Composition for improving sleep and application thereof

Abstract

The invention provides a composition for improving sleep and application thereof, and belongs to the technical field of biological medicine. The composition with the sleep improving effect comprises ginsenoside RK1 and gamma-aminobutyric acid, has a good sleep improving effect, can obviously improve the content of gamma-aminobutyric acid and the content of 5-hydroxytryptamine in brain tissues, achieves better sleep improving, relieves insomnia, anxiety and nervous mood, improves the sleep quality, improves the sleep quality and improves the sleep quality. The sleep quality is improved. Meanwhile, the composition has no side effect on a human body, the product safety is high, the preparation method is simple, the quality is controllable, the operation is convenient, the production cost is low, and industrial continuous production can be realized.

Description

Technical Field

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

[0002] Sleep problems have become a common problem in modern society. Good sleep has an important impact on physical and mental health. According to surveys, about one-third of the world's population does not get enough sleep, and the proportion of insomnia is even higher. The negative effects of insomnia and sleep disorders include daytime fatigue, lack of concentration, mood swings, and a weakened immune system, which seriously affect the quality of life and work efficiency.

[0003] At present, drugs for treating sleep are mainly divided into sleeping pills, antidepressants and sedatives, but long-term use of such drugs will not only cause side effects such as dizziness and nausea, but also lead to drug resistance and addiction, affecting physical health. Therefore, the development of natural source compositions with the effect of improving sleep has attracted more and more attention. Therefore, the development of products with the effect of improving sleep has become a current research hotspot.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] The object of the present invention is to provide a composition for improving sleep and its application. The composition is obtained by combining ginsenoside RK1 and GABA (γ-aminobutyric acid) to obtain a composition that can synergistically improve sleep.

[0006] The present invention is achieved in that:

[0007] In a first aspect, the present invention provides a composition for improving sleep, wherein the composition comprises ginsenoside RK1 and γ-aminobutyric acid.

[0008] In some embodiments, the mass ratio of ginsenoside RK1 to γ-aminobutyric acid in the above composition is: 1:(6-20).

[0009] In some embodiments, the mass ratio of ginsenoside RK1 to γ-aminobutyric acid in the above composition is: 1:(8-15).

[0010] In some embodiments, the mass ratio of ginsenoside RK1 and γ-aminobutyric acid in the above composition is 1:10.

[0011] In some embodiments, ginsenoside RK1 and γ-aminobutyric acid in the above composition are both monomeric components.

[0012] In a second aspect, the present invention provides use of the above composition in preparing a product for improving sleep.

[0013] In a third aspect, the present invention provides the use of the above composition in the preparation of a product for regulating the level of γ-aminobutyric acid in brain tissue.

[0014] In a fourth aspect, the present invention provides use of the above composition in preparing a product for regulating 5-hydroxytryptamine levels in brain tissue.

[0015] In a fifth aspect, the present invention provides a medicine comprising the above composition and pharmaceutically acceptable excipients.

[0016] In a sixth aspect, the present invention provides a food comprising the above composition and a food-acceptable auxiliary material.

[0017] The present invention has the following beneficial effects:

[0018] The composition prepared from raw materials ginsenoside RK1 and gamma-aminobutyric acid has a good effect of improving sleep, can significantly increase the content of gamma-aminobutyric acid and 5-hydroxytryptamine in brain tissue, achieve better sleep improvement, relieve insomnia, anxiety and nervousness, and improve sleep quality. At the same time, the composition of the present invention has no side effects on the human body, the product is highly safe, and the preparation method is simple, the quality is controllable, the operation is convenient, the production cost is low, and industrialized continuous production can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0020] Figure 1 is the structural formula of γ-aminobutyric acid;

[0021] Figure 2 This is the structural formula of ginsenoside RK1. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0023] GABA (γ-aminobutyric acid) is a neurotransmitter with the structural formula Figure 1As shown in Figure 2, it plays a role in inhibiting neuronal activity in the brain. Studies have shown that GABA can help reduce overexcitement in the brain by regulating the nervous system in the brain, thereby reducing insomnia, improving sleep quality and relieving sleep disorders. Ginsenoside RK1 (structural formula: Figure 2 (as shown) is a rare active ingredient from ginseng, which can regulate the human nervous system and endocrine system, thereby promoting relaxation and sleep, improving sleep quality, relieving insomnia, etc. However, ginsenoside RK1 is currently mainly used in anti-inflammatory, anti-cancer and antibacterial aspects, and there are no reports on the use of ginsenoside RK1 or its combination with other ingredients to prepare products for improving sleep.

