KR102028634B1

KR102028634B1 - A composition for preventing or treating menopausal cardiovascular disease comprising Cuscuta japonica Chois extract

Info

Publication number: KR102028634B1
Application number: KR1020150158301A
Authority: KR
Inventors: 고병섭; 육진아; 박인실; 이혜원
Original assignee: 한국 한의학 연구원
Priority date: 2015-11-11
Filing date: 2015-11-11
Publication date: 2019-10-04
Also published as: KR20170055614A

Abstract

The present invention is a composition for preventing or treating menopausal cardiovascular diseases, including the earth and sand extract or fractions thereof, a method for preventing or treating menopausal cardiovascular diseases using the composition, a menopausal cardiovascular system comprising the earth and sand extract or fractions thereof It relates to a food composition and a feed composition for the prevention or improvement of diseases. The composition comprising the earth and sand extract of the present invention as an active ingredient can be applied to various products including food compositions, cosmetic compositions, and quasi-drug compositions for the prevention or improvement of menopausal cardiovascular diseases as a natural drug.

Description

A composition for preventing or treating menopausal cardiovascular disease comprising Cuscuta japonica Chois extract}

The present invention relates to a composition for preventing and treating menopausal cardiovascular diseases comprising the earth or sand extract of the present invention, or a fraction thereof. More specifically, the present invention provides a method for preventing or treating menopausal cardiovascular diseases, including the earth and sand extract or a fraction thereof. The present invention relates to a therapeutic composition, a method for preventing or treating menopausal cardiovascular diseases using the composition, a food composition for preventing or improving menopausal cardiovascular diseases, including a tosa extract or a fraction thereof, and a composition for feed.

Menopausal disorders are caused by decreased secretion of estrogens, or female hormones, due to poor function of the ovaries after menopause, and changes in the musculoskeletal system such as muscle pain, arthralgia, and back pain due to vascular changes such as hot flashes, tachycardia, sweating, and headache. Symptoms, urinary incontinence and other changes in the genitourinary system, memory loss, depression, decreased concentration, dizziness, such as symptoms caused by changes in the nervous system, decreased vision, changes in skin and hair, etc. Although there are differences in hearing levels, about 80% of women before and after menopause are experiencing. In addition, the most notable fact is that important changes affecting the life of a woman over a period of menopause occur over a long period of time, increasing the risk of developing osteoporosis and cardiovascular disease.

Among these, cardiovascular diseases may include stroke, myocardial infarction, cerebral hemorrhage, heart failure, cerebral thrombosis, heart attack, vascular restenosis, and atherosclerosis caused by abnormalities of the heart and vascular system, all of which can be caused by thrombogenesis. . Thrombus refers to the formation of clumps of blood in the cardiovascular system of a living body, and when thrombus forms in the cardiovascular system, ischemic damage to organs or tissues is caused by a decrease or blockage of blood flow, and part or all of the thrombus falls off and is broken. Blood clots can cause embolism, leading to cardiovascular diseases including heart-related diseases (myocardial infarction, hypertension, heart failure, arrhythmia, arteriosclerosis) and vascular diseases (stroke).

Therefore, it is pointed out as a serious problem of cardiovascular diseases that excessive medical expenses and deterioration of quality of life are caused by serious physical and social sequelae after such disease itself and its occurrence.

As the problems with cardiovascular diseases are increasingly recognized, many investments have been made in the study of the pathogenesis of these diseases, as well as in the prevention and treatment of these diseases. Therefore, hormone replacement therapy and antithrombotic agents have been developed. Among them, hormone replacement therapy has been reported that its side effects such as breast cancer, coronary artery disease, stroke, thrombosis, etc. are being limited. Thus far, despite the steady research and development of the drug, the prevalence and incidence of cardiovascular disease is steadily increasing, and problems such as side effects occurring during the treatment process have not been solved. Therefore, there is an urgent need for the development of active materials and natural materials for the inhibition and prevention of cardiovascular diseases that do not have side effects along with the development of therapeutic agents.

