A composition capable of improving fatigue-related sleep disorders and uses thereof

Abstract

The present application relates to a kind of composition capable of improving fatigue-related sleep disorders and its application.The composition includes: and magnolol, schisandra extract, eucommia leaf extract, ginsenoside and pyrroloquinoline quinone.The present application creatively finds that and magnolol, schisandra extract, eucommia leaf extract have significant synergies in stabilizing circadian rhythm, promoting sleep, etc.;Ginsenoside and pyrroloquinoline quinone cooperate with each other, and can improve sleep disorders synergistically.The present application compounding the above two groups of compositions can significantly promote sleep, deepen sleep, restore rhythm control ability, remove metabolic waste interference, and improve sleep quality from multiple dimensions.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical or food technology, and specifically relates to a composition that can improve fatigue-related sleep disorders and its application. Background Technology

[0002] There is a close pathophysiological link between fatigue and sleep disorders. Long-term or excessive physical and mental fatigue can lead to dysfunction of the hypothalamus-pituitary-adrenal axis, imbalance of autonomic nervous system regulation, and elevated levels of inflammatory factors. These changes can prolong sleep latency, reduce sleep efficiency, and weaken the restorative function of sleep.

[0003] Fatigue-related sleep disorders manifest as difficulty falling asleep, shallow sleep, frequent awakenings, early awakenings, and non-restorative sleep (still feeling tired after waking up), forming a vicious cycle of "fatigue → poor sleep → more fatigue". Its core pathology includes: (1) excessive fatigue leads to hyperactivity of the HPA axis, abnormally high cortisol levels at night inhibit melatonin secretion, and interfere with falling asleep and deep sleep; (2) insufficient GABAergic system function leads to an imbalance of nerve excitation / inhibition, resulting in difficulty falling asleep; (3) decline in neuronal mitochondrial function leads to insufficient energy supply to the sleep-wake center and disordered sleep structure; (4) insufficient liver detoxification capacity leads to the accumulation of metabolic waste that interferes with the central nervous system; (5) decreased activity of energy sensing and circadian rhythm regulation pathways such as AMPK / SIRT1 leads to biological clock disorder.

[0004] CN108697645A discloses a pharmaceutical composition for initiating and maintaining the sleep process and for preventing conditions associated with various types of sleep disorders in animals and humans. The composition is characterized by comprising an effective amount of doxylamine succinate and sustained-release melatonin. The technical advantages lie in synergistic therapeutic effects, improved biological processes, and reduced side effects.

[0005] CN116983324A discloses a polysaccharide composition for improving sleep disorders and its application. The polysaccharide composition includes 0.1-1 parts melatonin and 1-200 parts Ganoderma lucidum polysaccharide. The melatonin has a purity of ≥99%. Animal experiments have confirmed that melatonin or Ganoderma lucidum polysaccharide alone can promote sleep or improve sleep disorders. The synergistic effect of melatonin and Ganoderma lucidum polysaccharide in promoting sleep or improving sleep disorders is even better. In particular, the sleep-promoting effect of low-dose Ganoderma lucidum polysaccharide combined with melatonin is better than that of high-dose Ganoderma lucidum polysaccharide combined with melatonin. Moreover, the amount of melatonin used in this polysaccharide composition is low and there are no adverse reactions. The combination of high-dose Ganoderma lucidum polysaccharide and high-dose melatonin has no significant effect on the body weight and organs of mice, and has high safety. Furthermore, its therapeutic effect on mice with sleep disorders is comparable to or even better than the commercially available drug Diazepam, showing great potential for drug development and broad market application prospects.

[0006] CN113491680A discloses the use of catechol and its derivatives in the preparation of medicaments for treating sleep disorders, wherein the use is primarily achieved through the orexin receptor of the medicament.

[0007] Existing sleep aids mainly consist of melatonin and benzodiazepines. Melatonin only addresses the "clock signal" problem but not the "ability to fall asleep," while benzodiazepines are addictive and cause drowsiness the following day. There is a lack of safe solutions for improving sleep in multiple dimensions.

