Use of a composition for the preparation of a formulation for improving sleep

Abstract

The application discloses application of a composition in preparation of sleep-improving preparations, and the composition comprises tert-butyl hydroquinone and linoleic acid. It is found by the application that neither the tert-butyl hydroquinone nor the linoleic acid can improve sleep alone, but the combination of the tert-butyl hydroquinone and the linoleic acid can improve sleep, increase total sleep time and single sleep time, and reduce the number of night awakenings and the number of night spontaneous activities. The composition of the application is safe and easy to obtain, has a good sleep-improving effect, and has a wide application prospect.

Description

Technical Field

[0001] This invention relates to the technical field of improving sleep, and more specifically, to the use of a composition in the preparation of a sleep-improving formulation. Background Technology

[0002] Sleep is a crucial physiological process regulated by the central nervous system, essential for the body's rest and physical recovery. Sleep plays a vital role not only in the maturation and development of the brain but also holds an irreplaceable position in maintaining physical and mental health and cognitive function. Insomnia is one of the most common sleep disorders, characterized by recurrent difficulty falling asleep, maintaining sleep, or both, leading to unsatisfactory sleep quality. Chronic insomnia significantly impacts an individual's daily life and work, increasing the risk of various health problems. Severe sleep deprivation can significantly reduce work efficiency and alertness, and may even lead to serious accidents, resulting in substantial social and economic losses. Currently, clinically used medications for insomnia mainly include benzodiazepine receptor agonists, melatonin receptor agonists, orexin receptor antagonists, and some antidepressants with hypnotic effects. While prescription drugs have good effects on improving sleep, their long-term effects are unclear, and they have significant adverse reactions, including dependence, cognitive impairment, drug tolerance, and withdrawal symptoms. Therefore, providing a formulation that helps improve sleep is of great importance.

[0003] Linoleic acid (LAA) is an omega-6 polyunsaturated fatty acid, an essential nutrient that the human body cannot synthesize on its own. LAA plays a variety of biological functions in the body. As an important component of cell membrane phospholipids, it plays a crucial role in maintaining cell structure and function. Furthermore, it participates in various physiological processes, including maintaining skin health, supporting immune function, and regulating blood pressure. However, research has shown that in multivariate adjustment models, for every standard deviation increase in LAA levels, the probability of poor sleep quality, insufficient sleep, excessive sleep, and a high risk of obstructive sleep apnea increases (PMID: 37451068).

[0004] tert-butylhydroquinone (TBHQ), also known as tert-butylhydroquinone, can enhance the stability of oils during their shelf life. TBHQ can be used as a food additive; it does not produce off-flavors when added to any oil or oily food. Its safety is widely recognized, and it is listed as a safe A(1) product and is widely used in the food industry. Summary of the Invention

[0005] To overcome the aforementioned defects and shortcomings in the prior art, the present invention provides an application of the composition in the preparation of a sleep-improving formulation.

[0006] The first object of the present invention is to provide an application of the composition in the preparation of a sleep-improving formulation.

[0007] A second objective of this invention is to provide a formulation for improving sleep.

[0008] Therefore, this invention claims protection for the following:

[0009] The use of a composition in the preparation of a sleep-improving formulation, said composition comprising tert-butylhydroquinone and linoleic acid.

[0010] Preferably, the mass ratio of tert-butylhydroquinone to linoleic acid is 1 g: (5-25) g.

[0011] More preferably, the mass ratio of tert-butylhydroquinone to linoleic acid is 1g:25g.

[0012] Preferably, the improvement in sleep refers to increasing the total sleep duration.

[0013] Preferably, the improvement in sleep refers to increasing the duration of a single sleep session.

[0014] Preferably, the improvement in sleep refers to reducing the number of nighttime awakenings.

[0015] Preferably, the improvement in sleep refers to reducing the number of spontaneous nighttime activities.

[0016] As one possible approach, the formulation is in solid, semi-solid, or liquid form.

[0017] As one possible approach, the dosage form of the formulation includes, but is not limited to, tablets, capsules, granules, powders, and pills.

[0018] As one possible approach, the formulation includes, but is not limited to, pharmaceuticals and health foods, wherein the pharmaceuticals also include pharmaceutically acceptable excipients and the health foods also include food-acceptable additives.

[0019] A formulation for improving sleep, the formulation containing tert-butylhydroquinone and linoleic acid.

