KR101525948B1

KR101525948B1 - Composition comprising carob extract for preventing, improving menopause of man

Info

Publication number: KR101525948B1
Application number: KR1020140177696A
Authority: KR
Inventors: 이정민; 주세환
Original assignee: 주식회사 엔에스웰니스
Priority date: 2014-12-10
Filing date: 2014-12-10
Publication date: 2015-06-05
Also published as: WO2016093637A1; JP2018500393A; JP6430659B2

Abstract

The present invention relates to a composition for preventing and improving menopausal symptoms comprising carob extract as an active ingredient.
Thus, there is a need for a method of treating a patient suffering from prostate hyperplasia, lower urinary tract symptoms, nervous irritation, emotional disturbance, depression, facial flushing, sleeping disorder, vitality loss, decreased work capacity, loss of sexual desire, erectile dysfunction, Such as a decrease in body weight, a decrease in body temperature, and the like.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention and improvement of menopausal symptoms comprising carob extract as an active ingredient,

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

In general, menopause is a term that refers to the period when various symptoms of female hormone deficiency occur after women's menopause, and it has nothing to do with men who do not develop menopause. However, men also show a decrease in the secretion of male hormones as they get older, and many other related symptoms are present. In recent years, these men are also referred to as menopause, mainly in fifties.

In men, menopausal symptoms are fatigue, depression, depression, increased body fat, decreased bone density, impotence, and hypogonadism. These symptoms are further promoted if external factors such as excessive drinking, smoking, and stress are added . Furthermore, the majority of elderly men have serious problems such as hypertension or adult diseases such as diabetes.

On the other hand, hormone therapy is typically used as a means of treating male menopausal symptoms. Hormone therapy is an artificial supplement to deficient male hormones and is known to be effective. However, if the above-mentioned treatment method is used merely because it is similar to male menopausal symptoms, serious side effects may be caused. In addition, Many side effects have occurred as a supplement, requiring accurate diagnosis by experts.

Therefore, it is necessary to research and develop a composition using a natural substance which can treat or prevent symptoms due to the decrease of male hormone and minimize side effects. The inventors of the present invention have found that a male hormone control syndrome and a novel While studying natural ingredients, carob { Ceratonia siliqua (L.) Taub.} The present inventors confirmed that the extract improves the symptoms caused by the menopausal period of the male, thereby completing the present invention.

Carob is an evergreen broad-leaved shrub belonging to the soybean family, tolerates drought, and contains resin in the leaves. There has been no study of the effect of these carrots on menopausal symptoms.

The object of the present invention is to provide a composition for preventing and improving menopausal symptoms, which comprises a carob extract which can effectively alleviate symptoms occurring in menopausal men and can minimize rejection to the body, .

In order to solve the above-mentioned problems, the composition according to the present invention is characterized by including carob extract as an active ingredient.

The composition comprising the carotenoid extract according to the present invention as an active ingredient can be used for the treatment of menopausal symptoms such as enlargement of the prostate gland, lower urinary tract symptoms, nervous irritation, emotional anxiety, depression, facial flushing, sleeping disorder, Erectile dysfunction, diminished tack, decreased physical fitness, reduced exercise capacity, and reduced body hair.

1 is a graph showing the results of measurement of weight gain of an animal under test
Fig. 2 is a graph showing the results of visceral fat weight measurement
3 is a graph showing the results of blood testosterone concentration measurement
FIG. 4 is a graph showing the improvement rate of the enlarged prostate and lower urinary tract symptoms in the test subjects measured by the IPSS test method
FIG. 5 is a graph showing the rate of improvement in menopausal symptom in the test subjects measured by the AMS test method

Before describing the present invention, the meaning of terms used in the present invention will be described.