[0008] Therefore, developing a composition that can promote sleep onset, deepen sleep, restore circadian rhythm, and eliminate metabolic waste that interferes with sleep has become one of the urgent technical problems to be solved. Summary of the Invention

[0009] In view of the shortcomings of the prior art, the purpose of this invention is to provide a composition that can improve fatigue-related sleep disorders and its application.

[0010] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides a composition capable of improving fatigue-related sleep disorders, the composition comprising: magnolol, schisandra extract, eucommia leaf extract, ginsenosides and pyrrolidone (PQQ).

[0011] In this invention, magnolol promotes sleep onset and prolongs deep sleep through positive allosteric regulation of GABAa receptors (non-benzodiazepine mechanism, non-addictive); Schisandra chinensis extract synergistically enhances GABA transmission with its sedative and calming effects and can clear metabolic waste products that interfere with sleep; Eucommia ulmoides leaf extract regulates the HPA axis and restores the cortisol circadian rhythm. This invention creatively discovers that magnolol, Schisandra chinensis extract, and Eucommia ulmoides leaf extract have significant synergistic effects in stabilizing circadian rhythms and promoting sleep onset.

[0012] In this invention, ginsenosides can inhibit NF-κB / NLRP3, reducing the interference of "inflammatory fatigue" on the sleep center; PQQ maintains mitochondrial energy in sleep center neurons. This invention creatively discovers that ginsenosides and pyrroloquinoline quinone work synergistically to improve sleep disorders.

[0013] The present invention combines the above two compositions, which can significantly promote falling asleep, deepen sleep, restore the ability to regulate rhythm, and eliminate metabolic waste interference, thereby improving sleep quality from multiple dimensions.

[0014] Preferably, the composition comprises, by weight parts: 10-300 parts of magnolol, 10-100 parts of Schisandra chinensis extract, 10-300 parts of Eucommia ulmoides leaf extract, 1-30 parts of ginsenosides and 1-50 parts of pyrroloquinoline quinone.

[0015] Among them, the specific point values ​​for 10-300 portions can be 10 portions, 50 portions, 100 portions, 150 portions, 200 portions, 250 portions, 300 portions, etc.; the specific point values ​​for 10-100 portions can be 10 portions, 30 portions, 50 portions, 70 portions, 90 portions, 100 portions, etc.; the specific point values ​​for 1-30 portions can be 1 portion, 5 portions, 10 portions, 15 portions, 20 portions, 25 portions, 30 portions, etc.; and the specific point values ​​for 1-50 portions can be 1 portion, 5 portions, 10 portions, 15 portions, 20 portions, 25 portions, 30 portions, 35 portions, 40 portions, 45 portions, 50 portions, etc.

[0016] Based on the synergistic effect of the components in the composition in improving sleep disorders, when the components in the composition are compounded in the above-mentioned mass proportions, the efficacy of the composition in improving sleep quality can be further enhanced.

[0017] Preferably, the ginsenosides include ginsenoside CK.

[0018] Ginsenoside CK stabilizes the expression and oscillation of core proteins of the circadian rhythm through the SIRT1 / CLOCK-BMAL1 pathway, restoring the disordered biological clock rhythm under fatigue. Its effect on improving sleep quality is better than that of traditional saponins such as Rb1.

[0019] Preferably, the Schisandra chinensis extract is prepared by a method comprising the following steps: (1) The Schisandra chinensis raw material was mixed with an aqueous solution of ethanol and then subjected to ultrasonic treatment; (2) The treated solution is refluxed to extract the extract, and the extract is concentrated under reduced pressure to obtain the concentrate; (3) The concentrate was purified using macroporous resin and eluted sequentially with aqueous solutions of water and ethanol. The aqueous fraction of ethanol was collected to obtain the eluent. (4) The eluent was subjected to flocculation treatment and dried to obtain Schisandra chinensis extract.

[0020] This invention involves ultrasonic treatment of Schisandra chinensis followed by hot reflux extraction and purification using a specific method. The resulting Schisandra chinensis extract can better exert the synergistic effect with components such as magnolol and Eucommia ulmoides leaf extract.

[0021] Preferably, the volume fraction of ethanol in the aqueous solution of ethanol in step (1) is 20%-60%, for example, it can be 20%, 30%, 40%, 50%, 60%, etc.