Meanwhile, Cuscuta japonica Chois is a perennial vine plant belonging to the Convolvulaceae family, also called Saesamseum or Geumsacho. The name of Tozaja originated from the fact that a rabbit-like rabbit was eaten by a rabbit whose back or leg bones were injured, and in Dongbobogam, it was recorded that the earthenware improves energy, revitalizes, and is effective in back pain and diabetes. . In addition, the effects of earth and sand are reported to be effective in improving the strength of the kidneys, reinforcing kidney function, strengthening bone function, diuretic effect, snowy effect, night blindness, and has been widely used as a related herbal medicine. In addition, the earth and sand has a bone resorption inhibitory activity, it has been known that can improve the bone disease occurring in postmenopausal women (Korea Patent Publication No. 2013-0059533), but it is known as a therapeutic use for menopausal cardiovascular disease This was first identified by the inventors.

Against this background, the present inventors have made intensive studies to develop a method for improving menopausal cardiovascular diseases using natural herbs, and as a result, Cucuta japonica Chois extract has a thrombus accompanying at the onset of menopausal cardiovascular disease. It was found that there is an effect of suppressing the production, and using the same to complete the composition for preventing, improving or treating menopausal cardiovascular diseases.

One object of the present invention is to provide a pharmaceutical composition for preventing or treating menopausal cardiovascular diseases comprising Cucuta japonica Chois extract or a fraction thereof as an active ingredient.

It is another object of the present invention to provide a method for preventing or treating menopausal cardiovascular diseases comprising administering the pharmaceutical composition to a subject in need thereof.

Another object of the present invention to provide a food composition for the prevention or improvement of menopausal cardiovascular diseases comprising the earth and sand extract or fractions thereof as an active ingredient.

As one embodiment for achieving the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of menopausal cardiovascular diseases comprising the earth and sand extract or fractions thereof as an active ingredient.

The term "Cuscuta japonica Chois" used in the present invention refers to the seeds of Saengsam, a perennial vine plant belonging to the family of the flowers, and also called Saengsam or Geumsacho. It is a parasitic plant in woody plants, and its main stem is like wire and yellowish red. The stem is 1.5 mm in diameter and the leaves are 2 mm or less in scale. The flower is white and blooms from August to September, and the seed is called tosa. The earth and sand are not known for the treatment of menopausal cardiovascular disease, which was first identified by the inventors. In the present invention, the earth and sand may be purchased commercially, or may be used collected or grown in nature.

As used herein, the term "extract" means an extract of the earth and sand. The extract may be prepared by grinding the ground powder of each component to about 5 to 30 times the dry weight, preferably about 10 to 20 times the volume of water, methanol, ethanol, and the like having 1 (C ₁ ) to 4 (C ₄ ) Eluting with a polar solvent, such as a lower alcohol, or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, and the extraction temperature is 20 to 100 ℃, preferably 60 to 100 ℃, extraction period May be an extract extracted by using an extraction method such as hot water extraction, cold extraction, reflux cooling extraction, filtration extraction, or ultrasonic extraction for about 1 hour to 4 days, but may exhibit a prophylactic or therapeutic effect of the cardiovascular disease of the present invention. As long as the extract is present, the present invention is not limited thereto, and the extract, a diluent or concentrate of the extract, a dried product obtained by drying the extract, or any of these modifiers or purified products may be included.

As used herein, the term "fraction" refers to the result obtained by performing a fractionation to separate a specific component or a specific component group from a mixture comprising various various components.

In the present invention, the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art. Solvent fractionation method by treating various solvents, ultrafiltration fractionation method through an ultrafiltration membrane having a constant molecular weight, cut-off value, various chromatography (made for separation according to size, charge, hydrophobicity or affinity) Chromatography), and combinations thereof. In one embodiment of the present invention was used a method of obtaining a fraction from the extract by treating a predetermined solvent to the extract obtained by extracting the earth and sand. The kind of solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohol: nonpolar solvents such as hexane (Hexane), ethyl acetate, chloroform, chloroform, dichloromethane, and the like. These may be used alone or in combination of two or more thereof. In the case of using alcohol in the fractionation solvent, alcohols of C ₁ to C ₄ may be preferably used.

