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WO2013042984A2 - Composition pour prévenir et atténuer le dysfonctionnement érectile comportant un extrait de plantes composite - Google Patents

Composition pour prévenir et atténuer le dysfonctionnement érectile comportant un extrait de plantes composite Download PDF

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Publication number
WO2013042984A2
WO2013042984A2 PCT/KR2012/007589 KR2012007589W WO2013042984A2 WO 2013042984 A2 WO2013042984 A2 WO 2013042984A2 KR 2012007589 W KR2012007589 W KR 2012007589W WO 2013042984 A2 WO2013042984 A2 WO 2013042984A2
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WO
WIPO (PCT)
Prior art keywords
extract
namgasae
cornus
composition
erectile dysfunction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/KR2012/007589
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English (en)
Korean (ko)
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WO2013042984A3 (fr
Inventor
심재석
김성기
김상현
이진희
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CJ CheilJedang Corp
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CJ CheilJedang Corp
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Publication of WO2013042984A2 publication Critical patent/WO2013042984A2/fr
Publication of WO2013042984A3 publication Critical patent/WO2013042984A3/fr
Anticipated expiration legal-status Critical
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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
    • 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)
    • A61K36/40—Cornaceae (Dogwood family)
    • 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)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence

Definitions

  • the present invention relates to a composition for preventing and improving erectile dysfunction comprising a composite herbal extract, and more particularly, to a composition for preventing and improving erectile dysfunction comprising a namgasae and cornus extract.
  • Erectile dysfunction is one of the major diseases suffered by men around the world, and it is estimated that approximately 10 to 20% of the male population suffers from clinical symptoms.
  • Penile erection is a complex physiological reaction in which the blood vessels, the endocrine system and the nervous system work together, which is followed by the relaxation of cavernous smooth muscle.
  • a series of penile erections are regulated by the smooth muscle tension of the cavernous body, which releases non-adrenergic, non-cholinergic transmitters (NANCs) and relaxants released from endothelial cells of cavernous pores.
  • NANCs non-adrenergic, non-cholinergic transmitters
  • EDRF Derived relaxing factor plays an important role in the relaxation of cavernous smooth muscle, the center of penile erection, the most important of which is identified as nitric oxide (NO).
  • NO is formed in the presence of calcium, calcium, NADPH (nicotinamide adenine dinucleotide phosphate), and calmoduline (arginine) as a precursor.
  • NO-producing substances bind to receptors on endothelial cell membranes to increase the concentration of free calcium in endothelial cells, which promotes NO synthesis and release.
  • the free NO enters the corpus cavernosum smooth muscle cells and activates guanylate cyclase (GC) of smooth muscle to increase the production of cyclic guanosine monophosphate (cGMP). This increase in cGMP leads to smooth muscle relaxation, leading to penile erection.
  • GC guanylate cyclase
  • cGMP cyclic guanosine monophosphate
  • the present invention has been made in order to solve the above problems, to prepare a complex extract from the namgasae and cornus milk as a raw material for cell experiments ( in vitro ), ex vivo ( in vivo ) and in vivo (animal) animal experiments As a result, it was confirmed that namgasae and cornus extracts showed excellent activity in improving erectile dysfunction, the composition containing this complex extract was found to be excellent in the prevention and improvement of erectile dysfunction was completed the present invention.
  • compositions for preventing and improving erectile dysfunction including namgasae and cornus extract.
  • Still another object of the present invention is to provide a health functional food comprising the composition.
  • the present invention is an erectile dysfunction comprising a namgasae extract containing 5-10% by weight of protodiosin as an active ingredient and a cornus extract containing 1-2% by weight of roganine as an active ingredient It provides a composition for prevention and improvement.
  • the present invention also provides a health functional food comprising the composition.
  • composition comprising the namgasae and cornus complex extract of the present invention showed an effective penile cavernous relaxation effect by increasing the production of NO and cGMP, which are penile stimulating factors, in the oral administration study of experimental animals, thereby increasing the maximum cavernosal pressure. .
  • NO and cGMP which are penile stimulating factors
  • safety was confirmed through a single-dose toxicity and genotoxicity test studies for the extracts of Namgasae and Cornus. Therefore, the composition including Namgasae and Cornus complex extract according to the present invention can be usefully used for the prevention and improvement of erectile dysfunction.
  • Figures 1a, 1b and 1c is a graph showing the NO (nitric oxide) generation ability through the cell culture ( In vitro ) experiments of Namgasae and Cornus extract and Namgasus Cornus complex extract of the present invention.
  • Figure 1a shows the amount of NO produced by the Namgasae extract treatment
