KR101772616B1 - Ant-stress Composition Using an Extract of Xylosma congesta - Google Patents

Abstract

The present invention discloses an anti-stress composition using a citron extract. The extract of the citron extract used in the present invention is effective for restoring the stress phenomenon such as adrenal weight increase, spleen weight decrease, erythrocyte and leukocyte count increase, GPT, GOT and LDH increase when administered to stressed experimental animals I have.

Description

[0001] The present invention relates to a composition for anti-stress using a citron extract and an antioxidant composition,

The present invention relates to a process for the preparation of The present invention relates to a composition for anti-stress using a congesta extract.

Stress is defined as a decrease in physical and mental ability, and is classified into physical stress (fatigue), which means mental stress, which means imbalance of body rhythm due to mental overload, and decreased ability to perform exercise Development of Functional Evaluation System for Fatigue Recovery of Health Functional Foods, Research Report).

Mental stress causes various symptoms such as tension headache, migraine headache, hypertension, dyspepsia, fatigue, pain, menopausal disorder, hair loss, skin roughness, etc., and when chronic persistent, various diseases including peptic ulcer, hypertension, diabetes, . ≪ / RTI > Especially, mental stress causes anxiety and emotional distress.

The physical response to this mental stress begins by stimulating the function of the sympathetic pituitary gland (HPA) and inducing hormone secretion. The adrenal glands stimulated by adrenocorticotropic hormone are increased in weight, and the spleen is significantly reduced in weight due to the decline of immune function. In addition, the adrenal glands secrete other steroid hormones and secrete blood cholesterol, blood sugar, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST or) GOT), and alanine transaminase (ALT or GPT). These stress responses ultimately reduce the homeostasis of the body and weaken the body's immune system, thus causing various diseases (Friedman et al., Psychosom Med. 1963, 25: 364-376; Snel J et al. Physiol. 1972, 65: Suppl: 328A; Groth W et al., Zentralbl Veterinarmed A. 1975, 22 (1): 57-75; Gold et al., Psychoneuroendocrinology 1985, 10 (4): 401-19; S et al., 1988, 20 (1): 36-42).

Physical stress causes fatigue by accumulating lactic acid in muscles. The accumulation of lactic acid involves muscle-mediated LDH (lactate dehydrogenase), which catalyzes the production of lactic acid from pyruvic acid. Physical stress increases LDH and causes accumulation of lactic acid in muscles (Fitts et al., Am J Physiol. 1976, 231 (2): 430-3; Savitski et al., Ukr Biokhim Zh. ): 45-9).

(Korean Patent No. 1120996), Hwanggi extract (Korean Patent Laid-open No. 10-2009-0073462) and water extract (Korean Patent No. 876440), which are currently separated from ginseng, Activity. ≪ / RTI >

The present invention discloses anti-stress activity of citron extract.

It is an object of the present invention to provide a composition for anti-stress.

Other and further objects of the present invention will be described below.

As stressed on experimental animals, the present inventors increased adrenal weight, decreased spleen weight, increased leukocyte count, and increased GPT, GOT, and LDH levels, as demonstrated in the following examples and experimental examples , And it was confirmed that when the citron extract was administered, these phenomena were recovered in a concentration-dependent manner.

The present invention is provided based on these experimental results, and the antistress composition of the present invention is characterized in that it contains a citrus extract as an active ingredient.

In the present specification, the term "citron extract" means a citron extract of a citron tree, leaf, fruit, flower, roots, mixture thereof and the like as a target to be extracted with water, a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, (DMF), dimethylsulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixed solvent thereof is used as a solvent in the presence of an organic solvent such as hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane And a fraction obtained by fractionating the crude extract with one or more of the above-listed solvents. The extraction method can be applied by any method such as cold-rolling, refluxing, heating, ultrasonic irradiation or the like in consideration of the degree of extraction and the degree of preservation of the active ingredient. In the case of the fractionated extract, the crude extract is suspended in a specific solvent, and the fractions obtained by mixing and leaving with a solvent having a different polarity are adsorbed on a column packed with silica gel or the like, and a hydrophobic solvent, a hydrophilic solvent or a mixture thereof Quot; means a fraction obtained by using a solvent as a mobile phase. Also, the meaning of the extract includes a concentrated liquid extract or a solid extract in which the extraction solvent is removed by a method such as freeze drying, vacuum drying, hot air drying, spray drying and the like. Preferably an extract obtained by using water, ethanol or a mixed solvent thereof as an extraction solvent, and more preferably an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.

