KR101333090B1 - Composition for preventing or treating postmenopausal syndrome comprising oriental herbal extract - Google Patents

Abstract

The present invention relates to a composition for the prevention or treatment of female menopausal syndrome comprising a mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower as an active ingredient. The composition of the present invention has a bio-safety, and has an excellent effect of treating lipid metabolism abnormality, hormonal metabolic abnormality, uterus and ovarian function deterioration, which cause female menopausal syndrome in an animal model, for preventing or treating female menopausal syndrome. It can be usefully used as a composition.

Description

Composition for preventing or treating female menopausal syndrome comprising oriental herbal extract as an active ingredient {composition for preventing or treating postmenopausal syndrome comprising oriental herbal extract}

The present invention relates to a composition for the prevention or treatment of female menopausal syndrome comprising a mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower 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 most common postmenopausal symptoms include febrile hot flashes, sweating and other vascular motor system symptoms, and depression, anxiety, nervousness, and insomnia. In addition, chronic symptoms are symptoms appearing many years after menopause, such as dyskinesia, atrophic vaginitis, urethritis, urogenital symptoms, arteriosclerosis circulatory system disease, osteoporosis and the like.

In response to the hormone replacement therapy most commonly used for the treatment of menopausal and postmenopausal symptoms, the 2002 Women's Health Initiative (WHI) in the United States found that the therapy tends to increase the risk of breast cancer, coronary artery disease, and stroke. Announced. Therefore, in Korea, hormonal therapy recommends individualized treatment and short-term use of low doses, considering the risks and benefits of each individual. It is recognized that it needs to be periodically reassessed as it changes.

Korea has traditionally treated various postmenopausal and postmenopausal symptoms through treatments such as acupuncture and herbal medicine, and recently, more women have solved clinical problems after menopause with oriental medicine due to side effects of hormone replacement therapy. I would like to.

Therefore, research on this is important because there is no therapeutic drug yet excellent in the treatment effect of menopause syndrome and the safety of long-term administration has not yet existed.

On the other hand, Cuscuta japonica is an annual parasitic herb that is parasitic on the leaves of horsetail ginseng, L. japonicum, and larvae, and known ingredients include vitamin A, β-carotene, γ-carotene, and 5,6. It has been reported to contain epoxy-α-carotene, terraxanthin, and rutin (Information and Shin Min-kyo, Hyangjeomsa, p.882, Yeonglimsa, 1998).

This is a medicinal herb (Korea) that dried leaves, stems, and branches of the mistletoe mulberry (Taxillus chinensis, Loranthus parasiticus), a semi-parasitic plant that lives on other trees. . They are called parasitic, rainforest, and tree because they look similar to birds standing on them, and are harvested between winter and spring, cut off branches, dried or steamed.

The genus is a perennial herb belonging to Labiatae, whose medicinal part is root and rhizome, and its scientific name is Phlomis umbrosa Turczaninow. Sokdan is known to be effective in treating symptoms such as Changgong poisoning and crayfish due to its efficacy of clearing and swelling.

Glue refers to a medicine made by gluing finely sliced glue and roasting it in a bead.

Herbal medicine (Dioscoreae Rhizoma) refers to the root of the perennial herbaceous plant of the family Dioscoreaceae, a herb that is dried and dried after removing the bark and mucus from the root of the horse. It is distributed in Korea, Japan, Taiwan, and China. The plant has purple color, roots are flesh, and deep into the ground.

Safflower (Carthami Semen) is dried flowers and seeds of Asteraceae (Carthamus tinctorius L.), and its effect is almost the same as safflower. (Western Il et al., Intuitive Herbology, Daegu Haany University Press, p295, 2004,).

However, there have been no reports on the prevention or treatment of female menopausal syndrome with the mixed extracts of earth, sand, liver, glue, powder and safflower.