[0022] The ratio of Schisandra chinensis raw material to aqueous ethanol solution is 1:5-1:15 g / mL, for example, it can be 1:5 g / mL, 1:7 g / mL, 1:9 g / mL, 1:11 g / mL, 1:13 g / mL, 1:15 g / mL, etc.

[0023] Preferably, the temperature of the ultrasonic treatment in step (1) is 30-70℃, the time is 10-40 min, and the power is 100-600 W.

[0024] Among them, the specific point values ​​in the 30-70℃ range can be 30℃, 40℃, 50℃, 60℃, 70℃, etc.; the specific point values ​​in the 10-40 min range can be 10 min, 20 min, 30 min, 40 min, etc.; and the specific point values ​​in the 100-600 W range can be 100 W, 200 W, 300 W, 400 W, 500 W, 600 W, etc.

[0025] Preferably, the reflux extraction in step (2) is performed 1-3 times, and the extraction time for each extraction is 1-3 hours independently.

[0026] Among them, 1-3 times can be 1 time, 2 times or 3 times, and the specific point values ​​in 1-3 h can be 1 h, 1.5 h, 2 h, 2.5 h, 3 h, etc.

[0027] Preferably, the macroporous resin in step (3) includes D101 type macroporous resin.

[0028] Preferably, the mass ratio of the macroporous resin to the Schisandra chinensis raw material is 3:1-10:1, for example, it can be 3:1, 5:1, 7:1, 9:1, 10:1, etc.

[0029] Preferably, the volume percentage of ethanol in the aqueous solution of ethanol in step (3) is 80%-98%, for example, it can be 80%, 85%, 90%, 95%, 98%, etc.

[0030] Preferably, the flow rate of the aqueous solution of water and ethanol used for elution is independently 0.5-2 BV / h, and the amount used is independently 1-5 BV.

[0031] Among them, the specific point values ​​in 0.5-2 BV / h can be 0.5 BV / h, 4 BV / h, 1.5 BV / h, 2 BV / h, etc., and the specific point values ​​in 1-5 BV can be 1 BV, 2 BV, 3 BV, 4 BV, 5 BV, etc.

[0032] Preferably, the flocculation treatment in step (4) uses a flocculant, the mass of which is 0.1-1.5% of the mass of the eluent, for example, 0.1%, 0.4%, 0.7%, 1%, 1.3%, 1.5%, etc.

[0033] This invention purifies the concentrated Schisandra chinensis extract with macroporous resin and then performs flocculation treatment, which can further enrich the sleep quality-enhancing components in Schisandra chinensis and further exert the synergistic effect of components such as magnolol and Eucommia ulmoides leaf extract in relieving sleep disorders.

[0034] Preferably, the flocculant comprises any one or a combination of at least two of citric acid, guar gum, or bone glue, and more preferably a combination of citric acid, guar gum, and bone glue.

[0035] Citric acid is a weak organic acid that is often used as a flocculant for flocculation treatment; guar gum is a natural high-molecular-weight polysaccharide that mainly causes suspended particles to flocculate and settle rapidly through an adsorption bridging mechanism; bone glue is a protein colloid extracted from animal bones that uses the adsorption bridging effect of its long molecular chains to flocculate suspended matter.

[0036] This invention creatively discovers that citric acid, guar gum, and collagen have a significant synergistic effect in flocculation and sedimentation, increasing the content of sleep-enhancing active ingredients in the eluent.

[0037] Preferably, the mass ratio of citric acid, guar gum, and bone glue is (1-5):(0.1-0.5):(5-10).

[0038] Among them, the specific point values ​​in 1-5 can be 1, 2, 3, 4, 5, etc.; the specific point values ​​in 0.1-0.5 can be 0.1, 0.2, 0.3, 0.4, 0.5, etc.; and the specific point values ​​in 5-10 can be 5, 2, 7, 8, 9, 10, etc.

[0039] Preferably, the flocculation treatment is performed at a temperature of 50-60℃ for 10-30 minutes.

