WO2016148545A1 - Composition for preventing or improving male menopause symptoms - Google Patents

Composition for preventing or improving male menopause symptoms Download PDF

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WO2016148545A1
WO2016148545A1 PCT/KR2016/002789 KR2016002789W WO2016148545A1 WO 2016148545 A1 WO2016148545 A1 WO 2016148545A1 KR 2016002789 W KR2016002789 W KR 2016002789W WO 2016148545 A1 WO2016148545 A1 WO 2016148545A1
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extract
composition
carob
present
kkujippong
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French (fr)
Korean (ko)
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노유헌
이지원
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Famenity Co Ltd
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Famenity Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/60Moraceae (Mulberry family), e.g. breadfruit or fig
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00Function of food ingredients
    • A23V2200/30Foods, ingredients or supplements having a functional effect on health
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2300/00Processes
    • A23V2300/14Extraction

Definitions

  • the present invention relates to a composition for preventing or improving menopausal symptoms.
  • male menopause also known as "late onset hypogonadism” (LOH), male hormone deficiency syndrome, and male climacteric syndrome
  • LH late onset hypogonadism
  • Representative symptoms include decreased blood testosterone, impaired erectile energy, decreased libido, passive attitude, depression, muscle weakness, osteoporosis sleep disorder, blood cholesterol metabolic abnormalities, and lowered the quality of life and the function of various organs. It can have a negative effect.
  • Testosterone supplementation has been applied or studied in diabetes mellitus, bone metabolism, body fat and muscle strength, cardiovascular, sexual and mood effects, and cognitive effects associated with male menopause, but incomplete, especially prostate by testosterone supplementation Side effects such as hypertrophy, prostate cancer, and heart disease have been reported and have limitations. Therefore, there is a need to develop improvers and treatments that can be used safely mentally and physically.
  • the present inventors have made intensive research efforts to develop male menopausal symptoms and male reproductive function effectively and to develop substances that are safe for human body, especially plant-derived substances.
  • the present invention was completed by experimentally clarifying that the combination of carob and kkujippong extract has a significantly increased male menopausal symptom improvement effect and a male reproductive function improvement effect compared to a single extract of carob or kkujippong.
  • Another object of the present invention to provide a food composition for improving male reproductive function comprising a complex extract of carob and kkujippong as an active ingredient.
  • the present invention provides a food composition for preventing or ameliorating male menopausal symptoms comprising a complex extract of carob and kkujippong as an active ingredient.
  • the present inventors have made diligent efforts to develop male menopausal symptoms and male reproductive function effectively, and to develop substances that are safe for the human body, especially plant-derived substances. In comparison, it was experimentally found that the male menopausal symptoms and the male reproductive function were improved significantly.
  • the combination extract of Carp and kkujippong of the present invention alleviates the decrease in testosterone, which is the cause of menopausal symptoms, improves exercise ability, and inhibits the activity of 5- ⁇ reductase to prevent and treat prostatic hyperplasia. It is effective in improving various male menopausal symptoms by showing effects.
  • the method for separating the carob and kkujippong extracts which are the active ingredients in the composition of the present invention, is carried out according to conventional methods known in the art for extracting extracts from natural products, that is, using conventional solvents under the conditions of conventional temperature and pressure. Can be separated.
  • polar solvents include (i) water, (ii) alcohols (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).
  • Suitable as 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, dichloro Methane, 1,2-dichloroethane, anneal, diethylamine, ether, carbon tetrachloride and THF.
  • the extraction solvent used in the present invention is (a) water, (b) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) the Mixed solvent of lower alcohol with water, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) Diethyl ether.
  • the extract of the present invention is obtained by treating hot water with carob or jacuzzi.
  • the term "extract" has the meaning commonly used as a crude extract in the art as described above, but also broadly includes a fraction additionally fractionating the extract. That is, the carob or kkujippong 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, fractions 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), etc. The fraction obtained through the purification method is also included in the carob or kkujippong extract of the present invention.
  • Carob and kkujippong 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.
  • the term 'comprising as an active ingredient' means to include an amount sufficient to achieve the efficacy or activity of the following carp and kkujippong.
  • the present invention is a composition extracted from the natural plant material, Carob and kkujippong, so even if excessive administration to the human body has no side effects, the upper limit of the quantity contained in the composition of the Carp and kkujippong extract of the present invention can be carried out by those skilled in the art selected within the appropriate range. .
  • Male menopausal symptoms to which the composition of the present invention can be applied include pain in the joints or muscles, osteoporosis, enlarged prostate, hyperhidrosis, sleep disorders, excitement, nervousness, emotional anxiety, lethargy, fatigue, muscle strength, weakness, vitality, facial Redness, sleep disorders, depression, decreased energy, lowered libido, lowered erection, decreased energy, decreased motor performance, reduced body hair, aging or decreased urogenital function.
  • Carob and kkujippong composite extract of the present invention is prepared by mixing the Carob and kkujippong extract in a 9: 1 to 6: 4 weight ratio.
  • the mixing ratio of the complex extract is 9: 1 to 6: 4, more preferably, the composition ratio of the mixture is 8: 2 to 6: 4, and most preferably, the mixing ratio of the complex extract is 7 : 3.
  • the composition of the present invention may be provided as a food composition.
  • the composition for the prevention or improvement of male menopausal symptoms including the complex extract of carotene and kkujippong of the present invention as an active ingredient is prepared as a food composition, as well as caropy and kkujippong as an active ingredient, it is commonly added during food preparation.
  • Ingredients include, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents.
  • Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol.
  • As the flavoring agent natural flavoring agents [tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.
  • the food composition of the present invention is prepared with a drink
  • citric acid liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract, and the like may be further included. have.
  • the present invention provides a food composition for improving male reproductive function comprising a complex extract of carob and kkujippong as an active ingredient.
  • Carob and kkujippong complex extract of the present invention is effective in improving male reproductive function by increasing sperm concentration in semen, increase sperm motility, and increase the secretion of testosterone.
  • composition of the present invention regulates the secretion of testosterone, a hormone associated with the sperm count and the mechanism of sperm motility in men, thereby restoring male sexual function and enhancing vitality.
  • the present invention provides a composition for the prevention or improvement of male menopausal symptoms comprising a complex extract of carob and kkujippong as an active ingredient.
  • composition of the present invention alleviates the decrease in testosterone, which is the cause of male menopausal symptoms, improves exercise ability, and inhibits the activity of 5- ⁇ reductase, thereby preventing and treating various menopausal symptoms by prostatic hypertrophy. Effective for improvement.
  • the present invention provides a composition for improving male reproductive function comprising a complex extract of carob and kkujippong as an active ingredient.
  • compositions of the present invention have an excellent effect on improving male reproductive function by increasing sperm concentration in semen, increasing sperm motility, and increasing the secretion of testosterone.
  • the composite extract of carob and kkujippong of the present invention shows a markedly increased male menopausal symptom improvement effect and male reproductive function improvement effect as compared to the single extract of carob and kkujippong.
  • Figure 1 shows the results of measuring the effect on the cell viability of the mixture of the carob extract and kkujippong extract on testicular Leidich cells.
  • 'HCG' refers to a human chorionic gonadotropin
  • 'Control' is a control
  • 'CS' is a carob extract
  • 'CT' is a kkujippong extract
  • 'Mix' is a complex of carob extract and kkujippong extract.
  • Figure 2 shows the results of measuring the effect on the testosterone production of the mixture of the Carob extract and kkujippong extract in testicular Leidihi cells.
  • 'HCG' refers to a human chorionic gonadotropin
  • 'Control' is a control
  • 'CS' is a carob extract
  • 'CT' is a kkujippong extract
  • 'Mix' is a complex of carob extract and kkujippong extract.
  • Figure 3 shows the results of measuring the effect of the mixture of the Carob extract and Cudrania extract on 5-alpha reductase activity in the male prostate tissue.
  • 'Control' refers to the control
  • 'CS' refers to the carob extract
  • 'CT' refers to the kkujippong extract
  • ‘Mix’ refers to the complex of carob and kkujippong extract.
  • Figure 4 shows the results of measuring the effect of the mixture of carob extract and kkujippong extract on the exercise ability of male rats.
  • 'Control' refers to the control
  • 'CS' refers to the carob extract
  • 'CT' refers to the kkujippong extract
  • ‘Mix’ refers to the complex of carob and kkujippong extract.
  • Figure 5 shows the results of measuring the effect of the mixture of Carob extract and kkujippong extract on the sperm number of male rats.
  • 'Control' refers to the control
  • 'CS' refers to the carob extract
  • 'CT' refers to the kkujippong extract
  • ‘Mix’ refers to the complex of carob and kkujippong extract.
  • Figure 7 shows the results of measuring the effect of the mixture of carob extract and kkujippong extract on the sperm water improvement rate of male rats.
  • 'Control' refers to the control
  • 'CS' refers to the carob extract
  • 'CT' refers to the kkujippong extract
  • ‘Mix’ refers to the complex of carob and kkujippong extract.
  • Figure 7 shows the results of measuring the effect of the mixture of Carob extract and kkujippong extract on the sperm motility of male rats.
  • 'Control' refers to the control
  • 'CS' refers to the carob extract
  • 'CT' refers to the kkujippong extract
  • ‘Mix’ refers to the complex of carob and kkujippong extract.
  • the extract is extracted by hot water extraction for about 4 hours using about 6 times the volume (w / v) of purified water as a solvent, followed by secondary extraction by adding 4 times purified water. .
  • the extract was directly filtered, concentrated in vacuo, mixed with dextrin in a 1: 1 ratio, and spray dried or lyophilized to obtain a carob extract.
  • Carob extract and kkujippong extract obtained from the above embodiment is mixed by 10: 1 to 1:10, preferably 9: 1 to 8: 2, more preferably 7: 3 to 6: 4 ratio and Prepare a mixture of Cudrania extract.
  • Test Example 1-1 Leidihi Cell Incubation and Treatment of Extracts
  • Leydig cells mouse TM3 cells, were cultured in DMEM medium with 10% FBS, penicillin (100 ⁇ g / ml) and streptomycin (100 ⁇ g / ml) at 37 ° C. and 5% CO 2 .
  • DMEM medium containing 1% FBS
  • carob extract, diverse extract, and a mixture of carob extract and diverse extract were treated, respectively.
  • hCG human chorionic gonadotropin, 6 mIU / 200 ⁇ l medium; Sigma-Aldrich, USA
  • TM3 cells were seeded in 96-well (Nunc, Slangerup, Denmark) at a density of 15,000 cells / well and incubated for 24 hours. The cell culture was changed to DMEM containing 1% FBS and further incubated for 2 hours. To 50 ⁇ l of the Carob extract in cultured cells; Kkujippong extract to 50 ⁇ l concentration; Or add a mixture of carob extract and kkujippong extract to 50 ⁇ concentration and the same amount of PBS (pH 7.4) as a negative control group, and then add hCG (6 mIU / 200 ⁇ medium) of Test Example 1-1 24 hours were further incubated.
  • hCG 6 mIU / 200 ⁇ medium
  • Test Example 1-3 Testosterone production measurement
  • Test Example 1-1 After 24 hours of treatment with the extract and hCG by the method of Test Example 1-1, using the ELISA kit (DRG Instruments, Marburg, Germany), the testosterone production was measured according to the manufacturer's instructions. Testosterone amount was calculated by dividing the amount of protein in each sample, and after three repeated measurements, averaged to obtain the result.
  • Benign prostatic hypertrophy is a menopausal symptom seen in middle-aged men after their 40s.
  • testosterone is known to have high blood levels of dihydrotestosterone (DHT) converted by 5-alpha reductase. Therefore, by confirming the inhibition rate of 5-alpha reductase activity of the present composition to determine the prophylactic effect of prostatic hyperplasia, one of the menopausal symptoms.
  • DHT dihydrotestosterone
  • Prostate glands were extracted from male rats of the Sparague-Dawley line of about 400-450 g body weight, washed once with physiological saline and homogenized with PBS. The homogeneous solution was centrifuged at 4 ° C. and 5,000 rpm for 5 minutes, and only the supernatant was used for the experiment. 5-alpha reductase II activity was measured as described using the rat 5- ⁇ reductase II ELISA kit (Cusabio). 200 ⁇ g of homogenate and carob extract, kkujippong extract, complex of carob extract and kkujippong extract were reacted at room temperature for 30 minutes, treated with testosterone 2 nM at 37 ° C.
  • mice Male rats (Sampaco Bio Korea, Korea) of Sparague-Dawley strains weighing around 400-450 g, respectively, control group (CTL), carob extract (CS), and cuzipan extract (CT) And 5 rats, each of which was divided into an experimental group in which a mixture of Carob extract and Cudrania extract (Mix) was ingested.
  • CTL control group
  • CS carob extract
  • CT cuzipan extract
  • the rats were allowed to freely eat the solid feed and distilled water, and after one week of adaptation, they were dissolved in physiological saline at the same time every morning, or kkujippong extract, or a combination of carops extract and kkujippong extract (7: 3).
  • Rat athletic performance was measured using the Rotarod test.
  • the rotarod test is a test that measures the amount of time a rat has run on a cylinder until it falls by running on a rotating cylinder. The rotational speed of the cylinder was maintained at 6 rpm for the first 30 seconds and then accelerated to 40 rpm over 5 minutes. The rotarod test was carried out before the initial administration and after the end of 1 month of administration, and the measured value was averaged by measuring three times the latency time on the cylinder.
  • Test Example 4 Effect of increasing sperm count and sperm motility
  • Sperm number and sperm motility were measured by extracting the left and right epididymis twice from the experimental animal of Test Example 1 before the start of the extract administration and after the end of the extract administration for 1 month. Respiratory anesthesia was performed with 4% isoflurane, and the left epididymis was extracted, chopped and diluted with PBS before starting administration, and sperm count was measured under an optical microscope with a cell counter. After epididymal extraction, the extraction site was closed, and after 1 month of administration, the right epididymis was taken out in the same manner to measure sperm count.
  • the male was ingested with the composition of the present invention to determine the effect of preventing and treating male menopausal symptoms through a male menopausal evaluation questionnaire before and after ingestion.
  • AMS is a test tool that Heinemann et al. Designed to objectively evaluate the effects of aging on men's quality of life. Its validity and reliability have been proved as an evaluation method. Heinemann LAJ, Zimmermann T, Vermeulen A, Thiel C. A New 'Aging Male's Symptom' (AMS) Scale.The Aging Male 1992, 2: 105-114.).
  • Representative male menopausal periods such as nervousness, emotional anxiety, depression, hot flashes, sleep disorders, vitality, decreased work ability, decreased libido, impotence, decreased energy, decreased physical strength, reduced exercise ability, and reduced body hair. Symptoms can be assessed.
  • the AMS results of the control group and the experimental group are categorized by symptoms of male menopausal symptoms, and the score change according to the symptoms in the control group and the experimental group is shown in Table 2. Results were listed as mean and standard deviation. For the significance test, statistical analysis was performed using Student's t-test, which was considered significant at p ⁇ 0.05 (* p ⁇ 0.05).
  • the control group showed no significant change in the male menopausal symptom score evaluated by the AMS test paper before and after the placebo intake.
  • Significantly reduced mental symptoms neural nervousness, emotional anxiety, depression), physical symptoms (hot flashes, sleep disorders, vigor, decreased work ability, physical weakness, reduced motor skills), sexual symptoms (sexual desire) Deterioration, erectile dysfunction, energy loss, hair loss) and the like can be seen to be effective.
  • composition for the prevention or improvement of male menopausal symptoms according to the present invention can be used in a wide range of fields, such as food, medicine for preventing or improving male menopausal symptoms.

