JP6842782B2 - Functional composition for improving and preventing hypoestrogenosis in menopausal women - Google Patents

Description

The present invention relates to new uses for thistle extracts or combined extracts of thistles and thyme. More specifically, the present invention relates to a functional composition containing a thistle extract as an active ingredient for efficiently improving menopausal hypoestrogenosis in women.

As women grow older, their ovaries become less functional, which results in a significant decrease in estrogen secretion. As a result, the response to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) is reduced, and the production of progesterone is also reduced. Especially from the late mid-40s, the probability of menopause, in which the function of the ovaries completely stops, becomes very high. The period after the onset of menopause is called the menopause, which lasts about 4 to 7 years on average.

When women reach menopause, they no longer produce female hormones, resulting in hot flashes, sweating, fatigue, anxiety, depression, memory loss, insomnia, increased blood cholesterol, increased weight, and decreased bone density. Various symptoms such as appear.

Conventionally, there have been attempts to utilize hormone therapy and phytoestrogens to treat the above-mentioned female diseases. It is known that phytoestrogens are exogenous estrogens isolated from plants and are not produced in the endocrine system in the living body, and are contained in most plants. Phytoestrogens are structurally similar to estrogens and are known to bind to estrogen receptors competitively with estrogens in vivo. However, the effect of the binding has not been clarified concretely, and it is known that the level of the binding is very small.

Non-Patent Document 1 discloses a configuration in which phytoestrogens are extracted using thistle among various plants. Specifically, Non-Patent Document 1 discloses the following contents.

First, there are substances in native thistles that bind to the estrogen receptor. Specifically, in Example 2 of Non-Patent Document 1, there is a substance that binds to an estrogen receptor in a native lizard extract using a transformed yeast strain lac operon. Was confirmed, and it was confirmed that the binding level was similar to that of quercetin known as phytoestrogen.

Second, phytoestrogens are present in native thistles. In Example 3 of Non-Patent Document 1, after extracting an extract from the roots of a native species of thistle using methanol, phytoestrogens contained in the extract, specifically genistein, daidzein, and quercetin, are used. It was confirmed by detection.

However, the only thing that can be known from the functional composition using conventional thistle is that there is a substance that binds to the estrogen receptor in thistle, and what kind of effect the thistle extract exerts. I don't know. And, phytoestrogens such as genistein, daidzein, and quercetin detected in native thistles are likely to bind to the estrogen receptor due to their structural similarity, but as mentioned above, they are actually due to the binding. The effect has not been clarified concretely, and it is known that the level of the binding ratio is very small. Furthermore, since phytoestrogens are known to be present in most plants, the thistle composition described in Non-Patent Document 1 has no new meaning.

Recently, in addition to secondary symptoms such as hot flushes caused by a decrease in estrogen concentration in the human body, the phenomenon of decreased estrogen concentration has come to be recognized as a disease, and the purpose is to directly treat it. Much research is being done. A disease in which the estrogen concentration in a woman's body decreases in this way is called hypoestrogenism. In the case of hypogonadism, it can be said that it is included in the category of hypoestrogenosis because it means that the function of the ovary is reduced and the sex hormones are reduced.

Therefore, there is a need for research and development of natural substances that radically prevent or ameliorate hypoestrogenosis and minimize side effects. The present inventors have confirmed that the thistle extract and the combined extract of thistle and thyme increase estrogen in the human body of menopausal women, and have completed the present invention.

Cirsium japonicum is a perennial plant of the dicotyledonous family, Campanulales, Asteraceae, also called thistle, and grows mainly in mountains and fields. The young shoots are edible and the leaves, trunks and roots are medicinal.

Thymes vulgaris is a deciduous semi-thyme of the family Lamiales, Lamiales, and Labiatae, and grows naturally in places with a lot of seaside rocks (Thymus quinquecostatus var. Japanica), and thyme with white flowers (Thymus quinque). . Albus YN Lee) and the like. Such thyme is a raw material or medicinal product for beverages, fungicides, cosmetics.

On the other hand, the technique for improving hypoestrogenosis using the thistle extract of the present invention or the composite extract of thistle and thyme can be considered to be similar to the description in Non-Patent Document 1. However, the fact that thistle extract is effective for hypoestrogenosis cannot be derived from the description in Non-Patent Document 1 that "phytoestrogens are present in thistles". In addition, studies that have already been published have led to the result that "phytoestrogens are not related to the regulation of female hormones in the human body."