In the present specification, 'extract' means to be used as a crude extract in the art, but broadly also includes the meaning of fractions in which the extract is further fractionated. That is, the carob extract includes not only those obtained using the above-mentioned extraction solvent but also those obtained by additionally applying a purification process thereto. For example, the extract may be fractionated by passing it through an ultrafiltration membrane having a constant molecular weight cut-off value, or by separation by various chromatographies (prepared for separation by size, charge, hydrophobicity or affinity) Fractions obtained through various purification methods are also included in the carob extract of the present invention.

As used herein, "comprising as an active ingredient" means containing an amount sufficient to achieve the potency or activity of the carob extract. The present invention is a composition extracted from carrots, which is a natural plant material, and there is no adverse effect on the human body even when administered in an excessive amount. Therefore, the quantitative upper limit of the carrots extract contained in the composition of the present invention can be selected by a person skilled in the art within a suitable range.

By "pharmaceutically effective amount" herein is meant an amount sufficient to achieve the potency or activity of the carob extract.

Male menopause refers to various symptoms that appear in middle-aged men similar to women's menopause. Externals include fatigue, memory loss, depression, increased body fat, decreased bone density, impotence, lower urinary tract symptoms, Hypogonadism and hypothyroidism. If the external factors such as excessive drinking, smoking, and stress are added, the above symptoms are further promoted. Furthermore, the majority of elderly men have serious problems such as hypertension or adult diseases such as diabetes.

The following is a detailed description of carob extract to alleviate this menopause.

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

(I) water, (ii) an alcohol having 1 to 6 carbon atoms (preferably, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, , 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) DMFO (Dimethyl-formamide) and (v) DMSO (dimethyl sulfoxide).

Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1 Chlorophenyl, 1-chlorobutane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethylsulfide, chloroform, Dichloromethane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride, methylene chloride, petroleum ether and THF.

(B) a water-soluble or lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) a mixed solvent of the lower alcohol and water, (d) ), Acetone, ethyl acetate, chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether, For easy extraction, it is more preferable to extract water, ethanol, or a mixture of water and ethanol into a carob.

In addition, the carob extract used in the present invention may be prepared in powder form by an additional process such as vacuum distillation and freeze-drying or spray-drying.

Accordingly, the present invention can produce an extract using the above-mentioned extraction solvent. Hereinafter, a method for producing a carob extract will be described.

1) Preparation of carrot extract

(1) After the carrots are selectively pulverized, (2) water containing purified water of a volume (v / w%), preferably 7 to 20 times the volume of the pulverized water, of about 1 to 25 times the weight, methanol, ethanol, Ethanol or a mixed solvent thereof, (3) at an extraction temperature of from 0 to 120 ° C, preferably from 50 to 100 ° C, and (4) For about 1 hour to 10 days, preferably for about 2 hours to 8 hours, and (5) by an extraction method such as a cold extraction, a hot water extraction, an ultrasonic extraction, a reflux cooling extraction or a heat extraction method, (6) Repeatedly extracts about 1 to 10 times, preferably 2 to 8 times. And (7) the extract is filtered with filter paper, (8) the filtrate is concentrated in vacuo, (9) freeze-dried, or (9) mixed with dextrin according to the mixing ratio to obtain a carob extract.

The carrot extract to be used in the experiment to be described later was obtained by primary extraction by hot water extraction method for 4 hours using purified water of a volume of 8 times the weight of the crushed powder of carob fruit as a solvent and secondary extraction by adding 4 times of purified water, Is filtered through a filter cloth, concentrated in vacuo, and then mixed with the extract and dextrin in a ratio of 1: 1 and spray-dried.

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

Hereinafter, the effect of the carob extract according to the present invention will be described in detail with reference to test examples.

Test Example 1: Animal test

<1-1> Subjects to be tested

Male Sprague-Dawley rats weighing about 250 g at 10 weeks of age were divided into 10 rats each as a control group and an experimental group.

The experimental group was orally administered carrot extract dissolved in physiological saline at a concentration of 50 mg / kg daily at the same time of day, and the control group was orally administered the same amount of physiological saline. For reference, breeding conditions were 24 ± 2 ℃, 50-55% humidity, and water and diet were provided without restriction.