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Abstract

The present invention provides a composition for preventing or improving male menopause symptoms, the composition comprising a complex extract of carob and Cudrania tricuspidata as an active ingredient. The composition of the present invention is effective in improving various male menopause symptoms, as the invention alleviates reduction in testosterone, which is a cause of male menopause symptoms, and improves capacity for exercise and inhibits the activity of 5α-reductase and thereby exhibits an effect in preventing and treating prostate hypertrophy. The present invention provides a composition for improving male reproductive function, the composition comprising a complex extract of carob and Cudrania tricuspidata as an active ingredient. The composition of the present invention exhibits an outstanding effect in improving male reproductive function by increasing the sperm concentration in seminal fluid, increasing sperm motility and increasing the secretion of testosterone. The complex extract of carob and Cudrania tricuspidata of the present invention exhibits a far better effect in improving male menopause symptoms and effect in improving male reproductive function than single extractions of carob and Cudrania tricuspidata.

Description

남성 갱년기 증상의 예방 또는 개선용 조성물Composition for preventing or improving menopausal symptoms

본 발명은 남성 갱년기 증상의 예방 또는 개선용 조성물에 관한 것이다.The present invention relates to a composition for preventing or improving menopausal symptoms.

여성은 폐경기가 오면서 여성호르몬의 급격한 감소를 보이며 남성도 유사하게 내분비 변화가 일어나게 된다. 남성 갱년기는 “후기발현 남성 성선기능 저하증”(late onset hypogonadism, LOH), 남성 호르몬결핍 증후군, 남성갱년기 증후군(Male Climacteric Syndrome) 이라고도 하며 남성에서 연령의 증가와 관련되어 있고 더불어 혈청 테스토스테론의 결핍과 그에 따른 특징적인 임상적, 생화학적 증상을 나타내는 증후군이다. 대표적인 증상으로는 혈중 테스토스테론의 감소와 더불어, 발기력 감퇴, 성욕감퇴, 수동적인 태도, 우울, 근력저하, 골다공증 수면장애, 혈중 콜레스테롤 대사이상에 영향을 미쳐 삶의 질을 저하시키고 여러 신체기관의 기능에 부정적인 영향을 초래할 수 있다. As menopause comes, there is a rapid decrease in female hormones, and men similarly endocrine changes. Male menopause, also known as "late onset hypogonadism" (LOH), male hormone deficiency syndrome, and male climacteric syndrome, is associated with an increase in age in men and is associated with deficiency of serum testosterone and According to the characteristic clinical and biochemical symptoms. Representative symptoms include decreased blood testosterone, impaired erectile energy, decreased libido, passive attitude, depression, muscle weakness, osteoporosis sleep disorder, blood cholesterol metabolic abnormalities, and lowered the quality of life and the function of various organs. It can have a negative effect.

이러한 남성갱년기 증후군을 개선하기 위하여 남성호르몬 보충요법이 시도되고 있으며, 남성갱년기에 동반하는 제반 증상들과 테스토스테론과의 관계에 대한 많은 연구결과가 알려지면서 남성 갱년기장애는 테스토스테론을 이용한 호르몬 치료의 새로운 적응증으로 관심이 대두되고 있다. Male hormone replacement therapy has been tried to improve menopausal syndrome, and many studies on the relationship between menopausal symptoms and testosterone have been known, and male menopausal disorder is a new indication of hormone therapy using testosterone. Attention is on the rise.