Thus, the inventors of the present invention, as a result of the study to develop a new drug with high prophylactic or therapeutic effects and low side effects of female menopausal syndrome, as a result of the mixed extract of earth and sand, fresh, fast, glue, powder and safflower The present invention was completed by confirming that it has a biosafety and excellent effect of treating lipid metabolism abnormality, hormonal metabolic abnormality, uterine and ovarian function deterioration in the menopausal animal model.

Domestic patent application number: 10-2009-0062112

The present invention relates to a composition for the prevention or treatment of female menopausal syndrome comprising a mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of female menopausal syndrome comprising a mixed extract of earth and sand, the raw, fast, glue, powder and safflower as an active ingredient.

In another aspect, the present invention provides a food composition for the prevention or improvement of female menopausal syndrome, including a mixed extract of earth and sand, raw, fast, glue, safflower and safflower.

The mixed extract of the earth and sand, the above-mentioned, fast, glucose, powder and safflower of the present invention has bio-safety, and to treat lipid metabolism abnormality, hormonal metabolic abnormality, uterine and ovarian dysfunction, which causes menopausal syndrome in a postmenopausal animal model. There is an excellent effect, it can be usefully used as a composition for the prevention or treatment of female menopausal syndrome.

1 is a diagram showing the cytotoxicity of the mixed extract of the present invention in breast cancer cell line.
Figure 2 is a diagram showing the effect of the mixed extract of the present invention on the phosphorylation of ER-α in breast cancer cell lines.
Figure 3 is a diagram showing the effect of the mixed extract of the present invention on phosphorylation of ERK in breast cancer cell line.
Figure 4 is a diagram showing the effect of the mixed extract of the present invention on weight gain in a postmenopausal animal model.
Figure 5 is a diagram showing the effect of the mixed extract of the present invention on blood GOT concentration in the postmenopausal animal model.
Figure 6 is a diagram showing the effect of the mixed extract of the present invention on blood GPT concentration in the postmenopausal animal model.
Figure 7 is a diagram showing the effect of the mixed extract of the present invention on blood HDL concentration in the postmenopausal animal model.
8 is a diagram showing the effect of the mixed extract of the present invention on blood triglyceride concentration in the postmenopausal animal model.
9 is a diagram showing the effect of the mixed extract of the present invention on blood glucose concentration in the postmenopausal animal model.
10 is a diagram showing the effect of the mixed extract of the present invention on blood phosphorus concentration in the postmenopausal animal model.
Figure 11 is a diagram showing the effect of the mixed extract of the present invention on blood calcium concentration in the postmenopausal animal model.
12 is a diagram showing the effect of the mixed extract of the present invention on the uterine index in the menopause animal model.
Figure 13 is a diagram showing the effect of the mixed extract of the present invention on blood estradiol-17β concentration in the postmenopausal animal model.
14 is a diagram showing the effect of the mixed extract of the present invention on blood NO concentration in the postmenopausal animal model.
15 is a diagram showing the effect of the mixed extract of the present invention on phosphorylation of ERK and AKT in uterine tissues in a menopausal animal model.
Figure 16 is a diagram showing the effect of the mixed extract of the present invention on uterine atrophy through menopause animal model through H & E staining.

The present invention provides a composition for the prevention or treatment of female menopausal syndrome, including a mixed extract of earth and sand, raw, fast, glue, powder and safflower as an active ingredient.

The composition comprises a pharmaceutical composition or a food composition.

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

The composition according to the present invention can be obtained as follows. The earth, sand, sesame, glue, powder and safflower are washed with water to remove foreign substances, dried in the shade and crushed. Earth and sand, velvet, fast, glue, sap and safflower can be used without limitation, such as grown or commercially available. Mix the ground pulverulent soil, the above-mentioned, fast-dry, glue, powder and safflower powder in a weight ratio of 15 to 35%: 5 to 25%: 5 to 25%: 5 to 25%: 15 to 35%: 5 to 25%, respectively. After that, an appropriate amount of solvent is added to ensure complete immersion. The mixed powder of earth and sand, the above-mentioned, fast, glue, powder and safflower is extracted using a solvent selected from water, alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, and preferably extracted with water. The extract may be impregnated or warmed at room temperature. The extract is filtered and concentrated to give the final extract.

