WO2023153794A1 - Composition pour améliorer la fonction ovarienne ou prévenir ou traiter l'ovotoxicité - Google Patents

Composition pour améliorer la fonction ovarienne ou prévenir ou traiter l'ovotoxicité Download PDF

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WO2023153794A1
WO2023153794A1 PCT/KR2023/001830 KR2023001830W WO2023153794A1 WO 2023153794 A1 WO2023153794 A1 WO 2023153794A1 KR 2023001830 W KR2023001830 W KR 2023001830W WO 2023153794 A1 WO2023153794 A1 WO 2023153794A1
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Prior art keywords
extract
malt
vcd
composition
ovarian
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PCT/KR2023/001830
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English (en)
Korean (ko)
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이주희
김동일
김선아
유성경
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동국대학교 와이즈캠퍼스 산학협력단
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Priority claimed from KR1020220076616A external-priority patent/KR20230122505A/ko
Priority claimed from KR1020220076618A external-priority patent/KR20230122507A/ko
Priority claimed from KR1020220076617A external-priority patent/KR20230122506A/ko
Priority claimed from KR1020220076615A external-priority patent/KR20230122504A/ko
Application filed by 동국대학교 와이즈캠퍼스 산학협력단 filed Critical 동국대학교 와이즈캠퍼스 산학협력단
Publication of WO2023153794A1 publication Critical patent/WO2023153794A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • 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)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • 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
    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a composition for enhancing ovarian function or preventing or treating dystocia.
  • the ovary is not only a female reproductive organ, but also an organ that maintains female health through the production of various hormones.
  • Female aging can be divided into general aging of the body and aging of reproductive function, among which aging of reproductive function generally means ovarian aging.
  • Ovarian aging is a phenomenon that occurs in all women. In general, from the age of 35, the number of follicles decreases along with the quality of oocytes, resulting in a decrease in fertility. It is known that it can cause not only polycystic ovary syndrome, infertility, and early menopause, but also systemic problems such as dementia, osteoporosis, heart disease, menopausal disease, and metabolic disorders.
  • Menopausal disease is a representative disease caused by ovarian aging (decreased ovarian function). It occurs when the secretion of estrogen, a female hormone, is reduced. In addition to physical symptoms such as skin aging, depression, poor concentration, insomnia, headache, tinnitus, and nervousness, symptoms can also appear in the mental nervous system.
  • Ovotoxicity refers to a toxic effect on ovarian tissue and germ cells of the ovary caused by various harmful factors.
  • Anticancer chemotherapeutic agents, polycyclic aromatic hydrocarbons (PAHs), etc. are known as representative infertility factors, and such intoxication triggers ovarian aging, causing premature ovarian failure or reduced fertility.
  • VCD 4-vinylcyclohexene diepoxide
  • Akt a member of the PI3K family, in the process.
  • Hormone therapy which uses herbal medicines and/or functional foods to improve various symptoms caused by ovarian function decline or supplements estrogen whose production is reduced due to ovarian function decline, is currently being used clinically, but ovarian function decline There is no way to fundamentally treat it.
  • An object of the present invention is Shin ( Magnoliae Flos ) or malt ( Hordei Fructus Germinatus ) To provide a composition for enhancing ovarian function containing an extract as an active ingredient.
  • Another object of the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and Astragalus ( Astragali Radix )
  • a pharmaceutical composition for preventing or treating premature ovarian failure or premature menopause comprising at least one extract selected from the group consisting of as an active ingredient.
  • Another object of the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and Astragalus ( Astragali Radix )
  • Shin Magnoliae Flos
  • peony Paeoniae Radix
  • malt Hordei Fructus Germinatus
  • Astragalus Astragali Radix
  • Another object of the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and Astragalus ( Astragali Radix )
  • Shin Magnoliae Flos
  • peony Paeoniae Radix
  • malt Hordei Fructus Germinatus
  • Astragalus Astragali Radix
  • Another object of the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and Astragalus ( Astragali Radix )
  • Shin Magnoliae Flos
  • peony Paeoniae Radix
  • malt Hordei Fructus Germinatus
  • Astragalus Astragali Radix
  • the present invention is Shin ( Magnoliae Flos ) or malt ( Hordei Fructus Germinatus ) Provides a composition for enhancing ovarian function containing an extract as an active ingredient.
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix ) Provides a pharmaceutical composition for preventing or treating premature ovarian failure or premature menopause containing at least one extract selected from the group consisting of as an active ingredient .
