JP2018500393A - A composition for preventing and improving menopause, comprising carob extract as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing and improving male menopause, which contains a carob extract as an active ingredient. As a result, prostatic hypertrophy, lower urinary tract symptoms, irritability, emotional instability, depression, flushing, sleep disorders, decreased vitality, decreased work ability, decreased libido, erectile dysfunction, decreased energy, appearing in menopausal men Symptoms such as reduced physical fitness, decreased motor ability, and reduced hair can be improved.

Description

  The present invention relates to a new use of carob extract, and more particularly to a composition for preventing and improving symptoms appearing in menopausal men by containing carob extract as an active ingredient.

  In general, menopause is a term that refers to the time when various symptoms appear due to female hormone deficiency after menopause, and has nothing to do with men who do not experience menopause. However, as men get older, the secretion of androgen decreases, so various related symptoms have appeared. In recent years, men with such symptoms are also referred to as menopause, mainly to men in their 50s. appear.

  In men's menopause, symptoms such as fatigue, decreased memory, depression, increased body fat, decreased bone density, erectile dysfunction, and decreased libido appear, but if external factors such as excessive drinking, smoking, and stress are added The symptoms as described above are further promoted. Furthermore, most older men have adult illnesses such as high blood pressure and diabetes, making the problem even more serious.

  On the other hand, hormone therapy is typically used as a means for treating male climacteric symptoms. Hormone therapy is a therapy that artificially replaces missing male hormones and is known to be effective. However, if the above treatment method is performed simply because it is similar to male climacteric symptoms, it may cause serious side effects. There are many cases that have occurred, and accurate diagnosis by specialists is required for their use.

  Therefore, there is a need for research and development on compositions using natural substances that can treat or prevent symptoms due to a decrease in androgen and minimize side effects. As a result of intensive research on new natural ingredients excellent in the syndrome and the symptom-improving effect, Carob [Ceratonia siliqa (L.) Taub. The extract was found to improve menopausal symptoms, leading to the completion of the present invention.

  Carob is an evergreen broad-leaved shrub belonging to the legume family, well tolerates drought and contains resin in its leaves. The effect of such carob in relation to menopausal symptoms has not been studied.

  The problem to be solved by the present invention is to provide a carob extract that can effectively alleviate symptoms appearing in menopausal men and can minimize rejection to the body by comprising a natural ingredient. It is intended to provide a composition for the prevention and amelioration of male menopause including as

  The composition according to the present invention for solving the above-mentioned problems is characterized by including a carob extract as an active ingredient.

  A composition containing the carob extract according to the present invention as an active ingredient is prostatic hypertrophy, lower urinary tract symptoms, irritability, emotional instability, depression, facial flushing, sleep disorder, decreased vitality, which appears in menopausal men. Symptoms such as decreased work ability, decreased libido, erectile dysfunction, decreased energy, decreased physical fitness, decreased motor ability, and decreased hair can be improved.

It is a graph which shows the measurement result of the weight gain of a test subject animal. It is a graph which shows the measurement result of the visceral fat weight of a test subject animal. It is a graph which shows the measurement result of the blood testosterone density | concentration. It is a graph which shows the improvement rate of the prostatic hypertrophy and the lower urinary tract symptom of the test subject male measured by the IPSS test | inspection method. It is a graph which shows the improvement rate of the menopausal symptom of the test subject male measured by the AMS test method.

  Before explaining the present invention, the meaning of terms used in the present invention will be explained.

  In the present specification, the “extract” means what is commonly used as a crude extract in the industry, but in a broad sense, it also means the fraction obtained by further fractionating the extract. Including. That is, the carob extract includes not only those obtained using the above-described extraction solvent but also those obtained by further applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a predetermined molecular weight cut-off value, various chromatographies (made for separation by size, charge, hydrophobicity or affinity). Further, fractions obtained by various purification methods carried out, such as separation by the above, are also included in the carob extract of the present invention.

  In the present specification, “containing as an active ingredient” means containing an amount sufficient to achieve the efficacy and activity of the carob extract. The present invention is a composition extracted from carob, which is a natural plant material, and since there are no side effects on the human body even if overdose is performed, the upper limit of the amount that the carob extract is contained in the composition of the present invention is A normal engineer can select and implement within an appropriate range.

  As used herein, “pharmaceutically effective amount” means an amount sufficient to achieve the efficacy or activity of a carob extract.

