KR20210138224A - Composition comprising Curcuma longa extract for the prevention, improvement or treatment of diseases caused by caffeinism - Google Patents

Abstract

The present invention relates to a composition for prevention, improvement or treatment of diseases caused by caffeinism that comprises a turmeric extract as an active ingredient. A composition comprising curcuma longa extract as an active ingredient according to the present invention is non-toxic, effectively improves sleep disorders caused by caffeinism, inhibits central nervous system excitation, has an excellent effect of preventing, improving, or treating diseases caused by caffeinism, and can be usefully used in the manufacture of competitive foods and pharmaceuticals.

Description

Composition comprising Curcuma longa extract for the prevention, improvement or treatment of diseases caused by caffeinism, comprising a turmeric extract as an active ingredient

The present invention relates to a composition for preventing, improving or treating diseases caused by caffeine poisoning, comprising a turmeric extract as an active ingredient.

According to westernized eating habits and busy lifestyles, modern people consume various types of beverages, and the trend of westernization in food selection criteria is also increasing, and consumption of beverages containing a lot of caffeine is increasing day by day. Accordingly, various caffeine-containing processed foods are being developed, and as the use of coffee shops and fast food increases, the consumption of caffeine-containing foods of all age groups is increasing. A study on the consumption status of the coffee market reported that per capita consumed 0.8 cups of coffee every day, and that the number of cups consumed per year was 300 (The case of Korea, USA, Japan market. Korean J Culinary Res 10(The case of Korea, USA, Japan market. 3): 65-82). In addition, a large number of adolescents drink caffeinated coffee, and if you consider beverages and chocolate containing excessive caffeine, it is time to consider the risk of excessive caffeine intake. Caffeine, a favorite food, is widely used in society, and not only coffee or tea, but also cola and chocolate, which are frequently sought out by children and adolescents, contain caffeine. Even over-the-counter medicines contain caffeine.

Caffeine is widely mixed in coffee, tea, beverages, and pharmaceuticals, and its main ingredient is 1,3,7-trimethylxanthine, which is a bitter-tasting alkaloid compound containing nitrogen. It is a component derived from purine and uric acid. Caffeine is odorless, white needles that sublimate at 176 °C, dissolves well in hot water, and has a unique bitter taste. In addition, it is currently known to exist in the leaves and fruits of about 60 plants, and is mainly extracted from the seeds of the coffee tree (coffee arabica). It is also extracted from the leaves of the tea tree (Camellia sinensis (L) O. Kuntze), the fruit of the cacao tree (Theobroma cacao), the fruit of the kola tree (Cola acuminata), and the leaves of the mate tree (Ilex paraguayensis).

Caffeine is a kind of central nervous system stimulant that stimulates the central nervous system and the sympathetic nervous system. The effect of caffeine absorption into the body has been revealed through an experimental study on the physical effects of caffeine. Caffeine is widely used as a stimulant for chasing drowsiness because it has a central nervous system excitatory action. However, long-term intake has a serious effect on normal sleep and wakefulness, and excessive intake of caffeine can lead to risks such as indigestion, palpitations, excitement, headache, insomnia, hyperacidic gastritis, diuresis, and mineral deficiency. has been

In particular, high-caffeine beverages, which are popular among adolescents, are mistaken for 'medicine for study study', and many adolescents drink it when the exam period comes. However, high-caffeine drinks only have the effect of temporarily waking up from drowsiness by stimulating the central nervous system, and there is no evidence that it can improve sexual performance. As such, there is a lack of correct understanding of high-caffeinated beverages, but there is still no special legal system for the protection of excessive drinking by adolescents and children in Korea, and there is no legal restriction on sales based on harmful contents. Moreover, specific preventive and therapeutic agents for improving caffeine addiction have not been presented to date.

Accordingly, the present inventors have made steady efforts to develop new food and beverage products that can minimize the side effects caused by caffeine. completed.

KR 10-1517843 B KR 10-1564200 B

It is an object of the present invention to provide a food composition for preventing or improving diseases caused by caffeine poisoning, comprising a turmeric extract as an active ingredient.

In addition, another object of the present invention is a caffeine-containing food; And to provide a food composition with reduced side effects of caffeine comprising a turmeric extract.

In addition, another object of the present invention is to provide a health functional food for preventing or improving diseases caused by caffeine poisoning comprising a turmeric extract as an active ingredient.

In addition, another object of the present invention is to provide a food additive for preventing or improving diseases caused by caffeine poisoning comprising a turmeric extract as an active ingredient.

In addition, another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of diseases caused by caffeine poisoning comprising a turmeric extract as an active ingredient.

In order to achieve the above object, the present invention provides a food composition for preventing or improving diseases caused by caffeine poisoning, comprising a turmeric extract as an active ingredient.

In the composition, the disease may be selected from among insomnia, sleep disturbance, agitation, increased blood pressure, heart palpitations, decreased concentration, tremor and muscle pain due to caffeine administration.