As an example, the fraction may be prepared by fractionating the Tosa extract with a solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane, ethyl acetate, and a mixed solvent thereof. As another example, the fraction may be prepared by fractionating the Tosa extract with water, hexane, ethyl acetate or butanol. It may also be extracted by hot water.

As used herein, the term "menopausal cardiovascular disease" is not only a direct disease caused by various causes such as abnormalities in the circulatory system, dysfunction, damage, etc. due to ovarian dysfunction in women's menopause, By generic disease it is meant comprehensively secondary diseases. Among these menopausal cardiovascular diseases, diseases caused by thrombosis may be at least one selected from the group consisting of stroke, myocardial infarction, cerebral hemorrhage, heart failure, cerebral thrombosis, heart failure, vascular restenosis, and atherosclerosis. This is not restrictive.

In the present invention, the menopausal cardiovascular disease may occur due to ovarian dysfunction in the postmenopausal women, resulting in female hormone secretion, which may be a disease occurring in the heart and major arteries, and the menopausal cardiovascular disease is caused by thrombogenesis. Can be. However, in order to treat this, the risk of developing breast cancer, coronary artery disease, stroke, and venous thrombosis is increased when women undergoing postmenopausal women or women who do not have a uterus and estrogen-progesterone or female hormone therapy. Side effects have been reported, and female hormone therapy has been limited.

In one embodiment of the present invention, the composition containing the Tosa extract did not affect the proliferation of breast cancer cells, and had an effect of inhibiting menopausal thrombus formation.

Specifically, while the positive control β-estradiol proliferated breast cancer cells significantly, the soil stalk did not affect the proliferation of breast cancer cells. In addition, thrombus generation time was 11.67 ± 0.58 in the group treated with sedimentary thrombus induced animal model, and the thrombus fish time was 7.00 ± 1.41 in the group animal group not treated with soil sediment extract. Indicated, by confirming that the Tosa extract extract administration group increased 1.67 times the thrombus generation time, it was confirmed the efficacy of inhibiting thrombogenesis (Fig. 2). Therefore, the pharmaceutical composition of the present invention does not affect the proliferation of breast cancer cells, and also improves compliance with treatment of menopausal cardiovascular disease by inhibiting thrombogenesis and alleviates side effects associated with the treatment, thereby improving the quality of life of patients. It is expected to increase.

In addition, by confirming that the composition of the present invention does not affect breast cancer cell proliferation, it can be used as a prophylactic or therapeutic agent for a cardiovascular disease that does not cause breast cancer. There is an advantage that can be used stably without causing or causing harmful action.

As used herein, the term "prevention" refers to any action that inhibits or delays the development of cardiovascular diseases by administering to the subject a pharmaceutical composition for preventing or treating menopausal cardiovascular diseases.

As used herein, the term "treatment" means all the actions of administering the composition of the present invention to a subject suspected of developing menopausal cardiovascular disease to improve or benefit from cardiovascular disease.

The pharmaceutical composition of the present invention may include 0.01 to 100% by weight of the earth and sand extract or fractions thereof, based on the weight of the total composition, specifically 1 to 80% by weight, but is not limited thereto.

The pharmaceutical composition for preventing or treating cardiovascular diseases according to the present invention may further include a pharmaceutically acceptable carrier, and may be formulated together with the carrier to be provided as food, pharmaceuticals, feed additives and drinking water additives. Can be.

As used herein, the term "pharmaceutically acceptable carrier" may refer to a carrier or diluent that does not interfere with the biological activity and properties of the compound to be administered without stimulating the organism.

The kind of the carrier usable in the present invention is not particularly limited, and any carrier can be used as long as it is a conventionally used and pharmaceutically acceptable carrier in the art. Non-limiting examples of the carrier include saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, meltodextrin solution, glycerol, ethanol, etc. These are used alone or in combination of two or more Can be used.

In addition, if necessary, other conventional additives such as antioxidants, buffers and / or bacteriostatic agents may be added and used, and diluents, dispersants, surfactants, binders, lubricants, and the like may be additionally added, such as aqueous solutions, suspensions, emulsions, and the like. It may be formulated into injectable formulations, pills, capsules, granules or tablets.

