition temperature of the sample. When using a differential scanning calorimeter to verify the new supramolecular structure, the sample is first placed in a crucible, then mounted on a sample stage. Under a nitrogen atmosphere, the temperature is raised from -20°C to 160°C at a rate of 5°C / min, and the cycle is repeated three times. The data is then analyzed. The product obtained in Example 1 was subjected to differential scanning calorimetry analysis, and the results are shown below. Figure 3 shown.

[0147] from Figure 3 It can be seen that an obvious change in heat absorption peak appears at around 120-130°C, which is significantly different from the heat absorption peak generated between GABA monomers (195°C) and the heat absorption peak generated between ferulic acid monomers (168-172°C), indicating that GABA and ferulic acid have formed a new molecular structure.

[0148] D. Determination of the molar ratio of GABA and ferulic acid by nuclear magnetic resonance

[0149] First, the sample was dissolved in deuterated methanol solvent. The nuclear magnetic resonance instrument used was a Bruker nuclear magnetic resonance spectrometer. The nuclear magnetic intensity was set to 400 MHz and scanned 1024 times. Liquid nitrogen was used to control the ambient temperature. The nuclear magnetic resonance of the product obtained in Example 1 was as follows: Figure 4 shown.

[0150] from Figure 4 It can be seen that δ3.30-3.31ppm is the solvent peak of deuterated methanol, among which the chemical shifts of the characteristic peaks of GABA are δ3.00-2.98ppm (t, 2H), 2.39-2.37ppm (t, 2H), and 1.93-1.88ppm (m, 2H), which correspond to the peak positions of the three methylene groups (CH2-) in the GABA molecular structure, respectively. The sum of the peaks of the six hydrogen atoms is about 6 (2.03+2.03+2.03), which is consistent with the characteristic peaks of 1 mol GABA.

[0151] The chemical shifts of the characteristic ferulic acid peaks are δ7.54-7.52 ppm (d, 1H) corresponding to methine (CH-), 7.17 ppm (d, 1H) corresponding to methine (CH-), 7.06-7.04 ppm (dd, 1H) corresponding to methine (CH-), 6.83-6.82 ppm (d, 1H) corresponding to methine (CH-), 6.35-6.33 ppm (d, 1H), and 3.90 ppm (s, 3H) corresponding to methyl (CH3-). The sum of the eight hydrogen atom peaks is approximately 8 (1.03+1.05+1.06+1.03+1.00+3.08), consistent with the characteristic peaks of 1 mole of ferulic acid. Other hydrogen atoms do not emit peaks under the test conditions, so the molar ratio of GABA to ferulic acid in the supramolecular GABA-ferulic acid is 1:1.

[0152] E. Infrared spectroscopy analysis

[0153] FTIR spectroscopy uses the selective absorption of specific wavelengths of infrared light by chemical bonds or functional groups in molecules, causing transitions in vibrational and rotational energy levels. Infrared spectroscopy detects changes in dipole moments produced by molecular vibration and is more sensitive to polar groups. When verifying supramolecular structures using Fourier transform infrared spectrometers, the scanning range is 4000-400 cm -1 The samples were compressed using the potassium bromide compression method, and each sample was scanned 64 times. The infrared spectrum of the product obtained in Example 1 is shown in FIG. Figure 7 shown.

[0154] The infrared spectrum of supramolecular GABA-ferulic acid showed the following peaks at 3160, 3050, 3000, 2950, 2920, 2900, 2620, 2510, 2020, 1940, 1900, 1870, 1690, 1640, 1630, 1600, 1540, 1500, 1470, 1440, 1400, 1380, 1310, 1240, 1210, 1160, 1120, 1040, 973, 935, 886, 863, 838, 823, 790, 661, 602, 582, and 569 cm -1 There is a characteristic peak of infrared spectrum at the position where the allowable deviation of the characteristic peak of infrared spectrum is ±2cm -1 .

