Composition for preventing or treating sleep disorders comprising Massa Medicata Fermentata and Maydis stigma extracts

Abstract

The present invention relates to a composition for preventing, improving, or treating sleep disorders, comprising extracts of *Massa Medicata Fermentata* and *Maydis stigma* as active ingredients. The composition according to the present invention exhibits excellent effects in reducing the time it takes to fall asleep and increasing the duration of sleep, and as a natural product, it does not cause side effects such as cytotoxicity, tolerance, or dependence even with long-term use.

Description

Technology Field

[0001] The present invention relates to a composition for preventing, improving, or treating sleep disorders comprising extracts of Massa Medicata Fermentata and Maydis stigma. Background Technology

[0002] Sleep is a naturally occurring state characterized by changes in consciousness, inhibition of sensory activity, and suppression of all voluntary muscles. As it restores the body's energy and provides rest, it is a vital physiological phenomenon for maintaining health and well-being. During sleep, most bodily systems enter an anabolic state, characterized by reduced recovery and growth of the immune, nervous, and musculoskeletal systems. However, in modern society, many people suffer from sleep disorders as a result of stress, anxiety, and nervousness, or as a cause or consequence of neurological diseases (Alzheimer's disease, Parkinson's disease, Attention Deficit Hyperactivity Disorder (ADHD), stroke, autism spectrum disorder, depression, and schizophrenia). Sleep disorder is a concept that encompasses a state in which one is unable to achieve healthy sleep, fails to maintain alertness during the day despite getting sufficient sleep, or experiences difficulties sleeping or staying awake due to a disrupted sleep rhythm; it varies depending on the patient's symptoms, including insomnia, narcolepsy, restless leg syndrome, and sleep apnea. Sleep disorders can be a cause of learning disabilities, reduced work efficiency, various safety accidents such as traffic accidents, emotional disorders, and social adjustment disorders; if not treated properly, medical, neurological, and psychiatric conditions may worsen or recovery may be delayed.

[0003] Disease states caused by sleep deprivation are similar to various phenomena observed in aging, neurological disorders such as Alzheimer's or Parkinson's disease, and alcoholism. Conversely, there are also reports that sleep disorders appear as common symptoms in neurological diseases such as dementia (including Alzheimer's disease), developmental disorders such as autism, and aging. As aging progresses, changes in language ability, quantitative and qualitative changes in sleep, and changes in cognitive function are closely linked. In particular, regarding sleep, various changes occur in sleep quality, including sleep quantity, slow-wave sleep, sleep spindle density, and sleep continuity / fragmentation.

[0004] Treatment for sleep disorders is broadly divided into pharmacotherapy and non-pharmacotherapy. While drug treatment, such as with sleeping pills, can be the easiest and fastest method, there are concerns regarding the risk of adverse reactions associated with drug use, particularly the effects of long-term use, the development of tolerance, and rebound and withdrawal symptoms upon discontinuation. Consequently, methods that minimize drug use while combining it with cognitive behavioral therapy are being used recently. As sleeping pills for the treatment of moderate to severe sleep disorders, GABA-A modulators such as zaleplon and zopiclone are widely used recently. Additionally, melatonin, which can inhibit the activity of the suprachiasmatic nucleus, is sometimes used to promote sleep based on the circadian rhythm.

[0005] In recent years, along with the growing interest in sleep induction and maintenance, effective and safe new sleeping pills have been released one after another. Drugs containing the sleep hormone melatonin as the main ingredient, which have a different mechanism of action from existing sleep disorder treatments, are currently being launched in Korea. These are expected to be new sleeping pills that induce sleep by normalizing the melatonin cycle without hallucinations or dependence; however, due to domestic regulations classifying them as psychotropic drugs, there is still a very high demand for high-efficiency, low-dependence, and low-side-effect sleep aids.

[0006] In addition to drug treatment, foods such as bananas, potatoes, honey, onions, and lettuce are known to induce sleep as a method to treat sleep disorders; while these are generally thought to be related to the production of melatonin, a sleep-regulating hormone, the detailed mechanism is unknown.

[0007] Natural sleep-inducing products include Ecklonia cava extract (phlorotannin), rice bran ethanol extract, and milk protein hydrolysate, which have been reported to induce the activation of GABAA benzodiazepines or inhibit histamine receptors. However, current natural sleep aids face limitations in market growth due to uncertainties regarding their effects and mechanisms.

