KR102527256B1 - A composition for the prevention, improvement or treatment of sleep disorders or insomnia containing Glehnia littoralis extract - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating sleep disorder or insomnia, containing an extract of Glehnia littorali s as an active ingredient.
The gaetbangpung extract of the present invention is very effective in reducing elevation time, increasing sleep duration, and increasing non-REM sleep. In addition, since it is derived from the sea breeze, which is a natural product, there are no side effects such as cognitive impairment, tolerance or dependence even when used for a long time. Therefore, the composition for the prevention, improvement or treatment of sleep disorder comprising the extract of the present invention as an active ingredient is very useful for the preparation of competitive food compositions and pharmaceutical compositions.

Description

A composition for the prevention, improvement or treatment of sleep disorders or insomnia containing Glehnia littoralis extract}

The present invention relates to a composition for the prevention, improvement or treatment of sleep disorder or insomnia, containing an extract of sea bream as an active ingredient.

Sleep can be defined from various perspectives, but it is mainly defined as a state of immobility in which the ability to recognize and respond to the external environment is reversible, repetitive, and normally stopped. The sleep is achieved by brain activity, but is also deeply related to physiological changes in other body parts.

Sleep disorder is one of the common problems of modern people, and it is a very common disease that more than 20% of the population has experienced or suffers from. Such a sleep disorder refers to a state in which a person does not have a sound sleep, does not maintain arousal during the day despite having enough sleep, or has difficulty falling asleep or waking up due to a disturbed sleep rhythm. Mental problems are also a major cause, and it occurs due to excessive stress, anxiety, tension, and fear.

Sleep disorders can cause various personal and social problems, and cause learning disabilities, reduced performance, traffic accidents, safety accidents, emotional disorders, social adjustment disorders, dissatisfaction in marriage, and industrial accidents. In addition, if sleep disorders are not properly treated, existing medical, neurological, and psychiatric diseases may worsen or recovery may be delayed, and serious diseases such as myocardial infarction and stroke may result.

In order to treat these sleep disorders, chemical hypnotics are used that reversibly suppress the central nervous system to induce sleep and maintain the sleep state. Conventional sleeping pills have a central depressant action like an anesthetic, so they have a sedative action in a small amount and a sleeping action in a moderate dose, but a coma, paralysis, and respiratory suppression action in a large amount. Barbital-based drugs have low safety, and tolerance and dependence easily occur, and when they are stopped after long-term continuous use, there is a problem in that sleep disorders such as nightmares occur.

Recently, benzodiazepine-based drugs with low harmful effects and anti-anxiety effects have been used. Many drugs, including the benzodiazepines, bind to GABA _A receptors to exert pharmacological action, and when drugs or adjuvants bind to benzodiazepine sites, the affinity of GABA _A receptors for GABA is enhanced, and chloride ions are released into cells. By increasing the influx, it exhibits anxiolytic, convulsive, sedative, and sleep inducing and improving effects. The GABA _A receptor is a pentameric protein that forms a membrane ion channel, and is closely related to the regulation of sedation, sleep, anxiety, muscle tension, convulsions, and memory loss, through which GABA (gamma-aminobutyric acid) acts. . When these drugs are used for a long time, they are accompanied by side effects such as tolerance and dependence, and symptoms such as muscle relaxation, forgetfulness, lethargy, coma, coronary vasodilation, and myocardial muscle block appear. .

Therefore, in the case of long-term users and restrictive users of sleeping pills, the need for alternative means is increasing, and the demand for health functional foods for sleep enhancement is increasing.

KR 10-1875307 B KR 10-1820761 B

An object of the present invention is to provide a food composition capable of preventing or improving sleep disorder or insomnia by containing an extract of sea bream as an active ingredient.

In addition, another object of the present invention is to provide a pharmaceutical composition capable of preventing or treating sleep disorder or insomnia by containing an extract of sea bream as an active ingredient.

In addition, another object of the present invention is to provide a health functional food composition that can prevent or improve sleep disorder or insomnia by containing the extract of sea bream as an active ingredient.

To achieve the above object, the food composition for preventing or improving sleep disorder or insomnia of the present invention may contain Glehnia littoralis extract as an active ingredient.

The sea bream extract may be extracted with water, lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

The mixed solvent may be a 20 to 80% volume % methanol, ethanol, butanol or propanol aqueous solution, preferably a 60 to 80% ethanol aqueous solution.

The sea bream extract may be extracted at an extraction temperature of 65 to 95 ° C.

The sleep disorder or insomnia may be due to caffeine administration.

Prevention or treatment of the sleep disorder or insomnia may be for reducing the sleeping time, increasing the duration of sleep, or increasing nonrem sleep.

The dosage form of the food composition may be powder, granule, tablet, capsule or beverage.

The food composition may be a coffee beverage.

In addition, the pharmaceutical composition for preventing or treating sleep disorder or insomnia of the present invention for achieving the above other object may include a Glehnia littoralis extract as an active ingredient.

In addition, the health functional food composition for preventing or improving sleep disorder of the present invention for achieving another object described above may include a Glehnia littorali s extract as an active ingredient.