[0155] The supramolecular GABA-ferulic acid structure also contains the characteristic peak of GABA (wave number 1640 cm -1 The peak is attributed to C=O stretching vibration, with a wave number of 1400 cm -1 The peak is attributed to the bending vibration of -OH, with a wave number of 1310 cm -1 Peak attributed to CO stretching vibration), characteristic peak of ferulic acid structure (wave number is 1500cm -1Peaks are attributed to the vibration peaks of the benzene ring skeleton); at the same time, some characteristic peaks of GABA (wave number is 2200cm- 1 The bending vibration peak assigned to NH is at 1595 cm -1 The deformation vibration peaks attributed to NH) disappeared, and some characteristic peaks of ferulic acid structure (wave number 3440 cm -1 The stretching vibration peak attributed to -OH is 3020 cm- 1 The stretching vibration peak of benzene ring CH is 1680 cm -1 The vibration peak attributed to the benzene ring) disappeared; the supramolecular GABA-ferulic acid structure had a wave number of 2920 cm -1 A broad hydrogen bond peak is formed at the cation, which is caused by the association of -OH and -NH, indicating the existence of supramolecular forces in the system.

[0156] Example 2

[0157] (1) Weigh 97 g (0.5 mol) of ferulic acid into a reaction kettle, then add 200 mL of methanol solvent, introduce inert nitrogen gas, and replace it 3 to 5 times until the air in the kettle is completely replaced. Stir and heat at a stirring speed of 300 rpm and a temperature of 70° C. until the ferulic acid is completely dissolved to obtain a clear and transparent solution;

[0158] (2) In another container, weigh 10.3 g of GABA (0.1 mol), add 30 mL of deionized water, and stir until the GABA is completely dissolved to obtain a colorless, clear, and transparent solution.

[0159] (3) Maintaining the stirring speed and stirring temperature in the reactor of step (3) unchanged, the GABA solution was added dropwise to the reactor at a rate of 1.8 mL / min via a pump-driven syringe, so that GABA and ferulic acid under these reaction conditions underwent supramolecular modification reaction, and the reaction time was 10 h. After the reaction, the material was slowly cooled to room temperature and transferred to a rotary evaporator, the temperature was set to 50° C., the vacuum was set to 0.09 MPa, and the rotary evaporation was performed for 1 h to remove most of the solvent. The rotary evaporator temperature was then adjusted to -7° C. and stirring was continued for 3 h until the supramolecular GABA-ferulic acid precipitated. After the supramolecular GABA-ferulic acid precipitated, it was filtered, the filtrate was discarded, the solid was collected, and it was placed in a 55° C. vacuum oven and dried for 12 h to obtain a final crystal sample with a purity of 99.73% and a yield of 89.92%.

[0160] The product obtained in Example 2 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0161] Example 3

[0162] The difference between Example 3 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 40° C., and the temperature during the precipitation process is −1° C. The purity of the obtained supramolecule is 90.02%, and the yield is 87.15%.

[0163] The product obtained in Example 3 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0164] Example 4

[0165] The difference between Example 4 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 40° C., the purity of the obtained supramolecule is 91.48%, and the yield is 88.15%.

[0166] The product obtained in Example 4 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0167] Example 5

[0168] The difference between Example 5 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 40°C, and the temperature during the precipitation process is -20°C. The purity of the obtained supramolecule is 89.88% and the yield is 85.62%.

[0169] The product obtained in Example 5 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0170] Example 6

[0171] The difference between Example 6 and Example 1 is that water is used as the solvent, the temperature during the precipitation process is -1°C, and the purity of the obtained supramolecule is 93.22% and the yield is 82.19%.

[0172] The product obtained in Example 6 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0173] Example 7

[0174] The difference between Example 7 and Example 1 is that water is used as the solvent, and the purity of the obtained supramolecule is 96.77% and the yield is 82.54%.

[0175] The product obtained in Example 7 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0176] Example 8

[0177] The difference between Example 8 and Example 1 is that water is used as the solvent, the temperature during the precipitation process is -20°C, and the purity of the obtained supramolecule is 95.23% and the yield is 80.67%.

[0178] The product obtained in Example 8 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0179] Example 9

[0180] The difference between Example 9 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 100° C., and the temperature during the precipitation process is −1° C. The purity of the obtained supramolecule is 89.95%, and the yield is 83.81%.

[0181] The product obtained in Example 9 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0182] Example 10

[0183] The difference between Example 10 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 100° C., the purity of the obtained supramolecule is 88.99%, and the yield is 85.42%.

[0184] The product obtained in Example 10 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0185] Example 11

[0186] The difference between Example 11 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 100° C., and the temperature during the precipitation process is −20° C. The purity of the obtained supramolecule is 91.03%, and the yield is 84.30%.

