Composition for improving sleep quality and preparation method and application thereof

Abstract

The present invention proposes a composition for improving sleep quality, a preparation method and an application thereof, and belongs to the field of medical technology. Lavender, violet, rose and agarwood are subjected to supercritical fluid extraction to obtain an extracted oil, solid enzymatic hydrolysis, immobilized ionic liquid extraction, desorption, and extraction oil. The extracted oil is mixed evenly with the extracted oil and a penetration enhancer to obtain a composition for improving sleep quality. The present invention mixes the obtained extracted oil and the extracted oil, adds a penetration enhancer, and the obtained composition for improving sleep quality is absorbed into the human body through the skin, achieving the effect of regulating the qi of the internal organs and harmonizing the yin and yang of the body, having the effects of calming the mind and helping sleep, prolonging sleep time, improving sleep efficacy, and relieving tension, and has broad application prospects.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a composition for improving sleep quality, a preparation method and an application thereof. Background Art

[0002] One third of a person's life is spent in sleep. High-quality sleep is the basis for us to complete our daily work and life and maintain a healthy body. According to changes in EEG, eye movement, electromyography, etc., sleep is usually divided into two stages: non-rapid eye movement sleep and rapid eye movement sleep or deep sleep. Studies have shown that the shallow sleep and light sleep periods, which account for about 55% of the total sleep time, have little effect on relieving fatigue, and only the middle sleep period, deep sleep period and rapid eye movement sleep period in the deep sleep state have a greater effect on relieving fatigue. Because in the deep sleep state, the cerebral cortex cells are in a state of full rest, which plays a vital role in eliminating fatigue, restoring energy, immunity and disease resistance. However, this deep sleep only accounts for 25% of the total sleep time. If the human body cannot get effective deep sleep for a long time, it is easy to cause insomnia and lead to a series of pathological reactions in the body.

[0003] Currently, there are many types of essential oils on the market, most of which are single essential oils. Most consumers are not familiar with the blending of essential oils, and their applicability is narrow, or the preparation methods are complicated and expensive. They are not effective in promoting sleep, which leads to poor consumer compliance. Summary of the invention

[0004] The purpose of the present invention is to provide a composition for improving sleep quality, a preparation method and an application thereof, which can promote uric acid excretion, inhibit sodium urate crystallization, improve antioxidant effect, repair intestinal barrier, reduce inflammation, inhibit xanthine oxidase (XOD) activity and expression, reduce blood uric acid level, have a good uric acid-lowering effect, and have broad application prospects.

[0005] The technical solution of the present invention is achieved in this way:

[0006] The invention provides a method for preparing a composition for improving sleep quality. The method comprises the following steps: subjecting lavender, violet, rose and agarwood to supercritical fluid extraction to obtain extraction oil, solid enzymatic hydrolysis, immobilized ionic liquid extraction and desorption to obtain extraction oil, and uniformly mixing the extraction oil with the extraction oil and a penetration enhancer to prepare the composition for improving sleep quality.

[0007] As a further improvement of the present invention, the following steps are included:

[0008] S1. freeze-dry lavender, violet, rose and agarwood, crush them, extract them with supercritical fluid, and collect the solid and extracted oil;

[0009] S2. The solid is added to water, a composite enzyme is added to hydrolyze the solid, the enzyme is inactivated, the solid is filtered, and the solvent is removed from the filtrate under reduced pressure to obtain an extract;

[0010] S3. Adding immobilized ionic liquid to the extract, adsorbing by ultrasonic stirring, filtering, adding the solid to ethanol, heating for desorption, filtering, washing the solid, recovering, reusing, recovering ethanol from the filtrate, and obtaining the extracted oil;

[0011] S4. Evenly mix the extraction oil, the extracted oil and the penetration enhancer to prepare a composition for improving sleep quality.

[0012] As a further improvement of the present invention, the mass ratio of lavender, violet, rose and agarwood in step S1 is 10-12:7-9:3-5:2-4, and the conditions of supercritical fluid extraction are extraction pressure: 20-25MPa, extraction temperature: 35-45°C, CO 2 Flow rate: 5-10 L / h, extraction time: 1-3 h, the addition amount of the entrainer is 1-2 wt%, and the entrainer is ethanol.