[0040] Among them, the specific point values ​​in the 50-60℃ range can be 50℃, 52℃, 54℃, 56℃, 58℃, 60℃, etc., and the specific point values ​​in the 10-30min range can be 10 min, 15 min, 20 min, 25 min, 30 min, etc.

[0041] Preferably, the Eucommia ulmoides leaf extract is prepared by a method comprising the following steps: Eucommia ulmoides leaf raw material was mixed with water and subjected to hot extraction to obtain Eucommia ulmoides leaf extract.

[0042] Preferably, the ratio of Eucommia ulmoides leaf raw material to water is 1:5-1:10 g / mL, for example, it can be 1:5 g / mL, 1:6 g / mL, 1:7 g / mL, 1:8 g / mL, 1:9 g / mL, 1:10 g / mL, etc.

[0043] Preferably, the hot extraction temperature is 50-65℃ and the hot extraction time is 0.5-2 h.

[0044] Among them, the specific point values ​​in 50-65℃ can be 50℃, 55℃, 60℃, 65℃, etc., and the specific point values ​​in 0.5-2 h can be 0.5 h, 1 h, 1.5 h, 2 h, etc.

[0045] In a second aspect, the present invention provides the use of the composition described in the first aspect in the preparation of a pharmaceutical or food product capable of improving fatigue-related sleep disorders.

[0046] Compared with the prior art, the present invention has the following beneficial effects: The composition involved in this invention includes magnolol, schisandra chinensis extract, eucommia ulmoides leaf extract, ginsenosides, and pyrrolquinone. This invention creatively discovers that magnolol, schisandra chinensis extract, and eucommia ulmoides leaf extract have significant synergistic effects in stabilizing circadian rhythms and promoting sleep onset; ginsenosides and pyrrolquinone work synergistically to improve sleep disorders. This invention, by combining the above two compositions, can significantly promote sleep onset, deepen sleep, restore circadian rhythm regulation, and eliminate metabolic waste interference, thus improving sleep quality from multiple dimensions.

[0047] Furthermore, by subjecting Schisandra chinensis to ultrasonic treatment followed by hot reflux extraction and purification using a specific method, the obtained Schisandra chinensis extract can better exert the synergistic effect with components such as magnolol and Eucommia ulmoides leaf extract.

[0048] Furthermore, in the preparation of Schisandra chinensis extract, a combination of citric acid, guar gum, and bone glue is used to flocculate the concentrated Schisandra chinensis solution purified by macroporous resin. This can further enrich the sleep-enhancing components in Schisandra chinensis and further enhance the synergistic effect of components such as magnolol and Eucommia ulmoides leaf extract in relieving sleep disorders. Attached Figure Description

[0049] Figure 1 This is a comparison chart of the movement distances of zebrafish in each experimental group in Test Example 1.

[0050] Figure 2 This is a comparison chart of the sleep improvement rates of zebrafish in each experimental group in Test Example 1. Detailed Implementation

[0051] To further illustrate the technical means and effects of the present invention, the following describes the technical solution of the present invention in conjunction with preferred embodiments of the present invention. However, the present invention is not limited to the scope of the embodiments.

[0052] The guar gum used in the following specific embodiments was purchased from Merck, product number G4129; the bone glue was purchased from Henan Guanqi Biotechnology Co., Ltd.

[0053] Preparation Example 1-1 This preparation example provides a Schisandra chinensis extract, prepared by the following method: (1) Take Schisandra chinensis and grind it into 80-mesh fine powder. Mix it with 40% ethanol aqueous solution at a material-to-liquid ratio of 1:10 g / mL and then perform ultrasonic treatment (50℃, 300 W, 20 min). (2) The mixture of Schisandra chinensis powder after ultrasonic treatment was refluxed and extracted twice, each time for 2 hours. After filtration, the extract was obtained. The extract was concentrated under reduced pressure at 60°C to 50% of the mass of Schisandra chinensis powder to obtain the concentrate. (3) Take 5 times the mass of Schisandra chinensis powder and pack it into a column of D-101 macroporous resin. Purify the concentrate obtained in step (2) by eluting with water (2 BV, 1 BV / h) and 95% ethanol aqueous solution (3 BV, 0.5 BV / h) in sequence. Collect the 95% ethanol aqueous solution fraction to obtain the eluent. (4) Add 1% flocculant (citric acid, guar gum and bone glue in a mass ratio of 3:0.2:8) to the eluent, stir at 50°C for 20 min, let stand and cool, filter, and then freeze dry to obtain Schisandra chinensis extract.