[0187] The product obtained in Example 11 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0188] Example 12

[0189] The difference between Example 12 and Example 1 is that isopropyl alcohol is used as the solvent, and the purity of the obtained supramolecule is 90.62% and the yield is 87.21%.

[0190] The product obtained in Example 12 was measured according to the method described in Example 1 and was found to be a 1:1 supramolecule.

[0191] Comparative Example 1

[0192] The difference between Comparative Example 1 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 40° C., and the temperature during the precipitation process is 4° C., and supramolecules cannot be formed.

[0193] Comparative Example 2

[0194] The difference between Comparative Example 2 and Example 1 is that water is used as the solvent, the temperature during the precipitation process is 4° C., and supramolecules cannot be formed.

[0195] Comparative Example 3

[0196] The difference between Comparative Example 3 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 100° C., and the temperature during the precipitation process is 4° C., and supramolecules cannot be formed.

[0197] Comparative Example 4

[0198] The difference between Comparative Example 4 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 30° C., and the temperature during the precipitation process is −1° C., and thus no supramolecules can be formed.

[0199] Comparative Example 5

[0200] The difference between Comparative Example 5 and Example 1 is that water is used as the solvent and the heating temperature during the synthesis process is 30° C., so supramolecules cannot be formed.

[0201] Comparative Example 6

[0202] The difference between Comparative Example 6 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 30° C., and the temperature during the precipitation process is −20° C., and thus no supramolecules can be formed.

[0203] Comparative Example 7

[0204] The difference between Comparative Example 7 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 30° C., and the temperature during the precipitation process is 4° C., and supramolecules cannot be formed.

[0205] Comparative Example 8

[0206] The difference between Comparative Example 8 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 120° C., and the temperature during the precipitation process is −1° C., and thus supramolecules cannot be formed.

[0207] Comparative Example 9

[0208] The difference between Comparative Example 9 and Example 1 is that water is used as the solvent and the heating temperature during the synthesis process is 120° C., so supramolecules cannot be formed.

[0209] Comparative Example 10

[0210] The difference between Comparative Example 10 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 120° C., and the temperature during the precipitation process is −20° C., and thus no supramolecules can be formed.

[0211] Comparative Example 11

[0212] The difference between Comparative Example 11 and Example 1 is that water is used as the solvent, the heating temperature during the synthesis process is 120° C., and the temperature during the precipitation process is 4° C., and supramolecules cannot be formed.

[0213] Comparative Example 12

[0214] The difference between Comparative Example 12 and Example 1 is that the heating temperature during the synthesis process is 30° C., and supramolecules cannot be formed.

[0215] Comparative Example 13

[0216] The difference between Comparative Example 13 and Example 1 is that the heating temperature during the synthesis process is 120° C., and supramolecules cannot be formed.

[0217] Comparative Example 14

[0218] The difference between Comparative Example 14 and Example 1 is that the temperature during the precipitation process is 4° C., and supramolecules cannot be formed.

[0219] Comparative Example 15

[0220] The difference between Comparative Example 15 and Example 1 is that n-hexane is used as the solvent and supramolecules cannot be formed.

[0221] Comparative Example 16

[0222] The difference between Comparative Example 16 and Example 1 is that carbon tetrachloride is used as the solvent, and supramolecules cannot be formed.

[0223] Comparative Example 17

[0224] The difference between Comparative Example 17 and Example 1 is that no solvent is used and supramolecules cannot be formed.

[0225] Example 13 Preparation of supramolecular GABA-cinnamic acid

[0226] (1) 14.8 g (0.1 mol) of cinnamic acid was weighed and added to a reaction kettle. 200 mL of methanol solvent was then added. Inert nitrogen was introduced into the kettle and replaced 3 to 5 times until the air in the kettle was completely replaced. Stirring and heating were started at a stirring speed of 300 rpm and a temperature of 70°C until the cinnamic acid was completely dissolved to obtain a clear and transparent solution.

[0227] (2) In another container, weigh 10.3 g (0.1 mol) of GABA, add 30 mL of deionized water, and stir until the GABA is completely dissolved to obtain a colorless, clear, and transparent solution.