Change et. al (2007) Isoflavone treatment for acute menopausal systems. Menopause, 14, pp468-473

The problem to be solved by the present invention is that it can effectively prevent and ameliorate the symptoms of estrogen depletion in menopausal women, efficiently alleviate the symptoms that appear in association with women's menopause, and consist of natural ingredients. It is an object of the present invention to provide a functional composition for preventing and ameliorating hypoestrogenosis using thistle, which can reduce the rejection reaction to the body.

The means for solving the problem of the present invention is to provide a food composition for improving and preventing hypoestrogenosis, which comprises a thistle extract as an active ingredient.

In addition, the means for solving the problems of the present invention is to provide a food composition for improving and preventing hypoestrogenosis, which comprises a complex extract of thistle and thyme as an active ingredient.

The thistle extract or the composition containing the complex extract of thistle and thyme according to the present invention can alleviate hypoestrogenosis, which is a symptom of decreased estrogen in menopausal women.

In addition, the composition of the present invention directly increases the estrogen concentration in the human body of menopausal women, resulting in facial hot flashes, sweating, fatigue, anxiety, depression, memory impairment, insomnia, etc. Symptoms such as increased blood cholesterol, increased body weight, and decreased bone density can be improved more efficiently.

It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the measurement result of the blood estradiol concentration of the test subject animal. It is a graph which shows the weight change of the test subject animal. It is a graph which shows the weight gain amount of the test subject animal. It is a graph which shows the increase amount of alkaline phosphatase in the blood of the test subject animal. It is a graph which shows the increase amount of osteocalcin in the blood of the test subject animal. It is a graph which shows the improvement rate of the menopausal symptom of the test subject woman measured by the KI test method. It is a graph which shows the MRS score of the test subject woman measured by the MRS inspection method.

Prior to explaining the present invention, the meanings of the terms used in the present invention will be described.

In the present specification, the term "extract" has the same meaning as a crude extract in the art, but in a broad sense, it also includes a fraction obtained by further fractionating the extract. That is, the thistle extract includes not only the one obtained by using the above-mentioned extraction solvent but also the one obtained by further applying the purification process to the extract. For example, fractions obtained by passing the extract through an ultrafiltration membrane with a constant molecular weight cutoff value, for various chromatographies (separation according to size, charge, hydrophobicity or affinity). Fractions obtained by various additional purification methods such as separation by (manufactured) are also included in the thistle extract used in the present invention.

As used herein, "included as an active ingredient" means that it contains an amount sufficient to achieve the efficacy or activity of thistle extract. In the present invention, an extract from thistle, which is a natural plant material, is used, and there is no side effect on the human body even if an overdose is administered. Therefore, the upper limit of the amount of thistle extract contained in the composition of the present invention is , Ordinary technicians can make a selection within the appropriate range.

Hereinafter, the composition of the present invention will be described in detail.

The thistle extract according to the present invention is extracted using an organic solvent, and the ones used as the extraction solvent are as follows.

First, suitable polar solvents are (i) water, (ii) alcohols having 1 to 6 carbon atoms (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1). -Pentanol, 2-butoxyethanol, or ethylene glycol), (iii) acetic acid, (iv) DMFO (Dimethyl methanol), and (v) DMSO (Dimethyl solvent) and the like.

Suitable non-polar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1-pentene. , 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, aniline, diethyl amine , Ether, carbon tetrachloride, methylene chloride, petroleum ether, THF and the like.

In the present invention, as the extraction solvent, (a) water, (b) anhydrous or lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) a mixed solvent of the lower alcohol and water, It is preferable to use (d) acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane, (j) diethyl ether and the like. For easy extraction, it is more preferred to treat water, ethanol, or a mixture of water and ethanol with a thistle for extraction.

In addition, the thistle extract used in the present invention can be produced in a powder state by an additional process such as vacuum distillation, lyophilization, or spray drying.

Therefore, in the present invention, an extract can be produced using the above-mentioned extraction solvent. The method for producing thistle extract will be described below.

