WO2016093637A1

WO2016093637A1 - Composition for preventing and improving andropause, comprising carob extract as active ingredient

Info

Publication number: WO2016093637A1
Application number: PCT/KR2015/013512
Authority: WO
Inventors: 이정민; 주세환
Original assignee: 주식회사 엔에스웰니스
Priority date: 2014-12-10
Filing date: 2015-12-10
Publication date: 2016-06-16
Also published as: JP6430659B2; KR101525948B1; JP2018500393A

Abstract

The present invention relates to a composition for preventing and improving andropause, comprising a carob extract as an active ingredient. Thereby, the present invention can improve symptoms which appear in men with andropause, such as prostatism, lower urinary tract symptoms, nervousness, mental instability, depression, facial blushing, sleep disorders, hypodynamia, reduction in job performance, loss of sexual desire, impotence, decline in stamina, deterioration of physical strength, reduction in exercise ability, and reduction of body hair.

Description

Male menopausal prevention and improvement composition comprising carob extract as an active ingredient

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

In general, menopausal term is a term used to describe various symptoms of female hormone deficiency after menopause, and has no relation to men without menopause. However, as men also age, the secretion of androgen decreases, so several symptoms appear. In recent years, these men are also referred to as menopause and occur mainly in men in their 50s.

In menopausal men, symptoms include fatigue, memory loss, depression, increased body fat, decreased bone density, erectile dysfunction, and decreased libido. If external factors such as excessive drinking, smoking, and stress are added, these symptoms are further promoted. . Moreover, the majority of older men have adult diseases such as high blood pressure and diabetes, which makes the problem worse.

Meanwhile, hormone therapy is typically used as a means for treating male menopausal symptoms. Hormone therapy is an artificial replenishment of deficiency of male hormones, and its effect is known to be good. However, if the above treatment is performed solely because it is similar to male menopausal symptoms, it may cause serious side effects. There are many cases of side effects caused by supplementation, which requires accurate diagnosis by experts.

Therefore, there is a need for research and development of compositions using natural substances that can treat or prevent symptoms caused by a decrease in testosterone and minimize side effects. While researching natural ingredients Carrot { Ceratonia siliqua (L.) Taub.} Extract was confirmed to improve the symptoms caused by menopausal men and completed the present invention.

Carob is an evergreen broad-leaved shrub belonging to the legume, drought-tolerant, and contains resin in the leaves. There has been no research on the effect of these carobs on menopausal symptoms.

The problem to be solved in the present invention is to effectively alleviate the symptoms occurring in menopausal men, it consists of natural ingredients for preventing and improving male menopausal composition comprising a carob extract as an active ingredient that can minimize rejection to the body To provide.

The composition according to the present invention for solving the above problems is characterized in that it comprises a carob extract as an active ingredient.

The composition comprising the extract according to the present invention as an active ingredient is prostatic hyperplasia, lower urinary tract symptoms, nervousness, emotional anxiety, depression, hot flashes, sleep disorders, vitality, decreased work ability, decreased sexual desire, which occurs in menopausal men Symptoms such as erectile dysfunction, loss of energy, weakness, loss of motor skills and hair loss can be improved.

1 is a graph showing the measurement results of the weight gain of the test animal

2 is a graph showing the result of measuring the visceral fat weight of the test animal

3 is a graph showing the results of blood testosterone concentration measurement

Figure 4 is a graph showing the rate of improvement of prostate hyperplasia and lower urinary tract symptoms of the test subjects measured by the IPSS test

5 is a graph showing the improvement rate of menopausal symptoms of test subjects measured by AMS test method

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

In the present specification, 'extract' is a meaning commonly used in the art as a crude extract (Crude extract), but broadly also includes the meaning of the fraction (Fractionation) additionally extract (Fractionation). That is, the carob extract includes not only those obtained by using the above-described extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, the fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) Fractions obtained through various purification methods are also included in the carob extract of the present invention.

In the present specification, 'including as an active ingredient' means containing an amount sufficient to achieve the efficacy or activity of the carob extract. The present invention is a composition extracted from a carp which is a natural plant material, and there is no side effect to the human body even when an overdose is administered, so that the upper limit of the amount of the carob extract contained in the composition of the present invention can be carried out by a person skilled in the art.

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

Male menopause is a collective term for several symptoms in middle-aged men, similar to female menopause. External manifestations include fatigue, decreased memory, depression, increased body fat, decreased bone density, erectile dysfunction, decreased libido, lower urinary tract symptoms, Hypogonadism, and internally, testosterone hypoplasia. If external factors such as excessive drinking, smoking and stress are added, the above symptoms are further promoted. Moreover, the majority of older men have adult diseases such as high blood pressure and diabetes, which makes the problem worse.

Below is a detailed description of the carob extract for relieving such menopausal age.