[0228] (3) Maintaining the stirring speed and stirring temperature in the reactor of step (1) unchanged, the GABA solution was added dropwise to the reactor at a rate of 1.5 mL / min via a pump-driven syringe, so that GABA and cinnamic acid under these reaction conditions underwent supramolecular modification reaction, and the reaction time was 10 h. After the reaction, the material was slowly cooled to room temperature and transferred to a rotary evaporator, the temperature was set to 50°C, the vacuum was 0.09 MPa, and the rotary evaporation was performed for 1 h to remove most of the solvent. The rotary evaporator temperature was then adjusted to -7°C, and stirring was continued for 4 h until supramolecular GABA-cinnamic acid precipitated. After the supramolecular GABA-cinnamic acid precipitated, it was filtered, the filtrate was discarded, the solid was collected, and it was placed in a 55°C vacuum oven and dried for 13 h to obtain a final crystal sample with a purity of 99.21% and a yield of 88.45%.

[0229] The structural formula of the obtained supramolecular is shown below:

[0230]

[0231] Its structure was identified by the following method:

[0232] A. Single crystal diffraction

[0233] The eutectic structure is formed by the assembly of different types of molecules through intermolecular forces (hydrogen bonds, van der Waals forces, π-π stacking and electrostatic interactions, etc.), and belongs to the category of supramolecular compounds. Single crystal diffraction is an experimental method that uses the diffraction effect of single crystals on X-rays to determine the crystal structure. A Bruker X-ray single crystal diffractometer was used to identify the supramolecular single crystal structure. A suitable single crystal was selected and mounted on a crystal stage. The test environment was controlled with liquid nitrogen, and data was then collected. The product obtained in Example 13 was subjected to single crystal diffraction, and the results are shown below. Figure 8 shown.

[0234] from Figure 8 It can be seen that the supramolecular cocrystal parameters are monoclinic, P21 / c space group, and the unit cell parameters are α=90°,β=97.847(16)°,γ=90°,Z=4,the unit cell volume is The molecular formula is C 13 H 17 NO4.

[0235] B. Differential Scanning Calorimetry

[0236] Differential Scanning Calorimetry (DSC) uses the heat change of a sample during a thermal reaction to detect the thermal transition temperature of the sample. Using a differential scanning calorimeter to verify the new supramolecular structure, the sample was first placed in a crucible and mounted on a sample stage. Under a nitrogen atmosphere, the temperature was raised from -20°C to 160°C at a rate of 5°C / min, and the cycle was repeated three times. Data analysis was then performed. The product obtained in Example 13 was subjected to differential scanning calorimetry analysis, and the results are shown below. Figure 9 shown.

[0237] from Figure 9 It can be seen that on the differential scanning calorimetry analysis curve of supramolecular GABA-cinnamic acid, there is an obvious change in the heat absorption peak at around 110-130°C, which is significantly different from the heat absorption peak of GABA monomer (195°C) and the heat absorption peak of cinnamic acid monomer (131-136°C), indicating that GABA and cinnamic acid have formed a new molecular structure.

[0238] C. Determination of the molar ratio of GABA and cinnamic acid by NMR

[0239] The sample obtained in Example 13 was dissolved in deuterated methanol solvent. The nuclear magnetic resonance instrument used was a Bruker nuclear magnetic resonance spectrometer with a nuclear magnetic intensity of 400 MHz and 1024 scans. Liquid nitrogen was used to control the ambient temperature. The results are shown in FIG. Figure 10 shown.

[0240] Deuterated methanol was used as the deuterated reagent (CD3OD), where δ3.30-3.31 ppm is the solvent peak of deuterated methanol; δ2.98-2.96 ppm (t, 2H), 2.37-2.35 ppm (t, 2H), and 1.91-1.86 ppm (m, 2H) correspond to the peak positions of the three methylene groups (CH2-) in the GABA molecular structure, respectively. The total peak area of the six hydrogen atoms is approximately 6 (2.08 + 2.01 + 2. 08), consistent with the characteristic peak of 1 mol of GABA; δ7.58-7.55 ppm (m, 3H) corresponds to three methine (CH-) groups, 7.37-7.35 ppm (m, 3H) corresponds to three methine (CH-) groups, and 6.50-6.48 ppm (d, 1H) corresponds to one methine (CH-). The sum of the peak areas of the seven hydrogen atoms is approximately 7 (3.08 + 3.00 + 1.00), consistent with the characteristic peak of 1 mol of cinnamic acid. The H NMR spectrum indicates that the molar ratio of GABA to cinnamic acid in the supramolecular GABA-cinnamic acid is 1:1, and besides the solvent peak, water peak, and the characteristic peak of GABA-cinnamic acid, there are no other impurity peaks.