[0020] Preferably, the mass ratio of tert-butylhydroquinone to linoleic acid is 1 g: (5-25) g.

[0021] More preferably, the mass ratio of tert-butylhydroquinone to linoleic acid is 1g:25g.

[0022] Preferably, the improvement in sleep refers to increasing the total sleep duration.

[0023] Preferably, the improvement in sleep refers to increasing the duration of a single sleep session.

[0024] Preferably, the improvement in sleep refers to reducing the number of nighttime awakenings.

[0025] Preferably, the improvement in sleep refers to reducing the number of spontaneous nighttime activities.

[0026] As one possible approach, the formulation is in solid, semi-solid, or liquid form.

[0027] As one possible approach, the dosage form of the formulation includes, but is not limited to, tablets, capsules, granules, powders, and pills.

[0028] As one possible approach, the formulation includes, but is not limited to, pharmaceuticals and health foods, wherein the pharmaceuticals also include pharmaceutically acceptable excipients and the health foods also include food-acceptable additives.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] This invention discloses the application of a composition in the preparation of a sleep-improving agent, the composition comprising tert-butylhydroquinone and linoleic acid. This invention reveals that neither tert-butylhydroquinone alone nor linoleic acid alone can improve sleep, while the combination of tert-butylhydroquinone and linoleic acid can improve sleep, increasing total sleep duration and single sleep duration, and reducing the number of nighttime awakenings and spontaneous nighttime activities. The composition of this invention is safe, readily available, and has a good sleep-improving effect, showing broad application prospects. Attached Figure Description

[0031] Figure 1 The effect of linoleic acid on the total sleep duration of fruit flies.

[0032] Figure 2 The effect of linoleic acid on the number of sleep cycles in fruit flies.

[0033] Figure 3 The effect of linoleic acid on the duration of a single sleep episode in fruit flies.

[0034] Figure 4 The effect of linoleic acid on the number of nocturnal activities in fruit flies.

[0035] Figure 5 The effect of a combination of TBHQ and linoleic acid on the total sleep duration of fruit flies.

[0036] Figure 6 The effect of a combination of TBHQ and linoleic acid on the number of sleep cycles in fruit flies.

[0037] Figure 7 The effect of a combination of TBHQ and linoleic acid on the duration of a single sleep episode in fruit flies.

[0038] Figure 8The effect of a combination of TBHQ and linoleic acid on the number of nocturnal activities in fruit flies.

[0039] Figure 9 A comparison of the effects of using linoleic acid alone, using TBHQ alone, and using a combination of linoleic acid and TBHQ to improve sleep in fruit flies. Detailed Implementation

[0040] The present invention will be further illustrated below with reference to specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field.

[0041] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0042] Example 1: Effect of linoleic acid on sleep in fruit flies

[0043] I. Experimental Methods

[0044] 1. Laboratory animals and their rearing

[0045] Wild-type Drosophila melanogaster (Canton S) was obtained from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. The flies were reared in an artificial climate chamber (temperature set at 25℃, relative humidity set at 60%), with a 12-hour daytime and 12-hour nighttime cycle.

[0046] 2. Preparation of Drosophila test culture medium

[0047] Basic culture medium: 2.5 mL propionic acid, 5 g agar, 25 g sucrose, 500 mL water. Accurately weigh the sucrose and agar into a beaker, transfer them to an iron pot, add water, heat to boiling, cool after boiling, then add propionic acid and stir well.

[0048] Caffeine medium: Based on the basal medium, caffeine is added according to the mass ratio to prepare a medium containing 0.05% caffeine (w / w).

[0049] Caffeine medium containing 0.05% linoleic acid (w / w): Based on the caffeine medium, add linoleic acid (brand: Maclean, catalog number: L812256) according to the mass ratio to prepare a caffeine medium containing 0.05% linoleic acid (w / w).

[0050] Caffeine medium containing 0.25% linoleic acid (w / w): Based on the caffeine medium, linoleic acid is added according to the mass ratio to prepare a caffeine medium containing 0.25% linoleic acid (w / w).

[0051] 3. Fruit fly sleep monitoring

[0052] Newborn male fruit flies within 8 hours were selected and placed in basal culture medium for rearing. After 3 days of normal culture, the flies were placed into fruit fly activity monitoring tubes containing different intervention media, and then placed in a fruit fly activity monitor (Trikinetics, model DAM5, USA). The specific experimental groups are shown in Table 1.

