KR101864719B1 - Composition for prevention and treatment of osteoporosis comprising the extract of medicinal herb mixture - Google Patents

Abstract

The present invention relates to a composition and health food for prevention and treatment of osteoporosis comprising an extract of a medicinal herb mixture of Angelica gigas, Paeonia japonica, Atractylodes japonica, Wolfiporia extensa, Gardenia jasminoides, Glycyrrhiza uralensis, Platycodon grandiflorum, Zingiber officinale and Mentha Canadensis, and specifically, to an extract of medicinal herb, which inhibits osteoporosis and increases bone formation in ovariectomized rats, wherein the composition containing the herbal medicine extract of the present invention can reliably improve symptoms of bone diseases without changing hormones, and thus can be usefully used for prevention and treatment of bone diseases by replacing existing therapeutic agents.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention and treatment of osteoporosis,

The invention Angelica (Angelica gigas), Paeonia japonica (Paeoniae Radix Alba), baekchul (Atractylodes macrocephala Koidzumi), Poria cocos (Wolfiporia Extensa , Gardeniae Fructus , Glycyrrhiza uralensis , Licorice), Geilyeong (root of Platycodon grandiflo rum A. DC.), health ( Zingiberis Siccatum Rhizoma) and mint ( Mentha I have arvensis . piperascens) as an active ingredient. The present invention also relates to a composition for preventing or treating bone diseases.

The bone tissue that forms our body is a dynamic tissue that is constantly absorbed and formed to maintain bone mass and skeletal homeostasis. Osteoclasts and osteoclasts act to destroy and initiate bone destruction. Osteoclast-derived osteoclasts remove old bone through destruction or resorption, releasing calcium into the blood stream to maintain body function , And the osteoblast cells that form in the bone cells make new bones and rebuild the skeleton. In normal adults, there is always a balance between the amount of bone resorption and the amount of bone formation, and the imbalance between osteoblast and osteoclast activity results in a total osteoclast or osteogenesis, resulting in skeletal abnormalities.

In adolescence, bone formation occurs more actively than bone destruction, and when adults are formed, normal bone remodeling occurs as the balance between formation and destruction becomes. However, when it becomes old, bone destruction becomes more active than bone formation, It causes it. Such a failure to achieve a balance between the amount of bone resorption and the amount of bone formation may be caused by rheumatoid arthritis, osteoporosis, osteopetrosis, which is caused by excessive activity of osteoblasts and bone density, Bone diseases such as Paget's disease, osteomalacia, osteopenia, bone atrophy and osteoarthritis are caused.

Specifically, osteoporosis is caused by a decrease in the lime of the bone tissue, a decrease in the density of the bone, a widening of the bone cavity, and progress of the symptoms. As a result, the bone is weakened. . The bone mass is affected by various factors such as genetic factors, nutritional intake, hormonal changes, exercise and lifestyle differences, and the causes of osteoporosis include age, lack of exercise, low birth weight, smoking, low calcium diet, Ovariectomy and the like are known. Although there are individual differences, blacks have a lower bone resorption level than blacks, and bone mass is higher. Usually, bone mass is highest at 14-18 years old and decreases about 1% per year at old age. Especially in women, bone reduction continues after 30 years of age, and bone turnover is rapidly progressed by hormonal changes in menopause. In the postmenopausal period, the concentration of estrogen rapidly decreases, and a large amount of B-lymphocyte is produced as in the case of IL-7 (interleukin-7), and the B-cell precursor ) Accumulates and increases the amount of IL-6, thereby increasing the activity of osteoclast, resulting in a decrease in bone mass. Thus, osteoporosis is an unavoidable symptom for elderly people, especially postmenopausal women. In the developed countries, as population ages, interest in osteoporosis and its therapeutic agents is gradually increasing. In addition, there is a market of about $ 130 billion related to the treatment of bone disease worldwide and is expected to increase further in the future, so that each research institute and pharmaceutical company in the world invests heavily in the development of bone disease treatments.

Currently, estrogen, androgenic anabolic steroids, calcium, phosphate, fluoride, ipriflavone, and vitamin D3 are used in osteoporosis treatment. In addition, aminobisphosphonate was used in Merck, USA in 1995, and raloxifene, a selective estrogen receptor modulator (SERM) in the US Lilly Co. in 1997, .

Angelica gigas is rooted in Umbeniferae, then cuts off the roots, uses them in the sun, and has a peculiar smell. It is known to be effective in the treatment of anemia, women's diseases, pregnant women, postpartum recovery, severe cough and swelling. In addition, it not only strengthens the uterus but also regulates the physiology to extract the waste materials such as the blood residue. It also helps the blood circulation, deficiency of blood color, restoration of prenatal and postnatal blood, blood purification and movement of the intestines So that your hands and feet can improve your cold symptoms.

