WO2018174448A1 - Composition for treating and preventing climacteric syndrome containing combined herbal medicinal extract of white atractylis, mori fructus, chinese matrimony vine, longan, achyranthes, eucommia bark, and asparagus cochinchinensis merr. as active ingredient, and use of same - Google Patents

Abstract

The present invention relates to a composition for treating and preventing climacteric syndrome, the composition containing a combined herbal medicinal extract of white atractylis, Mori fructus, Chinese matrimony vine, longan, Achyranthes, Eucommia bark, and Asparagus cochinchinensis Merr. as an active ingredient. The results of an endurance exercise ability evaluation test using a mouse and measurement of a hot flush alleviating effect using the tail skin temperature of a climacterium-induced mouse revealed that an experimental group administered with the extract is able to perform an endurance exercise for a longer period of time than a control group and that the increase in tail skin temperature is suppressed in the experimental group. Thus, it was confirmed that the extract has the effects of alleviating and treating climacteric symptoms, and the extract can be utilized as a raw material for producing a drug, a health functional food, and a heath supplement food.

Description

Composition and its use for the treatment and prevention of menopausal syndrome, which contains as extracts the extract of the combination herbal extracts of baekchul, heartache, goji berry, longan meat, hyssop, headworm and astronomical dong

The present invention relates to a composition for the prevention and treatment of menopausal syndrome and its use containing the extract of the combination herbal extract of baekchul, heartache, goji berry, longan meat, dew, tofu and astronomical dong as an active ingredient.

Menopause is an inevitable phenomenon in all women, but the resulting deficiency of female hormones is an important factor that causes physical and mental illness over a long period of time. The so-called "menopausal syndrome" includes a variety of symptoms and diseases, which can be divided into early acute symptoms, mid-term symptoms and long-term sequelae, depending on the time of onset. Symptoms of early menopausal period include vasomotor symptoms such as febrile flushing and night sweats, as well as mental and psychological symptoms. Mid-term symptoms include symptoms of urogenital atrophy and symptoms caused by decreased collagen from connective tissue in each part of the body. This mid-term symptom, unlike the acute early symptom, which is of limited nature, takes a worse course as the menopause progresses.

The long-term sequelae of late stages of menopause include osteoporosis, cardiovascular and cerebrovascular diseases, and senile dementia belongs to this category.

According to the study of menopause-related symptoms performed in Korea since the 1980s, the rate of menopausal symptoms among menopausal women in Korea ranged from 57% to 90% .The range of symptoms experienced was neurological sensitivity, musculoskeletal symptoms, fatigue and systemic weakness, and headache. The frequency and intensity were high. Among the menopausal symptoms, vasomotor symptoms such as hot flashes and sweating were reported to increase in the late 1990s than the 1980s. In the 2000s, 89% of women who experienced natural menopause experienced at least one of the symptoms of menopause, with 61% reported that hot flashes were the most common.

Hormone therapy is typically used to treat such female hormone regulation-related diseases or symptoms. However, hormone therapy has been shown to cause side effects such as breast cancer, stroke, heart attack, venous thrombosis, and cardiovascular disease. (Korean Patent No. 10-1400913)

In order to overcome the problems caused by the hormone therapy, the development of women's menopausal symptoms improver based on natural herbal medicine has been attempted.

Baekchul refers to the root of the perennial herb, Atractylodes macrocephala KOIDZ, and the related plant of the same genus, which contains essential oils, attractyllone, and attractyllol. , Arthritis, keratosis, urinary inflammation, etc. It is known to have been used (information interception, Dohae Hyangjeomsa, Yeonglimsa, pp1026, 1998).

The lettuce is a seed of the broad-leaved mulberry (Morus alba L.) belonging to the Moraceae family, and is related to sugar, tannic acid, linoloic acid, stearinic acid, etc. It contains a substance and is known to have been used for the treatment of thirst and joint bleeding (information disclosure, Dohae Hyangdae, Yeonglimsa, pp545-548, 1998).

Goji refers to the mature fruit of the vine shrub Lycium chinensis, Lycium barbarum L. belonging to the Solanaceae, and contains substances such as carotene, nicotinc acid, etc. It is known to have a blood sugar and cholesterol lowering effect, lowering blood pressure, etc. (Interpretation of Information, Dohae Hyangdae, Yeonglimsa, pp826-828, 1998).

Longan meat refers to the aphid of Euphoria lingan STEUD, an evergreen tree belonging to Sapinaceae. It contains substances such as glucose, sucrose and tartaric acid, and has been used to treat insomnia and forgetfulness. It is known to have been reported (Information Disclosure, Dohae Hyangjeomsa Dictionary, Younglim History, pp371-373, 1998).