[0008] Massa Medicata Fermentata, also known as Shinguk, Yukguk, Yuksingok, or Yaknuruk, refers in Korean traditional medicine to a type of yeast starter made by kneading wheat flour or wheat bran with ingredients such as red bean powder, crushed apricot kernels, Artemisia annua juice, and burdock juice, and then fermenting the mixture with yeast fungi. This Shinguk primarily acts on the spleen and stomach to strengthen digestive functions, aid digestion, and soothe the stomach. It is known to be effective for indigestion, chest tightness, vomiting and diarrhea, and postpartum abdominal pain caused by blood stasis. Dermatologically, it is effective for facial blood circulation and has wound healing properties.

[0009] On the other hand, Maydis stigma is the pistil and stigma of Zea mays.L, which is in the form of a thread or hair that goes to the pistil and stigma, and is also called corn silk, and is generally referred to as corn tassels. As recorded in ancient literature such as "Compendium of Materia Medica", the function of Maydis stigma is known to have medicinal effects when used in the treatment of urinary diseases, diuretics, blood coagulation, adult disease-related diseases, etc. In China, many people have used corn silk as a therapeutic agent because it is effective for diabetes, and in our country, it is also known to be good for the stomach, intestines, etc. In particular, it has a diuretic effect and a blood pressure-lowering effect, and has been widely used as a folk medicine for diabetes, hepatitis, urethral stones, hypertension, hematemesis, angina, and prevention of colds.

[0010] As a result of continuously conducting research on natural substances that can prevent, improve or treat sleep disorders related to melatonin receptors, the present inventors have confirmed that when used in combination with Xinguo and Maydis stigma, the effect of reducing sleep onset time and increasing sleep duration is very excellent, and completed the present invention. Prior art documents

[0012] Republic of Korea Patent Publication No. 10-2021-0096932 Problems to be solved

[0013] An object of the present invention is to provide a pharmaceutical composition for preventing, improving or treating sleep disorders, comprising an extract of Xinguo and Maydis stigma as an active ingredient.

[0014] However, the technical problems to be achieved by the present invention are not limited to the problems mentioned above, and other problems not mentioned can be clearly understood by those skilled in the art from the following description. Means for solving the problems

[0015] In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing or treating sleep disorders, comprising an extract of Xinguo and Maydis stigma as an active ingredient.

[0016] In addition, the present invention provides a quasi-drug composition for preventing or improving sleep disorders comprising extracts of Massa Medicata Fermentata and Maydis stigma as active ingredients.

[0017] In addition, the present invention provides a sleep aid comprising extracts of Singok and Okchokseoye as active ingredients.

[0018] In addition, the present invention provides a food composition for preventing or improving sleep disorders comprising extracts of Singok and Okchokseoye as active ingredients.

[0019] The above composition can reduce the time it takes to fall asleep and increase the duration of sleep.

[0020] The above composition can increase melatonin receptor expression.

[0021] The above-mentioned new grain extract can be extracted using water, an organic solvent, or a mixture thereof as a solvent.

[0022] The above organic solvent may include one or more solvents selected from the group consisting of lower alcohols having 1 to 6 carbon atoms, hexane, acetone, ethyl acetate, chloroform, and diethyl ether. Effects of the invention

[0023] The composition of the present invention, comprising extracts of Singok and Okchokseoye as active ingredients, has the effect of effectively preventing, improving, or treating sleep disorders and insomnia that occur during anxiety, stress, aging, degenerative neurological diseases such as dementia, and brain developmental disorders such as autism, by reducing the time required for sleep induction and increasing the time required for sleep.

[0024] In addition, the composition containing the extracts of the new crop and the jade plant of the present invention as active ingredients can be applied to various products, such as pharmaceutical compositions, food compositions, and quasi-drug compositions, as a natural medicine for the prevention, treatment, or improvement of sleep disorders or insomnia.

[0025] Furthermore, the extracts of the new crop and jade saplings of the present invention have not only been confirmed to exhibit no toxicity in animal experiments, but since they are derived from natural substances, they can be safely and continuously used without causing serious irritation to the body or inducing harmful effects, in addition to their efficacy in preventing and improving sleep disorders or insomnia. Brief explanation of the drawing

[0026] Figure 1 is a diagram showing the change in melatonin receptor expression after treating cultured nerve cells with a combination of Singok and Okchokseoye extracts. It is the result of quantifying the change in melatonin receptor expression by RT-PCR after treating primary cultured nerve cells with a combination of Singok extract and Okchokseoye extract. Figure 2 shows the results of confirming the effect of combined administration of Singok and Okchokseoye extracts on sleep latency and sleep duration. Figure 3 shows the results of confirming the presence or absence of toxicity caused by the extracts of Singok and Okchokseoye. Specific details for implementing the invention

[0027] The inventors completed the present invention by experimentally confirming that the combined use of extracts of *Singok* and *Okchokseoye*, which are natural products with little to no side effects, significantly increases melatonin receptor expression and is highly effective in inducing sleep and extending sleep duration.