Also, in the present specification, the term "active ingredient" alone means an ingredient which exhibits the desired activity or which can exhibit activity together with a carrier which is itself inactive.

In this specification, "anti-stress" means mental fatigue recovery and physical fatigue recovery, and specifically means relaxation of tension, relief of anxiety, improvement of concentration and / or improvement of exercise capacity.

The anti-stress composition of the present invention may contain an effective amount of the active ingredient in an arbitrary amount (effective amount) as long as it exhibits antistress activity, depending on the purpose of use, formulation, compounding purpose and the like. , It is determined within the range of 0.001 wt% to 99.990 wt%. Herein, "effective amount" refers to the amount of active ingredient capable of inducing an anti-stress effect. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.

The antistress composition according to the present invention may be used in combination with an extract of powdery mildew bean gum, whole herb extract / powder, extract of fir tree, leaf, roots or mixture thereof / powder , Extracts / powder of leaves, roots or mixtures thereof, extracts / powder of leaves, roots or mixtures thereof, extracts / powder of leaves, roots or mixtures thereof Extracts / powder of algae, leaves, roots or mixtures thereof, extracts / powder of leaves, roots or mixtures thereof, and the like. Here, the meaning of the extract is as described above in connection with the citron extract. These extracts may be obtained by mixing the above-mentioned extraction objects.

Also known that the anti-stress, etc. The compositions of the present invention in addition to active ingredient, the acid citron extract fatigue activity, immune system enhancement active ginseng (Panax (cellulase, pectinase, hemicellulase, etc.) and polysaccharide degrading enzyme (endo-xylenase, etc.) of ginseng root, ginseng extract / powder (Bahrke et al., Sports Med 2000, 29: , Beta-glucanase, glucoamylase, polygalactonose, arabinose, xylenes, beta -glucosidase, alpha-arabinosidase, alpha -lamaxosidase, alpha -amylase etc.) Water, Aspergillus sp., Rhizopus sp.), Yeast (especially Saccaromyces sp. cerevisiae), Bacillus subtilis (Bacillus sp., especially B. subtilis), honggukgyun (Monascus sp., especially M. purpureus), lactic acid bacterium (Lactobacillus sp ., Bifidobacterium sp ., Pediococcus sp ., Leuconostoc sp., Bifidobacterium sp . Etc., especially Lactobacillus plantarum , Lactobacillus bulgaricus, Lactobacillus casei , Lactobacillus acidophilus , Bifidobacterium bifidum ) or a mixture thereof, extracts / powder of ginseng seeds, leaves, fruits, stem or mixture thereof.

The term "ginseng" as used herein refers to red ginseng or white ginseng obtained by boiling and / or drying ginseng and the ginseng, and the extract is as described above in connection with the ginseng extract.

The anti-stress composition of the present invention can be identified as a food composition in a specific embodiment.

When the antistress composition of the present invention is identified as a food composition, the form of the food can be selected from the group consisting of tea, juice, carbonated beverage, beverage such as ionic beverage, milk processed, processed oil such as root, gum, rice cake, , Foods such as cotton, powders, tablets, capsules, and the like.

The food composition of the present invention may contain sweetening agents, flavoring agents, physiologically active ingredients, minerals and the like in addition to the active ingredients thereof.

Sweetening agents may be used in an amount that sweetens the food in a suitable manner, and may be natural or synthetic. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.

Flavors may be used to enhance taste or flavor, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used.

Examples of the physiologically active substance include catechins such as catechin, epicatechin, gallocatechin and epigallocatechin, and vitamins such as retinol, ascorbic acid, tocopherol, calciferol, thiamine and riboflavin.

