Anti-anxiety gamma-aminobutyric acid composition and preparation method thereof

Abstract

The invention belongs to the technical field of health care products, and particularly relates to an anti-anxiety gamma-aminobutyric acid composition and a preparation method thereof. The anti-anxiety gamma-aminobutyric acid composition disclosed by the invention is prepared from the following components in parts by weight: 1 to 2 parts of paeonol derivatives, 0.1 to 0.5 part of gamma-aminobutyric acid, 0.1 to 0.3 part of astaxanthin and 0.01 to 0.05 part of asterosaponin. The gamma-aminobutyric acid, the paeonol derivative and the asterosaponin are compounded for use, the paeonol derivative promotes the compound to passively diffuse into intestinal epithelial cells through cell membranes, so that the capacity of the compound to penetrate through the intestinal epithelial cell membranes through passive diffusion is greatly improved, and the asterosaponin has the effects of calming, resisting anxiety and regulating insomnia; the absorption effect of GABA can also be effectively promoted; the composition can effectively promote absorption of active substances, is high in bioavailability, and has the advantages of being small in taking dosage, good in anxiety relieving effect, long in sleep duration and the like.

Description

Technical Field

[0001] This invention belongs to the field of health product technology, and in particular relates to an anti-anxiety γ-aminobutyric acid composition and its preparation method. Background Technology

[0002] Insomnia, anxiety, and depression are often interconnected and mutually influential. Anxiety disorder, also known as anxiety neurosis, is characterized by excessive worry and fear in everyday situations, interfering with daily activities and being difficult to control. It often manifests as tension, fear, cognitive impairment, and low mood. Insomnia refers to the difficulty falling asleep even in a comfortable environment. Long-term insomnia leads to decreased prefrontal cortex function and enhanced fear responses, promoting anxiety and forming a closed loop of "anxiety-insomnia-more anxiety." In other words, anxiety is one of the important reasons why insomnia is difficult to cure; therefore, taking effective measures to intervene in anxiety is particularly important.

[0003] With the accelerating pace of life and increasing social pressure, the number of people experiencing anxiety is constantly expanding. Clinically, anxiety disorders are usually treated with psychotherapy and medication. Currently, the main anti-anxiety medications available in clinical practice include benzodiazepines and reuptake inhibitors. However, these medications also have certain limitations to varying degrees. For example, some medications have a slow onset of action and require long-term use; some medications are prone to addiction with long-term use; and they may also cause adverse reactions such as gastrointestinal discomfort, fatigue, drug tolerance, and liver damage.

[0004] Gamma-aminobutyric acid (GABA), as the most important inhibitory neurotransmitter in the mammalian central nervous system, plays a central role in regulating neuronal excitability and maintaining neural homeostasis. Current technology indicates that this drug has some effect in combating anxiety, but it also suffers from low bioavailability and relatively poor efficacy when used alone. While paeonol also has some anti-anxiety effects, its direct use in treating anxiety disorders presents challenges. For example, paeonol requires high doses to achieve significant effects, thus increasing the risk of adverse reactions.

[0005] Therefore, there is an urgent need for a γ-aminobutyric acid composition that is low in irritation and effectively regulates the gastrointestinal tract to relieve anxiety. Summary of the Invention

[0006] To overcome the shortcomings of the prior art, the present invention provides an anti-anxiety γ-aminobutyric acid composition and its preparation method. The resulting composition has the characteristics of small dosage and significant effects in relieving anxiety and improving sleep.

[0007] One of the objectives of this invention is to provide an anti-anxiety γ-aminobutyric acid composition.

[0008] A second objective of this invention is to provide a method for preparing an anti-anxiety γ-aminobutyric acid composition.

[0009] This invention is achieved using the following technical solution: An anti-anxiety γ-aminobutyric acid composition, comprising, by weight, the following components: 1-2 parts of paeonol derivative, 0.1-0.5 parts of γ-aminobutyric acid, 0.1-0.3 parts of astaxanthin, and 0.01-0.05 parts of starfish saponins.