[0028] The present invention will be described in detail below.

[0029] The present invention provides a composition for preventing, improving, or treating sleep disorders comprising extracts of Massa Medicata Fermentata and Maydis stigma as active ingredients.

[0030] The above composition can reduce the time it takes to fall asleep and increase the duration of sleep.

[0031] It can also increase melatonin receptor expression.

[0032] In this specification, "prevention" refers to any act of delaying the onset of a sleep disorder by administering a composition of the present invention, and "treatment" and "improvement" refer to any act of improving or beneficially altering the symptoms of a sleep disorder by administering a composition of the present invention.

[0033] The prevention, improvement, or treatment of the above-mentioned sleep disorder may mean reducing the onset time or increasing the duration of sleep.

[0034] "Sleep disorder" refers to any condition related to sleep, signifying symptoms that impair sleep due to various factors. Specifically, it encompasses conditions such as an inability to achieve healthy sleep, an inability to maintain alertness during the day despite sufficient sleep, or difficulties falling asleep or staying awake due to a disrupted sleep rhythm. Depending on the patient's symptoms, these disorders vary, including insomnia, narcolepsy, restless leg syndrome, and sleep apnea. Sleep disorders can be a cause of learning disabilities, reduced work efficiency, various safety accidents such as traffic accidents, emotional disorders, and difficulties in social adaptation. Furthermore, if left untreated, they can exacerbate internal, neurological, and psychiatric conditions or delay recovery.

[0035] The above sleep disorders may be one or more selected from the group consisting of sleep onset disorder, sleep deprivation disorder, mid-sleep awakening, early awakening, insomnia, nightmare, sleepwalking, narcolepsy, abnormal behavior during sleep, hypersomnia, narcolepsy, sleep attacks, breathing-related sleep disorders, apnea, circadian rhythm sleep disorders, parasomnia, restless legs syndrome, and periodic limb movement disorder, but are not limited thereto.

[0036] The above-mentioned "melatonin" is a biogenic hormone secreted by the pineal gland in the brain and is used as a drug for medically treating sleep disorders or insomnia. Different from existing drugs that suppress the brain to induce sleep, melatonin activates melatonin receptors to naturally induce sleep. Melatonin in the living body is synthesized by detecting light cycles such as the lengths of day and night, regulates the sleep-wake rhythm and daily and seasonal biological rhythms of humans, and induces natural sleep. In addition, it is known to have antioxidant and immune-stimulating effects.

[0037] "Shengqu (Massa Medicata Fermentata)" is also known as Shenqu, Yuguo, Yuxinshengqu, and Yaonuluk. In traditional Chinese medicine, it refers to the leaven obtained by kneading materials such as glutinous rice or wheat bran with red yeast rice, ground apricot seeds, bitter orange juice, and pogostemon juice and fermenting them with leaven bacteria. The above-mentioned Shengqu mainly acts on the spleen and stomach, strengthens the function of the digestive organs, helps digestion, and has the effect of making people feel comfortable. It is known to be effective in cases such as chest tightness, vomiting and diarrhea, and abdominal pain caused by postpartum blood stasis. Dermatologically, it has an effect on improving blood circulation on the face and also has a wound healing effect.

[0038] "Yumichuxu (Maydis stigma)" is the pistil and stigma of corn (Zea mays.L), which is in the shape of hair or filaments and is also called Yumixu (corn silk). Generally, it is called corn stigma. As recorded in ancient documents such as "Compendium of Materia Medica", the function of Yumichuxu is known to have medicinal effects when used in the treatment of urinary tract diseases, diuretics, blood coagulation, and adult disease-related diseases. Yumichuxu has traditionally been used as an edible raw material for folk remedies. Recently, with the increasing interest in flavonoid substances contained in corn stigma, academic research related to it has been actively carried out.

[0039] The above extract can be extracted using a polar solvent or / and a non-polar solvent.