It is the root of the perennial herb, Achyranthus japonica NAKAI, or Acyranthes bidentata Blume, which belongs to the Amaranthaceae. It contains substances such as (inokosterone), and is known to have been used for the treatment of uterine contraction, blood pressure lowering, analgesic, etc. (Interpretation of Information, Doha Hyangje Dictionary, Younglimsa, pp340-342, 1998).

The larvae refers to the bark of the Eucommia ulmoides OLIV, a broad-leaved arborescent, belonging to the Eucommiaceae family. Gutta-percha, alkaloid, pectin, ketose, It contains substances such as linoleic aicd, and it is known to lower blood pressure and diuretic effect (information consultation, Dohae medicine pharmacy dictionary, Yeonglimsa, pp605-606, 1998).

Astronomical dong is the tuber of Asparagus cochinchinensis MERR, a perennial herbaceous herb belonging to the Liliaceae family. , Antimicrobial activity, insecticidal action, anti-ulcer action are known (information disclosure, Dohaehyangsaemsa, Yeonglimsa, pp164-165, 1998).

Ginger refers to the root of Zingiber officinale ROSC, a perennial herb belonging to the family Zingiberaceae, and is known as zingiberol, zingiberone, phellandrene, gingerol, show It contains substances such as shogaol, and antibacterial and antiparasitic action is known (information disclosure, Dohae Hyangdae, Yeonglimsa, pp260-262, 1998).

Jujube refers to the fruit of Zizyphus jujubaMILL, a broad-leaved arborescent tree belonging to Rhamnaceae, and contains substances such as protein, organic acids, etc., and is known for strengthening muscles, protecting liver, and gaining weight. Sup-eup, Dohae Hyangjeomsa Dictionary, Younglim History, pp296-297, 1998).

However, none of the above documents discloses or teaches the prevention, suppression, amelioration, or treatment of climacteric syndrome or similar symptoms containing a combination of medicinal herbs such as baekrye, heartache, goji berry, yong'an meat, loin, tofu and astronomical dong as an active ingredient. There is no bar.

Accordingly, the present inventors studied to find natural products that are excellent for improving menopausal syndrome, and the combination extract of the present invention measured the global skin ability evaluation test using tail mice in vivo, and the tail skin temperature. The present invention was completed by confirming that the exercise time was increased, the increase in the tail skin temperature was suppressed, and the liver showed excellent menopausal symptoms improvement effect in clinical cases.

MEANS TO SOLVE THE PROBLEM The present inventors have made a technical task to develop the natural product therapeutic agent which is more excellent in the improvement of a menopausal syndrome.

In order to solve the above object, the present invention provides a pharmaceutical composition for treating and preventing menopausal syndrome, which contains a combination herbal extract consisting of baekchul, heartache, goji berry, longan meat, dew, tofu and astronomical dong as an active ingredient.

In another aspect, the present invention provides a health functional food for preventing and improving menopausal syndrome, which contains a combination herbal extract consisting of Baekchul, heartache, goji berry, longan meat, wort, tofu and astronomical dong as an active ingredient.

Combination herbal extracts as defined herein include water, including purified water, lower alcohols of C1 to C4 or mixed solvents thereof, preferably extracts available in water or mixed solvents of water and alcohol.

Combination herbal extracts as defined herein additionally include one or more herbal extracts consisting of ginger and jujube; At least one vitamin selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, biotin, nicotinamide, folic acid, and calcium pantothenate; And / or at least one mineral selected from the group consisting of ferrous sulfate, zinc oxide, magnesium carbonate, potassium monophosphate, dibasic calcium phosphate, potassium citrate, calcium carbonate, and magnesium chloride.