In the composition of the present invention, the mixing ratio of the earth and sand, the raw, fast, glue, powder and safflower is preferably 15 to 35%: 5 to 25%: 5 to 25%: 5 to 25%: 15 to 35%: 5 To 25% by weight, preferably 20 to 30%: 10 to 15%: 10 to 15%: 10 to 15%: 20 to 30%: 10 to 15% by weight. When it is out of the range of the mixing ratio, there is no significant difference in terms of the treatment effect of the female menopausal syndrome, compared to the case of using the soil extract, the raw, fast, glue, powder and safflower extract alone, there is a concern of side effects.

The mixed extract of the earth and sand, the above-mentioned, fast, glue, powder and safflower according to the present invention activates the estrogen receptor and estrogen protein in cells and uterine tissue in vivo. In addition, in menopausal animal models, there is no weight gain, no liver toxicity, and the lipid metabolism-related indicators, such as high-density lipoprotein, triglyceride and blood glucose levels, and bone metabolism-related indicators such as blood phosphorus and blood calcium Improve uterine index, regulate blood estradiol and blood NO levels, and improve atrophy of uterine tissue.

As described above, the extracts of the earth and sand, the raw, fast, glue, powder and safflower of the present invention are biosafety, lipid metabolism abnormality, hormonal metabolic abnormality, uterine and ovary of the menopausal syndrome in the postmenopausal animal model Since there is an excellent effect of treating hypofunction, it can be usefully used as a composition for the prevention or treatment of female menopausal syndrome.

The term "menopausal syndrome" of the present invention refers to a disease that is associated with decreased estrogen secretion in postmenopausal women, such as cardiovascular diseases such as atherosclerotic cardiovascular disease, tachycardia, hot flashes, palpitations, sweating, etc. Neurovascular system abnormalities, motor organ abnormalities such as osteoporosis, mental nervous system abnormalities such as depression, urinary incontinence, difficulty urinating, urinary gestation, recurrent urinary system inflammation, changes in skin tissue and alopecia and the like. However, if the symptoms caused by a drop in female hormones are all menopausal syndrome, and not limited to the above symptoms.

The composition of the present invention may contain at least one known active ingredient having a therapeutic effect of female menopausal syndrome with a mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. 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, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, 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 sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the mixed extract of the earth and sand, the raw, fast, glue, powder and safflower of the present invention may be administered in an amount of 1 to 10000 mg / kg per day. The composition may be administered once a day, or divided into several doses.

The pharmaceutical composition of the present invention can be administered to a subject by various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention or treatment of female menopausal diseases.

In the present invention, "health functional food" refers to a food having a bioregulatory function such as prevention and treatment of diseases, biodefence, immunity, recovery from illness, and inhibition of aging, and should be harmless to the human body when taken in the long term.

The composition of the present invention may be added to a dietary supplement for the purpose of preventing or ameliorating female menopausal diseases. When the composition of the present invention is used as a food additive, the composition can be added 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). In general, the composition of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage. However, in the case of long-term intake for the purpose of health and hygiene 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.

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including meats, sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, gums, ice cream, soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like . The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may include a pulp for the production of natural fruit juice, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred examples, experimental examples, and production examples are provided to facilitate understanding of the present invention. However, the following examples, experimental examples and production examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples, experimental examples and production examples.

Example  Earthenware, Reminder , Fast, Glue , Medicine  And Safflower  Preparation of mixed extracts

The earth and sand, the above-mentioned, fast-dry, glue, powder and safflower selected from Dongguk University Ilsan Oriental Hospital (South Korea) were selected and powdered. The powders of pulverized earthworms, the above-mentioned raw material, fasteners, glue, powder and safflower were mixed in the weight% described in Table 1, and then dissolved in sterile purified water to obtain a final mixture extract.