[0013] As a further improvement of the present invention, in step S2, the mass ratio of the solid to the composite enzyme is 10:1-2, the composite enzyme is cellulase and pectinase, the mass ratio is 4-6:3, the temperature of the enzymatic hydrolysis is 40-50°C, and the time is 2-4h.

[0014] As a further improvement of the present invention, the mass ratio of the extract and the immobilized ionic liquid in step S3 is 10:3-4, the ultrasonic stirring adsorption time is 0.5-1.5h, the power is 500-1000W, the heating temperature is 45-55°C, and the preparation method of the immobilized ionic liquid is as follows:

[0015] T1. Add silica gel powder to ethanol, add a silane coupling agent with a double bond, heat and stir to react, filter, wash, and dry to obtain modified silica gel powder;

[0016] T2. The modified silica gel powder and N-vinyl imidazole were added to dichloromethane, an initiator was added, and the reaction was heated and stirred to obtain imidazole-modified silica gel powder;

[0017] T3. The imidazole-modified silica powder and n-butyl chloride were added to acetone, heated to reflux, filtered, washed, and dried to obtain substituted imidazole-modified silica powder;

[0018] T4. Add substituted imidazole-modified silica gel powder and sodium 2-naphthalenesulfonate into water, stir at room temperature, filter, wash and dry to obtain an immobilized ionic liquid.

[0019] As a further improvement of the present invention, the mass ratio of the silica gel powder and the silane coupling agent with double bonds in step T1 is 10:3-5, the silane coupling agent with double bonds is selected from at least one of KH570, A151, and A171, the temperature of the heating and stirring reaction is 40-50°C, and the time is 2-4h; the mass ratio of the modified silica gel powder, N-vinyl imidazole, and the initiator in step T2 is 15-20:7-10:0.01-0.02, the initiator is selected from at least one of potassium persulfate, sodium persulfate, and ammonium persulfate, the temperature of the heating and stirring reaction is 45-55°C, and the time is 3-5h; the mass ratio of the imidazole-modified silica gel powder and n-butyl chloride in step T3 is 10:3-4, and the time of the heating reflux reaction is 20-24h; the mass ratio of the substituted imidazole-modified silica gel powder and sodium 2-naphthalenesulfonate in step T4 is 12-15:4-7, and the time of stirring at room temperature is 7-9h.

[0020] As a further improvement of the present invention, the mass ratio of the extraction oil, the extracted oil, and the penetration enhancer in step S4 is 10:7-10:0.01-0.02; the penetration enhancer is a mixture of laurocapram and a penetration enhancer compound, the mass ratio is 10:3-5, and the structure of the penetration enhancer compound is shown in Formula I:

[0021]

[0022] The preparation method of the penetration-enhancing compound is as follows:

[0023] U1. Salicylic acid and carveol react under the action of a catalyst to obtain an intermediate with the following structure:

[0024] U2. The intermediate is reacted with nicotinic acid in the presence of a catalyst to obtain a penetration-enhancing compound.

[0025] As a further improvement of the present invention, the molar ratio of salicylic acid to carveol in step U1 is 1-1.1:1, the catalyst is concentrated sulfuric acid, the addition amount is 2-3wt% of salicylic acid, the reaction temperature is 100-110°C, and the time is 4-6h; the molar ratio of the intermediate to nicotinic acid in step U2 is 1:1-1.1, the catalyst is concentrated sulfuric acid, the addition amount is 2-3wt% of the intermediate, the reaction temperature is 100-110°C, and the time is 3-5h.

[0026] The present invention further protects a composition for improving sleep quality prepared by the above preparation method.

[0027] The present invention further protects the use of the above-mentioned composition for improving sleep quality in the preparation of a medicine for promoting sleep, improving sleep quality, and prolonging sleep time.

[0028] The present invention has the following beneficial effects:

[0029] Aromatherapy refers to the process of making natural plants with aromatic smells into appropriate dosage forms, which act on local or systemic areas to achieve the medical and health care effects of preventing and treating diseases and promoting health. It uses the aromatic smell of Chinese herbal medicines or the extraction of aromatic essential oils to act on the human body through oral administration, inhalation, skin absorption, etc., to achieve the effect of regulating the qi of the internal organs and harmonizing the yin and yang of the body.