Preferred blending weight parts of the combination herbal extract as defined herein include (a) Baekchul 1, 10, beetle 1-10, Gojija 1 to 1 in the case of the combination of Baekchul, Wokjak, Gojija, Longan meat, dew, tofu and astronomical dong. 10, longan meat 1 to 10, waddle 1 to 10, tofu 1 to 10, and 1 to 10 parts by weight of astronomical dong (w / w), more preferably Baekchul 1 to 5, heart 1 to 5, wolfberry 1 to 5 , Yongan 1 to 5, dew 1 to 5, tortoise 1 to 5 and astronomical dong 1 to 5 parts by weight (w / w), even more preferably white 1 to 3, heart 1 to 3, wolfberry 1 to 3, A combination of formulated in parts by weight (w / w) of 1 to 3 of longeye, 1 to 3 of wedges, 1 to 3 of worms and 1 to 3 of astronomical dong; (b) If the combination of baekchul, sirloin, wolfberry, longan, beef, bean curd, astronomical dong, ginger and jujube, baekchul 1-10, beetle 1-10, wolfberry 1-10, yongan 1-10, dew 1 To 10, tofu 1 to 10, astronomical dong 1 to 10, ginger 1 to 10 and jujube 1 to 10 parts by weight (w / w), more preferably white 1 to 5, heart 1 to 5, wolfberry 1 to 5 , Yongan 1-5, dew 1-5, tofu 1-5, astronomical 1-5, ginger 1-5 and jujube 1-5 parts by weight (w / w), even more preferably Baekchul 1-3, 1 to 3, wolfberry 1 to 3, yongan 1 to 3, wort 1 to 3, tofu 1 to 3, astronomical 1 to 3, ginger 1 to 2 and jujube 1 to 2 parts by weight (w / w) of Combinations.

As defined herein, “menopausal syndrome” is preferably fatigue, febrile flushing, vasomotor symptoms, depression, anxiety, dizziness, headache, associated with changes in menopausal syndrome, more preferably sex hormones, before or after menopause or by disease. , Joint pain, muscle pain, osteoporosis, insomnia, vaginal dryness, and the symptoms or symptoms, including all or part of the syndrome.

Hereinafter, the present invention will be described in detail.

The combination herbal extract of the present invention can be obtained as follows.

The herbal extract of the present invention is mixed with herbal medicines such as baekchul, sirloin, goji berry, longan meat, hyssop, tofu and astronomical dong, if necessary, ginger and jujube in a certain compounding ratio, and wash each combination sample with water. After drying, they are all ground and ground to a volume of water ranging from about 1 to 20 times, preferably about 2 to 10 times the weight of the herbal ingredient, C1 to C4 lower alcohol, or a mixed solvent thereof, preferably water. Extraction, such as hot water extraction, cold extraction, reflux cooling extraction, ultrasonic extraction or supercritical extraction, for about 1 hour to 1 day, preferably 2 hours to 8 hours at a temperature of from 120 to 120 ° C., preferably from 20 to 100 ° C. After extracting by a method, preferably a hot water extraction method, the extract is cooled and then filtered, and the filtrate is lyophilized to obtain the combination herbal extract of the present invention.

In another aspect, the present invention provides a health functional food for improving and preventing menopausal syndrome, which contains a combination herbal extract consisting of baekchul, sirloin, goji berry, yongan meat, dew, worm and cheonmundong as an active ingredient.

The extract as defined herein is a polar solvent selected from water, alcohol, lower alcohols having 1 to 4 carbon atoms or mixed solvents thereof, preferably water or water and alcohol mixed solvents, more preferably water or 20 to 90% water And extracts soluble in alcohol mixed solvents.

In another aspect, the present invention provides a pharmaceutical composition and health functional food for the treatment and prevention of menopausal syndrome containing the preparation method and the combination herbal extract prepared by the manufacturing method as an active ingredient.

Using the combined herbal extracts prepared above, the global movement ability and tail skin temperature were measured using the menopausal induced mice in vivo, and the experimental group to which the extracts of Examples 1 to 3 were administered was compared to the negative control group. By increasing the time, suppressing the increase of the tail skin temperature, and confirming the excellent effect of improving menopausal symptoms in the simple clinical cases, manufacturing health supplement foods, health functional foods, etc. for preventing and treating menopausal syndrome, menopausal nutritional supplements, etc. The first discovery that a combination extract can be used as a raw material to prove that it is useful for suppressing, preventing and treating menopausal syndrome.

Accordingly, the present invention provides a menopausal syndrome improvement agent containing a combination herbal extract consisting of Baekchul, heartache, goji berry, longan meat, wedge, head worm and astronomical dong as an active ingredient.

The composition of the present invention comprises 0.01 to 99% by weight of the herbal extract based on the total weight of the composition.

However, the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.

The composition comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

Compositions comprising extracts according to the invention are formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. The carriers, excipients and diluents that may be included in the formulation may include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one or more excipients in the compound, at least cotton, starch, calcium carbonate, sucrose. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol gelatin and the like can be used.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral and rectal or intravenous methods.

In another aspect, the present invention provides a therapeutic method for treating a climacteric syndrome patient, comprising administering a combination herbal extract consisting of baekchul, heartache, goji berry, longan meat, wedge, head worm and astronomical dong to patients with menopausal syndrome.

In another aspect, the present invention provides the use of a combination herbal extract consisting of baekchul, heartache, gojija, longan meat, dew, head worm and astronomical dong for the manufacture of a medicament for treating menopausal syndrome.