The mode of administration of the pharmaceutical composition for preventing or treating cardiovascular diseases according to the present invention is not particularly limited and may be in accordance with a method commonly used in the art. As a non-limiting example of the mode of administration, the composition may be administered by oral or parenteral administration. The pharmaceutical composition for preventing, ameliorating or treating the cardiovascular disease of the present invention may be prepared in various formulations according to a desired administration method.

The pharmaceutical composition of the present invention may also be used as a single agent, and may be prepared and used as a complex preparation, further including a drug known to have a recognized cardiovascular treatment effect, and formulated using a pharmaceutically acceptable carrier or excipient. It may be prepared in unit dose form or incorporated into a multi-dose container.

In another aspect, the present invention provides a method for preventing or treating menopausal cardiovascular diseases, comprising administering the pharmaceutical composition of the present invention to a subject having or likely to develop a menopausal cardiovascular disease.

At this time, the earth and sand, extracts, fractions, menopausal cardiovascular disease, the definition of prevention and treatment is as described above.

As used herein, the term "individual" means all animals, such as rats, mice, and livestock, including humans, who may or may not develop menopausal cardiovascular diseases. As a specific example, it may be a mammal including a human.

The method of preventing or treating the menopausal cardiovascular disease of the present invention may specifically include administering the pharmaceutical composition in an pharmaceutically effective amount to an individual except a human having or at risk of developing a cardiovascular disease. Can be.

As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the sex, age, weight, Well-known in the field and other medical fields, including health status, type of disease, severity, drug activity, drug sensitivity, method of administration, time of administration, route of administration, and rate of release, duration of treatment, combination or drug used simultaneously Depending on the factor, it can be readily determined by one skilled in the art.

The pharmaceutical compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. In consideration of all the above factors, it is important to administer an amount that can achieve the maximum effect in a minimum amount without causing side effects, and can be easily determined by those skilled in the art.

Specifically, the composition of the present invention may be administered at 0.0001 to 100 mg / kg body weight per day, more specifically at 0.001 to 100 mg / kg body weight, based on solids. Dosing may include administering the recommended dose once daily, or in divided doses.

As used herein, the term "administration" means introducing the pharmaceutical composition of the present invention to a patient in any suitable manner, and the route of administration of the composition of the present invention is oral or parenteral as long as the target tissue can be reached. Administration can be via a variety of routes.

The route of administration and mode of administration for administering the composition is not particularly limited and may be in accordance with any route of administration and mode of administration so long as the composition comprising the composition can reach the desired site of interest. Specifically, the composition may be administered through various routes, oral or parenteral, and non-limiting examples of the route of administration include oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, nasal What is administered through intralateral or inhalation etc. are mentioned.

As another aspect, the present invention provides a food composition for preventing or improving menopausal cardiovascular disease.

The earth and sand has been used for a long time as a natural substance has been proved to be stable, and can be prepared and consumed in the form of a food that can prevent or improve cardiovascular disease while common sense.

Terms used in the present invention. "Improvement" means all actions that reduce various parameters associated with the condition being treated for the menopausal cardiovascular disease, such as the extent of symptoms, recovery time, and the like.

The kind of the food is not particularly limited, and may include all foods in a general sense. Non-limiting examples of foods to which the substance may be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, drinks, tea , A drink, an alcoholic beverage, and a vitamin complex. When the composition is used as a food additive, the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to conventional methods.

The food composition may comprise a food acceptable carrier.

The food composition may be a health functional food. Functional food is the same term as food for special health (FOSHU), and refers to foods with high medical and medical effects, which are processed to efficiently display bioregulatory functions in addition to nutrition. The food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. in order to obtain useful effects in the prevention or improvement of cardiovascular diseases.

At this time, the content of the extract contained in the food is not particularly limited, but may be included in 0.01 to 100% by weight, more preferably 1 to 80% by weight relative to the total weight of the food composition. If the food is a beverage it may be included in a ratio of 1 to 30 g, preferably 3 to 20 g based on 100 mL.

The health functional food can be prepared by a method commonly used in the art, and the preparation can be prepared by adding the raw materials and ingredients commonly added in the art. In addition, unlike the general medicine has the advantage that there is no side effect that may occur when taking a long-term use of the drug as a raw material and can be excellent in portability.