As the mineral, calcium, magnesium, chromium, cobalt, copper, fluoride, germanium, iodine, iron, lithium, magnesium, manganese, molybdenum, phosphorus, potassium, selenium, silicon, sodium, sulfur, vanadium and zinc can be used.

In addition, the food composition of the present invention may contain preservatives, emulsifiers, acidifiers, thickeners and the like as needed in addition to the above sweeteners.

Such preservatives, emulsifiers and the like are preferably added in a very small amount as long as they can attain an application to which they are added. The term " trace amount " means, when expressed numerically, in the range of 0.0005% by weight to about 0.5% by weight based on the total weight of the food composition.

Examples of the preservative which can be used include calcium sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid).

Examples of the emulsifier which can be used include acacia gum, carboxymethyl cellulose, xanthan gum, pectin and the like.

Examples of the acidulant that can be used include acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, and phosphoric acid. Such an acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste.

Agents that may be used include suspending agents, sedimentation agents, gel formers, bulking agents and the like.

The anti-stress composition of the present invention can be identified as a pharmaceutical composition in another specific embodiment.

The pharmaceutical composition of the present invention may be formulated into a wide variety of dosage forms, including pharmaceutically acceptable carriers, excipients and the like, in addition to the active ingredient, and may be formulated into a wide variety of preparations such as creams, lotions, ointments (semi-solid external medicine) (TTS) (e.g., patches, bandages, etc.), and the like.

The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.

Examples of pharmaceutically acceptable carriers include lactose, glucose, sucrose, starch (e.g., corn starch, potato starch and the like), cellulose, derivatives thereof (e.g. sodium carboxymethylcellulose, ethylcellulose, etc.), malt, gelatin, talc, (E.g., peanut oil, cottonseed oil, sesame oil, olive oil, etc.), polyols (e.g., propylene glycol, glycerin and the like), alginic acid, and the like. Depending on the formulation of the pharmaceutical composition of the present invention, one or more suitable ones may be selected and used. Suitable pharmaceutically acceptable carriers and formulations are described in Remington's Pharmaceutical Sciences (19th ed., 1995). The pharmaceutical composition of the present invention may further comprise an emulsifier (e.g., TWEENS), a wetting agent (e.g., sodium lauryl sulfate), a coloring agent, a flavoring agent, a stabilizer, a preservative, water, saline, a phosphate buffer solution and the like.

The excipient may be selected according to the formulation of the pharmaceutical composition of the present invention. For example, suspending agents such as sodium carboxymethyl cellulose, methyl cellulose, hydropropyl methyl cellulose, sodium alginate, polyvinyl pyrrolidone, .

The daily dose of the pharmaceutical composition of the present invention is usually 0.001 to 150 mg / kg body weight, and may be administered once or several times. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as route of administration, age, sex, weight, and patient's severity of the patient, the dose is limited in any aspect to the scope of the present invention Should not be understood to be.

As described above, according to the present invention, it is possible to provide a composition for anti-stress using a citrus fruit extract.

The anti-stress composition of the present invention can be produced into food or medicine.

Fig. 1 shows the results of showing that the citron extract restores the shrinkage of the spleen due to stress in a concentration-dependent manner.
Fig. 2 shows the result that the extract of the citron extract restores the adrenal hypertrophy due to stress in a concentration-dependent manner.
FIGS. 3 and 4 are results showing that the extract of the citron extract restores the increase of leukocyte count and red blood cell count due to stress, respectively, in a concentration-dependent manner.
Figs. 5 to 7 show the results that the citron extract recovered GPT, GOT and LDH levels, respectively, in a concentration-dependent manner.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.

< Example > Production of citron extract

10 g of dried and pulverized citrus leaf powder was added to 70% ethanol and extracted with stirring at room temperature for 48 hours. After filtration, the obtained filtrate and the extract residue separated by filtration were added to 70% ethanol and stirred at room temperature for 24 hours. After sonification, the filtrate obtained by filtration was mixed, and the mixture was concentrated under reduced pressure and lyophilized to obtain a solid citron extract.

