Composition for improving sleep containing cordycepin

Abstract

The invention discloses a composition for improving sleep containing cordycepin, wherein the composition comprises cordycepin, ginsenoside and salidroside; the mass ratio of the cordycepin, ginsenoside and salidroside is 0.5-1.5:0.2-2:1.5-5. The composition provided by the invention can effectively improve sleep, prevent or treat sleep disorders, and shorten the onset time.

Description

Technical Field

[0001] The invention relates to a composition for improving sleep, in particular to a composition for improving sleep containing cordycepin. Background Art

[0002] Insomnia, also known as sleep continuity disorder, is a common experience of difficulty sleeping. It refers to the subjective experience that people cannot get satisfactory sleep time and quality even in an environment and conditions suitable for sleep, which even affects their daytime social functions. The pace of modern life has obviously accelerated, and the pressure of people's lives has become more complicated and heavy. The prevalence of insomnia has also increased year by year, and the patient population has become younger. Insomnia is also accompanied by anxiety, depression, etc. The decline in sleep quality leads to reduced work efficiency, the body is in a sub-healthy or even unhealthy state, and a series of clinical symptoms such as irritability, loss of appetite, and hair loss will appear. Long-term insomnia may lead to the occurrence of cardiovascular disease, diabetes and other diseases.

[0003] Traditional Chinese medicine's understanding of insomnia was already described in the Yellow Emperor's Classic of Internal Medicine, which called insomnia "not being able to lie down" and "restless lying down", etc., which fall into the category of insomnia. Traditional Chinese medicine believes that the main causes of insomnia are imbalances of yin and yang, disharmony of qi and blood, and dysfunction of the five internal organs. The main organ that causes the disease is the heart, and it is also inseparable from the liver, spleen, and brain. It has proposed many treatment concepts, including yin and yang balance, coordination of nutrition and defense, fullness of qi and blood, stability of the five internal organs, harmonization of the spleen and stomach, and phlegm and blood stasis. In the treatment of insomnia, it adheres to the treatment principle of regulating yin and yang and balancing the five internal organs to achieve "yin and yang balance", conducts syndrome differentiation and treatment, and overall review, and improves patients' insomnia by treating phlegm, fire, blood stasis, and deficiency in the human body. Traditional Chinese medicine, acupuncture, acupoint application, massage, five-tone and other treatment methods are often used

[0004] Western medicine believes that insomnia is mostly related to various neurotransmitters in the brain, such as glutamate and γ-aminobutyric acid. Neurotransmitters in the brain exist between neuronal synapses and play an important role in the process of chemical signal transmission. Insomnia is often treated with drugs to promote sleep, including benzodiazepine receptor agonists, orexin antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants and antipsychotics, etc., which can induce and (or) maintain sleep and have a good therapeutic effect on acute insomnia, but the effect on chronic insomnia is uncertain, and there are many side effects, affecting sleep structure and physiological function.

[0005] Sleep is regulated and controlled by the interaction between circadian rhythm and homeostasis. The circadian rhythm of sleep is regulated by the suprachiasmatic nucleus receiving light signals through retinal ganglion cells and acting on transcriptional activators BMAL1 and CLOCK, thereby regulating the expression of period genes Per1 and Per2 and inhibiting BMAL1-CLOCK binding. Among them, wakefulness-promoting neurotransmitters include orexin, norepinephrine, histamine, etc., while sleep-promoting neurotransmitters include γ-aminobutyric acid, adenosine, etc. In addition, the hypothalamus-pituitary-adrenal axis and sleep have mutual effects. In addition, glial cells drive changes in local network states through the adenosine triphosphate-cytokine-AD mechanism, changing their intrinsic membrane properties and sensitivity to neurotransmitters and neuromodulators (such as AD, glutamate and GABA), thereby regulating sleep. Cytokines IL-1β, IL-6 and TNF-α can participate in the regulation of sleep-wakefulness by regulating the wakefulness regulation center located in the hypothalamus, basal forebrain and brainstem through affecting AD, nitric oxide, nuclear factor transcription factor, prostaglandin D2, GABA, glutamate and NA, as well as hormones such as growth hormone-releasing hormone and adrenocorticotropic hormone.

