KR101272602B1 - Pomegranate extract containing a high content of ellagic acid, and a method for improving effect of pomegranate extract related to postmenopausal syndrome - Google Patents

Abstract

The present invention relates to a pomegranate pulp extract, comprising a high content of ellagic acid, characterized in that the improvement effect of female menopausal symptoms of the pomegranate extract. The present invention also provides a method for further improving the female climacteric symptom improving effect of the pomegranate extract by increasing the content of ellagic acid.

Description

Pomegranate extract containing a high content of ellagic acid, and a method for improving effect of pomegranate extract related to postmenopausal syndrome}

The present invention relates to a pomegranate extract, the effect of improving the female menopausal symptoms of the pomegranate extract and a method for improving this effect of the pomegranate extract.

Estrogen, one of endocrine hormones, is synthesized from cholesterol in the body, and the secretory sources are mainly follicles and corpus luteum of the ovaries. When the gonadotropin secreted by the anterior pituitary gland transmits signals to the reproductive organs, follicle stimulating hormone (FSH) and luteinizing hormone (LH) are hormones that regulate the menstrual cycle and enable pregnancy Is secreted, which in turn acts on the ovary, releasing estrogen and progesterone. The estrogens collectively include estradiol, estrone, estriol, and the like.

In premenopausal women, the ovary is a major source of estrogen. As a woman enters menopause, as the ovary ages, the response to pituitary gonadotropins (follicle stimulating hormone and luteinizing hormone) decreases, which further shortens the early follicular phase, further shortening the menstrual cycle. Is further shortened, progesterone production is reduced, and the cycle becomes more irregular. Eventually, the follicles will not react and will not produce estrogens. Reduced secretion of estrogen has a significant effect not only on the urogenital system of women, but also throughout the body, and menopausal symptoms due to hormonal decline before or after menstruation is stopped and menstruation disappears.

In postmenopausal women, the rapid decrease in estrogens significantly increases the risk of developing psychological and emotional signs such as fatigue, excitement, insomnia, poor concentration, depression, memory loss, headache, anxiety, and nervousness or timidity, and recurrence. Fatigue and excitement due to sleep disturbance, intermittent dizziness, paresthesia, palpitations and tachycardia, nausea, constipation, diarrhea, arthralgia, myalgia, cold hands and legs, and weight gain are also significantly increased. In addition, osteoporosis is not only easily induced, but also mortality due to cardiovascular diseases such as heart disease, high blood pressure and stroke is increased (Kalin MF & Zumoff B. Steroids 55: 330-352, 1990). In addition, it causes changes in the skin and urogenital system and increases the likelihood of developing autoimmune diseases, cataracts and colorectal cancer.

Currently, the most effective known method for improving menopausal symptoms such as hot flashes is known to supplement estrogens by administering estrogens.

However, there is a serious problem that long-term administration of synthetic estrogens can lead to breast and uterine cancer (Tamini RT et. al . Arch intern med 166: 1483-1489, 2006, Gertig DM. Menopause 13: 178-184, 2006, Strom BL et al . Am J Epidemiol 164: 775-586, 2006, AraJr NL & Athanazio DA. Cad Saude Publica 23: 2613-2622, 2007). In recent years, controversy has been heating up among scholars and across society, with a number of credible claims that long-term synthetic estrogen replacement therapy is likely to cause breast cancer. Although not yet proven, it is believed that the risk of developing breast cancer in women receiving synthetic estrogen replacement therapy is associated with estrogen exposure doses over time.

Therefore, there is a recent trend to actively search for phytoestrogen, a phytoestrogen as a safer substitute of synthetic estrogens used in the hormone replacement therapy. The phytoestrogens refer to nonsteroidal compounds present in plants that exert an estrogenous effect in the body of animals, and most of the grains, fruits, and vegetables known to be effective in anticancer activity and heart disease contain trace amounts of phytoestrogens. It is included.