  Men's menopause is a common name for various symptoms that appear in middle-aged men, like women's menopause.External symptoms include fatigue, memory loss, depression, increased body fat, decreased bone density, and erectile dysfunction. , Decreased libido, lower urinary tract symptoms, hypogonadism, etc., internally there is testosterone hypoxia. If external factors such as excessive drinking, smoking, and stress are added, the above symptoms are further promoted. Furthermore, most older men have adult illnesses such as high blood pressure and diabetes, making the problem even more serious.

  In the following, the carob extract for alleviating such menopause is described in detail.

  The carob extract according to the present invention is extracted using an organic solvent, and the following can be used as the extraction solvent.

  First, those suitable as polar solvents are (i) water, (ii) alcohols having 1 to 6 carbon atoms (preferably methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, normal-butanol, 1- Pentanol, 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) DMFO (dimethyl-formamide), and (v) DMSO (dimethylsulfoxide).

  Also suitable as 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, diethylamine, There are ether, carbon tetrachloride, methylene chloride, petroleum ether and THF.

  The present invention provides, as an 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 and (j) diethyl ether. Further, for easy extraction, it is more preferable to extract by treating a carob with water, ethanol, or a mixture of water and ethanol.

  Moreover, the carob extract used in the present invention may be produced in a powder form by further processes such as vacuum distillation and freeze-drying or spray-drying.

  Therefore, this invention can manufacture an extract using the above extraction solvents, and demonstrates the method of manufacturing a carob extract below.

1) Manufacture of carob extract
(a) After selecting and pulverizing the carob, (b) water containing purified water having a volume (v / w%) of about 1 to 25 times the weight of the pulverized product, preferably 7 to 20 times the volume. (C) 0-120 ° C., preferably a solvent selected from lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, butanol or a mixed solvent thereof, more preferably water, ethanol or a mixed solvent thereof. At an extraction temperature of 50-100 ° C., (d) about 1 hour to 10 days, preferably about 2 hours to 8 hours, (e) cold immersion extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction or (F) Extraction is repeated about 1 to 10 times, preferably 2 to 8 times, by an extraction method such as a heat extraction method, preferably by hot water extraction or reflux cooling extraction method. Further, (g) the extract is filtered through a filter cloth, (h) the filtrate is concentrated in vacuo, and then (i)-(a) freeze-dried or (i)-(b) depending on the blending ratio. Dextrin is mixed and spray dried to obtain the carob extract.

  In addition, the carob extract used in the experiment described later is subjected to primary extraction for 4 hours by hot water extraction method using purified water having a volume of 8 times the weight of the ground carob fruit as a solvent. Double purified water is added for secondary extraction, and the extract is filtered through a filter cloth, concentrated in vacuo, and then the extract and dextrin are mixed 1: 1 and spray dried.

  On the other hand, the carob extract may be produced by a subcritical extraction method using a subcritical fluid or a supercritical extraction method using a supercritical fluid.

  Below, the effect by the carob extract which concerns on this invention is demonstrated in detail by a test example.

Test Example 1: Animal subject test <1-1> Test subject Ten male rats (Rat) of 10 weeks old and weighing approximately 250 g of SD (Sprague-Dawley) strain were classified into a control group and an experimental group, respectively.

  The experimental group was orally administered with carob extract dissolved in physiological saline at a concentration of 50 mg / kg every day in the morning, and the control group was orally administered with the same amount of physiological saline. For reference, the breeding conditions were temperature 24 ± 2 ° C., humidity 50-55%, water and food provided without limitation.

<1-2> Measurement of body weight gain The effect of the composition of the present invention on body weight gain was confirmed, and it was confirmed whether it was effective in preventing or treating menopause.

  For the body weight, the weight of each group classified as the <1-1> test subject was measured at the same time as the start date and the end date of the test, and the increased amount was used as a result value. The result is illustrated in FIG. In order to test the significance of the test results, statistical processing was performed using the Student's t-test of the statistical program, and when p <0.05, it was regarded as significant and displayed.

  As shown in FIG. 1, the weight gain of the control group (CTL) ingesting only saline is about 103 g, while the weight gain of the experimental group (CA) ingesting the carob extract is about 84 g. It was confirmed that the weight gain was statistically significantly lower than that of the control group. Thereby, it turns out that a carob extract has the effect which suppresses the weight gain which is one of the menopausal symptoms.