Herb name English name Yang (g) Tosa Semen cuscutae 16 Reminder Ramulus taxilli 8 Fast Radix Dipsaci 8 Glue Colla corii asini 8 Medicine Rhizoma Dioscoreae 16 Safflower Cartjami semen 8 Total amount 64

Experimental Example  1. Safety Verification

The MTT assay was performed to confirm the stability of the mixed extracts of the earthworms, the above-mentioned, fast-growing, glue, powder and safflower prepared in Example 1.

More specifically, after incubating the breast cancer cell line MDA-MB-231 cells (5x10 ⁵ cells / well) for 12 hours in a 24-well plate, they were exchanged with RPMI-1640 (Invitrogen) medium without FBS (serum free medium). It stabilized for 4 hours. Thereafter, various concentrations (0.01, 0.1, 1 or 5μg) of the extracts of the earthworm, the above-mentioned life, fast, glue, powder and safflower were added to the cells and incubated for 48 hours. Then, 2 mg / ml of MTT solution (3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyl-tetra-zolium bromide, Sigma) was added and incubated for 4 hours, followed by DMSO (dimethylsulfoxide, Sigma). The cell viability was calculated by measuring the absorbance at a wavelength of 590 nm. The results are shown in Fig.

As shown in Figure 1, it was confirmed that the mixed extract of the earth and sand, the above-mentioned, fast, glue, powder and safflower of the present invention does not affect cell survival up to a concentration of 5μg. Therefore, in the subsequent cell experiments, a drug of 1 μg concentration was used.

Experimental Example  2. Verification of the effect on estrogen activity

In order to determine the effect on the intracellular estrogen activity of the mixed extracts of the earth and sand, raw, fast, glue, powder and safflower prepared in Example 1, experiments were performed using MDA-MB-231, a breast cancer cell line. MDA-MB-231 cell line was treated with a concentration of 1 μg / ml of the extracts of the earth and sand, fresh, fast, glue, powder and safflower of the present invention, and time-dependent (5, 10, 30, 60, 120 minutes) Phosphorylation of intracellular ERα (Estrogen receptor-alpha) and extracellular signal-regulated kinase (ERK) was measured via Western blot. ERK is an estrogen protein enzyme that is activated by ERα. Phosphorylation results of ERα and ERK are shown in FIGS. 2 and 3, respectively.

As shown in Figures 2 and 3, in the cells treated with the mixed extract of the earth, sand, fast, glue, powder and safflower of the present invention all phosphorylation of ERα or ERK compared to the control (C) not treated with the material It was confirmed that increases. Through the above results, it was confirmed that the mixed extract of the present invention activates the estrogen receptor and estrogen protein.

Experimental Example  3. Verification of therapeutic effect in postmenopausal animal model

3-1. Design of Menopause Animal Models

Eight-week-old Wister albino female rats (Orient, Korea) were used, and diet and drinking water were freely consumed in a controlled breeding room (Dongguk University Ilsan Hospital Animal Room) with a temperature of 22 ± 1 ° C, a humidity of 55 ± 1%, and a 12-hour contrast cycle. After adaptation, the animals were used for experiments for 7 days.

The experimental group was divided into four groups of 10 animals evenly by weight, and each group was treated as follows.

Group 1 (C; control group): Sham OVX, ovarian resection without abdominal resection after suture, no treatment afterwards,

-Group 2 (N; Negative Control group): OVX (ovarian ablation) + no treatment, ovarian ablation and no treatment,

-Group 3 (Ex group): OVX (ovary ablation) + herbal medicine treatment group, the group administered with a mixed extract of earth and sand, fresh, fast, glue, powder and safflower at a concentration of 500 mg / kg after ovarian ablation,

Group 4 (P group): OVX (ovarian resection) + Raloxifene Tx, raloxifene (selective estrogen receptor modulator used as a postmenopausal osteoporosis treatment) at 5.4 mg / kg after ovarian resection group.

In ovarian extraction, after anesthesia, the left and right 1cm incisions of the spine were incised laterally from the posterior rib, and then the peritoneum was cut again and the body fat around the ovary was taken out to remove the ovaries accumulated in the ovarian follicles. After the fallopian tube was ligated with a suture and the ovaries were extracted, the peritoneum and the myosphere were sewn with an absorbent suture and the skin was sutured with a nonabsorbable suture. The drug was administered for a total of 3 months, and then mixed with feed after freeze drying.