[0054] Preparation Examples 1-2 This preparation example provides a Schisandra chinensis extract, prepared by the following method: (1) Take Schisandra chinensis and grind it into 80-mesh fine powder. Mix it with 20% ethanol aqueous solution at a material-to-liquid ratio of 1:15 g / mL and then perform ultrasonic treatment (30℃, 100 W, 40 min). (2) The mixture of schisandra powder after ultrasonic treatment was refluxed and extracted once for 3 hours. After filtration, the extract was obtained. The extract was concentrated under reduced pressure at 60°C to 50% of the mass of schisandra powder to obtain the concentrate. (3) Take 3 times the mass of Schisandra chinensis powder and pack it into a column of D-101 macroporous resin. Purify the concentrate obtained in step (2) by eluting with water (1 BV, 0.5 BV / h) and 80% ethanol aqueous solution (1 BV, 0.5 BV / h) in sequence. Collect the 80% ethanol aqueous solution fraction to obtain the eluent. (4) Add 1.5% flocculant (citric acid, guar gum and bone glue in a mass ratio of 5:0.1:5) to the eluent, stir for 10 min at 60°C, let stand and cool, filter, and then freeze dry to obtain Schisandra chinensis extract.

[0055] Preparation Examples 1-3 This preparation example provides a Schisandra chinensis extract, prepared by the following method: (1) Take Schisandra chinensis and grind it into 80-mesh fine powder. Mix it with 60% ethanol aqueous solution at a material-liquid ratio of 1:5 g / mL and then perform ultrasonic treatment (70℃, 600 W, 10 min). (2) The mixture of Schisandra chinensis powder after ultrasonic treatment was refluxed and extracted 3 times, 1 h each time. After filtration, the extract was obtained. The extract was concentrated under reduced pressure at 60°C to 50% of the mass of Schisandra chinensis powder to obtain the concentrate. (3) Take 10 times the mass of Schisandra chinensis powder and pack it into a column of D-101 macroporous resin. Purify the concentrate obtained in step (2) by eluting with water (5 BV, 2 BV / h) and 98% ethanol aqueous solution (4 BV, 1.5 BV / h) in sequence. Collect the 98% ethanol aqueous solution fraction to obtain the eluent. (4) Add 0.5% flocculant (citric acid, guar gum and bone glue in a mass ratio of 1:0.5:10) to the eluent, stir at 55°C for 30 min, let stand and cool, filter, and then freeze dry to obtain Schisandra chinensis extract.

[0056] Preparation Examples 1-4 This preparation example provides a Schisandra chinensis extract, which differs from Preparation Example 1-1 only in that it does not undergo ultrasonic treatment. Instead, Schisandra chinensis is ground into 80-mesh fine powder, mixed with a 40% ethanol aqueous solution, and subjected to hot reflux extraction. The parameters and subsequent steps of the hot reflux extraction are consistent with those of Example 1.

[0057] Preparation Examples 1-5 This preparation example provides a Schisandra chinensis extract, which differs from Preparation Example 1-1 only in that, in step (4), the total amount of flocculant added remains unchanged, and the flocculant is adjusted to citric acid and guar gum in a mass ratio of 3:0.2. The remaining steps are consistent with Example 1.

[0058] Preparation Examples 1-6 This preparation example provides a Schisandra chinensis extract, which differs from Preparation Example 1-1 only in that, in step (4), the total amount of flocculant added remains unchanged, and the flocculant is adjusted to citric acid and bone glue in a mass ratio of 3:8. The remaining steps are consistent with Example 1.

[0059] Preparation Examples 1-7 This preparation example provides a Schisandra chinensis extract, which differs from Preparation Example 1-1 only in that, in step (4), the total amount of flocculant added remains unchanged, and the flocculant is adjusted to guar gum and bone glue with a mass ratio of 0.2:8. The remaining steps are consistent with Example 1.