The gaetbangpung extract of the present invention is very effective in reducing elevation time, increasing sleep duration, and increasing non-REM sleep. In addition, since it is derived from the sea breeze, which is a natural product, there are no side effects such as cognitive impairment, tolerance or dependence even when used for a long time. Therefore, the composition for the prevention, improvement or treatment of sleep disorder comprising the extract of the present invention as an active ingredient is very useful for the preparation of competitive food compositions and pharmaceutical compositions.

Figure 1a is a graph showing the effect of each concentration of the sea bream extract (KS-093) on the elevation time of mice administered with pentobarbital sleep dose (45 mg / kg, ip), Figure 1b is pentobarbital This is a graph showing the effect of each concentration of sea bream extract (KS-093) on the sleep time of mice administered with a sleeping dose (45 mg/kg, ip) compared to that of diazepam, a representative sleeping pill. Control group (5% tween 80-saline 10 mL/kg), diazepam (2 mg/kg), and KS-093 (50, 100, 200, 300 mg/kg) were orally administered (po) and 45 minutes later pentobarbital was administered. Each graph represents the average value (meansㅁSEM, n=10). *** means that there is a significant difference at p<0.001 compared to the control group (Tukey's test). KS-093 is an abbreviation for sea bream extract.
Figure 2a is a graph showing typical examples of electroencephalogram (EEG), electromyography (EMG), and hypnograms of a single mouse for each group measured for sleep structure analysis. Figure 2b is a graph showing the effect of each concentration of sea bream extract (KS-093) on the elevation time of mice through sleep structure analysis compared to zolpidem, a commercially available sleeping pill, Figure 2c is non-REM sleep (NREMS) This is a graph showing the effect of each concentration of sea bream extract (KS-093) on the increasing effect compared to zolpidem, a commercially available sleeping pill. Vehicle represents the control group, * indicates a significant difference at p<0.05 compared to the control group, and ** indicates a significant difference at p<0.01 compared to the control group ( t -test). KS-093 is an abbreviation of seaweed extract, Wake is an abbreviation of wakefulness, and NREMS and REMS are abbreviations of non-rapid eye movement sleep and rapid eye movement sleep, respectively. Also, EEG and EMG are abbreviations of electroencephalogram and electromyogram, respectively.
Figure 3 is an example of the change in non-REM sleep (NREMS), REM sleep (REMS) and wakefulness (Wake) for each time period for 24 hours (KS-093, 300 mg / kg) and zolpidem (zolpidem, It is a graph showing the effect of 10 mg/kg). Vehicle represents the control group, * indicates a significant difference at p<0.05 compared to the control group, and ** indicates a significant difference at p<0.01 compared to the control group ( t -test). KS-093 is an abbreviation of seaweed extract, Wake is an abbreviation of wakefulness, and NREMS and REMS are abbreviations of non-rapid eye movement sleep and rapid eye movement sleep, respectively.
Figure 4 shows the mean duration, number of bouts, and number of stage transitions for detailed water surface structure analysis in Example 1 for the extract (KS-093, 300 mg/kg) and zolpidem (zolpidem, 10 mg/kg). ) is a graph showing the effect of Vehicle represents the control group, * indicates a significant difference at p<0.05 compared to the control group, and ** indicates a significant difference at p<0.01 compared to the control group ( t -test). KS-093 is an abbreviation for seaweed extract, Wake (or W) is an abbreviation for wakefulness, and NREMS (or N) and REMS (or R) are an abbreviation for non-rapid eye movement sleep and rapid eye movement sleep, respectively.
Figure 5 is a graph showing the number of bouts by duration of sea bream extract (300 mg / kg) and zolpidem (10 mg / kg), and the electroencephalogram (EEG) power density and delta activity in non-REM sleep. . Vehicle represents the control group, * indicates a significant difference at p<0.05 compared to the control group, and ** indicates a significant difference at p<0.01 compared to the control group ( t -test). KS-093 is an abbreviation for sea bream extract, and NREMS is an abbreviation for non-rapid eye movement sleep.
Figure 6a is a graph showing the effect of each concentration of the sea bream extract (KS-093) of Example 1 on the elevation time through the pentobarbital sleep induction experiment in the caffeine-induced sleep disorder mouse model, Figure 6b is caffeine-induced sleep disorder It is a graph showing the effect of each concentration of sea bream extract (KS-093) on sleep time through a pentobarbital sleep induction experiment in a mouse model. A general control group (CON; 5% tween 80-saline 10 mL/kg), caffeine alone, caffeine and examples, caffeine and zolpidem were orally administered (po). Each graph represents the average value (meansㅁSEM, n=10). # and ## mean that there is a significant difference at p<0.05 and p<0.01, respectively compared to the general control group, and *, **, and *** are respectively p<0.05, p compared to the caffeine alone administration group <0.01, and p<0.001 means that there is a significant difference (Tukey's test). CON represents the general control group, KS-093 is an abbreviation of sea bream extract, and Ca and ZPD are abbreviations of caffeine and zolpidem, respectively.
Figure 7a shows typical examples of brain waves (EEG), electromyography (EMG), and hypnograms of a single mouse for each group in a caffeine-induced sleep disorder mouse model, and Figure 7b is a caffeine-induced sleep disorder mouse model, elevation time, Non-REM sleep (NREMS) time, it is a graph showing the effect of the sea breeze extract (KS-093) of the examples for the REM sleep (REMS) time. General control (Vehicle; 5% tween 80-saline 10 mL/kg), caffeine (25 mg/kg), caffeine (25 mg/kg) + ZPD (10 mg/kg) and caffeine (25 mg/kg) + run The extract (300 mg/kg) of Example 1 was orally administered (po). Each graph represents the average value (meansㅁSEM, n=7). ** means there is a significant difference at p <0.01 compared to the control group, ## means there is a significant difference at p <0.01 compared to the caffeine alone administration group (t-test). Vehicle represents the control group, KS-093 is an abbreviation of sea bream extract, and Wake, NREMS, and REMS are abbreviations of wakefulness, non-rapid eye movement sleep, and rapid eye movement sleep, respectively. Also, EEG and EMG are abbreviations of electroencephalogram and electromyogram, respectively.