[0010] Furthermore, the preparation process of the paeonol derivative includes the following steps: (1) Paeonol was added to a solvent, and chloromethyl methyl ether was added dropwise to react. After filtration, washing and drying, intermediate 1 was obtained. (2) Intermediate 1, tert-butyldimethylchlorosilane, imidazole and 1-butyl-3-methylimidazolium hexafluorophosphate were added to a solvent and reacted. After washing, concentration and purification, intermediate 2 was obtained. (3) Add 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate and intermediate 2 to a solvent, heat and react, and then wash, concentrate and purify to obtain intermediate 3; (4) Add intermediate 3 and tetrabutylammonium fluoride to the solvent for reaction, and then filter, concentrate, purify and dry to obtain the paeonol derivative.

[0011] Further, in step (1), the molar ratio of paeonol to chloromethyl methyl ether is 1:(2-2.2), the concentration of paeonol in the solvent is 1-2 mol / L, the solvent is acetic acid, and the reaction time is 5-8 h.

[0012] Further, in step (2), the molar ratio of intermediate 1, tert-butyldimethylchlorosilane, imidazole and 1-butyl-3-methylimidazolium hexafluorophosphate is 5:(6-8):(12-15):(8-10); the concentration of intermediate 1 in the solvent is 0.5-1 mol / L, and the solvent is acetone; the reaction time is 2-5 h.

[0013] Further, in step (3), the molar ratio of intermediate 2, 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, and potassium carbonate is 1:(1.2-1.5):(2-2.5), the concentration of intermediate 2 in the solvent is 0.2-0.5 mol / L, and the solvent is anhydrous N,N-dimethylformamide.

[0014] Furthermore, in step (3), the heating reaction temperature is 95~110℃ and the time is 4~8h.

[0015] Further, in step (4), the molar ratio of intermediate 3 to tetrabutylammonium fluoride is 1:(1.2-1.5), the concentration of intermediate 3 in the solvent is 0.2-0.5 mol / L, and the solvent is tetrahydrofuran.

[0016] Furthermore, the reaction is carried out at a temperature of 15-20°C for 3-6 hours.

[0017] The preparation method of the anti-anxiety γ-aminobutyric acid composition of the present invention includes the following steps: weighing the prescribed amounts of paeonol derivative, γ-aminobutyric acid, astaxanthin, and starfish saponin, mixing them evenly, and adding excipients to obtain the product.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention combines γ-aminobutyric acid (GABA), paeonol derivatives, and starfish saponins to effectively promote the absorption and bioavailability of active substances. The composition offers advantages such as low dosage, good anxiety relief, and prolonged sleep duration. Specifically, this invention utilizes the introduction of 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one into paeonol to prepare the paeonol derivative. The naphthalene ring structure has higher hydrophobicity than the benzene ring, and its introduction enhances the derivative's lipophilicity, promoting passive diffusion across the cell membrane into intestinal epithelial cells. This significantly improves its ability to cross the intestinal epithelial cell membrane through passive diffusion, resulting in high bioavailability. Starfish saponins also have sedative, anti-anxiety, and insomnia-regulating effects, and can effectively promote GABA absorption.

[0019] 2. The preparation method of the anti-anxiety γ-aminobutyric acid composition provided by the present invention is simple and easy to operate, which is conducive to industrial production and provides a new technical approach for anti-anxiety and sleep improvement. Detailed Implementation

[0020] The present invention will now be further described in conjunction with specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments. Specific conditions not specified in the embodiments shall be performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all reagents or instruments used are conventional products obtained through commercial channels.

[0021] Example 1

[0022] An anti-anxiety γ-aminobutyric acid composition, comprising the following components by weight: 1.5 parts of paeonol derivative, 0.3 parts of γ-aminobutyric acid, 0.2 parts of astaxanthin, and 0.03 parts of starfish saponin.