In other words, there is a need for a safe drug or functional foods that are effective in improving women's menopausal symptoms and do not cause breast cancer or uterine cancer.

Therefore, the technical problem to be achieved by the present invention is to provide an effective composition for improving female menopausal symptoms.

In addition, another technical problem to be achieved by the present invention is to provide a method for improving the female menopausal improvement effect of the pomegranate extract.

In order to achieve the above technical problem, the present invention provides a pomegranate pulp extract with an improved effect of improving the menopausal symptoms, characterized in that it contains a high content of ellagic acid (ellagic acid).

Preferably, the present invention is the content of ellagic acid is 0.8 mg / g or more, more preferably the content of ellagic acid is 0.8 to 1.8 mg / g, even more preferably the content of ellagic acid is 0.8 to 1.4 mg / g It provides a pomegranate pulp extract with an improved effect of improving the menopausal symptoms, characterized in that.

If the content of ellagic acid is less than 0.8 mg / g is a slight improvement effect of the menopausal symptoms, if it exceeds 1.8 mg / g there is a risk of side effects such as liver function values GOT and GPT is out of the normal range.

The present invention is based on the surprising discovery that the use of pomegranate pulp extract with a high content of ellagic acid improves the effect of improving women's menopausal symptoms. Based on this finding, the present invention includes a female of pomegranate extract containing ellagic acid in a high content. The present invention provides a method of further improving the effect of improving the menopausal symptoms of the pomegranate extract by increasing the content of the pomegranate extract and the ellagic acid.

In the present invention, menopausal symptoms are hot flashes, sweating, insomnia, nervousness, depression, dizziness, lack of concentration, joint pain, headache, palpitations, vaginal dryness, fatigue, excitement, insomnia, memory loss, anxiety, atherosclerosis Etc., but is not limited thereto.

Pomegranate is a native plant of Southwest Asia, Northwest India, and California, USA, and is now widely distributed in subtropical and tropical regions. Pomegranate, especially red pomegranate, has been known as a tonic for a long time, and is known to have a particularly good effect on preventing hypertension and atherosclerosis. In addition, it contains a large amount of water-soluble sugars of 38 to 47%, and contains a variety of vitamins and minerals.

Although there is no particular limitation on the kind of pomegranate used in the present invention, red pomegranate is preferred, and specific examples include red pomegranate from Iran, California, Taiwan, Uzbekistan, Turkey, and Korea. Pomegranate extract according to the present invention may be different depending on the production time and harvesting time of the pomegranate used, the ellagic acid content of the final extract is more than 0.8 mg / g, more preferably 0.8 to 1.8 mg / g, even more preferably Should use pomegranate, which may be between 0.8 and 1.4 mg / g.

Pomegranate pulp extract according to the present invention can be prepared by the following method. For example, first wash the pomegranate, then completely remove the shell and seeds, and add enzymes such as pectinase, proteinase, amylase, cellulase to break down polysaccharides such as starch contained in the pomegranate. do. Thereafter, additives such as gelatin, silicon dioxide, bentonite, silicasol, tannin, cellulose, and potassium casinate are optionally added to adjust the turbidity, color, viscosity, and the like of the pomegranate extract, and heat-concentrate. To prepare a pomegranate extract containing a specific content of ellagic acid.

The present invention provides an extract using only pomegranate pulp which does not contain pomegranate peel and fruit. Pomegranate skin and fruit can have side effects, for example, certain alkaloids contained in pomegranate skin can degrade the body's function, affect the respiratory system and muscles, and if poisoned, seizures and cramps , Coma can occur. In addition, side effects such as tongue swelling, which are allergic, may occur in some people when the extract of pomegranate fruit is taken.

In the pomegranate pulp extract according to the present invention, the contents of representative other components of the pomegranate extract, such as dydzein, genistein, quercetin, estriol, 17β-estradiol, were almost the same as those of commercial pomegranate extract products, but ellagic acid The content of was a big difference between the pomegranate pulp extract and the commercially available products according to the present invention, it is assumed that this difference brought about the improvement of the menopausal symptoms improvement effect. Therefore, the present invention also provides a composition for improving menopausal symptoms containing ellagic acid as an active ingredient.