[0006] However, most of the current sedative hypnotic drugs are developed with an eye on regulating neurotransmitters and a small amount of adjusting circadian rhythms. Therefore, natural medicines are gaining more and more attention as sedative hypnotic drugs. Chemical components contained in plants, such as terpenes, flavonoids, alkaloids, steroids, saponins, lactones, cannabinoids, cinnamate, nitrite, valerate and iridoid compounds, have been shown to improve insomnia by regulating the GABA system, 5HT system, melatonin neurotransmitter, and His neurotransmitter.

[0007] Cordycepin is an adenosine analogue and a non-specific agonist of adenosine receptors. It can regulate sleep by acting on adenosine receptors. Korean invention patent KR1020100120858 discloses that cordycepin isolated and extracted from Cordyceps sinensis has the effect of reducing the sleep / wake cycle, reducing the number of awakenings during sleep, thereby inducing continuous sleep and increasing the total sleep time. Hu et al.'s study on rat sleep showed that cordycepin can effectively reduce the rat's wake cycle and prolong the NREM stage. The EEG results showed that cordycepin increased the power density of theta waves in the NREM stage. In addition, cordycepin can also regulate the levels of adenosine A1, A2a, and A3 receptors related to sleep regulation. Clinically, there are case reports that taking 15-30 mg of cordycepin can improve insomnia symptoms within 1-2 weeks without adverse reactions. The applicant conducted further research on this basis to provide a composition containing cordycepin to improve sleep to further improve the efficacy. Summary of the invention

[0008] Purpose of the invention: The technical problem to be solved by the present invention is to provide a composition containing cordycepin for improving sleep in view of the deficiencies in the prior art.

[0009] Another technical problem to be solved by the present invention is to provide a preparation of a composition containing cordycepin for improving sleep.

[0010] A further technical problem to be solved by the present invention is to provide applications of the above-mentioned composition and preparation.

[0011] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0012] In a first aspect, the present invention discloses a composition for improving sleep.

[0013] In some embodiments, the composition for improving sleep includes cordycepin, ginsenosides and salidroside. In some embodiments, the mass ratio of cordycepin, ginsenosides and salidroside is 0.5-1.5:0.2-2:1.5-5; in some embodiments, the mass ratio of cordycepin, ginsenosides and salidroside is 1:0.2-1:2-4; in some embodiments, the mass ratio of cordycepin, ginsenosides and salidroside is 1:0.2-0.8:2.5-3.5. In some embodiments, the composition further includes any one or more combinations of soybean saponins, gynostemma soap, kudzu root extract, astragalus extract and tanshinone ⅡA. In some embodiments, the mass ratio of any one or more combinations of soybean saponins, gynostemma soap, kudzu root extract, astragalus extract and tanshinone ⅡA to cordycepin is 0.01-10:1. In some embodiments, the mass ratio of kudzu root extract to cordycepin is 0.01-0.1:1.

[0014] In some embodiments, the composition for improving sleep includes cordycepin, ginsenosides and kudzu root extract. In some embodiments, the mass ratio of cordycepin, ginsenosides and kudzu root extract is 0.5-1.5:0.01-0.1:0.1-2, and in some embodiments, the mass ratio of cordycepin, ginsenosides and kudzu root extract is 1:0.01-0.1:0.5-1.5. In some embodiments, the composition further includes any one or more combinations of soybean saponins, gynostemma soap, salidroside, astragalus extract and tanshinone ⅡA; the mass ratio of any one or more combinations of soybean saponins, gynostemma soap, salidroside, astragalus extract and tanshinone ⅡA to cordycepin is 0.01-10:1.