[0023] The preparation process of the paeonol derivative includes the following steps:

[0024] (1) Dissolve paeonol in acetic acid, and then add chloromethyl methyl ether dropwise to the glacial acetic acid solution of paeonol, wherein the molar ratio of paeonol to chloromethyl methyl ether is 1:2, and the concentration of paeonol in acetic acid is 1 mol / L; react for 7 h after the addition of chloromethyl methyl ether is completed; filter the reaction solution, wash the filter cake with anhydrous ethanol, and dry to obtain intermediate 1; The NMR results for intermediate 1 are as follows: 1 H NMR (400 MHz, CDCl3): δ 12.85 (s, 1H), 7.68 (s,1H), 6.41 (s, 1H), 4.58 (s, 2H), 3.90 (s, 3H), 2.60 (s, 3H); HRMS(ESI) calcdfor C 10 H 11 ClO3, [M+H] + 215.04, found 215.04. (2) Under nitrogen protection, intermediate 1, tert-butyldimethylchlorosilane (TBDMSCl), imidazole, and 1-butyl-3-methylimidazolium hexafluorophosphate were added sequentially to acetone, wherein the molar ratio of intermediate 1, tert-butyldimethylchlorosilane, imidazole, and 1-butyl-3-methylimidazolium hexafluorophosphate was 5:7:14:9, and the concentration of intermediate 1 in acetone was 0.5 mol / L; the reaction was carried out for 4 h; the mixture was quenched with water to extinguish the reaction, the acetone in the reaction solution was concentrated, the reaction solution was extracted with ethyl acetate, the combined ethyl acetate phases were washed with pure water, filtered, concentrated, and chromatographically purified (eluent, V 石油醚 V 乙酸乙酯 =88:12) thus yields intermediate 2; The NMR results for intermediate 2 are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.68 (s, 1H), 6.41 (s,1H), 4.58 (s, 2H), 3.90 (s, 3H), 2.60 (s, 3H), 0.99 (s, 9H), 0.23 (s, 6H);HRMS(ESI) calcd for C 16 H 25 ClO3Si, [M]328.13, found 328.10. (3) 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate, and intermediate 2 were added to anhydrous N,N-dimethylformamide, wherein the molar ratio of intermediate 2, 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate, and intermediate 2 was 1:1.4:2.3, and the concentration of intermediate 2 in anhydrous N,N-dimethylformamide was 0.4 mol / L. After stirring evenly, the mixture was reacted at 100°C for 6 h. The reaction solution was cooled to room temperature, poured into ice water, and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, concentrated, and then subjected to column chromatography (V... 石油醚 V 乙酸乙酯 After purification with a ratio of 90:10, intermediate 3 was obtained; The NMR results for intermediate 3 are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.86-7.84 (m, 1H), 7.68 (s, 1H), 7.52-7.50 (m, 1H), 7.38-7.35 (m, 2H), 6.41 (s, 1H), 4.58 (s, 2H), 4.45 (t, 1H), 3.90 (s, 3H), 2.60 (s, 3H), 2.54-2.45 (m, 2H), 2.04-1.80 (m,2H), 0.99 (s, 9H), 0.23 (s, 6H); HRMS(ESI) calcd for C 26 H 34 O5Si, [M]454.22, found 454.23. (4) Under nitrogen protection, intermediate 3 was added to tetrahydrofuran, cooled to -5°C, and tetrabutylammonium fluoride was added. The molar ratio of intermediate 3 to tetrabutylammonium fluoride was 1:1.3, and the concentration of intermediate 3 in tetrahydrofuran was 0.2 mol / L. The reaction was carried out at 15°C for 5 h. The reaction was quenched with saturated ammonium chloride solution, and the reaction solution was extracted with ethyl acetate. The organic phase was filtered, concentrated, and purified by chromatography (eluent, V). 正己烷 V 乙酸乙酯 =85:15), then dried to obtain the paeonol derivative.

[0025] The NMR results of the paeonol derivatives are as follows: 1H NMR (400 MHz, CDCl3): δ 12.85 (s, 1H),7.86-7.84 (m, 1H), 7.68 (s, 1H), 7.52-7.50 (m, 1H), 7.38-7.35 (m, 2H), 6.41(s, 1H), 4.58 (s, 2H), 4.45 (t, 1H), 3.90 (s, 3H), 2.60 (s, 3H), 2.54-2.45(m, 2H), 2.04-1.80 (m, 2H); HRMS(ESI) calcd for C 20 H 20 O5, [M+H] + 341.13, found341.13. The preparation method of the above-mentioned anti-anxiety γ-aminobutyric acid composition includes the following steps: weighing the prescribed amounts of paeonol derivative, γ-aminobutyric acid, astaxanthin, and starfish saponins, mixing them evenly, and adding excipients.