[0241] D. Infrared spectroscopy analysis

[0242] FTIR spectroscopy uses the selective absorption of specific wavelengths of infrared light by chemical bonds or functional groups in molecules, causing transitions in vibrational and rotational energy levels. Infrared spectroscopy detects changes in dipole moments produced by molecular vibration and is more sensitive to polar groups. When verifying supramolecular structures using Fourier transform infrared spectrometers, the scanning range is 4000-400 cm -1 The samples were compressed using the potassium bromide compression method, and each sample was scanned 64 times. The infrared spectrum of the product obtained in Example 13 is shown in FIG. Figure 12 shown.

[0243] The infrared spectrum of supramolecular GABA-cinnamic acid shows the following peaks at 3430, 3030, 2950, 2920, 2850, 2650, 2550, 2180, 1730, 1640, 1580, 1500, 1450, 1400, 1310, 1250, 1200, 1070, 976, 944, 918, 875, 848, 777, 728, 716, 690, 669, 590, 539, 486 cm -1 There is a characteristic peak of infrared spectrum at the position where the allowable deviation of the characteristic peak of infrared spectrum is ±2cm -1 .

[0244] The supramolecular GABA-cinnamic acid structure also contains the characteristic peak of GABA (wave number 2200cm- 1 The bending vibration peak assigned to NH is at 1640 cm -1 The peak is attributed to C=O stretching vibration, with a wave number of 1400 cm -1 The peak is attributed to the bending vibration of -OH, with a wave number of 1310 cm -1 Peak attributed to CO stretching vibration), characteristic peak of cinnamic acid (wave number is 1500cm -1 The peaks belong to the vibration peaks of the benzene ring skeleton); at the same time, some characteristic peaks of GABA (wave number 1595cm -1 The deformation vibration peaks attributed to NH) disappeared, and some characteristic peaks of cinnamic acid (wave number 3020cm -1 The stretching vibration peak of benzene ring CH is at 1680 cm -1 The vibration peak attributed to the benzene ring disappears; the supramolecular GABA-cinnamic acid structure has a wave number of 2920 cm -1 A broad hydrogen bond peak is formed at the cation, which is caused by the association of -OH and -NH, indicating the existence of supramolecular forces in the system.

[0245] Example 14 Preparation of supramolecular GABA-cinnamic acid

[0246] (1) 74 g (0.5 mol) of cinnamic acid was weighed and added to a reaction kettle. 200 mL of methanol solvent was then added. Inert nitrogen was introduced into the kettle and replaced 3 to 5 times until the air in the kettle was completely replaced. Stirring and heating were started at a stirring speed of 300 rpm and a temperature of 70°C until the cinnamic acid was completely dissolved to obtain a clear and transparent solution.

[0247] (2) In another container, weigh 10.3 g (0.1 mol) of GABA, add 30 mL of deionized water, and stir until the GABA is completely dissolved to obtain a colorless, clear, and transparent solution.

[0248] (3) Maintaining the stirring speed and stirring temperature in the reactor of step (1) unchanged, the GABA solution was added dropwise to the reactor at a rate of 1.5 mL / min via a pump-driven syringe, so that GABA and cinnamic acid under these reaction conditions underwent supramolecular modification reaction, and the reaction time was 10 h. After the reaction, the material was slowly cooled to room temperature and transferred to a rotary evaporator, the temperature was set to 50°C, the vacuum was 0.09 MPa, and the rotary evaporation was performed for 1 h to remove most of the solvent. The rotary evaporator temperature was then adjusted to -7°C, and stirring was continued for 4 h until supramolecular GABA-cinnamic acid precipitated. After the supramolecular GABA-cinnamic acid precipitated, it was filtered, the filtrate was discarded, the solid was collected, and it was placed in a vacuum oven at 55°C for 13 h to obtain a final crystal sample with a purity of 99.62% and a yield of 87.23%.

[0249] The product obtained in Example 14 was measured according to the method described in Example 13 and was found to be a 1:1 supramolecule.