[0024] Based on this, the present invention proposes to combine ginsenoside RK1 with GABA to prepare a new composition with the effect of improving sleep.

[0025] The experimental results show that the sleep-improving effects of ginsenoside RK1 and GABA at different ratios are significantly different. The preferred ratio screened out by the present invention is: the mass ratio of ginsenoside RK1 to GABA is 1:(6-20).

[0026] In order to obtain better effects, the inventors optimized the above mass ratio and found that when the mass ratio of the two components is 1:(8-15), the combination of ginsenoside RK1 and GABA exhibits a synergistic effect, while beyond this range, the combination of the two exhibits an antagonistic effect. Specifically, the combination index CI of the combination of ginsenoside RK1 and GABA is less than 1.

[0027] Furthermore, when the mass ratio of the two components is 1:10, the synergistic effect of the combination of ginsenoside RK1 and GABA is optimal, which can more effectively improve sleep effects.

[0028] Among them, ginsenoside RK1 and GABA are both known compounds, which can be obtained by conventional preparation methods in the art or purchased. The preparation methods or sources thereof are not limited in the present invention.

[0029] The improvement of sleep in the present invention is manifested in that the composition can regulate the content of γ-aminobutyric acid and 5-hydroxytryptamine in brain tissue. Specifically, the composition can increase the content of γ-aminobutyric acid and 5-hydroxytryptamine in brain tissue.

[0030] The composition of the present invention can be used to prepare related sleep-improving products, including food and medicine.

[0031] In some embodiments, the composition of the present invention can be made into a medicine using techniques known to those skilled in the art. The medicine may or may not contain other raw materials, and the other raw materials may be substances that can improve sleep or pharmaceutically acceptable excipients.

[0032] In some embodiments, the medicine prepared from the composition of the present invention may further include pharmaceutically acceptable excipients, which may be diluents, disintegrants, lubricants, excipients, adhesives, glidants, fillers, surfactants, etc. Other adjuvants, such as flavoring agents and sweeteners, may also be added to the composition.

[0033] Among them, the diluent can be one or more ingredients that increase the weight and volume of the tablet. Commonly used diluents include lactose, starch, pregelatinized starch, microcrystalline cellulose, sorbitol, mannitol, and inorganic calcium salts. Disintegrants can be one or more mixtures of cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, alginic acid, and microcrystalline cellulose. Lubricants include one or more mixtures of stearic acid, sodium stearate, magnesium stearate, calcium stearate, polyethylene glycol, talc, and hydrogenated vegetable oil. Binders can be one or more ingredients that are conducive to granulation, which can be starch slurry, hydroxypropyl methylcellulose, and polyvinyl pyrrolidone. Glidants can be one or more mixtures of micropowdered silica gel, talc, and magnesium trisilicate. Surfactants can be one or more ingredients that can improve wettability and increase drug dissolution, such as sodium lauryl sulfate.

[0034] In some embodiments, the medicine prepared by the composition of the present invention can be a solid dosage form, a liquid dosage form, an oral dosage form or an injection. Oral dosage forms include but are not limited to the following dosage forms: hard capsules, soft capsules, sustained-release capsules, compressed tablets, sugar-coated tablets, powders, granules, dripping pills, honeyed pills, syrups or oral liquids. The injection dosage form can be a solution type, a suspension type, an emulsion type or a lyophilized powder.

[0035] In some embodiments, the composition of the present invention can be made into food using techniques known to those skilled in the art. The food may or may not contain other raw materials, and the other raw materials may be substances that can improve sleep or may be acceptable excipients for food.

[0036] In some embodiments, the food prepared from the composition of the present invention includes food-acceptable excipients, such as solvents, binders, fillers, sugars, sweeteners, and the like.

[0037] In some embodiments, the food prepared from the composition of the present invention can be in the following types: tablets, capsules, pills, granules, decoctions, pastes, lotions, oral solutions, drop pills or syrups.