[0026] Example 2

[0027] An anti-anxiety γ-aminobutyric acid composition, comprising the following components by weight: 1 part paeonol derivative, 0.1 part γ-aminobutyric acid, 0.1 part astaxanthin, and 0.01 part starfish saponin.

[0028] The preparation process of the paeonol derivative includes the following steps: (1) Dissolve paeonol in glacial acetic acid, then add chloromethyl methyl ether dropwise to the paeonol glacial acetic acid solution, wherein the molar ratio of paeonol to chloromethyl methyl ether is 1:2.1, and the concentration of paeonol in acetic acid is 1.5 mol / L; react for 5 h after the addition of chloromethyl methyl ether is completed; filter the reaction solution, wash the filter cake with anhydrous ethanol, and dry to obtain intermediate 1; intermediate 1 1 The H NMR results are the same as in Example 1.

[0029] (2) Under nitrogen protection, intermediate 1, tert-butyldimethylchlorosilane (TBDMSCl), imidazole, and 1-butyl-3-methylimidazolium hexafluorophosphate were added sequentially to acetone, wherein the molar ratio of intermediate 1, tert-butyldimethylchlorosilane, imidazole, and 1-butyl-3-methylimidazolium hexafluorophosphate was 5:6:12:8, and the concentration of intermediate 1 in acetone was 0.5 mol / L; the reaction was carried out for 2 h; the mixture was quenched with water to extinguish the reaction, the acetone in the reaction solution was concentrated, the reaction solution was extracted with ethyl acetate, the combined ethyl acetate phases were washed with pure water, filtered, concentrated, and chromatographically purified (eluent, V 石油醚 V 乙酸乙酯 =88:12) thus obtaining intermediate 2; intermediate 21 The H NMR results are the same as in Example 1.

[0030] (3) 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate, and intermediate 2 were added to anhydrous N,N-dimethylformamide, wherein the molar ratio of intermediate 2, 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate, and intermediate 2 was 1:1.2:2, and the concentration of intermediate 2 in anhydrous N,N-dimethylformamide was 0.3 mol / L. After stirring evenly, the mixture was reacted at 95°C for 8 h. The reaction solution was cooled to room temperature, poured into ice water, and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, concentrated, and then subjected to column chromatography (V... 石油醚 V 乙酸乙酯 =90:10) Purification yielded intermediate 3; intermediate 3 1 The H NMR results are the same as in Example 1.

[0031] (4) Under nitrogen protection, intermediate 3 was added to tetrahydrofuran, cooled to -5°C, and tetrabutylammonium fluoride was added. The molar ratio of intermediate 3 to tetrabutylammonium fluoride was 1:1.4, and the concentration of intermediate 3 in tetrahydrofuran was 0.2 mol / L. The reaction was carried out at 18°C ​​for 6 h. The reaction was quenched with saturated ammonium chloride solution, and the reaction solution was extracted with ethyl acetate. The organic phase was filtered, concentrated, and purified by chromatography (eluent, V). 正己烷 V 乙酸乙酯 =85:15) to obtain paeonol derivatives. Paeonol derivatives 1 The H NMR results are the same as in Example 1.

[0032] The preparation method of the above-mentioned anti-anxiety γ-aminobutyric acid composition is the same as that in Example 1.

[0033] Example 3

[0034] An anti-anxiety γ-aminobutyric acid composition, comprising the following components by weight: 2 parts of paeonol derivative, 0.5 parts of γ-aminobutyric acid, 0.3 parts of astaxanthin, and 0.05 parts of starfish saponin.