테스토스테론 보충요법은 남성갱년기에 동반되는 당뇨, 골대사, 체지방 및 근력, 심혈관계, 성기능 및 기분에 대한 효과, 인지능력에 대한 효과에 적용되거나 연구가 되고 있지만 미비한 상태이며, 특히 테스토스테론 보충요법에 의한 전립선 비대증, 전립선암, 심장질환과 같은 부작용이 보고되는바 제한성을 지니고 있으므로 정신적 신체적으로 안전하게 사용할 수 있는 개선제 및 치료제의 개발이 요구된다. Testosterone supplementation has been applied or studied in diabetes mellitus, bone metabolism, body fat and muscle strength, cardiovascular, sexual and mood effects, and cognitive effects associated with male menopause, but incomplete, especially prostate by testosterone supplementation Side effects such as hypertrophy, prostate cancer, and heart disease have been reported and have limitations. Therefore, there is a need to develop improvers and treatments that can be used safely mentally and physically.

본 명세서 전체에 걸쳐 다수의 논문 및 특허문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.Throughout this specification, many papers and patent documents are referenced and their citations are indicated. The disclosures of cited papers and patent documents are incorporated herein by reference in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly explained.

본 발명자들은 남성 갱년기 증상 및 남성의 생식기능을 효과적으로 개선할 수 있으며 인체에 안전한 물질, 특히 식물-유래 물질을 개발하고자 예의 연구 노력하였다. 그 결과 캐롭 및 꾸지뽕 추출물의 조합이 캐롭 또는 꾸지뽕 단일 추출물과 비교하여 현저히 증가된 남성 갱년기 증상 개선 효과 및 남성 생식기능 개선효과를 가짐을 실험적으로 규명함으로써 본 발명을 완성하였다. The present inventors have made intensive research efforts to develop male menopausal symptoms and male reproductive function effectively and to develop substances that are safe for human body, especially plant-derived substances. As a result, the present invention was completed by experimentally clarifying that the combination of carob and kkujippong extract has a significantly increased male menopausal symptom improvement effect and a male reproductive function improvement effect compared to a single extract of carob or kkujippong.

따라서 본 발명의 목적은 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 갱년기 증상의 예방 또는 개선용 식품 조성물을 제공하는데 있다.Therefore, it is an object of the present invention to provide a food composition for preventing or improving menopausal symptoms of men and women including a complex extract of carops and kkujippong as an active ingredient.

본 발명의 다른 목적은 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 생식기능 개선용 식품 조성물을 제공하는데 있다. Another object of the present invention to provide a food composition for improving male reproductive function comprising a complex extract of carob and kkujippong as an active ingredient.

본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명 및 청구범위에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become apparent from the following detailed description and claims.

본 발명의 일 양태에 따르면, 본 발명은 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 갱년기 증상의 예방 또는 개선용 식품 조성물을 제공한다. According to one aspect of the invention, the present invention provides a food composition for preventing or ameliorating male menopausal symptoms comprising a complex extract of carob and kkujippong as an active ingredient.

본 발명자들은 남성 갱년기 증상 및 남성의 생식기능을 효과적으로 개선할 수 있으며 인체에 안전한 물질, 특히 식물-유래 물질을 개발하고자 예의 연구 노력하였고, 그 결과 캐롭 및 꾸지뽕 추출물의 조합이 캐롭 또는 꾸지뽕 단일 추출물과 비교하여 현저히 증가된 남성 갱년기 증상 개선 효과 및 남성 생식기능 개선효과를 가짐을 실험적으로 규명하였다. The present inventors have made diligent efforts to develop male menopausal symptoms and male reproductive function effectively, and to develop substances that are safe for the human body, especially plant-derived substances. In comparison, it was experimentally found that the male menopausal symptoms and the male reproductive function were improved significantly.

본 발명에 따르면, 본 발명의 캐롭 및 꾸지뽕 복합추출물은 남성 갱년기 증상의 원인인 테스토스테론의 감소를 완화하고 운동능력을 향상시키며, 5-α 리덕타아제의 활성을 억제하여 전립선 비대증에 대하여 예방 및 치료 효과를 나타냄으로써 다양한 남성 갱년기 증상을 개선하는데 유효하다. According to the present invention, the combination extract of Carp and kkujippong of the present invention alleviates the decrease in testosterone, which is the cause of menopausal symptoms, improves exercise ability, and inhibits the activity of 5-α reductase to prevent and treat prostatic hyperplasia. It is effective in improving various male menopausal symptoms by showing effects.

본 발명의 조성물에서의 유효성분인 캐롭 및 꾸지뽕 추출물을 분리하는 방법은 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건하에서 통상적인 용매를 사용하여 분리할 수 있다.The method for separating the carob and kkujippong extracts, which are the active ingredients in the composition of the present invention, is carried out according to conventional methods known in the art for extracting extracts from natural products, that is, using conventional solvents under the conditions of conventional temperature and pressure. Can be separated.

본 발명의 조성물에서 이용되는 캐롭 및 꾸지뽕 추출물을 캐롭 또는 꾸지뽕에 추출용매를 처리하여 수득하는 경우에 다양한 추출용매가 이용될 수 있다. 본 발명의 일 구현예에 따르면, 극성 용매 또는 비극성 용매를 이용할 수 있다. 극성 용매로서 적합한 것은, (i) 물, (ii) 알코올(바람직하게는, 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜), (iii) 아세트산, (iv) DMFO(dimethyl-formamide) 및 (v) DMSO(dimethyl sulfoxide)를 포함한다. 비극성 용매로서 적합한 것은, 아세톤, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 헥산, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린,디에틸아민, 에테르, 사염화탄소 및 THF를 포함한다.Various extractive solvents may be used in the case where the extract of carob and kkujippong used in the composition of the present invention is obtained by treating the extract with carob or jacuzzi. According to one embodiment of the present invention, a polar solvent or a nonpolar solvent may be used. Suitable polar solvents include (i) water, (ii) alcohols (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). Suitable as 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, dichloro Methane, 1,2-dichloroethane, anneal, diethylamine, ether, carbon tetrachloride and THF.

본 발명의 다른 구현예에 따르면, 본 발명에서 이용되는 추출용매는 (a) 물, (b) 탄소수 1-4의 무수 또는 함수 저급 알코올 (메탄올, 에탄올, 프로판올, 부탄올 등), (c) 상기 저급 알코올과 물과의 혼합용매, (d) 아세톤, (e) 에틸 아세테이트, (f) 클로로포름, (g) 부틸아세테이트, (h) 1,3-부틸렌글리콜, (i) 헥산 및 (j) 디에틸에테르를 포함한다. 본 발명의 특정 구현예에 따르면, 본 발명의 추출물은 열수를 캐롭 또는 꾸지뽕에 처리하여 수득한 것이다.According to another embodiment of the present invention, the extraction solvent used in the present invention is (a) water, (b) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) the Mixed solvent of lower alcohol with water, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) Diethyl ether. According to a particular embodiment of the present invention, the extract of the present invention is obtained by treating hot water with carob or jacuzzi.

본 명세서에서 사용되는 용어 ‘추출물’은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 캐롭 또는 꾸지뽕 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 캐롭 또는 꾸지뽕 추출물에 포함되는 것이다.As used herein, the term "extract" has the meaning commonly used as a crude extract in the art as described above, but also broadly includes a fraction additionally fractionating the extract. That is, the carob or kkujippong 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, fractions 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), etc. The fraction obtained through the purification method is also included in the carob or kkujippong extract of the present invention.

본 발명에서 이용되는 캐롭 및 꾸지뽕 추출물은 감압증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.Carob and kkujippong 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.

본 명세서에서 용어 ‘유효성분으로 포함하는’이란 하기의 캐롭 및 꾸지뽕의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명은 천연식물재료인 캐롭 및 꾸지뽕으로부터 추출한 조성물로서 과량 투여하여도 인체에 부작용이 없으므로 캐롭 및 꾸지뽕 추출물이 본 발명의 조성물에 포함된 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.In the present specification, the term 'comprising as an active ingredient' means to include an amount sufficient to achieve the efficacy or activity of the following carp and kkujippong. The present invention is a composition extracted from the natural plant material, Carob and kkujippong, so even if excessive administration to the human body has no side effects, the upper limit of the quantity contained in the composition of the Carp and kkujippong extract of the present invention can be carried out by those skilled in the art selected within the appropriate range. .

본 발명의 조성물이 적용될 수 있는 남성 갱년기 증상은 관절 또는 근육의 통증, 골다공증, 전립선 비대증, 다한증, 수면장애, 흥분, 신경과민, 정서불안, 무기력증, 피로, 근력 저하, 체력저하, 활력저하, 안면홍조, 수면장애, 우울증, 정력 저하, 성욕 저하, 발기력 저하, 정력감소, 운동능력저하, 체모감소, 노화 또는 비뇨생식기 기능 저하이다. Male menopausal symptoms to which the composition of the present invention can be applied include pain in the joints or muscles, osteoporosis, enlarged prostate, hyperhidrosis, sleep disorders, excitement, nervousness, emotional anxiety, lethargy, fatigue, muscle strength, weakness, vitality, facial Redness, sleep disorders, depression, decreased energy, lowered libido, lowered erection, decreased energy, decreased motor performance, reduced body hair, aging or decreased urogenital function.