In addition, the present invention is a caffeine-containing food; And it provides a food composition with reduced side effects of caffeine comprising a turmeric extract.

In addition, the present invention provides a health functional food for preventing or improving diseases caused by caffeine poisoning, comprising a turmeric extract as an active ingredient.

In addition, the present invention provides a food additive for the prevention or improvement of diseases caused by caffeine poisoning comprising a turmeric extract as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of diseases caused by caffeine poisoning comprising a turmeric extract as an active ingredient.

The composition comprising the turmeric extract of the present invention as an active ingredient is non-toxic, effectively improving sleep disorders caused by caffeine poisoning, and preventing, improving or treating diseases caused by caffeine poisoning, such as suppressing central nervous excitement, is very effective. Excellent, it can be usefully used in the manufacture of competitive foods and pharmaceuticals.

1 is a graph showing the effect of the turmeric extract (KFRI-S075) of the embodiment on the rise time, non-REM sleep (NREMS) time, REM sleep (REMS) time through sleep structure analysis in a caffeine-induced sleep disorder mouse model. A general control (Vehicle; 0.5% CMC-saline 10 mL/kg), caffeine (25 mg/kg), ZPD (10 mg/kg) and the turmeric extract of Examples (50 mg/kg) were orally administered (po). Each graph represents the mean value (means±SEM, n=8). ZPD is an abbreviation for zolpidem.
Figure 2 is a graph showing the effect of the turmeric extract of Examples on changes in non-REM sleep (NREMS), REM sleep (REMS) and wakefulness (Wake) for 24 hours in a caffeine-induced sleep disorder mouse model.
3 is a graph showing the effect of the turmeric extract of Example on the mean duration, number of bouts, and the number of bouts per duration for detailed sleep structure analysis in a caffeine-induced sleep disorder mouse model.
Figure 4 is a caffeine-induced sleep disorder mouse model, caffeine alone administered group, caffeine and Example administration group, and caffeine and ZPD administered group during non-REM sleep during non-REM sleep (EEG, elctroencephalogram) power density and delta activity (Delta activity) compared. It is a graph. Vehicle represents a general control group, and ** means that there is a significant difference at p<0.01 compared to the control group ( t- test).
Figure 5a is a graph showing the comparison of the retention time of the center zone in the caffeine-induced central nervous system excitability mouse model, the group administered with caffeine alone, and the group administered with caffeine and Examples (25 mg/kg, 50 mg/kg, 100 mg/kg). Vehicle denotes a general control group, # denotes a control group, and * denotes a significant difference at p<0.05 compared to the control group ( t- test).
Figure 5b is a graph showing the comparison of the total movement distances of the caffeine-induced central nervous system excitation mouse model, the caffeine alone administration group, the caffeine and Example administration groups (25 mg / kg, 50 mg / kg, 100 mg / kg). Vehicle denotes a general control group, # denotes a control group, and * denotes a significant difference at p<0.05 compared to the control group ( t- test).

Hereinafter, the present invention will be described in detail.

The food composition for the prevention or improvement of diseases caused by caffeine addiction of the present invention contains a turmeric extract as an active ingredient.

Turmeric is a perennial plant belonging to the ginger family, and is mainly cultivated in tropical and subtropical regions centered on India, and its stems and roots are used for food and medicinal purposes. It is widely cultivated in India, China, and Southeast Asia, and in Korea, it is cultivated in Jindo, Jeollanam-do, Haenam, Jeollanam-do, Buan, Siheung, Gyeonggi, and Cheongyang, Chungcheongnam-do. Ears of flowers come out before leaves, are broad egg-shaped, and are wrapped in light green bracts. Yellow flowers bloom in the leaf axils from April to June. The upper bract has a slightly narrow butterfly, and the tip is pale magenta, and there are no flowers in the leaf axil. The outside of the rhizome is pale yellow, and the inside is scarlet and smells like camphor. The rhizome of turmeric is used as an herbal medicine. It is a yellowish medicine with a spicy and bitter taste. It is effective in anticancer, Alzheimer's treatment, antioxidant, anti-inflammatory, detoxification, liver disorder suppression, pain relief, and menstrual irregularities. In India, it is used as a medicine for bruises and sprains, and is also used as a spice for curry powder.

On the other hand, there is turmeric, which is difficult to distinguish from turmeric. Although turmeric and turmeric are from the same ginger family and contain a large amount of curcumin, there is a difference in basic properties. In terms of weakness, turmeric is warm and turmeric is cool, and turmeric is used by drying the rhizome of turmeric, but turmeric is used by drying the tuber of turmeric.

The main components of turmeric (薑黃; Curcuma longa L.) are curcuminoid pigment components such as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, and ar-turmerone, curlone, α -Volatile essential oil components such as turmerone, β-turmerone, bisacumol, and zingiberene and starch.

The turmeric extract of the present invention may include the bisdimethoxycurcumin:curcumin in a weight ratio of 1: 15 to 150, and the bisdimethoxycurcumin:dimethoxycurcumin in a weight ratio of 1:1.5 to 15.