[0035] The preparation process of the paeonol derivative includes the following steps: (1) Dissolve paeonol in glacial acetic acid, then add chloromethyl methyl ether dropwise to the paeonol glacial acetic acid solution, wherein the molar ratio of paeonol to chloromethyl methyl ether is 1:2.2, and the concentration of paeonol in acetic acid is 2 mol / L; react for 8 hours after the addition of chloromethyl methyl ether is completed; filter the reaction solution, wash the filter cake with anhydrous ethanol, and dry to obtain intermediate 1; intermediate 1 1 The H NMR results are the same as in Example 1.

[0036] (2) Under nitrogen protection, intermediate 1, TBDMSCl, imidazole, and 1-butyl-3-methylimidazolium hexafluorophosphate were added sequentially to acetone, wherein the molar ratio of intermediate 1, tert-butyldimethylchlorosilane, imidazole, and 1-butyl-3-methylimidazolium hexafluorophosphate was 5:8:15:10, and the concentration of intermediate 1 in acetone was 0.5 mol / L; the reaction was carried out for 5 h; the mixture was quenched with water to extinguish the reaction, the acetone in the reaction solution was concentrated, the reaction solution was extracted with ethyl acetate, the combined ethyl acetate phase was washed with pure water, filtered, concentrated, and chromatographically purified (eluent, V 石油醚 V 乙酸乙酯 =88:12) thus obtaining intermediate 2; intermediate 2 1 The H NMR results are the same as in Example 1.

[0037] (3) 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate, and intermediate 2 were added to anhydrous N,N-dimethylformamide, wherein the molar ratio of intermediate 2, 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate, and intermediate 2 was 1:1.5:2.5, and the concentration of intermediate 2 in anhydrous N,N-dimethylformamide was 0.5 mol / L. After stirring evenly, the mixture was reacted at 110°C for 4 h. The reaction solution was cooled to room temperature, poured into ice water, and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, concentrated, and then subjected to column chromatography (V... 石油醚 V 乙酸乙酯 =90:10) Purification yielded intermediate 3; intermediate 3 1 The H NMR results are the same as in Example 1.

[0038] (4) Under nitrogen protection, intermediate 3 was added to tetrahydrofuran, cooled to -5°C, and tetrabutylammonium fluoride was added. The molar ratio of intermediate 3 to tetrabutylammonium fluoride was 1:1.5, and the concentration of intermediate 3 in tetrahydrofuran was 0.5 mol / L. The reaction was carried out at 20°C for 4 h. The reaction was quenched with saturated ammonium chloride solution, and the reaction solution was extracted with ethyl acetate. The organic phase was filtered, concentrated, and purified by chromatography (eluent, V). 正己烷 V 乙酸乙酯 =85:15), and then dried to obtain paeonol derivatives. Paeonol derivatives 1 The 1H NMR results are the same as in Example 1. The preparation method of the above-mentioned anti-anxiety γ-aminobutyric acid composition is the same as in Example 1.

[0039] Comparative Example 1 This comparative example is basically the same as Example 1, except that the paeonol derivative is replaced with paeonol; otherwise, it is consistent with Example 1.

[0040] Comparative Example 2 This comparative example is basically the same as Example 1, except that the addition of starfish saponins is omitted; otherwise, it remains the same as Example 1.

[0041] Test Example 1 1.1 Laboratory Animals C57BL / 6 mice, weighing 20-24g and SPF grade, were selected as experimental animals. A total of 70 mice were randomly divided into 7 groups: model group, blank control group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, and Comparative Example 2 group, with 10 mice in each group. The mice were acclimatized for one week and had free access to water and food.

[0042] 1.2 Constructing an animal insomnia model Except for the blank control group, all other C57BL / 6 mice were intraperitoneally injected with DL-4-chlorophenylalanine (PCPA) at a dose of 350 mg / kg / day for 7 consecutive days. The mice exhibited anxiety and depression-like behaviors (such as weight loss, irritability, and increased aggression), which indicated successful model establishment. The blank control group was administered an equal volume of physiological saline by gavage daily.