Carob extract according to the present invention is extracted using an organic solvent, which can be used as an extraction solvent is as follows.

Firstly 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) dimethyl-formamide (DMFO) and (v) dimethyl sulfoxide (DMSO).

And nonpolar 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, anneal, diethylamine, ether, carbon tetrachloride, methylene chloride, petroleum ether and THF.

The present invention is 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, (d Acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether, and the like. It is more preferable to extract water, ethanol or a mixture of water and ethanol in a carob for easy extraction.

In addition, the carob extract used in the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying or spray drying.

Therefore, the present invention can be used to extract the extract using the above extraction solvent, the following describes a method for producing a carob extract.

1) Preparation of Carob Extract

① After sorting and pulverizing the carp ② Water, methanol, ethanol, butanol containing about 1 to 25 times the volume (v / w%), preferably 7 to 20 times the volume of purified water A solvent selected from a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, more preferably water, ethanol or a mixed solvent thereof, at an extraction temperature of 0 to 120 캜, preferably 50 to 100 캜, For about 1 hour to 10 days, preferably about 2 hours to 8 hours, ⑤ extraction method such as cold needle extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction or heat extraction method, preferably by hot water extraction or reflux cooling extraction method (6) Repeated extraction about 1 to 10 times, preferably 2 to 8 times. And ⑦ the extract is filtered with a filter cloth, ⑧ the filtrate is concentrated in vacuo and then ⑨-① freeze-dried, or IX-x mixed by dextrin according to the mixing ratio to obtain a carob extract.

Carp extract to be used in the experiment to be described later, the first extraction by hot water extraction method for 4 hours using a purified water of 8 times the weight of the crushed powder of carob fruit as a solvent, the second extraction by adding 4 times purified water, the extract The mixture was filtered with a filter cloth, concentrated in vacuo, and then prepared by spray drying by mixing the extract with dextrin in a 1: 1 ratio.

Meanwhile, the carob extract may be prepared by a subcritical extraction method using a subcritical fluid or a supercritical extraction method using a supercritical fluid.

In the following the effect by the carob extract according to the present invention will be described in detail by the test example.

시험예 1: 동물대상시험Test Example 1: Animal Test

<1-1> 시험 대상<1-1> Test subject

At 10 weeks of age, male rats of Sprague-Dawley strains weighing around 250 g were divided into 10 groups.

The experimental group orally administered Carob extract dissolved in physiological saline at a concentration of 50 mg / kg at the same time every morning, the control group was orally administered the same amount of physiological saline. For reference, conditions for breeding were provided at a temperature of 24 ± 2 ° C., a humidity of 50 to 55%, and water and diet.

<1-2> 체중 증가량 측정<1-2> Weight gain measurement

By confirming the effect of the composition of the present invention on the weight gain was confirmed whether it is effective in preventing or treating menopausal menopause.

Body weight was measured at the same time on the test start date and the end date of each group classified in the <1-1> test subjects, and the increase was used as a result. The results are shown in FIG. To verify the significance of the test results, the statistical program Student's t-test was used for statistical processing, and it was considered as significant at p <0.05.

As shown in FIG. 1, the weight gain of the control group (CTL) ingesting only saline was about 103g, whereas the weight gain of the experimental group (CA) ingesting Carob extract was about 84g. It was confirmed that it was significantly low. This shows that carob extract has the effect of inhibiting weight gain, one of the menopausal symptoms.

<1-3> 내장지방 무게 측정<1-3> visceral fat weight measurement

Checking the effect of the composition of the present invention on the weight of visceral fat was confirmed whether the effect is effective in preventing or treating menopausal men.

Specifically, each group classified in the <1-1> test subjects was fasted for 8 hours after the last oral administration, followed by ether anesthesia, laparotomy to separate visceral fat, and the weight thereof was measured. The result was converted to the weight of the visceral fat of the control group (CTL) to 100% and the weight of the visceral fat of the experimental group was expressed as a relative ratio value to the control (CTL). The results are shown in FIG. 2, and statistically processed using a 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. 2, the visceral fat weight of the experimental group (CA) ingesting the caprope extract was about 66% of the visceral fat weight of the control group (CTL) ingesting only saline. This shows that carob extract has the effect of reducing the increase in visceral fat, one of menopausal symptoms.

<1-4> 체내 테스토스테론 측정<1-4> measurement of testosterone in the body

Checking the effect of the composition of the present invention on the amount of male hormone in the blood to determine whether it is effective in preventing or treating menopausal men.