본 발명의 일 구현예에 따르면, 본 발명의 캐롭 및 꾸지뽕 복합추출물은 캐롭 및 꾸지뽕 추출물을 9:1 내지 6:4 중량비로 혼합하여 제조한다. According to one embodiment of the present invention, Carob and kkujippong composite extract of the present invention is prepared by mixing the Carob and kkujippong extract in a 9: 1 to 6: 4 weight ratio.

바람직하게는, 상기 복합추출물의 혼합비는 9:1 내지 6:4이고, 보다 바람직하게는, 상기 혼합물의 구성비는 8:2 내지 6:4이고, 가장 바람직하게는, 상기 복합추출물의 혼합비는 7:3이다. Preferably, the mixing ratio of the complex extract is 9: 1 to 6: 4, more preferably, the composition ratio of the mixture is 8: 2 to 6: 4, and most preferably, the mixing ratio of the complex extract is 7 : 3.

본 발명의 조성물은 식품 조성물로 제공될 수 있다. 본 발명의 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 갱년기 증상의 예방 또는 개선용 조성물이 식품 조성물로 제조되는 경우, 유효성분으로서 캐롭 및 꾸지뽕 뿐 만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 백미 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다.The composition of the present invention may be provided as a food composition. When the composition for the prevention or improvement of male menopausal symptoms including the complex extract of carotene and kkujippong of the present invention as an active ingredient is prepared as a food composition, as well as caropy and kkujippong as an active ingredient, it is commonly added during food preparation. Ingredients, and include, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents [tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared with a drink, in addition to the white rice extract of the present invention, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract, and the like may be further included. have.

본 발명의 다른 일 양태에 따르면, 본 발명은 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 생식기능 개선용 식품 조성물을 제공한다. According to another aspect of the present invention, the present invention provides a food composition for improving male reproductive function comprising a complex extract of carob and kkujippong as an active ingredient.

본 발명의 캐롭 및 꾸지뽕 복합추출물은 정액 내 정자 농도를 증가시키고, 정자 운동성을 증가시키며, 테스토스테론의 분비를 증가시킴으로써 남성의 생식기능을 개선하는 데 유효하다.Carob and kkujippong complex extract of the present invention is effective in improving male reproductive function by increasing sperm concentration in semen, increase sperm motility, and increase the secretion of testosterone.

본 발명의 조성물은 남성의 정자 수 및 정자 운동성의 기전과 관련된 호르몬인 테스토스테론의 분비를 조절하여 저하되는 남성의 성기능을 회복시키며 활력을 증진시킨다.The composition of the present invention regulates the secretion of testosterone, a hormone associated with the sperm count and the mechanism of sperm motility in men, thereby restoring male sexual function and enhancing vitality.

본 발명의 특징 및 이점을 요약하면 다음과 같다:The features and advantages of the present invention are summarized as follows:

본 발명은 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 갱년기 증상의 예방 또는 개선용 조성물을 제공한다. The present invention provides a composition for the prevention or improvement of male menopausal symptoms comprising a complex extract of carob and kkujippong as an active ingredient.

본 발명의 조성물은 남성 갱년기 증상의 원인인 테스토스테론의 감소를 완화하고 운동능력을 향상시키며, 5-α 리덕타아제의 활성을 억제하여 전립선 비대증에 대하여 예방 및 치료 효과를 나타냄으로써 다양한 남성 갱년기 증상을 개선하는데 유효하다. The composition of the present invention alleviates the decrease in testosterone, which is the cause of male menopausal symptoms, improves exercise ability, and inhibits the activity of 5-α reductase, thereby preventing and treating various menopausal symptoms by prostatic hypertrophy. Effective for improvement.

본 발명은 캐롭 및 꾸지뽕의 복합추출물을 유효성분으로 포함하는 남성 생식기능 개선용 조성물을 제공한다. The present invention provides a composition for improving male reproductive function comprising a complex extract of carob and kkujippong as an active ingredient.

본 발명의 조성물은 정액 내 정자 농도를 증가시키고, 정자 운동성을 증가시키며, 테스토스테론의 분비를 증가시킴으로써 남성의 생식기능을 개선하는 데 뛰어난 효과를 나타낸다. The compositions of the present invention have an excellent effect on improving male reproductive function by increasing sperm concentration in semen, increasing sperm motility, and increasing the secretion of testosterone.

본 발명의 캐롭 및 꾸지뽕의 복합추출물은 캐롭 및 꾸지뽕 단일 추출물과 비교하여 현저히 증가된 남성 갱년기 증상 개선 효과 및 남성 생식기능 개선 효과를 나타낸다.The composite extract of carob and kkujippong of the present invention shows a markedly increased male menopausal symptom improvement effect and male reproductive function improvement effect as compared to the single extract of carob and kkujippong.

도 1은 고환 라이디히 세포에 대한 캐롭 추출물과 꾸지뽕 추출물의 혼합물의 세포 생존율에 미치는 영향을 측정한 결과를 나타낸다. ‘hCG’는 인간 융모성 고나도트로핀,‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 1 shows the results of measuring the effect on the cell viability of the mixture of the carob extract and kkujippong extract on testicular Leidich cells. 'HCG' refers to a human chorionic gonadotropin, 'Control' is a control, 'CS' is a carob extract, 'CT' is a kkujippong extract, and 'Mix' is a complex of carob extract and kkujippong extract.

도 2는 고환 라이디히 세포에서 캐롭 추출물과 꾸지뽕 추출물의 혼합물의 테스토스테론 생성에 미치는 영향을 측정한 결과를 나타낸다. ‘hCG’는 인간 융모성 고나도트로핀,‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 2 shows the results of measuring the effect on the testosterone production of the mixture of the Carob extract and kkujippong extract in testicular Leidihi cells. 'HCG' refers to a human chorionic gonadotropin, 'Control' is a control, 'CS' is a carob extract, 'CT' is a kkujippong extract, and 'Mix' is a complex of carob extract and kkujippong extract.

도 3은 웅성 랫트의 전립선 조직에서 캐롭 추출물과 꾸지뽕 추출물의 혼합물이 5-알파 리덕타아제 활성에 미치는 영향을 측정한 결과를 나타낸다. ‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 3 shows the results of measuring the effect of the mixture of the Carob extract and Cudrania extract on 5-alpha reductase activity in the male prostate tissue. 'Control' refers to the control, 'CS' refers to the carob extract, 'CT' refers to the kkujippong extract, and ‘Mix’ refers to the complex of carob and kkujippong extract.

도 4는 웅성 랫트의 운동능력에 대해 캐롭 추출물과 꾸지뽕 추출물의 혼합물이 미치는 영향을 측정한 결과를 나타낸다. ‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 4 shows the results of measuring the effect of the mixture of carob extract and kkujippong extract on the exercise ability of male rats. 'Control' refers to the control, 'CS' refers to the carob extract, 'CT' refers to the kkujippong extract, and ‘Mix’ refers to the complex of carob and kkujippong extract.

도 5는 웅성 랫트의 정자수에 대해 캐롭 추출물과 꾸지뽕 추출물의 혼합물이 미치는 영향을 측정한 결과를 나타낸다. ‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 5 shows the results of measuring the effect of the mixture of Carob extract and kkujippong extract on the sperm number of male rats. 'Control' refers to the control, 'CS' refers to the carob extract, 'CT' refers to the kkujippong extract, and ‘Mix’ refers to the complex of carob and kkujippong extract.

도 7은 웅성 랫트의 정자수 개선율에 대해 캐롭 추출물과 꾸지뽕 추출물의 혼합물이 미치는 영향을 측정한 결과를 나타낸다. ‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 7 shows the results of measuring the effect of the mixture of carob extract and kkujippong extract on the sperm water improvement rate of male rats. 'Control' refers to the control, 'CS' refers to the carob extract, 'CT' refers to the kkujippong extract, and ‘Mix’ refers to the complex of carob and kkujippong extract.

도 7은 웅성 랫트의 정자운동성에 대해 캐롭 추출물과 꾸지뽕 추출물의 혼합물이 미치는 영향을 측정한 결과를 나타낸다. ‘Control’은 대조군, ‘CS’는 캐롭 추출물, ‘CT’는 꾸지뽕 추출물, ‘Mix’는 캐롭 추출물과 꾸지뽕 추출물의 복합물을 의미한다.Figure 7 shows the results of measuring the effect of the mixture of Carob extract and kkujippong extract on the sperm motility of male rats. 'Control' refers to the control, 'CS' refers to the carob extract, 'CT' refers to the kkujippong extract, and ‘Mix’ refers to the complex of carob and kkujippong extract.

이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. .

실시예 1: 캐롭 추출물 또는 꾸지뽕 추출물의 제조 및 혼합물의 제조Example 1 Preparation of Carob Extract or Cudrania Extract and Preparation of Mixture

캐롭Carob (( CeratoniaCeratonia siliquasiliqua ) 추출물의 제조) Preparation of Extract

캐롭을 선별하여 분쇄한 뒤, 분쇄물 중량의 약 6배의 부피량(w/v)의 정제수를 용매로 하여 약 4시간 동안 열수추출방법으로 추출하고, 4배의 정제수를 가하여 2차 추출한다. 본 추출물을 바로 여과하여 진공농축한 후 덱스트린과 1:1로 혼합하여 분무건조하거나 동결건조하여 캐롭 추출물을 수득하였다.After selecting and pulverizing the carob, the extract is extracted by hot water extraction for about 4 hours using about 6 times the volume (w / v) of purified water as a solvent, followed by secondary extraction by adding 4 times purified water. . The extract was directly filtered, concentrated in vacuo, mixed with dextrin in a 1: 1 ratio, and spray dried or lyophilized to obtain a carob extract.