[0043] 1.3 Drug intervention Examples 1-3 and Comparative Examples 1-2 were administered 100 mg / kg / day of the composition by gavage (e.g., Example 1 group was administered the composition of Example 1 by gavage), while the blank control group and model group were administered an equal volume of physiological saline by gavage for 7 consecutive days.

[0044] 1.4 Animal Behavioral Experiments 1.4.1 Open Field Experiment One hour after the last administration, mice in each group were placed in an open field box and allowed to acclimatize for 1 minute. The mice were then removed and placed back in the center of the open field box. The mice's activity within the box was recorded for 10 minutes. The experiment was conducted in a quiet environment, and the total distance and speed of movement of the mice were measured.

[0045] Table 1 Group Total distance traveled (cm) Average speed (cm / s) Blank control group 2567.63 5.65 Model Group 3651.54 11.23 Example 1 2678.12 6.01 Example 2 2735.78 6.58 Example 3 2706.15 6.36 Comparative Example 1 2856.54 7.82 Comparative Example 2 3010.27 8.25 The distance and time spent moving in mice can serve as indicators of mouse behavior, reflecting the impact of drug intervention on anxiety or depression. Total distance and average speed are positively correlated with the activity level of the mice. Observing the experimental results in Table 1, it can be seen that compared with the blank control group, the model group showed a significant increase in distance and a significant increase in average speed; these results indicate that the mice in the model group exhibited higher levels of exploratory behavior, anxiety, and tension in the new environment. Compared with the model group, the distance and average speed of mice in Examples 1-3 decreased. This indicates that the composition obtained in this invention alleviates anxiety symptoms to some extent. Compared with Example 1, the mice in Comparative Examples 1 and 2 showed an increase in total distance and an increase in average speed, indicating more severe anxiety levels, suggesting that at the same dosage, the paeonol derivative is more effective than paeonol.

[0046] 1.4.2 Elevated Cross Maze Experiment The elevated cruciate maze for mice consisted of two opposing open arms, two opposing closed arms, and a central platform connecting all four arms. The central platform connected the two open arms and the two closed arms. One hour after the last drug administration, the mice were placed in the box at the central platform and allowed to explore for approximately 10 minutes while white noise was played to eliminate distracting sounds. The time the mice spent in the closed arms was recorded within each 5-minute interval. The percentage of time the mice spent in the open arms was calculated as a percentage of the total time, and this was used as an indicator of the mice's anxiety level. The shorter the time the mice spent in the open arms, the more severe their anxiety symptoms. The experimental results are shown in Table 2.

[0047] Table 2 Group Percentage of time spent in the open arm out of total time (%) Blank control group 29.54 Model Group 12.31 Example 1 28.52 Example 2 26.95 Example 3 28.13 Comparative Example 1 23.28 Comparative Example 2 20.35 As shown in Table 2, the mice in Examples 1-3 spent a longer time in the open arm than those in Comparative Examples 1 and 2, indicating that in the maze experiment, both paeonol derivatives and starfruit saponins could increase the time mice spent in the open arm. Comparing Example 1 and Comparative Example 1, it can be seen that within a smaller dosage range, the introduction of paeonol derivatives is much more effective than paeonol itself. That is, compared to paeonol, paeonol derivatives can reduce the dosage, and when used in combination with γ-aminobutyric acid and starfruit saponins, they can still maintain good efficacy and alleviate anxiety symptoms.

[0048] 1.4.3 Sodium pentobarbital sleep experiment One hour after the last administration of the drug, each group of mice was intraperitoneally injected with sodium pentobarbital suspension at a dose of 50 mg / kg. The mice were placed on a mat with their abdomens facing upwards, and the sleep latency and sleep duration were recorded. Sleep latency was recorded from the end of the intraperitoneal injection until more than 1 minute after the disappearance of the righting reflex (defined as falling asleep), and sleep time was recorded from the time the righting reflex returned (defined as waking). The experimental results are recorded in Table 3.