In another aspect, the present invention provides a health functional food for the improvement and prevention of climacteric syndrome, which contains a combination herbal extract consisting of baekchul, sirloin, goji berry, longan meat, dew, tofu and cheonmundong as an active ingredient.

As defined herein, "health functional food" refers to physical or mental functionality by adding the extract of the present invention to a conventional specimen for preventing or ameliorating a target disease in a human body or a mammal according to Korean Health Functional Food Act No. 6723. It includes a functional food to improve the functionality such as.

In another aspect, the present invention provides a menopausal nutritional supplement containing a combination herbal extract consisting of Baekchul, heartache, goji berry, longan meat, dew, tofu and astronomical dong as an active ingredient.

Health functional foods containing the extract of the present invention can be used in a variety of drugs, foods and beverages for the improvement and prevention of menopausal syndrome. Foods to which the extract of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, leach teas, health supplements, and the like, and are in the form of powders, granules, tablets, capsules, or beverages. Can be used.

The dietary supplement for the prevention and improvement of the menopausal syndrome of the present invention, the total weight of the composition comprises 0.01 to 95%, preferably 1 to 80% by weight percentage.

Moreover, the composition of the present invention can be used as a major component or additive and adjuvant in the manufacture of various dietary supplements and dietary supplements for the purpose of preventing or treating menopausal syndrome.

In addition, for the purpose of preventing and improving menopausal syndrome, it is prepared as a pharmaceutical dosage form such as powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups, or health functional foods in the form of tea bags, leach teas, and health drinks. And processing is possible.

Therefore, the present invention also provides a food additive for improving and preventing fatigue syndrome, menopausal syndrome, containing a combination herbal extracts of Baekchul, heartache, goji berry, longan meat, dew, tofu and cheonmundong as an active ingredient.

Food forms to which the extract of the present invention can be added include various foods, beverages, gums, teas, vitamin complexes, or health supplements of candy.

The health beverage composition of the present invention contains a mixture of the extract as an essential ingredient in the indicated proportions, and there is no particular limitation on the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. have. Examples of the above-mentioned natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like. Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

In addition, the extract of the present invention may be added to food or beverages for the purpose of preventing menopausal syndrome. At this time, the amount of the extract in the food or beverage can be added in 0.01 to 15% by weight of the total food weight, the health beverage composition is added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml Can be.

Global exercise capacity evaluation experiment using mice in vivo, using the combination herbal extract of the present invention, the tail skin temperature was measured, the experimental group increased the global exercise time and the increase of the tail skin temperature compared to the control group By confirming that the liver shows an excellent effect of improving menopausal symptoms in clinical cases, it is the first time that a combination extract can be used as a raw material for manufacturing health functional foods or supplements such as drugs for treating menopausal symptoms or menopausal nutritional supplements. F. It can be applied as a pharmaceutical composition, health functional food and health supplement food useful for suppressing, treating, preventing and improving menopausal syndrome.

Those skilled in the art will appreciate that various modifications and variations can be used in the compositions, uses and preparations of the invention without departing from the spirit or scope of the invention.

Although described in more detail by the following examples of the present invention, it should be understood that they are not intended to be limited to the following examples in any way of the present invention.

.

However, the following Examples and Experimental Examples are only illustrative in a range not limiting the scope of the present invention, the contents of the present invention is not limited by the following Examples and Experimental Examples.

Example 1 Preparation of Combination Example 1 (CB1)

Twenty times the weight of the formulation of dry herbs purchased from OmniHub with a certain weight compounding ratio: Baekchul 1.5, Loach 1.5, Gugija 1.5, Longan meat 2, Emulsion 1, Tofu 1, Astronomical Dong 1, Ginger 0.5, Jujube 0.5 After adding a volume of water and refluxing with a extractor (COSMOS660, Kyungseo Machinery Co., Ltd.) at 100 ° C. for 5 hours, the mixture was filtered using a filter tank equipped with a 100 mesh filter network, and the supernatant was decompressed and concentrated, followed by freeze drying. A crude extract was obtained and the other ingredients were added to the formulation by combining a certain weight ratio {calcium (KMF) 0.3, vitamin B1 (Germany DSM) 0.003, and vitamin B2 0.001 (Korea BASF)}. (CB1) was obtained and used as a sample for the following experiment.