The turmeric is mixed with an extraction solvent in a weight ratio of 1: 5 to 25, preferably 1: 8 to 15, at 40 to 70 °C, preferably 50 to 60 °C for 10 to 20 hours, preferably 15 to 18 hours. After extraction for a while, concentration under reduced pressure is performed to prepare an extract. When the weight ratio of the turmeric and the extraction solvent is out of the above range, the active ingredient of the turmeric may be extracted in a small amount in the extract.

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

The extraction solvent is not particularly limited, but the extract extracted with an aqueous solution of 60 to 80% ethanol preferably acts in the prevention, improvement or treatment of diseases caused by caffeine poisoning.

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

The term "extract" used while referring to turmeric in the present specification includes not only the crude extract obtained by treating the extraction solvent but also the processed product of the turmeric extract. For example, the turmeric extract may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze-drying or spray-drying.

In addition, the turmeric extract of the present invention is broadly meant to include a processed turmeric product formulated so that turmeric can be administered to animals, for example, turmeric powder. Although the present invention conducted the experiment with turmeric, it will be expected by those skilled in the art that the desired effect can be achieved even in the form of a turmeric processed product.

Meanwhile, in the present specification, the term "contained as an active ingredient" means including an amount sufficient to achieve the efficacy or activity of the turmeric extract. The daily dose of the turmeric extract of the present invention may be 10 to 1,000 mg/kg, preferably 20 to 500 mg/kg, more preferably 20 to 300 mg/kg, and further It may be preferably 50 to 300 mg/kg, more preferably 50 to 200 mg/kg, and most preferably 50 to 100 mg/kg. If the dosage of the turmeric extract of the present invention is less than the lower limit, the improvement or therapeutic effect of the disease caused by caffeine poisoning may not appear to the desired degree, and if it exceeds the upper limit, the dose is increased as much as the dose of the disease caused by caffeine poisoning. It is undesirable because it does not increase the therapeutic effect or may be toxic. On the other hand, as a result of animal experiments, when the dosage of the turmeric extract of the present invention was within the above range, a significant effect was exhibited, but side effects such as cytotoxicity did not appear.

As used herein, the term "caffeine poisoning" refers to poisoning due to caffeine, and refers to a case of addiction to or dependence on caffeinated foods such as coffee, high-caffeine energy drinks, cola, green tea, black tea, and cocoa. say The disease caused by caffeine poisoning is a generic term for diseases and symptoms caused by caffeine administration regardless of the dose and number of administration of caffeine, for example, sleep disturbance, insomnia, diarrhea, excitement symptoms, blood pressure rise, heart palpitation. , headache, poor concentration. It is preferable that at least one selected from the group consisting of nausea, vomiting, depression, anxiety, tremor, muscle pain and withdrawal symptoms, but is not limited thereto.

In a specific embodiment of the present invention, as a result of administering the turmeric extract of the present invention to a mouse model having increased motor activity due to central nerve excitation due to caffeine poisoning, it was confirmed that there was an effect of inhibiting central nerve excitation ( see Fig. 8). In addition, in a specific embodiment of the present invention, as a result of administering the turmeric extract of the present invention to a mouse model having a sleep disorder caused by caffeine poisoning, it was specifically confirmed that there is an effect of improving sleep disorder caused by caffeine administration ( 1 to 4). This suggests that the turmeric extract of the present invention can be usefully used for prevention, treatment or improvement of diseases caused by caffeine addiction.

As used herein, the term “prevention” refers to anything that inhibits or delays one or more symptoms of the disease.

As used herein, the term "treatment", unless otherwise stated, means reversing, alleviating, inhibiting the progression, or preventing one or more symptoms of the disease.

As used herein, the term “improvement” means at least reducing a parameter, eg, severity, of a condition associated with a condition to be treated by administration of a composition comprising a turmeric extract of the present invention.

The food composition according to the present invention may be, for example, beverages, alcoholic beverages, confectionery, diet bar, dairy product, meat, chocolate, pizza, ramen, other noodles, 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 not only the turmeric extract as an active ingredient, but also ingredients commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatine, 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 prepared as a drink or beverage, citric acid, high fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be additionally included in addition to the turmeric extract of the present invention.

The content of the turmeric extract in the food composition is 0.001 to 0.5% by weight, preferably 0.002 to 0.3% by weight, 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 is a caffeine-containing food; And it provides a food composition with reduced side effects of caffeine comprising a turmeric extract. In the composition, the contents of the turmeric extract and the food composition are the same as described above.

As used herein, the term "caffeine side effect" may be one or more symptoms selected from excitability, blood pressure increase, heart palpitation, decreased concentration, tremor, muscle pain, insomnia, and sleep disturbance due to caffeine administration.

As used herein, the term "reducing side effects of caffeine" means alleviating, alleviating, or alleviating one or more symptoms of the side effects of caffeine.