<1-2> Measurement of weight gain

The effect of the composition of the present invention on body weight gain was confirmed and it was confirmed whether it is effective in preventing or treating male menopausal period.

The body weights were measured at the same time of the start and end dates of the test, and the increase was used as a result. The results are shown in FIG. Statistical analysis was performed using the Student's t-test for statistical significance, and was considered significant at p <0.05.

As shown in FIG. 1, the body weight gain of the control group (CTL) fed only with physiological saline was about 103 g, while the weight gain of the experimental group (CA) ingested with carab oil extract was about 84 g, Respectively. This shows that carab extract has the effect of inhibiting weight gain, one of the male menopausal symptoms.

<1-3> Built-in fat weight measurement

The effect of the composition of the present invention on the visceral fat weight was confirmed and it was confirmed that it is effective in preventing or treating male menopausal period.

Specifically, the groups classified in the <1-1> test subjects were fasted for 8 hours from the last oral administration time, and ether anesthesia was performed, and visceral fat was separated from the groups and then weighed. The results were expressed as the ratio of visceral fat in the experimental group to that of the control group (CTL) after converting the visceral fat weight of the control group (CTL) to 100%. The results are shown in FIG. 2 and statistically processed using the statistical program Student's t-test to verify the significance of the test results, and expressed as being significant at p <0.05.

As shown in FIG. 2, the visceral fat weight of the experimental group (CA) ingested with carob extract was found to be about 66% of the visceral fat weight of the control group (CTL) containing only physiological saline. This shows that carob extract has the effect of reducing visceral fat gain, one of the male menopausal symptoms.

<1-4> Measurement of testosterone in the body

It was confirmed that the composition of the present invention has an effect on the amount of male hormone in the blood, and thus it is confirmed that the composition is effective for preventing or treating menopausal period.

Specifically, each group of the <1-1> subjects to be tested was fasted for 8 hours before the oral administration and at the last oral administration, and then anesthetized with ether, and blood was collected from the abdominal vein. Before and after the oral administration, the blood was transferred to a heparin-treated tube, and the plasma was separated by centrifugation (2,500 rpm, 15 min, 4 ° C). Steroid displacement reagent was then applied to the separated plasma and total serum testosterone content was measured using an immunoassay kit (R & D Systems, USA). The results were expressed as a value relative to the plasma testosterone content before administration. The results are shown in FIG. 3 and were statistically processed using the statistical program Student's t-test to verify the significance of the test results, and were considered to be significant at p < 0.05.

As shown in FIG. 3, the control group (CTL) fed only with physiological saline did not show statistically significant change after the administration, whereas the test group (CA) ingested with the carob extract showed a blood testosterone level of about 46% . This suggests that the carotenoid extract has an effect on blood testosterone levels.

Test Example 2: Human body test

<2-1> Subjects to be tested

Thirty male subjects aged 40 or older who agreed to this test were randomly divided into control group and experimental group. Each control group received placebo and carrots were administered 40 mg / kg / day for 4 weeks.

<2-2> Prostate Symptom Score Questionnaire

The International Prostate Symptom Score (I-PSS) is a test designed to objectively assess the lower urinary tract symptoms and the resulting discomfort associated with prostate health. IPSS has been translated into languages of the world and has been validated and used globally. In Korea, the validity and reliability of the test method have been proved and the representative test method used in Korean prostate health evaluation is shown in Table 1.

Item Not at all 1 out of 5 times 1 out of 3 times Once in 2 times 2 out of 3 times always 1. Do you feel that you still have urine even after you have seen it? 2. Do you occasionally urinate again within 2 hours of your usual urination? 3. How often did urine stop and restart when I was on urination? 4. Is it difficult for you to keep urine when your urine is dry? 5. How often did the urine stalk weaken or sag? 6. How often have you had to wait or urge to urinate? none 1 time Episode 2 3rd time 4 times 5 times 7. How many times do you usually sleep and get up and urinate in one night? Extremely
satisfied satisfied Generally satisfied Half Generally dissatisfied Unhappy cruelty What do you think of this if urinary symptoms persist?

