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WO2016148545A1 - Composition pour prévenir ou améliorer des symptômes d'andropause - Google Patents

Composition pour prévenir ou améliorer des symptômes d'andropause Download PDF

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Publication number
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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WIPO (PCT)
Prior art keywords
extract
composition
carob
present
kkujippong
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Ceased
Application number
PCT/KR2016/002789
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English (en)
Korean (ko)
Inventor
노유헌
이지원
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Famenity Co Ltd
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Famenity Co Ltd
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Priority to JP2017535679A priority Critical patent/JP6309175B2/ja
Publication of WO2016148545A1 publication Critical patent/WO2016148545A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2300/00—Processes
    • A23V2300/14—Extraction

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

La présente invention concerne une composition pour prévenir ou améliorer des symptômes d'andropause, la composition comprenant un extrait complexe de caroube et de Cudrania tricuspidata comme principe actif. La composition de la présente invention est efficace pour améliorer divers symptômes d'andropause, car l'invention atténue la réduction de testostérone, qui est une cause de symptômes d'andropause, et améliore la capacité d'exercice et inhibe l'activité de 5α-réductase et présente ainsi un effet de prévention et de traitement d'hypertrophie de la prostate. La présente invention concerne une composition pour améliorer la fonction reproductrice masculine, la composition comprenant un extrait complexe de caroube et de Cudrania tricuspidata comme principe actif. La composition de la présente invention présente un effet remarquable d'amélioration de fonction reproductrice masculine par augmentation de la concentration de spermatozoïdes dans le fluide séminal, augmentation de la motilité des spermatozoïdes, et augmentation de la sécrétion de testostérone. L'extrait complexe de caroube et de Cudrania tricuspidata de la présente invention présente un bien meilleur effet d'amélioration de symptômes d'andropause et un meilleur effet d'amélioration de fonction reproductrice masculine que des extractions uniques de caroube et de Cudrania tricuspidata.
PCT/KR2016/002789 2015-03-18 2016-03-18 Composition pour prévenir ou améliorer des symptômes d'andropause Ceased WO2016148545A1 (fr)

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JP2017535679A JP6309175B2 (ja) 2015-03-18 2016-03-18 男性更年期症状の予防または改善用組成物

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KR10-2015-0037589 2015-03-18
KR1020150037589A KR101621072B1 (ko) 2015-03-18 2015-03-18 남성 갱년기 증상의 예방 또는 개선용 조성물

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CN108096313A (zh) * 2018-02-06 2018-06-01 张南 一种治疗男性疾病的药物组合物及其制备方法和用途

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KR102335267B1 (ko) 2017-03-16 2021-12-06 주식회사 자연과학기술 무지개송어 정소로부터 테스토스테론의 추출방법
WO2020246863A1 (fr) * 2019-06-07 2020-12-10 연세대학교 산학협력단 Composition comprenant du chlorhydrate de cudrania comme composant efficace pour soulager, traiter ou prévenir les maladies musculaires, ou améliorer les fonctions musculaires
KR102843115B1 (ko) 2024-04-18 2025-08-07 주식회사 한미양행 갈색거저리 유충의 효소처리물을 함유하는 남성 갱년기 증상의 예방 또는 치료용 조성물

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KR20050119134A (ko) * 2003-03-21 2005-12-20 넥스메드 홀딩스 인코포레이티드 발기 부전 치료용 프로스타글란딘 조성물
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