The present invention relates to a composition capable of preventing, improving, or treating sleep disorder or insomnia by containing an extract of sea bream as an active ingredient.

The sleep disorder or insomnia may be caused by various causes. The sleep disorder or insomnia may be due to caffeine administration, and specifically may be due to consumption of caffeine-containing foods such as coffee, high-caffeine energy drinks, cola, green tea, black tea, and cocoa, but is not limited thereto.

Prevention, improvement or treatment of the sleep disorder or insomnia may be an effect of reducing sleep latency, an effect of increasing sleep duration, or an effect of increasing nonrem sleep, but is not limited thereto.

In addition, the sleep disorder is disrupted sleep caused by a number of causes, including dysfunctional sleep mechanisms, abnormal physiological functions during sleep, abnormalities in the biological clock, and sleep disorders induced by factors unrelated to the sleep process. It means a pattern, and can be, for example, insomnia. The insomnia may include middle-of-the-night insomnia, late night insomnia, prolonged waking insomnia after the onset of sleep, sleep maintenance insomnia, and subsequent insomnia after waking up at night.

In the following examples, it was confirmed that sea bream extract showed almost the same level or improved effect of reducing sleep time and increasing sleep duration compared to zolpidem or diazepam, which were conventionally used as sleeping pills, and increased non-REM sleep time. . Therefore, sea bream extract can be used as an active ingredient of a composition for preventing, improving or treating sleep disorders. Unlike conventional sleeping pills, sea bream extract is a food-approved, harmless ingredient to the human body that has no side effects and has excellent sleep-inducing and sleep-prolonging effects, so it can be usefully used to prevent, improve, or treat sleep disorders. there is.

Hereinafter, the present invention will be described in detail.

The composition for preventing, improving, or treating sleep disorders of the present invention contains the extract of sea bream as an active ingredient.

Gaetbangpung is a perennial plant belonging to the family Umbelliferae, and is a medicinal plant that grows wild in sandy soil along the coast of Korea and is distributed in Japan, Manchuria, and China. Its roots are called northern ginseng (北沙蔘), binbang wind (濱防wind), or liberation wind (海防風), and are said to have positive effects on yin, clearing the lungs, expectoration, and retardation. It has been traditionally used as an anti-inflammatory, antitussive expectorant and digestive contracture.

On the other hand, there is a windbreak ( ledebouriella seseloides ) as a plant with a similar name to the windbreak ( Glehnia littorali s ). very important in doing Specifically, the windshield is effective for all wind symptoms such as external headache, chills, fever, systemic pain, and sore throat, and is effective for all wind symptoms such as wind and damp dampness, tetanus, muscle spasms, paraplegia due to paralysis, paralysis, It is used for skin itching and ringworm, and pharmacological actions have been reported for antipyretic, anti-inflammatory, antispasmodic, immune activation, anti-allergy, anti-ulcer, antibacterial, and suppression of skin improving bacteria.

In addition, there is Sikbangpung as a plant with a similar name to Gaetbangpung. In the case of Sikbangpung, it is called 'Bangpungnamul' and is more popular for food than medicinal use.

The windbreak, windbreak, and windbreak have similar names, but are different plants with different scientific names, habitats and shapes, different genes, and different index components. In particular, the windbreak, windbreak, and windbreak show different medicinal effects due to differences in index components or physiologically active components. Specifically, it was confirmed that imperatorin and panaxydiol, which are index components contained in the windbreak, were not contained in the windbreak and the windbreak (refer to "Discrimination of windbreak, windbreak, and windbreak", Korea Food and Drug Safety Evaluation Institute).

The windbreak of the present invention may be one or more above-ground parts, rhizomes, or roots selected from flowers, stems, leaves, immature fruits and fruits, and preferably one selected from flowers, stems, leaves, immature fruits and fruits. It may be more than one species of aerial parts, more preferably one or more kinds of aerial parts selected from leaves and stems. Gaetbangpung, which was previously used as a medicinal material, means the root of Gaetbangpung, and items listed in the "Korean Pharmacopoeia (KP)" are also listed as the root of Gaetbangpung. However, in the present invention, it is more preferable in terms of sleep effect to use the aerial part of the sea breeze as a raw material.

