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WO2016144125A2 - Nouvelle utilisation d'extrait de solanum nigrum l. - Google Patents

Nouvelle utilisation d'extrait de solanum nigrum l. Download PDF

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Publication number
WO2016144125A2
WO2016144125A2 PCT/KR2016/002427 KR2016002427W WO2016144125A2 WO 2016144125 A2 WO2016144125 A2 WO 2016144125A2 KR 2016002427 W KR2016002427 W KR 2016002427W WO 2016144125 A2 WO2016144125 A2 WO 2016144125A2
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Prior art keywords
extract
yonggyu
endometriosis
pharmaceutical composition
fraction
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Korean (ko)
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WO2016144125A3 (fr
Inventor
최정혜
조윤진
류효정
강희철
김진표
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Daewoong Pharmaceutical Co Ltd
Kyung Hee University
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Daewoong Pharmaceutical Co Ltd
Kyung Hee University
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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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • 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
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • 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

Definitions

  • the present invention relates to a yonggyu extract, and more particularly to a novel use of the yonggyu extract.
  • Endometriosis is a very common gynecological disorder that occurs in 3-10% of women of childbearing age and 25-35% of infertile women, and the endometrial tissue abnormally proliferates in places other than the uterus (ovary, abdominal cavity, intestine, bladder). Disease.
  • Endometriosis is a symptom of dysmenorrhoea, dyspareunia, and various pains (eg, lung involvement: pneumothorax, hemothorax / ureteral involvement: ureter obstruction, hematuria), 30-50% of patients. Has been identified as the cause of infertility.
  • Endometriosis is not fatal, but it is a disease that causes discomfort in daily life due to extreme pain and even infertility in severe cases, and is a disease that must be seriously recognized and must be overcome in women's quality of life and pregnancy problems. So far, there is no prevention and treatment.
  • Yonggyu extract is known to have an AIDS therapeutic effect (Korean Patent Publication No. 1020060034178).
  • Patent Document 1 Republic of Korea Patent Publication No. 1020060034178, April 21, 2006, Summary
  • the problem to be solved by the present invention is to provide a novel use of the extract.
  • Yonggyu extract has an effect on the treatment, improvement and / or prevention of endometriosis or its complications and completed the present invention.
  • the present invention provides a medicament and / or food use for treating, ameliorating and / or preventing endometriosis or complications thereof.
  • the present invention also provides a pharmaceutical composition for treating or preventing endometriosis or its complications, comprising the extract of Yonggyu as an active ingredient.
  • the yonggyu (Solani Nigri Herba) is listed in the Korean Pharmacopoeia (Herbal Medicine) standard collection, may be the ground portion of the solarum nigrum (Solanum nigrum Linne (branch family Solanaceae)).
  • the ground portion includes stems and leaves, and may include flowers.
  • the pharmaceutical composition may further include a pharmaceutically acceptable additive, and may be composed of the yonggyu extract and the additive.
  • the endometriosis or complications thereof may be due to one or more overexpression selected from MMP-2, MMP-9, COX-2, TNF-alpha ( ⁇ ), or MCP-1.
  • the complication may be one or more selected from the group consisting of pelvic inflammatory disease, pelvic adhesion, ovarian cyst, uterine myoma, ectopic pregnancy and infertility.
  • the yonggyu extract is a solvent extract extracted from the yonggyu as a solvent, the solvent may be at least one selected from water, alcohol, or a mixture thereof.
  • the alcohol may be a lower alcohol having 1 to 5 carbon atoms.
  • the solvent may be 70% by volume ethanol.
  • the Yonggyu extract may be a butanol fraction extract obtained by fractionating 70% by volume of ethanol extract with 70% by volume of ethanol, butanol.
  • the butanol fraction extract (A) preparing a 70 volume% ethanol extract extracted with 70 volume% ethanol; (B) adding water to the 70% by volume ethanol extract of step (A); (C) fractionating 70 vol% ethanol extract added with water of step (B) with n-hexane; (D) removing the n-hexane fraction of step (C) and fraction-extracting the remaining aqueous layer with dichloromethane; (E) removing the dichloromethane fraction of step (D) and fractionating the remaining aqueous layer with ethyl acetate; And (F) may be a fraction extract obtained by removing the ethyl acetate fraction of step (E) and fraction extraction of the remaining aqueous layer with butanol.
