Supramolecular Structure, Preparation Method and Its Application

Abstract

The present application discloses a supramolecular structure, a preparation method thereof and an application thereof. The supramolecular structure comprises γ-aminobutyric acid and α-hydroxypropionic acid linked by hydrogen bonds. The supramolecular structure is relatively stable, and when added to cosmetics, it can effectively reduce the irritation of the cosmetics.

Description

Technical Field

[0001] This application relates to the technical field of cosmetics, and particularly to a supramolecular structure, a preparation method thereof, and an application thereof. Background Art

[0002] GABA (γ-aminobutyric acid) is an inhibitory neurotransmitter. When applied to cosmetics, it can effectively combat wrinkles. On the one hand, GABA can bind to GABA A receptors in the human body, causing hyperpolarization of the cell membrane, inhibiting neuronal excitation, and thus effectively slowing down the excitatory degree of muscle cell contraction, soothing dynamic expression lines; on the other hand, GABA can promote the production of hyaluronic acid (HA) and collagen in the skin, fading static wrinkles.

[0003] However, because GABA can act on nerve cells, when applying cosmetics containing GABA, a transient sense of irritation will occur. Although this sense of irritation is not skin irritation defined clinically and will not cause damage to the skin, a considerable number of consumers, especially consumers with sensitive skin, find it unacceptable. This has restricted the application of GABA in cosmetics. Summary of the Invention

[0004] In order to solve the problem of the irritation of GABA in the prior art, this application provides a supramolecular structure, and adding the supramolecular structure to cosmetics can reduce the sense of irritation of the cosmetics.

[0005] The specific technical solution of this application is as follows:

[0006] 1. A supramolecular structure, wherein the supramolecular structure comprises γ-aminobutyric acid and α-hydroxypropionic acid linked by hydrogen bonds.

[0007] 2. The supramolecular structure according to item 1, wherein in the spectrum detected by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure has characteristic peaks at a chemical shift δ of 4.44 - 4.54 ppm;

[0008] Preferably, in the spectrum detected by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure has characteristic peaks at chemical shifts δ of 1.19 - 1.3 ppm, 1.71 - 1.9 ppm, 2.29 - 2.4 ppm,

[0009] 2.77 - 3.0 ppm, and 3.92 - 4.2 ppm;

[0010] 3. The supramolecular structure according to any one of items 1 - 2, wherein a hydrogen bond is formed between the carboxyl group of the α-hydroxypropionic acid and the amino group of the γ-aminobutyric acid.

[0011] 4. A method for preparing a supramolecular structure, comprising:

[0012] Mixing γ-aminobutyrate and α-hydroxypropionate under an atmosphere of a mixed gas of nitrogen and carbon dioxide, and stirring to react to obtain the supramolecular structure.

[0013] 5. The method according to item 4, wherein the γ-aminobutyrate includes one or more selected from the hydrochloride, sulfate, carbonate, and bicarbonate of γ-aminobutyric acid;

[0014] Preferably, the α-hydroxypropionate includes a metal salt of α-hydroxypropionic acid, preferably including one or more selected from the sodium salt, potassium salt, copper salt, and calcium salt of α-hydroxypropionic acid;

[0015] Preferably, the molar ratio of the γ-aminobutyrate and the α-hydroxypropionate undergoing the reaction is 1:0.8 - 1.2.

[0016] 6. The method according to item 4 or 5, wherein, calculated by volume percentage in the mixed gas, nitrogen is 1 - 30%;

[0017] Preferably, γ-aminobutyrate and α-hydroxypropionate are mixed under an atmosphere of a mixed gas of nitrogen and carbon dioxide at a pressure of 0.1 - 20 MPa;

[0018] Preferably, the reaction is carried out at a temperature of 0 - 60 °C;

[0019] Preferably, the reaction time is 20 - 72 h;

[0020] Preferably, the stirring is ultrasonic stirring, and preferably, the ultrasonic frequency of the ultrasonic stirring is 5 - 100 kHz;

[0021] Preferably, the ultrasonic power is 20 - 3000 W.

[0022] 7. The method according to any one of items 4 - 6, wherein the method further comprises:

[0023] Separating the obtained mixed solution of the reaction to obtain the supramolecular structure; preferably, the separation method is membrane filtration or centrifugation.

[0024] 8. The method according to any one of items 4 - 7, wherein the supramolecular structure is the supramolecular structure according to any one of claims 1 - 3.

[0025] 9. Application of the supramolecular structure according to any one of items 1 - 3 or the supramolecular structure prepared by the method according to any one of items 4 - 8 in the field of cosmetics,

[0026] Preferably, calculated by the mass percentage in the cosmetic, the supramolecular structure is 0.1 - 30%, preferably 1 - 5%.

[0027] 10. A cosmetic, which comprises the supramolecular structure described in any one of items 1 - 3 or the supramolecular structure prepared by the method described in any one of items 4 - 8. Preferably, calculated by the mass percentage in the cosmetic, the supramolecular structure is 0.1 - 30%, preferably 1 - 5%;

[0028] Preferably, the cosmetic further comprises free γ-aminobutyric acid and / or free α-hydroxypropionic acid;

[0029] Preferably, the cosmetic further comprises excipients.

[0030] 11. Application of the supramolecular structure described in any one of items 1 - 3 or the supramolecular structure prepared by the method described in any one of items 4 - 8 in reducing the irritation of γ-aminobutyric acid in cosmetics.

[0031] Effects of the invention

[0032] The supramolecular structure provided by the present application is a supramolecular structure formed by γ-aminobutyric acid and α-hydroxypropionic acid (LA). Its structure is relatively stable. When added to cosmetics, it can exert the effects of γ-aminobutyric acid and α-hydroxypropionic acid and can effectively reduce the irritation of the prepared cosmetics. Description of the drawings

[0033] Figure 1A is the NMR spectrum (qualitative) of the supramolecular structure in Example 1.