The reason why the ellagic acid content of the pomegranate pulp extract according to the present invention is high is due to the difference in pomegranate as a raw material, the use of only pulp, and a specific manufacturing method (for example, the concentration temperature and time of the pomegranate extract (about 55-90 ° C. (about 1 -5 minutes), about 105-110 ° C (about 30-150 seconds), about 100-105 ° C (about 30-150 seconds), etc., but the present invention is not limited to this.

The present invention also provides a health functional food for improving women's menopausal symptoms comprising the pomegranate pulp extract or ellagic acid as an active ingredient according to the present invention.

The health functional food according to the present invention, in addition to pomegranate extract, Earl, Cornus, Dermis, Ganoderma lucidum, Dermis, Cuttlefish, Angelica, Gardenia, Astragalus, Malt, Tanga, Vitamin C, Fructooligosaccharide, Stevioside, Purified water, Malto Dextrin and the like may be further included alone or in a mixture within the range that does not inhibit for the purposes of the present invention, other medicinal ingredients and / or additives that may be further included in the health functional food of the present invention is limited to the above examples It doesn't happen.

For example, the health functional food according to the present invention may include thiamine (vitamin B ₁ ), riboflavin, ascorbic acid, niacin, and vitamin B ₆ as water-soluble vitamins, and myristic acid, palmitic acid, stearic acid as fatty acids. , Oleic acid, linoleic acid, and the like, the weak acid component may include glycolic acid and acetic acid, and as amino acids, threonine, valine, methionine, isoleucine, leucine, phenylalanine, tryptophan, and eight essential amino acids of lysine In addition, it may include aspartic acid, serine, glutamic acid, proline, glycine, alanine, cysteine, tyrosine, histidine, arginine and the like.

The present invention also provides a method for improving the female menopausal symptom improving effect of the pomegranate extract, characterized in that to increase the content of ellagic acid, preferably in the method to control the content of ellagic acid to 0.8 mg / g or more More preferably, to adjust the content of ellagic acid to 0.8 to 1.8 mg / g in the method, and even more preferably to adjust the content of ellagic acid to 0.8 to 1.4 mg / g in the method.

In one embodiment of the present invention, the pomegranate pulp extract according to the present invention is preferably taken 0.3 to 1 ml per kg body weight in a daily dose. When the pomegranate pulp extract according to the present invention is taken at less than 0.3 ml per kg body weight per day, the effect of improving menopausal symptoms is insignificant, and even when taken in excess of 1 ml per kg body weight per day, 1 ml per kg body weight per day. Since there is no greater effect on improving menopausal symptoms than when taken, it is preferable to take 0.3 to 1 ml per kg body weight per day in terms of utilization and economic efficiency in the body.

In one embodiment of the present invention, if the pomegranate pulp extract according to the present invention is taken in a dose of 0.3 to 1 ml per kg body weight per day, the health indicators of the human body (eg, red blood cell count (RBC), blood elements) even after its administration Nitrogen (BUN) levels, aspartate amino transferase (AST) levels, alanine amino transferase (ALT) levels, creatine levels, glucose levels, SG levels, etc.) are all within the normal range and safe to the body without side effects. The effect of improving menopausal symptoms can be achieved.