  • the treatment or prevention may be by inhibiting adhesion or migration of endometriosis cells.
  • the attachment or migration inhibition may be by inhibition of expression of one or more selected from MMP-2 or MMP-9.
  • the treatment or prevention may be due to one or more selected from inhibition of inflammation and pain related enzyme expression or inhibition of inflammatory cytokine expression.
  • the present invention also provides a food composition for improving or preventing endometriosis or its complications, comprising the extract of Yonggyu as an active ingredient.
  • the food composition is equally applicable unless the contradictions mentioned in the pharmaceutical composition of the present invention are contradictory.
  • the term 'improvement' is included in the 'treatment' and means that the condition or symptom is improved.
  • the food composition may be included in a variety of foods, including beverages, may be in the form of beverages, gum, tea, health functional foods, etc.
  • the health functional foods may be formulated in the form of tablets, capsules and the like.
  • the health functional food refers to a food manufactured using a raw material or ingredient having functional functionality useful for the human body according to Korean Health Functional Food Act No. 12669 (including processing. The following is referred to). By means of nutrient control or physiological effects on the structure and function of the human body to obtain useful effects for health purposes.
  • the food composition may include a conventional food additive, the food additive is a natural chemical such as ketones, glycine, sodium citrate, nicotinic acid, cinnamon acid, navy, licorice extract, crystalline cellulose, high pigment, guar gum And mixed preparations such as additives, sodium L-glutamate preparations, noodle addition alkalis, preservatives, and tar dyes.
  • the food additive is a natural chemical such as ketones, glycine, sodium citrate, nicotinic acid, cinnamon acid, navy, licorice extract, crystalline cellulose, high pigment, guar gum
  • mixed preparations such as additives, sodium L-glutamate preparations, noodle addition alkalis, preservatives, and tar dyes.
  • the present invention also provides a treatment, or prophylaxis, of endometriosis or a complication thereof, comprising administering the yonggyu extract to a mammal, including a human being in need thereof, and the treatment of endometriosis or a complication thereof. Or for the preparation of prophylactic formulations.
  • the administered yonggyu extract may be an effective amount of yonggyu extract.
  • the present invention also provides a extract of yonggyu for use in the treatment, improvement or prevention of endometriosis or complications thereof.
  • the Yonggyu extract or composition can be administered orally or parenterally to mammals, including humans, and can be administered by formulating an active ingredient in combination with a pharmaceutically acceptable additive.
  • additives commonly used may be carriers, fillers, extenders, binders, wetting agents, disintegrants, surfactants, diluents, excipients and the like other than the active ingredient.
  • Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid form preparations include at least one excipient such as starch, calcium carbonate, sucrose, lactose, and And / or by adding gelatin or the like.
  • Lubricants such as magnesium and talc are also used.
  • Liquid preparations for oral administration include suspensions, liquid solutions, emulsions and syrups, and various excipients such as wetting agents, sweeteners, fragrances and / or preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. May be included.
  • Formulations for parenteral administration include injectable solutions, suspensions, emulsions, lyophilizers, nasal washes and suppositories. Injectable solutions, suspensions and emulsions can be prepared by mixing water, non-aqueous solvents or suspending solvents with the active ingredient.
  • non-aqueous solvents and suspending solvents vegetable oils such as propylene glycol, polyethylene glycol and olive oil, and ethyl oleate Injectable esters such as and the like.
  • a suppository base witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol and / or gelatin may be used.
  • Parenteral administration may be by subcutaneous injection, intravenous injection or intramuscular injection.
  • Yonggyu extract contained in the composition of the present invention or used in the use and method is a dose of 0.0001 to 1000 mg / kg, preferably 0.0001 to 100 mg / kg, more preferably 0.001 to 10 mg / kg per day, based on an adult woman Can be used as Administration can be administered once a day or in divided doses.