Paeoniaceae is a perennial plant of the family Ranunculaceae, Ranunculaceae, and paeonia . There are Paeoniae Radix Alba and Paeoniae Radix Rubra. Rev., 6 (5), pp. 495-499, 2001), and the peeled and peeled peel is called the peel. Veterinary medicines have the effect of suppressing atherosclerosis, decreasing blood pressure and improving blood flow, as well as anti-constipation effect, coronary artery dilatation effect and vascular disease in stomach, intestinal smooth muscle and uterine smooth muscle. This effect of the peony extract was confirmed by the antioxidant effect (Ohsugi M et al., J. Ethnopharmacol., 67, pp 111-119, 1999), platelet aggregation inhibitory effect (Lin HC et al., Planta Med, 65, pp 595-599, 1999 (Yang Ho et al., Fitoterapia, 75 (1), pp 45-49, 1987), anti-thrombotic effect (Ishida H et al., Chem. Pharm. Bull, 2004) and vascular endothelial cell protection from hyperlipidemia (Goto H et al., Phytother. Res., 13 (6), pp 526-528, 1999). In addition, it has been reported that glycoside, which is one of the constituents of peonies, is effective in the treatment of cerebral infarction (Yang J et al., Zhong Yao Cai, 23 (2), pp95-97, (Zhang GQ et al., Acta Pharmacol. Sin., 24 (12), pp. 1248-1252, 2003), as the constituent paeoniflorin protects against neurons.

Atractylodes macrocephala Koidzumi) is a perennial herb that belongs to Asteraceae and has a unique fragrance as a medicinal substance that helps digestion and diuretic action. Ingredients contain essential oils and vitamins A and D. Serine in the essential oil component has anti-inflammatory effect [Chem. Pham. Bull., 27 (12), 2965, 1979], anti-dementia effect (JP09094452) and the like have been reported and skin whitening agents (Korea Patent Publication 1999-0085303) have been reported to have excellent effects. In addition to the blood pressure lowering and promoting effect, Bacillus has anti-bacterial, anti-bacterial effect, and has a dryness, soothing and analgesic effect. The extracts may contain atractylion, atractylenolide I, II, III, diacetyl-atractylodiol, furfural, beta- Desmol (β-eudesmol) Other polysaccharides such as atractan A, B, and C have hypoglycemic substances.

Wolfiporia (茯) extensa ) belongs to the genus Staphylococcus aureus, the genus Bacillus subtilis (bacillus subtilis) It is a kind of fungus belonging to bacillus, which is a brown rot fungus which is mainly parasitized by pine trees but is linked to the roots of living pine trees. Mycelium grows while branching to white and hyphae begin to grow together. When the proper environmental conditions such as temperature and humidity are maintained, a hard lump-shaped sclerotia is formed. We call this the Bokryeong, and if it is white according to the color of the inside, it is called Baekbokgyeong, and if it is pale pink, it is called Baekbokryeong. The main constituents of the gyeongryeong were selected from the group consisting of Parchymic acid (C33H52O5), Pinicolic acid (C30H18O30), 3β-Hyderoxy-lanosta- 7.9 (11), 24-Trien-21-Oic aicd and Tumulosic acid ), Ebricoic acid (C31H50O3), etc. The most important among them is Pachyman content of 93%. In addition, Byeongryeong is known to have the functions of mind and body, It is known that amnesia, insomnia, chronic gastritis, and physical weakness have a high therapeutic effect.

Gardeniae Fructus is a plant belonging to the family Rubiaceae. Its main components are Crocin, Crocetin, Gardonin, Genipin and Geniposide. Alpha-crochine, xanthan gum, xylenes, xanthanole methyl, and esters. Gardenia has been used in folk remedies for bruises and scratches for a long time, and Dongbangbo has been proved to be effective for tropical forest, pesotanic acid, anti-inflammation, blood, blood and jaundice.

Licorice ( Glycyrrhiza uralensis , Licorice) is a perennial plant of eastern Siberia and the northeastern part of China. It is called licorice because its roots are rooted. It is an important medicinal herb that is almost contained in Chinese medicine. Licorice ( Glycyrrhiza ) is a medicinal plant with rosemary beans. Licorice is known to be an effective ingredient, glycyrrhizin, and other ingredients have been shown to inhibit gastric juice secretion and repair ulcer. In addition, licorice extract has been found to have estrogen action, anti-inflammatory action, anti-inflammatory action, anti-allergic action, detoxification action, and hyperlipidemia-improving action.

Gilgyeong is a campanulaceae plants (Campanulaceae) Bellflower (Platycodon grandiflorum A. DC.), Gakgyeong has been mainly used for the treatment of gadam, Jinhae, cough and bronchitis. It has anti-inflammatory, anti-cancer effect, pain relieving effect, digestive enzyme secretion through NF- Inhibitory effect, and cholesterol metabolism.

Health ( Zingiberis Siccatum Rhizoma) refers to the dried root of ginger root, the water extract of health suppresses the stimulation of starch digestion by saliva and vomiting due to copper sulphate, and the health powder is effective for nausea, postoperative nausea and vomiting of pregnant woman , And it is known that this septic effect acts directly on the gastrointestinal tract rather than on the action of the central nervous system (Pharmacodynamic Textbook Compilation Committee, Pharmacology, Dongmyung, 2006). In addition, anti-diabetic agents (Vishwakarma SL et el., Et al., Antidiabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats, J. Pharm. Pharmacol., 56 (1), pp. , Anxiolytic and antiemetic activity of Zingiber officinale, Phytother. Res., 16 (7), pp.621-626, 2002).