꾸지뽕Cudrania (( CudraniaCudrania tricuspidatatricuspidata ) 추출물의 제조) Preparation of Extract

꾸지뽕를 선별하여 분쇄한 뒤, 분쇄물 중량의 약 6배의 부피량(w/v)의 정제수를 용매로 하여 약 5시간 동안 열수추출방법으로 추출하고, 5배의 정제수를 가하여 2차 추출한다. 본 추출물을 바로 여과하여 진공농축한 후 덱스트린과 1:1로 혼합하여 분무건조하거나 동결건조하여 꾸지뽕 추출물을 수득하였다.After crushing and crushing kkujippong, using about 6 times the volume (w / v) of purified water of purified water as a solvent and extracted by hot water extraction method for about 5 hours, 5 times purified water is added to the second extraction. The extract was immediately filtered and concentrated in vacuo, mixed with dextrin in a 1: 1 ratio, and spray dried or lyophilized to obtain a zigzag extract.

캐롭Carob 추출물 및  Extract and 꾸지뽕Cudrania 추출물의 혼합물 제조 Preparation of mixtures of extracts

상기 실시예로부터 수득한 캐롭 추출물 및 꾸지뽕 추출물을 10:1 내지 1:10, 바람직하게는 9:1 내지 8:2, 보다 바람직하게는 7:3 내지 6:4의 비율로 혼합하여 캐롭 추출물 및 꾸지뽕 추출물의 혼합물을 제조한다.Carob extract and kkujippong extract obtained from the above embodiment is mixed by 10: 1 to 1:10, preferably 9: 1 to 8: 2, more preferably 7: 3 to 6: 4 ratio and Prepare a mixture of Cudrania extract.

시험예 1: 테스토스테론 증가 효과Test Example 1 Testosterone Increasing Effect

시험예Test Example 1-1:  1-1: 라이디히세포Leidihi Cell 배양 및 추출물의 처리  Incubation and Treatment of Extracts

라이디히 세포(Leydig cell)인 마우스 TM3 세포는 37℃, 5% CO2 조건에서 10% FBS, 페니실린(100 ㎍/ml), 스트렙토마이신(100 ㎍/ml)이 첨가된 DMEM 배지에서 배양하였다. 1% FBS가 포함된 DMEM 배지로 바꿔준 후, 캐롭 추출물, 꾸지뽕 추출물, 그리고 캐롭 추출물과 꾸지뽕 추출물의 혼합물을 각각 처리하였다. 그리고 테스토스테론 생성과 분비를 유도하기 위하여 hCG(human chorionic gonadotropin, 6 mIU/200 ㎕ medium; 시그마알드리치, 미국)를 처리하여 24시간 동안 추가 배양하였다. Leydig cells, mouse TM3 cells, were cultured in DMEM medium with 10% FBS, penicillin (100 μg / ml) and streptomycin (100 μg / ml) at 37 ° C. and 5% CO 2 . After changing to DMEM medium containing 1% FBS, carob extract, courageous extract, and a mixture of carob extract and courageous extract were treated, respectively. In addition, hCG (human chorionic gonadotropin, 6 mIU / 200 μl medium; Sigma-Aldrich, USA) was further incubated for 24 hours to induce testosterone production and secretion.

시험예Test Example 1-2: 세포생존율 측정  1-2: Cell viability measurement

TM3 세포를 각각 96-웰(Nunc, Slangerup, Denmark)에 15,000 세포/웰의 밀도로 깔아주고 24시간동안 배양하였다. 세포 배양액을 1% FBS가 들어있는 DMEM으로 갈아주고 2시간동안 추가로 배양하였다. 배양된 세포에 캐롭 추출물을 50 μ농도가 되도록; 꾸지뽕 추출물을 50 μ농도가 되도록; 또는 캐롭 추출물과 꾸지뽕 추출물의 혼합물을 50 μ농도가 되도록 첨가하고 음성대조군으로는 PBS (pH 7.4)를 동일한 양을 첨가한 다음, 시험예 1-1의 hCG(6 mIU/200 ㎕ medium)를 첨가하여 24시간을 추가로 배양하였다. alamarblue(Serotec, Oxford, UK)를 10 μ처리한 후 3시간 배양하고, ELISA Reader (Molecular Divices, Sunnycale, CA, USA)를 이용하여 570 nm에서 흡광도를 측정하여 세포생존율을 분석하였다. 배경 흡광도(blank count)는 600 nm에서 측정한 값을 사용하였다. 세포 생존율은 다음과 같은 공식을 이용하였다. TM3 cells were seeded in 96-well (Nunc, Slangerup, Denmark) at a density of 15,000 cells / well and incubated for 24 hours. The cell culture was changed to DMEM containing 1% FBS and further incubated for 2 hours. To 50 μl of the Carob extract in cultured cells; Kkujippong extract to 50 μl concentration; Or add a mixture of carob extract and kkujippong extract to 50 μ concentration and the same amount of PBS (pH 7.4) as a negative control group, and then add hCG (6 mIU / 200 μ medium) of Test Example 1-1 24 hours were further incubated. After 10 μ treatment of alamarblue (Serotec, Oxford, UK) and incubated for 3 hours, the cell viability was analyzed by measuring the absorbance at 570 nm using an ELISA Reader (Molecular Divices, Sunnycale, CA, USA). The background absorbance (blank count) was used as measured at 600 nm. Cell viability was calculated using the following formula.

Figure PCTKR2016002789-appb-M000001
Figure PCTKR2016002789-appb-M000001

결과는 평균과 표준오차로 나타내었으며 유의성 검증을 위해 통계처리는 스튜던트's t-테스트를 이용하였고, 그 결과를 도 1에 나타내었다.The results are expressed as mean and standard error, and statistically, Student's t-test was used for statistical significance. The results are shown in FIG. 1.

실험 결과, 도 1에서 보는 바와 같이 캐롭 추출물(CS), 꾸지뽕 추출물(CT), 그리고 캐롭 추출물과 꾸지뽕 추출물의 복합물(Mix)의 처리로 인해 대조군(Control)에 비해 약간의 세포생존율 증가가 일어나는 것처럼 보이지만, 통계적으로 유의한 변화는 없었다. 따라서 본 발명의 조성물이 세포생존율에는 영향을 미치지 않는 것으로 확인되었다. As a result of the experiment, as shown in Figure 1, a slight increase in cell viability compared to the control (Control) due to the treatment of the carob extract (CS), kkujippong extract (CT), and the complex (Mix) of the carob extract and kkujippong extract Although there was no statistically significant change. Therefore, it was confirmed that the composition of the present invention does not affect the cell viability.

시험예Test Example 1-3: 테스토스테론 생성 측정  1-3: Testosterone production measurement

상기 시험예 1-1의 방법으로 추출물과 hCG 24시간 처리 후, 배양액에서 ELISA 키트(DRG Instruments, Marburg, Germany)를 이용하여 테스토스테론 생성량을 제조사의 설명서대로 측정하였다. 테스토스테론 양은 각각의 시료에서 단백질량으로 나누어서 계산하였으며, 3회 반복 측정 후, 평균하여 결과값을 구하였다.After 24 hours of treatment with the extract and hCG by the method of Test Example 1-1, using the ELISA kit (DRG Instruments, Marburg, Germany), the testosterone production was measured according to the manufacturer's instructions. Testosterone amount was calculated by dividing the amount of protein in each sample, and after three repeated measurements, averaged to obtain the result.

결과는 평균과 표준오차로 나타내었으며 유의성 검증을 위해 통계처리는 스튜던트's t-테스트를 이용하였고, p<0.05 시에 유의한 것으로 간주하여 표시하였다. 그 결과를 도 2에 나타내었다.The results were expressed as mean and standard error. For statistical significance test, Student's t-test was used and it was considered as significant at p <0.05. The results are shown in FIG.

측정 결과, 도 2에서 확인할 수 있듯이, hCG 처리에 의해 라이디히 세포에서 테스토스테론 생성이 증가한 것을 확인할 수 있다. 거기에 캐롭 추출물(CS)과 꾸지뽕 추출물(CT)을 각각 처리한 경우에는 PBS를 처리한 대조군(Control)에 비해 테스토스테론 생성량이 각각 약 25% 및 23% 증가하였다. 그리고 복합물(Mix)을 처리한 경우에는 테스토스테론 생성량이 이보다 더 증가하여 대조군에 비해 55% 이상 증가한 것을 확인하였다. 이로써 복합물이 단일 추출물에 비해 라이디히 세포의 테스토스테론 생성을 더 증가시키는 것을 확인하였다. As a result of the measurement, as can be seen in Figure 2, it can be confirmed that the testosterone production in the Leidihi cells increased by hCG treatment. In the case of carob extract (CS) and kkujippong extract (CT), respectively, testosterone production increased by about 25% and 23%, respectively, compared to the control group treated with PBS. And when treated with the complex (Mix) it was confirmed that the testosterone production increased more than this increased by more than 55% compared to the control. This confirmed that the complex further increased testosterone production of Leidihi cells compared to a single extract.