Example 2. Preparation of Combination Example 2 (CB2)

Twenty times the weight of the formulation of dry herbs purchased from OmniHub with a certain weight compounding ratio: Baekchul 1.5, Loach 1.5, Gugija 1.5, Longan Meat 2, Emulsion 2, Tofu 2, Astronomical Dong 2, Ginger 0.5, Jujube 0.5 After adding 70% of ethanol by volume and refluxing with a extractor (COSMOS660, Kyungseo Machinery Co., Ltd.) at 100 ° C. for 5 hours, it was filtered through a filter tank with a 100 mesh filter network, and the supernatant was decompressed and concentrated, followed by freeze drying. Was used as a sample for the following experiment.

Example 3. Preparation of Combination Example 3 (CB3)

Add 20 times the volume of water to the dry weight of herbal ingredients purchased from OmniHub with a certain weight compounding ratio: Baekchul 1.5, Loach 1.5, Gugijagi 1.5, Longan meat 2, Wooslung 1, Tofu 1, Astronomical 1 After refluxing with an extractor (COSMOS660, Kyungseo Machinery Co., Ltd.) at 100 ° C. for 5 hours, the resultant was filtered using a filter tank with a 100 mesh filter net, and the supernatant was decompressed and concentrated and then lyophilized to combine the present invention (CB3). ) Was used as a sample for the following experiment.

Experimental Example 1. Menopause Animal Experiment

In order to confirm the effectiveness of improving the menopausal syndrome of the sample samples, the experiment was performed as follows in the menopausal animal model subjected to ovarian resection described in the literature.

1-1. Experimental animals

Seven-week-old ICR mice (28-30 g) were supplied from Orient Bio Co., Ltd. (Seoul, Korea) and used in animal laboratories for about 5 days. The water and feed were freely consumed, and the temperature (23 ± 2 ℃), Humidity (50 ± 10%) and contrast period (12 hours) were allowed to adjust automatically.

1-2. Experiment method

1-2-1. Mouse Ovariectomy

Based on Park et al. (Park et al., J Korean Neurosurg Soc. 2010, 48; p309), anesthetize an 8-week-old ICR mouse, cut the dorsal area with scissors, and then tie the left and right lower ovaries with sutures. The ovary was excised, the back was closed with a suture, disinfected, antibiotics were administered, and body temperature was maintained until waking up from a heating pad. After the recovery period for 2 weeks, it was used for the experiment.

1-2-2. Tail skin temperature measurement

Two weeks after ovarian resection, the samples of the present invention were administered orally in one dose group. The control group (Sham) and negative control group (OVX + saline) were orally administered with saline. After 2 weeks of administration, weigh the mouse and measure the tail skin temperature before starting exercise. Place the mouse in the restrainer, stabilize for 5 minutes, and remove 1 cm from the base of the tail every 3 minutes. The tail temperature was measured using a thermal imaging camera (FLIR T600, USA) (Basal temperature, T _B ), followed by 10 minutes at 15 m / min on a treadmill (Exer-3 / 6, Columbus instruments, USA). After exercise, the body was moved back to the fixing frame, and the tail temperature (Forced Exercise Temperature, T _E ) was measured using a thermal imaging camera three times at 1 minute intervals (Hideki et al., J Pharmacol Sci, 2005, 98: 323). The average temperature before exercise was calculated three times (T _B ), and the tail skin temperature measured after exercise was calculated according to Equation 1 below.

[Equation 1]

Total ΔTST = (T _E1 -T _B ) + (T _E2 -T _B ) + (T _E3 -T _B )

T _B : mean of three measurements of tail skin temperature before exercise

T _E1 : Tail skin temperature measurement 1 minute after exercise

T _E2 : Tail skin temperature measurement 2 minutes after exercise

T _E3 : Tail skin temperature measurement 3 minutes after exercise

In order to experiment with hot flushes, one of the symptoms of menopausal syndrome, the ovaries of the mice were excised and orally administered with the extracts of Examples 1 to 3 for 2 weeks, and the tail skin temperature was measured using a thermal imaging camera. .

As a result of the experiment, as shown in Table 1, a significant increase in the TST in the negative control group (OVX + saline) was confirmed that the ovarian resection was successful. In each of the experimental groups administered the extracts of Examples 1 to 3, it was confirmed that the TST, which is an indicator of febrile flushing, was significantly reduced compared to the negative control group.