  • Figure 1b shows the amount of NO produced by the cornus extract treatment
  • Figure 1c shows the amount of NO produced by the treatment of Namgasae cornus extract.
  • Figure 2a and 2b is a graph showing the relaxation effect of the corpus cavernosum tissue through the ex vivo experiment of each of the namgasae and cornus extract of the present invention.
  • Figure 2a shows the corpus cavernosum tissue relaxation activity by Namgasae extract treatment
  • Figure 2b shows the corpus cavernosum tissue relaxation activity by the cornus extract treatment.
  • Figure 3 is a graph showing the relaxation effect of the corpus cavernosum tissue through the experimental animal Ex vivo ( ex vivo ) experiments of the complex extract according to the ratio of Namgasae and Cornus milk of the present invention.
  • Figure 4 is a graph showing the effect of penis erection through oral administration ( In vivo ) experiments of the namgasae and cornus extract of the present invention.
  • Figures 5a and 5b is a graph showing the production of NO and cGMP (cyclic guanosine monophosphate) in the corpus cavernosum tissue through oral administration ( In vivo ) experiments of Namgasae and cornus lactose extract of the present invention.
  • NO and cGMP cyclic guanosine monophosphate
  • the present invention provides a composition for preventing and improving erectile dysfunction comprising a namgasae and cornus extract.
  • the main components used in the present invention are as follows.
  • Tribulus terrestris is an annual herb that grows on the sandy beaches of Jeju Island, Geoje Island and Myeongcheon County in North Hamgyong province.
  • the fruit of Namgasae contains saponins, essential oils, alkaloids, gums, potassium salts, etc. It is known to soften blood vessels, dissolve cholesterol, improve blood circulation, lower blood pressure, eliminate inflammation, and act as a diuretic.
  • Namgasae is known to be the basis of the activity of an indicator component called protodioscin, which is converted to dehydroepiandrosteorone (DHEA), which is expected to be effective in improving sexual function in vivo, and ultimately DHEA Increase the concentration of DHEA
  • the main ingredients are Morroniside, Loganin, Cornin (Verbenalin), Saponin, Tannin, Ursolic acid, Gallic acid, It contains malic acid, tartaric acid and vitamin A.
  • namgasae and cornus extract there is no limitation in the preparation method of namgasae and cornus extract, but preferably at least one solvent selected from the group consisting of water, C 1 to C 6 organic solvents and subcritical or supercritical fluids from plants or plant parts. It can be prepared by extraction. In addition, if necessary, it may be prepared by further including filtration and concentration steps according to methods known to those skilled in the art.
  • Hot water extraction and ethanol (ethanol) extraction using the same method as described above, through the process of filtration and concentration can be prepared namgasae and cornus oil extract.
  • Namgasae extract according to the present invention is characterized in that it contains 5-10% by weight protodioscin (protodioscin) as an active ingredient. If the protodiosin content is less than 5% by weight, the extraction yield may be low and the functionality may be degraded. If the protodiosin content is more than 10% by weight, an additional manufacturing process is required to increase the content, which may weaken the economic efficiency. have.
  • protodioscin protodioscin
  • Cornus extract according to the present invention is characterized in that it contains 1-2% by weight loganin (loganin) as an active ingredient. If the loganine content is less than 1% by weight, the extraction yield may be low and the functionality may be degraded. If the loganine content is more than 2% by weight, an additional manufacturing process is required to increase the content, which may weaken the economics. have.
  • loganin loganin
  • the complex ratio of namgasae and cornus extract prepared as described above may be mixed in a ratio of 90: 10-60: 40% by weight of namgasae extract and cornus extract, respectively, preferably by mixing in a ratio of 80: 20% by weight Manufacture.
  • Namgasae and cornus of 90: 10 to 60: 40% ratio was outside a result of using a specific compound extract measured ED improved effectiveness through animal experiments in vivo (ex vivo) experiments confirm the corpus cavernosum tissue relaxation performance, especially with namgasae Cornus weight
  • the composite extract prepared by mixing at 80: 20% by weight showed a superior effect (synergy effect) when treated with Namgasae and Cornus alone (see FIG. 3).
  • composition comprising the namgasae and cornus extract as an active ingredient of the present invention according to the conventional methods known in the art functional food (functional food), nutritional supplement (nutritional supplement), health food (health food) and It may be prepared in various forms such as food additives.
  • Example 1 namgasae extract preparation
  • the dried namgasae was pulverized with a mixer, and 100 g of the pulverized sample was first extracted with a reflux condenser (95 ° C) using 1000 ml of distilled water as an extraction solvent.
  • the extracted sample was separated from the extract and the residue using a centrifuge (3,200 rpm / 4 ° C / 30 minutes), and the extracted residue was secondly extracted at room temperature using 500 ml of 90% by volume ethanol as the extraction solvent.
  • the extracted primary and secondary samples were mixed and filtered through Whatman No. 2 filter paper, the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, and then lyophilized to remove the water component. This was analyzed by high performance liquid chromatography to obtain a extract of Namgasae containing 5-10% by weight of protodiosin.