The sea breeze is mixed with the extraction solvent at a weight ratio of 1: 10 to 30, preferably 1: 15 to 25, more preferably 1: 18 to 22, and the temperature is 65 to 95 ℃, preferably 70 to 90 ℃, more Preferably, the extract is prepared by performing extraction at 75 to 85 ° C. for 1 to 10 hours, preferably 1 to 5 hours, and then concentrated under reduced pressure. When the weight ratio of the sea breeze and the extraction solvent is out of the above range, the active ingredient of the sea breeze may be extracted in a small amount in the extract.

The extraction solvent for extracting each extract is water, lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. Examples of the lower alcohol include 20 to 80% methanol, ethanol, butanol or propanol.

The extraction solvent is not particularly limited, but the extract extracted with 60 to 80% aqueous ethanol solution preferably acts to prevent, improve or treat sleep disorders or insomnia.

The extract of the sea bream may be a fraction obtained by re-fractionating an extract obtained by extracting the sea bream with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof with a second organic solvent. Preferably, the bay wind extract may be a fraction obtained by re-fractionating the ethanol extract of sea bay wind with hexane, ethyl acetate, butanol or water.

The term "extract" used herein while referring to the sea breeze includes not only the crude extract obtained by treating the extraction solvent, but also the processed product of the sea breeze extract. For example, sea bream extract can be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze drying or spray drying.

In a broad sense, the extract of the present invention also has a meaning that includes a sea breeze processed product formulated to be administered to animals, such as a sea breeze powder. Although the experiment was conducted with the sea breeze in the present invention, it will be expected by those skilled in the art that the desired effect can be achieved even in the same form as the sea breeze.

On the other hand, in the present specification, the term "contained as an active ingredient" means that it contains a sufficient amount to achieve the efficacy or activity of the sea chestnut extract. The daily dose of the lobster extract of the present invention may be 10 to 1,000 mg/kg, preferably 20 to 500 mg/kg, and more preferably 50 to 500 mg/kg, It may be more preferably 100 to 500 mg/kg, more preferably 100 to 300 mg/kg or 200 to 500 mg/kg, more preferably 200 to 400 mg/kg, and most preferably 200 to 400 mg/kg. It may be preferably 200 to 300 mg/kg. If the dosage of the sea bream extract of the present invention is less than the lower limit, the sleep effect may not appear as desired, and if it exceeds the upper limit, the sleep effect may not increase as much as the dosage increases. As a natural product, there is no side effect on the human body even when administered in excess, so the upper limit of the amount of the extract contained in the composition of the present invention can be selected and carried out by those skilled in the art within an appropriate range.

In addition, the gaetbangpung extract of the present invention shows a significant sleep effect only at a concentration of 500 mg / kg or more of existing plant extracts such as windbreak extract, Ecklonia cava extract, or rice bran extract, respectively. May have a sleep effect.

In a specific embodiment of the present invention, in a pentobarbital sleep induction experiment, as a result of administering the sea bream extract of the present invention to a mouse model, the effect of increasing sleep duration or non-REM sleep was shown, resulting in sleep disorders or insomnia. It was specifically confirmed that there is an improvement effect (see FIGS. 1 to 5). In addition, as a result of administering the sea bream extract of the present invention to a mouse model having sleep disorders due to caffeine addiction, it was specifically confirmed that there is an effect of improving sleep disorders caused by caffeine administration (see FIGS. 6 to 7). This suggests that the sea bream extract of the present invention can be usefully used for preventing, improving or treating sleep disorders or insomnia.

The term "prevention" of the present invention means anything that suppresses or delays the sleep disorder or insomnia.

The term "treatment" of the present invention, unless otherwise stated, means reversing, alleviating, inhibiting the progression of, or preventing the symptoms of the sleep disorder or insomnia.

The term "improvement" of the present invention means at least a decrease in the parameters related to the condition to be treated, for example, the severity of symptoms, by administration of a composition comprising the extract of the present invention.

The food composition according to the present invention may be formulated into a powder, granule, tablet, capsule, etc. using a food-appropriate and physiologically-acceptable auxiliary agent and used as a functional food. As the adjuvant, excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, lubricants, or flavoring agents may be used.

In addition, the food composition according to the present invention may be, for example, beverages, alcoholic beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, chewing gum, ice cream, and the like. Preferably, the food composition of the present invention may be a coffee beverage.

The food composition of the present invention may include ingredients that are commonly added during food preparation, as well as sea bream extract as an active ingredient, and include, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. . Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides such as conventional sugars such as dextrins and cyclodextrins and sugar alcohols such as xylitol, sorbitol and erythritol. As flavoring agents, natural flavoring agents [thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made into drinks and beverages, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be further included in addition to the seaweed extract of the present invention. . The dosage form of the food composition may be powder, granule, tablet, capsule or beverage.

The content of the sea bream extract in the food composition is 0.001 to 5% by weight, preferably 0.001 to 1% by weight, more preferably 0.001 to 0.5% by weight, more preferably 0.002 to 0.3% by weight, still more preferably 0.005 to 0.3% by weight, more preferably 0.01 to 0.2% by weight, more preferably 0.02 to 0.1% by weight.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of sleep disorders containing the extract of sea bream as an active ingredient.