Menopause of extract Hot flush  Therapeutic effect

Product ＼ Mean ± SEM	Basal temp.	Exercise temp.	ΔTST
Sham	27.0 ± 0.4	28.5 ± 0.5	4.4 ± 0.7
Negative Control (OVX + saline)	29.9 ± 0.8	34.8 ± 0.6 *	14.7 ± 2.4 *
Example 1 (2 g / kg)	27.3 ± 0.1	29.1 ± 0.5	4.9 ± 1.0 #
Example 2 (2 g / kg)	27.6 ± 0.2	28.5 ± 0.6	4.8 ± 2.1 #
Example 3 (2 g / kg)	27.9 ± 0.5	29.2 ± 0.7	4.3 ± 1.9 #

1-2-3. Anti-fatigue experiment using treadmill

Menopausal-induced mice were evaluated for the effects of menopausal fatigue by the extract administration of Examples 1 to 3 in the treadmill exercise experiment. Modify the method of Minghua et al. (Mechanisms of Ageing and Development, 2003, 124: 771) to raise the angle of the treadmill by 10 degrees, then start driving at 15 m / min, in steps of 5 m / min every three minutes. The speed was raised to a maximum of 30 m / min, and the time until the mouse became inoperable (maximum travel time) was measured.

As a result of measuring the maximum running time using the treadmill after administering the extracts of Examples 1 to 3 for 2 weeks, the control group traveled 26.2 ± 1.4 minutes and showed a significant decrease of 13.7 ± 1.0 minutes in the negative control group. Are significantly increased compared to the negative control. The maximum travel time is shown (Table 2).

Menopausal Antifatigue Effect of Extracts

Product ＼ Mean ± SEM	Max driving time (minutes)
Sham	26.2 ± 1.4
Negative Control (OVX + saline)	13.7 ± 1.0 *
Example 1 (2 g / kg)	31.0 ± 3.7 #
Example 2 (2 g / kg)	27.1 ± 1.9 #
Example 3 (2 g / kg)	29.9 ± 2.9 #

1-3. Statistical processing

All experimental results were statistically analyzed using ANOVA (one way analysis of variance), and the significance test was performed at p <0.05 level using Student-Newman-Keuls Test when significance was recognized.

In conclusion Samples of the present invention exhibited excellent hot flush reduction effect in caudal skin test of climacteric-induced mice and showed excellent maximum running time even in climacteric antifatigue experiments. It is believed to improve or treat menopausal hot flush and menopausal fatigue.

Experimental Example 2. Simple Clinical Experiment

50 females with mean age 50 with menopausal syndrome symptoms before and after menopause were randomly divided into five groups. The average value of the Kupperman index (Table 3), which is a menopausal evaluation scale, was obtained, and the results are shown in Table 4.

Kupperman Index

	Symptom	none	slightly	usually	Severe
One	Flushing, hot, burning	0	4	8	12
2	Sweating	0	2	4	6
3	insomnia	0	2	4	6
4	nervousness	0	One	2	3
5	depression	0	One	2	3
6	whirl	0	One	2	3
7	Fatigue	0	One	2	3
8	Arthralgia, myalgia	0	One	2	3
9	headache	0	One	2	3
10	Heartbeat	0	One	2	3
11	Dryness	0	One	2	3

From Table 4, there was no obvious change in the control without the sample, while the sample combinations of the present invention showed a marked improvement, it was confirmed that the samples of the present invention is excellent in improving the menopausal syndrome.

Clinical Effect on Menopausal Syndrome (Kupperman Index Change)

sample	Score before taking	Score after taking 2 weeks
Climacteric control	28.8	24.3
Menopause Example 1	29.9	10.9
Menopause Example 2	28.5	9.8
Menopause Example 3	30.2	10.3

Hereinafter, the formulation method and the type of carrier of the present invention will be described, but the present invention is not intended to be limited thereto, but specifically, a representative formulation example will be described below.

Formulation Example 1 Preparation of Powder

CB1 ----------------------------------------------- 200 mg

Lactose ---------------------------------------------- 100 mg

Talc ----------------------------------------------- 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

CB2 ----------------------------------------------- 200 mg

Corn Starch ---------------------------------------- 100 mg

Lactose ---------------------------------------------- 100 mg

Magnesium Stearate --------------------------------- 2 mg

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

CB3 ----------------------------------------------- 200 mg

Crystalline Cellulose ----------------------------------- 3 mg

Lactose ----------------------------------------- 14.8 mg

Magnesium Stearate ----------------------------- 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

CB1 ----------------------------------------------- 200 mg

Mannitol -------------------------------------------- 180 mg

Sterile Distilled Water for Injection ------------------------------- 2974 mg

Na ₂ HPO _4, 12H ₂ O ---------------------------------------- 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

CB2 ----------------------------------------------- 200 mg

Isomerized sugar -------------------------------------------- 10 g

Mannitol ----------------------------------------------- 5 g

Purified Water ----------------------------------------------- Proper

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding a proper amount of lemon aroma, and then mixing the above components, adding purified water and adjusting the whole to 100 ml by adding purified water and filling into a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Health Food (Nutrition Supplement)