Mentha I have arvensis . piperascens) is a perennial herbaceous perennial plant of the dicotyledonous plant with a monocotyledonous plant. Its main components are alpha-pinene (+, -), anisaldehyde, daucosterol, eugenol ), Linalool, Menthone, (+) - neomenthol ((+) - Neomenthol), and the action of contracting the mucous membrane and blood vessels of the skin, paralyzing the peripheral nerve, , It has the effect of stopping the feeling of pungency, giving skin a unique feeling of refreshing to improve skin diseases, and has a sedative and antioxidant effect on the skin.

Korean Patent Publication No. 2005-0072625 discloses a composition for preventing and treating osteoporosis comprising a herbal medicine extract and a composition for preventing and treating osteoporosis. A composition for improving and preventing osteoporosis, which comprises ginseng, antler, antiperspirant, sine, and the like, is disclosed. In the Korean Oriental gynecological Society, Vol. 21, No. 1, 2008, there is disclosed a composition for ovariectomized white rats On osteoporosis of < / RTI > However, since the mixed composition disclosed in the above document has some osteoporosis treatment effect but does not exhibit a remarkable effect of treating osteoporosis, it is urgent to develop a composition having a significant osteoporosis treatment effect.

As a result, the present inventors have made efforts to develop a therapeutic agent for bone disease which is not toxic to the human body. As a result, it has been found that the herbal extract of Angelica gigas, Pseudomonas aeruginosa, The present invention has been completed based on the finding that bone mineral density is significantly increased in a rat model and thus can be effectively used for preventing and treating osteoporosis.

Korean Patent Publication No. 2005-0072625 JP-A-09094452 Korean Patent Publication No. 1999-0085303

Chan Soo Park, Young Joo Sohn Department of Oriental Obstetrics and Gynecology, Volume 21, Number 1, 2008 Altern. Med. Rev., 6 (5), pp495-499, 2001 Ohsugi M et al., J. Ethnopharmacol., 67, pp111-119, 1999 Lin HC et al., Planta Med, 65, pp 595-599, 1999 Ishida H et al., Chem. Pharm. Bull, 35 (2), pp. 849-852, 1987 Yang HO et al., Fitoterapia, 75 (1), pp 45-49, 2004 Goto H et al., Phytother. Res., 13 (6), pp 526-528, 1999 Yang J et al., Zhong Yao Cai, 23 (2), pp95-97, 2000 Zhang GQ et al., Acta Pharmacol. Sin., 24 (12), pp1248-1252, 2003 Akhani SP et al., Antidiabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats, J. Pharm. Pharmacol., 56 (1), pp. 101-105, 2004 Vishwakarma SL et al., Anxiolytic and antiemetic activity of Zingiber officinale, Phytother. Res., 16 (7), pp. 621-626, 2002

Conventional osteoporosis medicines are mostly estrogenic substances, and estrogenic substances have side effects such as cancer, gallstones, and thrombosis when administered over a long period of time. However, osteoporosis can not be treated by only short-term administration of the drug, and long-term administration of the drug is essential. Therefore, even when the drug is administered for a long period of time, there is a need for a new substance that has the above-mentioned side effects and has a medicinal effect sufficiently high enough to replace estrogen. Accordingly, an object of the present invention is to provide a pharmaceutical composition or a health food for prevention and treatment of osteoporosis using a herbal medicine extract which has no side effects even when administered for a long period of time and can exert excellent osteoporosis prevention and therapeutic effect.

In order to achieve the above object, the present invention provides a method for producing Angelica gigas , Paeoniae Radix Alba, Atractylodes macrocephala Koidzumi and Wolfiporia extensa extract, and Gardeniae Fructus , Licorice ( Glycyrrhiza uralensis , Licorice), Gyungyong ( Platycodon grandiflorum A. DC.)), Health ( Zingiberis Siccatum Rhizoma) and mint ( Mentha I have arvensis . piperascens). The present invention also provides a pharmaceutical composition for preventing or treating bone diseases.

In order to achieve the above object, the present invention provides a method for preventing or ameliorating osteoporosis, which comprises an extract of Angelica keiskei, Veterinary medicine, Health food.

The Angelica gigas , Paeoniae Radix Alba, Atractylodes macrocephala Koidzumi and Wolfiporia extensa extract, and Gardeniae Fructus ), licorice ( Glycyrrhiza uralensis , Licorice, Root of Platycodon grandiflorum A. DC), Health ( Zingiberis Siccatum Rhizoma) and mint ( Mentha arvensis there is. piperascens) is safe in the body, increases the weight and length of bones, increases bone mineral density, and can be used as a composition for prevention and treatment of bone diseases. , Can be used as a substitute for prevention and treatment of existing bone diseases in which side effects are present, and can also be used as a health food.

Hereinafter, the present invention will be described in more detail.

The present invention relates to the use of Angelica gigas , Paeoniae Radix Alba, Atractylodes macrocephala Koidzumi and Wolfiporia extensa extract,

Gardeniae Fructus ), licorice ( Glycyrrhiza uralensis , Licorice, Root of Platycodon grandiflorum A. DC), Health ( Zingiberis Siccatum Rhizoma) and mint ( Mentha arvensis there is. piperascens). The present invention also provides a pharmaceutical composition for preventing or treating bone diseases.

Wherein said composition comprises Angelica keiskei kei, Baekjak medicine, Baekjoo, Bokryeong, Gardenia, Licorice,

Health, or peppermint extract, and more preferably, the composition includes, but is not limited to, Angelica keiskei, Veterinary medicine, Lycoris chejuensis, Bacillus cereus, Gardenia, Licorice, Ginkgo, Health and peppermint extract.