3-2. Weight change

After 3 months of drug administration, the weight of the experimental animals in each group was measured. The results are shown in Fig.

As shown in FIG. 4, the weight was significantly increased in the negative control group (N) in which the ovary was extracted and the other treatments were not compared with the group C (the normal group) in which the ovary was not extracted. In addition, compared to the negative control group (N) after the ovary extraction, the experimental group (Ex) administered the mixed extract of the earth and sand, the above-mentioned, fast, glucose, powder and safflower of the present invention (Ex) slightly reduced in weight, but there was no significant, raloxifene after ovarian extraction In group (P), weight was significantly decreased. Through the above results, it was confirmed that the mixed extract of the present invention does not cause post-menopausal weight gain.

3-3. Hepatotoxicity  inspection

In order to determine the effect of the mixed extracts of the earthworms, the above-mentioned, fast, glucose, powder and safflower prepared in Example 1 on the hepatotoxicity of experimental animals, the concentrations of GOT (glutamic oxalacetic transaminase) and GPT (glutamic pyruvate transaminase) were measured. Measured. To separate the serum, rats were first anesthetized with ether, and blood was collected from the abdominal vein. The blood was incubated at 25 ° C. for 30 minutes and then centrifuged at 2000 g at 4 ° C. for 15 minutes to carefully separate the supernatant. The separated serum was stored at -80 ° C. Measurement results of blood GOT and GPT are shown in FIGS. 5 and 6, respectively.

As shown in Figure 5 and Figure 6, the group (Ex) and the raloxifene administered group (P) to which the mixed extracts of the earth and sand, fresh, fast, glue, powder and safflower of the present invention (P) is administered to the negative control group (N) In comparison, blood GOT and GPT were significantly decreased. Through the above results, it was confirmed that the mixed extract of the present invention has no hepatotoxicity to the experimental animals.

Experimental Example  4. Analysis of indicators related to lipid metabolism

To determine the effect of the mixed extracts of earthworms, the above-mentioned, fast-growing, glue, powder and safflower prepared in Example 1 on the lipid metabolism-related indicators in the postmenopausal animal model, high density lipoprotein (HDL), triglyceride (TG) and glucose The concentration of was measured.

The results are shown in FIGS. 7 to 9, respectively.

As shown in FIG. 7, the concentration of HDL in the blood was slightly increased in the group (Ex) to which the mixed extracts of the earth and sand, fresh, fast, glucocorticoid, powdered safflower and safflower of the present invention were compared with the negative control group (N). It was.

In addition, as shown in Figure 8, the concentration of triglycerides (TG) in the blood is compared to the negative control group (N) in the group (Ex) to which the mixed extracts of the earth and sand, the raw, fast, glue, powder and safflower of the present invention (Ex) Significantly decreased.

In addition, as shown in Fig. 9, the concentration of glucose in the blood was slightly increased in the group (Ex) administered with the mixed extract of the earth and sand, the above-mentioned, fast, glue, powder and safflower of the present invention compared to the negative control group (N).

Through the above results, it was confirmed that the mixed extract of the present invention has an effect of somewhat improving the lipid metabolism-related indicators in the postmenopausal animal model.

Experimental Example  5. Metabolism  Related Indicator Analysis

The effects of the mixed extracts of the earthworms, the above-mentioned, fast-growing, glue, powder and safflower prepared in Example 1 on the bone metabolism-related indicators in the postmenopausal animal model were confirmed.

5-1. Blood  Concentration measurement

P is an important component of all cells and 85% of the human body is present in bone. Blood P is involved in energy metabolism, muscle contraction, and oxygen supply to tissues. It is known that P and Ca are closely related to bone metabolism because bone decreases with Ca and serum concentrations of Ca and P rise when bone is absorbed. . The change in the phosphorus concentration in blood according to the administration of the mixed extract of the present invention is shown in FIG.