The pharmaceutical composition of the present invention can be prepared using pharmaceutically suitable and physiologically acceptable adjuvants in addition to the above active ingredients, and the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, and lubricants. agents or flavoring agents may be used.

The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients for administration.

Formulations of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

In compositions formulated as liquid solutions, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare formulations for injections such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.

Furthermore, using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field, it can be preferably formulated according to each disease or component.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.

The suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, sex, medical condition, food, administration time, administration route, excretion rate and reaction sensitivity, usually This allows the skilled physician to readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention may be 0.001-10 g/kg.

The pharmaceutical composition of the present invention may be prepared in a unit dose form by formulation using a pharmaceutically acceptable carrier and/or excipient, or prepared by putting it into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally contain a dispersing agent or stabilizer.

In addition, the present invention provides a health functional food composition for the prevention, improvement or treatment of sleep disorders, comprising the extract of sea bream as an active ingredient. Health functional food refers to a food made by adding turmeric extract to various food materials, encapsulating, powdering, or suspension. As a raw material, it has the advantage of not having side effects that may occur when taking drugs for a long time. The health functional food of the present invention obtained in this way is very useful because it can be consumed on a daily basis. The addition amount of turmeric extract in such a health functional food cannot be uniformly defined depending on the type of target health functional food, but it can be added within a range that does not impair the original taste of the food. It ranges from 0.01 to 50% by weight, preferably from 0.1 to 20% by weight. In addition, in the case of health functional foods in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a powder, granule, tablet, capsule or beverage.

In addition, the present invention provides a use of the extract of the sea bream for the manufacture of a medicine or food for preventing, improving or treating sleep disorders. As described above, sea bream extract can be used for the prevention, improvement or treatment of sleep disorders or insomnia.

In addition, the present invention provides a method for preventing, improving or treating sleep disorder or insomnia, which comprises administering an effective amount of an effective amount of an extract to a mammal.

As used herein, the term "mammal" refers to a mammal that is a subject of treatment, observation or experimentation, and preferably refers to a human.

As used herein, the term "effective amount" means an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, which is considered by a researcher, veterinarian, physician or other clinician, which is An amount that induces relief of the symptoms of a disease or disorder is included. The effective amount and frequency of administration of the active ingredient of the present invention can be varied depending on the desired effect. Therefore, the optimal dose to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of the active ingredient and other ingredients contained in the composition, the type of formulation, and the patient's age, weight, and general health Condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, can be adjusted according to various factors including drugs used simultaneously. In the prevention, improvement or treatment method of the present invention, in the case of adults, it is preferable to administer the extract of sea bream at a dose of 0.001 g/kg to 10 g/kg when administered once to several times a day.

In the treatment method of the present invention, the composition containing the extract of sea bream as an active ingredient is conventionally administered through oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. can be administered with

Hereinafter, a composition for preventing, improving, or treating sleep disorder or insomnia, including the extract of sea bream according to the present invention as an active ingredient, will be described in detail with Examples and Comparative Examples.

<Example>

Example 1. Sea breeze ethanol extract (KS-093)

After mixing the freeze-dried ground parts (leaves and stems) of domestic sphagnum japonica with a 70% aqueous ethanol solution at a weight ratio of 1:20, extraction was performed at 80 ° C. for 3 hours to obtain an ethanol extract of sphagnum sphagnum. The obtained extract was used after being pulverized by lyophilization through filtration and concentration under reduced pressure.

<Test method>

laboratory animals

ICR mice (18-22 g, male) and C57BL/6N mice (28-30 g, male) were purchased from Coretech Co., Ltd. (Pyeongtaek, Gyeonggi-do) and used in the experiment after adapting to the experimental animal breeding box for a week. . Breeding of the animals was carried out under the conditions of temperature 23ㅁ 1℃, humidity 55ㅁ 5%, light-dark cycle (light: 7:00 AM-7:00 PM), illumination intensity 3000 Lux, and feed and drinking water were freely fed. All animals were managed according to the guidelines for use of laboratory animals of the Korea Food Research Institutional Animal Care and Use Committee (KFRI-IACUC).

Pentobarbital-induced sleep test

The pentobarbital sleep induction experiment was conducted within a certain time between 1:00 pm and 5:00 pm, and 10 mice per group (n = 10) were used after fasting for 24 hours before the experiment. All samples were prepared using 5% tween 80-saline solution and orally administered (p.o.) to mice 45 minutes before administration of pentobarbital. The general control group was treated with 5% tween 80-saline solution at a concentration of 10 mg/kg, and diazepam (Myeongin Pharmaceutical Co., Ltd.) was used as a positive control drug to compare the sleep enhancing effect of the extract as a representative sleeping pill. Pentobarbital (Hanlim Pharmaceutical Co., Ltd.) was administered through intraperitoneal injection (i.p.) at a concentration of 45 mg/kg (hypnotic dosage) according to the experimental design. After pentobarbital treatment, each object was moved to an independent space to measure sleep latency and sleep duration. The elevation time was set to the elapsed time until the righting reflex was lost for 1 minute or more after intraperitoneal injection of pentobarbital, and the sleep time was set to the time until the righting reflex was restored again. Mice that did not show sleep behavior even after 10 minutes after pentobarbital administration were excluded from the experiment.