[0040] The above polar solvent may include one or more selected from the group consisting of (i) water, (ii) alcohol (preferably methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, normal-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) DMFO (dimethyl-formamide), and (v) DMSO (dimethyl sulfoxide). The above non-polar solvent may include one or more selected from the group consisting of acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkanes, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1-pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, and THF.

[0041] More specifically, the extract may be extracted using water, an organic solvent, or a mixture thereof as a solvent, and according to a specific embodiment of the present invention, the extract of the present invention may be obtained by treating water with a new grain and / or a jade shovel.

[0042] The above organic solvent may include one or more solvents selected from the group consisting of lower alcohols having 1 to 6 carbon atoms (methanol, ethanol, propanol, butanol, etc.), hexane, acetone, ethyl acetate, chloropurum, and diethyl ether.

[0043] As used in this specification, the term 'extract' has the meaning commonly understood in the art as a crude extract, as described above, but in a broader sense, it also includes fractions obtained by further fractionating the extract. That is, the above-described grain extract includes not only that which is obtained using the extraction solvent described above, but also that which is obtained by additionally applying a purification process thereto. For example, fractions obtained through various additional purification methods, such as a fraction obtained by passing the above-described extract through an ultrafiltration membrane having a certain molecular weight cut-off value, or separation by various chromatographs (designed for separation based on size, charge, hydrophobicity, or affinity), are also included in the natural product extract of the present invention.

[0044] The extract used in the present invention can be prepared in a powder state by additional processes such as vacuum distillation and freeze-drying or spray-drying.

[0045] Specifically, the extract is preferably prepared by adding water, an organic solvent, or a mixture thereof to the fermented grain and / or jade plant in an amount of 5 to 50 times the weight of the fermented grain and / or jade plant, and more preferably by adding 10 to 30 times the weight, but is not limited thereto. The extraction temperature is preferably 50°C to 150°C, and more preferably 70°C to 120°C, but is not limited thereto. The extraction time is preferably 1 to 20 hours, and more preferably 2 to 8 hours, but is not limited thereto. Cold maceration, ultrasonic extraction, or reflux cooling extraction methods may all be used as extraction methods, but are not limited thereto. The number of extractions is preferably 1 to 5 times, and more preferably 2 to 3 times, but is not limited thereto. Additionally, the extract may be diluted, concentrated, or purified and dried after dilution or concentration for use.

[0046] In this specification, the term "containing as an active ingredient" means containing an amount sufficient to achieve the efficacy or activity of the following extracts of Shenqu and Yuchuxue. The present invention is a composition extracted from Shenqu and Yuchuxue, which are natural plant materials, and the quantitative upper limit of the Shenqu and Yuchuxue extracts included in the composition of the present invention may be selected and implemented by a person skilled in the art within an appropriate range.

[0047] The composition according to the present invention can exhibit significantly improved effects of reducing the time it takes to fall asleep and increasing the duration of sleep by using extracts of Singok and Okchokseoye together. Furthermore, as a natural product, it does not cause side effects such as cytotoxicity, tolerance, or dependence even with long-term use.

[0048] More specifically, the composition of the present invention can increase the expression levels of melatonin receptor genes MT1 and MT2, which regulate sleep and circadian rhythms.

[0049] According to one embodiment of the present invention, it was confirmed that when a new grain extract and a jade porridge extract are used in combination, melatonin receptor expression is significantly increased (Fig. 1).

[0050] In addition, the composition of the present invention can exhibit an excellent sleep-inducing effect.

[0051] According to one embodiment of the present invention, it was confirmed that when the Singok extract and the Okchokseoye extract are used in combination, compared to when the Singok extract and the Okchokseoye extract are used individually, a significantly superior effect of reducing the onset time and increasing the sleep time is shown (Fig. 2).

[0052] In addition, according to one embodiment of the present invention, when the weight change during the intake period was checked after orally administering the fermented rice extract of the present invention to 3-week-old rats for 7 days, no weight change was observed due to the administration of the fermented rice extract and the jade rhizome extract, confirming that there was no effect on growth inhibition (Fig. 3).

[0053] Pharmaceutical composition for the prevention or treatment of sleep disorders containing extracts of Singok and Okchokseoye as active ingredients

[0054] The composition of the present invention can be prepared as a pharmaceutical composition.

[0055] When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier.