The present invention provides an effective method for enhancing the effect of improving the menopausal symptoms of the pomegranate pulp extract and the pomegranate extract of the women to improve the menopausal symptoms.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

Example 1 Preparation of Pomegranate Extract with High Content of Ellagic Acid

First, foreign matter in the pomegranate was removed, and the broken fruit was separated and washed. The sorted raw fruit was cut to remove the shell, and pressed to 160 bar to separate the seeds. After pasteurization, pectinase (pectinase) was added to 100-150 gr per 6000 L of pomegranate juice and starch was decomposed for 1 hour at 50-60 ℃. In order to maintain turbidity and color, and to produce a viscosity that is advantageous for taking, gelatin 1200-1800 gr per 6000 liters of pomegranate juice, 6000 gr of silicon dioxide, and 14 kg bentonite per 10000 liters of pomegranate juice were added, and 30 at 50-60 ° C. Stirred for a minute. Vacuum filtered and then concentrated by heat (55-90 ° C. (3 minutes), 105-110 ° C. (90 seconds), and 100-105 ° C. (90 seconds)) to extract pomegranate containing 0.8-1.4 mg / g of ellagic acid. Was prepared. It was then cooled and pasteurized (20 seconds at 90-94 ° C.). The same procedure was repeated six times to use the samples of Example 2 below.

Example 2 Evaluation of Content of Ellagic Acid in Pomegranate Extract

Three commercially available products and the ellagic acid content of the pomegranate extracts prepared in Example 1 were evaluated according to the following method, the results are shown in Table 1. Six samples with different lot numbers for each product were purchased to evaluate the content of ellagic acid.

The content of ellagic acid was measured using a high performance liquid chromatography method. SP C18 UG 120 (4.6mm × 50mm, 5㎛) was used as a column, and the mobile phase was separated by a gradient method using a 6: 4 mixture of purified water, 0.85% phosphoric acid and methanol and pure methanol. Ellagic acid was detected at a wavelength of 370 nm with a UV detector.

(Unit: mg / g) A product B products  C product Invention Extract 1 sample 0.21 0.39 0.27 0.80 2 samples 0.18 0.22 0.40 0.87 Sample 3 0.46 0.08 0.21 1.01 4 samples 0.19 0.13 0.27 1.40 5 samples 0.34 0.21 0.35 1.28 Sample 6 0.32 0.19 0.37 1.09 Content range of ellagic acid 0.18-0.46 0.08-0.39 0.21-0.40 0.80 to 1.40

In Table 1, product A is a pomegranate extract product of Shadaab Co., product B is a pomegranate extract product of Pashapour Trading Co., and product C is a pomegranate extract product of Noosh Iran Co.

As shown in Table 1, the pomegranate extract according to the present invention can be seen that the content of ellagic acid is very high compared to other commercially available products.

<Example 3> Evaluation of the degree of improvement of menopausal symptoms according to the content of ellagic acid

The degree of improvement of female menopausal symptoms of pomegranate pulp extract containing high content ellagic acid according to the present invention was evaluated by the following method.

Subject

Blood tests and Kupperman index were open to volunteers for women with FSH levels of 40 or more among women with amenorrhea over 6 months after menopause, aged 45 to 65 years. Subjects took 56 pouches of pomegranate concentrate for 4 weeks. A total of 50 subjects (10 in each group) were given 20 ml of pomegranate extract twice a day for 4 weeks. The experimental group was the control group (purified water containing 70 g of fructooligosaccharide and 13 g of isomerized sugar), product A (0.18-0.46 mg / g ellagic acid), product B (0.08-0.39 mg / g ellagic acid), and product C (ela Carboxylic acid 0.21-0.40 mg / g), and a pomegranate extract (0.8-1.4 mg / g ellagic acid) according to the present invention. To rinse your mouth, take 80 ml of water with you.

Research method

The study period was 5 weeks in total, and the volunteers recorded the subject's basic information such as demographic data and past medical history one week before the test extract was administered, and nutritional status, skin / mucosa, ear throat, cardiovascular system, urogenital system. Respiratory system, metabolic / endocrine system, digestive system, musculoskeletal system, neurological / psychologic and other physical examinations were performed to record normal status.

Subjects with cardiovascular menopausal disorder who have had or had undergone hormonal replacement therapy at least 6 months before, those with heart disease (heart failure, angina pectoris, myocardial infarction), uncontrolled hypertensive subjects, malignant tumors, angular angle glaucoma or lung disease Subjects who should be excluded from the normally performed Cooperman test, such as subjects with or with severe renal or hepatic impairment.