<1-3> Weight measurement of visceral fat The effect of the composition of the present invention on the weight of visceral fat was confirmed, and it was confirmed whether it was effective in preventing or treating menopause.

  Specifically, each group classified as <1-1> test subject was fasted for 8 hours from the time of the last oral administration, then anesthetized with ether, and the visceral fat was separated and the weight was measured. did. As a result value, the weight of the visceral fat of the control group (CTL) was converted to 100%, and then the weight of the visceral fat of the experimental group was expressed as a relative ratio value with respect to the control group (CTL). The results are shown in FIG. 2. For the significance test of the test results, statistical processing is performed using Student's t-test of the statistical program, and when p <0.05. Displayed as significant.

  As shown in FIG. 2, the weight of the visceral fat of the experimental group (CA) ingesting the carob extract was about 66% relative to the weight of the visceral fat of the control group (CTL) ingesting only saline. It was confirmed. Thereby, it can be seen that the carob extract has an effect of decreasing the visceral fat increase which is one of the menopausal symptoms.

<1-4> Measurement of testosterone in the body The effect of the composition of the present invention on the amount of male hormone in blood was confirmed, and it was confirmed whether it was effective in preventing or treating menopause.

  Specifically, each group classified according to the above <1-1> test subjects was fasted for 8 hours from the time before oral administration and the time of the last oral administration, and then anesthetized with ether and laparotomized, and blood from the abdominal vena cava Were collected. The blood collected before and after oral administration was transferred to a tube treated with heparin, and then centrifuged (2,500 rpm, 15 min, 4 ° C.) to separate plasma. Moreover, after processing the steroid substitute agent (Steroid displacement reagent) to the isolate | separated plasma, the total testosterone content in the blood was measured using the immunoassay kit (R & D Systems, USA). The result value is shown as a value relative to the plasma testosterone content before administration. The results are shown in FIG. 3 and are statistically processed using the Student's t-test of the statistical program to test the significance of the test results and are significant when p <0.05. Displayed as being considered.

  As shown in FIG. 3, the control group (CTL) ingesting only saline did not show a statistically significant change after administration, whereas the experimental group (CA) ingesting the carob extract was The blood testosterone value increased by about 46% compared to before administration. Thereby, it can be seen that the carob extract affects the increase in blood testosterone concentration.

Test Example 2: Human subject test <2-1> Test target Thirty men over 40 years of age who agreed to the test were arbitrarily classified into 15 groups each in the control group and the experimental group. Placebo) and the experimental group was ingested 40 mg of carob extract for 4 weeks per day.

<2-2> Questionnaire survey of prostate symptom score I-PSS (International Prostate Symptom Score) objectively evaluates lower urinary tract symptoms that may be caused by a decrease in prostate health and the resulting inconveniences of life This is an inspection designed for this purpose. IPSS has been translated into various languages around the world and has been validated and used globally. In Korea, the validity and reliability of the test method has been proven and is currently used for the assessment of prostate health in Korea. This is a typical inspection method, and each item is as shown in Table 1.

  The result of calculating the improvement rate of the IPSS score before and after ingestion is shown in FIG. The results were statistically processed with the statistical program SPSS (version 12.0) and tested for significance at a level of p <0.05.

  As shown in FIG. 4, the control group (Placebo) had an IPSS score changed by about 2.8%, while the carob extract intake group (experimental group) had an IPSS score decreased by about 48% or more, It was confirmed that prostatic hypertrophy and lower urinary tract symptoms were effectively improved. Thus, it can be seen that the carob extract, which is the composition of the present invention, is effective in improving prostatic hypertrophy and lower urinary tract symptoms that can appear in male menopause.