[0053] Table 1 Experimental Groups

[0054] Group Number of fruit flies (individuals) culture medium normal group ≥16 basal culture medium Caffeine group ≥16 Caffeine culture medium low-dose linoleic acid group ≥16 Caffeine culture medium containing 0.05% linoleic acid (w / w) High-dose linoleic acid group ≥16 Caffeine culture medium containing 0.25% linoleic acid (w / w)

[0055] Each group was equipped with one fruit fly activity monitor, with each monitor corresponding to 32 individual fruit fly activity monitoring tubes. One fruit fly was placed in each tube, with culture medium at one end and a vent plug at the other. The tubes were placed in a temperature- and humidity-controlled incubator and connected to the fruit fly activity monitor. The activity and sleep status of the fruit flies were continuously monitored for 3 days. The fruit fly's sleep status was defined by its activity behavior; any period of stillness lasting 5 minutes or more was considered a sleep state.

[0056] Each fruit fly activity monitor can simultaneously monitor the activity of 32 fruit flies. The monitor uses four infrared beams to monitor fly activity, emitting and receiving the beams from one side. When a fruit fly moves within the monitoring tube, it blocks the reception of the infrared beams. The status of beam blocking is transmitted back to the computer at a frequency of once per minute to monitor the fly's activity. Monitoring data is transmitted to the corresponding computer in real time. The fruit fly's sleep state is determined by its behavior, specifically any period of stillness lasting 5 minutes or more. Monitoring was conducted for three consecutive days using the number of nocturnal activities, total sleep duration, number of sleep episodes, and duration of each sleep episode as evaluation indicators. All monitoring was carried out in a dark environment.

[0057] 4. Data Processing and Analysis

[0058] For the Drosophila sleep study, GraphPad Prism 9.0 software was used to create images, and SPSS 20.0 software was used for statistical analysis of the data. Depending on whether the variances were homogeneous, the Least Significant Difference test or Tamhane's T²(M) and the nonparametric Kruskal-Wallis test were selected from one-way ANOVA. Data are expressed as Mean ± SEM. * indicates p < 0.05 compared to the normal group, ** indicates p < 0.01 compared to the normal group; # indicates p < 0.05 compared to the caffeine group, and ## indicates p < 0.01 compared to the caffeine group.

[0059] II. Experimental Results

[0060] 1. Effect of linoleic acid on total sleep duration in fruit flies

[0061] The results are as follows Figure 1 As shown in the figure. On day 1, there was no significant change in the caffeine group compared with the normal group; compared with the caffeine group, there was no significant trend in the total sleep duration of the fruit flies in the low-dose linoleic acid group and the high-dose linoleic acid group.

[0062] On day 2, compared with the normal group, the total sleep duration of fruit flies in the caffeine group was significantly reduced (p < 0.05). Compared with the caffeine group, there was no significant trend in the total sleep duration of fruit flies in the low-dose linoleic acid group and the high-dose linoleic acid group.

[0063] On day 3, compared with the normal group, the total sleep duration of fruit flies in the caffeine group was significantly reduced (p < 0.01). Compared with the caffeine group, there was no significant trend in the total sleep duration of fruit flies in the low-dose linoleic acid group and the high-dose linoleic acid group.

[0064] The above results indicate that linoleic acid, at a specific dose, cannot reverse the shortening of total sleep time induced by caffeine in fruit flies, and failed to prolong the total sleep time of insomnia-prone fruit flies.

[0065] 2. Effect of linoleic acid on the number of sleep cycles in fruit flies

[0066] The results are as follows Figure 2 As shown in the figure, on day 1, compared with the normal group of fruit flies, the number of sleep episodes in the caffeine group was significantly increased (p < 0.01), indicating that caffeine intervention began to induce fragmented sleep in fruit flies, leading to a decline in sleep quality; compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group and the high-dose linoleic acid group did not change significantly.

[0067] On day 2, compared with the normal group, the number of sleep episodes in the caffeine group was significantly increased (p < 0.01). Compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group and the high-dose linoleic acid group did not change significantly.

[0068] On day 3, compared with the normal group, the number of sleep episodes in the caffeine group was significantly increased (p < 0.01). Compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group and the high-dose linoleic acid group did not change significantly.