1) Production of thistle extract
(i) After sorting and crushing thistles,
(ii) The number of carbon atoms of water containing purified water, methanol, ethanol, butanol, etc., which is about 1 to 25 times the volume of the pulverized product (v / w%), preferably 7 to 15 times the volume. Using 1 to 4 lower alcohols and a solvent selected from a mixed solvent thereof, more preferably water, ethanol, or a mixed solvent thereof.
(iii) At an extraction temperature of 0 ° C to 120 ° C, preferably 50 ° C to 100 ° C.
(iv) Approximately 1 to 10 days, preferably approximately 3 to 6 hours,
(v) By an extraction method such as a cold immersion extraction method, a hot water extraction method, an ultrasonic extraction method, a reflux cooling extraction method, or a heating extraction method, preferably by a hot water extraction method or a reflux cooling extraction method.
(vi) Extraction is repeated about 1 to 10 times, preferably 2 to 8 times.
And
(vii) The extract is filtered through a filter cloth and
(viii) After concentrating the filtrate in vacuum,
(ix)-(1) Freeze-dry or
(ix)-(2) Dextrin is mixed according to the blending ratio and then spray-dried to obtain a thistle extract.

Further, the thistle extract may be produced by a subcritical extraction method that extracts using a subcritical fluid or a supercritical extraction method that extracts using a supercritical fluid.

In the test described later, a thistle extract produced by performing organic solvent extraction (ethanol, methanol) according to a hot water extraction method was used. Each extraction condition is as follows.

The thistle extract 1 is first extracted at 121 ° C. for 5 hours using 7 times the volume of purified water with respect to the weight of the pulverized product, and then 2 times extracted by adding 5 times the volume of purified water. After concentrating this in vacuum, the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thistle extract 2 is first extracted at 100 ° C. for 5 hours using 7 times the volume of purified water with respect to the weight of the pulverized product, and then added 5 times the volume of purified water for secondary extraction. After concentrating this in vacuum, the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thistle extract 3 is first extracted at 70 ° C. for 5 hours using 7 times the volume of purified water with respect to the weight of the pulverized product, and then secondary extracted by adding 5 times the volume of purified water. After concentrating this in vacuum, the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thistle extract 4 is first extracted at 70 ° C. for 5 hours using 7 times the volume of 40% ethanol with respect to the weight of the ground product, and then added 5 times the volume of 40% ethanol for secondary extraction. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thistle extract 5 is first extracted at 50 ° C. for 5 hours using 90% ethanol having a volume 7 times the weight of the ground product, and then extracted with 90% ethanol having a volume 5 times the volume. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thistle extract 6 is first extracted at 70 ° C. for 5 hours using 7 times the volume of 40% methanol with respect to the weight of the ground product, and then added 5 times the volume of 40% methanol for secondary extraction. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thistle extract 7 is first extracted at 50 ° C. for 5 hours using 90% methanol having a volume 7 times the weight of the pulverized product, and secondary extraction by adding 90% methanol having a volume 5 times. Then, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

2) Production of thyme extract The thyme extract is also produced in the same manner as the method for producing thistle extract.

In the test described later, a thyme extract produced by performing organic solvent extraction (ethanol, methanol) according to a hot water extraction method was used. Each extraction condition is as follows.

The thyme extract 1 is first extracted at 121 ° C. for 6 hours using 6 times the volume of purified water with respect to the weight of the pulverized product, and then added 6 times the volume of purified water for secondary extraction. , This is concentrated in vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thyme extract 2 is first extracted at 100 ° C. for 6 hours using 6 times the volume of purified water with respect to the weight of the pulverized product, and then added 6 times the volume of purified water for secondary extraction. , This is concentrated in vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thyme extract 3 is first extracted at 70 ° C. for 6 hours using 6 times the volume of purified water with respect to the weight of the pulverized product, and then added 6 times the volume of purified water for secondary extraction. , This is concentrated in vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thyme extract 4 is first extracted at 70 ° C. for 6 hours using 6 times the volume of 40% ethanol with respect to the weight of the ground product, and then added 6 times the volume of 40% ethanol for secondary extraction. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried.

The thyme extract 5 is first extracted at 50 ° C. for 6 hours using 90% ethanol having a volume 6 times the weight of the ground product, and then added with 90% ethanol having a volume 6 times the volume to perform secondary extraction. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried.