시험예 2: 전립선비대증 개선 효과Test Example 2: Improvement of Prostatic Hyperplasia

5-알파 5-alpha 리덕타아제Reductase 활성 감소 효과  Active reduction effect

양성전립선비대는 40대 이후의 중년 남성에서 나타나는 남성갱년기 증상 중 하나로 전립선비대증 환자에서는 테스토스테론이 5-알파 리덕타아제로 인해 전환된 DHT(dihydrotestosterone)의 혈중 농도가 높게 측정되는 것으로 알려져 있다. 따라서 본 조성물의 5-알파 리덕타아제 활성 저해율을 확인함으로써 남성갱년기 증상 중 하나인 전립선비대증의 예방 효과를 확인하고자 한다. Benign prostatic hypertrophy is a menopausal symptom seen in middle-aged men after their 40s. In patients with prostatic hyperplasia, testosterone is known to have high blood levels of dihydrotestosterone (DHT) converted by 5-alpha reductase. Therefore, by confirming the inhibition rate of 5-alpha reductase activity of the present composition to determine the prophylactic effect of prostatic hyperplasia, one of the menopausal symptoms.

체중 400-450 g 내외의 스프라그-다우리(Sparague-Dawley) 계통의 웅성 랫트에서 전립선을 적출하여 생리식염수로 1회 세척하고 PBS를 넣어 균질화하였다. 균질액은 4℃, 5,000 rpm에서 5분간 원심분리하여 상층액만 취하여 실험에 사용하였다. 5-알파 리덕타아제 Ⅱ 활성은 랫트 5-α 리덕타아제 Ⅱ ELISA 키트(Cusabio)를 이용하여 설명서대로 측정하였다. 200 ㎍의 균질액과 캐롭 추출물, 꾸지뽕 추출물, 캐롭 추출물과 꾸지뽕 추출물의 복합물을 30분 동안 실온에서 반응시키고, 테스토스테론 2 nM를 처리하여 1시간 동안 37℃에서 반응시킨 후, 450 nm 파장에서 흡광도를 측정하였다. 결과는 테스토스테론 단독 처리군을 100%로 하여 백분율로 표기하였으며, 평균과 표준오차로 나타내었으며 유의성 검증을 위해 통계처리는 스튜던트's t-테스트를 이용하였고, p<0.05 시에 유의한 것으로 간주하여 표시하였다. 그 결과를 도 3에 나타내었다.Prostate glands were extracted from male rats of the Sparague-Dawley line of about 400-450 g body weight, washed once with physiological saline and homogenized with PBS. The homogeneous solution was centrifuged at 4 ° C. and 5,000 rpm for 5 minutes, and only the supernatant was used for the experiment. 5-alpha reductase II activity was measured as described using the rat 5-α reductase II ELISA kit (Cusabio). 200 μg of homogenate and carob extract, kkujippong extract, complex of carob extract and kkujippong extract were reacted at room temperature for 30 minutes, treated with testosterone 2 nM at 37 ° C. for 1 hour, and then absorbance at 450 nm wavelength. Measured. The results were expressed in percentage with 100% of testosterone alone, expressed as mean and standard error, and statistically used Student's t-test for statistical significance, and considered as significant at p <0.05. It was. The results are shown in FIG.

측정 결과, 도 3에서 확인할 수 있듯이, 캐롭 추출물(CS)과 꾸지뽕 추출물(CT) 처리군에서 테스토스테론만을 처리한 대조군(Control)에 비해 5-알파 리덕타아제 활성이 감소한 것을 알 수 있다. 그리고 복합물(Mix) 처리군에서는 효소 활성이 이보다 더 감소하여 대조군 대비 약 10%의 5-알파 리덕타아제 활성만을 보였다. 이로써 캐롭 추출물과 꾸지뽕 추출물이 테스토스테론을 DHT로 전환시키는 작용 효소인 5-알파 리덕타아제의 활성을 저해시키며, 특히 복합물이 단일 추출물에 비해 효소 활성 저해율이 더 높아 남성갱년기 증상 중 하나인 전립선비대 증상의 예방 및 치료제로 작용할 수 있음을 확인하였다. As can be seen in Figure 3, it can be seen that the 5-alpha reductase activity in the carob extract (CS) and kkujippong extract (CT) treated group compared to the control group treated only testosterone (Control). In the mixed (Mix) treatment group, the enzyme activity was further reduced, showing only about 10% of 5-alpha reductase activity compared to the control group. As a result, carob extract and kkujippong extract inhibit the activity of 5-alpha reductase, an action enzyme that converts testosterone to DHT.In particular, the complex has a higher inhibitory rate of enzyme activity than a single extract. It was confirmed that it can act as a prophylactic and therapeutic agent of.

시험예Test Example 3:  3: 운동능력 증가Increased athletic ability 효과 effect

랫트 운동능력 증가 효과 Rat exercise ability increase effect

체중 400-450 g 내외의 스프라그-다우리(Sparague-Dawley) 계통의 웅성 랫트((주)샘타코바이오코리아, 대한민국)를 각각 대조군(CTL), 캐롭 추출물(CS), 꾸지뽕 추출물(CT) 및 캐롭 추출물과 꾸지뽕 추출물의 혼합물(Mix)을 섭취한 실험군으로 나누어 각각 랫트 5 마리씩 실험에 이용하였다. 사육기간 중에는 랫트 고형 사료와 증류수를 자유롭게 섭취하도록 하였고, 일주일간의 적응 기간을 거친 후, 매일 오전 같은 시간에 생리식염수에 녹인 캐롭 추출물, 또는 꾸지뽕 추출물, 또는 캐롭 추출물 및 꾸지뽕 추출물의 복합물(7:3의 혼합비)을 각각 50 ㎎/㎏의 농도로 경구투여하고, 대조군은 동량의 생리식염수를 1개월 동안 경구투여 하였다. 랫트의 운동능력은 로타로드 시험법을 이용하여 측정하였다. 로타로드 시험은 랫트를 회전하는 원통 위에서 달리게 하여 떨어질 때까지 원통 위에서 달린 시간을 측정하는 검사이다. 원통의 회전 속도는 초기 30초동안 6 rpm으로 유지하다가 40 rpm까지 5분에 걸쳐 가속하였다. 로타로드 시험은 최초 투여 전과 1개월간의 투여가 종료된 후 각각 실시하였으며, 측정 값은 원통 위에서 달린 시간(latency time)을 3회 반복 측정하여 평균값을 구하였다.Male rats (Sampaco Bio Korea, Korea) of Sparague-Dawley strains weighing around 400-450 g, respectively, control group (CTL), carob extract (CS), and cuzipan extract (CT) And 5 rats, each of which was divided into an experimental group in which a mixture of Carob extract and Cudrania extract (Mix) was ingested. During the breeding period, the rats were allowed to freely eat the solid feed and distilled water, and after one week of adaptation, they were dissolved in physiological saline at the same time every morning, or kkujippong extract, or a combination of carops extract and kkujippong extract (7: 3). (Mixture ratio of)) was orally administered at a concentration of 50 mg / kg, respectively, and the control group was orally administered the same amount of saline solution for 1 month. Rat athletic performance was measured using the Rotarod test. The rotarod test is a test that measures the amount of time a rat has run on a cylinder until it falls by running on a rotating cylinder. The rotational speed of the cylinder was maintained at 6 rpm for the first 30 seconds and then accelerated to 40 rpm over 5 minutes. The rotarod test was carried out before the initial administration and after the end of 1 month of administration, and the measured value was averaged by measuring three times the latency time on the cylinder.

결과는 평균과 표준오차로 나타내었으며 유의성 검증을 위해 통계처리는 스튜던트's t-테스트를 이용하였고, p<0.05 시에 유의한 것으로 간주하여 표시하였다. 그 결과를 도 4에 나타내었다.The results were expressed as mean and standard error. For statistical significance, statistical analysis was performed using Student's t-test, which was considered significant at p <0.05. The results are shown in FIG.

측정 결과, 도 4에서 확인할 수 있듯이, 캐롭 추출물(CS)과 꾸지뽕 추출물(CT)을 각각 섭취한 경우, 로타로드 시험법으로 측정한 운동능력이 섭취 전에 비해 각각 19% 및 약 25% 증가하여 통계적으로 유의하게 향상되었다. 그리고 복합물(Mix)을 섭취한 경우, 로타로드의 달린 시간(latency time)이 섭취 전에 비해 40% 이상 증가하여 운동능력의 통계적으로 유의한 향상을 보였으며, 이로써 복합물이 단일 추출물에 비해 운동능력을 더 향상시키는 것을 확인하였다. As a result, as shown in Figure 4, when the carob extract (CS) and kkujippong extract (CT) ingested, respectively, the exercise capacity measured by the rotarod test method was increased by 19% and about 25%, respectively, compared to before intake statistically Significantly improved. In addition, when the compound was ingested, the latency time of rotarod was increased by more than 40% compared to before ingestion, which showed a statistically significant improvement in exercise ability. It was confirmed to further improve.

시험예 4: 정자수 및 정자운동성 증가 효과Test Example 4: Effect of increasing sperm count and sperm motility

랫트Rat 정자수Sperm count 및 정자 운동성 증가 효과  And sperm motility effect

상기 시험예 1의 실험동물을 추출물 투여 시작 전과 1개월간의 추출물 투여 종료 후 두 번에 걸쳐 각각 좌우의 부고환을 적출하여 정자수 및 정자 운동성을 측정하였다. 실험동물을 4% 이소플루란으로 호흡마취하고, 투여 시작 전 좌측 부고환을 각각 적출하여 잘게 썰어 PBS로 희석한 후, 세포계수기로 광학현미경 하에서 정자수를 측정하였다. 부고환 적출 후에는 적출 부위를 봉합한 후, 1개월간의 투여 종료 후, 동일한 방법으로 우측 부고환을 적출하여 정자수를 측정하였다.Sperm number and sperm motility were measured by extracting the left and right epididymis twice from the experimental animal of Test Example 1 before the start of the extract administration and after the end of the extract administration for 1 month. Respiratory anesthesia was performed with 4% isoflurane, and the left epididymis was extracted, chopped and diluted with PBS before starting administration, and sperm count was measured under an optical microscope with a cell counter. After epididymal extraction, the extraction site was closed, and after 1 month of administration, the right epididymis was taken out in the same manner to measure sperm count.