[0015] In some embodiments, the ginsenosides include ginsenoside Rk1, ginsenoside Rg3, ginsenoside Rg5, and ginsenoside Re.

[0016] In some embodiments, the kudzu root extract and astragalus extract are obtained by extracting kudzu root or astragalus with water and / or alcohol, preferably by extracting with a mixed solution of water and alcohol; preferably, the alcohol is a C1-C3 alcohol; preferably, the mass concentration of alcohol in the mixed solution of water and alcohol is 30%-110%, preferably 50%-100%, preferably 70%-90%; preferably, the mass of the water and / or alcohol is 6-10 times the mass of kudzu root; preferably, the extraction time is 0.5-3h. In some embodiments, the kudzu root extract includes puerarin.

[0017] In a second aspect, the present invention discloses a preparation for improving sleep.

[0018] In some embodiments, the preparation for improving sleep comprises a) any one of the following compositions for improving sleep; and b) a pharmaceutically acceptable excipient.

[0019] In some embodiments, the composition for improving sleep includes cordycepin, ginsenosides and salidroside. In some embodiments, the mass ratio of cordycepin, ginsenosides and salidroside is 0.5-1.5:0.2-2:1.5-5; in some embodiments, the mass ratio of cordycepin, ginsenosides and salidroside is 1:0.2-1:2-4; in some embodiments, the mass ratio of cordycepin, ginsenosides and salidroside is 1:0.2-0.8:2.5-3.5. In some embodiments, the composition further includes any one or more combinations of soybean saponins, gynostemma soap, kudzu root extract, astragalus extract and tanshinone ⅡA. In some embodiments, the mass ratio of any one or more combinations of soybean saponins, gynostemma soap, kudzu root extract, astragalus extract and tanshinone ⅡA to cordycepin is 0.01-10:1. In some embodiments, the mass ratio of kudzu root extract to cordycepin is 0.01-0.1:1.

[0020] In some embodiments, the composition for improving sleep includes cordycepin, ginsenosides and kudzu root extract. In some embodiments, the mass ratio of cordycepin, ginsenosides and kudzu root extract is 0.5-1.5:0.01-0.1:0.1-2, and in some embodiments, the mass ratio of cordycepin, ginsenosides and kudzu root extract is 1:0.01-0.1:0.5-1.5. In some embodiments, the composition further includes any one or more combinations of soybean saponins, gynostemma soap, salidroside, astragalus extract and tanshinone ⅡA; the mass ratio of any one or more combinations of soybean saponins, gynostemma soap, salidroside, astragalus extract and tanshinone ⅡA to cordycepin is 0.01-10:1.

[0021] In some embodiments, the sleep improving composition comprises cordycepin, ginsenoside and salidroside.

[0022] In some embodiments, the kudzu root extract and astragalus extract are obtained by extracting kudzu root or astragalus with water and / or alcohol, preferably by extracting with a mixed solution of water and alcohol; preferably, the alcohol is a C1-C3 alcohol; preferably, the mass concentration of alcohol in the mixed solution of water and alcohol is 30%-110%, preferably 50%-100%, preferably 70%-90%; preferably, the mass of the water and / or alcohol is 6-10 times the mass of kudzu root; preferably, the extraction time is 0.5-3h. In some embodiments, the kudzu root extract includes puerarin.

[0023] The preparations described in the present invention include tablets, capsules, injections, aerosols, etc.

[0024] The pharmaceutically acceptable excipients used in the drug of the present invention include fillers, stabilizers, antioxidants, binders, lubricants, disintegrants, etc. In some embodiments, the fillers include starch, microcrystalline cellulose, lactose, etc.; in some embodiments, the stabilizers include Tween, Span, mannitol, etc.; in some embodiments, the antioxidants include vitamin C, sorbic acid, etc.; in some embodiments, the binders include povidone, hydroxypropyl methylcellulose, povidone, etc.; in some embodiments, the lubricants include stearic acid, magnesium stearate, talc, etc.; in some embodiments, the disintegrants include cross-linked polyvinylpyrrolidone, hydroxypropyl cellulose, etc.