  • the dry cornus oil was pulverized with a mixer, and then 100 g of the pulverized sample was first extracted with a reflux condenser (95 ° C) using 1000 ml of distilled water as an extraction solvent.
  • the extracted sample was separated from the extract and the residue using a centrifuge (3,200 rpm / 4 ° C / 30 minutes), and the residue was extracted by secondary extraction at room temperature using 500 ml of 70% by volume ethanol as the extraction solvent.
  • the extracted primary and secondary samples were mixed, filtered with Whatman No. 2 filter paper, the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, and then lyophilized to remove the water component. This was subjected to a high performance liquid chromatography analysis to obtain a cornus extract containing 1-2% by weight of a lignin component.
  • the safety test was performed by Biotoxtec, a KGLP organization, for the single-dose toxicity test and genotoxicity test items in white rats using the namgasae and cornus lactose extract prepared according to Example 3 according to the Food and Drug Administration's published toxicity test criteria.
  • the male and female coriander extract extract according to Example 3 was orally administered to rat male and female at a dose of 5,000 mg / kg, and a single dose toxicity test and genotoxicity test were performed at Biotoxtech Co., Ltd. No dead animals were observed, and no specific symptoms were observed with regard to the administration of Namgasae and Cornus extracts of Example 3. In addition, toxicological abnormalities due to the administration of the extract of Namgasae and Cornus extract of Example 3 were not observed in the autopsy findings after the test, and the LD 50 value was confirmed to be 5,000 mg / kg or more.
  • the cells used to measure NO production capacity were washed three times with passaged human vascular endothelial cells (HUVEC) with phosphate buffered saline solution and the cells were transferred to fetal bovine cells at a concentration of 5 ⁇ 10 5 cells / well.
  • the cells were suspended in DMEM medium containing 10% serum (FBS), aliquoted into 24 well plates, and incubated at 37 ° C for 24 hours.
  • the extracts prepared in Examples 1 and 2 were added thereto at concentrations of 10, 50, and 100 ⁇ g / ml, and then cultured under conditions of 48 hours, 37 ° C., and 5% CO 2 to obtain supernatants.
  • the measurement of NO in the supernatant was measured for absorbance with an ELISA microplate reader according to the Grees method.
  • the supernatant was mixed with grease reagent (1% sulfanilamide, 0.1% naphythylethylendiamine dihydrochloride, 2.5% H 3 PO 4 ), reacted at room temperature for 30 minutes, and absorbance was measured at 548 nm using an ELISA microplate reader.
  • the concentration of NO was calculated from the standard curve prepared based on the concentration of sodium nitrite, and the basic control was a cell culture medium without the extract.
  • Figure 1a shows the NO production amount by Namgasae extract treatment
  • 1b represents the NO production amount by the cornus extract treatment
  • 1c shows the NO production amount by the Namgasae cornus extract extract treatment.
  • the corpus cavernotomy sections of rabbits were cut into pens from 2.5-3.0 kg of male New Zealand rabbits and cut into connective and adipose tissue in KHB (Krebs-Henseleit Buffer) solution to produce a loop of 4-5 mm in length. It was.
  • the rabbit corpus cavernosum sections were transferred to a double walled test vessel containing 5 ml of KHB solution, one end of which was connected to the muscle stabilizer and the other end of force displacement transducers (TSD 125C ® , Biopac Inc, USA) and connect the signal to the PC using the 4-channel data acquisition and analysis system for window (MP36R 4-Channel Systems, Biopac Inc, USA). personal computer).
  • the KHB solution in the test vessel was maintained at 37 ° C, and a mixture gas of 95% O 2 and 5% CO 2 was continuously supplied to pH 7.4, and phenylephrine (PE, 10 -6 M) in the test vessel. After pretreatment to shrink the tissue, the changes in tension curves were observed by administering the namgasae and cornus extract prepared in Examples 1 and 2 for each concentration.
  • the relaxation rate (% relaxation) in this experiment was 100% by the treatment of sodium nitroprusside (10 -3 M) to the sections contracted with PE 10 -5 M.
  • the results are shown in FIGS. 2A and 2B, and as shown in FIGS. 2A and 2B, the cavernous corpus cavernosum tissue was effectively relaxed and the corpus cavernosum tissue relaxation was maintained when the extracts were treated at different concentrations.
  • Figures 2a and 2b 2a shows the corpus cavernosum tissue relaxation activity by Namgasae extract treatment
  • 2b shows the corpus cavernosum tissue relaxation activity by the cornus extract treatment, respectively.
  • a total of 40 white papers were prepared according to the method of Example 3
  • Namgasae: Cornus 80: 20% by weight according to the oral administration dose of Namgasae and Cornus extract, control, 10 mg / kg, 50 mg / kg and 100
  • penis cavernous pressure measurement was performed after oral administration of Namgasae and Cornus extracts to each group for 1 month.
  • Peak ICP, peak ICP / mean arterial pressure (ICP / MAP), and maximum cavernosal pressure were measured.
  • the time to peak ICP was investigated.
  • the cavernous nerve stimulation was repeated at least 5 times, and the time interval between each stimulation was maintained at least 10 minutes. In order to see the response by nerve stimulation, the ratio of cervical arterial pressure and intracavernosal pressure was measured.