In addition, the food composition may include additional ingredients that are commonly used in food compositions to improve the smell, taste, time and the like. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu) and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, valine and the like.

In addition, the food composition is a preservative (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetic acid, etc.), fungicides (bleaching powder and highly bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisol (BHA), butylhydride) Oxytoluene (BHT), etc.), colorant (such as tar pigment), colorant (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite), seasoning (MSG glutamate, etc.), sweetener (ducin, cyclate, saccharin Foods such as sodium, etc.), fragrances (vanillin, lactones, etc.), swelling agents (alum, potassium D-tartrate, etc.), reinforcing agents, emulsifiers, thickeners (foils), coatings, gum herbicides, foam inhibitors, solvents, modifiers, etc. It may include food additives. The additive may be selected according to the type of food and used in an appropriate amount.

An example of the food composition of the present invention may be used as a health beverage composition, in which case it may contain various flavors or natural carbohydrates and the like as additional ingredients, such as a general beverage. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; Sugar alcohols such as xylitol, sorbitol, and erythritol. Sweeteners include natural sweeteners such as taumartin, stevia extract; Synthetic sweeteners such as saccharin and aspartame; The ratio of the natural carbohydrate may be generally about 0.01 0.04 g, specifically about 0.02 0.03 g, per 100 mL of the health beverage composition of the present invention.

In addition to the above, the health beverage composition includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, Alcohol or carbonation agent and the like. Others may contain fruit flesh for the production of natural fruit juices, fruit juice drinks, or vegetable drinks. These components can be used independently or in combination. Although the ratio of such an additive is not critical, it is generally selected from the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.

The composition comprising the earth and sand extract of the present invention as an active ingredient has the effect of effectively preventing, improving, and treating menopausal cardiovascular diseases by inhibiting thrombus formation.

In addition, the composition comprising the earth and sand extract of the present invention as an active ingredient is to be applied to a variety of products including a food composition, animal feed composition, cosmetic composition, and quasi-drug composition for the prevention or improvement of menopausal cardiovascular diseases as a natural drug. Can be.

In addition, the composition of the present invention is derived from natural products and can be used safely without causing serious irritation or harmful effects in the body in addition to preventing, treating, and improving cardiovascular diseases.

1 is a graph showing the results of evaluating the effects of estrogen (17β-estradiol) and tosa extract on breast cancer cell proliferation using MCF-7 cell line.
Figure 2 is a graph showing the results of examining the antithrombotic activity of the earth and sand extract using the menopausal thrombus induced model animals (Sham; ovary extraction rat, OVX-control group; Rats treated with Tosa extract in thrombus-induced mice, and the results were expressed as mean ± SD (N = 3) Statistical significance values were compared with control data by Student's t-test (** p). <0.01)).

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are only for illustrating the present invention by way of example, and the scope of the present invention should not be construed as being limited by these examples.

Example 1: Preparation of Tosa Extract

Earthenware according to the invention was purchased from Daejeon Baekjaedang. In order to prepare the earth and sand extract, after adding 10 times the amount of water or ethanol of the earth and sand sample amount, and then treated at 70 ℃ for 12 hours to obtain a hot sand extract. The soil extract was filtered with a 0.4μm filter, and then concentrated and lyophilized using a rotary evaporator to prepare a soil extract.

Example 2: MCF Of Estrogen and Tosa Extracts on Breast Cancer Cell Proliferation Using -7 Cell Line

Example 2-1. MCF-7 Cell Culture

Human breast adenocarcinoma-derived cancer cells, the MCF-7 cell line (Human breast adenocarcinoma cell line) were distributed from the Korea Cell Line Bank. For cell culture, 37 ° C., 5% CO in RPMI 1640 (Roswell Park Memorial Institute) medium containing 10% fetal bovine serum (FBS) and 1% penicilin-streptomycin. Cells were cultured under ₂ conditions. The cell culture was changed every 2 days and passaged when cells reached 80% to 90% cell confluence in 100 mm Petri dishes. After passage, the cell number was measured using cytometry to measure estrogen activity, seeded in each well of a 96 well plate at a cell density of 1.0 × 10 ⁵ , and the rest was cryopreserved.