[0034] Figure 1B is the 2D NOESY spectrum (qualitative) of the supramolecular structure in Example 1.

[0035] Figure 1C is the NMR spectrum (quantitative) of the supramolecular structure in Example 1.

[0036] Figure 2A is the schematic diagram of the thermal stability and light stability test of the supramolecular structure in Experimental Example 1.

[0037] Figure 2B is the schematic diagram of the change of the conductivity of the supramolecular structure with time in Experimental Example 1.

[0038] Figure 2C is the schematic diagram of the change of the pH value of the supramolecular structure with time in Experimental Example 1.

[0039] Figure 3A is the schematic diagram of the test area of the triangular blind test in Experimental Example 2.

[0040] Figure 3B It is the result of the triangular blind test in Experimental Example 2. Specific implementation manners

[0041] The implementation manners described below in conjunction with the accompanying drawings will be used to explain the present application in detail, where the same numbers in all the drawings represent the same features. Although specific embodiments of the present application are shown in the drawings, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described 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.

[0042] It should be noted that certain terms 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. The specification and claims do not use the difference in nouns as a way to distinguish components, but use the difference in the functions of components as the criterion for distinction. As mentioned throughout the specification and claims, "comprising" or "including" is an open-ended term and should be interpreted as "including but not limited to". The subsequent description in the specification is the preferred implementation manner for implementing the present application, but the description is for the purpose of the general principles of the specification and is not used to limit the scope of the present application. The protection scope of the present application shall be determined by the scope defined by the appended claims.

[0043] The present application provides a supramolecular structure, wherein the supramolecular structure includes γ-aminobutyric acid and α-hydroxypropionic acid linked by hydrogen bonds.

[0044] The supramolecular structure refers to an aggregate formed by two or more molecules bound together by intermolecular interactions, which is complex, organized, and maintains a certain integrity so as to have a clear microscopic structure and macroscopic properties. In the present application, the supramolecular structure is the structure formed by γ-aminobutyric acid and α-hydroxypropionic acid, and the γ-aminobutyric acid is connected to the α-hydroxypropionic acid by a hydrogen bond. In some implementation manners, the amino group of the γ-aminobutyric acid is mainly connected to the carboxyl group of the α-hydroxypropionic acid by a hydrogen bond.

[0045] In some embodiments, in the spectrum obtained by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure has characteristic peaks at a chemical shift δ of 4.44 - 4.54 ppm, preferably at a chemical shift δ of 4.49 ppm. In some embodiments, in the spectrum obtained by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure has characteristic peaks at chemical shifts δ of 1.19 - 1.3 ppm, 1.71 - 1.9 ppm, 2.29 - 2.4 ppm, 2.77 - 3.0 ppm, and 3.92 - 4.2 ppm. In some embodiments, in the spectrum obtained by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the chemical shift δ of the supramolecular structure is as Figure 1A shown.

[0046] For example, in the spectrum obtained by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure may have characteristic peaks at chemical shifts δ of 4.44 ppm, 4.45 ppm, 4.46 ppm, 4.47 ppm, 4.48 ppm, 4.49 ppm, 4.50 ppm, 4.51 ppm, 4.52 ppm, 4.53 ppm, 4.54 ppm, etc.

[0047] The chemical shift δ is the chemical shift obtained based on tetramethylsilane, which is obtained by dissolving the supramolecular structure in a deuterated dimethyl sulfoxide solvent and placing it in a nuclear magnetic resonance spectrometer. Preferably, it is obtained by dissolving the supramolecular structure in a deuterated dimethyl sulfoxide solvent and placing it in a Bruker nuclear magnetic resonance spectrometer. Further preferably, the nuclear magnetic intensity of the nuclear magnetic resonance spectrometer is set to 400 MHz, scanned 1024 times, and liquid nitrogen is used to control the ambient temperature.

[0048] Those skilled in the art can understand that the above-described chemical shifts may have certain differences due to different instrument detection equipment and conditions. For example, in this article, the chemical shift is 1.19 - 1.3 ppm, and its lower limit of 1.19 ppm or upper limit of 1.3 ppm can be extended within a certain range. For example, for the lower limit of 1.19 ppm, it can vary within the range of 1.19 ± 0.1 ppm. Similarly, for the upper limit of 1.3 ppm, it can vary within the range of 1.3 ± 0.1 ppm;

[0049] Similarly, for example, in this application, for the above 4.44 - 4.54 ppm, its lower limit of 4.44 ppm can vary within the range of 4.44 ± 0.1 ppm; the upper limit of 4.54 ppm can vary within the range of 4.54 ± 0.1 ppm;

[0050] For example, in the present application, for a chemical shift of 4.49 ppm, it can vary within the range of 4.49 ± 0.1 ppm;

[0051] For example, in the present application, for 1.71 - 1.9 ppm, its lower limit of 1.71 ppm can vary within the range of 1.71 ± 0.1 ppm, and its upper limit of 1.9 ppm can vary within the range of 1.9 ± 0.1 ppm;

[0052] For example, in the present application, for 2.29 - 2.4 ppm, its lower limit of 2.29 ppm can vary within the range of 2.29 ± 0.1 ppm, and its upper limit of 2.4 ppm can vary within the range of 2.4 ± 0.1 ppm;

[0053] For example, in the present application, for 2.77 - 3.0 ppm, its lower limit of 2.77 ppm can vary within the range of 2.77 ± 0.1 ppm, and its upper limit of 3.0 ppm can vary within the range of 3.0 ± 0.1 ppm;

[0054] For example, in the present application, for 3.92 - 4.2 ppm, its lower limit of 3.92 ppm can vary within the range of 3.92 ± 0.1 ppm, and its upper limit of 4.2 ppm can vary within the range of 4.2 ± 0.1 ppm.