[0030] The main chemical components of lavender essential oil are linalool, linalyl acetate, lavandin acetate, etc. Among them, linalool can stimulate the parasympathetic nervous system and has a calming effect. Linalyl acetate has a calming, relaxing and hypnotic effect. Aromatherapy with lavender essential oil can effectively prevent sleep disorders. Its mechanism of action may be related to increasing the level of 5-hydroxytryptamine (5-HT) in the body. Violet essential oil contains a large amount of monoterpenes and sesquiterpenes. Linalool (a monoterpene alcohol) is the main component of common violet essential oil and can be used as an antioxidant and neuroprotectant. Rose essential oil is a natural essential oil derived from rose petals with multiple effects, including antioxidant, antibacterial, soothing and mood regulation. Agarwood has multiple medicinal values, with multiple effects such as clearing the mind and calming the nerves, nourishing qi and essence, detoxifying and preventing epidemics. Agarwood essential oil has volatile components such as linalool, linalool acetate, and santalol, which are believed to have the effects of calming the nerves, helping sleep, and relieving tension. The present invention obtains the composite extraction oil by supercritical fluid extraction method, which is rich in active components and has good effects of regulating mood and helping sleep. However, the active components of the product obtained by direct extraction are not completely extracted, which reduces the utilization rate of the raw materials.

[0031] The present invention further hydrolyzes the extracted solid with a composite enzyme (including cellulase and pectinase), which promotes the breaking of plant cell walls, and a large amount of active components are dissolved, and a large amount of impurities also enter the solution. The present invention prepares and adds an immobilized ionic liquid with high enrichment efficiency and adsorption capacity, which enables them to effectively extract active molecules from samples in solid phase extraction, facilitate separation and desorption, and thus greatly improve the purification effect of active components.

[0032] The immobilized ionic liquid of the present invention uses silica gel as a carrier. After the surface is modified by a silane coupling agent with double bonds, it can be copolymerized with N-vinyl imidazole, and then further reacted by anion exchange, thereby preparing an immobilized ionic liquid with good stability, strong solubility, easy separation and other characteristics. It can reduce the loss of ionic liquid during operation, reduce costs and reduce environmental pollution, and there is no residual anxiety of ionic liquid.

[0033] The invention mixes the prepared extraction oil and the extracted oil, adds a penetration enhancer, and the prepared composition for improving sleep quality is absorbed into the human body through the skin, thereby achieving the effects of regulating the qi of the internal organs and harmonizing the yin and yang of the body, having the effects of calming the mind and promoting sleep, prolonging sleep time, improving sleep efficacy, and relieving nervous emotions, and has broad application prospects.

[0034] The invention uses carveol and salicylic acid esterification reaction to prepare the intermediate, which solves the problem that carveol and salicylic acid have strong skin irritation when used alone. The combined intermediate can break and fuse the fatty acid arrangement between cells or directly extract fatty acids in the epidermis, thereby weakening the barrier function of the skin, thereby increasing the permeability of chemical substances, and further reacting with nicotinic acid, thereby solving the problems of nicotinic acid directly causing skin allergies and changing the pH value of the skin, improving the anti-inflammatory, antibacterial and antioxidant properties of the skin, and further improving the penetration-promoting effect on other substances. The preparation method of the penetration-promoting compound of the invention is simple, the conditions are mild, the yield is high, the obtained product has good effect, and has an unexpected synergistic effect with laurocapron. The essential oil itself has good penetration-promoting property. After the penetration enhancer is added, the penetration-promoting effect is further improved and the efficacy is enhanced. DETAILED DESCRIPTION

[0035] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] Silica gel powder, 150-250μm, specific surface area 600-800㎡ / g.

[0037] Cellulase, 50,000 U / g, and pectinase, 50,000 U / g, were purchased from Shanghai Yuanye Biotechnology Co., Ltd.

[0038] Preparation Example 1 Preparation of immobilized ionic liquid

[0039] Here’s how:

[0040] T1. Add 10 g silica gel powder to 200 mL ethanol, add 3 g silane coupling agent A151, heat to 40 ° C, stir and react for 2 h, filter, wash and dry to obtain modified silica gel powder;

[0041] T2. Add 15 g of modified silica gel powder and 7 g of N-vinyl imidazole to 500 mL of dichloromethane, add 0.01 g of sodium persulfate, heat to 45 ° C, stir and react for 3 h to obtain imidazole-modified silica gel powder;

[0042] T3. 10 g of imidazole-modified silica gel powder and 3 g of n-butyl chloride were added to 200 mL of acetone, heated under reflux for 20 h, filtered, washed, and dried to obtain substituted imidazole-modified silica gel powder;

[0043] T4. Add 12 g of substituted imidazole-modified silica gel powder and 4 g of sodium 2-naphthalenesulfonate into 200 mL of water, stir at room temperature for 7 h, filter, wash, and dry to obtain an immobilized ionic liquid.