[0250] Table 1 Process conditions for preparing supramolecules in Example

[0251]

[0252]

[0253] Experimental Example: Anti-wrinkle Effect of Supramolecular Materials

[0254] Ultraviolet radiation can cause skin cells to produce a large number of free radicals, which will induce the production of a large number of matrix metalloproteinases (MMP-1), thereby promoting the degradation of collagen. In addition, ultraviolet radiation can also cause cellular oxidative stress, affecting ECM synthesis and degradation. Therefore, this experiment used fibroblasts as the research object and used UVA irradiation to establish an in vitro photoaging model, that is, the group that needed irradiation was irradiated with UVA at a dose of 30J / cm 2 After irradiation, the cells were placed in an incubator (37°C, 5% CO2) for 24 hours, and the anti-wrinkle efficacy of the samples was evaluated by detecting changes in MMP-1 and elastin content.

[0255] The method for determining the MMP-1 content is as follows:

[0256] Press 2×10 5 Cells were inoculated into 6-well plates at a seeding density of cells / well and incubated overnight in an incubator (37°C, 5% CO2). According to the test plan, when the cell plating rate in the 6-well plate reached 40% to 60%, the drugs were divided into groups and administered. The negative control group was not administered but UVA irradiation was increased. The sample group was administered normally and UVA irradiation was increased. The sample group dissolved the free monomer, free mixture and supramolecule in water, and the dosage per well was 2 mL. Each group had 3 replicates and was incubated in an incubator (37°C, 5% CO2) for 24 hours. According to the test grouping, the groups that needed to be irradiated were irradiated with UVA, and the irradiation dose was 30 J / cm 2 After irradiation, the cells were placed in an incubator (37°C, 5% CO2) and cultured for 24 hours. After incubation, the cell culture medium was collected and the MMP-1 content was assayed by ELISA.

[0257] The method for determining elastin content is as follows:

[0258] Press 2×10 5 Cells were inoculated into 6-well plates at a seeding density of cells / well and incubated overnight in an incubator (37°C, 5% CO2). According to the test plan, when the cell plating rate in the 6-well plate reached 40% to 60%, the drugs were divided into groups and administered. The negative control group was not administered but UVA irradiation was increased. The sample group was administered normally and UVA irradiation was increased. The sample group dissolved the free monomer, free mixture and supramolecule in water, and the dosage per well was 2 mL. Each group had 3 replicates and was incubated in an incubator (37°C, 5% CO2) for 24 hours. According to the test grouping, the groups that needed to be irradiated were irradiated with UVA, and the irradiation dose was 30 J / cm 2 After irradiation, the cells were placed in an incubator (37°C, 5% CO2) and cultured for 24 hours. After incubation, the cell culture medium was collected and the elastin content was tested by ELISA.

[0259] A. Anti-wrinkle efficacy of GABA-ferulic acid supramolecular

[0260] Matrix metalloproteinase-1 (MMP-1) is a key enzyme in collagen degradation. The lower the content, the less collagen degradation and the better the anti-wrinkle effect. This study used a fibroblast model to damage the fibroblasts by ultraviolet light UVA stimulation. After administration, the differences in the regulation of MMP-1 content by the supramolecular GABA-ferulic acid of Example 1, monomeric ferulic acid, and monomeric GABA were compared. The results are shown in Table 3 and Figure 13 As shown, Table 2 is the dosage table of different groups.

[0261] Table 2

[0262]

[0263] Table 3

[0264] No. MMP-1 content (pg / mL) 1 142932.44 2 110885.89 3 135957.83 4 100052.71 5 53742.60

[0265] From Table 3 and Figure 13 It can be seen that the supramolecular composition of the present application reduced the MMP-1 content by 62.40% compared with the negative control group (NC group), which is significantly higher than the reduction of the physical mixture of free GABA and ferulic acid (30.00%); it is also significantly higher than the reduction of monomeric ferulic acid (22.41%) and the reduction of GABA (4.88%). The q value calculated according to King's formula is 2.38>1.15, that is, it has synergistic properties, indicating that the GABA-ferulic acid supramolecular composition can synergistically enhance the effect in reducing the level of MMP-1.

[0266] B. Anti-wrinkle effects of GABA-cinnamic acid

[0267] Matrix metalloproteinase-1 (MMP-1) is a key enzyme in collagen degradation. Lower levels indicate less collagen degradation and greater anti-wrinkle effects. This test utilizes a fibroblast model, damaging the fibroblasts through UVA stimulation. Following administration, the effects of GABA-cinnamic acid supramolecular, monomeric cinnamic acid, and monomeric GABA on MMP-1 levels were compared.