The results of calculating the IPSS score improvement rate before and after ingestion are shown in FIG. Results were statistically analyzed by SPSS (version 12.0), and significance was confirmed at p <0.05 level.

As shown in FIG. 4, the IPSS score of the control group (placebo) was changed by 2.8%, while the ingestion of carob extract decreased the IPSS score by about 48%, indicating that the enlargement of the prostate gland and the lower urinary tract were effectively improved . Thus, it can be seen that the carob extract, which is a composition of the present invention, is effective in improving benign prostatic hyperplasia and lower urinary tract symptoms which may appear in male menopausal period.

<2-3> Korean version of AMS Aging Males' Symptom )

The AMS rating developed in this German language is based on the age of the aging process, which is characterized by aging (eg, aging, depression, anxiety and depression). In 1999, Heinemann et al. (Heinemann LAJ, Zimmermann T, Vermeulen A, (Daig I, Heinemann LA, Kim S, Kwon S, Lee JH, Kim JH, Kim JH, Kim JH, Leungwattanaki S, Badia X, Myon E, et al. Aging Males' Symptoms (AMS) scale: review of its methodological characteristics. The Korean version of AMS is composed of 17 items as shown in Table 2. All items are quantified as no symptom (1 point), lightness (2 points), normal (3 points), severe (4 points) do. A score of 27 points or more was judged to be positive. According to the degree of symptom, 17-26 points were absent (No), 27-36 points were mild (Little), 37-49 points were moderate, (Severe). AMS 17 items were classified into symptom-based questionnaire items such as nervousness, emotional anxiety, depression, facial flushing, sleeping disorder, vitality depression, decreased work ability, sexual desire, erectile dysfunction, Decrease in exercise capacity, and decrease in body hair.

Item none lightness usually Severe Very severe 1. I feel unwell (subjective feeling of overall health). 2. Joints and muscles are sore (waist, joints, back pain or palms) 3. I sweat too much (the swelling of my stomach does not make me nervous or my face gets hot) 4. There is sleep disturbance (difficult to fall asleep, sleeping often, tired early in the morning, unable to sleep deeply, unable to sleep) 5. Sleep time is getting longer but I am tired. 6. Be excited (aggressive, easily angry at minor things, or whimsical) 7. Nerves are sensitive (nervous, nervous, impatient) 8. I am always anxious. 9. I feel physically awkward and vigorous (I feel compelled to do something because I do not have the ability to work, I do not work, I become indifferent to leisure activities, I can not achieve my goal, For example, I felt like going to work because I was sick. 10. My strength is weakening (feeling weak) 11. I feel depressed (I feel that my mood sinks, sad, tears, no motivation, changes in emotions, or uselessness) 12. It feels like the prime has passed. 13. Feeling emotionally exhausted (physical and mental exhaustion, negative attitude, feelings of helplessness and hopelessness) 14. Beard grows slower. 15. I have less energy and fewer sex lives. 16. The number of erections in the morning is decreasing. 17. Reduces sexual desire and reduces sexual impulses (eliminating the joy of sexual life or desire to have sex)

The AMS results of the control group and the experimental group are shown in Table 3 and FIG. 5 as the improvement rate and the overall improvement rate by item, and the results were written as mean and standard deviation. The statistical program was statistically processed by Student's t-test And were considered to be significant at p <0.05.