CB3 --------------------------------------------- 1000 mg

Vitamin Mixture -------------------------------------- Proper

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 ------------------------------------ 0.5mg

Mineral Mixtures -------------------------------------- Suitable

Ferrous Sulfate --------------------------------------- 1.75 mg

Zinc Oxide ---------------------------------------- 0.82 mg

Magnesium Carbonate ------------------------------------ 25.3 mg

Potassium monophosphate -------------------------- 15 mg

Dicalcium Phosphate --------------------------------------- 55 mg

Potassium Citrate ---------------------------------------- 90 mg

Calcium Carbonate ----------------------------------------- 100 mg

Magnesium Chloride ------------------------------------ 24.8 mg

Although the composition ratio of the said vitamin and mineral mixture was mixed and comprised in the preferable embodiment the component suitable for a healthy food, you may change arbitrarily the compounding ratio considered that it does not deviate from the mind and range of this invention.

Formulation Example 7 Preparation of Healthy Drink

CB1 -------------------------------------------- 1000 mg

Citric Acid ----------------------------------------- 1000 mg

Oligosaccharide ----------------------------------------- 100 g

Taurine --------------------------------------------- 1 g

By adding purified water ---------------------------- 900 ml total

After mixing the above components in accordance with the conventional healthy beverage manufacturing method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare the healthy beverage composition of the invention.

As described above, the present invention may be modified in various ways, and such modifications are deemed without departing from the spirit and scope of the present invention, and all such modifications are obvious to those skilled in the art to be included within the scope of the following claims. something to do.

As described above, the global exercise capacity evaluation experiment using the in vivo mouse targeting the combination herbal extract of the present invention, the tail skin temperature was measured, the experimental group increased the global exercise time compared to the control group, the tail The increase in skin temperature is suppressed, and by confirming that the liver shows excellent menopausal symptoms improvement in clinical cases, the combination extract can be used as a raw material for manufacturing health functional foods or supplements such as drugs for treating menopausal symptoms or menopausal nutritional supplements. It was found for the first time that it can be applied as pharmaceutical composition, health functional food and health supplement food which is useful for suppression, treatment, prevention and improvement of menopausal syndrome.

Claims (16)

1. A pharmaceutical composition for treating and preventing menopausal syndrome, which contains a combination herbal extract consisting of baekchul, sirloin, goji berry, longan meat, hyssop, head worm and astronomical dong as an active ingredient.
2. According to claim 1, wherein the combination herbal extract further comprises one or more herbal extracts consisting of ginger and jujube; At least one vitamin selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, biotin, nicotinamide, folic acid, and pantothenic acid, calcium; And / or at least one mineral selected from the group consisting of ferrous sulfate, zinc oxide, magnesium carbonate, monobasic calcium phosphate, dibasic calcium phosphate, calcium citrate, calcium lactate, calcium carbonate, and magnesium chloride. Pharmaceutical composition.
3. The method according to claim 1 or 2,

   The combined weight of the combination herbal extract is (a) when the combination of Baekchul, Sanggi, Wolfberry, Longan meat, dew, tofu and astronomical dong, Baekchul 1 to 10, beetle 1 to 10, Wolfberry 1 to 10, Yongan meat 1 to 10, wedges 1 to 10, worms 1 to 10, and 1 to 10 parts by weight of astronomical dong (w / w); (b) If the combination of baekchul, sirloin, wolfberry, longan, beef, bean curd, astronomical dong, ginger and jujube, baekchul 1-10, beetle 1-10, wolfberry 1-10, yongan 1-10, dew 1 To 10, Tochung 1 to 10, astronomical dong 1 to 10, ginger 1 to 10 and jujube 1 to 10 parts by weight (w / w) of the pharmaceutical composition.
4. The method according to claim 1 or 2,

   The combination herbal extract is a pharmaceutical composition, characterized in that the extract containing water, C1 to C4 lower alcohol or a mixed solvent thereof, including purified water.
5. The method according to claim 1 or 2,

   The menopausal syndrome is characterized by all or part of the symptoms or signs of fatigue, hot flashes, vasomotor symptoms, depression, anxiety, dizziness, headache, joint pain, myalgia, osteoporosis, insomnia, vaginal dryness and the like associated with changes in sex hormones Pharmaceutical composition.
6. Health functional food for improving and preventing menopausal syndrome, which contains a combination herbal extract consisting of baekchul, heartache, goji berry, longan meat, hyssop, tofu and astronomical dong as an active ingredient.
7. The method of claim 6, wherein the combination herbal extract further comprises one or more herbal extracts consisting of ginger and jujube; At least one vitamin selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, biotin, nicotinamide, folic acid, and calcium pantothenate; And / or at least one mineral selected from the group consisting of ferrous sulfate, zinc oxide, magnesium carbonate, monobasic calcium phosphate, dibasic calcium phosphate, calcium citrate, calcium lactate, calcium carbonate, and magnesium chloride. Health functional food.
8. The method according to claim 6 or 7,