The caffeine-containing food may be coffee, tea, cola, cocoa, chocolate, energy drink, or a food containing the same. As used herein, the term "energy drink" refers to a functional beverage containing electrolytes and caffeine, etc., manufactured for the purpose of chasing drowsiness and helping recovery from fatigue.

In the present invention, the caffeine-containing food means a food containing 5 mg/g or more of caffeine. In addition, the caffeine-containing food may be a beverage containing 5 to 150 mg/100 mL of caffeine.

The content of the turmeric extract in the food composition is 0.001 to 1% by weight, preferably 0.002 to 0.5% by weight, 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 health functional food for the prevention or improvement of diseases caused by caffeine poisoning comprising the turmeric extract as an active ingredient. In the health functional food, the effect of the turmeric extract and the effect on the disease caused by caffeine poisoning is the same as described above. Since the health functional food of the present invention can be consumed on a daily basis, an improvement effect of a disease caused by caffeine addiction can be expected, and thus it can be very usefully used for health promotion purposes.

The term "health functional food" of the present invention is the same term as food for special health use (FoSHU), and it refers to food with high medical and medical effects processed to efficiently exhibit bioregulatory functions in addition to nutrition supply. it means. Here, the term 'function' refers to obtaining useful effects for health purposes, such as regulating nutrients or physiological effects on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art. In addition, the formulation of the health functional food may also be prepared without limitation as long as it is a formulation recognized as a food. The health functional food of the present invention can be manufactured in various forms, and unlike general drugs, it has the advantage that there are no side effects that may occur when taking the drug for a long period of time by using food as a raw material, and because it is excellent in portability, caffeine It can be taken as an adjuvant to enhance the effect of improving addiction.

The health functional food means a food having an active health maintenance or promotion effect compared to general food, and health supplement food means a food for the purpose of health supplementation. In some cases, the terms health functional food, health food, and health supplement are used interchangeably.

In one embodiment, the health functional food of the present invention may be in the form of powder, granule, tablet, capsule or beverage. In the case of health functional food in the form of pills, granules, tablets or capsules, the amount of turmeric extract added in such health functional food is usually 0.1 to 100% by weight, preferably 0.5 to 80% by weight. .

In addition, the present invention provides a food additive for the prevention or improvement of diseases caused by caffeine poisoning comprising the turmeric extract as an active ingredient. In the food additive, the effect on the disease caused by caffeine poisoning and the turmeric extract are the same as described above. In the food additive of the present invention, the turmeric extract may be added as it is or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment), and since the composition of the present invention is environmentally friendly and there is no problem in terms of stability, there is no great limitation on the mixing amount.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of diseases caused by caffeine poisoning comprising the turmeric extract as an active ingredient. In the pharmaceutical composition, the effects on diseases caused by caffeine poisoning and those related to the turmeric extract are as described above.

The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, a swelling agent, a lubricant, and a lubricant. agent or flavoring agent, etc. may be used.

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 a tablet or capsule, the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or required, suitable binders, lubricants, disintegrants and color-developers 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 the composition formulated as a liquid solution, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection, 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 bacteriostats may be added as needed. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.

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

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

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient, usually Thus, a skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prevention. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention may be 0.001-10 g/kg. Specifically, the daily dose of the turmeric extract of the present invention may be 10 to 1,000 mg/kg, preferably 20 to 500 mg/kg, more preferably 20 to 300 mg/kg and more preferably 50 to 300 mg/kg, more preferably 50 to 200 mg/kg, and most preferably 50 to 100 mg/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 may be prepared by internalizing in a multi-dose container. In this case, the formulation may be in the form of a solution, suspension, or emulsion in oil or an aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.

In addition, the present invention provides a method for preventing or treating a disease caused by caffeine poisoning, comprising administering an effective amount of the turmeric extract to a subject other than humans. In the method, the effect of the turmeric extract on the disease caused by caffeine poisoning is as described above.

As used herein, the term “subject” refers to a subject to whom caffeine has been administered.

As used herein, the term “effective amount” refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human as conceived by a researcher, veterinarian, physician or other clinician, which an amount that induces amelioration of the symptoms of a disease or disorder. The effective amount and frequency of administration for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimal dosage 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 components contained in the composition, the type of formulation, and the age, weight, and general health of the patient It can be adjusted according to various factors including condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and concurrently used drugs. In the prevention, improvement or treatment method of the present invention, in the case of adults, the turmeric extract is preferably administered at a dose of 0.001-10 g/kg when administered once to several times a day. Specifically, the daily dose of the turmeric extract of the present invention may be 10 to 1,000 mg/kg, preferably 20 to 500 mg/kg, more preferably 20 to 300 mg/kg and more preferably 50 to 300 mg/kg, more preferably 50 to 200 mg/kg, and most preferably 50 to 100 mg/kg.

In the treatment method of the present invention, the composition comprising turmeric extract as an active ingredient is administered in a conventional manner via oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. can be administered.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited by the following examples.