[0069] The above results indicate that linoleic acid, at a specific dose, failed to reverse caffeine-induced sleep fragmentation in fruit flies and failed to reduce the number of nighttime sleep episodes in insomnia-prone fruit flies.

[0070] 3. Effects of linoleic acid on the duration of a single sleep episode in fruit flies.

[0071] The results are as follows Figure 3As shown in the figure. On day 1, compared with the normal group, the duration of a single sleep episode was significantly reduced in the caffeine group (p < 0.01). Compared with the caffeine group, the duration of a single sleep episode did not change significantly in the low-dose linoleic acid group and the high-dose linoleic acid group.

[0072] On day 2, compared with the normal group, the duration of a single sleep episode was significantly reduced in the caffeine group (p < 0.01). Compared with the caffeine group, the duration of a single sleep episode did not change significantly in the low-dose linoleic acid group and the high-dose linoleic acid group.

[0073] On day 3, compared with the normal group, the duration of a single sleep episode was significantly reduced in the caffeine group (p < 0.01). Compared with the caffeine group, the duration of a single sleep episode did not change significantly in the low-dose linoleic acid group and the high-dose linoleic acid group.

[0074] The results above indicate that linoleic acid, at a specific dose, failed to increase the duration of a single sleep episode in insomnia-prone fruit flies, thereby failing to improve sleep quality.

[0075] 4. Effect of linoleic acid on the number of nocturnal activities in fruit flies

[0076] The results are as follows Figure 4 As shown in the figure, on day 1, compared with the normal group, the number of nocturnal activities of fruit flies in the caffeine group showed an increasing trend. Compared with the caffeine group, the number of nocturnal activities of fruit flies in the low-linoleic acid group and the high-linoleic acid group showed a decreasing trend.

[0077] On day 2, compared with the normal group, the number of nocturnal activities of fruit flies in the caffeine group was significantly increased (p < 0.05). Compared with the caffeine group, the number of nocturnal activities of fruit flies in the low-dose linoleic acid group and the high-dose linoleic acid group showed a decreasing trend, but the changes were not significant.

[0078] On day 3, compared with the normal group, the number of nocturnal activities of fruit flies in the caffeine group was significantly increased (p < 0.05). Compared with the caffeine group, the number of nocturnal activities of fruit flies in the low-dose linoleic acid group and the high-dose linoleic acid group did not change significantly.

[0079] The above results indicate that linoleic acid, at a specific dose, failed to reduce the number of nocturnal activities in insomnia-prone fruit flies.

[0080] Example 2: Effect of the combination of TBHQ and linoleic acid on sleep in fruit flies

[0081] I. Experimental Methods

[0082] 1. Laboratory animals and their rearing

[0083] Performed according to Example 1.

[0084] 2. Preparation of Drosophila test culture medium

[0085] The preparation methods for the basal culture medium and caffeine culture medium are the same as in Example 1.

[0086] Caffeine medium containing 0.01% TBHQ (w / w) and 0.05% linoleic acid (w / w): Based on the caffeine medium, linoleic acid (brand: Maclean, catalog number: L812256) and TBHQ were added in the mass ratio to prepare a caffeine medium containing 0.01% TBHQ (w / w) and 0.05% linoleic acid (w / w).

[0087] Caffeine medium containing 0.01% TBHQ (w / w) and 0.25% linoleic acid (w / w): Based on the caffeine medium, linoleic acid (brand: Maclean, catalog number: L812256) and TBHQ were added in the mass ratio to prepare a caffeine medium containing 0.01% TBHQ (w / w) and 0.25% linoleic acid (w / w).

[0088] 3. Fruit fly sleep monitoring

[0089] The experiment was conducted according to Example 1, and the specific test groups are shown in Table 2.

[0090] Table 2 Experimental Groups

[0091]

[0092] 4. Data Processing and Analysis

[0093] Performed according to Example 1.

[0094] II. Experimental Results

[0095] 1. Effect of the combination of TBHQ and linoleic acid on the total sleep duration of fruit flies.

[0096] The results are as follows Figure 5 As shown. On day 1, compared with the normal group, the total sleep time of fruit flies in the caffeine group was significantly reduced (p < 0.01); compared with the caffeine group, the total sleep time of fruit flies in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed an increasing trend, among which the high-dose linoleic acid group with TBHQ significantly increased the total sleep time of fruit flies (p < 0.01).