[0044] Preparation Example 2 Preparation of immobilized ionic liquid

[0045] Here’s how:

[0046] T1. Add 10 g of silica gel powder to 200 mL of ethanol, add 5 g of silane coupling agent A171, heat to 50 ° C, stir and react for 4 hours, filter, wash and dry to obtain modified silica gel powder;

[0047] T2. Add 20 g of modified silica gel powder and 10 g of N-vinyl imidazole to 500 mL of dichloromethane, add 0.02 g of potassium persulfate, heat to 55 ° C, stir and react for 5 h to obtain imidazole-modified silica gel powder;

[0048] T3. 10 g of imidazole-modified silica gel powder and 4 g of n-butyl chloride were added to 200 mL of acetone, heated under reflux for 24 h, filtered, washed, and dried to obtain substituted imidazole-modified silica gel powder;

[0049] T4. Add 15 g of substituted imidazole-modified silica gel powder and 7 g of sodium 2-naphthalenesulfonate into 200 mL of water, stir at room temperature for 9 h, filter, wash, and dry to obtain an immobilized ionic liquid.

[0050] Preparation Example 3 Preparation of immobilized ionic liquid

[0051] Here’s how:

[0052] T1. Add 10 g of silica gel powder to 200 mL of ethanol, add 4 g of silane coupling agent KH570, heat to 45 ° C, stir and react for 3 hours, filter, wash and dry to obtain modified silica gel powder;

[0053] T2. Add 17 g of modified silica gel powder and 8 g of N-vinyl imidazole to 500 mL of dichloromethane, add 0.015 g of ammonium persulfate, heat to 50 ° C, stir and react for 4 hours to obtain imidazole-modified silica gel powder;

[0054] T3. 10 g of imidazole-modified silica powder and 3.5 g of n-butyl chloride were added to 200 mL of acetone, heated under reflux for 22 h, filtered, washed, and dried to obtain substituted imidazole-modified silica powder;

[0055] T4. Add 13 g of substituted imidazole-modified silica gel powder and 5 g of sodium 2-naphthalenesulfonate into 200 mL of water, stir at room temperature for 8 h, filter, wash, and dry to obtain an immobilized ionic liquid.

[0056] Comparative Preparation Example 1

[0057] Compared with Preparation Example 3, the difference is that step S4 is not performed.

[0058] Test Example 1

[0059] The specific surface area and total pore volume of the immobilized ionic liquids prepared in Preparation Examples 1-3 were measured using a 3-FLEX 3500 multi-station high-throughput gas adsorption instrument.

[0060] The results are shown in Table 1.

[0061] Table 1

[0062] Group <![CDATA[Specific surface area (m 2 / g)]]> <![CDATA[Total pore volume (cm 3 / g)]]> Preparation Example 1 856.7 0.52 Preparation Example 2 859.2 0.54 Preparation Example 3 863.4 0.55 Comparative Preparation Example 1 821.4 0.49

[0063] It can be seen from the above table that the immobilized ionic liquids prepared in Preparation Examples 1-3 of the present invention have a relatively high specific surface area.

[0064] Preparation Example 4 Preparation of penetration enhancing compounds

[0065] The synthetic route is as follows:

[0066]

[0067] Here’s how:

[0068] U1. Dissolve 10 mmol salicylic acid and 10 mmol carveol in 200 mL toluene, add concentrated sulfuric acid in an amount of 3 wt% of salicylic acid, heat under reflux for 5 h, remove the solvent under reduced pressure, wash with water, dry, and recrystallize from acetone to obtain an intermediate; ESI-MS calculated value: C 17 H 21 O 3 (M+H) + 243.14, found value: 243.1, yield: 78%.