[0025] In a third aspect, the present invention discloses the use of the composition described in the first aspect or the preparation described in the second aspect in the preparation of a sleep improving product.

[0026] Wherein, improving sleep includes preventing, improving or treating sleep disorders.

[0027] Among them, the sleep disorders include insomnia, sleep-related breathing disorders, central sleep disorders, circadian rhythm sleep-wake disorders, parasomnias, and sleep-related movement disorders.

[0028] The cordycepin, ginsenoside and salidroside described in the present invention interact with each other, and the cordycepin, ginsenoside and kudzu root extract interact with each other, by activating AMPK, PI3K / Akt / mTOR signaling pathways, upregulating NRF2 / SIRT3 pathways, reducing Aβ neurotoxicity; inhibiting NLRP3 / Caspase-1 signaling pathways, activating Nrf2 / HO-1 signaling pathways, and reducing neuronal apoptosis; reducing neuroinflammatory response, regulating SIRT1 / NF-κB signaling pathways, reducing hippocampal inflammatory response, delaying neuronal aging, and promoting mitochondrial synthesis, thereby preventing or treating sleep disorders and shortening the onset time.

[0029] Beneficial effects:

[0030] The composition provided by the present invention interacts with each other, activates AMPK, PI3K / Akt / mTOR signaling pathways, upregulates NRF2 / SIRT3 pathways, reduces Aβ neurotoxicity; inhibits NLRP3 / Caspase-1 signaling pathways, activates Nrf2 / HO-1 signaling pathways, and reduces neuronal apoptosis; reduces neuroinflammatory response, regulates SIRT1 / NF-κB signaling pathways, reduces hippocampal inflammatory response, delays neuronal aging, promotes mitochondrial synthesis, effectively improves sleep, prevents or treats sleep disorders, and shortens the onset time. DETAILED DESCRIPTION

[0031] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0032] In the following examples, the Pueraria extract is puerarin.

[0033] In the following embodiments, the astragalus extract is prepared by the following method: adding 90% methanol solution of 6 times the mass of astragalus, reflux extraction for 1.5 hours, filtering and concentrating; the obtained filter residue is refluxed and extracted again for 1.5 hours; the extracts are combined and concentrated to a relative density of 1.18-1.36 (60°C).

[0034] Compositions for improving sleep in Examples 1-4 and Comparative Example 1

[0035] As shown in Table 1, the raw materials and amounts used in the various embodiments and comparative examples are different, as shown in the table below.

[0036] Table 1

[0037]

[0038] Application Example 1: Sleep Analysis

[0039] 90 male rats weighing about 300g were raised in a humidity environment of 20-24℃ and relative humidity of 60%±5%. They were randomly divided into 9 groups, 10 rats in each group. The experimental group and the comparative group were gavaged with the same dose of normal saline according to Table 1, and the drug was administered at about 12:30 noon every day, once a day, for one week. The sleep latency and sleep duration of each group of rats were recorded; wherein, the sleep latency is the time when the righting reflex disappears, and the sleep duration is the time from the disappearance of the righting reflex to the recovery. The results are shown in Table 2.

[0040] Table 2

[0041] Sleep latency / min Sleep duration / min Blank control group 7.65±0.69 15.01±1.68 Example 1 <![CDATA[4.65±0.35 # ]]> <![CDATA[22.21±4.06 # ]]> Example 2 <![CDATA[4.08±0.27 # ]]> <![CDATA[23.52±3.54 ## ]]> Example 3 <![CDATA[3.06±0.04 ## ]]> <![CDATA[29.47±3.15 ## ]]> Example 4 <![CDATA[4.25±0.94 # ]]> <![CDATA[23.59±1.92 # ]]> Example 5 <![CDATA[4.56±0.51 ## ]]> <![CDATA[28.54±2.14 # <!-- 4 -->]]> Example 6 <![CDATA[4.05±0.18 ## ]]> <![CDATA[30.17±3.27 # ]]> Comparative Example 1 <![CDATA[6.05±0.57 # ]]> 19.54±2.67 Comparative Example 2 6.57±0.63 18.99±2.34

[0042] Note: Compared with the blank control group, # indicates P < 0.05, ## indicates P < 0.01.