[0038] By taking, injecting or eating the medicine or food prepared from the composition provided by the present invention, the sleep effect can be effectively improved. The object of taking, injecting or eating can be a mammal, such as a human, rat, rabbit, sheep, pig, cow, cat, dog, monkey, etc., preferably a human.

[0039] When the composition provided by the present invention is prepared as a medicine or food, the dosage or consumption depends on factors such as the specific symptom degree, the age, sex, weight, sensitivity difference of the user, the method of administration, the period of administration, the interval of administration, the nature of the preparation, the type of active ingredient, etc. As a guide, the dosage: the amount of the composition in the food or medicine used by an adult (weight 60 kg) per day is usually 1 μg to 400 mg, preferably 1 mg to 400 mg, more preferably 100 mg to 400 mg, more preferably 200 mg to 400 mg, more preferably 200 mg to 350 mg, more preferably 300 mg to 350 mg (based on the total amount of ginsenoside RK1 and GABA (γ-aminobutyric acid)), and the above dosage can usually be administered 1 to 2 times a day.

[0040] The present invention will be further described below in conjunction with specific embodiments.

[0041] The ginsenoside RK1 used in the embodiments of the present invention was purified in this laboratory. The specific purification method is referenced from "Study on the Inhibitory Effect of Ginsenoside Rk1 on the Growth and Metastasis of Hepatocellular Carcinoma", Lu Haoping, 2022, Northwest University, DOI: 10.27405 / d.cnki.gxbdu.2022.001760.; GABA was purchased from Shanghai Licheng Nutrition Technology Co., Ltd.

[0042] Example 1

[0043] This embodiment is a composition for improving sleep, comprising the following components in parts by weight:

[0044] 1 part of ginsenoside RK1, 4 parts of GABA.

[0045] Ginsenoside RK1 and GABA are mixed according to a certain proportion and mixed evenly to obtain composition 1.

[0046] Example 2

[0047] This embodiment is a composition for improving sleep, comprising the following components in parts by weight:

[0048] 1 part of ginsenoside RK1, 6 parts of GABA.

[0049] Ginsenoside RK1 and GABA acid are mixed according to a certain proportion and mixed evenly to obtain composition 2.

[0050] Example 3

[0051] This embodiment is a composition for improving sleep, comprising the following components in parts by weight:

[0052] 1 part of ginsenoside RK1, 8 parts of GABA.

[0053] Ginsenoside RK1 and GABA are mixed according to a certain proportion and mixed evenly to obtain composition 3.

[0054] Example 4

[0055] This embodiment is a composition for improving sleep, comprising the following components in parts by weight:

[0056] 1 part of ginsenoside RK1, 10 parts of GABA.

[0057] Ginsenoside RK1 and GABA are mixed according to a certain proportion and mixed evenly to obtain composition 4.

[0058] Example 5

[0059] This embodiment is a composition for improving sleep, comprising the following components in parts by weight:

[0060] 1 part of ginsenoside RK1, 12 parts of GABA.

[0061] Ginsenoside RK1 and GABA are mixed according to a certain proportion and mixed evenly to obtain composition 5.

[0062] Experimental Example 1

[0063] This experiment was to verify the effects of the compositions of Examples 1-5 on the GABA levels in the brain tissue of mice, wherein the experimental groups were Composition 1, Composition 2, Composition 3, Composition 4, and Composition 5 of Examples 1-5; and a group to which ginsenoside RK1 and GABA were administered alone was set as a control.

[0064] Animal source: 120 Kunming mice, male, weighing 18-22 g, provided by the Animal Center of Xi'an Jiaotong University, and acclimatized for 3 days before the experiment.

[0065] Animal grouping: There were 10 experimental groups, namely ginsenoside RK1 group, GABA group 1, GABA group 2, GABA group 3, GABA group 4, GABA group 5, combination 15 group and blank control group, with 10 mice in each group. The control group was given an equal volume of blank solution, and the gavage volume for each mouse was 0.2 ml / 10 g, once a day, for 30 consecutive days.

[0066] Instruments and reagents: GABA (γ-aminobutyric acid) kit (Nanjing Jiancheng Biotechnology Co., Ltd.); microplate reader (BioTek Epoch).