Wherein said composition comprises 10 to 20 parts by weight of Angelica gigas Nakai, 10 to 20 parts by weight of Baekjong medicine, 10 to 20 parts by weight of Baekje, and 10 to 20 parts by weight of Baekjil,

5 to 15 parts by weight of germanium, 5 to 15 parts by weight of licorice, 5 to 15 parts by weight of germanium, 1 to 10 parts by weight of health and 1 to 10 parts by weight of peppermint are further preferably contained .

Also included were an extract consisting of 15 parts by weight of Angelica keiskei koidz., 15 parts by weight vetch, 15 parts by weight of alum, 15 parts by weight of germanium and 10 parts by weight of gardenia,

10 parts by weight of licorice, 10 parts by weight of ginseng, 5 parts by weight of health, and 5 parts by weight of peppermint are further preferably added but not limited thereto. More preferably, 15 parts by weight of Angelica gigantosa, 15 parts by weight, 15 parts by weight, 15 parts by weight of gum, 10 parts by weight of gardenia, 10 parts by weight of licorice, 10 parts by weight of gum, 5 parts by weight of health and 5 parts by weight of peppermint.

The herbal medicine extract is preferably, but not necessarily, prepared by a manufacturing method comprising the following steps.

1) Extracting a mixture of Angelica gigas Nakai, Veterinary medicine, Baekyoung, Gyungyoung, Gardenia, Licorice, Gyeonggyeong, Health and Mint mixture with an extraction solvent;

2) cooling the extract of step 1) and filtering; And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In this method, the extraction solvent of step 1) is preferably extracted with water, C ₁ to C ₂ lower alcohol or a mixture thereof, and the lower alcohol is preferably ethanol or methanol, It is not. The extraction solvent is preferably added in an amount of 0.1 to 10 times, more preferably 0.3 to 5 times, to the dried mixed herbal medicines, but is not limited thereto. The extraction temperature is preferably 20 to 70 DEG C, but is not limited thereto. In addition, the extraction time may be 12 to 48 hours, but is not limited thereto. In this method, the vacuum concentration of step 3) may be by using a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. The drying may be, but not limited to, vacuum drying, vacuum drying, boiling, spray drying or lyophilization.

The mixed extract may be extracted after mixing the herbal medicines, and the extracted extracts of the herbal medicines may be mixed and used, but the present invention is not limited thereto.

In a specific example of the present invention, the present inventors prepared a herbal medicine extract in order to confirm the effect of preventing and treating osteoporosis in a mixed extract of Angelica gigas Nakai, Veterinary Medicine, Baekyoung, Gyungyu, Gardenia, Licorice, In addition, the present inventors have found that in the case of ovariectomized rats, ovariectomized rats, ovariectomized rats, ovariectomized rats, ovariectomized rats, osteoporosis, acanthopanax, licorice, licorice, licorice, (See Table 2), body weight gain, dietary intake and dietary efficiency (see Table 3) and organ weights (see Table 4), after the diets were mixed with a mixture of herbal medicines for a certain period of time ) Was measured to confirm the safety of the herbal medicament mixture of the present invention.

The inventors also measured the femur weight and length (see Table 5), bone mineral density (see Table 6), blood biochemical index (see Table 7) and blood calcium and phosphorus content (Table 8) The osteoporosis improvement effect of the mixture was confirmed.

In addition, the present inventors have found that the blood cholesterol index is increased in comparison with the normal group when the herbal medicine mixture of the present invention is ingested. However, it was confirmed that this was better than the positive control group.

In conclusion, the pharmaceutical composition and the health food containing the mixed extract of Angelica gigantosa, Bacillus thuringiensis, Bacillus thuringiensis, Glycyrrhizae, Gardenia, Licorice, Bone mineral density and calcium and phosphorus content in the blood, and thus can be effectively used for prevention and treatment of bone diseases.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, the term " pharmaceutically effective amount " means an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the composition according to the present invention may vary depending on the age, sex, and body weight of the patient, and is generally in the range of 0.1 mg to 100 mg, preferably 0.2 mg to 17 mg per kg of body weight per day or every other day Or one to three times a day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.

The mixed herbal extract may be administered orally or parenterally at the time of clinical administration and may be used in the form of a general pharmaceutical preparation. That is, the mixed herbal medicine extract of the present invention may be administered in various formulations of oral or parenteral administration at the time of actual clinical administration. In the case of formulation, diluents such as fillers, extenders, binders, humectants, disintegrants, Or an excipient. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose and gelatin . In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. Various excipients such as wetting agents, sweeteners, fragrances and preservatives may be included in addition to water and liquid paraffin, which are commonly used simple diluents. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol and gelatin can be used. The dosage unit may contain, for example, 1, 2, 3 or 4 times the individual dose or may contain 1/2, 1/3 or 1/4 times the dose. The individual dosages preferably contain amounts in which the active drug is administered in a single dose, which usually corresponds to the full, half, one-third or one-fourth of the daily dose. The effective dose of the mixed herbal extract is 10 to 1,000 mg / kg, preferably 30 to 3,000 mg / kg, and can be administered 1-6 times a day.