The thyme extract 6 is first extracted at 70 ° C. for 6 hours using 40% methanol having a volume 6 times the weight of the ground product, and then secondary extraction is added with 40% methanol having a volume 6 times the volume. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

The thyme extract 7 is first extracted at 50 ° C. for 6 hours using 90% methanol having a volume 6 times the weight of the ground product, and then secondary extraction is added with 90% methanol having a volume 6 times the volume. After that, this is concentrated in a vacuum, and then the extract and dextrin are mixed at a ratio of 1: 1 and spray-dried to produce the extract.

3) Production of composite extract of thistle and thyme The thistle extract and thyme extract corresponding to each condition are mixed at a ratio (weight ratio) of 6: 4. For example, the thistle and thyme composite extract 1 mixes thistle extract 1 and thyme extract 1, and the thistle and thyme composite extract 2 mixes thistle extract 2 and thyme extract 2. Then, up to the composite extract 7 of thistle and thyme is produced. Then, the thistle extract 1 and the thyme extract 1 are further mixed at a ratio (weight ratio) of 2: 8, 4: 6, and 8: 2 to produce a composite extract.

The thistle extract according to the present invention is produced as a food composition. That is, it can be produced as a food composition for preventing and ameliorating hypoestrogenosis, which contains a thistle extract as an active ingredient.

When the thistle extract according to the present invention is produced as a food composition, it contains components usually added during food production. For example, proteins, carbohydrates, fats, nutrients, and seasonings fall into this category. When it is produced as a drink, a flavoring agent, a natural carbohydrate, or the like may be contained as an additional ingredient in addition to the thistle extract as an active ingredient. For example, natural carbohydrates include monosaccharides (glucose, fructose, etc.), disaccharides (martose, sucrose, etc.), oligosaccharides, polysaccharides (dextrin, cyclodextrin, etc.), and sugar alcohols (xylitol, sorbitol, erythritol, etc.). .. As the flavoring agent, a natural flavoring agent (for example, thaumatin, stevia extract, etc.) and a synthetic flavoring agent (for example, saccharin, aspartame, etc.) can be used.

On the other hand, the same applies to the case where the complex extract of thistle and thyme is produced as a food composition.

In the following, the effect of the thistle extract according to the present invention will be described in detail with reference to test examples.

Test Example 1: Animal test <1-1> Test target A 7-week-old female rat (Rat) weighing 200 g to 250 g was adapted for 1 week in the laboratory, and then partly ovariectomy was performed. A menopausal model was induced, and the rest was subjected to a week-operation to be sutured after an abdominal incision to induce a non-menopausal model. Then, after the wound was healed by giving solid feed to each model for one week, the control group in which the ovaries were not resected (hereinafter referred to as "normal control group") and the control group in which the ovaries were resected (hereinafter, "" Five animals were classified into each of the "negative control group"), and 21 animals were classified into the first experimental group (hereinafter referred to as "first experimental group") in which the ovaries were resected, and the second ovary was resected. Thirty animals were classified into the experimental group (hereinafter referred to as "second experimental group").

The first experimental group was divided into 7 groups of 3 animals each, and each group was orally administered with thistle extracts 1 to 7 dissolved in physiological saline at a concentration of 50 mg / kg. The second experimental group was divided into 10 groups of 3 animals each, and then each of the 7 groups contained composite extracts 1 to 7 of thistle and thyme dissolved in physiological saline at a concentration of 50 mg / kg. Orally administered, and the remaining three groups were orally given a composite extract of thistle and thyme, which was a mixture of thistle extract 1 and thyme extract 1 at a ratio of 2: 8, 4: 6, and 8: 2. It was administered. The same amount of physiological saline was orally administered to the normal control group and the negative control group. The administration period was 8 weeks, the breeding conditions were a temperature of 24 ± 2 ° C., a humidity of 50% to 55%, and water and food were provided without limitation.

<1-2> Measurement of Estrogen in the Body Decrease in estrogen is a typical cause of menopausal symptoms in women. Therefore, the present invention measured the blood estradiol-17β concentration after drug administration in order to confirm the effect of thistle extract on estrogen. Since estradiol is a typical estrogen and has much higher activity than estrone and estriol, it is used as an estrogen measurement target.