[0268] Elastin is a key component of skin proteins. Its content determines skin elasticity and wrinkle severity, making it a valuable indicator of anti-aging efficacy; the higher the elastin content, the better the effect. This test utilizes a fibroblast model to simulate oxidative stress. Ultraviolet (UVA) light is used to damage the fibroblasts. Following administration, elastin levels are measured.

[0269] Among them, Table 4 is the dosage table of different groups, and Table 5 is the MMP-1 content and elastin content table of different groups. Figure 14 and Figure 15 Schematic diagrams of the MMP-1 content and elastin content in different groups.

[0270] Table 4

[0271]

[0272] Table 5

[0273] No. MMP-1 content (pg / mL) Elastin content (pg / mL) P1 142917.87 293.78 P2 135957.83 300.99 P3 135698.37 392.71 P4 128626.09 393.67 P5 96083.69 485.95

[0274] From Table 5 and Figure 14It can be seen that the supramolecular composition of the present application can reduce the MMP-1 content by 32.77% relative to the negative control group (NC), which is significantly higher than the reduction amount of the physical mixture of free GABA and cinnamic acid (10.00%); it is also significantly higher than the reduction amount of GABA (4.86%) and cinnamic acid (5.05%). According to King's formula, q = 3.39 > 1.15 is obtained, that is, it has synergistic properties, indicating that the GABA-cinnamic acid supramolecular composition can synergistically enhance the effect in reducing the MMP-1 content.

[0275] From Table 5 and Figure 15 It can be seen that the supramolecular composition of the present application can increase the elastin content by 65.41% compared with the negative control group (NC), which is significantly higher than the increase rate of the physical mixture of free GABA and cinnamic acid (34.00%); it is also significantly higher than the increase rate of GABA monomer (2.45%) and the increase rate of cinnamic acid monomer (33.67%). According to King's formula, q = 1.85 > 1.15 is obtained, that is, there is synergy, indicating that the GABA-cinnamic acid supramolecular has synergistic synergy in increasing the elastin content, indicating that the supramolecular GABA-cinnamic acid has excellent anti-aging effect.

[0276] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application in any other manner. Any person skilled in the art may utilize the above disclosed technical content to modify or modify the present application into equivalent embodiments with equivalent variations. However, any simple modifications, equivalent variations, and modifications to the above embodiments that do not depart from the technical content of the present application and are based on the technical essence of the present application shall still fall within the scope of protection of the present application.

Claims

1. A supramolecule of γ-aminobutyric acid and a substance having a phenylacrylic acid structure, wherein the supramolecule connects the γ-aminobutyric acid and the substance having a phenylacrylic acid structure via a non-covalent bond; The substance having a phenylacrylic acid structure includes one of ferulic acid, cinnamic acid, hydroxycinnamic acid, and sinapinic acid.

2. The supramolecule according to claim 1, wherein The molar ratio of the γ-aminobutyric acid to the substance having a phenylacrylic acid structure is 1:

1.

3. The supramolecule according to claim 1, wherein When the supramolecule was analyzed by infrared spectroscopy, the -1 There is an absorption peak at.

4. The supramolecule according to claim 3, wherein Still at 1640±10cm -1 、1500±10cm -1 One or two of them have absorption peaks.

5. The supramolecule according to claim 4, wherein Still at 1400±10cm -1 、1310±10cm -1 One or two of them have absorption peaks.

6. The supramolecule according to any one of claims 1 to 5, wherein The supramolecule is a γ-aminobutyric acid-ferulic acid supramolecule. When the supramolecule is analyzed using nuclear magnetic resonance, the nuclear magnetic resonance conditions are: CD3OD, 400 MHz, ppm, and the nuclear magnetic characteristics are: 1 HNMR: δ3.00-2.98ppm(t,2H), 2.39-2.37ppm(t,2H), 1.93-1.88ppm(m,2H), δ7.54-7.52ppm(d,1H), 7 .17ppm(d,1H), 7.06-7.04ppm(dd,1H), 6.83-6.82ppm(d,1H), 6.35-6.33ppm(d,1H), 3.90ppm(s,3H).

7. The supramolecule according to any one of claims 1 to 5, wherein The supramolecule is a γ-aminobutyric acid-cinnamic acid supramolecule. When the supramolecule is analyzed using nuclear magnetic resonance, the nuclear magnetic resonance conditions are: CD3OD, 400 MHz, ppm, and the nuclear magnetic characteristics are: 1 HNMR: δ2.98-2.96ppm(t,2H), 2.37-2.35ppm(t,2H), 1.91-1.86ppm(m,2H), δ7.58-7.55ppm(m,3H), 7.37-7.35ppm(m,3H), 6.50-6.48ppm(d,1H).