The present invention also relates to a composition containing Angelica keiskei koidz., Veterinary medicine,

There is provided a health food for preventing or ameliorating bone diseases, which additionally contains any one or more extracts selected from the group consisting of gardenia, licorice, Jilin, health, and peppermint.

The health food includes Angelica keiskei, Veterinary medicine, Bacillus sp., Bacillus sp., Gardenia sp., Licorice root,

Health, or peppermint extract, and more preferably, it contains, but not limited to, Angelica keiskei, Veterinary medicine, Lycoris chejuensis, Bacillus cereus, Gardenia, Licorice root,

Wherein the health food comprises an extract consisting of 10-20 parts by weight of Angelica gigas, 10-20 parts by weight of a vinegar, 10-20 parts by weight of an extract and 10-20 parts by weight of a sea tangle,

5 to 15 parts by weight of germanium, 5 to 15 parts by weight of licorice, 5 to 15 parts by weight of germanium, 1 to 10 parts by weight of health and 1 to 10 parts by weight of peppermint are further preferably contained .

Also included were an extract consisting of 15 parts by weight of Angelica keiskei koidz., 15 parts by weight vetch, 15 parts by weight of alum, 15 parts by weight of germanium and 10 parts by weight of gardenia,

10 parts by weight of licorice, 10 parts by weight of ginseng, 5 parts by weight of health, and 5 parts by weight of peppermint are further preferably added but not limited thereto. More preferably, 15 parts by weight of Angelica gigantosa, 15 parts by weight, 15 parts by weight, 15 parts by weight of gum, 10 parts by weight of gardenia, 10 parts by weight of licorice, 10 parts by weight of gum, 5 parts by weight of health and 5 parts by weight of peppermint.

The combined extracts of Angelica gigas Nakai, Baekjaek, Baekyoung, Gyungyong, Gardenia, Licorice, Gyungyang, Healthy, and Mint of the present invention showed significant increase in femur weight and length and bone mineral density in ovariectomized rats that caused osteoporosis. And it was confirmed that it showed excellent osteoporosis prevention or improvement effect as compared with the positive control group. Therefore, it was confirmed that the mixed extracts of Angelica gigas, Glycyrrhiza uralensis, Bacillus sp., Bacillus sp., Gardenia, Licorice, Gakgyeong, Health and Mint can be effectively used as a health food for preventing or improving osteoporosis.

There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense. When the mixture of the mushroom and radish mixed extract of the present invention is used as a food additive, the extract can be used as it is, or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Generally, the amount of the compound in the health food may be 0.1 to 90 parts by weight of the total food. However, in the case of long-term intake intended for health and hygiene purposes or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural flavors such as tau Martin and stevia extract, synthetic flavors such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the composition of the present invention. In addition to the above, the mushroom and ragwort mixed extract of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, Glycerin, alcohols, carbonating agents used in carbonated beverages, and the like. In addition, the mushroom and radish mixed extract of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination.

Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples.

However, the following examples and experimental examples are illustrative of the present invention, and the content of the present invention is not limited by the following examples and experimental examples.

< Example  1> Mix Herbal medicine  Preparation of extract

<1-1> Herbal medicine  Screening and Pretreatment Process

150 g of Angelica gigantosa, 150 g of whitening agent, 150 g of gum, 150 g of gum, 150 g of gardenia, 100 g of licorice, 100 g of licorice, 100 g of gum, 50 g of health and 50 g of peppermint. Washed thoroughly with water. The trimming of herbal medicines is to facilitate their handling and extraction.

<1-2> Herbal medicine Heat number  Preparation of extract

The material obtained in the above process was put into an extraction device and extracted with an extraction solvent. Pure water as an extraction solvent was added 5 times as much as the herbal medicines and extracted with a cooling extraction apparatus at 95 ° C for 6 hours. The extracts were spontaneously spiked for 1-2 hours and then filtered with a cloth filter paper to separate the herbal medicines and the hot water extract. The filtered hot water extract solution was concentrated under reduced pressure and the water was removed by freeze drying to obtain a hot water extract of a herbal medicine.

<1-3> Herbal medicine  Preparation of ethanol extract

To the material obtained in the above process, 95% ethanol was added 5 times as much as the herbal medicines, and the mixture was extracted with a stirring reactor at 80 ° C for at least 12 hours, filtered using a filter, centrifuged (5,000 rpm, 4 ° C, 10 minutes) And lyophilized to obtain a herbal medicine ethanol extract.

< Experimental Example  1> Animal experiments on ovariectomized rats in osteoporosis model

<1-1> Preparation and breeding of experimental animals

A female ICR mouse (Dooyol Biotech Co., Ltd.) was used, from which 6-week-old ovaries were isolated without specific pathogen-free pathogen. Purchased rats were selected for healthy rats without a weight loss after 1 week of quarantine and adaptation and used for the experiment. Experimental rats were housed in a raising environment with a temperature of 23 ± 3 ℃, a relative humidity of 50 ± 10%, a ventilation frequency of 10-15 times / hour, a lighting time of 12 hours (08:00 ~ 20:00) . During the adaptation period of 1 week, the animals were freely consecutively fed with a solid feed for experimental animals (Cargill Agri Purina, Gunsan, Korea).