[0097] On day 2, compared with the normal group, the total sleep duration of fruit flies in the caffeine group was significantly reduced (p < 0.01). Compared with the caffeine group, the total sleep duration of fruit flies in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ was significantly increased (p < 0.05).

[0098] On day 3, compared with the normal group, the total sleep duration of fruit flies in the caffeine group was significantly reduced (p < 0.01). Compared with the caffeine group, the total sleep duration of fruit flies in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed an increasing trend, with the high-dose linoleic acid group with TBHQ showing a significant increase in total sleep time (p < 0.01).

[0099] The above results indicate that the combination of TBHQ and linoleic acid can reverse the shortening of total sleep time induced by caffeine at specific doses in fruit flies, and can significantly prolong the total sleep time of insomnia-prone fruit flies, thereby improving sleep.

[0100] 2. Effect of the combination of TBHQ and linoleic acid on the number of sleep cycles in fruit flies.

[0101] The results are as follows Figure 6 As shown in the figure, on day 1, compared with the normal group of fruit flies, the number of sleep episodes in the caffeine group showed an increasing trend, indicating that caffeine intervention began to induce fragmented sleep in fruit flies, leading to a decline in their sleep quality. Compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed a decreasing trend, with the high-dose linoleic acid group with TBHQ showing a significant decrease in the number of sleep episodes.

[0102] On day 2, compared with the normal group of fruit flies, the number of sleeps in the caffeine group was significantly increased (p < 0.01). Compared with the caffeine group, the number of sleeps in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed a decreasing trend. Among them, the high-dose linoleic acid group with TBHQ significantly reduced the number of sleeps in the fruit flies (p < 0.05).

[0103] On day 3, compared with the normal group of fruit flies, the number of sleeps in the caffeine group was significantly increased (p < 0.01). Compared with the caffeine group, the number of sleeps in the low-dose group of linoleic acid with added TBHQ and the high-dose group of linoleic acid with added TBHQ showed a decreasing trend. Among them, the high-dose group of linoleic acid with added TBHQ significantly reduced the number of sleeps in the fruit flies (p < 0.05).

[0104] The above results indicate that the combination of TBHQ and linoleic acid can reverse caffeine-induced sleep fragmentation in fruit flies at specific doses, significantly reducing the number of sleep episodes in insomnia-prone fruit flies, thereby improving sleep quality.

[0105] 3. Effect of the combination of TBHQ and linoleic acid on the duration of a single sleep episode in fruit flies.

[0106] The results are as follows Figure 7As shown in the figure. On day 1, compared with the normal group, the duration of a single sleep episode in the caffeine group showed a decreasing trend. Compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed an increasing trend, with the high-dose linoleic acid group with TBHQ significantly increasing the duration of a single sleep episode (p < 0.05).

[0107] On day 2, compared with the normal group, the duration of a single sleep episode was significantly reduced in the caffeine group (p < 0.01). Compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed an increasing trend, with the duration of a single sleep episode being significantly increased in the high-dose linoleic acid group with TBHQ (p < 0.05).

[0108] On day 3, compared with the normal group, the duration of a single sleep episode was significantly reduced in the caffeine group (p < 0.01). Compared with the caffeine group, the number of sleep episodes in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed an increasing trend, with the duration of a single sleep episode being significantly increased in the high-dose linoleic acid group with TBHQ (p < 0.01).

[0109] The above results indicate that the combination of TBHQ and linoleic acid, at a specific dosage, can increase the duration of a single sleep episode in insomnia-prone fruit flies, thereby improving sleep quality.

[0110] 4. Effect of the combination of TBHQ and linoleic acid on the number of nocturnal activities in fruit flies.

[0111] The results are as follows Figure 8 As shown in the figure. On day 1, compared with the normal group, the number of nocturnal activities of fruit flies in the caffeine group was significantly increased (p < 0.01). Compared with the caffeine group, the number of nocturnal activities of fruit flies in the low-dose group with TBHQ-added linoleic acid and the high-dose group with TBHQ-added linoleic acid showed a decreasing trend, with the number of nocturnal activities of fruit flies in the high-dose group with TBHQ-added linoleic acid being significantly reduced (p < 0.01).

[0112] On day 2, compared with the normal group, the number of nocturnal activities of fruit flies in the caffeine group showed an increasing trend. Compared with the caffeine group, the number of nocturnal activities of fruit flies in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed a decreasing trend, with the high-dose linoleic acid group with TBHQ showing a significant decrease in nocturnal activities (p < 0.01).