[0043] As can be seen from Table 2, the composition provided by the present invention can interact, complement and synergize through cordycepin, ginsenoside and salidroside, or through cordycepin, ginsenoside and kudzu root extract, effectively promote the sleep of rats, shorten the sleep latency and prolong the sleep duration, especially after adding a trace amount of kudzu root extract to the mixture of cordycepin, ginsenoside and salidroside, the sleep latency can be further shortened and the sleep duration can be prolonged, which is significantly different from the blank control group (P<0.01).

[0044] Examples 7-10: Preparation and application of a composition for improving sleep

[0045] The raw materials and dosage of the active ingredients in each preparation are detailed in the table below.

[0046] Table 3

[0047]

[0048] Take 60 g of the active ingredient described in Example 7, add appropriate amounts of conventional excipients to prepare 1000 tablets.

[0049] Take 50 g of the active ingredient described in Example 8 and add appropriate amounts of conventional excipients to prepare 1000 tablets.

[0050] Take 40 g of the active ingredient described in Example 9 and add appropriate amounts of conventional excipients to prepare 1000 capsules.

[0051] Take 40 g of the active ingredient described in Example 10, add appropriate amounts of conventional excipients to prepare 1000 capsules.

[0052] The preparations described in Examples 7-10 were used to conduct sleep analysis experiments, and all of them were able to improve sleep, significantly shorten the sleep onset latency, and significantly prolong the sleep duration.

[0053] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A composition for improving sleep, characterized in that: The invention comprises cordycepin, ginsenoside and salidroside, wherein the mass ratio of the cordycepin, ginsenoside and salidroside is 0.5-1.5:0.2-2:1.5-5.

2. The composition according to claim 1, characterized in that The mass ratio of cordycepin, ginsenoside and salidroside is 1:0.2-1:2-4.

3. The composition according to claim 1, characterized in that The mass ratio of cordycepin, ginsenoside and salidroside is 1:0.2-0.8:2.5-3.

5.

4. The composition according to claim 1, characterized in that The composition further comprises any one or more combinations of soybean saponin, gynostemma pentaphyllum soap, kudzu root extract, astragalus extract and tanshinone ⅡA.

5. The composition according to claim 4, characterized in that The mass ratio of any one or more combinations of soybean saponin, gynostemma pentaphyllum soap, kudzu root extract, astragalus extract and tanshinone ⅡA to cordycepin is 0.01-10:

1.

6. The composition according to claim 4, characterized in that The mass ratio of the kudzu root extract to cordycepin is 0.01-0.1:

1.

7. The composition according to any one of claims 4 to 6, characterized in that The kudzu root extract is obtained by extraction with water and / or alcohol.

8. The composition according to any one of claims 4 to 6, characterized in that The kudzu root extract includes puerarin.

9. A preparation for improving sleep, characterized in that: The invention comprises a) the composition according to any one of claims 1 to 8; and b) a pharmaceutically acceptable excipient.

10. Use of the composition according to any one of claims 1 to 8 or the preparation according to claim 9 in the preparation of a product for improving sleep.

11. The use according to claim 10, characterized in that: Improving sleep includes preventing, improving or treating sleep disorders.

12. The use according to claim 11, characterized in that: The sleep disorders include insomnia, sleep-related breathing disorders, central sleep disorders, circadian rhythm sleep-wake disorders, parasomnias, and sleep-related movement disorders.

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