   The combined weight of the combination herbal extract is (a) when the combination of Baekchul, Sanggi, Wolfberry, Longan meat, dew, tofu and astronomical dong, Baekchul 1 to 10, beetle 1 to 10, Wolfberry 1 to 10, Yongan meat 1 to 10, wedges 1 to 10, worms 1 to 10, and 1 to 10 parts by weight of astronomical dong (w / w); (b) If the combination of baekchul, sirloin, wolfberry, longan, beef, bean curd, astronomical dong, ginger and jujube, baekchul 1-10, beetle 1-10, wolfberry 1-10, yongan 1-10, dew 1 Health functional foods, characterized in that the weight part (w / w) of 10 to 10, tofu 1 to 10, astronomical dong 1 to 10, ginger 1 to 10 and jujube 1 to 10.
9. A dietary supplement for the improvement and prevention of fatigue syndrome or menopausal syndrome, which contains as an active ingredient a combination herbal extract consisting of baekchul, sirloin, goji berry, longan meat, hyssop, tofu and astronomical dong.
10. 10. The method of claim 9, wherein the combination herbal extract further comprises one or more herbal extracts consisting of ginger and jujube; At least one vitamin selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, biotin, nicotinamide, folic acid, and calcium pantothenate; And / or at least one mineral selected from the group consisting of ferrous sulfate, zinc oxide, magnesium carbonate, monobasic calcium phosphate, dibasic calcium phosphate, calcium citrate, calcium lactate, calcium carbonate, and magnesium chloride. Health supplement food.
11. The method according to claim 9 or 10,

    The combined weight of the combination herbal extract is (a) when the combination of Baekchul, Sanggi, Wolfberry, Longan meat, dew, tofu and astronomical dong, Baekchul 1 to 10, beetle 1 to 10, Wolfberry 1 to 10, Yongan meat 1 to 10, wedges 1 to 10, worms 1 to 10, and 1 to 10 parts by weight of astronomical dong (w / w); (b) If the combination of baekchul, sirloin, wolfberry, longan, beef, bean curd, astronomical dong, ginger and jujube, baekchul 1-10, beetle 1-10, wolfberry 1-10, yongan 1-10, dew 1 To 10, Tochung 1-10, Cheonmundong 1-10, Ginger 1-10 and Jujube 1 to 10 parts by weight (w / w) of the health supplement.
12. A menopausal nutritional supplement containing as an active ingredient a combination herbal extract consisting of baekchul, sirloin, goji berry, longan meat, hyssop, tofu and astronomical dong.
13. The method of claim 12, wherein the combination herbal extract further comprises one or more herbal extracts consisting of ginger and jujube; At least one vitamin selected from the group consisting of vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, biotin, nicotinamide, folic acid, and calcium pantothenate; And / or at least one mineral selected from the group consisting of ferrous sulfate, zinc oxide, magnesium carbonate, potassium monophosphate, dibasic calcium phosphate, potassium citrate, calcium carbonate, and magnesium chloride. Supplements.
14. The method according to claim 12 or 13,

    The combined weight of the combination herbal extract is (a) when the combination of Baekchul, Sanggi, Wolfberry, Longan meat, dew, tofu and astronomical dong, Baekchul 1 to 10, beetle 1 to 10, Wolfberry 1 to 10, Yongan meat 1 to 10, wedges 1 to 10, worms 1 to 10, and 1 to 10 parts by weight of astronomical dong (w / w); (b) If the combination of baekchul, sirloin, wolfberry, longan, beef, bean curd, astronomical dong, ginger and jujube, baekchul 1-10, beetle 1-10, wolfberry 1-10, yongan 1-10, dew 1 Menopausal nutritional supplements, characterized in that the weight part (w / w) of 10 to 10, tofu 1 to 10, astronomical dong 1 to 10, ginger 1 to 10 and jujube 1 to 10.
15. A therapeutic method for treating a climacteric syndrome patient, comprising administering to a climacteric syndrome patient a combination herbal extract consisting of baekchul, heartache, goji berry, longan meat, pulp, head worm and astronomical dong.
16. Use of a combination herbal extract consisting of Baekchul, Bokja, Gugija, Longan meat, dew, head worm and astronomical dong to prepare a medicament for treating menopausal syndrome.