정자 운동성은 상기의 실험방법으로 모은 정자를 0.5% BSA가 포함된 M199 배지(GIBCO, Thermo Fisher Scientific Inc., MA, USA)에서 5분간 배양한 후, 활동하는 정자수를 전체 정자수로 나누어 백분율로 환산하였다. Sperm motility was incubated for 5 minutes in M199 medium (GIBCO, Thermo Fisher Scientific Inc., MA, USA) containing 0.5% BSA after sperm motility collected by the above method, divided by the total sperm count percentage Converted to.

결과는 평균과 표준오차로 나타내었으며 유의성 검증을 위해 통계처리는 스튜던트's t-테스트를 이용하였고, p<0.05 시에 유의한 것으로 간주하여 표시하였다(*p<0.05). 추출물 투여 전과 후의 정자수 및 정자수 개선율을 도 4 및 도 5에 나타내었으며, 추출물 투여 전과 후의 정자운동성은 도 4에 나타내었다.The results were expressed as mean and standard error. For statistical significance, statistical analysis was performed using Student's t-test, which was considered significant at p <0.05 (* p <0.05). The sperm count and sperm count improvement rate before and after the extract administration are shown in FIGS. 4 and 5, and the sperm motility before and after the extract administration is shown in FIG. 4.

측정 결과, 도 5 및 도 6에서 확인할 수 있듯이, 캐롭 추출물(CS)과 꾸지뽕 추출물(CT)을 각각 섭취한 경우와 복합물(Mix)을 섭취한 경우 모두 섭취 전에 비해 정자수가 유의하게 증가하였다. 반면, 대조군(CTL)에서는 섭취 전에 비해 정자수가 유의하게 변화하지 않았다. 정자수 개선율은 캐롭 추출물(CS)과 꾸지뽕 추출물(CT) 단독을 섭취한 경우에는 각각 약 11%와 10%의 정자수가 증가된 반면, 복합물(Mix) 섭취군에서는 30% 이상의 정자수 개선율을 보여, 추출물의 각각을 섭취한 것에 비해 복합물 섭취 시 정자수 개선 효과가 뛰어난 것을 확인하였다. As can be seen in Figures 5 and 6, when the carob extract (CS) and kkujippong extract (CT) respectively ingested and the intake of the complex (Mix), the number of sperm significantly increased compared to before ingestion. In contrast, the control group (CTL) did not significantly change sperm count compared to before ingestion. The sperm count was increased by about 11% and 10% when carotene extract (CS) and kkujippong extract (CT) alone were used, whereas sperm count was improved by more than 30% in the mixed group (Mix). In comparison with the intake of each of the extracts, it was confirmed that the effect of improving sperm count when ingesting the complex.

또한, 도 7에서 나타나듯이, 정자 운동성 측정 결과, 대조군은 섭취 전과 후의 정자 운동성이 통계적으로 유의한 변화가 없는 반면, 캐롭 추출물(CS) 또는 꾸지뽕 추출물(CT) 단독 투여군에서는 투여 전에 비해 각각 약 19%와 15%의 정자 운동성 향상 효과가 나타났으며, 복합물(Mix) 투여군에서는 투여 전에 비해 40% 이상의 정자 운동성 향상을 보여 캐롭 추출물 및 꾸지뽕 추출물의 단독 효과에 비해 복합물에서 더 뛰어난 정자 운동성 향상 효과가 있었다. In addition, as shown in Figure 7, sperm motility measurement results, the control group before and after ingestion of sperm motility was not statistically significant, while in the carob extract (CS) or kkujippong extract (CT) administration group compared to before the administration each about 19 The sperm motility effect was increased by 15% and 15%, and the group (Mix) group showed more than 40% sperm motility improvement compared to before administration. there was.

시험예 5: 임상시험을 통한 남성 갱년기 예방 효과Test Example 5: Preventing Menopausal Men through Clinical Trials

남성에게 본 발명의 조성물을 섭취하게 하여 섭취 전후 남성 갱년기 평가 설문지를 통해 남성 갱년기 증상 예방 및 치료 효과를 확인하였다.The male was ingested with the composition of the present invention to determine the effect of preventing and treating male menopausal symptoms through a male menopausal evaluation questionnaire before and after ingestion.

연구 대상 및 기간Study subject and period

본 검사에 동의한 만 40세 이상 중년 남성 40명을 위약을 섭취한 대조군(placebo)과 본 발명의 캐롭 추출물과 꾸지뽕 추출물의 복합물(캐롭:꾸지뽕=7:3)을 섭취한 실험군으로 각 20명씩 임의로 분류하여 4주 동안 위약 또는 실험약을 일일 400 mg씩 섭취하도록 하였다. 섭취 전과 후에 표 1의 검사지에 답하도록 하여 본 조성물의 섭취로 인한 남성 갱년기 평가를 실시하였다.Forty adults aged 40 years or older who agreed to this test were placed in a control group (placebo) who received placebo and an experimental group who consumed the complex of Carob and Cudrania extracts of the present invention (Carob: Cudrania = 7: 3). They were randomized to receive 400 mg of placebo or experimental drug daily for four weeks. Male menopausal evaluation due to ingestion of the composition was performed by answering the test sheet in Table 1 before and after ingestion.

한글판 AMS (Aging AMS (Aging) Male’sMale ’s Symptoms) Symptoms)

AMS는 Heinemann 등이 노화가 남성의 삶의 질에 미치는 영향을 객관적으로 평가하기 위해 고안되어 평가방법으로 그 타당성과 신뢰도가 입증되어 전 세계적으로 남성갱년기 증상 검사도구로 많이 사용하고 있는 검사도구이다(Heinemann LAJ, Zimmermann T, Vermeulen A, Thiel C. A New 'Aging Male's Symptom'(AMS) Scale. The Aging Male 1992, 2:105-114.). 한글판은 김세현 등의 번역판이 타당도가 신뢰도가 입증되었다(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.). 한글판 AMS 설문지는 정신적 증상 5문항, 신체적 증상 7문항, 성적 증상 5문항 등 총 17문항으로 구성되어 있다(표 1). 모든 항목은 증상없음(1점), 가벼움(2점), 보통(3점), 심함(4점), 매우 심함(5점)으로 정량화하여 점수가 높을수록 증상이 높은 것으로 평가한다. AMS의 각 문항을 통해 신경과민, 정서불안, 우울증, 안면홍조, 수면장애, 활력저하, 업무능력감소, 성욕감퇴, 발기부전, 정력감소, 체력저하, 운동능력감소, 체모감소 등의 대표적인 남성갱년기 증상을 평가할 수 있다.AMS is a test tool that Heinemann et al. Designed to objectively evaluate the effects of aging on men's quality of life. Its validity and reliability have been proved as an evaluation method. Heinemann LAJ, Zimmermann T, Vermeulen A, Thiel C. A New 'Aging Male's Symptom' (AMS) Scale.The Aging Male 1992, 2: 105-114.). In the Korean version, the validity of Kim Se-hyun's translation has been proved to be reliable (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 the AMS questionnaire consists of 17 questions including 5 mental symptoms, 7 physical symptoms, and 5 sexual symptoms (Table 1). All items were quantified as no symptoms (1 point), light (2 points), moderate (3 points), severe (4 points), and very severe (5 points), and the higher the score, the higher the symptom. Representative male menopausal periods such as nervousness, emotional anxiety, depression, hot flashes, sleep disorders, vitality, decreased work ability, decreased libido, impotence, decreased energy, decreased physical strength, reduced exercise ability, and reduced body hair. Symptoms can be assessed.

몸의 증상Symptoms of the body 증상의 정도Severity of symptoms 없음none 가벼움lightness 보통usually 심함Severe 매우심함Very severe 1. 몸상태가 안 좋아진 느낌이다.(전반적인 건강에 대한 주관적인 느낌)1. Feeling poorly ill (subjective feeling of overall health) 2. 관절과 근육이 아프다.(허리, 관절, 등이 아프다거나 팔다리가 쑤신다)2. Pain in joints and muscles (sick back, joints, back pain or limb pain) 3. 땀이 지나치게 많이 난다.(감자기 식은땀이 나거나 긴장하지 않아도 얼굴이 화끈거린다)3. I sweat too much (potatoes are cold even if I don't feel cold) 4. 수면장애가 있다.(잠들기 어렵거나, 자다가 자주 깨거나, 아침에 일찍 깨서 피곤하거나, 깊은 잠을 못자거나, 잠을 못 이룬다)4. Have trouble sleeping (difficult to sleep, wake up often, sleep early, get tired, can't sleep deep, or can't sleep) 5. 수면시간이 늘지만 그래도 피곤하다.5. I have more sleep but still tired. 6. 잘 흥분한다.(공격적이거나, 사소한 일에 쉽게 화를 내거나, 변덕스럽다)6. Excited well (being angry, easily angry, or capricious) 7. 신경이 과민하다.(긴장하거나, 들뜨거나 조바심을 낸다)7. My nerves are sensitive (tense, upset or nervous) 8. 항상 불안하다.(전전긍긍한다)8. I'm always anxious. 9. 신체적으로 기진맥진하고 활력이 떨어진다.(업무수행능력이 떨어지거나, 활발하지 못하거나, 여가활동에 무관심해지거나, 목표량을 달성하지 못하거나, 기력이 없어서 어떤 일을 억지로 해야만 하는 느낌, 즉 예를 들면 아플 때 일 때문에 직장에 억지로 나가는 느낌이다)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. 근력이 저하되고 있다.(허약해진 느낌이다)10. My strength is falling (I feel weak) 11. 기분이 우울하다.(기분이 가라앉거나, 슬프거나, 눈물이 맺히거나, 의욕이 없거나, 감정의 변화가 심하거나, 아무 쓸모가 없다고 느껴진다)11. I feel depressed (feels calm, sad, tearful, motivated, feelings change, or useless) 12. 전성기가 지나버린 느낌이다.12. I feel like my prime is gone. 13. 정서적으로 탈진한 느낌이다.(신체적, 정신적 고갈된 상태로 부정적 태도와 무력감 및 절망감 등을 겪고 있는 느낌이다)13. Feeling exhausted emotionally (feeling negative, helpless and hopeless with physical and mental exhaustion) 14. 수염이 자라는 속도가 떨어진다.14. The beard grows slowly. 15. 정력이 떨어지고 성생활 횟수도 줄고 있다.15. Less energetic and less sexual life. 16. 아침에 발기되는 횟수가 줄고 있다16. The number of erections in the morning is decreasing 17. 성욕이 줄고 성적충동도 줄고 있다.(성생활의 즐거움이 없어지거나, 성생활을 하고 싶은 욕망이 없어진다)17. Less libido and less sexual impulse (no pleasure in sex life, no desire to live sex life)