  • the scope of the present invention is not limited by the dose and frequency of administration.
  • composition of the present invention may contain 0.1 to 99.9% by weight of the active ingredient relative to the total weight of the composition.
  • the Yonggyu extract can be formulated by adding a pharmaceutically or food-acceptable carrier, excipient or diluent, etc.
  • a pharmaceutically or food-acceptable carrier for formulation, see Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA, etc. Reference may be made.
  • the present invention can effectively treat, ameliorate and / or prevent endometriosis or complications thereof.
  • Figure 1 is a view showing the results of the MMP-2 expression inhibitory effect confirmation experiment of Yonggyu alcohol extract.
  • Figure 2 is a view showing the results of confirming the inhibitory effect of MMP-9 expression of Yonggyu alcohol extract.
  • Figure 3 is a diagram showing the results of confirming the inhibitory effect of COX-2 expression of Yonggyu alcohol extract.
  • Figure 4 is a view showing the results of experiments confirming the inhibitory effect of TNF alpha expression of Yonggyu alcohol extract.
  • Figure 5 is a view showing the results of the MCP-1 expression inhibitory effect confirmation experiment of Yonggyu alcohol extract.
  • Figure 6 is a view showing the results of experiments confirming the effect of endometriosis cell adhesion and implantation inhibition of the alcoholic alcohol extract.
  • Figure 7 is a diagram showing the results of experiments confirming the inhibitory effect of endometriosis cell migration of the alcoholic extract of Yonggyu.
  • FIG. 8 is a view showing the results of the effect confirmation experiment in the intraperitoneal administration model of Yonggyu alcohol extract.
  • Figure 9 is a diagram showing the results of effect verification experiments in the surgical induction model of Yonggyu alcohol extract.
  • FIG. 10 is a view showing the results of the MMP-2 expression inhibitory effect confirmation experiment of Yonggyu butanol fraction extract.
  • Figure 11 is a view showing the results of the MMP-9 expression inhibitory effect confirmed by the extract of Yonggyu butanol fraction.
  • Figure 12 is a view showing the results of the COX-2 expression inhibitory effect confirmed by the extract of Yonggyu butanol fraction.
  • Figure 13 is a view showing the results of the test TNF alpha expression inhibition effect of Yonggyu butanol fraction extract.
  • 15 is a diagram showing the results of experiments confirming the effect of endometriosis cell adhesion and implantation inhibition of the extract of Yonggyu butanol fraction.
  • Figure 16 is a diagram showing the results of confirming the inhibitory effect of MMP-2 expression of Yonggyu water extract.
  • Figure 17 is a diagram showing the results of confirming the inhibitory effect of COX-2 expression of Yonggyu water extract.
  • 19 is a view showing the results of confirming the inhibitory effect of MCP-1 expression of Yonggyu water extract.
  • the endometriosis model cells described in the following examples were prepared with a 12Z cell line, human immortalized endometriotic epithelial cells, developed using active endometriosis tissue of an endometriosis woman (Johann-Wolfgang-Goethe-). Dr. Universitaet (Germany) Offered by Starzinski-Powitz ⁇ . These cells have been shown to be similar to the molecular biology of known active endometotric tissues (Banu et al., 2008), and have been used as a new in vitro model for the molecular biology of endometriosis.
  • Cells were 37 degrees Celsius, 5% carbon dioxide-95 in RPMI 1640 and DMEM / F12 medium (10% fetal bovine serum, 100 U / ml penicillin G, 100 g / ml streptomycin added; Life Technology, Grand Island, New York) % was maintained in air conditions.
  • Dried yonggyu (Solanum nigrum, production area: Yeongcheon, Gyeongsangbuk-do) was purchased at Gyeongdong market, South Korea, and yonggyu outpost was pulverized to 400um particle size.
  • 100 liters of a 70% (v / v) ethanol aqueous solution was added to 10 kg of the prepared solu- tion, and the filtrate was immersed at room temperature for 24 hours, and the extract was repeated once in the same manner.