[0055] The hydrogen bond includes the hydrogen bond formed between the carboxyl group of α - hydroxypropionic acid and the amino group of γ - aminobutyric acid.

[0056] The supramolecular structure contains a structural schematic formula as shown in formula (I):

[0057]

[0058] In the above formula (I), what the dotted square represents is the formed hydrogen bond, that is, the hydrogen bond linking γ - aminobutyric acid and α - hydroxypropionic acid.

[0059] In some embodiments, the supramolecular structure includes γ - aminobutyric acid and α - hydroxypropionic acid linked by a hydrogen bond. In some embodiments, in the spectrum detected by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure has a characteristic peak at a chemical shift δ of 4.44 - 4.54 ppm; preferably, in the spectrum detected by a nuclear magnetic resonance spectrometer, relative to tetramethylsilane, the supramolecular structure has characteristic peaks at chemical shifts δ of 1.19 - 1.3 ppm, 1.71 - 1.9 ppm, 2.29 - 2.4 ppm, 2.77 - 3.0 ppm, and 3.92 - 4.2 ppm. In some embodiments, the hydrogen bond includes the hydrogen bond formed between the carboxyl group of α - hydroxypropionic acid and the amino group of γ - aminobutyric acid.

[0060] In the supramolecular structure described in this application, since γ-aminobutyric acid therein is connected to α-hydroxypropionic acid through hydrogen bonds, the formed supramolecular structure remains clear and transparent after being placed under a light lamp and in an oven at 45 °C for 30 days, with no obvious impurities generated and no obvious solid precipitation, indicating that the supramolecular structure system is stable.

[0061] The conductivity of the described supramolecular structure is higher than that of the simple mixture of γ-aminobutyric acid and α-hydroxypropionic acid, and its conductivity shows no obvious change, indicating that the described supramolecular structure is different from the simple mixture of γ-aminobutyric acid and α-hydroxypropionic acid and is relatively stable.

[0062] The pH of the described supramolecular structure shows weak acidity and has no obvious change, indicating that the supramolecular structure described in this application is stable.

[0063] When the described supramolecular structure is added to cosmetics, it can significantly reduce the stinging sensation of the cosmetics while still retaining the functions of γ-aminobutyric acid and α-hydroxypropionic acid themselves.

[0064] This application provides a method for preparing a supramolecular structure, which includes:

[0065] Mix γ-aminobutyrate and α-hydroxypropionate under the atmosphere of a mixed gas of nitrogen and carbon dioxide, and stir to react to obtain the supramolecular structure.

[0066] In some embodiments, the γ-aminobutyrate includes one or more selected from the hydrochloride, sulfate, carbonate, and bicarbonate of γ-aminobutyric acid;

[0067] Preferably, the α-hydroxypropionate includes the metal salt of α-hydroxypropionic acid, preferably including one or more selected from the sodium salt, potassium salt, copper salt, and calcium salt of α-hydroxypropionic acid;

[0068] Preferably, the molar ratio of the γ-aminobutyrate to the α-hydroxypropionate in the reaction is 1:0.8 - 1.2.

[0069] For example, the molar ratio (n γ-氨基丁酸 :n α-羟基丙酸 ) of the γ-aminobutyrate to the α-hydroxypropionate in the reaction can be 1:0.8, 1:0.9, 1:1, 1:1.1, etc.

[0070] For this molar ratio, it refers to the molar ratio when the γ-aminobutyrate reacts with the α-hydroxypropionate.

[0071] In some embodiments, the γ-aminobutyrate and α-hydroxypropionate are separately dissolved in a solvent and then mixed. The solvent may be an alcohol solvent, such as ethanol.

[0072] In some embodiments, calculated by volume percentage in the mixed gas, nitrogen is 1-30%, preferably 5-20%.

[0073] For example, calculated by volume percentage in the mixed gas, nitrogen can be 1%, 5%, 3%, 10%, 15%, 20%, 25%, 30%, etc.

[0074] In some embodiments, the γ-aminobutyrate and α-hydroxypropionate are mixed under the atmosphere of a mixed gas of nitrogen and carbon dioxide at a pressure of 0.1-20 MPa, preferably 10-15 MPa;

[0075] Preferably, the reaction is carried out at a temperature of 0-60 °C, preferably 30-50 °C;

[0076] Preferably, the reaction time is 20-72 h, preferably 22-36 h.

[0077] For example, the pressure can be 0.1 MPa, 0.5 MPa, 1 MPa, 2 MPa, 3 MPa, 4 MPa, 5 MPa, 6 MPa, 7 MPa, 8 MPa, 9 MPa, 10 MPa, 11 MPa, 12 MPa, 13 MPa, 14 MPa, 15 MPa, 16 MPa, 17 MPa, 18 MPa, 19 MPa, 20 MPa, etc.;

[0078] The temperature can be 0, 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, 55 °C, 60 °C, etc.;

[0079] The reaction time can be 20 h, 22 h, 24 h, 26 h, 28 h, 30 h, 32 h, 34 h, 36 h, 38 h, 40 h, 42 h, 44 h, 46 h, 48 h, 50 h, 52 h, 54 h, 56 h, 58 h, 60 h, 62 h, 66 h, 68 h, 70 h, 72 h, etc.

[0080] In some embodiments, the stirring is ultrasonic stirring. Preferably, the ultrasonic frequency of the ultrasonic stirring is 5-100 kHz, preferably 10-50 kHz;

[0081] Preferably, the ultrasonic power is 20-3000 W, preferably 100-1000 W.