[0067] Experimental method: After continuous gavage for 30 days, the animals were fasted but not watered for 1 day. The animals were weighed the next morning and then killed by cervical dislocation. The brain was removed by decapitation on ice, and the hypothalamic tissue was separated. The tissue was rinsed with pre-cooled saline, dried with filter paper, and weighed. According to the ratio of body weight (g): volume (mL) = 1:9, 9 times the volume of saline was added, and the tissue was homogenized with a glass homogenizer under ice water bath. The centrifugal radius was 13.5 cm, 2500r / min, and the supernatant was taken for testing. The detection and analysis were carried out according to the operating procedures of the GABA kit.

[0068] The combination index of the acid ginsenoside RK1 / GABA combination was calculated as CI = (A × B) / AB, where T is the GABA content of the control group, and C is the GABA content of each experimental group. For example, A and B are the C / T values ​​of the ginsenoside RK1 group and the group with different doses of GABA administered alone, and AB is the C / T value of the ginsenoside RK1 group and GABA when used together. When CI < 1, the administration of the two combinations has a synergistic effect.

[0069] The statistical results are shown in Table 1:

[0070] Table 1 Effects of various compositions on GABA content in mouse brain tissue (n=10, x±s)

[0071]

[0072]

[0073] Note: The dosage of Composition 15 is the dosage of Ginsenoside RK1 group combined with GABA group 15.

[0074] As can be seen from Table 1, the drug combination index CI values ​​of compositions 2-5 are all less than 1 when compared with ginsenoside RK1 and the corresponding dose of GABA group acting alone, but the medicinal combination index CI value of composition 1 is greater than 1, indicating that ginsenoside RK1 group and GABA can synergistically increase the GABA level in the brain tissue of mice within a certain ratio range and thus play an effect of improving sleep, but outside the scope of the present invention, there is no synergistic effect. GABA is an inhibitory neurotransmitter, which mainly exerts a sedative and hypnotic effect by specifically binding to the GABA receptor (GABAA).

[0075] Experimental Example 2

[0076] This experiment is to verify the effect of the composition of Examples 1-5 on the 5 HT level in the brain tissue of mice.

[0077] The setting of dosing groups, animal sources and animal grouping refer to Experimental Example 1.

[0078] Instruments and reagents: 5-hydroxytryptamine (5HT) kit (Nanjing Jiancheng Biotechnology Co., Ltd.); microplate reader (BioTek Epoch).

[0079] Methods: After continuous gavage for 30 days, the animals were fasted but not watered for 1 day. The animals were weighed the next morning and then killed by cervical dislocation. The brain was removed by decapitation on ice, and the hypothalamic tissue was separated. The tissue was rinsed with pre-cooled saline, dried with filter paper, and weighed. According to the ratio of body weight (g): volume (mL) = 1:9, 9 times the volume of saline was added, and the tissue was homogenized with a glass homogenizer under ice water bath. The centrifugal radius was 13.5 cm, 2500r / min, and the supernatant was taken for testing. The detection and analysis were carried out according to the operating procedures of the 5HT kit.

[0080] The drug combination index of the ginsenoside RK1 / GABA combination was calculated as CI = (AxB) / AB, where T is the 5HT content of the control group and C is the 5HT content of each experimental group. For example, A and B are the C / T values ​​of the group in which ginsenoside RK1 and different doses of GABA were administered alone, and AB is the C / T value of the group in which ginsenoside RK1 and different doses of GABA were administered together. When CI < 1, the administration of the two saponin combinations has a synergistic effect.

[0081] The statistical results are shown in Table 2:

[0082] Table 2 Effects of various compositions on 5HT content in mouse brain tissue (n=10, x±s)

[0083]

[0084] Note: The dosage of Composition 15 is the dosage of Ginsenoside RK1 group combined with GABA group 15.

[0085] As can be seen from Table 2, the medicinal combination index CI values ​​of compositions 2-5 are all less than 1, while the medicinal combination index CI value of composition 1 is greater than 1 when compared with the single action of ginsenoside RK1 and the corresponding dose of GABA, indicating that ginsenoside RK1 and GABA can synergistically increase the 5HT level in the brain tissue of mice within a certain ratio range, but there is no synergistic effect outside the scope of the present invention. 5HT is an important monoamine neurotransmitter involved in sleep regulation, and a decrease in the 5HT content in the brain can lead to insomnia.