<2-3> Korean version of AMS (Aging Male's Symptom)
1999 Heinemann et al. (Developed by Heinemann LAJ, Zimmermann T, Vermeulen A, Thiel C. A New 'Aging Male's Symptom' (AMS) Scale. The Aging Male 1992, 105: 105). AMS grade is a tool that has been validated and reliable, designed to objectively evaluate the effects of aging on men's quality of life. Translated version proved valid and reliable (Daig I, Heinemann LA, Kim S, Leungwattanakij S, Badia X, Myon E, et al. E Aging Male 'Symptoms (AMS) scale: review f its methodological characteristics.Health Qual Life Outcomes 2003; 1: 77).. As shown in Table 2, the Korean version of AMS consists of a total of 17 questions. All items are asymptomatic (1 point), mild (2 points), normal (3 points), and heavy (4 Point) and very heavy (5 points). If the total score is 27 points or more, it is determined as positive, and 17-26 points are absent (No), 27-36 points are light (Little), 37-49 points are moderate (Moderate), 50 according to the degree of symptoms. A point or more is classified into severe. AMS's 17 question items are classified according to each item according to the symptom. Typical symptoms of menopause are neurosensitivity, emotional instability, depression, hot flush, sleep disorder, decreased vitality, and reduced work ability. Can be classified and evaluated as decreased libido, erectile dysfunction, decreased energy, decreased physical fitness, decreased motor ability, and decreased hair.

  The AMS results of the control group and the experimental group are shown in Table 3 and FIG. 5 as the improvement rate by item and the overall improvement rate. The result values are entered as the mean and standard deviation. Statistical analysis was performed with the t test (Student's t-test), and was considered significant when p <0.05.

  As a result of the test, the AMS score of the control group was not so different before and after the ingestion, whereas the ingestion group of the composition showed an improvement rate of male climacteric symptoms of about 57% or more in the AMS score as compared with before the intake. In addition, as a result of confirming the improvement rate of symptoms for each item, it was confirmed that symptoms corresponding to each item were improved overall. Thus, it was confirmed that the carob extract generally alleviates various menopausal symptoms appearing in middle-aged men.

<2-4> Korean version of ADAM (Androgenency in Aging Males)
2000 Morley et al. (Morley JE, Charleston E, Patrick P, Kaiser FE, Cadeau P, McCreready D, et al. Validation of a screening quest for medicine. This is a questionnaire developed to evaluate androgen deficiency by confirming 10 typical symptoms based on their clinical experience, and can select male hormone deficiency status from men over 40 years old Validity as a diagnostic test. It is often used as a male hormone deficiency screening test because there are not many question items and the sensitivity of diagnosis is high. The Korean version of the ADAM questionnaire is from Kim Soo-eun et al. {Kim Soo-eun, Oh Seung-joon, Bak Ze-soon, Kim Se-chul, Androgen Definitive in Aging Males (ADAM) Questionnaire Translation, Korean Journal of Urology 2004, 45 (7): 674-679. ] Is a questionnaire that selects male menopausal patients and translates the English version into the Korean version so that it can be used for clinical research. The 10 ADAM questions can be answered “yes” or “no” for each symptom, and males can be assessed by assessing the presence or absence of sexual function or other symptoms. It is a test that can evaluate the presence or absence of hormone deficiency. If you answered yes to question item 1 or 7 among the test items, or if you answered 3 or more yes to items other than question items 1 and 7, you have male hormone deficiency symptoms and male menopause There may be symptoms.

  The ADAM results of the experimental group that ingested the carob extract and the control group that ingested the placebo were expressed as the percentage of people suspected of having menopausal prevalence (%) based on the questionnaire in Table 4. The male menopause prevalence before and after the intake of the experimental group and the control group is described in Table 5, the result values are entered as the mean and standard deviation, and the Student's t-test of the statistical program ) And was considered significant when p <0.05 (* p <0.05 vs. before ingestion).

  Test results show that in the control group, male menopausal prevalence before and after ingestion of placebo did not change much, while in the experimental group that ingested the carob composition, males evaluated by ADAM questionnaire after ingestion The menopause prevalence has decreased by about 38%. Therefore, it can be seen that the composition of the present invention alleviates male hormone deficiency symptoms and improves male climacteric symptoms.

Claims (4)

  A food composition for preventing and improving male climacteric symptoms comprising carob extract as an active ingredient.   A pharmaceutical composition for preventing and treating male climacteric symptoms comprising a carob extract as an active ingredient.   The composition according to claim 1, wherein the male climacteric symptoms are testosterone hypoxia. Men's menopausal symptoms include hypogonadism, benign prostatic hyperplasia, lower urinary tract symptoms, irritability, emotional instability, depression, flushing of the face, sleep disorders, decreased vitality, decreased work capacity, decreased libido, erectile dysfunction 3. The composition according to claim 1, wherein the composition is any one of a decrease in vigor, a decrease in physical strength, a decrease in exercise ability, and a decrease in body hair.