<1-2> Osteoporosis induction and drug administration

After 1 week of adaptation period, healthy animals were selected and classified into 6 groups based on the nodule method. That is, the experimental group was fed with the herbal medicine extract prepared in Example <1-1> at a dose of 300 mg / kg / day to the sham group, the ovariectomized mouse group, and the ovariectomized mouse in the normal control group, The mice were fed a diet containing 600 mg / kg / day of herbal extracts, 900 mg / kg / day of herbal extracts in ovariectomized rats, positive control (Chong Kun Dang, healthy dart joints) Were grouped into positive control group (400 mg / kg / day).

All diets were fed a basic diet of AIN-93 diet (Research Diets, Inc., New Brunswick, NJ, USA) (see Table 1) for 6 weeks. After the onset of osteoporosis, diets containing herbal extracts were quantified Were fed for 8 weeks. During the experimental period, diets and negative water were freely consumed.

Ingredient grams / kg Casein 200.00 Cornstarch 397.486 DYETROSE 132.00 Sucrose 100.00 Cellulose 50.00 Soybean Oil 70.00 t-Butylhydroquinone 0.014 Salt Mix # 210025 65.00 Vitamin Mix # 310025 10.00 l-Cystine 3.00 Choline bitarte 2.50 Total 1,000.00

&Lt; 1-3 > Weight change, weight gain, Dietary intake  And Eating efficiency measurement .

The body weights of the experimental animals administered with the mixed herbal medicine extracts were measured weekly by the method of <1-2>, and the weight gain, the dietary intake and the diet efficiency were measured after administration for a certain period of time to compare the body weights of the Shamshuman group, the experimental group and the control group . The body weight changes of the animals are shown in Table 2, and the weight gain, the dietary intake, and the diet efficiency of the animals are shown in Table 3.

As shown in Table 2, the ovariectomized mouse group showed a rapid increase in body weight as compared with the Sham group, and the 900 mg / kg / day group of the herbal extract of the present invention showed a weight gain similar to that of the positive control group.

As shown in Table 3, the dietary efficiency was not increased as the intake of the herbal medicine extract of the present invention was increased, and it was confirmed that the dietary efficiency was moderate between the sham group and the ovariectomized mouse group.

Therefore, the herbal medicine extract of the present invention was compared with the ovariectomized mouse group and the positive control group, and it was confirmed that there was no change in body hormone and it was safe without affecting body weight change, dietary intake and diet efficiency.

OVX Herbal medicine extract
(mg / kg / day) positivity
Control group
(mg / kg / day) 0 week 1 week 2 week 3 week 4 week 5 week 6 week 7 week - - - 32.5 ± 1.1 34.0 ± 1.2 34.9 ± 1.3 36.2 ± 1.3 35.4 ± 1.3 36.2 ± 1.4 37.7 ± 1.8 37.7 ± 1.7 + - - 38.4 ± 1.2 ^* 40.6 ± 1.2 ^* 42.0 ± 1.3 ^* 43.9 ± 1.4 ^** 45.4 ± 1.4 ^*** 47.0 ± 1.3 ^*** 48.1 ± 1.3 ^*** 49.1 ± 1.2 ^*** + 300 - 38.0 ± 1.2 ^* 39.4 ± 1.3 40.6 ± 1.4 42.2 ± 1.5 43.4 ± 1.6 ^* 44.3 ± 1.6 ^* 44.9 ± 1.5 ^* 45.4 ± 1.6 ^* + 600 - 38.4 ± 1.1 ^* 40.4 ± 1.2 ^* 42.0 ± 1.3 ^* 43.4 ± 1.4 ^* 43.9 ± 1.7 ^** 44.4 ± 1.8 ^* 45.7 ± 1.8 ^* 45.8 ± 1.8 ^* + 900 - 38.4 ± 1.7 ^* 40.1 ± 2.0 ^* 41.2 ± 2.0 ^* 43.1 ± 2.1 ^* 43.8 ± 2.3 ^** 44.8 ± 2.4 ^** 45.3 ± 2.4 ^* 46.2 ± 2.5 ^* + - 400 38.4 ± 1.0 ^* 40.1 ± 1.0 ^* 41.8 ± 1.2 ^* 43.5 ± 1.2 ^* 44.8 ± 1.1 ^** 45.4 ± 1.2 ^** 46.5 ± 1.0 ^** 47.3 ± 1.2 ^**

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^# p < 0.05, ^## p < 0.01, ^### p < 0.001 compared with the B group.

OVX Mixed herbal extract
(mg / kg / day) positivity
Control group
(mg / kg / day) Body weight gain
(g / day) Food intake
(g / day) Food efficiency ratio - - - 0.11 + 0.02 3.27 ± 0.02 0.03 ± 0.01 + - - 0.22 ± 0.01 ^** 3.30 ± 0.01 0.07 ± 0.01 ^** + 300 - 0.15 + 0.02 3.04 ± 0.01 ^{*** ###} 0.05 ± 0.01 + 600 - 0.15 + 0.02 2.98 ± 0.01 ^{*** ###} 0.05 ± 0.01 + 900 - 0.16 ± 0.01 3.06 ± 0.01 ^{*** ###} 0.05 ± 0.01 + - 400 0.18 + 0.02 3.31 ± 0.01 ^{*** ###} 0.06 ± 0.01

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^# p < 0.05, ^## p < 0.01, ^### p < 0.001 compared with the B group.