8. A supramolecule crystal form according to any one of claims 1 to 5, wherein The crystal form is a crystal form of γ-aminobutyric acid-ferulic acid, and the X-ray powder diffraction pattern of the crystal form has characteristic peaks at 27.1°±0.2°, 30.8°±0.2°, and 24.3°±0.2° in terms of 2θ expressed in degrees.

9. The supramolecular crystal form according to claim 8, wherein There are characteristic peaks at one, two or three of 10.5°±0.2°, 20.6°±0.2° and 34.5°±0.2°.

10. A supramolecule crystal form according to any one of claims 1 to 5, wherein The crystal form is a crystal form of gamma-aminobutyric acid-ferulic acid, and a differential scanning calorimetry diagram of the crystal form produces a heat absorption peak between 120-130°C.

11. A supramolecule crystal form according to any one of claims 1 to 5, wherein The crystal form is a crystal form of γ-aminobutyric acid-ferulic acid, and the crystal form is a monoclinic system, the space group is C2 / c, and the unit cell parameters are α=90°, β=93.2540(10)°, γ=90°.

12. The supramolecular crystal form according to claim 11, wherein The number of molecules in the unit cell is Z=4, and the unit cell volume is 13. A supramolecule crystal form according to any one of claims 1 to 5, wherein The crystal form is a crystal form of γ-aminobutyric acid-cinnamic acid, which is a monoclinic crystal system with a space group of P21 / c and a unit cell parameter of α=90°, β=97.847(16)°, γ=90°.

14. The supramolecular crystal form according to claim 13, wherein The number of molecules in the unit cell is Z=4, and the unit cell volume is 15. A supramolecule crystal form according to any one of claims 1 to 5, wherein The crystal form is a crystal form of gamma-aminobutyric acid-cinnamic acid, and a differential scanning calorimetry diagram of the crystal form produces a heat absorption peak between 110-130°C.

16. A method for preparing the supramolecule according to any one of claims 1 to 15, comprising: Dissolving a substance having a phenyl acrylic acid structure in a solvent I to obtain a solution I; dissolving γ-aminobutyric acid in solvent II to obtain solution II; Solution II is added to solution I to carry out supramolecular modification reaction; After the reaction is completed, the obtained material is crystallized to obtain supramolecules; The reaction temperature is 40-100°C; The temperature during the crystallization is -1°C to -20°C; The solvent I and solvent II are polar solvents.

17. The preparation method according to claim 16, wherein The solvent I and solvent II are the same or different.

18. The preparation method according to claim 16, wherein the solvent comprises water, methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran or N,N-dimethylformamide.

19. The preparation method according to claim 16, wherein The reaction temperature is 50-90°C.

20. The preparation method according to claim 16, wherein The temperature during the crystallization is -5°C to -10°C.

21. The preparation method according to any one of claims 16 to 20, wherein The molar ratio of γ-aminobutyric acid to the substance having a phenylacrylic acid structure is 1:0.1-10.

22. The preparation method according to any one of claims 16 to 20, wherein The molar ratio of γ-aminobutyric acid to the substance having a phenylacrylic acid structure is 1:1-5.

23. Use of the supramolecule according to any one of claims 1 to 15 or the supramolecule prepared by the preparation method according to any one of claims 16 to 22 in the preparation of cosmetics.

24. The use according to claim 23, wherein: Application of the supramolecule in anti-aging.

25. Use of gamma-aminobutyric acid and a substance having a phenylacrylic acid structure in preparing supramolecules, wherein the substance having a phenylacrylic acid structure comprises one of ferulic acid, cinnamic acid, hydroxycinnamic acid, and sinapinic acid.

26. A cosmetic composition comprising the supramolecule according to any one of claims 1 to 15 or the supramolecule prepared by the preparation method according to any one of claims 16 to 22.

27. The composition according to claim 26, wherein Calculated by mass percentage in the composition, the supramolecule accounts for 0.1-30%.

28. The composition according to claim 26, wherein Calculated by mass percentage in the composition, the supramolecule accounts for 0.5-5%.

29. The composition according to any one of claims 26 to 28, wherein The composition further comprises excipients and / or other functional ingredients.

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