대조군 및 실험군의 AMS 결과는 각각의 항목을 남성갱년기의 증상별로 분류하여 대조군과 실험군에서 증상에 따른 점수변화량을 표 2에 나타내었다. 결과값은 평균과 표준편차로 기입하였으며, 유의성 검증을 위해 통계처리는 스튜던트's t-테스트를 이용하였고, p<0.05 시에 유의한 것으로 간주하여 표시하였다(*p<0.05). The AMS results of the control group and the experimental group are categorized by symptoms of male menopausal symptoms, and the score change according to the symptoms in the control group and the experimental group is shown in Table 2. Results were listed as mean and standard deviation. For the significance test, statistical analysis was performed using Student's t-test, which was considered significant at p <0.05 (* p <0.05).

구분division 증상 (AMS 문항번호)Symptom (AMS Item Number) 점수변화량 (평균±표준편차)Score change (mean ± standard deviation) 대조군Control 실험군Experimental group 정신적 증상 (5문항)Mental Symptoms (5 questions) 신경과민 (6, 7)Nervousness (6, 7) 0.06±0.120.06 ± 0.12 -1.99±1.08*-1.99 ± 1.08 * 정서불안 (8)Emotional Anxiety (8) 0.10±1.410.10 ± 1.41 -0.70±1.05*-0.70 ± 1.05 * 우울증 (11, 13)Depression (11, 13) -0.30±1.32-0.30 ± 1.32 -2.47±1.95*-2.47 ± 1.95 * 신체적 증상 (7문항)Physical symptoms (7 questions) 안면홍조 (3)Hot flashes (3) 0.31±1.270.31 ± 1.27 -0.73±0.95*-0.73 ± 0.95 * 수면장애 (4, 5)Sleep disorders (4, 5) 0.29±1.050.29 ± 1.05 -1.99±0.92*-1.99 ± 0.92 * 활력저하, 업무능력감소 (9)Decreased vitality, reduced work capacity (9) 0.34±0.940.34 ± 0.94 -0.81±0.48*-0.81 ± 0.48 * 체력저하, 운동능력감소 (1, 2, 10)Decrease in fitness, loss of motor skills (1, 2, 10) 0.31±1.600.31 ± 1.60 -2.92±1.28*-2.92 ± 1.28 * 성적 증상 (5문항)Sexual symptoms (5 questions) 성욕감퇴, 발기부전, 정력감소 (12, 15, 16, 17)Decreased libido, erectile dysfunction, decreased energy (12, 15, 16, 17) 0.27±2.080.27 ± 2.08 -4.51±2.38*-4.51 ± 2.38 * 체모감소 (14)Hair Loss (14) 0.60±1.580.60 ± 1.58 -1.04±1.05*-1.04 ± 1.05 * 총 점Total points 1.98±4.251.98 ± 4.25 -16.82±6.02*-16.82 ± 6.02 *

시험 결과, 대조군에서는 위약 섭취 전후 AMS 검사지로 평가한 남성갱년기 증상 점수에 큰 변화가 없는 반면, 캐롭 추출물과 꾸지뽕 추출물의 복합물을 섭취한 실험군은 섭취 후 AMS 검사지로 평가한 남성갱년기 증상 점수가 통계적으로 유의하게 감소하여 남성갱년기에서 나타날 수 있는 정신적 증상(신경과민, 정서불안, 우울증), 신체적 증상(안면홍조, 수면장애, 활력저하, 업무능력감소, 체력저하, 운동능력감소), 성적 증상(성욕감퇴, 발기부전, 정력감소, 체모감소) 등의 개선에 효과가 있음을 알 수 있다. As a result, the control group showed no significant change in the male menopausal symptom score evaluated by the AMS test paper before and after the placebo intake. Significantly reduced mental symptoms (nervous nervousness, emotional anxiety, depression), physical symptoms (hot flashes, sleep disorders, vigor, decreased work ability, physical weakness, reduced motor skills), sexual symptoms (sexual desire) Deterioration, erectile dysfunction, energy loss, hair loss) and the like can be seen to be effective.

이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that such a specific technology is only a preferred embodiment, and the scope of the present invention is not limited thereto. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that such a specific technology is only a preferred embodiment, and the scope of the present invention is not limited thereto. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

본 발명에 따른 남성 갱년기 증상의 예방 또는 개선용 조성물은 남성 갱년기 증상의 예방 또는 개선용의 식품, 의약품 등 넓은 분야로 활용될 수 있다.The composition for the prevention or improvement of male menopausal symptoms according to the present invention can be used in a wide range of fields, such as food, medicine for preventing or improving male menopausal symptoms.

Claims (10)

캐롭(Ceratonia siliqua) 및 꾸지뽕(Cudrania tricuspidata)의 복합추출물을 유효성분으로 포함하는 남성 갱년기 증상의 예방 또는 개선용 식품 조성물. Carob ( Ceratonia siliqua and Cudrania tricuspidata ) Food composition for the prevention or improvement of male menopausal symptoms comprising a complex extract of. 제 1 항에 있어서,The method of claim 1, 상기 복합추출물은 물, 메탄올, 에탄올 또는 이의 조합을 추출용매로 하여 추출한 것을 특징으로 하는 조성물. The composite extract is a composition, characterized in that extracted with water, methanol, ethanol or a combination thereof as an extraction solvent. 제 1 항에 있어서,The method of claim 1, 상기 남성 갱년기 증상은 관절 또는 근육의 통증, 골다공증, 전립선 비대증, 다한증, 수면장애, 흥분, 신경과민, 정서불안, 무기력증, 피로, 근력 저하, 체력저하, 활력저하, 안면홍조, 수면장애, 우울증, 정력 저하, 성욕 저하, 발기력 저하, 정력감소, 운동능력저하, 체모감소, 노화 또는 비뇨생식기 기능 저하인 것을 특징으로 하는 조성물. The male menopausal symptoms include joint or muscle pain, osteoporosis, prostate hyperplasia, hyperhidrosis, sleep disorders, excitement, nerve hypersensitivity, emotional anxiety, lethargy, fatigue, muscle weakness, weakness, vitality, hot flashes, sleep disorders, depression, A composition characterized in that the lowered energy, lowered libido, lowered erection, reduced energy, reduced athletic performance, reduced body hair, aging or lower urogenital function. 제 1 항에 있어서,The method of claim 1, 상기 복합추출물은 테스토스테론의 생성을 증가시키는 것을 특징으로 하는 조성물. The composite extract composition, characterized in that to increase the production of testosterone. 제 1 항에 있어서,The method of claim 1, 상기 복합추출물은 운동 능력을 증가시키는 것을 특징으로 하는 조성물. The composite extract composition, characterized in that to increase the exercise ability. 제 1 항에 있어서,The method of claim 1, 상기 복합추출물은 5-α 리덕타아제(reductase)의 활성을 저해하는 것을 특징으로 하는 조성물. The complex extract is a composition, characterized in that to inhibit the activity of 5-α reductase (reductase). 제 1 항에 있어서,The method of claim 1, 상기 복합추출물은 캐롭 추출물 및 꾸지뽕 추출물을 9:1 내지 6:4 중량비로 혼합한 것을 특징으로 하는 조성물. The complex extract is a composition characterized in that the carob extract and kkujippong extract in a 9: 1 to 6: 4 weight ratio. 캐롭(Ceratonia siliqua) 및 꾸지뽕(Cudrania tricuspidata)의 복합추출물을 유효성분으로 포함하는 남성 생식기능 개선용 식품 조성물. Carob ( Ceratonia siliqua and Cudrania tricuspidata ) Food composition for improving male reproductive function comprising a complex extract of. 제 8 항에 있어서,The method of claim 8, 상기 복합추출물은 정액 내 정자 농도를 증가시키는 것을 특징으로 하는 조성물. The composite extract composition, characterized in that to increase the sperm concentration in semen. 제 8 항에 있어서,The method of claim 8, 상기 복합추출물은 정자 운동성을 증가시키는 것을 특징으로 하는 조성물. The composite extract composition, characterized in that to increase sperm motility.
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