Specifically, the blood of each group for which administration was completed in the <1-1> test subject was collected, centrifuged (1000 g, 15 minutes, 4 ° C), and an ultra-low temperature freezer at -80 ° C until analysis. It was stored in (Deep freezer). Then, estradiol in blood was measured using Rat estradiol (E2) ELISAKit (Cayman, Ann Arbor, MI, USA). The test results were statistically processed by the statistical program SPSS (version 12.0) and their significance was verified at the p <0.05 level. The measurement results of estradiol in blood for each extract are shown in FIGS. 1 to 8. That is, the result corresponding to the thistle extract 1 and the composite extract 1 of thistle and thyme is shown in FIG. 1, and the result corresponding to the thistle extract 2 and the composite extract 2 of thistle and thyme is shown in FIG. The results according to the substance 3 and the complex extract 3 of thistle and thyme are shown in FIG. 3, the results according to the compound extract 4 of thistle and thistle and thyme are shown in FIG. 4, and the results according to the compound extract 4 of thistle and thistle are shown in FIG. The results according to the thistle extract 6 and the thistle and thyme composite extract 6 are shown in FIG. 5, and the results according to the thistle extract 7 and the thistle and thyme composite extract 6 are shown in FIG. The results according to the extract 7 are shown in FIG. 7, and the results according to the mixing ratio of the thistle extract 1 and the thyme extract 1 are shown in FIG. 8, respectively.

For reference, for smooth comparison, FIGS. 1-7 include the results of the normal control group (Sham) and the negative control group (OVX-Con), respectively.

As shown in FIG. 1, since the blood estradiol concentration in the negative control group (OVX-Con) is significantly lower than that in the normal control group (Sham), it can be seen that the activity of estrogen decreases due to menopause. The blood estradiol concentration in the first experimental group (OVX-Cirs) was higher than that in the negative control group (OVX-Con). It can be seen that it has a relaxing effect. Then, since the estradiol concentration was measured higher in the second experimental group (OVX-CT) than in the first experimental group (OVX-Cirs), the combined extract of thistle and thyme increased the estrogen concentration in blood. It turns out to be more effective.

Since FIGS. 2 to 7 also showed only a slight difference from FIG. 1 and the results were obtained in a similar pattern, the extraction solvent or temperature was used to determine the efficacy of the thistle extract and the combined extract of thistle and thyme. It can be seen that it does not have a significant effect on.

Then, FIG. 8 shows the result of measuring the estradiol concentration according to the mixing ratio of the azalea extract 1 and the thyme extract 1, and when the ratio of the azalea extract 1 is high and the ratio of 8: 2 is mixed and administered. It can be seen that the highest concentration of estradiol was measured.

<1-3> Measurement of body weight Weight gain is one of the typical symptoms of female menopause. Therefore, in the present invention, in order to confirm the effect of thistle extract on body weight, the change in body weight according to the administration period was measured.

Specifically, each group (in the case of the first experimental group: the group to which thistle extract 1 was administered, the second experiment) for a total of 9 weeks from before the drug administration to 1 week after the drug administration was completed. In the case of group: Thistle and thyme complex extract 1 (group in which the ratio of 6: 4) was administered) was weighed. The results of the test were statistically processed by the statistical program SPSS (version 12.0) and verified for significance at the p <0.05 level compared to the normal control group. The results are shown in FIGS. 9 and 10.

As shown in FIG. 10, since the body weight of the negative control group (OVX-Con) is significantly increased as compared with that of the normal control group (Sham), it can be seen that menopause has some influence on the body weight increase. It can be seen that the first experimental group (OVX-Cirs) gains a relatively small amount of body weight as compared with the negative control group (OVX-Con). Further, as shown in FIG. 9, it can be seen that after 9 weeks, there is no significant difference in body weight gain between the first experimental group (OVX-Cirs) and the normal control group (Sham). Therefore, it can be seen that thistle extract has the effect of alleviating postmenopausal weight gain.

On the other hand, the weight gain of the second experimental group (OVX-CT) was lower than that of the first experimental group (OVX-Cirs). It turns out that it works effectively.

<1-4> Measurement of Body Cholesterol Healthy young women have lower total blood cholesterol, LDL cholesterol, and triglyceride, and higher HDL cholesterol than men of the same age. However, during menopause, triglycerides and HDL cholesterol are generally unchanged, but total cholesterol and LDL cholesterol are increased, and such changes can increase the incidence of postmenopausal vascular disease in women. Are known. Therefore, the present invention measured the blood cholesterol concentration after drug administration in order to confirm the effect of thistle extract, thistle and thyme complex extract on blood cholesterol.