[0086] Experimental Example 3

[0087] This experiment is to verify the effect of the composition of Examples 1-5 on the sleep time and sleep latency of mice with pentobarbital sodium

[0088] The setting of dosing groups, animal sources and animal grouping refer to Experimental Example 1.

[0089] Instruments and reagents: Pentobarbital sodium (Sigma, USA)

[0090] Methods: After continuous gavage for 30 days, 15 minutes after the last administration of the animals, the mice in the control group and other dose groups were intraperitoneally injected with 45 mg / kg·BW of sodium pentobarbital solution at 0.1 mL / 10 g·BW. The sleeping conditions of the mice were observed after administration. The sleeping time and sleep latency of each group of mice after sodium pentobarbital were recorded. The absence of righting reflex in the mice at the last time was an indicator of sleep. When the mice did not respond to touching, pulling, turning, etc. and lasted for more than 60 seconds, it was considered that they had no righting reflex and the mice were considered to have entered a sleeping state. When the righting reflex of the mice was restored, they were considered to be awake, and the time from the disappearance of the righting reflex to the occurrence was recorded, which was the sleeping time; at the same time, the time from the intraperitoneal injection to the mice without response was recorded, which was considered the sleep latency. The sleep extension rate and sleep latency shortening rate of the mice were calculated.

[0091] The statistical results are shown in Table 3:

[0092] Table 3 Effects of various compositions on the sleeping time of mice with sodium pentobarbital (n=10, x±s)

[0093]

[0094] Note: The dosage of Composition 15 is the dosage of Ginsenoside RK1 group combined with GABA group 15.

[0095] As shown in Table 3, after each group of mice was injected with sodium pentobarbital, compared with the blank control group, the sleep time extension rate and sleep latency shortening rate of mice in the composition 1 administration group were lower than those of the ginsenoside RK1 group alone, while the sleep time extension rate and sleep latency shortening rate of mice in the composition 2-4 administration group were higher than those of the single administration group. This indicates that ginsenoside RK1 and GABA can synergistically extend the sleep time of mice and shorten the sleep latency within a certain ratio range, but there is no synergistic effect outside the scope of the present invention.

[0096] In summary, the combination of ginsenoside RK1 and GABA in the present invention can upregulate the levels of GABA and 5-HT in the brain tissue of mice, thereby prolonging sleep time, shortening sleep latency, and achieving the effect of treating insomnia or improving sleep. In all animal experiments involved in the present invention, the animals in each group moved freely, without abnormal body weight, food intake and diet compared with the control group. There was no statistical difference, which shows that the combination of ginsenoside RK1 and GABA is safe for in vivo treatment of mice.

[0097] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A composition for improving sleep, characterized in that: The composition comprises ginsenoside RK1 and gamma-aminobutyric acid.

2. The composition according to claim 1, characterized in that The mass ratio of ginsenoside RK1 to gamma-aminobutyric acid in the composition is 1:(6-20).

3. The composition according to claim 1, characterized in that The mass ratio of ginsenoside RK1 to gamma-aminobutyric acid in the composition is 1:(8-15).

4. The composition according to claim 1, characterized in that The mass ratio of ginsenoside RK1 to γ-aminobutyric acid in the composition is 1:

10.

5. The composition according to any one of claims 1 to 4, characterized in that In the composition, ginsenoside RK1 and γ-aminobutyric acid are both monomer components.

6. Use of the composition as claimed in claim 5 in preparing a product for improving sleep.

7. Use of the composition as claimed in claim 5 in the preparation of a product for regulating the level of γ-aminobutyric acid in brain tissue.

8. Use of the composition as claimed in claim 5 in the preparation of a product for regulating the level of 5-hydroxytryptamine in brain tissue.

9. A drug, characterized in that The composition comprises the composition according to any one of claims 1 to 4 and a pharmaceutically acceptable excipient.

10. A food, characterized in that The invention comprises the composition according to any one of claims 1 to 4 and a food-acceptable auxiliary material.

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