Sleep structure analysis

After adapting the C57BL/6N mice for 1 week, electrode insertion was performed to measure the EEG and electromyogram (EMG). Mice were anesthetized with pentobarbital (50 mg/kg, i.p.) and head-fixed in a stereotaxic instrument. After incising the head subcutaneous connective tissue, a Mouse EEG/EMG Headmount (Pinnacle Technology Inc, Oregon, USA) was inserted for EEG and EMG measurement. After fixation with dental cement, disinfection of the surgical site and administration of antibiotics were performed for 3 days to prevent inflammation caused by surgery, and a 7-day recovery period was allowed. In order to adapt to the EEG measurement environment, the recording device was connected 4 days before the measurement to induce adaptation to this experimental process. EEG and EMG were measured for 24 hours from 17:00 using a PAL-8200 series (Pinnacle Technology Inc, Oregon, USA) after stabilization for 5 minutes after oral administration of the sample. The sampling rate of EEG and EMG was set to 200 Hz (epoch time: 10 s), and the data was recorded by setting the filter area of 0.1-25 Hz for EEG and 10-100 Hz for EMG. The sleep structure analysis was performed by the fast Fourier transform (FFT) algorithm, and the SleepSign program (Ver. 3.0, Kissei Comtec, Nagono, Japan) was used. The analysis results were divided into wake (wakefulness), REMS (rapid eye movement sleep, theta band: 6-10 Hz), and NREMS (non-rapid eye movement sleep, delta band: 0.65-4 Hz), and sleep latency ( Elevation time) was set as the time required for 10-second epoch units of NREM sleep to appear more than 12 consecutively.

<Test Example>

Test Example 1: Pentobarbital sleep induction experiment using the example of sea bream extract (KS-093)

Through a pentobarbital sleep induction experiment, it was attempted to confirm what kind of sleep effect the sea bream extract (KS-093) of Example 1 exhibits. To this end, the mice were prepared by dividing them into 6 groups of 10 mice per group. The general control group was administered with 5% tween 80-saline, and after oral administration (p.o.) of the extract (KS-093) of Example 1 at concentrations of 50, 100, 200 and 300 mg/kg, pentobarbital (45 The sleep induction effect by mg/kg, i.p.) was analyzed.

As a result, the sea bream extract (KS-093) of Example 1 showed a significant increase in sleep duration at concentrations of 200 mg/kg and 300 mg/kg, which are relatively low doses for a plant extract (see FIG. 1 ).

Test Example 2: Water surface structure analysis using the example of sea bream extract (KS-093)

In order to evaluate the amount and quality of sleep of the sea bream extract (KS-093) of Example 1, the sleep structure of mice was analyzed. For this purpose, 4 groups of mice, 8 mice in each group, were prepared. In addition, it was intended to compare the sleeping effect of the present invention's sea bream extract (KS-093) by concentration and the efficacy with zolpidem, a commercially available sleeping pill.

As a result of the sleep structure analysis, the sea bream extract (KS-093) of the present invention increased nonrem sleep in a concentration-dependent manner, and significantly reduced the elevation time at all concentrations. In addition, when 300 mg/kg of sea bream extract (KS-093) was administered, it showed a sleep effect similar to that of zolpidem (10 mg/kg). On the other hand, no change in REM sleep was observed in all experimental groups (see FIGS. 2 b and c).

In addition, after oral administration of the sea bream extract (KS-093, 300 mg/kg) and zolpidem (zolpidem 10 mg/kg) of Example 1, each hourly wake and NREM while measuring the EEG of C57BL/6N mice , and changes in REM sleep time are shown in FIG. Referring to FIG. 3, sea bream extract (KS-093) showed a significant increase in NREM sleep for the first 2 hours after oral administration (see FIG. 3a), and zolpidem, a positive control group, was better than the control group (Vehicle). There was a significant increase in NREM sleep for 5 hours (see Fig. 3b). From these results, it can be seen that marigold extract (KS-093) induces natural sleep after exhibiting a sleep-enhancing effect at the beginning of sleep, whereas zolpidem, a sleeping pill, has a sleep-promoting effect like KS-093. Although it showed a sleep enhancing effect at the beginning, it was confirmed that the effect lasted for an excessively long time, causing typical side effects of sleeping pills.

In addition, in order to more specifically identify changes in the sleep-wake profile of mice caused by oral administration of sea bream extract (KS-093, 300 mg/kg) and zolpidem (zolpidem, 10 mg/kg), mean duration, number of blows, stage transition number and episode number were analyzed. The mean duration of wake was significantly decreased by oral administration of sea bream extract (KS-093) and zolpidem, and there was no change in NREMS and REMS (see Fig. 4a).