Specifically, each group in which administration was completed in the <1-1> test subject (in the case of the first experimental group: the group to which the thistle extract 1 was administered, in the case of the second experimental group: a combination of thistle and thyme). Blood was collected from Extract 1 (group to which the 6: 4 ratio) was administered. Then, the serum is separated, and the triglyceride, total cholesterol, and HDL cholesterol concentrations in the serum are measured using a slide for automatic measurement (manufactured by FUJIFILM Corporation) using a clinical chemistry analyzer (Fuji Drychem 3500i, FUJIFILM Corporation). ), Measured at a wavelength of 400 nm to 600 nm. In the case of HDL cholesterol, chylomicrons, low density lipoproteins, and very low density lipoproteins were precipitated with a precipitating agent, and HDL cholesterol in the supernatant was measured. LDL cholesterol was calculated by the following Friedewald formula.
LDL cholesterol = {total cholesterol- (HDL cholesterol-triglyceride / 5)}

The results of the study were shown as mean ± standard deviation and statistically processed by the statistical program SPSS (version 12.0) to verify significance at the p <0.05 level. The results are shown in Table 1.

As a result of the test, as shown in Table 1, the negative control group significantly increased the total cholesterol, triglyceride, and LDL cholesterol in the blood and decreased the HDL cholesterol as compared with the normal control group. In contrast, the first and second experimental groups had significantly lower total cholesterol, triglyceride, and LDL cholesterol in the blood and increased HDL cholesterol than the negative control group (OVX-Con). did.

Therefore, from the results of this test example, the thistle extract, the complex extract of thistle and thyme contained in the composition of the present invention, the lipid content in blood and the hyperlipidemia caused by it in the menopausal situation, etc. It can be seen that it has an effect on the improvement of.

<1-5> Measurement of bone markers Decreased bone density is one of the symptoms that appear in menopausal women and is the cause of inducing diseases such as osteoporosis. Therefore, in order to confirm the effect of the azalea extract and the composite extract of azalea and thyme on the bone mineral density, the concentration of alkaline phosphatase (Alkaline phosphatase, hereinafter referred to as "ALP") and osteocalcin in the blood after administration of the drug are examined. , Hereinafter referred to as "OC") concentration was measured.

Specifically, each group in which administration was completed in the <1-1> test subject (in the case of the first experimental group: the group to which the thistle extract 1 was administered, in the case of the second experimental group: a combination of thistle and thyme). Blood was collected from Extract 1 (group to which the 6: 4 ratio) was administered. The ALP concentration in blood was analyzed using an automatic analyzer (ADVIA 1650, manufactured by Bayer), and the OC concentration in blood was analyzed using an ELISA kit (Metal OC, Quidel Corporation, San diego, CA, USA). analyzed.

The results of the test were statistically processed by the statistical program SPSS (version 12.0) and verified for significance at the p <0.05 level compared to the normal control group. The results are shown in FIGS. 11 and 12.

As a result of the test, as shown in FIGS. 11 and 12, the negative control group (OVX-Con) had an increased ALP concentration and OC concentration in blood as compared with the normal control group (Sham). Such a result is considered to be due to an increase in the bone remodeling process due to a decrease in bone density due to oophorectomy, and an improvement in the bone turnover index in this process. Therefore, in this process, the ALP concentration in blood, which is a typical bone turnover index, increases, and the OC concentration, which is a bone reabsorption and bone formation index, increases (Hertranmpf T., Schleipen B., Offermanns). C., Velders M., Laudenbach U., Diel P., Comparison of the bone protective effects of anisoflavone-rich diet with dietary and subcutaneous administrations of genistein in ovariectomized rats.Toxicol.Lett.2009,184,198-203.) .. On the other hand, in the first experimental group (OVX-Cirs), the ALP concentration and OC concentration in blood were lower than those in the negative control group (OVX-Con). Moreover, in the second experimental group (OVX-CT), the ALP concentration and the OC concentration in the blood were further lowered, and the values were the closest to those in the normal control group (Sham).

Therefore, since the ALP concentration and OC concentration in blood increase relatively slightly as described above, the thistle extract, thistle and thyme complex extract have an effect of alleviating the decrease in bone density due to menopause. You can see that.