Example 2-2. Review of the effects on breast cancer cell proliferation

17β-estradiol was used as a positive control for evaluating whether sedimentary hydrothermal extracts on MCF-7 cells affected breast cancer cell proliferation. 5% Charcoal stripped FBS pretreated with dextran-coated charcoal (Sigma, USA) to remove steroid hormones in fetal bovine serum (FBS) in MCF-7 cell culture Incubated for 48 hours using RPMI 1640 medium containing. Aliquots of 1.0 × 10 ⁴ cells / well into 96 well plates were incubated for 24 hours. Then, the soil extract was treated at 10 μg / mL concentration, and after 24 hours of incubation, 10 μL of assay reagent was added and reacted in the incubator for 3 hours, followed by a microplate reader at 450 nm. Changes in absorbance were measured to show cell viability as a percentage in the control group (FIG. 1).

1 is a graph examining whether estrogens (17β-estradiol) and soils affect breast cancer cell proliferation using MCF-7 cell lines.

As shown in FIG. 1, the number of MCF-7 cells increased significantly in the positive control group 17β-estradiol added group compared to the control group in the steroid hormone-free medium. In contrast, the sediment extract group did not affect breast cancer cell proliferation. From these results, it was confirmed that 17β-estradiol proliferated breast cancer cells significantly, as reported as a side effect of conventional hormone treatment, but the tosa extract did not affect breast cancer cell proliferation, breast cancer development It is expected to be used as a preventive and therapeutic agent for menopausal diseases that do not cause side effects.

Example 3: Menopausal Extraction of Tosa Extract Using Thrombus-Induced Model Animals Antithrombotic Active search

Example 3-1. Ovarian Extraction Menopause Model

The model animal was purchased from Orient Bio for 7 weeks of age (Sprague Dawley) female red, and then adapted to the basic diet for 1 week, and then separated into Sham and Ovarian extraction by randomized block design. Was carried out. Animal anesthesia for ovarian extraction was induced by inhalation anesthesia with a mixed gas of 2% isoflurane and nitrogenous oxygen at 7: 3, and was performed using a heating pad to maintain a constant body temperature during the procedure. ) Was maintained at 37 ° C. After the anesthetized animals were lying and fixed, shaving was performed to prevent hair loss and infection around both right and left ovaries. After cutting the left and right 1cm of the spine, the body fat around the ovary was grasped and the ovary wrapped in the ovary was fixed with a suture and removed. The peritoneum and the mesial layer were closed with absorbent sutures and the skin was closed with nonabsorbable sutures. After closure, the model animals were reared freely with water and diet under breeding conditions of 55% to 60% humidity at a temperature of 24 ± 2 ° C. One week after the ovarian extraction procedure, OVX-control model animals and sediment hot water extracts in which physiological saline was administered for two weeks were dissolved in physiological saline to prepare earth and sand model animals administered orally at 100 mg / kg daily for two weeks.

Example 3-2. Evaluation of Menopausal Rats in Ovarian Extracted Rats

In order to determine whether the rats induce menopause, uterine weight and serum levels of 17β-estradiol, a type of female hormone, were measured. Specifically, after the rats were sacrificed, the uterus was extracted and weighed. Serum 17β-estradiol concentration was measured by RIA kit (Linco). The results measured according to the above are summarized in Table 1 below.

(Ovarian maintenance normal control group; ovarian extraction normal control group, Sham group; ovarian extraction red, positive control group; ovarian extraction red 17β-estradiol administration group, all values were expressed as mean ± SD. The statistical significance of each result was Tukey It was confirmed by the test, and different subscripts represented by a and b in the same column means that there is a significant difference at p <0.05.)

As shown in Table 1, it was confirmed that the serum 17β-estradiol level was significantly decreased in the Sham group from which the ovary was extracted compared to the ovarian maintenance normal control rats, whereas in the ovarian extraction positive control group administered with hormones, the normal control rats And hormone levels were similar.

Through the above results, it was confirmed that the rats from which the ovaries were removed were well induced menopause.