  • the extracted filtrate was concentrated under reduced pressure at 60 degrees Celsius, and the concentrated solution was lyophilized to obtain 1.5 kg of powdered 70% ethanol extract.
  • RNA was extracted from RNA, followed by reverse transcription polymerase chain reaction (RT-PCR).
  • RT-PCR reverse transcription polymerase chain reaction
  • the yonggyu extract untreated group as a control (control; CON), except that the treatment was the same as the yonggyu extract treated group.
  • 70% ethanol extract inhibited the mRNA expression of endogenous MMP-2 and MMP-9 which is a representative protein expressed in endometriosis and plays an important role in cell migration and infiltration. It confirmed (refer FIG. 1, FIG. 2).
  • Figure 1 is a view showing the results of the MMP-2 expression inhibitory effect confirmed experiment of Yonggyu alcohol extract
  • Figure 2 is a road showing the results of MMP-9 expression inhibitory effect confirmed by the alcoholic extract
  • 25 represents a 70 ⁇ g% ethanol extract 25ug / mL administration group
  • the y-axis of Figure 1 shows the relative MMP2 mRNA expression (Relative MMP2 mRNA expression)
  • the y-axis of Figure 2 relative MMP9 mRNA expression Relative MMP9 mRNA expression.
  • 70% by volume ethanol extract can be seen that effectively inhibits the expression of MMP-2 and MMP-9, even at a concentration of 25ug / mL.
  • Real-time PCR was performed to determine the effect of 70% by volume ethanol extract on the mRNA expression of COX-2, which is known to be associated with endometriosis pain. Specifically, erythrocytes were treated with 25% ug / mL, 50 ug / mL, or 100 ug / mL, respectively, for 24 hours in 12% (epithelial endometriotic cells) of endometriosis cells, followed by TRIzol (Invitrogen Canada, Burlington, ON, Canada) was used to extract the total RNA, and reverse transcription polymerase chain reaction (RT-PCR) was performed.
  • TRIzol Invitrogen Canada, Burlington, ON, Canada
  • Figure 3 is a road showing the results of the COX-2 expression inhibitory effect confirmed by Yonggyu alcohol extract, con on the x-axis of Figure 3 is a control, 25 is a 70wt% ethanol extract 25ug / mL administration group, y of Figure 3 The axis shows the relative COX2 mRNA expression. As shown in the figure, it can be seen that the 70% by volume ethanol extract effectively inhibits COX-2 expression even at a concentration of 25ug / mL.
  • Real-time PCR was performed to determine whether 70% by volume ethanol extract affects inflammatory cytokine mRNA expression, which is known to be overexpressed in endometriosis cells.
  • erythrocytes were treated with 25% ug / mL, 50 ug / mL, or 100 ug / mL, respectively, for 24 hours in 12% (epithelial endometriotic cells) of endometriosis cells, followed by TRIzol (Invitrogen Canada, Burlington, ON, Canada) was used to extract the total RNA, and reverse transcription polymerase chain reaction (RT-PCR) was performed.
  • TRIzol Invitrogen Canada, Burlington, ON, Canada
  • a Thermal Cycler Dice Real Time PCR System (Takara, Japan) denaturation for 5 seconds at 95 degrees Celsius, annealing for 10 seconds at 57 degrees Celsius, 72 degrees Celsius SYBR Green real-time PCR was performed by repeating 45 times under the condition of performing extension for 20 seconds in the figure.
  • the TNF-a primer, MCP-1 primer, and calibration GAPDH primers used in the SYBR Green real-time PCR are shown in Table 3 below, and the average of Ct values of TNF-a and MCP-1 is tripletlicate ( triplicate) and corrected by the Ct value of GAPDH.
  • the yonggyu extract untreated group as a control (control; CON), except that the treatment was the same as the yonggyu extract treated group.