[0082] For example, the ultrasonic frequency can be 5 kHz, 10 kHz, 20 kHz, 30 kHz, 40 kHz, 50 kHz, 60 kHz, 70 kHz, 80 kHz, 90 kHz, 100 kHz, etc.;

[0083] The ultrasonic power can be 20 W, 50 W, 100 W, 150 W, 200 W, 300 W, 400 W, 500 W, 1000 W, 2000 W, 3000 W, etc.

[0084] In some embodiments, the method further includes:

[0085] Separating the obtained mixture of the reaction to obtain the supramolecular structure; preferably, the separation method is membrane filtration or centrifugation.

[0086] Preferably, the precipitate obtained by separating the obtained mixture of the reaction is the supramolecular structure.

[0087] For membrane filtration, the present application does not impose any restrictions, and it can be operated by conventional methods in the art. For example, polyamide ultrafiltration membranes can be used for filtration.

[0088] In some embodiments, the supramolecular structure is the supramolecular structure described above.

[0089] In some embodiments, the method includes: mixing γ-aminobutyrate and α-hydroxypropionate under an atmosphere of a mixed gas of nitrogen and carbon dioxide, and stirring to react to obtain the supramolecular structure. In some embodiments, the γ-aminobutyrate includes one or more selected from the hydrochloride, sulfate, carbonate, and bicarbonate of γ-aminobutyric acid; preferably, the α-hydroxypropionate includes a metal salt of α-hydroxypropionic acid, preferably including one or more selected from the sodium salt, potassium salt, copper salt, and calcium salt of α-hydroxypropionic acid; preferably, in some embodiments, calculated by volume percentage in the mixed gas, nitrogen is 1-30%, preferably 5-20%. In some embodiments, γ-aminobutyrate and α-hydroxypropionate are mixed under an atmosphere of a mixed gas of nitrogen and carbon dioxide at a pressure of 0.1-20 MPa, preferably 10-15 MPa; preferably, the reaction is carried out at a temperature of 0-60 °C, preferably 30-50 °C; preferably, the reaction time is 20-72 h, preferably 22-36 h. In some embodiments, the stirring is ultrasonic stirring, preferably, the ultrasonic frequency of the ultrasonic stirring is 5-100 kHz, preferably 10-50 kHz; preferably, the ultrasonic power is 20-3000 W, preferably 100-1000 W. In some embodiments, the method further includes: separating the reaction mixture to obtain the supramolecular structure; preferably, the separation method is membrane filtration or centrifugation.

[0090] The present application provides the application of the above-mentioned supramolecular structure or the supramolecular structure prepared by the above-mentioned method in the field of cosmetics. The dosage forms of the cosmetics include but are not limited to aqueous solutions, emulsions, gels, creams, or facial masks.

[0091] The supramolecular structure described in the present application can significantly reduce the irritation of cosmetics when used in cosmetics.

[0092] The supramolecular structure described in the present application binds γ-aminobutyric acid and α-hydroxypropionic acid through hydrogen bonds, and it is bound by weak interactions. The supramolecular structure can effectively combat wrinkles. When the supramolecular structure penetrates into the skin, there is a dissociation equilibrium. When GABA is gradually consumed by biochemical reactions, the dissociation equilibrium moves to the right. Therefore, GABA forms a sustained release in the skin, thereby reducing irritation without affecting its functionality.

[0093] In some embodiments, calculated by mass percentage in the cosmetics, the supramolecular structure is 0.1-30%, preferably 1-5%.

[0094] For example, calculated as the mass percentage in the cosmetic, the supramolecular structure is 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, etc.

[0095] The present application provides a cosmetic, which comprises the supramolecular structure described above or the supramolecular structure prepared by the method described above. Preferably, calculated as the mass percentage in the cosmetic, the supramolecular structure is 0.1 - 30%, preferably 1 - 5%. In some embodiments, the cosmetic further comprises free γ-aminobutyric acid and / or free α-hydroxypropionic acid. In some embodiments, the dosage form of the cosmetic includes but is not limited to aqueous solution, emulsion, gel, cream or facial mask. In some embodiments, the cosmetic further comprises excipients.

[0096] Regarding the excipients, the present application does not impose any restrictions, and they can be conventionally selected. For example, the excipients can be polyols, sodium hyaluronate, sodium citrate, phenoxyethanol, etc.

[0097] The present application provides the application of the supramolecular structure described above or the supramolecular structure prepared by the method described above in reducing the irritation of cosmetics.

[0098] Examples

[0099] The present application generally and / or specifically describes the materials and test methods used in the experiments. In the following examples, if there is no other special description, % represents wt%, that is, weight percentage. For the reagents or instruments whose manufacturers are not indicated, they are all conventional reagent products that can be obtained through commercial purchase. Among them, Table 1 shows the raw materials and equipment information used in the examples.

[0100] Table 1 Raw materials and equipment information used in the examples

[0101]

[0102] Example 1 Preparation of the supramolecular structure

[0103] (1) Preparation of GABA sulfate: This GABA sulfate is prepared by reacting GABA with sulfuric acid. Equal volumes of a 2 mol / L GABA aqueous solution and a 1 mol / L sulfuric acid solution are mixed. After mixing evenly, a vacuum distillation device is used for vacuum distillation until it is dried to obtain solid powder of GABA sulfate.

[0104] (2) Preparation of calcium α-hydroxypropionate (calcium lactate, LA): 0.3 mol of LA is dissolved in 300 mL of water, and 0.25 mol of calcium hydroxide is made into a 150 mL suspension, and then the two are mixed evenly and dried to obtain solid powder of calcium lactate.

[0105] (3) Pre-place the high-pressure reactor in a supercritical fluid device. Subsequently, add 66 g (0.3 mol) of calcium lactate solid powder into the high-pressure reactor, add 300 ml of ethanol solution, and continuously stir to obtain solution a. Take another flask, add 90 g (0.3 mol) of GABA sulfate solid powder, add 600 ml of ethanol solution, and stir to completely dissolve it to obtain solution b.