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  • Health & Medical Sciences (AREA)
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Abstract

La présente invention concerne une composition qui permet d'atténuer le dysfonctionnement érectile et qui contient un principe actif sous la forme d'un extrait composite de Tribulus terrestris et de Cornus officinalis, qui sont des préparations végétales et, plus particulièrement, concerne une composition, pour prévenir et atténuer le dysfonctionnement érectile, qui comporte : un extrait de Tribulus terrestris contenant un principe actif sous la forme de protodioscine en une quantité se situant entre 5 et 10 pour cent en poids ; un extrait de Cornus officinalis contenant un principe actif sous la forme de loganine en une quantité se situant entre 1 et 2 pour cent en poids.
PCT/KR2012/007589 2011-09-23 2012-09-21 Composition pour prévenir et atténuer le dysfonctionnement érectile comportant un extrait de plantes composite Ceased WO2013042984A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020110095993A KR20130032419A (ko) 2011-09-23 2011-09-23 복합생약추출물을 포함하는 발기부전 예방 및 개선용 조성물
KR10-2011-0095993 2011-09-23

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WO2013042984A2 true WO2013042984A2 (fr) 2013-03-28
WO2013042984A3 WO2013042984A3 (fr) 2013-06-13

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Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20020994A1 (it) * 2002-05-10 2003-11-10 Indena Spa Formulazioni utili nel trattamento dell'impotenza maschile e femminile
KR100364684B1 (en) * 2002-09-04 2002-12-16 Korea Medical Science Inst Composition containing plant extract for promoting and maintaining erection
KR100758364B1 (ko) * 2006-12-29 2007-09-14 주식회사 케이엠에스아이 발기부전 예방 또는 치료용 약학 조성물

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WO2013042984A3 (fr) 2013-06-13

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