<Example>

Example. Turmeric Ethanol Extract (KFRI-S-075)

The pulverized turmeric root and 70% aqueous ethanol solution were mixed at a weight ratio of 1:10 and extracted at 50° C. for 16 hours to obtain a turmeric ethanol extract (KFRI-S-075).

The obtained turmeric ethanol extract was used after filtration and concentration under reduced pressure, and then powdered by freeze-drying.

On the other hand, as a result of analyzing the composition of the turmeric ethanol extract, bisdimethoxycurcumin at 9.33 μg/mg, curcumin at 312.82 μg/mg, dimethoxycurcumin at 27.60 μg/mg, dihydrocurcumin at 7.74 μg/mg and tetrahydrocurcumin was specifically confirmed to contain 0.09 μg/mg.

<Test Example>

<Experiment method>

laboratory animal

ICR mice (18-22 g, male) and C57BL/6N mice (28-30 g, male) were purchased from Coretech Co., Ltd. and adapted to a breeding box for experimental animals for one week, and then used in the experiment. Animals were reared under the conditions of temperature 23±1° C., humidity 55±5%, light-dark cycle (light: 9:00 am - 9:00 pm), and illumination intensity of 3000 Lux, and feed and drinking water were freely provided. 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 (n=10) per group were used after fasting for 24 hours before the experiment. All samples were prepared using a 5% tween 80-saline solution and administered orally (p.o.) to mice 45 minutes before pentobarbital administration. The general control group was treated with a 5% tween 80-saline solution at a concentration of 10 mg/kg, and caffeine was used as a negative control drug for the sleep disorder mouse model. Pentobarbital (Hanlim Pharmaceutical Co., Ltd.) was administered through an intraperitoneal injection (i.p.) at a concentration of 45 mg/kg (hypnotic dosage) according to the experimental design. After pentobarbital treatment, each individual was moved to an independent space and sleep latency and sleep duration were measured. Elevation time was set as the elapsed time from intraperitoneal injection of pentobarbital to loss of righting reflex for more than 1 minute, and sleep time was set as the time until specular reflex was restored again. Mice that did not show sleep behavior even after 10 minutes after pentobarbital administration were excluded from the experiment.

Sleep efficacy analysis (sleep structure analysis, elevation time and sleep time measurement)

After adapting C57BL/6N mice for 1 week, electrode insertion surgery was performed for EEG (Electroencephalogram, EEG) and EMG (Electromyogram, EMG) measurements. The mouse was anesthetized with pentobarbital (50 mg/kg, i.p.) and the head was fixed on a stereotaxic instrument. After incision of the subcutaneous connective tissue of the head, a Mouse EEG/EMG Headmount (Pinnacle Technology Inc, Oregon, USA) was inserted for EEG and EMG measurement. After fixing with dental cement, disinfection of the surgical site and administration of antibiotics were performed for 3 days to prevent inflammation due to surgery, and a recovery period was provided for 7 days. In order to adapt to the EEG measurement environment, 5% tween 80-saline solution used in the control group was orally administered (p.o.) 4 days before the measurement, and then a recording device was connected to induce compliance with the experimental procedure. EEG and EMG were measured for 24 hours from 17:00 using the PAL-8200 series (Pinnacle Technology Inc, Oregon, USA) after the sample was orally administered and then stabilized for 5 minutes. The sampling rate of EEG and EMG was set to 200 Hz (epoch time: 10 s), and data was recorded by setting a filter area of 0.1-25 Hz for EEG and 10-100 Hz for EMG. 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 are divided into wake, REM sleep (rapid eye movement, theta band: 6-10 Hz), and non-REM sleep (NREMS) (non-rapid eye movement, delta band: 0.65-4 Hz). and sleep latency was set as the time it takes for NREM sleep in units of 10 s epoch to appear more than 12 times consecutively.

Test Example 1. Improvement of sleep disorders caused by caffeine

Test Example 1-1. Comparison of sleep disorder improvement effect according to the concentration of the turmeric extract of Example

The purpose of the pentobarbital sleep induction experiment was to confirm the efficacy of the turmeric extract of Example for caffeine-induced sleep disorders in mice. To this end, mice were prepared by dividing the mice into 7 groups of 10 mice in each group. The general control group (Vehicle) was administered with 5% tween 80-saline, the negative control group was administered with caffeine 50 mg/kg alone, the positive control group was administered with doxepin 30 mg/kg + caffeine 50 mg/kg, the turmeric extract of the example (KFRI- S-075) 10 mg/kg + caffeine 50 mg/kg administration group, Example turmeric extract (KFRI-S-075) 25 mg/kg + caffeine 50 mg/kg administration group, Example turmeric extract (KFRI-S-075) 50 mg/kg + caffeine 50 mg/kg administration group, Example turmeric extract (KFRI-S-075) 100 mg/kg + caffeine 50 mg/kg administration group, Example turmeric extract (KFRI-S-075) 250 mg/kg The experiment was divided into + caffeine 50 mg/kg administration group, and the results of analysis of sleep efficacy (elevation time and sleep time measurement) are shown in Table 1 below.