[0049] Table 3 Group Sleep latency (s) Sleep duration (min) Blank control group 215.52 65.13 Model Group 365.19 41.12 Example 1 218.51 85.89 Example 2 219.34 81.76 Example 3 219.63 83.45 Comparative Example 1 232.13 75.23 Comparative Example 2 246.45 64.12 As shown in Table 3, compared with the blank control group, the sleep latency of the model group mice was significantly prolonged, and the sleep duration was also shortened. Compared with the model group, the sleep latency of the mice in Examples 1-3 was shortened, and the sleep duration was prolonged.

[0050] Comparative Examples 1 and 2 replaced paeonol derivatives with paeonol, omitting star saponins. Compared with Example 1, the sleep latency of both was prolonged and the sleep duration tended to be shortened. This indicates that the paeonol derivatives of the present invention can work synergistically with components such as star saponins to shorten the sleep latency and prolong the sleep time, thereby increasing the therapeutic effect on insomnia and anxiety.

[0051] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. An anti-anxiety γ-aminobutyric acid composition, characterized in that, By weight, it includes the following components: 1-2 parts of paeonol derivative, 0.1-0.5 parts of γ-aminobutyric acid, 0.1-0.3 parts of astaxanthin, and 0.01-0.05 parts of starfish saponins.

2. The anti-anxiety γ-aminobutyric acid composition according to claim 1, characterized in that, The preparation process of the paeonol derivative includes the following steps: (1) Paeonol was added to a solvent, and chloromethyl methyl ether was added dropwise to react. After filtration, washing and drying, intermediate 1 was obtained. (2) Intermediate 1, tert-butyldimethylchlorosilane, imidazole and 1-butyl-3-methylimidazolium hexafluorophosphate were added to a solvent and reacted. After washing, concentration and purification, intermediate 2 was obtained. (3) Add 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, potassium carbonate and intermediate 2 to a solvent, heat and react, and then wash, concentrate and purify to obtain intermediate 3; (4) Add intermediate 3 and tetrabutylammonium fluoride to the solvent for reaction, and then filter, concentrate, purify and dry to obtain the paeonol derivative.

3. The anti-anxiety γ-aminobutyric acid composition according to claim 2, characterized in that, In step (1), the molar ratio of paeonol to chloromethyl methyl ether is 1:(2-2.2), the concentration of paeonol in the solvent is 1-2 mol / L, the solvent is acetic acid, and the reaction time is 5-8 h.

4. The anti-anxiety γ-aminobutyric acid composition according to claim 2, characterized in that, In step (2), the molar ratio of intermediate 1, tert-butyldimethylchlorosilane, imidazole and 1-butyl-3-methylimidazolium hexafluorophosphate is 5:(6-8):(12-15):(8-10); the concentration of intermediate 1 in the solvent is 0.5-1 mol / L, and the solvent is acetone; the reaction time is 2-5 h.

5. The anti-anxiety γ-aminobutyric acid composition according to claim 2, characterized in that, In step (3), the molar ratio of intermediate 2, 4-hydroxy-3,4-dihydronaphthyl-1(2H)-one, and potassium carbonate is 1:(1.2-1.5):(2-2.5), the concentration of intermediate 2 in the solvent is 0.2-0.5 mol / L, and the solvent is anhydrous N,N-dimethylformamide.

6. The anti-anxiety γ-aminobutyric acid composition according to claim 2, characterized in that, In step (3), the heating reaction is carried out at a temperature of 95~110℃ for 4~8h.

7. The anti-anxiety γ-aminobutyric acid composition according to claim 2, characterized in that, In step (4), the molar ratio of intermediate 3 to tetrabutylammonium fluoride is 1:(1.2-1.5), the concentration of intermediate 3 in the solvent is 0.2-0.5 mol / L, and the solvent is tetrahydrofuran.

8. The anti-anxiety γ-aminobutyric acid composition according to claim 2, characterized in that, In step (4), the reaction temperature is 15-20°C and the time is 3-6h.

9. A method for preparing the anti-anxiety γ-aminobutyric acid composition according to any one of claims 1-8, characterized in that, The process includes the following steps: weigh out the prescribed amounts of paeonol derivative, γ-aminobutyric acid, astaxanthin, and starfish saponins, mix them evenly, and add excipients to obtain the final product.

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