<1-4> Measurement of organ weight change by drug administration

The organ weight of the experimental animals was measured by the method of <1-2> after the herbal medicine extract was administered for a predetermined period, and the organ weights of the sham group, the experimental group and the control group were compared. The organ weight changes of the animals are shown in Table 4.

As shown in Table 4, in the ovariectomized mouse group, the organs weighed overall compared to the sham group. On the other hand, in the experimental group, it was confirmed that the weight of organs decreased as the intake of the herbal medicine extract increased and recovered to the normal group level, and 900 mg / kg / day of the herbal medicine extract group showed similar organs weight as the positive control group.

Therefore, the herbal medicine extract of the present invention was found to be safe when ingested in the body, since it did not change the long-term weight as a whole compared with the sham group and the positive control group.

OVX Mixed herbal extract
(mg / kg / day) positivity
Control group
(mg / kg / day) Liver
(g) Spleen
(g) Kidney (left)
(g) Kidney (right)
(g) - - - 1.50 0.08 0.13 + - 0.01 0.15 + - 0.01 0.14 ± 0.01 + - - 1.97 + - 0.12 0.15 + - 0.01 0.15 + - 0.01 0.15 + - 0.01 + 300 - 1.96 + 0.11 0.15 + - 0.01 0.14 ± 0.01 0.14 ± 0.01 + 600 - 1.73 ± 0.11 0.14 + 0.02 0.14 ± 0.01 0.13 + - 0.01 + 900 - 1.65 + 0.13 0.12 + - 0.01 0.12 + - 0.01 0.12 + - 0.01 + - 400 1.72 + 0.13 0.12 + - 0.01 0.14 ± 0.01 0.13 + - 0.01

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^# p < 0.05, ^## p < 0.01, ^### p < 0.001 compared with the B group.

<1-5> Changes in femur weight and length and bone mineral density

On the day of the autopsy, the femur was removed from the test animals and the muscle, ligament, and fat attached to the skeleton were removed, and the weight and length of the femur were measured. The bone mass was measured using a bone mineral density meter (PIXImus ^TM , GELUVAR, Medison, WI, USA) was used to measure bone mineral density (BMD). The weight and length of the femur are shown in Table 5 and the bone density is shown in Table 6.

As a result, as shown in Table 5, the weight and length of the femur increased rapidly in the ovariectomized mouse group as compared with that of the sham group, and the weight and length of the femur increased in the group treated with the herbal medicine mixed extract. And the weight and length of each of them increased in proportion. In the 900 mg / kg / day group of mixed extracts of herbal medicines, the values of bone mass and bone length of the positive control group and sham group were about 1/2.

As shown in Table 6, bone mineral density (BMD) decreased rapidly in the ovariectomized mouse group. In the group treated with the herbal medicine mixed extract, the bone mineral density increased with the increase in the dose, and 900 mg / kg / day group did not differ from the positive control group.

Therefore, it was confirmed that the ovariectomized mouse group resulted in osteoporosis due to a decrease in BMD compared to the increase in the weight and length of the femur. In the group administered with the herbal medicine extract of the present invention, BMD was increased with increasing the weight and length of the femur, And there was no significant difference from the control group, and it was confirmed that there was a significant effect on prevention and treatment of osteoporosis.

OVX Herbal medicine extract
(mg / kg / day) positivity
Control group
(mg / kg / day) Bone weight
(mg) Bone length
(mm) - - - 90.80 ± 5.69 16.43 + - 0.48 + - - 99.35 + - 5.61 17.83 ± 0.32 ^** + 300 - 96.95 + - 3.46 17.43 ± 0.18 + 600 - 97.00 + - 4.20 17.42 ± 0.12 + 900 - 98.22 + 4.96 17.44 + 0.22 + - 400 109.25 ± 4.10 17.53 + - 0.16

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^{# P <0.05, ## p <} 0.01, ### p <0.001 compared with the B ## p <0.01, ### p <0.001 compared with the B group.

OVX Herbal medicine extract
(mg / kg / day) positivity
Control group
(mg / kg / day) BMD
(g / cm ² ) - - - 0.830 0.010 + - - 0.768 + - 0.014 ^* + 300 - 0.777 + 0.012 + 600 - 0.781 + 0.014 + 900 - 0.805 + 0.012 + - 400 0.802 + 0.016

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^# p < 0.05, ^## p < 0.01, ^### p < 0.001 compared with the B group.

<1-6> Measurement of blood biochemical index

The animals were fasted for 12 hours before sacrifice, and anesthesia was made using anesthetic prepared by diluting tribromoethanol with tertiary amyl alcohol, and orbital blood was collected. Blood was placed in a plasma separate tube (Becton Dickinson, USA), left at room temperature for 30 minutes, centrifuged at 3,000 rpm for 20 minutes, and the plasma was separated and stored at -70 ° C until analysis.

Serum isolated from the blood samples collected on the day of the autopsy was analyzed by aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alanine aminotransferase (ALT) using a blood biochemical analyzer (KoneLab 20 XT, Thermo Fisher Scientific, Waltham, Finland) ), Triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) - cholesterol and low density lipoprotein (LDL) - cholesterol were measured.