  • Figure 4 is a view showing the results of the test TNF-alpha expression inhibitory effect of Yonggyu alcohol extract
  • Figure 5 is a road showing the results of MCP-1 expression inhibitory effect confirmed by Yonggyu alcohol extract
  • 25 denotes the administration volume of the 70% by volume ethanol extract 25ug / mL
  • the y-axis of Figure 4 shows the relative TNF-alpha mRNA expression
  • the y-axis of Figure 5 is the relative MCP-1 mRNA Expression (Relative MCP-1 mRNA expression).
  • the 70% by volume ethanol extract effectively inhibits TNF-alpha and MCP-1 expression even at a concentration of 25ug / mL.
  • Met-5A a human peritoneal methothelial cells
  • Met-5A a human peritoneal methothelial cells
  • yonggyu 70% ethanol extract inhibited endometriosis cells which are characteristic of endometriosis, from attaching and implanting to organs peritoneal peritoneal cavity.
  • Cells (American Type Culture Collection (ATCC)) were treated with 10% FBS, 100 U / ml penicillin G and 100 g / ml streptomycin (Life Technologies, Grand Island, NY, USA), and 400 nM hydrocortisone (Sigma Chemical). Co, St. Louis, Mo., USA) was incubated in a 5% CO 2 incubator in 199 medium.
  • the Met-5A cells were dispensed into 96-well plates.
  • Cell tracker green DMEM / F12 containing 50 ug / mL, 100 ug / mL, or 200 ug / mL of 70% ethanol extract of 12Z cells (2 X 10 3 / well), an endometriosis cell line labeled with CMFDA. After mixing with the medium, it was added to previously dispensed Met-5A cells. The mixed cells were incubated in a 5% CO 2 -incubator at 37 degrees Celsius for one hour, then the plates were inverted and washed with a phosphate-buffered solution containing calcium and magnesium. Attached cells were analyzed at a wavelength of 490 nm, with the calibration control set at 100% and the percentage of attached cells calculated. In addition, the yonggyu extract untreated group was treated as a control (control; CON), the same as the yonggyu extract treated group except for the extract treatment.
  • control control
  • CON the same as the yonggyu extract treated group except for the extract treatment.
  • Figure 6 is a road showing the results of endometriosis cell adhesion and anti-implantation inhibitory effect of Yonggyu alcohol extract
  • the x-axis of Figure 6 is the control group
  • 50ug / ml is 70ug% ethanol extract 50ug / mL administration group
  • the y-axis of FIG. 6 shows the ratio of attachment cells (Optical Density (OD) ratio,% ⁇ ).
  • OD Optical Density
  • Transwell-migration assay was repeated three times to confirm the effect of Yonggyu 70% ethanol extract on the migration of endometriosis cells. Specifically, after dispensing 12Z cells, which are endometriosis cells, into an upper part of a transwell plate in a 24-well-transwell plate (8 um pore size), respectively, 25 ug / mL, 50 ug / mL, and 100 ug / mL of 70% ethanol extract was treated. After treatment with 70% ethanol extract, cells transferred to the membrane on the outer side of the transwell were fixed with methanol and stained with 0.5% crystal violet for 10 minutes.
  • FIG. 7 is a road showing the results of experiments to confirm the effect of inhibiting endometriosis cell migration of the alcoholic alcohol extract, on the x-axis of Figure 7 con is a control, 25ug / ml is a 70ug% ethanol extract 25ug / mL administration group, Figure 7 The y-axis represents the percentage of migration. As shown in the figure, it can be seen that the 70% by volume ethanol extract effectively inhibits cell adhesion even at a concentration of 25ug / mL.
  • Induction of endometriosis was induced by extracting the uterus to be implanted in a donor mouse and then sculpted into the abdominal cavity of the recipient mouse, drug administration is shown in [Table 4] below, 70% ethanol extract 125 mg / kg, 250 mg / kg and 500 mg / kg were orally administered for 5 weeks, respectively.
  • the abdominal cavity was opened at the expense of endometriosis-induced animal models to determine the number of implantations in the peritoneum and intraperitoneal (small intestine, large intestine, stomach, liver, bladder, ovary, etc.).