Symptom
AMS question number
Improvement rate Control group Experimental group Nervousness 6, 7 5.89% 55.42% Emotional disturbance 8 8.05% 62.96% depression 11, 12, 13 9.14% 56.75% Facial flushing 3 7.14% 50.20% Sleep disorder 4, 5 9.98% 57.78% Reduced vitality and reduced work capacity 9 2.79% 56.56% Decreased libido, impotence, decreased tack 15, 16, 17 5.16% 64.54% Decreased physical strength, reduced exercise capacity 1, 2, 10 1.96% 58.96% Hair loss 14 8.29% 43.85% Total score - 6.49% 57.51%

As a result of the test, the AMS score of the control group was not significantly different before and after the ingestion, whereas the intake group of the composition showed an improvement in the menopausal symptom of about 57% or more in the AMS score before the ingestion. In addition, the symptom improvement rate of each item was checked, and it was confirmed that symptoms corresponding to each item improved overall. These results suggest that carob extract generally alleviates the various menopausal symptoms in middle-aged men.

<2-4> Localization ADAM ( Androgen Deficiency in Aging Males )

In 2000, Morley et al. (Morley JE, Charlton E, Patrick P, Kaiser FE, Cadeau P McCready D et al., Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000, 49: 1239-1242) , Which was developed to evaluate male hormone deficiency by examining 10 representative symptoms based on clinical experience of men and women over 40 years of age. The number of questions is low and the sensitivity of diagnosis is high, so it is often used as a test for sex hormone deficiency. The ADAM test site in Korea is Kim Soo-woong (Kim Su-woong, Oh Seung-joon, Baek Jae-seung, Development of a Korean translation of the Androgen Deficiency in Aging Males (ADAM) Questionnaire. The Korean Journal of Urology 2004, 45 (7): 674-679.) This is an English-language version of the Korean version of the manuscript for screening male menopausal women and using them for clinical research. The ADAM's 10 questions are able to answer "Yes" or "No" to each symptom and are tests that can assess male hormone deficiency by assessing sexual dysfunction or other symptoms. If you answer 'Yes' in question 1 or 7 of the test items, or if you answered 'Yes' to more than 3 items in items other than items 1 and 7, you may have menopausal symptoms because of male hormone deficiency.

Item Yes no 1. Do you have loss of libido? 2. Do you have energy? 3. Are there any declines in physical fitness or endurance? 4. Has the key decreased? 5. Have you ever felt that the joy of life was reduced? 6. Do you feel depressed or annoyed? 7. Is the erection less severe than before? 8. Have you ever felt that your athletic ability has recently fallen? 9. Do you fall asleep right after dinner? 10. Has your work performance recently dropped?

The ADAM results of the carrots extract and the placebo-treated control rats were expressed as the percentage of men suspected of having menopausal age (%) based on the table in Table 4. The male pre-menopausal prevalence before and after intake of the experimental group and the control group is shown in Table 5 and the results are expressed as means and standard deviation and statistically treated with the Student's t-test statistical program at p <0.05 Were considered significant. (* p <0.05 vs. before ingestion)

In the control group, there was no significant change in male menopausal prevalence as assessed by the ADAM test before and after the placebo intake, whereas in the experimental group consuming the carob composition, the menopausal prevalence estimated by the ADAM test was reduced by 38%. Therefore, it can be seen that the composition of the present invention alleviates the symptoms of male hormone deficiency and improves male menopausal symptoms.

Prevalence (%) Before ingestion After ingestion Control group 69.8 70.1 Experimental group 71.2 33.2 *

Claims

A food composition for prevention and improvement of male menopausal symptoms comprising carob extract as an active ingredient.

A pharmaceutical composition for preventing and treating male menopausal symptoms comprising carob extract as an active ingredient.

The method according to claim 1 or 2,
Wherein the male menopausal symptoms are testosterone hypoglycemia.

The method according to claim 1 or 2,
The male menopausal symptoms may include hypogonadism, prostatic hypertrophy, lower urinary tract symptoms, nervousness, emotional anxiety, depression, facial flushing, sleeping disorder, dysfunctional vitality, decreased work capacity, loss of sexual desire, erectile dysfunction, A decrease in ability, and a decrease in body hair.