As a result, as shown in Table 7, the total cholesterol level (TC) was increased in the ovariectomized mouse group compared to the Sham group. In the case of the herbal medicine extract group of the present invention, the total cholesterol level was increased as the intake of the herbal medicine extract increased. However, the increase was not significant compared with the positive control group.

Therefore, the total amount of cholesterol in the body can be increased when the herbal medicine extract is taken, but it is relatively safe compared to the case of taking the positive control group.

OVX Herbal medicine extract
(mg / kg / day) positivity
Control group
(mg / kg / day) TC
(mg / dl) HDL
(mg / dl) LDL
(mg / dl) TG
(mg / dl) - - - 118.21 + - 4.94 48.50 ± 2.16 16.78 ± 1.12 85.68 + - 8.33 + - - 134.67 ± 5.99 52.48 ± 2.56 28.96 + 1.95 85.18 + - 8.22 + 300 - 141.18 ± 12.33 55.76 ± 5.16 28.98 + - 2.82 83.50 ± 10.17 + 600 - 141.26 ± 14.88 56.22 + -5.69 30.19 + - 4.42 86.78 ± 13.01 + 900 - 171.36 ± 14.04 ^** 68.68 + - 5.44 ^* 36.99 ± 4.05 ^*** 87.82 + - 7.34 + - 400 178.08 ± 5.97 ^{** #} 71.49 + - 2.00 ^{** #} 37.16 ± 3.76 ^*** 91.01 + - 5.45

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^# p < 0.05, ^## p < 0.01, ^### p < 0.001 compared with the B group.

<1-7> Measurement of blood calcium and phosphorus content

Calcium and phosphorus contents of blood collected according to the method of <1-6> were measured, and the results are shown in Table 8.

As a result, as shown in Table 8, the ovariectomized mouse group showed a decrease in calcium and phosphorus content compared with the sham group, and the calcium and phosphorus levels of the sham group were 300 mg / kg / day of the herbal medicine extract of the present invention The calcium and phosphorus contents in the blood were significantly increased in proportion to the dose of the herbal medicine extract of the present invention.

Therefore, it is confirmed that the herbal medicine extract of the present invention increases calcium and phosphorus contents, which are the main constituents of bone in the blood, as compared with ovariectomized group and sham group, and thus it can be effectively used for prevention and treatment of osteoporosis.

OVX Herbal medicine extract
(mg / kg / day) positivity
Control group
(mg / kg / day) Ca
(mg / dl) P
(mg / dl) - - - 6.25 ± 0.17 5.34 0.31 + - - 5.49 0.25 4.85 ± 0.23 + 300 - 6.23 0.30 5.49 ± 0.27 + 600 - 6.23 ± 0.29 5.48 ± 0.26 + 900 - 7.10 ± 0.21 ^{* ###} 6.08 ± 0.22 ^## + - 400 7.39 ± 0.11 ^### 6.91 ± 0.18 ^{*** ###}

Values are expressed as mean ± SEM

^* p <0.05, ^** p <0.01, ^*** p <0.001 compared with the group.

^# p < 0.05, ^## p < 0.01, ^### p < 0.001 compared with the B group.

Claims (13)

It is known that Angelica gigas , Paeoniae radix Alba, Atractylodes macrocephala Koidzumi, Wolfiporia extensa , Gardeniae fructus , Glycyrrhiza uralensis , Licorice, Platycodon grandiflorum A. DC. ), Health ( Zingiberis Siccatum Rhizoma), and peppermint ( Mentha arvensis var. Piperascens) as an active ingredient.
delete delete 2. The composition of claim 1,
10-20 parts by weight of Angelica gigantosa extract, 10-20 parts by weight of Baekjang extract, 10-20 parts by weight of extract, 10-20 parts by weight of ginseng extract, 5-15 parts by weight of gardenia extract, 5-15 parts by weight of licorice extract, 5 to 15 parts by weight, health extract 1 to 10 parts by weight, and peppermint extract 1 to 10 parts by weight.
delete 2. The composition of claim 1,
15 parts by weight of Angelica keiskei koidz. Extract, 15 parts by weight of Baekjang extract, 15 parts by weight of extract, 15 parts by weight of ginseng extract, 10 parts by weight of gardenia extract, 10 parts by weight of licorice extract, 10 parts by weight of Gakyung extract, 5 parts by weight of health extract, 5 &lt; / RTI &gt; parts by weight of the composition.
The pharmaceutical composition for preventing or treating bone diseases according to claim 1, wherein the extract is extracted with water, a C ₁ to C ₂ lower alcohol or a mixed solvent thereof.
The pharmaceutical composition for preventing or treating bone diseases according to claim 1, wherein the composition increases bone density and bone content.
Health food for prevention or improvement of bone diseases, containing Angelica gigas, Veterinary medicine, Baekyoung, Byeongryeong, Gardenia, Licorice, Gakyung, Health and peppermint extract as active ingredients.
delete delete 10. The method according to claim 9,
10-20 parts by weight of Angelica gigantosa extract, 10-20 parts by weight of Baekjang extract, 10-20 parts by weight of extract, 10-20 parts by weight of ginseng extract, 5-15 parts by weight of gardenia extract, 5-15 parts by weight of licorice extract, 5 to 15 parts by weight, health extract 1 to 10 parts by weight and peppermint extract 1 to 10 parts by weight.
The health food according to claim 9, wherein the health food increases bone density and bone content.