In addition, sea bream extract (KS-093) and zolpidem significantly increased the number of bouts of NREM and Wake (see Fig. 4b), and the number of bouts from Wake to NREMS and from NREMS to Wake was also significant. increased progressively (see Fig. 4c). In addition, the number of episodes in which NREMS was maintained for 10-30 seconds and 10-120 seconds, respectively, was significantly increased by the use of sea bream extract (KS-093) and zolpidem (see Fig. 5a). This tendency means that the administration of sea bream extract (KS-093) and zolpidem interfered with the maintenance of wakefulness of the mice, which in turn improved sleep.

In addition, changes in delta activity during non-REM sleep can be said to be a physiological indicator of sleep quality and depth [Behav. Brain Res. 210, 5456. Huang et al., 2010]. It has also been reported that zolpidem increases non-REM sleep and decreases delta power during non-REM sleep [PNAS. 101, 3674-3679. Kopp et al., 2004]. These typical characteristics of zolpidem were also evident in this study. As expected, zolpidem significantly (p<0.01) reduced the delta activity during non-REM sleep, and no significant change was observed in the delta activity of the sea breeze extract (KS-093) (see FIG. 5b). These results indicate that the sea bream extract (KS-093) increases NREM sleep without affecting physiological sleep.

An ideal sleeping agent is a drug that has fast awakening time, sustained sleep maintenance, and does not change physiological sleep [Sleep. 31, 259-270. Alexandre et al., 2008]. Therefore, it is believed that the sea bream extract (KS-093) of the present invention can promote natural sleep more safely than BDZ and non-BDZ drugs with side effects such as zolpidem.

Test Example 3: Improvement effect of sleep disorder or insomnia due to caffeine administration

Test Example 3-1: Pentobarbital sleep induction experiment

Through the pentobarbital sleep induction experiment, it was intended to confirm the effect of the extracts of the examples on the sleep disorder or insomnia of mice induced by caffeine. To this end, mice were prepared by dividing into 6 groups of 10 mice in each group. The general control group (Vehicle) was administered with 5% tween 80-saline, caffeine 50 mg/kg alone administration group, caffeine 50 mg/kg + seaweed extract of Example 1 (KS-093) 100 mg/kg administration group, caffeine 50 mg/kg + 200 mg/kg administration group of the sea breeze extract (KS-093) of Example 1, caffeine 50 mg/kg + 300 mg/kg administration group of the sea breeze extract (KS-093) of Example 1, caffeine 50 mg/kg It was divided into kg + zolpidem 10 mg/kg administration group, and after oral administration (p.o.) at each concentration, the sleep induction effect by pentobarbital (45 mg/kg, i.p.) was analyzed. Caffeine was used as a negative control drug for a sleep disorder mouse model.

As a result, the sea bream extract (KS-093) of Example 1 significantly reduced the elevation time increased due to caffeine administration (see FIG. 6a), and 100 mg/kg, 200 mg/kg and 300 mg/kg of concentration showed a significant increase in sleep duration (see Fig. 6b). This indicates that the sea bream extract (KS-093) of the present invention has an effect of improving sleep disorder or insomnia caused by caffeine administration.

Test Example 3-2: Sleep structure analysis

In order to evaluate the quantity and quality of sleep of the sea bream extract (KS-093) of Example 1, the sleep structure of mice was analyzed. To this end, the mice were prepared by dividing them into 3 groups of 7 mice per group. The general control group (Vehicle) was administered with 5% tween 80-saline, 25 mg/kg caffeine alone administration group, Example 1's seaweed extract (KS-093) 300 mg/kg + caffeine 25 mg/kg administration group, ZPD ( 10 mg/kg) + caffeine 25 mg/kg administration group.

Looking at the hypnograms of Figure 7a, the caffeine alone administration group showed a very long wake time (Wake) compared to the general control group (Vehicle), and the non-REM sleep (NREMS) time decreased. When compared, it can be seen that there is no significant difference between wake time and non-REM sleep time (NREMS). More clearly, looking at Figure 7b, the caffeine alone administration group significantly increased the elevation time significantly (p <0.01) compared to the general control group (Vehicle), nonrem sleep time was reduced by about 56%. However, the caffeine + marigold extract (KS-093) administration group and the caffeine + zolpidem (ZPD) administration group showed similarity to the general control group in terms of both hypnotic time and NREM sleep time. From this, it can be seen that the sea bream extract (KS-093) of the present invention has an effect of improving sleep disorder or insomnia caused by caffeine, that is, an effect of suppressing arousal caused by caffeine.

Hereinafter, formulation examples of compositions containing the extract of the present invention will be described, but the present invention is not intended to limit them, but only to be specifically described.

Formulation Example 1. Preparation of powder

300 mg of extract powder obtained in Example 1

Lactose 100 mg

Talc 10 mg

A powder is prepared by mixing the above ingredients and filling them in an airtight bag.

Formulation Example 2. Preparation of tablets

300 mg of extract powder obtained in Example 1

Corn Starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet manufacturing method.

Formulation Example 3. Preparation of capsule formulation

200 mg of extract powder obtained in Example 1

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium stearate 0.2 mg

Capsules are prepared by mixing the above ingredients and filling them into gelatin capsules according to a conventional capsule preparation method.

Formulation Example 4. Preparation of Injections

600 mg of extract powder obtained in Example 1

Mannitol 180 mg

Sterile Distilled Water for Injection 2974 mg

Na ₂ HPO ₄ , 12H ₂ O 26 mg

It is prepared with the above component content per 1 ampoule according to the conventional method for preparing injections.