  • the vehicle (Vehicle) administration group was treated in the same manner as the Yonggyu extract administration group except that 200ul of 10% Tween 80 instead of the extract.
  • the positive control was treated in the same manner as the Yonggyu extract administration group, except that 0.3mg / kg dienogest instead of Yonggyu extract.
  • FIG. 8 is a road showing the results of experiments confirmed the effect of the ingestion model of the alcoholic extract of Yonggyu, vehicle on the x-axis of Figure 8 vehicle administration, dienogest dienogest administration group, Yonggyu 125 is 70% by volume ethanol extract 125mg / kg The administration group is shown, and the y-axis of FIG. 8 represents the number of implants. As shown in the figure, it can be seen that 70% by volume of ethanol extract, even at 125 mg / kg, effectively exhibited an endometriosis tissue formation inhibitory effect.
  • Induction of endometriosis was induced by implanting endometrial cells by cutting the left uterus of SD rat (female) to 7 mm length and suturing both ends with silkam so that the endometrial part was in contact with the peritoneum. 5], and 100 mg / kg, 300 mg / kg, and 500 mg / kg of 70% ethanol extract were orally administered for 4 weeks.
  • the implant size (inflammation site size) in the peritoneum where the endometriosis cells were transplanted by abdominal ablation was sacrificed at the expense of an endometriosis induced animal model.
  • vehicle (Vehicle) administration group was treated in the same manner as Yonggyu extract administration group, except that the solvent for dissolving the extract instead of the extract in proportion to the body weight.
  • the extract was dissolved in 10% Tween 80.
  • a positive control (Positive control) was treated in the same manner as the Yonggyu extract administration group, except that 0.3mg / kg dienogest instead of Yonggyu extract.
  • Figure 9 is a road showing the results of experiments confirming the effect of the surgical extract of Yonggyu alcohol extract, vehicle on the x-axis of Figure 9 vehicle administration vehicle, positive control group dienogest administration group, Yonggyu 100mg / kg Yonggyu extract 100mg / kg administration group
  • the y-axis represents the implant size. As shown in the figure, 70% by volume of ethanol extract, even 100mg / kg, it can be seen that effectively shows the effect of inhibiting endometriosis tissue formation.
  • Yonggyu butanol fraction extract was prepared by dividing into normal hexane fraction, dichloromethane fraction, ethyl acetate fraction, butanol fraction, and water layer through a systematic fraction of 1 kg of 70% ethanol extract prepared in the same manner as in 1-1. . Specifically, 4 L of water was added to 1 kg of the powdered extract, and the alcohol extract to which water was added was fractionated with 20 L of n-hexane, the n-hexane fraction was taken separately, and the remaining aqueous layer was fractionated with 20 L of dichloromethane to dichloromethane fraction.
  • the remaining aqueous layer was fractionated with 40 liters of ethyl acetate, the ethyl acetate fraction was separated separately, and the remaining aqueous layer was fractionated with 40 liters of butanol to obtain a butanol fraction, and the butanol fraction obtained by this procedure was concentrated under reduced pressure, The concentrated solution was lyophilized to obtain 141 g of butanol fraction extract in powdered 70% ethanol extract. In addition, the water layer remaining after the butanol fraction extraction was obtained separately.
  • the endometriosis cell is a representative protein expressed in endometriosis and the butanol fraction extract of 70% ethanol extract inhibits the mRNA expression of endogenous MMP-2 and MMP-9 which plays an important role in cell migration and infiltration. It was confirmed in the phosphorus 12Z cells (see Fig. 10, 11).
  • Figure 10 is a view showing the results of the MMP-2 expression inhibitory effect confirmed by Yonggyu butanol fraction extract
  • Figure 11 is a road showing the results of the MMP-9 expression inhibitory effect confirmed by Yonggyu butanol fraction extract
  • Figures 10 and 11 x In the axis, con denotes the control group, 0.5 denotes the 0.5ug / mL administration group of the silica gel butanol fraction extract, and the y-axis of FIG. 10 represents the relative levels of MMP-2 mRNA, and the y-axis of FIG. Relative levels of MMP-9 mRNA are shown. As shown in the figure, it can be seen that the extract of butyol butanol extract effectively inhibits MMP-2 and MMP-9 expression even at a concentration of 0.5 ug / mL.