[0069] NMR results: 1 H NMR (300 MHz, CDCl 3 )δ7.8 (d, J=6.5Hz, 1H), 7.3 (m, 1H), 6.89-6.92 (m, 2H), 5.37 (t, 1H), 5.0 (br, 1H), 4.85 (d, J= 4.2Hz, 1H), 4.65 (d, J=4.4Hz, 1H), 4.42 (t, 1H), 2.33 (m, 1H), 1.89-2.2 (m, 4H), 1.72 (s, 6H).

[0070] U2. Dissolve 10 mmol of the intermediate and 10 mmol of nicotinic acid in 200 mL of toluene, add concentrated sulfuric acid in an amount of 2 wt% of the intermediate, heat under reflux for 4 h, wash with water, dry, and recrystallize from acetone to obtain a permeation-enhancing compound. ESI-MS calculated value: C 23 H 24 NO 4 (M+H) + 378.16, found: 378.2, yield: 72%.

[0071] NMR results: 1 H NMR (300 MHz, CDCl 3 ) δ9.05 (s, 1H), 8.72 (d, J = 6.7Hz, 1H), 8.17 (d, J = 6.2Hz, 1H), 7.92 (d, J = 6.0Hz, 1H), 7.54 (m, 1H), 7.42 (m, 1H), 7.19 (m, 2H), 5.37 (t, 1H), 4.82 (d, 1H), 4.62 (d, 1H), 4.41 (t, 1H), 2.32 (m, 1H), 1.82-2.05 (m, 4H), 1.75 (s, 6H).

[0072] Example 1

[0073] This embodiment provides a method for preparing a composition for improving sleep quality, comprising the following steps:

[0074] S1. 10 g lavender, 7 g violet, 3 g rose, and 2 g agarwood were freeze-dried, crushed, and subjected to supercritical fluid extraction to collect the solid and extracted oil;

[0075] The conditions of the supercritical fluid extraction are: extraction pressure: 20 MPa, extraction temperature: 35°C, CO 2 Flow rate: 5 L / h, extraction time: 1 h, the amount of the entrainer added is 1 wt%, and the entrainer is ethanol;

[0076] S2. 10 g of the solid was added to 200 mL of water, 1 g of the complex enzyme was added, and the enzyme was hydrolyzed at 40 ° C for 2 h, the enzyme was inactivated, and the filtrate was filtered and the solvent was removed under reduced pressure to obtain an extract;

[0077] The complex enzyme is cellulase and pectinase, with a mass ratio of 4:3;

[0078] S3. Add 3 g of the immobilized ionic liquid prepared in Preparation Example 1 to 10 g of the extract, adsorb for 0.5 h under 500 W ultrasonic stirring, filter, add the solid to 50 mL of ethanol, heat to 45 ° C, desorb for 30 min, filter, wash the solid, recover, reuse, recover ethanol from the filtrate, and obtain the extracted oil;

[0079] S4. 10 g of the extract oil, 7 g of the extract oil, and 0.01 g of the penetration enhancer were mixed to obtain a composition for improving sleep quality;

[0080] The penetration enhancer is a mixture of laurocapram and the penetration enhancer compound prepared in Preparation Example 4, with a mass ratio of 10:3.

[0081] Example 2

[0082] This embodiment provides a method for preparing a composition for improving sleep quality, comprising the following steps:

[0083] S1. 12 g lavender, 9 g violet, 5 g rose, and 4 g agarwood were freeze-dried, crushed, and subjected to supercritical fluid extraction to collect the solid and extracted oil;

[0084] The conditions of the supercritical fluid extraction are: extraction pressure: 25 MPa, extraction temperature: 45°C, CO 2 Flow rate: 10 L / h, extraction time: 3 h, the amount of the entrainer added is 2 wt%, and the entrainer is ethanol;

[0085] S2. 10 g of the solid was added to 200 mL of water, 2 g of the complex enzyme was added, and the enzyme was hydrolyzed at 50 ° C for 4 h, the enzyme was inactivated, and the filtrate was filtered and the solvent was removed under reduced pressure to obtain an extract;

[0086] The complex enzyme is cellulase and pectinase, with a mass ratio of 6:3;

[0087] S3. Add 4 g of the immobilized ionic liquid prepared in Preparation Example 2 to 10 g of the extract, stir and adsorb under 1000 W ultrasonic stirring for 1.5 h, filter, add the solid to 50 mL of ethanol, heat to 55 ° C, desorb for 30 min, filter, wash the solid, recover, reuse, and recover ethanol from the filtrate to obtain an extracted oil;

[0088] S4. 10 g of the extract oil, 10 g of the extracted oil, and 0.02 g of the penetration enhancer were mixed to obtain a composition for improving sleep quality;

[0089] The penetration enhancer is a mixture of laurocapram and the penetration enhancer compound prepared in Preparation Example 4, with a mass ratio of 10:5.