As a result, the Example showed the effect of improving sleep disorders caused by caffeine even at a concentration of 25 mg/kg, which is an exceptionally low concentration of the plant extract, and the sleep time was higher than that of the control group at concentrations of 100 and 250 mg/kg. Confirmed.

division Sleep latency (min) sleep duration (minutes) Vehicle 3.3 73.6 Caffeine 3.9 45.5 caffeine + doxepin 3.3 76.4 Caffeine+Example+25 mg/kg 3.2 58.9 Caffeine+Example+50 mg/kg 3.1 68.3 Caffeine+Example+100 mg/kg 3.6 89.4 Caffeine+Example+250 mg/kg 3.3 96.3

Test Example 1-2. Sleep Efficacy of Turmeric Extract of Examples

In the caffeine-induced sleep disorder mouse model, it was attempted to determine what kind of sleep effect the turmeric extract of Example shows.

For this purpose, mice were prepared by dividing the mice into 3 groups of 8 mice in each group. The general control group (Vehicle) was administered with 5% tween 80-saline, caffeine 25 mg/kg alone, turmeric extract of Example (KFRI-S-075) 50 mg/kg + caffeine 25 mg/kg, ZPD (10) mg/kg) + caffeine 25 mg/kg administration group.

Figure 1a is a graph showing typical examples of brain waves (EEG), electromyogram (EMG), and hypnograms of a single mouse for each group in a caffeine-induced sleep disorder mouse model, Figure 1b is a caffeine-induced sleep disorder mouse model, elevation time , Non-REM sleep (NREMS) time, REM sleep (REMS) time is a graph showing the effect of the turmeric extract of the embodiment.

Referring to Figure 1a, the caffeine-only administration group significantly increased the wake-up time (Wake) compared to the general control group (Vehicle), and the non-REM sleep time was decreased, but the turmeric extract administration group of the example had a wake-up time (Wake) and non-REM sleep time compared to the general control group. No significant difference was observed in REM sleep time.

In addition, referring to FIG. 1b, the caffeine alone administration group significantly increased the waking time compared to the general control group (Vehicle), and the non-REM sleep time was reduced by 2.4 times, but the turmeric extract administration group of the example had the elevation time and non-REM sleep time compared to the general control group. No significant difference was observed.

For this reason, it can be seen that the turmeric extract of the present invention has an effect of improving sleep disturbance due to caffeine and suppressing arousal due to caffeine.

Test Example 1-3. Sleep Efficacy of Turmeric Extract of Example (2)

In the caffeine-induced sleep disorder mouse model, it was attempted to determine what kind of sleep effect the turmeric extract of Example shows.

For this purpose, mice were prepared by dividing the mice into 3 groups of 8 mice in each group. The general control group (Vehicle) was administered with 5% tween 80-saline, caffeine 25 mg/kg alone, turmeric extract of Example (KFRI-S-075) 50 mg/kg + caffeine 25 mg/kg, ZPD (10) mg/kg) + caffeine 25 mg/kg administration group.

Figure 2 is a graph showing the effect of the turmeric extract of Examples on changes in sleep structure by time period, that is, non-REM sleep (NREMS), REM sleep (REMS) and wakefulness (Wake) by time in a caffeine-induced sleep disorder mouse model.

Referring to FIG. 2, in the case of the caffeine-only administration group, the rice fields measured in the first (17:00-18:00), second (18:00-19:00) and fifth (21:00-22:00) time zones The REM sleep time was significantly decreased compared to the control group, and the awakening time was significantly increased compared to the control group, but in the case of the turmeric extract administration group and the ZPD administration group of Example, the sleep structure did not change for 24 hours. It can be seen that ZPD attenuates the arousal effect induced by caffeine.

3 is a graph showing the effect of the turmeric extract of Example on the mean duration, number of bouts, and the number of bouts per duration for detailed sleep structure analysis in a caffeine-induced sleep disorder mouse model.

Referring to FIG. 3A , the caffeine-only administration group significantly increased the mean duration of wake compared to the general control group (Vehicle), whereas the turmeric extract administration group and the ZPD administration group of the Example showed a significant increase compared to the general control group (Vehicle). No difference was observed.

In addition, referring to FIGS. 3b and 3c , the caffeine-only administration group significantly decreased Wake and NREM bouts compared to the general control group (Vehicle), and the number of NREM bouts in the range of 60 seconds to 240 seconds significantly decreased compared to the general control group. seemed However, in the case of the turmeric extract-administered group and the ZPD-administered group of Examples, there was no significant difference compared to the general control group (Vehicle), so it can be seen that the turmeric extract and ZPD of the Example suppressed the maintenance of arousal of the experimental animals by caffeine.

For this reason, it can be seen that the turmeric extract of the present invention has an effect of improving sleep disturbance due to caffeine and suppressing arousal due to caffeine.

Test Example 1-4. Sleep structure analysis using the turmeric extract of Examples

In the caffeine-induced sleep disorder mouse model, it was attempted to determine whether the turmeric extract of Example improves the quality of sleep in mice.