Test Example 2: Human Body Test <2-1> Test Target 60 middle-aged women aged 45 years or older who agreed to this test received a control group (Placebo) that took a placebo and a thistle extract. A second experimental group (C + Time) ingesting a group (Cirsium), a thistle and thyme complex extract was arbitrarily classified by 20 persons each, and included a placebo, thistle extract, or a thistle and thyme complex extract. The experimental drug was taken at 400 mg daily for 12 weeks.

<2-2> Hangul version KI (Kupperman index)
Based on Kupperman's clinical experience of treating menopause in 1953, 11 typical symptoms of menopause shown in Table 2 below were set as items, and the degree and characteristics of menopause were grasped and announced. It is a self-assessment question test method that has been used most frequently as a symptom evaluation scale in studies related to menopausal symptoms in women to date. Grasp the degree and characteristics of each symptom of menopause, and add up the points assigned to each item. 20 points or less is mild, 20 points or more and less than 40 points is moderate, 40 points or more and less than 60 points is severe, 60 points. A point or higher is judged to be in a critical state. The result of calculating the improvement rate after ingestion is shown in FIG. The results were statistically processed by the statistical program SPSS (version 12.0) and their significance was verified at the p <0.05 level.

As shown in FIG. 13, the control group (Placebo) ingesting the placebo showed only a 4.2% symptom improvement rate after ingestion for 3 months, whereas the first experimental group (Cirsim) showed a symptom improvement rate of only 4.2%. , KI-assessed female menopausal symptoms were reduced by 30%, and menopausal symptoms were significantly improved compared to the control group (Placebo). In addition, in the second experimental group (C + Time), it can be seen that the menopausal symptoms of women decreased by 45% or more.

Therefore, from these results, hot flashes, sweating, insomnia, nervousness, depression, dizziness, tiredness, joint pain and myalgia, chest upset, vaginal dryness, with a combination extract of thistle, azalea and thyme. It was confirmed that complex female menopausal symptoms such as decreased secretions were effectively improved.

<2-3> Hangul version MRS (Menopause Rating Scale)
The MRS test method is a test method newly created in 1996 by complementing the MENQOL (Menopause-Special Quality of Life Questionnaire) test method created by Hildic et al. In 1992 as a complement to Kupperman index. MRS has been cited in many studies worldwide and has been recognized for its reliability and validity. It is composed of a total of 11 items such as physical symptoms, psychiatric symptoms, and genitourinary symptoms, and has the advantage of being simple with a small number of items. This MRS evaluates symptoms according to the criteria shown in Table 3 below.

From the calculated total score, 0 to 4 points indicate a good menopausal state and a good menopausal period. A score of 5 to 8 indicates a slight menopausal condition that requires management. A score of 9 to 15 indicates that the patient is in a severe menopausal state and has menopause, so that specialist diagnosis and treatment are required. A score of 16 or higher indicates a severe menopausal condition and a great need for long-term planning and treatment.

These results are shown in FIG. The results were statistically analyzed by the statistical program SPSS (version 12.0) before and after ingestion of each experimental group, and the significance was verified at the p <0.05 level.

As shown in FIG. 14, in the control group (Placebo), no statistically significant difference was shown in the MRS score after ingestion for 3 months. On the other hand, in the first experimental group (Cirsium), it was confirmed that the MRS score decreased by about 30% after ingestion for 3 months, and the menopausal symptoms of women were significantly decreased. In addition, in the second experimental group (C + Time), after ingestion for 3 months, the score decreased by a large difference as compared with the first experimental group (Cirsium), indicating that the menopausal symptoms can be improved more effectively.

The thistle extract, thistle and thyme complex extract contained in the composition according to the present invention can alleviate hypoestrogenosis, which is a symptom of a decrease in estrogen in menopausal women. It can be provided as food or medicine.

Claims (1)

It contains a complex extract of Cirsium japonicum and Thymus vulgaris as an active ingredient.
The complex extract of thistle and thyme is a mixture of thistle hot water extract and thyme hot water extract.
The weight ratio of the thistle hot water extract to the thyme hot water extract is 2: 8, 4: 6, 6: 4, or 8: 2, which is characterized by hypoestrogenosis in menopausal women. Food compositions for improvement and prevention.