Formulation Example 5. Preparation of liquid formulation

2 g of extract powder obtained in Example 1

Isomerized sugar 10 g

5 g mannitol

Appropriate amount of purified water

According to the conventional liquid formulation manufacturing method, each component is dissolved in purified water, lemon flavor is added in an appropriate amount, the above components are mixed, and then purified water is added to adjust the total amount to 100g, and then filled into a brown bottle to be sterilized. to prepare a liquid.

Formulation Example 6. Preparation of granules

1,000 mg of extract powder obtained in Example 1

Appropriate amount of vitamin mixture

Vitamin A Acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

Folic acid 50 μg

Calcium Pantothenate 0.5 mg

Appropriate amount of mineral mixture

Ferrous sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium Carbonate 25.3 mg

Potassium Phosphate Monobasic 15 mg

Dibasic Calcium Phosphate 55 mg

Potassium citrate 90 mg

Calcium Carbonate 100 mg

Magnesium Chloride 24.8 mg

Although the composition ratio of the above vitamin and mineral mixture was prepared by mixing ingredients suitable for granules in a preferred embodiment, the mixing ratio may be arbitrarily modified, and after mixing the above ingredients according to a conventional granule manufacturing method, It can be prepared and used for preparing a health functional food composition according to a conventional method.

Formulation Example 7. Manufacturing of functional beverages

1,000 mg of extract powder obtained in Example 1

Citric Acid 1,000 mg

100 g of oligosaccharides

2 g plum concentrate

1 g of taurine

Add purified water to total 900 mL

After mixing the above ingredients according to the usual health drink manufacturing method, stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered and collected in a sterilized 2 L container, sealed and sterilized, and then refrigerated. It is used for preparing the functional beverage composition of the present invention.

Although the composition ratio is a mixture of ingredients suitable for a relatively favorite beverage in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the class of demand, the country of demand, and the purpose of use.

Although the present invention has been described in terms of the preferred embodiments mentioned above, various modifications and variations are possible without departing from the spirit and scope of the invention. The appended claims also cover such modifications and variations as fall within the subject matter of this invention.

Claims (16)

A food composition for preventing or improving sleep disorder or insomnia using Glehnia littorali s aboveground extract as an active ingredient,
The aerial part is at least one selected from the leaves and stems of the sea breeze,
The sleep disorder or insomnia is a food composition for preventing or improving sleep disorders or insomnia, characterized in that at least one selected from the sleeping disorder that increases the sleeping time and sleep disorder that reduces nonrem sleep time. According to claim 1,
The aerial part extract of the sea bream is a food composition for preventing or improving sleep disorders or insomnia, characterized in that extracted with water, lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. According to claim 2,
The mixed solvent is a food composition for preventing or improving sleep disorders or insomnia, characterized in that 20 to 80% by volume of methanol, ethanol, butanol or propanol aqueous solution. According to claim 2,
The mixed solvent is a food composition for preventing or improving sleep disorders or insomnia, characterized in that 60 to 80% by volume of ethanol aqueous solution. According to claim 1,
The extract of the aerial part of the sea breeze is a food composition for preventing or improving sleep disorders or insomnia, characterized in that extracted at an extraction temperature of 65 to 95 ℃. delete delete According to claim 1,
The formulation of the food composition is a food composition for preventing or improving sleep disorders or insomnia, characterized in that the powder, granules, tablets, capsules or drinks. delete A pharmaceutical composition for the prevention or treatment of sleep disorder or insomnia, comprising an extract of the aerial part of Glehnia littorali s as an active ingredient,
The aerial part is at least one selected from the leaves and stems of the sea breeze,
The sleep disorder or insomnia is a pharmaceutical composition for preventing or treating sleep disorders or insomnia, characterized in that at least one selected from the sleeping disorder that increases the sleeping time and sleep disorder that reduces the non-REM sleep time. According to claim 10,
The extract of the aerial part of the sea bream is a pharmaceutical composition for preventing or treating sleep disorders or insomnia, characterized in that extracted with water, lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. According to claim 11,
The mixed solvent is a pharmaceutical composition for preventing or treating sleep disorders or insomnia, characterized in that 20 to 80% by volume of methanol, ethanol, butanol or propanol aqueous solution. According to claim 11,
The mixed solvent is a pharmaceutical composition for preventing or treating sleep disorders or insomnia, characterized in that 60 to 80% by volume of ethanol aqueous solution. According to claim 10,
The pharmaceutical composition for preventing or treating sleep disorder or insomnia, characterized in that the extract of the aerial part of the sea bream is extracted at an extraction temperature of 65 to 95 ° C. delete A health functional food composition for preventing or improving sleep disorder or insomnia using Glehnia littorali s aerial part extract as an active ingredient,
The aerial part is at least one selected from the leaves and stems of the sea breeze,
The sleep disorder or insomnia is a health functional food composition for preventing or improving sleep disorder or insomnia, characterized in that at least one selected from the sleep disorder in which the sleeping time is increased and the sleep disorder in which the non-REM sleep time is reduced.

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