< Experimental Example > Citron extract Antistress  Active experiment

<1> Experimental Method

<1-1> Animals

Male Sprague-Dawley rats (Koatech, Korea), 6 weeks of age, were purchased. For the experiment animals to be adapted to the changed environment, temperature, humidity and food, The experiment was started.

The experimental animal room was conditioned at a temperature of 22 ± 2 ° C, a relative humidity of 45 ± 10%, a ventilation rate of 10-15 times / hr, illumination intervals of 12 hours, illumination of 150-250 Lux and noise of 60dB or less. Polycarbonate was kept in three rabbits per week and the box was changed twice a week to keep the ammonia concentration below 20ppm. Feeds were prepared by autogenous feeding of Harlen 's sterilized solid feed, and negative water was sterilized at high pressure to be freely ingested. Ten rats were used in each experimental group.

<1-2> Evaluation of fatigue recovery efficacy

The experimental group was classified into the normal group (stress non-group) and the stress-induced group of the 4th group in the first group and the low-concentration group (100mg / kg) 400 mg / kg), and the citrus juice extract was mixed with drinking water for oral administration once a day for 14 days (Table 1)

Classification of whole experimental group Group Treatment No. of Rat I Normal (normal group)
Drinking water -> 1.2 mg / Mari PO 10 Ⅱ Stress-inducing group (control group)
Drinking water -> 1.2 mg / Mari PO 10 Ⅲ Low-dose citrate citrate group
-> 1.2 mg / mari PO 10 IV Citrus juice concentrate
-> 1.2 mg / mari PO 10 V High concentration of citrate
-> 1.2 mg / mari PO 10

<1-3> Measurement of anti-stress markers

Blood samples were taken for 14 days, and after restraint stress, blood samples were taken for biochemical test. Plasma ALT (GPT), AST (GOT) and LDH levels were measured using a blood auto-biochemical analyzer (Hitachi, model: Hitachi 7020). After 14 days of sample administration and restraint stress, the organ weights of the spleen and adrenal gland were measured, and the changes of leukocyte and erythrocyte counts were also measured.

The anti-fatigue effect was carried out on the 14th day of the experiment by the Immobilization Stress test for 18 hours (Yakhak Hoeji, 1995, 39 (5): 548-553; Korean J. Orient.Int. 4): 683-689). The restraint stress was made on a restrained cage (BioLink, Model DH-SC03) 20 cm in height and 15 cm in diameter for 18 hours (p.m 3 o'clock to the following day a.m 9 o'clock) on the 14th day.

&Lt; 2 & Experiment result

<2-1> Long term weight

The organ weights of the spleen and adrenal glands of each experimental group were measured and are shown in FIG. 1 and FIG. 2. In the stress-induced group, spleen contraction and adrenal hypertrophy were observed as compared with the normal group (non-stressed group), and in the group treated with citrate extract, And the enlargement of the adrenal gland is suppressed.

<2-2> Leukocyte count

The number of leukocytes (granulocyte and monocyte) in each experimental group was measured and is shown in [Figure 3] and [Figure 4]. 3 and 4, leukocyte counts were increased in the stress-induced group compared to the normal group (non-stressed group), and the concentration-dependent recovery was observed in the group treated with the citrate extract.

<2-3> Concentration of blood marker

The GPT, GOT and LDH values of the respective experimental groups were measured and are shown in [FIG. 5] to [FIG. 7]. 5 to 7, an increase in the levels of these factors was observed in the stress-induced group compared to the normal group (non-stressed group), and a concentration-dependent recovery was observed in the group treated with the citrate extract have.

Claims (4)

A composition for mental fatigue depression comprising Xylosma congesta leaf extract as an active ingredient.
The method according to claim 1,
Wherein the Xylosma congesta leaf extract is obtained by extracting citronellum leaves and using water, ethanol or a mixed solvent thereof as an extraction solvent.
3. The method according to claim 1 or 2,
Wherein the composition is a food composition.


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