[0056] According to a preferred embodiment of the present invention, the composition of the present invention may be a pharmaceutical composition comprising (a) a pharmaceutically effective amount of the extracts of the Shenqu and Yuchuxue of the present invention as described above; and (b) a pharmaceutically acceptable carrier. In this specification, the term "pharmaceutically effective amount" means an amount sufficient to achieve the efficacy or activity of the extracts of the Shenqu and Yuchuxue of the present invention as described above.

[0057] Pharmaceutically acceptable carriers are those commonly used in formulations and include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

[0058] The pharmaceutical composition of the present invention can be administered orally or parenterally.

[0059] Suitable dosages of the pharmaceutical composition of the present invention may be prescribed in various ways depending on factors such as the formulation method, mode of administration, patient's age, body weight, sex, pathological condition, food, time of administration, route of administration, excretion rate, and response sensitivity. The general dosage of the active ingredient included in the pharmaceutical composition of the present invention is within the range of 0.001 to 100 mg / kg / day for adults. Administration may be performed once a day or divided into several doses. However, the scope of the present invention is not limited by the above dosages.

[0060] The pharmaceutical composition of the present invention may be prepared in a unit volume form or contained in a multi-volume container by formulation using a pharmaceutically acceptable carrier and / or excipient, according to a method that can be easily carried out by a person skilled in the art to which the invention belongs. In this case, the formulation may be in the form of a solution, suspension, syrup, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, powder, granule, tablet, or capsule, and may additionally include a dispersant or a stabilizer.

[0061] A quasi-drug composition for preventing or improving sleep disorders, or a sleep aid, comprising extracts of Singok and Okchokseoye as active ingredients.

[0062] The composition of the present invention may be provided as a quasi-drug composition or a sleep aid.

[0063] The above-mentioned extracts of the new grain and jade porcelain may be added as is, used in combination with other ingredients of quasi-drugs, etc., and may be used appropriately according to conventional methods. The amount of the active ingredients can be appropriately determined according to the purpose of use (prevention, health, or therapeutic treatment). The above-mentioned quasi-drug composition may be used in the manufacture of disinfectants, shower foams, mouthwash, wet wipes, detergent soaps, hand washes, humidifier fillers, masks, ointments, or filter fillers, but is not limited thereto.

[0064] The aforementioned sleep aids refer to over-the-counter medications with sleep-inducing or sedative effects that can be purchased without a doctor's prescription, unlike sleeping pills.

[0065] Food composition for preventing or improving sleep disorders containing extracts of Singok and Okchokseoye as active ingredients

[0066] The composition of the present invention may be provided as a food composition or a health functional food composition. When a composition for the prevention, improvement, or treatment of sleep disorders containing the extracts of the fermented rice and *Okchokseoye* of the present invention as active ingredients is prepared as a food composition, it includes not only the fermented rice extract as an active ingredient but also ingredients that are typically added during food preparation, such as, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavorings. Examples of the carbohydrates mentioned above include monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, oligosaccharides, etc.; and polysaccharides, such as dextrin, cyclodextrin, etc., which are conventional sugars, and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As flavorings, natural flavorings [taumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)] and synthetic flavorings (saccharin, aspartame, etc.) may be used. For example, when the food composition of the present invention is manufactured as a drink, in addition to the natural product extract of the present invention, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, Eucommia ulmoides extract, jujube extract, licorice extract, etc. may be additionally included.

[0067] The formulation of the above food composition or health functional food composition can be in the form of powder, granule, pill, tablet, or capsule, as well as any form of general food or beverage.

[0068] There are no specific restrictions on the types of food mentioned above, and examples of food to which the substance may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and may include all food in the conventional sense.

[0069] Generally, when manufacturing food or beverages, the above-mentioned extracts of the fermented grain and the jade plant may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, per 100 parts by weight of the raw material. However, in the case of long-term consumption for the purpose of health and hygiene or health control, the above amount may be less than the above range, and furthermore, since the present invention uses natural substances, there is no problem in terms of safety, so it may be used in an amount greater than the above range.

[0070] The present invention will be described in more detail below through examples. These examples are intended solely to illustrate the invention more specifically, and it will be obvious to those skilled in the art that the scope of the invention is not limited by these examples.

[0071] Example 1. Preparation of Shengok extract and Jade porcelain extract

[0072] The Singok extract used in this invention was supplied by the Korea Plant Extract Bank of the Korea Research Institute of Biotechnology and Bioengineering and the College of Pharmacy at Kyung Hee University for use in experiments. The Singok extract of this invention is a crude drug sample prepared by mixing Singok (100 g) with 1 L of water and extracting it using a medicinal decoction machine at 100 ℃ for 2 hours and 30 minutes. The extracted substance was filtered using non-fluorescent cotton as filter paper and dried using a Vacuum Freeze Dryer (Biotron, Clean-vac 12) at -70 ℃ for 24 hours. The dried extract was stored as the original sample in a cold room at -4 ℃.