[0106] Under stirring conditions, quickly add solution b into the high-pressure reactor placed in the supercritical fluid device to make solution a and solution b mix evenly. Then, introduce a nitrogen / carbon dioxide (5% / 95%) mixed gas into the reactor for 1 h to fully exhaust the air in the reactor. Subsequently, raise the temperature and pressure in the reactor to 40 °C and 12 MPa respectively. Turn on the 20 kHz / 200 W ultrasound and continuously stir, while keeping the temperature and pressure stable. After 24 hours, filter using a polyamide ultrafiltration membrane (pore size 0.1 - 0.5 μm). After filtration, transfer it to a conventional pressure vessel with a pressure resistance > 150 MPa, and continue to introduce a nitrogen / carbon dioxide (5% / 95%) mixed gas for 2 hours to obtain a supramolecular structure with a yield of 87% and a purity of 98.3%. Among them, the supramolecular structure is identified by the following method:

[0107] Dissolve the sample in deuterated dimethyl sulfoxide solvent, and use a Bruker nuclear magnetic resonance spectrometer for qualitative detection (the nuclear magnetic intensity is set at 400 MHz, scan 1024 times, and at the same time use liquid nitrogen to control the ambient temperature) to measure the nuclear magnetic resonance. The obtained spectrum is as Figure 1A shown.

[0108] From Figure 1A it can be seen that relative to tetramethylsilane, the supramolecular structure shows characteristic peaks at chemical shifts δ of 1.3 ppm, 1.9 ppm, 2.4 ppm, 3.0 ppm, and 4.2 ppm, which are the characteristic peaks of GABA and LA, and a relatively broad peak appears at the position of chemical shift δ 4.49 ppm, indicating that GABA and LA in the prepared supramolecular structure are connected by hydrogen bonds, that is, a hydrogen atom migration occurs in the supramolecular structure relative to GABA and LA to form hydrogen bonds.

[0109] Dissolve the sample in deuterated water, and use a Bruker nuclear magnetic resonance spectrometer for quantitative detection to verify the GABA-LA supramolecular ratio (the nuclear magnetic intensity is set at 400 MHz, scan 1024 times, and at the same time use liquid nitrogen to control the ambient temperature) to measure the nuclear magnetic resonance. The obtained spectrum is as Figure 1C shown.

[0110] Use the nuclear magnetic resonance spectrum (as Figure 1C) Further deduce the molar ratio of GABA and LA in the supramolecular structure. As can be seen from the spectrum, relative to tetramethylsilane, GABA shows characteristic peaks at chemical shifts δ of 1.9 ppm (m, 2H), 2.4 ppm (t, 2H), and 3.0 ppm (t, 2H), corresponding to the peak positions of the three methylene groups (CH2-) in the GABA molecular structural formula respectively. The total peak area of 6 hydrogen atoms is approximately 6 (2.38 + 2.02 + 2); LA shows characteristic peaks at chemical shifts δ of 1.3 ppm (d, 3H) and 4.2 ppm (q, 1H), corresponding to the methyl group (CH3-) and methine group (CH-) in LA respectively. The peak area of the methyl group is 3.00, and the peak area of the methine group is 0.93. The total peak area of 4 hydrogen atoms is approximately 4 (3.00 + 0.93). Other hydrogen atoms do not show peaks under this test condition.

[0111] And a further identification was made on whether hydrogen bonds were formed between them, using a 2D NOESY spectrum for identification:

[0112] Dissolve the sample in deuterated dimethyl sulfoxide solvent, use a Bruker nuclear magnetic resonance spectrometer (the nuclear magnetic intensity is set at 400 MHz, scan 1024 times, and at the same time use liquid nitrogen to control the ambient temperature. Under the 2D NOESY mode, measure the nuclear magnetic resonance, and the presence or absence of the star-shaped surface enclosed by the contour lines indicates the presence or absence of the supramolecular structure. The results are as Figure 1B shown.

[0113] From Figure 1B it can be seen that hydrogen bonds are formed between GABA and LA, forming a GABA-LA supramolecular structure.

[0114] Example 2 Preparation of Supramolecular Structure

[0115] (1) Preparation of GABA sulfate: This GABA sulfate is made by reacting GABA with sulfuric acid. Mix equal volumes of a 2 mol / L GABA aqueous solution and a 1 mol / L sulfuric acid solution. After mixing evenly, use a vacuum distillation device for vacuum distillation until dryness to obtain solid powder of GABA sulfate.

[0116] (2) Preparation of calcium α-hydroxypropionate (calcium lactate, LA): Dissolve 0.3 mol of LA in 300 mL of water, prepare a 150 mL suspension of 0.25 mol of calcium hydroxide, then mix the two evenly and dry to obtain solid powder of calcium lactate.

[0117] (3) Place the high-pressure reactor in a supercritical fluid device in advance. Subsequently, add 66 g (0.3 mol) of solid calcium lactate powder to the high-pressure reactor, add 300 ml of ethanol solution, and continuously stir to obtain solution a. Take another flask, add 90 g (0.3 mol) of solid GABA sulfate powder, add 600 ml of ethanol solution, and stir to completely dissolve it to obtain solution b.

[0118] Under stirring conditions, quickly add solution b to the high-pressure reactor placed in the supercritical fluid device to make solution a and solution b mix evenly. Then, introduce a nitrogen / carbon dioxide (20% / 80%) mixed gas into the reactor for 1 h to fully exhaust the air in the reactor. Subsequently, raise the temperature and pressure in the reactor to 30 °C and 15 MPa respectively. Turn on the 50 kHz / 800 W ultrasonic wave and continuously stir, while keeping the temperature and pressure stable. After 22 h, filter with a polyamide ultrafiltration membrane (pore size 0.1 - 0.5 μm). After filtration, transfer it to a conventional pressure vessel with a pressure resistance > 150 MPa, and continue to introduce a nitrogen / carbon dioxide (20% / 80%) mixed gas for 2 h to obtain a supramolecular structure with a yield of 83% and a purity of 97.5%.