[0060] Preparation Examples 1-8 This preparation example provides a Schisandra chinensis extract, which differs from Preparation Example 1-1 only in that no flocculation treatment is performed. After obtaining the eluent in step (3), the Schisandra chinensis extract is directly freeze-dried. The remaining steps are consistent with those in Example 1.

[0061] Preparation Example 2-1 This preparation example provides an extract of Eucommia ulmoides leaves, prepared by the following method: Wash the Eucommia ulmoides leaves with clean water, dry and pulverize them to 80 mesh to obtain Eucommia ulmoides leaf powder; mix the Eucommia ulmoides leaf powder with water at a material-to-liquid ratio of 1:7 g / mL, and perform hot extraction (extract at 60℃ for 1 h) to obtain an extract. Concentrate the extract and freeze dry to obtain Eucommia ulmoides leaf extract.

[0062] Preparation Example 2-2 This preparation example provides an extract of Eucommia ulmoides leaves, prepared by the following method: Wash the Eucommia ulmoides leaves with clean water, dry and pulverize them to 80 mesh to obtain Eucommia ulmoides leaf powder; mix the Eucommia ulmoides leaf powder with water at a material-to-liquid ratio of 1:5 g / mL, and perform hot extraction (extract at 50℃ for 2 h) to obtain an extract; concentrate the extract and freeze dry to obtain Eucommia ulmoides leaf extract.

[0063] Preparation Examples 2-3 This preparation example provides an extract of Eucommia ulmoides leaves, prepared by the following method: Wash the Eucommia ulmoides leaves with clean water, dry and pulverize them to 80 mesh to obtain Eucommia ulmoides leaf powder; mix the Eucommia ulmoides leaf powder with water at a material-to-liquid ratio of 1:10 g / mL, and perform hot extraction (extract at 65℃ for 0.5 h) to obtain an extract; concentrate the extract and freeze-dry to obtain Eucommia ulmoides leaf extract.

[0064] Example 1 This embodiment provides a composition comprising, by weight parts: 100 parts of magnolol, 50 parts of Schisandra chinensis extract from Preparation Example 1-1, 100 parts of Eucommia ulmoides leaf extract from Preparation Example 2-1, 15 parts of ginsenoside CK, and 25 parts of PQQ.

[0065] Example 2 This embodiment provides a composition comprising, by weight parts: 250 parts of magnolol, 30 parts of Schisandra chinensis extract from Preparation Examples 1-2, 250 parts of Eucommia ulmoides leaf extract from Preparation Examples 2-2, 25 parts of ginsenoside CK, and 10 parts of PQQ.

[0066] Example 3 This embodiment provides a composition comprising, by weight parts: 50 parts of magnolol, 100 parts of Schisandra chinensis extract from Preparation Examples 1-3, 10 parts of Eucommia ulmoides leaf extract from Preparation Examples 2-3, 5 parts of ginsenoside CK, and 40 parts of PQQ.

[0067] Examples 4-8 Examples 4-8 each provide a composition, which differs from Example 1 only in that the Schisandra chinensis extract of Preparation Example 1-1 is replaced with equal parts by mass of Schisandra chinensis extract of Preparation Example 1-4-Preparation Example 1-8.

[0068] Comparative Example 1 This comparative example provides a composition that, compared to Example 1, removes the Eucommia ulmoides leaf extract and includes: 167 parts of magnolol, 83 parts of Schisandra chinensis extract from Preparation Example 1-1, 15 parts of ginsenoside CK, and 25 parts of PQQ.

[0069] Comparative Example 2 This comparative example provides a composition that, compared to Example 1, removes the Schisandra chinensis extract and includes: 125 parts of magnolol, 125 parts of Eucommia ulmoides leaf extract from Preparation Example 2-1, 15 parts of ginsenoside CK, and 25 parts of PQQ.

[0070] Comparative Example 3 This comparative example provides a composition that, compared to Example 1, removes magnolol and comprises: 83 parts of Schisandra chinensis extract from Preparation Example 1-1, 167 parts of Eucommia ulmoides leaf extract from Preparation Example 2-1, 15 parts of ginsenoside CK, and 25 parts of PQQ.