Specifically, each group classified in the <1-1> test subjects was fasted for 8 hours at the time before oral administration and at the time of the last oral administration, followed by ether anesthesia, and laparotomy to collect blood from the abdominal vein. The blood collected before and after oral administration was transferred to heparin-treated tubes, and centrifuged (2,500 rpm, 15 min, 4 ° C.) to separate plasma. After treatment with steroid replacement reagents (Steroid displacement reagent) to the separated plasma, the total testosterone content in blood was measured using an immunoassay kit (R & D Systems, USA). The results are expressed as plasma testosterone content before administration. The results are shown in FIG. 3, and statistically processed using the 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 Figure 3, the control group ingested only saline (CTL) showed no statistically significant change after administration, whereas the experimental group (CA) ingested Carob extract was about 46% of blood testosterone levels before administration. Increased. This shows that carob extract affects the increase in blood testosterone levels.

시험예 2: 인체대상시험Test Example 2: Human Subject Test

<2-1> 시험 대상<2-1> test object

Thirty males over 40 years of age who agreed to the test were randomly divided into 15 groups of control and experimental groups. The control group received placebo, and the experimental group received 40 mg of carob extract for 4 weeks per day.

<2-2> 전립선증상 점수 설문조사<2-2> Prostate Symptom Score Survey

The International Prostate symptom score (I-PSS) is a test designed to objectively assess the lower urinary tract symptoms and consequent life discomforts that may be caused by decreased prostate health. IPSS has been translated into various languages around the world and its validity has been proved and used throughout the world. The validity and reliability of the test method have been proved in Korea, and are the representative test methods currently used for prostate health evaluation in Korea.

Table 1

Item		None at all	1 out of 5	1 of 3	1 of 2	2 of 3	always
1. Do you sometimes feel like urine remains after you have seen it?
2. Do you usually urinate again within 2 hours after you urinate?
3. How often have you stopped and resumed when you urinate?
4. Is it difficult to hold urine when you are urinating?
5. How often have the urine stems become weak or limp?
6. How often have you had to be energized or waited to urinate?
		none	1 time	Episode 2	3rd time	4 times	5 times
7. How many times per night do you wake up and urinate?
	very good	satisfied	Generally satisfied	Half and a half	Mostly dissatisfied	Unhappy	cruelty
What do you think of this if the symptoms of urination persist?

The results of calculating the IPSS score improvement rate before and after ingestion are shown in FIG. 4. The results were statistically analyzed with the statistical program SPSS (version 12.0) to verify the significance at p <0.05 level.

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 reduced by about 48% or more, thereby effectively improving the prostate enlargement and lower urinary tract symptoms. It became. This can be seen that the carob extract of the composition of the present invention is effective in improving the prostate hypertrophy and lower urinary tract symptoms that may appear in the menopausal period.

<2-3> 한글판 AMS(Aging Males' Symptom)<2-3> Korean Version of Aging Males' Symptom

AMS grades, developed in German by Heinemann et al. (Heinemann LAJ, Zimmermann T, Vermeulen A, Thiel C. A New 'Aging Male's Symptom' (AMS) Scale.The Aging Male 1992, 2: 105-114.) The validity and reliability of the Korean version of Kim Se-hyun's translation was proved to be valid and reliable in 2003, designed to objectively assess the effect of males on the quality of life of men (Daig I, Heinemann LA, Kim S, Leungwattanakij S, Badia X, Myon E, et al.e Aging Males' Symptoms (AMS) scale: review of its methodological characteristics.Health Qual Life Outcomes 2003; 1: 77.). The Korean version of AMS consists of 17 questions as shown in Table 2, and all items are quantified as no symptoms (1 point), light (2 points), moderate (3 points), severe (4 points), and very severe (5 points). do. A total score of 27 or more is considered as positive.No 17-26 (No), 27-36 (Little), 37-49 (Moderate) and 50 or more severe Separate with (Severe). Each of the 17 AMS questions was classified according to the symptom, and the questionnaire was analyzed for symptoms of nervousness, emotional anxiety, depression, hot flashes, sleep disorders, reduced vitality, decreased work ability, decreased libido, impotence, decreased energy, and stamina. It can be categorized and evaluated as deterioration, motor loss, and hair loss.

TABLE 2

Item	none	lightness	usually	Severe	Very severe
1. Feeling poorly ill (subjective feeling of overall health)
2. Pain in joints and muscles (sick back, joints, back pain or limb pain)
3. I sweat too much (potatoes are cold even if I don't feel cold)
4. Have trouble sleeping (difficult to sleep, wake up often, sleep early, get tired, can't sleep deep, or can't sleep)
5. I have more sleep but still tired.
6. Excited well (being angry, easily angry, or capricious)
7. My nerves are sensitive (tense, upset or nervous)
8. I'm always anxious.
9. Physically exhausted and lacking energy (a feeling of being forced to do something because of poor performance, lack of activity, indifference to leisure activities, inability to meet targets, or lack of energy, ie For example, when I am sick, I feel like I am forced to go to work.)
10. My strength is falling (I feel weak)
11. I feel depressed (feels calm, sad, tearful, motivated, feelings change, or useless)
12. I feel like my prime is gone.
13. Feeling exhausted emotionally (feeling negative, helpless and hopeless with physical and mental exhaustion)
14. The beard grows slowly.
15. Less energetic and less sexual life.
16. The number of erections in the morning is decreasing
17. Less libido and less sexual impulse (no pleasure in sex life, no desire to live sex life)

The AMS results of the control group and the experimental group are shown in Table 3 and FIG. 5 as itemized improvement rate and overall improvement rate, and the result values are written as mean and standard deviation, and statistically processed by Student's t-test. Was considered significant at p <0.05.