As shown in FIG. 10, the concentration of phosphorus in the blood was slightly increased in the group (Ex) to which the mixed extracts of the earth and sand, fresh, fast, glucocorticoid, powdered safflower and safflower of the present invention were administered compared to the negative control group (N).

5-2. Measurement of blood calcium level

Changes in blood calcium levels are affected by calcium in the bones, and the increase in bone replacement rate due to ovarian extraction leads to a decrease in bone quality resulting in elevated calcium in the blood. It is known. The change in blood calcium concentration according to the administration of the mixed extract of the present invention is shown in FIG. 11.

As shown in FIG. 11, the concentration of calcium in the blood was slightly decreased in the group (Ex) to which the mixed extracts of earth and sand, fresh, fast, glucocorticoid, powdered safflower and safflower of the present invention were administered compared to the negative control group (N).

Through the above results, it was confirmed that the mixed extract of the present invention has an effect of somewhat improving the bone metabolism-related index in the menopause animal model.

Experimental Example  6. Verification of efficacy on uterine and ovarian function

The effects of the mixed extracts of the earth and sand, the above-mentioned, fast, glue, powder and safflower prepared in Example 1 on the uterine and ovarian function in the postmenopausal animal model was confirmed.

6-1. Uterine Index

Uterine index was measured to determine whether the mixed extract of the present invention prevents atrophy of the uterus that appears after menopause and helps physical recovery. Uterine index was calculated as a percentage of uterine weight relative to the weight of the experimental animals. The results are shown in Fig.

As shown in Fig. 12, compared with the negative control group (N), the uterine index significantly increased in the group (Ex) to which the mixed extracts of the earth and sand, the fresh, fast, glue, powder and safflower of the present invention were administered. Through the above results, it was confirmed that the mixed extract of the present invention has an effect of improving the uterine index without negative effects of the metabolic system such as weight gain.

6-2. Blood Estradiol  ( estradiol ) -17β concentration measurement

The concentration of estradiol-17β in blood, a natural estrogen in blood, was the most important indicator of menopause. The results are shown in Fig.

As shown in FIG. 13, the concentration of estradiol-17β in the blood was higher than that of the negative control group (N). Significantly increased. Through the above results, it was confirmed that the mixed extract of the present invention by controlling the concentration of estrogen in the blood, there is a therapeutic effect of menopausal diseases.

6-3. Blood NO  Concentration measurement

NO is a vascular relaxation factor released from vascular endothelial cells and is a potent vasodilator that plays a very important role in the function and structure formation of anti-inflammatory and antithrombosis. Nitric oxide produced in the uterus plays an important role in the contractile force and vascular tension of the uterine muscles, which affects uterine contraction, menstrual pain and blood loss during menstruation. It is known. Recent studies have also shown that estrogen and progesterone influence the expression of nitric oxide synthase in the uterus.

Blood NO was measured using a nitric oxide colorimetric assay kit (Biovision). More specifically, nitrate was converted to nitrite by mixing serum 85ul and nitrate reductase isolated from rats and reacting at room temperature for 1 hour. Thereafter, the Griess reagent was mixed and reacted at room temperature for 10 minutes. After the reaction was completed, absorbance at 540 nm was measured. The results are shown in Fig.

As shown in Figure 14, the concentration of NO in the blood is Compared to the negative control group (N), it was decreased in the group (Ex) to which the mixed extracts of the earth and sand, the above-mentioned, fast, gluco, powder and safflower of the present invention were administered.

6-4. In uterine tissue ERK  And AKT Phosphorylation of

To investigate the effect on the protein of uterine tissue, we measured the phosphorylation of ERK, which is involved in cell proliferation, and AKT, which acts as a regulator in bone formation. The results are shown in FIG. 15, respectively.

As shown in Fig. 15, compared with the negative control group (N), phosphorylation of ERK and AKT in the group (Ex) to which the mixed extracts of the earth and sand, the above-mentioned, fast-growing, glucocorticoid, powdered safflower and safflower of the present invention were administered. Phosphorylation increased significantly.