  • Figure 12 is a road showing the results of the COX-2 expression inhibitory effect of the extract of the yonggyu butanol fraction extract, in the x-axis of Figure 12 con represents the control group, 0.5 represents the yonggyu butanol fraction extract 0.5ug / mL administration group, y-axis is COX- Relative levels of 2 mRNA (Relative levels of COX-2 mRNA) are shown. As shown in the figure, it can be seen that the extract of butyol butanol extract effectively inhibits COX-2 expression even at a concentration of 0.5 ug / mL.
  • Figure 13 is a view showing the results of the test TNF-alpha expression inhibitory effect of Yonggyu butanol fraction extract
  • Figure 14 is a road showing the results of MCP-1 expression inhibition test of Yonggyu butanol fraction extract
  • Figure 13 and 14 x In the axis, con represents the control group, 0.5 represents the 0.5ug / mL administration group of Yonggyu butanol fraction extract, the y axis of FIG. 13 represents the relative levels of TNF-a mRNA, and the y axis of FIG. Relative levels of MCP-1 mRNA are shown. As shown in the figure, it can be seen that the extract of Yonggyu butanol fraction effectively inhibits TNF-alpha and MCP-1 expression even at a concentration of 0.5 ug / mL.
  • Figure 15 is a road showing the results of confirming the effect of endometriosis cell adhesion and implantation inhibitory effect of the extract of Yonggyu butanol fraction
  • the x-axis of Figure 15 is the control group
  • 1 represents the 1ug / mL administration group of the extract of Yonggyu butanol fraction
  • y-axis The ratio of Attachment cells (Optical Density (OD) ratio,%) is shown.
  • OD Optical Density
  • Example 2-2 In the same manner as in Example 2-2, except that the fraction extract described in Table 6 or Table 7 was used instead of the extract of Butyol fraction.
  • Table 6 is the results for MMP-2
  • Table 7 shows the results for MMP-9.
  • each fraction extract inhibits MMP-2 and / or MMP-9 expression.
  • Table 9 is the results for TNF-alpha, the results for MCP-1 in Table 10.
  • Table 9 is the results for TNF-alpha, the results for MCP-1 in Table 10.
  • Yonggyu fraction extract is effective in the treatment, improvement or prevention of endometriosis and complications.
  • Dried Yonggyu (Solanum nigrum, production area: Yeongcheon, Gyeongsangbuk-do) was purchased at Gyeongdong Market (South Korea) and pulverized. 1 liter of distilled water was added to 500 g of the prepared silicon broth and extracted using a water bath for 3 hours. The extract was filtered using filter paper and lyophilized for 48 hours to obtain a powdered red water extract.
  • Example 1-2 In the same manner as in Example 1-2, except that 100 ug / mL of the water extract of 4-1. Was used instead of 25 ug / mL, 50 ug / mL, or 100 ug / mL of the 70% by volume ethanol extract. Was carried out.
  • Figure 16 is a road showing the results of the MMP-2 expression inhibitory effect of Yonggyuk water extract, in the x-axis of Figure 16 is the control group, 100ug / ml is 100ug / mL administration group of the water-based water extract, y-axis is MMP-2 Relative levels of MMP-2 mRNA are shown. As shown in the figure, it can be seen that yonggyu water extract effectively inhibits MMP-2 expression.
  • Example 1-3 In the same manner as in Example 1-3, except that 100 ug / mL of the water extract of 4-1. Was used instead of 25 ug / mL, 50 ug / mL, or 100 ug / mL of the 70% ethanol extract. It was.
  • Figure 17 is a road showing the results of the inhibitory effect of COX-2 expression of Yonggyu water extract, on the x-axis of Figure 17 con represents a control, 100ug / ml represents a 100ug / mL administration group, y-axis is COX-2 Relative levels of COX-2 mRNA are shown. As shown in the figure, it can be seen that the yonggyu water extract effectively inhibits COX-2 expression.