[0090] Example 3

[0091] This embodiment provides a method for preparing a composition for improving sleep quality, comprising the following steps:

[0092] S1. 11 g lavender, 8 g violet, 4 g rose, and 3 g agarwood were freeze-dried, crushed, and subjected to supercritical fluid extraction to collect the solid and extracted oil;

[0093] The conditions of the supercritical fluid extraction are: extraction pressure: 22 MPa, extraction temperature: 40°C, CO 2 Flow rate: 7 L / h, extraction time: 2 h, the amount of the entrainer added is 1.5 wt%, and the entrainer is ethanol;

[0094] S2. 10 g of the solid was added to 200 mL of water, 1.5 g of the complex enzyme was added, and the enzyme was hydrolyzed at 45 ° C for 3 h, the enzyme was inactivated, and the filtrate was filtered and the solvent was removed under reduced pressure to obtain an extract;

[0095] The complex enzyme is cellulase and pectinase, with a mass ratio of 5:3;

[0096] S3. Add 3.5 g of the immobilized ionic liquid prepared in Preparation Example 1 to 10 g of the extract, stir and adsorb under 700 W ultrasonic stirring for 1 h, filter, add the solid to 50 mL of ethanol, heat to 50 ° C, desorb for 30 min, filter, wash the solid, recover, reuse, and recover ethanol from the filtrate to obtain the extracted oil;

[0097] S4. 10 g of the extract oil, 8 g of the extract oil, and 0.015 g of the penetration enhancer were mixed to obtain a composition for improving sleep quality;

[0098] The penetration enhancer is a mixture of laurocapram and the penetration enhancer compound obtained in Preparation Example 4, with a mass ratio of 10:4.

[0099] Example 4

[0100] Compared with Example 3, the difference is that the penetration enhancer is a single laurocapram.

[0101] Example 5

[0102] Compared with Example 3, the difference is that the penetration enhancer is a single penetration enhancer compound prepared in Preparation Example 4.

[0103] Example 6

[0104] Compared with Example 3, the difference is that the composite enzyme is a single cellulase.

[0105] Example 7

[0106] Compared with Example 3, the difference is that the complex enzyme is a single pectinase.

[0107] Comparative Example 1

[0108] Compared with Example 3, the difference is that no penetration enhancer is added.

[0109] The details are as follows:

[0110] S4. Evenly mix 10 g of the extracted oil and 8 g of the extracted oil to prepare a composition for improving sleep quality.

[0111] Comparative Example 2

[0112] Compared with Example 3, the difference is that no complex enzyme is added.

[0113] The details are as follows:

[0114] S2. Add 10 g of the solid to 200 mL of water, heat and boil to extract for 3 h, filter, and remove the solvent from the filtrate under reduced pressure to obtain an extract.

[0115] Comparative Example 3

[0116] Compared with Example 3, the difference is that step S3 is not performed.

[0117] The details are as follows:

[0118] S1. 11 g lavender, 8 g violet, 4 g rose, and 3 g agarwood were freeze-dried, crushed, and subjected to supercritical fluid extraction to collect the solid and extracted oil;

[0119] The conditions of the supercritical fluid extraction are: extraction pressure: 22 MPa, extraction temperature: 40°C, CO 2 Flow rate: 7 L / h, extraction time: 2 h, the amount of the entrainer added is 1.5 wt%, and the entrainer is ethanol;

[0120] S2. 10 g of the solid was added to 200 mL of water, 1.5 g of the complex enzyme was added, and the enzyme was hydrolyzed at 45 ° C for 3 h, the enzyme was inactivated, and the filtrate was filtered and the solvent was removed under reduced pressure to obtain an extract;

[0121] The complex enzyme is cellulase and pectinase, with a mass ratio of 5:3;

[0122] S3. 10 g of the extract oil, 8 g of the extract, and 0.015 g of the penetration enhancer were mixed to obtain a composition for improving sleep quality;

[0123] The penetration enhancer is a mixture of laurocapram and the penetration enhancer compound obtained in Preparation Example 4, with a mass ratio of 10:4.