6-5. Histological Analysis of the Uterus

For histological analysis of the uterus, Rompun (0.04 ml / 100 g) and Zoletil 50 (0.04 ml / 100 g) were injected into the abdominal cavity of the rat, anesthetized, and the uterus was extracted. The uterine tissue was fixed in 10% paraformaldehyde for 24 hours at room temperature. The fixed uterine tissue was embedded in paraffin in a conventional manner, and then serial sections of 4 μm thickness were prepared. The sections were stained with hematoxylin and eosin and observed with an optical microscope (BX50). The results are shown in Fig.

As shown in Fig. 16, the negative control group (B) from which the ovaries were extracted had uterine tissue atrophy compared to the normal group (A) from which the ovaries were not extracted. Group (C) administered the mixed extract of the uterine atrophy did not occur compared to the negative control group (B).

Through the above experimental results, the mixed extracts of the earth and sand, the above-mentioned, fast, glue, powder and safflower of the present invention has an effect of improving the uterine atrophy, etc. occurring after menopause, can be used as a treatment for women menopausal syndrome Confirmed.

Hereinafter will be described a pharmaceutical composition containing the composition of the present invention and a preparation example of a health functional food, but not intended to limit the present invention only specifically described .

Formulation example  1. Preparation of pharmaceutical compositions

1-1. Manufacture of Powder

Mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

1-2. Manufacture of tablets

Mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

1-3. Preparation of capsules

Mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

1-4. Injection preparation

Mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ 2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

1-5. Manufacture of liquid agent

Mixed extract of earth and sand, raw fruit, fast, glue, powder and safflower 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation example  2. Preparation of food composition

2-1. Manufacture of health food

100 mg of mixed extract of earth and sand, raw fruit, fast, glucose, powder and safflower 100 mg

Vitamin mixture quantity

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

Folic acid 50 μg

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2-2. Manufacture of health drinks

100 mg of mixed extract of earth and sand, raw fruit, fast, glucose, powder and safflower

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 liter container, It is used in the production of the health beverage composition of the invention.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (7)

Pharmaceutical composition for the prevention or treatment of female menopausal syndrome comprising a mixed extract of earth and sand, said life, fast, glue, powder and safflower.
The method of claim 1, wherein the mixed extract is extracted from the mixed powder of earth and sand, the raw, fast, glue, powder and safflower with any one or more solvents selected from the group consisting of water, alcohol having 1 to 4 carbon atoms and mixed solvents thereof. Characterized in that the pharmaceutical composition for the prevention or treatment of female menopausal syndrome.
According to claim 1, wherein the earth, sand, fast, glue, powder and safflower are 15 to 35%: 5 to 25%: 5 to 25%: 5 to 25%: 15 to 35%: 5 to 25% by weight A pharmaceutical composition for the prophylaxis or treatment of female menopausal syndrome, characterized in that the formulation.
The method of claim 1, wherein the menopausal syndrome is characterized in that caused by a decrease in estrogen secretion, pharmaceutical composition for the prevention or treatment of female menopausal syndrome.
The method of claim 1, wherein the menopausal syndrome is selected from the group consisting of atherosclerotic cardiovascular disease, tachycardia, hot flashes, palpitations, sweating, osteoporosis, depression, incontinence, difficulty urination, urinary fetus, recurrent urinary system inflammation and alopecia A pharmaceutical composition for preventing or treating female menopausal syndrome, characterized in that at least one.
Food composition for the prevention or amelioration of female menopausal syndrome comprising a mixed extract of earth and sand, said life, fast, glue, powder and safflower.
The method of claim 6, wherein the menopausal syndrome is selected from the group consisting of atherosclerotic cardiovascular disease, tachycardia, hot flashes, palpitations, sweating, osteoporosis, depression, incontinence, difficulty urination, urinary fetus, recurrent urinary system inflammation and alopecia Food composition for the prevention or improvement of female menopausal syndrome, characterized in that at least one.

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