TABLE 3

Symptom	AMS item number	Improvement
Symptom	AMS item number	Control	Experimental group
Nervousness	6, 7	5.89%	55.42%
Anxiety	8	8.05%	62.96%
depression	11, 12, 13	9.14%	56.75%
Hot flashes	3	7.14%	50.20%
Sleep disorder	4, 5	9.98%	57.78%
Decreased vitality, reduced work capacity	9	2.79%	56.56%
Decreased libido, erectile dysfunction, decreased energy	15, 16, 17	5.16%	64.54%
Weakness, reduced motor skills	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 control group's AMS score was not significantly different before and after ingestion, whereas the group receiving the composition showed an improvement in male menopausal symptoms by about 57% or more in the AMS score compared to before the intake. In addition, as a result of confirming the symptom improvement rate of each item, it was confirmed that the symptoms corresponding to each item were improved as a whole. As a result, it was confirmed that the carob extract alleviated various menopausal symptoms in middle-aged men.

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

Morley et al., 2000 (Morley JE, Charlton E, Patrick P, Kaiser FE, Cadeau P, McCready D, et al. Validation of a screening question naire for androgen deficiency in aging males. Metabolism 2000, 49: 1239-1242.) The test paper was developed to evaluate male hormone deficiency by identifying 10 representative symptoms based on the clinical experience. It has been proved as a valid diagnostic test for screening male hormone deficiency in men over 40 years old. The number of questions is not very high and the sensitivity of diagnosis is high, so it is commonly used for male hormone deficiency screening. The Korean version of the ADAM test paper was Kim Soo-woong {Kim Soo-woong, Oh Seung-jun, Baek Jae-seung, Kim Se-cheol. Development of a Korean translation of the Androgen Deficiency in Aging Males (ADAM) questionnaire. Korean Journal of Urology 2004, 45 (7): 674-679.} Is a Korean version of the Korean version of the Korean version of the Korean version for the purpose of screening male menopausal patients. Ten questions in ADAM can answer yes or no for each symptom, and can test for male hormone deficiency by evaluating sexual dysfunction or other symptoms. If you answered 'yes' to questions 1 or 7 in the test items, or if you answered 3 or more 'yes' to items other than questions 1 and 7, you may be considered to have male menopausal symptoms because of a testosterone deficiency.

Table 4

Item	Yes	no
1. Is there a decrease in libido?
2. Do you have energy?
3. Do you have a decline in stamina or endurance?
4. Have you reduced your height?
5. Have you ever felt that your joy in life has diminished?
6. Are you crying or irritating?
7. Is erection less intense than before?
8. Have you ever noticed a recent drop in athletic performance?
9. Do you fall asleep right after dinner?
10. Has your performance recently declined?

The ADAM results of the experimental group and the placebo-controlled group ingesting the Carob extract were expressed as the percentage of men suspected of having a male menopausal prevalence (%) based on the test sheet in Table 4. The prevalence of menopausal age before and after ingestion of the experimental and control groups is shown in Table 5, and the results are listed as mean and standard deviation, and statistically treated by Student's t-test at p <0.05. Considered significant. (* p <0.05 vs. before intake)

As a result, the control group showed no significant change in the premenstrual prevalence rate before and after placebo intake, whereas the experimental group who consumed the carob composition showed a 38% reduction in premenstrual prevalence after the ADAM test. Therefore, it can be seen that the composition of the present invention improves male menopausal symptoms by alleviating male hormone deficiency.

Table 5

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

Claims

Food composition for the prevention and improvement of male menopausal symptoms comprising a carob extract as an active ingredient.
A pharmaceutical composition for preventing and treating male menopausal symptoms, including a carob extract as an active ingredient.
The method according to claim 1 or 2,

The male menopausal symptom is a testosterone lowering composition.
The method according to claim 1 or 2,

The menopausal symptoms include hypogonadism, prostate hyperplasia, lower urinary tract symptoms, nervousness, emotional anxiety, depression, hot flashes, sleep disorders, vitality, decreased work ability, decreased libido, impotence, stamina, decreased stamina, exercise A composition, characterized in that any one of reduced ability, hair loss.