[0113] On day 3, compared with the normal group, the number of nocturnal activities of fruit flies in the caffeine group was significantly increased (p < 0.05). Compared with the caffeine group, the number of nocturnal activities of fruit flies in the low-dose linoleic acid group with TBHQ and the high-dose linoleic acid group with TBHQ showed a decreasing trend, with the number of nocturnal activities of fruit flies in the high-dose linoleic acid group with TBHQ being significantly reduced (p < 0.01).

[0114] The above results indicate that the combination of TBHQ and linoleic acid can reduce the number of nocturnal activities in insomnia-prone fruit flies to a certain extent at a specific dosage, thereby inducing sleep.

[0115] Example 3: Comparison of the effects of linoleic acid alone, TBHQ alone, and a combination of linoleic acid and TBHQ on improving sleep in fruit flies.

[0116] I. Experimental Methods

[0117] 1. Laboratory animals and their rearing

[0118] Performed according to Example 1.

[0119] 2. Preparation of Drosophila test culture medium

[0120] The preparation methods for the basal culture medium, caffeine culture medium, caffeine culture medium containing 0.05% linoleic acid (w / w), and caffeine culture medium containing 0.25% linoleic acid (w / w) are the same as in Example 1. The preparation methods for the caffeine culture medium containing 0.01% TBHQ (w / w) and 0.05% linoleic acid (w / w) and the caffeine culture medium containing 0.01% TBHQ (w / w) and 0.25% linoleic acid (w / w) are the same as in Example 2.

[0121] Basic medium containing 0.01% TBHQ (w / w): Based on the basic medium, add TBHQ according to the mass ratio to prepare a basic medium containing 0.01% TBHQ (w / w).

[0122] Caffeine medium containing 0.01% TBHQ (w / w): Based on the caffeine medium, TBHQ is added at a certain mass ratio to prepare a caffeine medium containing 0.01% TBHQ (w / w).

[0123] 3. Fruit fly sleep monitoring

[0124] The experiment was conducted according to Example 1, and the specific test groups are shown in Table 3.

[0125] Table 3 Experimental Groups

[0126]

[0127] 4. Data Processing and Analysis

[0128] For the Drosophila sleep study, GraphPad Prism 9.0 software was used to create images, and SPSS 20.0 software was used for statistical analysis of the data. Depending on whether the variances were homogeneous, the Least Significant Difference test or Tamhane's T²(M) and the nonparametric Kruskal-Wallis test were selected from one-way ANOVA. Data are expressed as Mean ± SEM, * indicates p < 0.05 between groups, and ** indicates p < 0.01 between groups.

[0129] II. Experimental Results

[0130] The results are as follows Figure 9 As shown, for the normal group, the addition of TBHQ did not significantly affect the average total sleep time of the fruit flies.

[0131] For the caffeine group, the addition of TBHQ did not significantly affect the average total sleep time of the fruit flies.

[0132] For the low-dose linoleic acid group, the average total sleep time of fruit flies in the low-dose linoleic acid group with TBHQ was significantly higher than that of fruit flies in the low-dose linoleic acid group without TBHQ (p < 0.05).

[0133] For the high-dose linoleic acid group, the average total sleep time of fruit flies in the high-dose linoleic acid group with TBHQ was significantly higher than that of fruit flies in the high-dose linoleic acid group without TBHQ (p < 0.01).

[0134] In summary, in both the caffeine and normal groups, the addition of TBHQ did not significantly affect the average total sleep duration of fruit flies. However, in both the low- and high-dose linoleic acid groups, the addition of TBHQ significantly affected the average total sleep duration of fruit flies (p < 0.05). These results suggest that the combination of TBHQ and linoleic acid can improve sleep.

[0135] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. The use of a composition in the preparation of a medicament for improving sleep, characterized in that, The composition is tert-butylhydroquinone and linoleic acid; The mass ratio of tert-butylhydroquinone to linoleic acid is 1g:5-25g; The improvement in sleep refers to improving insomnia caused by caffeine.

2. The application according to claim 1, characterized in that, The drug is in solid, semi-solid, or liquid form.

3. The application according to claim 1, characterized in that, The dosage forms of the drug include tablets, capsules, granules, powders, and pills.

4. The application according to claim 1, characterized in that, The drug also includes pharmaceutically acceptable excipients.

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