  • Example 1-4 In the same manner as in Example 1-4, except that 100 ug / mL of the water extract of 4-1. Was used instead of 25 ug / mL, 50 ug / mL, or 100 ug / mL of the 70% ethanol extract. It was.
  • FIG. 18 is a view showing the results of the TNF-alpha expression inhibitory effect confirmed by Yonggyu water extract
  • Figure 19 is a road showing the results of MCP-1 expression inhibitory effect confirmed by Yonggyu water extract
  • 100ug / ml represents a 100ug / mL administration group yonggyu water extract
  • y-axis in Figure 18 represents the relative levels of TNF-alpha mRNA
  • y-axis in Figure 19 is MCP- Relative levels of 1 MCP-1 mRNA.
  • the water extract effectively inhibits TNF-alpha and MCP-1 expression.
  • the yonggyu water extract is effective in the treatment, improvement or prevention of endometriosis and complications.
  • Yonggyu extract is endometriosis or its complications by inhibiting cell migration and adhesion related enzyme expression, inhibiting inflammation and pain related enzyme expression, inhibiting inflammatory cytokine expression, endometriosis cell migration, endometriosis cell adhesion and / or implantation inhibition, etc. It can be seen that there is a treatment, improvement and / or prophylactic effect of.
  • a capsule was prepared by filling a gelatin capsule with 300 mg of yonggyu extract, corn starch 100 mg, lactose 100 mg, and magnesium stearate 2 mg prepared in the same manner as in any of the methods described in Examples 1-1 to 4-1.
  • Yonggyu extract (4% by weight), liquid fructose (0.5% by weight), oligosaccharide (2% by weight), sugar (2% by weight) prepared in the same manner as in any of the methods described in Examples 1-1 to 4-1. ), And salt (0.5% by weight) was added water to adjust the balance, and then homogeneously blended to instant sterilization to prepare a healthy beverage.
  • the present invention can effectively treat, ameliorate and / or prevent endometriosis or complications thereof, there is industrial applicability.

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Abstract

La présente invention concerne une nouvelle utilisation d'un extrait de Solanum nigrum L. La présente invention présente l'avantage de traiter, de soulager et/ou de prévenir efficacement l'endométriose ou une complication de celle-ci.
PCT/KR2016/002427 2015-03-12 2016-03-11 Nouvelle utilisation d'extrait de solanum nigrum l. Ceased WO2016144125A2 (fr)

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KR10-2015-0034679 2015-03-12
KR1020150034679A KR102324233B1 (ko) 2015-03-12 2015-03-12 용규 추출물의 신규 용도

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108324798A (zh) * 2018-05-10 2018-07-27 李明慧 一种少花龙葵的加工产品与用途
WO2019191151A1 (fr) * 2018-03-26 2019-10-03 Rhode Island Hosptial Administration intracellulaire in vitro et in vivo d'arnsi par l'intermédiaire de nano-pièces auto-assemblées

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060034178A (ko) 2004-10-18 2006-04-21 한국 한의학 연구원 용규 추출물을 유효성분으로 함유하는 ａｉｄｓ 치료제
KR20140099394A (ko) * 2013-02-01 2014-08-12 한국식품연구원 용규 추출물, 백선피 추출물 또는 이의 조합을 유효성분으로 포함하는 Ｔｈ1－매개 면역 질환 또는 Ｔｈ2-매개 면역 질환의 예방, 개선 또는 치료용 조성물

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019191151A1 (fr) * 2018-03-26 2019-10-03 Rhode Island Hosptial Administration intracellulaire in vitro et in vivo d'arnsi par l'intermédiaire de nano-pièces auto-assemblées
US11701379B2 (en) 2018-03-26 2023-07-18 Rhode Island Hospital In vitro and in vivo intracellular delivery of siRNA via self-assembled nanopieces
CN108324798A (zh) * 2018-05-10 2018-07-27 李明慧 一种少花龙葵的加工产品与用途

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