[0119] Refer to the method of Example 1 to identify the prepared supramolecular structure. The obtained supramolecular structure has a hydrogen atom migration relative to GABA and LA, forming a hydrogen bond and forming a GABA-LA supramolecular structure.

[0120] Preparation of the supramolecular structure in Example 3

[0121] (1) Preparation of GABA sulfate: This GABA sulfate is made by reacting GABA and sulfuric acid. Mix equal volumes of a 2 mol / L GABA aqueous solution and a 1 mol / L sulfuric acid solution. After mixing evenly, use a vacuum distillation device for vacuum distillation until it is dry to obtain solid GABA sulfate powder.

[0122] (2) Preparation of calcium α-hydroxypropionate (calcium lactate, LA): Dissolve 0.3 mol of LA in 300 mL of water, prepare a 150 mL suspension of 0.25 mol of calcium hydroxide, then mix the two evenly and dry to obtain solid calcium lactate powder.

[0123] (3) Place the high-pressure reactor in a supercritical fluid device in advance. Subsequently, add 66 g (0.3 mol) of solid calcium lactate powder to the high-pressure reactor, add 300 ml of ethanol solution, and continuously stir to obtain solution a. Take another flask, add 90 g (0.3 mol) of solid GABA sulfate powder, add 600 ml of ethanol solution, and stir to completely dissolve it to obtain solution b.

[0124] Under stirring conditions, solution b was rapidly added to a high-pressure reactor placed in a supercritical fluid device, so that solution a and solution b were mixed evenly. Then, a nitrogen / carbon dioxide (30% / 70%) mixed gas was introduced into the reactor for 1 h to fully exhaust the air in the reactor. Subsequently, the temperature and pressure in the reactor were increased to 20 °C and 5 MPa, respectively. 5 kHz / 3000 W ultrasound was turned on and continuous stirring was maintained, while keeping the temperature and pressure stable. After 72 h, filtration was carried out using a polyamide ultrafiltration membrane (pore size 0.1–0.5 μm). After filtration, it was transferred to a conventional pressure vessel with a pressure resistance >150 MPa, and a nitrogen / carbon dioxide (20% / 80%) mixed gas was continuously introduced for 2 h to obtain a supramolecular structure with a yield of 83% and a purity of 98.1%.

[0125] The prepared supramolecular structure was identified according to the method of Example 1. The obtained supramolecular structure underwent a hydrogen atom migration with respect to GABA and LA, forming a hydrogen bond and forming a GABA-LA supramolecular structure.

[0126] Preparation of the supramolecular structure in Example 4

[0127] (1) Preparation of GABA sulfate: This GABA sulfate was prepared by reacting GABA with sulfuric acid. An equal volume of a 2 mol / L GABA aqueous solution and a 1 mol / L sulfuric acid solution were mixed. After mixing evenly, a vacuum distillation device was used for vacuum distillation until dryness to obtain solid powder of GABA sulfate.

[0128] (2) Preparation of calcium α-hydroxypropionate (calcium lactate, LA): 0.3 mol of LA was dissolved in 300 mL of water, and 0.25 mol of calcium hydroxide was made into a 150 mL suspension. Then the two were mixed evenly and dried to obtain solid powder of calcium lactate.

[0129] (3) The high-pressure reactor was pre-placed in a supercritical fluid device. Subsequently, 79.2 g (0.36 mol) of solid powder of calcium lactate was added to the high-pressure reactor, and 360 ml of an ethanol solution was added. Continuous stirring was carried out to obtain solution a; another flask was taken, 90 g (0.3 mol) of solid powder of GABA sulfate was added, and 600 ml of an ethanol solution was added and stirred to completely dissolve it to obtain solution b;

[0130] Under stirring conditions, solution b was quickly added to a high-pressure reactor placed in a supercritical fluid device, so that solution a and solution b were mixed evenly. Then, a nitrogen / carbon dioxide (5% / 95%) mixed gas was introduced into the reactor for 1 h to fully exhaust the air in the reactor. Subsequently, the temperature and pressure in the reactor were increased to 40 °C and 12 MPa, respectively. 20 kHz / 200 W ultrasound was turned on and continuous stirring was maintained, while keeping the temperature and pressure stable. After 24 hours, filtration was carried out using a polyamide ultrafiltration membrane (pore size 0.1 - 0.5 μm). After filtration, it was transferred to a conventional pressure vessel with a pressure resistance > 150 MPa, and the nitrogen / carbon dioxide (5% / 95%) mixed gas was continuously introduced for 2 hours to obtain a supramolecular structure with a yield of 83% and a purity of 97.2%.

[0131] The prepared supramolecular structure was identified according to the method of Example 1. The obtained supramolecular structure underwent a hydrogen atom migration with respect to GABA and LA, forming hydrogen bonds to form a GABA-LA supramolecular structure.

[0132] Preparation of the supramolecular structure in Example 5

[0133] (1) Preparation of GABA sulfate: This GABA sulfate was prepared by reacting GABA with sulfuric acid. An equal volume of a 2 mol / L GABA aqueous solution and a 1 mol / L sulfuric acid solution were mixed. After mixing evenly, a vacuum distillation device was used for vacuum distillation until dryness to obtain solid powder of GABA sulfate.