For this purpose, mice were prepared by dividing the mice into 3 groups of 8 mice in each group. The general control group (Vehicle) was administered with 5% tween 80-saline, caffeine 25 mg/kg alone, turmeric extract of Example (KFRI-S-075) 50 mg/kg + caffeine 25 mg/kg, and ZPD ( Zolpidem) 10 mg/kg + caffeine 25 mg/kg administration group was divided into the experiment.

After oral administration of each sample, a sleep structure analysis experiment (measuring EEG power density and delta activity during non-REM sleep time) was performed and shown in FIG. 4 .

Figure 4 is a caffeine-induced sleep disorder mouse model, caffeine alone administered group, caffeine and Example administration group, and caffeine and ZPD administered group during non-REM sleep during non-REM sleep (EEG, elctroencephalogram) power density and delta activity (Delta activity) compared. It is a graph.

Changes in delta activity during non-REM sleep are physiological indicators of sleep quality and depth [Behav. Brain Res. 210, 5456. Huang et al., 2010].

Referring to FIG. 4 , in the case of the group administered with caffeine alone and the group administered with Examples, there was no significant change in EEG power density including delta activity compared to the control group. These results mean that caffeine and the turmeric extract of Examples do not affect sleep quality.

On the other hand, the ZPD-administered group significantly (p<0.01) decreased delta activity during non-REM sleep. It is generally known that ZPD, a GABAA-benzodiazepine receptor agonist, increases the amount of sleep but decreases the delta activity.

An ideal sleeping pill is a drug that has the characteristics of rapidly increasing waking time, maintaining sleep, and not changing physiological sleep [Sleep. 31, 259-270. Alexandre et al., 2008]. Therefore, it is judged that the turmeric extract (Example) of the present invention can improve sleep disorders caused by caffeine more safely and naturally than drugs with side effects such as ZPD.

Test Example 2. Inhibitory effect of caffeine on central nervous system excitability

It was attempted to confirm the inhibitory effect of the turmeric extract of Example on caffeine-induced central nervous system excitation.

For this purpose, mice were divided into 5 groups of 10 mice in each group. The general control group (Vehicle) was administered with 5% tween 80-saline, caffeine 25 mg/kg alone administration group, turmeric extract of Example (KFRI-S-075) 25 mg/kg + caffeine 25 mg/kg administration group, turmeric of Example The experiment was divided into a group administered with the extract (KFRI-S-075) 50 mg/kg + caffeine 25 mg/kg, and the turmeric extract of Example (KFRI-S-075) 100 mg/kg + caffeine 25 mg/kg administration group.

After oral administration of each sample, 1 hour later, put it in the exercise capacity measurement box (diameter: 30x30x30 cm) and use the video measurement analysis system to stay in the center zone for 6 minutes (Time in center zone (s)) and total travel distance (Total distance) was measured.

Figure 5a is a graph showing the comparison of the retention time in the center zone of the caffeine-induced central nervous system excitation mouse model, the caffeine alone administration group, and the caffeine and Example administration group (25 mg / kg, 50 mg / kg, 100 mg / kg).

Referring to FIG. 5a, it appears that the center zone retention time of the caffeine 25 mg/kg group (57.5±6.3 seconds) increased significantly (p<0.01) compared to the control group (26.5±4.7 seconds), and the central nervous system caused by caffeine It can be seen that the excitatory effect was significantly increased. On the other hand, it can be seen that the center zone retention time of the 100 mg/kg + caffeine 25 mg/kg administration group of the example was 34.6±4.3 seconds, which was significantly reduced compared to the caffeine 25 mg/kg alone administration group.

Figure 5b is a graph showing the comparison of the total travel distances of the caffeine-induced central nervous system excitation mouse model, the caffeine alone administration group, the caffeine and Example administration groups (25 mg / kg, 50 mg / kg, 100 mg / kg).

Referring to FIG. 5b, the total movement distance of the caffeine 25 mg/kg single administration group (232.0±26.2 mm) was significantly increased (p<0.01) compared to the control group (131.8±16.9 mm), and the central nervous system excitation by caffeine It can be seen that the effect is significantly increased. On the other hand, it can be seen that the total movement distance of the turmeric extract 100 mg/kg + caffeine 25 mg/kg administration group of Example was 145.4±10.7 mm, which was significantly reduced compared to the caffeine 25 mg/kg alone administration group.

Through these results, it was confirmed that the turmeric extract of the present invention can effectively inhibit the central nervous system excitatory effect caused by caffeine administration.

Hereinafter, an example of the preparation of the composition containing the extract of the present invention will be described, but the present invention is not intended to limit the present invention, but merely to describe it in detail.

<Production Example>

Preparation Example 1: Food Composition - Coffee

Coffee containing the turmeric extract in the components and contents of Table 2 below was prepared according to a conventional method.