[0124] Comparative Example 4

[0125] Compared with Example 3, the difference is that no extraction oil is added in step S4.

[0126] The details are as follows:

[0127] S4. 18 g of the extracted oil and 0.015 g of the penetration enhancer were mixed to obtain a composition for improving sleep quality;

[0128] The penetration enhancer is a mixture of laurocapram and the penetration enhancer compound obtained in Preparation Example 4, with a mass ratio of 10:4.

[0129] Comparative Example 5

[0130] Compared with Example 3, the difference is that no extraction oil is added in step S4.

[0131] The details are as follows:

[0132] S4. 18 g of the extract oil and 0.015 g of the penetration enhancer were mixed to obtain a composition for improving sleep quality;

[0133] The penetration enhancer is a mixture of laurocapram and the penetration enhancer compound obtained in Preparation Example 4, with a mass ratio of 10:4.

[0134] Comparative Example 6

[0135] Compared with Example 3, the difference is that the immobilized ionic liquid is prepared by Comparative Preparation Example 1.

[0136] Test Example 2

[0137] Take 150 healthy ICR mice (half male and half female) and be randomly divided into 15 groups, 10 in each group, respectively embodiment 1-7 group, comparative example 1-6 group, control group, linalool group, embodiment 1-7 group, comparative example 1-6 group mice are evenly coated with 1mL / only corresponding prepared composition improving sleep quality on belly, linalool group gives 5mg / kg linalool, then each group of mice is intraperitoneally injected with 50mg / kg sodium pentobarbital, after administration, mice righting reflex disappears and reaches 1min person, indicating that sleep has been entered. The time between injection of sodium pentobarbital to the disappearance of righting reflex of mice is sleep latency, and the time between the disappearance of righting reflex of mice to the recovery of righting reflex is sleep time. Record the moment of sodium pentobarbital injection of each group of mice, the moment of righting reflex disappearance and the moment of righting reflex recovery, calculate sleep latency and sleep time. The results are shown in Table 2.

[0138] Table 2

[0139]

[0140]

[0141] Note: * compared with the control group, P < 0.05.

[0142] It can be seen from the above table that the compositions for improving sleep quality prepared in Examples 1-3 of the present invention can significantly prolong the sleep time of mice and shorten the sleep latency.

[0143] Test Example 3

[0144] 150 healthy ICR mice (half male and half female) were randomly divided into 15 groups, each with 10 mice, namely, Example 1-7 group, Comparative Example 1-6 group, control group, L-linalool group, Example 1-7 group, Comparative Example 1-6 group of mice were evenly coated with 1mL / a corresponding composition for improving sleep quality on the belly, L-linalool group was given 5mg / kg L-linalool, and then each group of mice was intraperitoneally injected with 30mg / kg of sodium pentobarbital, and the mice whose righting reflex disappeared within 30min for more than 1min were taken as sleep indicators, and the number of sleeps in each group of mice within 30min was recorded, and the sleep rate of each group of mice was calculated. The results are shown in Table 3.

[0145] Table 3

[0146] Group Sleep rate (%) Control group 10 L-linalool group 40 Example 1 90 Example 2 90 Example 3 100 Example 4 60 Example 5 50 Example 6 70 Example 7 70 Comparative Example 1 40 Comparative Example 2 50 Comparative Example 3 60 Comparative Example 4 50 Comparative Example 5 40 Comparative Example 6 80

[0147] It can be seen from the above table that the compositions for improving sleep quality prepared in Examples 1-3 of the present invention can significantly improve the sleep rate of mice.