[0134] (2) Preparation of calcium α-hydroxypropionate (calcium lactate, LA): 0.3 mol of LA was dissolved in 300 mL of water, and 0.25 mol of calcium hydroxide was made into a 150 mL suspension. Then the two were mixed evenly and dried to obtain solid powder of calcium lactate.

[0135] (3) The high-pressure reactor was pre-placed in a supercritical fluid device. Subsequently, 52.8 g (0.24 mol) of solid powder of calcium lactate was added to the high-pressure reactor, and 240 ml of an ethanol solution was added, followed by continuous stirring to obtain solution a; Another flask was taken, 90 g (0.3 mol) of solid powder of GABA sulfate was added, and 600 ml of an ethanol solution was added and stirred to completely dissolve it to obtain solution b;

[0136] Under stirring conditions, solution b was quickly added to a high-pressure reactor placed in a supercritical fluid device, so that solution a and solution b were mixed evenly. Then, a nitrogen / carbon dioxide (5% / 95%) mixed gas was introduced into the reactor for 1 h to fully exhaust the air in the reactor. Subsequently, the temperature and pressure in the reactor were increased to 40 °C and 12 MPa, respectively. 20 kHz / 200 W ultrasound was turned on and continuous stirring was maintained, during which the temperature and pressure were kept stable. After 24 h, filtration was carried out using a polyamide ultrafiltration membrane (pore size 0.1 - 0.5 μm). After filtration, it was transferred to a conventional pressure vessel with a pressure resistance > 150 MPa, and the nitrogen / carbon dioxide (5% / 95%) mixed gas was continuously introduced for 2 h to obtain a supramolecular structure with a yield of 82% and a purity of 97.3%.

[0137] The prepared supramolecular structure was identified according to the method of Example 1. The obtained supramolecular structure underwent a hydrogen atom migration relative to GABA and LA, forming hydrogen bonds to form a GABA-LA supramolecular structure.

[0138] Table 2 Reaction parameters for preparing the supramolecular structure

[0139]

[0140] Experimental Example 1 Stability data of the GABA-LA supramolecular structure

[0141] A. Tests on thermal stability and photostability

[0142] The GABA-LA supramolecular structure obtained in Example 1 was placed under a 100 W xenon lamp light source and in an oven at 45 °C. After 30 days, as Figure 2A shown.

[0143] From Figure 2A it can be seen that the solution was clear and transparent, without obvious impurities generated and without obvious solid precipitation, indicating that the supramolecular structure system obtained in this application was stable.

[0144] B. Test on conductivity

[0145] The conductivities of the supramolecular structure, GABA monomer, and LA monomer obtained in Example 1 were measured using a conductivity tester (DDSJ-318T conductivity meter, Shanghai Yidian Scientific Instrument Co., Ltd.). The results are as Figure 2B shown.

[0146] From Figure 2B it can be seen that the conductivities of the GABA monomer and LA monomer were stable, while the conductivity of the GABA-LA supramolecular structure was significantly higher than that of the monomer mixture and showed no obvious change, indicating that the supramolecular structure was stable.

[0147] C. pH value test

[0148] The pH values of the supramolecular structure, GABA monomer, and LA monomer obtained in Example 1 were measured using a pH tester (PHSJ-5T laboratory pH meter, Shanghai Yidian Scientific Instrument Co., Ltd.). The results are as Figure 2C shown.

[0149] From Figure 2C it can be seen that the supramolecular structure exhibits weak acidity and shows no obvious change, indicating that the supramolecular structure is stable.

[0150] Based on the same above tests, the supramolecular structures obtained in Examples 2-5 have similar effects to those in Example 1-1.

[0151] Experimental Example 2: Irritation test of GABA-LA supramolecular structure

[0152] The irritation of the GABA-LA supramolecular structure obtained in Example 1 when physically mixed with GABA monomer and LA monomer was tested using the following method:

[0153] Preparation of GABA-LA supramolecular structure solution: Weigh 0.306 g of the prepared GABA-LA supramolecular structure with a purity of 98.3%, add it to 10 mL of deionized water for dissolution, and obtain a GABA-LA supramolecular structure solution with a GABA content of 3% and an LA concentration of 3%.

[0154] Preparation of GABA-LA physically mixed solution: Weigh 0.6 g of GABA powder, add it to 20 mL of deionized water, stir with a magnetic stirrer for 15 min at a rotation speed of 300 rpm. Then weigh 0.6 g of LA and add it to the GABA aqueous solution, and continue to stir at the same rotation speed for 10 min to finally obtain a 3% GABA and 3% LA physically mixed solution.

[0155] Triangle test method:

[0156] This method is an objective method for evaluating the sensory differences between two samples A and B. The experimental design was carried out according to the national standard GB / T12311-2012. The subjects received a set of three samples and were informed that two of the samples were the same and the other was different. The subjects selected the sample they thought was different and gave reasons.

[0157] Among them, if 15 subjects are selected to participate in the evaluation, if 9 or more subjects make the correct selection, it indicates that there is a statistically significant difference between samples A and B. The specific operation method is as follows:

[0158] Sample Test: 3 samples (two A's and one B, or two B's and one A), namely AAB, ABA, BAA, BBA, BAB, ABB. The occurrences of the two types of samples are equal. First, clean the test areas 1, 2, 3, 4 with wet paper as Figure 3A shown, and smooth for more than 10 minutes. Apply the samples to three areas in a certain order. Select 1 drop of each sample (about 0.2 ml) and apply it to the test areas. Hide the labels of A and B for these three samples and conduct a blind test on consumers. After application, wait for 30 s - 1 min and ask the subjects about the sample with different stinging sensations.