Grind coffee beans (Colombia Supremo, Ewol Roasters) with a hand drip grinder (0.7-1.0 mm), put 500 g of ground coffee beans in a beaker, pour water at a temperature of 90 to 100° C., and leave it for 5 minutes. After stirring for 10 minutes with a stirrer (overhead stirrer), vacuum filtration using filter paper (filter paper 5A) to prepare a bean extract.

Ingredients Preparation Example 1 Curcuma Extract of Examples 1000 mg milk 40.0 wt% Bean extract (solid content) 26.1 wt% milk cream 5.72 wt% white sugar 5.60% by weight skim milk 0.85 wt% Sodium bicarbonate (potassium carbonate) 0.12% by weight sodium caseinate 0.10 wt% sucrose fatty acid ester 0.08 wt% Purified water remaining amount

Preparation Example 2: Preparation of health functional food

A health functional food composition comprising a turmeric extract in the components and contents of Table 3 was prepared according to a conventional method.

The composition ratio of the vitamin and mineral mixture in the table below is a composition that is relatively suitable for health functional food in a preferred embodiment, but the mixing ratio may be arbitrarily modified and mixed according to a conventional method, and then prepared into an appropriate formulation. can

Ingredients Preparation Example 2 Curcuma Extract of Examples 1000 mg 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 mg vitamin C 10 mg biotin 10 μg Nicotinamide 1.7 mg folic acid 50 μg Calcium Pantothenate 0.5 mg ferrous sulfate 1.75 mg zinc oxide 0.82 mg magnesium carbonate 25.3 mg monobasic potassium phosphate 15 mg Dibasic Potassium Phosphate 55 mg Potassium Citrate 90 mg calcium carbonate 100 mg magnesium chloride 24.8 mg

Preparation Example 3: Pharmaceutical composition

Preparation Example 3-1. Preparation of powders

After mixing 50 mg of the turmeric extract of Example and 2 g of crystalline cellulose, it was filled in an airtight bag according to a conventional powder preparation method to prepare a powder.

Preparation Example 3-2. manufacture of tablets

After mixing 50 mg of the turmeric extract of Example, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate, tablets were prepared by tableting according to a conventional tablet manufacturing method.

Preparation Example 3-3. manufacture of capsules

After mixing 30 mg of the turmeric extract of Example, 100 mg of whey protein, 400 mg of crystalline cellulose, and 6 mg of magnesium stearate, it was filled into a gelatin capsule according to a conventional capsule preparation method to prepare a capsule.

Preparation 3-4. manufacture of injections

According to a conventional injection preparation method, the active ingredient is dissolved in distilled water for injection, the pH is adjusted to about 7.5, 100 mg of the turmeric extract of Example, distilled water for injection, and a pH adjusting agent are mixed, filled in an ampoule with a capacity of 2 mL, and sterilized. Injections were prepared.

Although the present invention has been described as the above-mentioned preferred embodiment, it is possible to make various modifications and variations without departing from the spirit and scope of the invention. It is also intended that the appended claims cover such modifications and variations as fall within the scope of the present invention.

Claims (15)

A food composition for preventing or improving diseases caused by caffeine poisoning, comprising a turmeric extract as an active ingredient. According to claim 1,
The disease is a food composition, characterized in that it is selected from excitement symptoms, blood pressure increase, heart palpitations, decreased concentration, tremor, muscle pain, insomnia and sleep disorders due to caffeine administration. According to claim 1,
The disease is a food composition, characterized in that arousal or sleep disorders due to caffeine administration. According to claim 1,
The turmeric extract is a food composition, characterized in that it is extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. According to claim 1,
The turmeric extract is a food composition, characterized in that administered at a concentration of 20 to 300 mg / kg / day. According to claim 1,
The food composition is a food composition, characterized in that the coffee beverage. Caffeine-containing foods; And a food composition with reduced side effects of caffeine comprising a turmeric extract. 8. The method of claim 7,
The caffeine-containing food is coffee, tea, cola, cocoa, chocolate, energy drink, or a food composition with reduced side effects of caffeine, characterized in that the food containing the same. 8. The method of claim 7,
The caffeine-containing food is a food composition with reduced side effects of caffeine, characterized in that it contains 5 mg/g or more of caffeine. 8. The method of claim 7,
The caffeine-containing food is a food composition with reduced side effects of caffeine, characterized in that the beverage containing caffeine in an amount of 5 to 150 mg/100 mL. 8. The method of claim 7,
A food composition with reduced side effects of caffeine, characterized in that the content of the turmeric extract is 0.001 to 1% by weight. A health functional food for preventing or improving diseases caused by caffeine poisoning, comprising turmeric extract as an active ingredient. 13. The method of claim 12,
The dosage form of the health functional food is a health functional food, characterized in that it is a powder, granules, tablets, capsules or beverages. A food additive for preventing or improving diseases caused by caffeine poisoning, comprising turmeric extract as an active ingredient. A pharmaceutical composition for the prevention or treatment of diseases caused by caffeine poisoning, comprising a turmeric extract as an active ingredient.

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