[0148] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a composition for improving sleep quality, characterized in that: The following steps are involved: S1. freeze-drying lavender, violet, rose, and agarwood, crushing, supercritical fluid extraction, collecting solids and extracted oil; the mass ratio of lavender, violet, rose, and agarwood is 10-12:7-9:3-5:2-4; S2. The solid is added to water, a composite enzyme is added for enzymolysis, the enzyme is inactivated, the filtrate is filtered, and the solvent is removed from the filtrate under reduced pressure to obtain an extract; the mass ratio of the solid to the composite enzyme is 10:1-2, and the composite enzyme is cellulase and pectinase, and the mass ratio is 4-6:3; S3. Adding immobilized ionic liquid to the extract, adsorbing by ultrasonic stirring, filtering, adding solid to ethanol, heating for desorption, filtering, washing the solid, recovering, reusing, recovering ethanol from the filtrate, and obtaining an extracted oil; the mass ratio of the extract to the immobilized ionic liquid is 10:3-4; The preparation method of the immobilized ionic liquid is as follows: T1. Add silica gel powder to ethanol, add a silane coupling agent with a double bond, heat and stir to react, filter, wash, and dry to obtain modified silica gel powder; T2. The modified silica gel powder and N-vinyl imidazole were added to dichloromethane, an initiator was added, and the reaction was heated and stirred to obtain imidazole-modified silica gel powder; T3. The imidazole-modified silica powder and n-butyl chloride were added to acetone, heated to reflux, filtered, washed, and dried to obtain substituted imidazole-modified silica powder; T4. The substituted imidazole-modified silica gel powder and sodium 2-naphthalenesulfonate were added to water, stirred at room temperature, filtered, washed, and dried to obtain an immobilized ionic liquid; S4. The extract oil, the extracted oil, and the penetration enhancer are mixed evenly to prepare a composition for improving sleep quality; the mass ratio of the extract oil, the extracted oil, and the penetration enhancer is 10:7-10:0.01-0.

02.

2. The preparation method according to claim 1, characterized in that: The conditions of the supercritical fluid extraction in step S1 are extraction pressure: 20-25MPa, extraction temperature: 35-45°C, CO2 flow rate: 5-10L / h, extraction time: 1-3h, the addition amount of the entrainer is 1-2wt%, and the entrainer is ethanol.

3. The preparation method according to claim 1, characterized in that: The temperature of the enzymatic hydrolysis in step S2 is 40-50° C. and the time is 2-4 hours.

4. The preparation method according to claim 1, characterized in that: The ultrasonic stirring adsorption time in step S3 is 0.5-1.5h, the power is 500-1000W, and the heating temperature is 45-55°C.

5. The preparation method according to claim 1, characterized in that: The mass ratio of the silica gel powder and the silane coupling agent with double bonds in step T1 is 10:3-5, the silane coupling agent with double bonds is selected from at least one of KH570, A151, and A171, the temperature of the heating and stirring reaction is 40-50°C, and the time is 2-4h; the mass ratio of the modified silica gel powder, N-vinyl imidazole, and the initiator in step T2 is 15-20:7-10:0.01-0.02, the initiator is selected from at least one of potassium persulfate, sodium persulfate, and ammonium persulfate, the temperature of the heating and stirring reaction is 45-55°C, and the time is 3-5h; the mass ratio of the imidazole modified silica gel powder and n-butyl chloride in step T3 is 10:3-4, and the time of the heating reflux reaction is 20-24h; the mass ratio of the substituted imidazole modified silica gel powder and sodium 2-naphthalenesulfonate in step T4 is 12-15:4-7, and the time of stirring at room temperature is 7-9h.

6. The preparation method according to claim 1, characterized in that: The penetration enhancer in step S4 is a mixture of laurocapram and a penetration enhancer compound, with a mass ratio of 10:3-5. The structure of the penetration enhancer compound is shown in Formula I: The preparation method of the penetration-enhancing compound is as follows: U1. Salicylic acid and carveol react under the action of a catalyst to obtain an intermediate with the following structure: U2. The intermediate is reacted with nicotinic acid in the presence of a catalyst to obtain a penetration-enhancing compound.

7. The preparation method according to claim 6, characterized in that: In step U1, the molar ratio of salicylic acid to carveol is 1-1.1:1, the catalyst is concentrated sulfuric acid, the addition amount is 2-3wt% of salicylic acid, the reaction temperature is 100-110°C, and the time is 4-6h; in step U2, the molar ratio of the intermediate to nicotinic acid is 1:1-1.1, the catalyst is concentrated sulfuric acid, the addition amount is 2-3wt% of the intermediate, the reaction temperature is 100-110°C, and the time is 3-5h.

8. A composition for improving sleep quality obtained by the preparation method according to any one of claims 1 to 7.

9. Use of the composition for improving sleep quality as claimed in claim 8 in the preparation of a medicine for promoting sleep, improving sleep quality and prolonging sleep time.

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