Example 3-3. Thrombus Induction and Screening of Antithrombotic Activity in Tosa

In order to measure the antithrombotic activity by the administration of Tosa hot water extract, inhalation anesthesia was induced with a mixed gas of a 2% isopulan and a nitrogenous oxygen ratio of 7: 3, and a constant body temperature was used during the experiment. In order to maintain the temperature of the heating pad (heating pad) was maintained at 37 ℃. The median cervix of the model animal was dissected and the right carotid artery was exposed so as not to damage the vagus nerve and peripheral blood vessels, and then thrombus was induced by contacting FeCl 3 with 2 × 2 mm of filter paper soaked with FeCl 3. After the filter paper was removed, the resultant was wiped with saline and blood flow measurement was performed for up to 30 minutes using a flowmeter. The thrombus generation time was analyzed using the chart (ADI, Australia) program. The base unit of the measured value was the tissue perfusion unit (TPU), and the thrombus generation time was based on the point where the TPU value completely dropped to zero. (FIG. 2). Figure 2 is a graph showing the results of examining the antithrombotic activity of the earth and sand extract using the menopausal thrombogenic model animals.

As shown in FIG. 2, in the OVX-control group in which the ovary was removed and physiological saline was administered for 2 weeks to induce thrombus in comparison with the blood clot generation time of 30.00 ± 0.00 minutes in the Sham group (normal control group) that did not cause blood clots. It was confirmed that the thrombus generation time was significantly reduced to 7.00 ± 1.41 minutes to establish a menopausal thrombus-induced model animal.

In addition, the thrombus generation time of the group administered with Tosa extract for 2 weeks to the menopausal thrombus-induced model animal was 11.67 ± 0.58 minutes, and the thrombus time was increased by 4.6 minutes or more compared with the OVX-control group, which was significantly increased by 1.67 times or more. . From these results, it was confirmed that the tosa extract showed excellent efficacy in inhibiting thrombus formation. Therefore, it can be seen that the earth and sand extract or fractions thereof can be effectively used for the prevention, treatment, and improvement of cardiovascular diseases.

Taken together, the earth and sand does not affect breast cancer cell proliferation and also suppresses menopausal thrombosis, so breast cancer and coronary artery disease caused by the use of conventional hormone therapy It can be used for the prevention or treatment of cardiovascular diseases without causing side effects such as stroke and thrombosis. That is, from the above results, the earth and sand may have a different action depending on the organ or tissue part, so that the sediment may not cause breast cancer, and at the same time, a selective estrogen receptor modulator (SERM) capable of preventing or treating cardiovascular diseases. It is expected to be used as).

From the above description, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without changing the technical spirit or essential features. In this regard, it is to be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed that all changes or modifications derived from the meaning and scope of the following claims and equivalent concepts rather than the detailed description are included in the scope of the present invention.

Claims

Cuscuta japonica Chois A pharmaceutical composition for preventing or treating menopausal cardiovascular diseases comprising water extract or fractions thereof as an active ingredient. Pharmaceutical composition, wherein the sedimentary water extract or a fraction thereof inhibits thrombogenesis, selected from the group consisting of paralysis, vascular restenosis and atherosclerosis.

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The method of claim 1,
The menopausal cardiovascular disease is a pharmaceutical composition that is caused by thrombogenesis.

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A method for preventing or treating menopausal cardiovascular diseases, comprising administering the pharmaceutical composition according to claim 1 or 5 to an individual except for a human having or likely to develop menopausal cardiovascular diseases. Menopausal cardiovascular disease is selected from the group consisting of stroke, myocardial infarction, cerebral hemorrhage, heart failure, thrombosis, heart failure, stenosis and arteriosclerosis.

A food composition for preventing or improving menopausal cardiovascular diseases comprising water extract or fractions thereof as an active ingredient, wherein the menopausal cardiovascular diseases include stroke, myocardial infarction, cerebral hemorrhage, heart failure, cerebral thrombosis, heart attack, vascular restenosis, and Atherosclerosis is selected from the group consisting of, wherein the sediment water extract or fractions thereof is to inhibit thrombogenesis.