[0073] The corn silk extract used in this invention was supplied by the Korea Plant Extract Bank of the Korea Research Institute of Biotechnology and Bioengineering and used in the experiment. The corn silk extract of this invention is a herbal medicine sample prepared by mixing corn silk with 1 L of water and extracting it using a medicinal decoction machine at 100 ℃ for 2 hours and 30 minutes. The extracted substance was filtered using non-fluorescent cotton as filter paper and dried using a vacuum freeze dryer (Biotron, Clean-vac 12) at -70 ℃ for 24 hours. The dried extract was stored as the original sample in a cold room at -4 ℃.

[0074] Experimental Example 1. Confirmation of changes in melatonin receptor expression by treating nerve cells with Singok extract and Okchokseoye extract (Fig. 1)

[0075] Neurons isolated from the brains of 17.5-day-old white rat fetuses and cultured for 7 days were treated with a complex composition consisting of Singok extract (1 µg / ml) and Okchokseoye extract (1 µg / ml), and RNA extraction (isolation) was performed using Trizol 24 hours later. The extracted RNA was quantified, and 0.5 µg of cDNA was synthesized by RT-PCR. Changes in melatonin receptor expression were confirmed using PCR.

[0076] As a result, it was confirmed that when the Singok extract and the Okchokseoye extract were used in combination, melatonin receptor expression was significantly increased (Fig. 1).

[0077] Experimental Example 2. Sleep induction and sleep-promoting effects of Shenqu extract and Yuchuxue extract in experimental animals (Fig. 2)

[0078] 3-week-old ICR mice were used as experimental animals. Ten animals were prepared per group, comprising a negative control group (water intake only), a group administered with *Okchokseoye* extract alone, a group administered with *Singok* extract alone, and a group administered with both *Okchokseoye* and *Singok* extracts. 3-week-old mice were orally administered *Singok* extract (5 mg / kg) and / or *Okchokseoye* extract (5 mg / kg) for one week. After one week, sedation was induced in the experimental and control mice by intraperitoneal injection of 42 mg / kg of pentobarbital. After treatment with pentobarbital, if the rats were lying on their backs with their bellies exposed, they were considered to be asleep; if the rats changed their position to face their backs, they were considered to be fully awake. The onset time (sleep induction time) and duration of sleep were then measured.

[0079] As a result, it was confirmed that when the Singok extract and Okchokseoye extract were used in combination, compared to when the Singok extract and Okchokseoye extract were used individually, a significantly superior effect was shown in reducing the onset time and increasing the sleep duration (Fig. 2).

[0080] Experimental Example 3. Confirmation of body weight change after administration of Shenqu extract and Yuchuxue extract to experimental animals (Fig. 3)

[0081] Changes in body weight during the intake period were observed while administering drinking water, fermented rice extract, and / or *Okchokseoye* extract orally to 3-week-old white rats for 7 days. Since no changes in body weight were observed due to the administration of fermented rice extract and *Okchokseoye* extract, it was confirmed that there was no effect on growth inhibition (Fig. 3).

Claims

Claim 1 A pharmaceutical composition for the prevention or treatment of sleep disorders comprising extracts of Massa Medicata Fermentata and Maydis stigma as active ingredients, wherein the composition is characterized by reducing the time to fall asleep and increasing the duration of sleep. Claim 2 delete Claim 3 A pharmaceutical composition according to claim 1, characterized in that the composition increases melatonin receptor expression. Claim 4 A quasi-drug composition for preventing or improving sleep disorders comprising extracts of Massa Medicata Fermentata and Maydis stigma as active ingredients, wherein the composition is characterized by reducing the time to fall asleep and increasing the duration of sleep. Claim 5 A sleep aid comprising extracts of Massa Medicata Fermentata and Maydis stigma as active ingredients, wherein the aid is characterized by reducing the time to fall asleep and increasing the duration of sleep. Claim 6 A food composition for preventing or improving sleep disorders comprising extracts of Massa Medicata Fermentata and Maydis stigma as active ingredients, wherein the composition is characterized by reducing the time to fall asleep and increasing the duration of sleep.

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