[0071] Comparative Example 4 This comparative example provides a composition that, compared to Example 1, removes magnolol, schisandra extract, and eucommia leaf extract, and includes only 15 parts of ginsenoside CK and 25 parts of PQQ.

[0072] Comparative Example 5 This comparative example provides a composition that, compared to Example 1, removes ginsenosides CK and PQQ, and includes only: 100 parts of magnolol, 50 parts of Schisandra chinensis extract from Preparation Example 1-1, and 100 parts of Eucommia ulmoides leaf extract from Preparation Example 2-1.

[0073] Comparative Example 6 This comparative example provides a composition that, compared to Example 1, removes ginsenoside CK and comprises: 100 parts of magnolol, 50 parts of Schisandra chinensis extract from Preparation Example 1-1, 100 parts of Eucommia ulmoides leaf extract from Preparation Example 2-1, and 40 parts of PQQ.

[0074] Comparative Example 7 This comparative example provides a composition that, compared to Example 1, removes PQQ and comprises: 100 parts of magnolol, 50 parts of Schisandra chinensis extract from Preparation Example 1-1, 100 parts of Eucommia ulmoides leaf extract from Preparation Example 2-1, and 40 parts of ginsenoside CK.

[0075] Test Example 1 Sleep Disorder Relief Ability Test: (1) Trial grouping and intervention method: Wild-type AB strain zebrafish, 5 days post-fertilization (5 dpf), were randomly selected and divided into 17 groups (1 control group, 1 model group, and 15 experimental groups), with 10 fish in each group. Different treatments were then administered, as detailed below: Control group: fed regular feed for two weeks, twice a day, 0.1 g of feed each time; Model group: After being fed a normal diet for two weeks (feeding twice a day, 0.1 g of feed each time), zebrafish were soaked in a caffeine solution with a concentration of 200 μmol / L for 24 h. Experimental group: Zebrafish were fed with the compositions obtained from each example or comparative example by adding 50 mg / kg of feed to ordinary feed for two weeks (feeding twice a day, 0.1 g of feed each time), and then soaked in a caffeine solution with a concentration of 200 μmol / L for 24 h. (2) Zebrafish behavioral analysis: After each experimental group was treated in the above manner, the movement distance of each group of zebrafish within 10 minutes was measured using a behavior analyzer. Then, the sleep improvement rate (%) was evaluated according to the formula: Sleep improvement rate (%) = (Movement distance of model group - Movement distance of experimental group) / (Movement distance of model group - Movement distance of control group) × 100%.

[0076] The movement distance of zebrafish in each experimental group is as follows: Figure 1 As shown in the figure (*** indicates a comparison with the model control group, p<0.001; #, ##, and ### indicate a comparison with Example 1, p<0.05, p<0.01, and p<0.001, respectively).

[0077] The sleep improvement rate of zebrafish in each experimental group was as follows: Figure 2 As shown (*, *, ** represent comparisons with Example 1, p<0.05, p<0.01, p<0.001, respectively).

[0078] Depend on Figure 1-2 The data shows that after the composition involved in this invention intervened in zebrafish, the movement distance was significantly reduced compared with the model group, indicating an excellent sleep improvement effect.

[0079] A comparison of the data from Example 1 with Comparative Examples 1-3 shows that magnolol, schisandra chinensis extract, and eucommia ulmoides leaf extract have a significant synergistic effect on improving sleep in insomnia-stricken zebrafish. A comparison of the data from Example 1 with Comparative Examples 6-7 shows that ginsenosides CK and PQQ have a significant synergistic effect on improving sleep in insomnia-stricken zebrafish. Furthermore, a comparison of the data from Example 1 with Comparative Examples 4 and 5 shows that by combining the above two compositions, insomnia can be significantly alleviated, and the two compositions can synergistically improve sleep.

[0080] A comparison of the data from Examples 1 and 4 shows that by subjecting Schisandra chinensis to ultrasonic treatment followed by hot reflux extraction, the resulting Schisandra chinensis extract can better exert the synergistic effect with components such as magnolol and Eucommia ulmoides leaf extract.