The biosignals and concomitant medications were checked while the pomegranate extract used for the test was distributed, and the Kupperman index was evaluated. Drugs and antioxidants that could affect hot flashes were banned. After the administration, the pouches were stored and returned for the correct dosing of volunteers. After 4 weeks of administration, the biological signs, adverse reactions, and concomitant medications were examined, and laboratory tests were performed.

Cooper only  Indicators( Kupperman Index ) evaluation

The Cooperman index test, which is commonly used to evaluate menopausal symptoms, was conducted. Immediately before and after the end of the administration, the investigator directly evaluated the Cooperman index items for the symptom onset, intensity, frequency, etc. of the subjects, and scored the questionnaire, thereby obtaining high content of ellagic acid of the present invention. The effect of the containing pomegranate extract was evaluated. Evaluation items of the Cooperman index are shown in Table 2 below.

No symptoms (0 points) Poor (1 point) Normal (two points) Severe (3 points) Hot flashes Sweat insomnia nervousness depression dizziness Lack of concentration Arthralgia headache Heartbeat Dryness

The weight consists of 51 points including hot flashes (4 points), sweating, insomnia and nervousness (2 points), depression, dizziness, poor concentration, joint pain, headache, palpitations, and vaginal dryness (1 point).

Test results (e.g., Cooper only  Indicator evaluation result)

The postmenopausal women aged 45-65 were classified as 50-53, 54-57, 58-61, and 62-65. There were 10 subjects in each test group. The demographic information of each group is shown in Table 3 below, and the Cooperman index difference (mean ± standard deviation) before and after taking is shown in Table 4 below.

50-53 years old 54-57 years old 58-61 years old 62-65 years Control group 2 people 4 people 2 people 2 people Product A 2 people 5 people 2 people 1 person Product B 2 people 4 people 2 people 2 people Product C 3 people 3 people 2 people 2 people Extract of the Invention 2 people 4 people 2 people 2 people

Control group Product A Product B Product C Invention Extract Kupperman Index 5.32 ± 0.98 8.43 ± 1.09 11.87 ± 2.75 8.21 ± 2.16 25.12 ± 3.48

As shown in the results of Table 4, the pomegranate pulp extract containing the high content of ellagic acid according to the present invention was superior to the control and other pomegranate extract with a low content of ellagic acid to improve the menopausal symptoms.

Example 4 Evaluation of Content of Other Components in Pomegranate Extract

In order to evaluate whether the effect of the high content of ellagic acid-containing pomegranate pulp extract according to the present invention is not simply caused by the more concentrated, the content of the other components known to be contained in the pomegranate extract is known as high-speed liquid chromatography already known in the art. Evaluation was performed by the graphing method, and the results are shown in Table 5 below.

(Unit: mg / kg) Product A Product B Product C Extract of the Invention Dyed Jane 0.09 0.09 0.11 0.09 Genistein 0.08 0.14 0.07 0.11 Quercetin 0.19 0.23 0.21 0.20 Estriol 10.17 10.02 10.34 10.40 17β-estradiol 0.13 0.15 0.13 0.06

As shown in Table 5, while the ellagic acid content of the pomegranate extract of the present invention was very high compared to the existing products, the content of other components did not have a significant difference between the existing products and the extracts according to the present invention. These results clearly show that the effect of the high content of ellagic acid-containing pomegranate pulp extract according to the present invention is not simply more concentrated.

Claims (11)

delete delete delete delete delete delete delete A pharmaceutical composition for improving women's menopausal symptoms comprising the pomegranate extract, characterized in that it comprises 0.8 to 1.8 mg / g of ellagic acid. The pharmaceutical composition according to claim 8, wherein the content of ellagic acid is 0.8 to 1.4 mg / g. Health functional food for improving women's menopausal symptoms comprising the pomegranate extract, characterized in that it comprises 0.8 to 1.8 mg / g of ellagic acid. delete