[0159] Results of the triangular blind test:

[0160] Compare "3% GABA - 3% LA supramolecular structure" (Example 1) and "3% GABA - 3% LA physical mixture" according to the above triangular blind test experimental method. The results are as Figure 3B shown,

[0161] From Figure 3B it can be seen that 11 (more than 9) subjects identified correctly, indicating that there is a significant difference in the stinging sensations between the supramolecular and the physical mixture. At the same time, it was pointed out that the stinging sensation of the supramolecular is significantly weaker, demonstrating that the GABA - LA supramolecular structure prepared in Example 1 can significantly reduce the stinging sensation caused by simple physical mixing.

[0162] Conduct a triangular blind test on the supramolecular structures prepared in Examples 2 - 5 according to the test method of Experimental Example 2 as follows:

[0163] Table 3 Triangular blind test results of Examples 2 - 5

[0164]

[0165] It can be seen that for the supramolecular structures obtained in Examples 2 - 5, more than 9 subjects identified correctly, indicating that there is a significant difference in the stinging sensations between the supramolecular structures obtained in Examples 2 - 5 and the physical mixture.

[0166] The above are only the preferred embodiments of the present application, and are not intended to limit the present application in other forms. Any person skilled in the art may use the disclosed technical content to make changes or modifications into equivalent embodiments with equivalent changes. However, any simple modification, equivalent change, and modification made to the above embodiments based on the technical essence of the present application without departing from the technical solution content of the present application still fall within the protection scope of the technical solution of the present application.

Claims

1. A supramolecular structure, wherein The supramolecular structure includes gamma-aminobutyric acid and alpha-hydroxypropionic acid linked by hydrogen bonds; In the spectrum obtained by nuclear magnetic resonance spectrometer detection, the supramolecular structure has a characteristic peak at a chemical shift δ of 4.44-4.54 ppm relative to tetramethylsilane.

2. The supramolecular structure according to claim 1, wherein In the spectrum obtained by nuclear magnetic resonance spectrometer detection, relative to tetramethylsilane, the supramolecular structure has characteristic peaks at chemical shifts δ of 1.19-1.3 ppm, 1.71-1.9 ppm, 2.29-2.4 ppm, 2.77-3.0 ppm and 3.92-4.2 ppm.

3. The supramolecular structure according to any one of claims 1 to 2, wherein The hydrogen bond includes a hydrogen bond formed between the carboxyl group of α-hydroxypropionic acid and the amino group of γ-aminobutyric acid.

4. A method for preparing a supramolecular structure, comprising: mixing γ-aminobutyrate and α-hydroxypropionate in an atmosphere of a mixed gas of nitrogen and carbon dioxide, and stirring to react to obtain the supramolecular structure; In the spectrum obtained by nuclear magnetic resonance spectrometer detection, the supramolecular structure has a characteristic peak at a chemical shift δ of 4.44-4.54 ppm relative to tetramethylsilane.

5. The method according to claim 4, wherein The γ-aminobutyrate includes one or more selected from the group consisting of hydrochloride, sulfate, carbonate and bicarbonate of γ-aminobutyric acid.

6. The method according to claim 4, wherein: The α-hydroxypropionate salts include metal salts of α-hydroxypropionic acid.

7. The method according to claim 6, wherein: The metal salt of α-hydroxypropionic acid includes one or more selected from sodium salt, potassium salt, copper salt and calcium salt of α-hydroxypropionic acid.

8. The method according to claim 4, wherein: The molar ratio of the γ-aminobutyrate to the α-hydroxypropionate in the reaction is 1:0.8-1.

2.

9. The method according to claim 4, wherein: Calculated by volume percentage in the mixed gas, nitrogen accounts for 1-30%.

10. The method according to claim 4, wherein: γ-aminobutyrate and α-hydroxypropionate are mixed under a mixed gas atmosphere of nitrogen and carbon dioxide at a pressure of 0.1-20 MPa.

11. The method according to claim 4, wherein The reaction is carried out at a temperature of 0-60°C.

12. The method according to claim 4, wherein: The reaction time is 20-72h.

13. The method according to claim 4, wherein: The stirring is ultrasonic stirring.

14. The method according to claim 13, wherein The ultrasonic frequency of the ultrasonic stirring is 5-100 kHz.

15. The method according to claim 13, wherein The ultrasonic power is 20-3000W.

16. The method according to any one of claims 4 to 15, wherein: The method further comprises: The mixed solution obtained by the reaction is separated to obtain the supramolecular structure.

17. The method according to claim 16, wherein: The separation method is membrane filtration or centrifugation.

18. The method according to any one of claims 4 to 15, wherein: The supramolecular structure is the supramolecular structure according to any one of claims 1 to 3.

19. Use of the supramolecular structure according to any one of claims 1 to 3 or the supramolecular structure prepared by the method according to any one of claims 4 to 18 in the preparation of cosmetics.

20. The use according to claim 19, wherein: Calculated by mass percentage in the cosmetics, the supramolecular structure accounts for 0.1-30%.

21. The use according to claim 19, wherein: Calculated by mass percentage in the cosmetics, the supramolecular structure accounts for 1-5%.

22. A cosmetic comprising the supramolecular structure according to any one of claims 1 to 3 or the supramolecular structure prepared by the method according to any one of claims 4 to 18.

23. The cosmetic according to claim 22, wherein Calculated by mass percentage in the cosmetics, the supramolecular structure accounts for 0.1-30%.

24. The cosmetic according to claim 22, wherein Calculated by mass percentage in the cosmetics, the supramolecular structure accounts for 1-5%.

25. The cosmetic according to claim 22, wherein The cosmetic also comprises free gamma-aminobutyric acid and / or free alpha-hydroxypropionic acid.

26. The cosmetic according to any one of claims 22 to 25, wherein The cosmetic also includes auxiliary materials.

27. Use of the supramolecular structure according to any one of claims 1 to 3 or the supramolecular structure prepared by the method according to any one of claims 4 to 18 in reducing the irritation of cosmetics.

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