[0081] A comparison of the data from Examples 1 and 5-8 shows that, in the preparation of Schisandra chinensis extract, the use of a combination of citric acid, guar gum, and bone glue to flocculate the concentrated Schisandra chinensis solution purified by macroporous resin can further enrich the sleep-enhancing components in Schisandra chinensis and further enhance the synergistic effect of components such as magnolol and Eucommia ulmoides leaf extract in relieving sleep disorders.

[0082] The applicant declares that the technical solution of this invention is illustrated by the above embodiments, but this invention is not limited to the above embodiments, that is, it does not mean that this invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of raw materials for the products of this invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of this invention.

[0083] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0084] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

Claims

1. A composition capable of improving fatigue-related sleep disorders, characterized in that, The composition comprises: magnolol, schisandra extract, eucommia leaf extract, ginsenosides, and pyrrolidone.

2. The composition according to claim 1, characterized in that, The composition comprises, by weight parts: 10-300 parts of magnolol, 10-100 parts of Schisandra chinensis extract, 10-300 parts of Eucommia ulmoides leaf extract, 1-30 parts of ginsenosides and 1-50 parts of pyrroloquinoline quinone.

3. The composition according to claim 1 or 2, characterized in that, The ginsenosides include ginsenoside CK.

4. The composition according to any one of claims 1-3, characterized in that, The Schisandra chinensis extract was prepared using a method comprising the following steps: (1) The Schisandra chinensis raw material was mixed with an aqueous solution of ethanol and then subjected to ultrasonic treatment; (2) The treated solution is refluxed to extract the extract, and the extract is concentrated under reduced pressure to obtain the concentrate; (3) The concentrate was purified using macroporous resin and eluted sequentially with aqueous solutions of water and ethanol. The aqueous fraction of ethanol was collected to obtain the eluent. (4) The eluent was subjected to flocculation treatment and dried to obtain Schisandra chinensis extract.

5. The composition according to claim 4, characterized in that, In step (1), the volume fraction of ethanol in the aqueous solution is 20%-60%. The ratio of Schisandra chinensis raw material to ethanol aqueous solution is 1:5-1:15 g / mL; Preferably, the temperature of the ultrasonic treatment in step (1) is 30-70℃, the time is 10-40 min, and the power is 100-600W.

6. The composition according to claim 4 or 5, characterized in that, The reflux extraction in step (2) is performed 1-3 times, and the extraction time for each extraction is 1-3 hours independently.

7. The composition according to any one of claims 4-6, characterized in that, The macroporous resin in step (3) includes D101 type macroporous resin; Preferably, the mass ratio of the macroporous resin to the Schisandra chinensis raw material is 3:1-10:1; Preferably, the volume percentage of ethanol in the aqueous solution of ethanol in step (3) is 80%-98%; Preferably, the flow rate of the aqueous solution of water and ethanol used for elution is independently 0.5-2 BV / h, and the amount used is independently 1-5 BV.

8. The composition according to any one of claims 4-7, characterized in that, The flocculation treatment in step (4) uses a flocculant, the mass of which is 0.1-1.5% of the eluent mass; Preferably, the flocculant comprises any one or a combination of at least two of citric acid, guar gum, or bone glue, and more preferably a combination of citric acid, guar gum, and bone glue. Preferably, the mass ratio of citric acid, guar gum, and bone glue is (1-5):(0.1-0.5):(5-10); Preferably, the temperature of the flocculation treatment is 50-60℃, and the flocculation treatment time is 10-30 min.

9. The composition according to any one of claims 1-8, characterized in that, The Eucommia ulmoides leaf extract was prepared using a method comprising the following steps: Eucommia ulmoides leaf raw material was mixed with water and subjected to hot extraction to obtain Eucommia ulmoides leaf extract; Preferably, the ratio of Eucommia ulmoides leaf raw material to water is 1:5-1:10 g / mL; Preferably, the hot extraction temperature is 50-65℃ and the hot extraction time is 0.5-2 h.

10. Use of the composition of any one of claims 1-9 in the preparation of a pharmaceutical or food product capable of improving fatigue-related sleep disorders.

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