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix )
  • Shin Magnoliae Flos
  • peony Paeoniae Radix
  • malt Hordei Fructus Germinatus
  • astragalus Astragali Radix
  • a health functional food composition for preventing or improving premature ovarian failure or early menopause containing at least one extract selected from the group consisting of as an active ingredient to provide.
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix ) It provides a pharmaceutical composition for preventing or treating ovotoxicity containing at least one extract selected from the group consisting of as an active ingredient.
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix ) Provides a health functional food composition for preventing or improving ovotoxicity containing at least one extract selected from the group consisting of as an active ingredient do.
  • the extracts of Shinyi, Peony, Maltger and Astragalus Astragalus inhibit the production of reactive oxygen species, thereby protecting ovarian cells against VCD-induced ovotoxicity, inhibiting apoptosis, and activating the PI3K/Akt signaling pathway. By confirming that, it can be used for strengthening ovarian function or preventing, treating, or improving dystocia.
  • Figure 1 is the result of analyzing the DPPH radical and superoxide anions scavenging activity of peony extract.
  • Figure 2 shows the results of analyzing the cytotoxicity of the extracts of Shinyi (MFMW and MFME), peony (PR), malt (HFG) and Astragalus (AR) on ovarian cells.
  • FIG. 3 shows the ovarian cell protective effect of Shinyi (MFMW and MFME), peony (PR), malt (HFG) and Astragalus (AR) extracts against ovotoxicity induced by 4-vinylcyclohexene diepoxide (hereinafter referred to as VCD) is the result of analyzing
  • Figure 4 analyzes the inhibitory effect of reactive oxygen species (hereinafter referred to as ROS) production of kidneys (MFMW and MFME), peony (PR), malt (HFG) and astragalus (AR) extracts in ovarian cells treated with VCD is a result
  • FIG. 5 is a result of analyzing changes in morphology of whole cell morphology or intracellular nuclei through DAPI staining when treatment with MFMW and Astragalus (AR) extracts in VCD-treated ovarian cells.
  • Figure 7 is a result of analyzing the activity change of the PI3K / Akt signaling pathway according to the treatment time of Shinyi (MFMW), peony (PR), malt (HFG) and Astragalus (AR) extracts.
  • MFMW Shinyi
  • PR peony
  • HFG malt
  • AR Astragalus
  • Con vehicle
  • V VCD 160mg/ kg/day
  • V+ML VCD 160mg/kg + MFMW Low dose 100mg/kg
  • V+MH VCD 160mg/kg + MFMW High dose 300mg/kg
  • Figure 9 shows the results of measuring the weight index of the uterus + ovary and ovary according to the treatment with Shinyi extract in an animal model of premature ovarian failure (Con vs group: ## p ⁇ 0.01, ### p ⁇ 0.001, VCD vs group: * p ⁇ 0.05, ***p ⁇ 0.001).
  • FIG. 10 shows the results of measuring serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) of each group in an animal model of premature ovarian failure (NS: not significant).
  • GAT serum glutamic oxaloacetic transaminase
  • GPT glutamic pyruvic transaminase
  • 11 is a histopathological analysis result of ovarian tissue through H&E staining.
  • the present invention is Shin ( Magnoliae Flos ) or malt ( Hordei Fructus Germinatus ) Provides a composition for enhancing ovarian function containing an extract as an active ingredient.
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix ) Provides a pharmaceutical composition for preventing or treating premature ovarian failure or premature menopause containing at least one extract selected from the group consisting of as an active ingredient .
  • Shinyi Magnoliae flos .
  • Magnolia is a deciduous tree that has been cultivated for horticultural purposes since ancient times. Flowers bloom before leaves, and the flowering period is between March and April.
  • oriental medicine its nature is regarded as warm, and it is effective for headache, back pain and rhinitis, treats sinusitis, and sees that it has medicinal properties as a pain reliever.
  • Peony ( Paeoniae Radix ) is a dicotyledonous perennial plant belonging to the peony genus and is mainly distributed in Korea, Mongolia, China, and East Siberia.
  • the peony root contains a large amount of benzoic acid, asparagine, and paeoniflorin. It is mainly used to treat amenorrhea, hematemesis, anemia, and bruises.
  • Peony flowers are widely used for horticultural purposes, and recently, peony seeds have been reported to have excellent anticancer and antimutagenic effects because they contain a large amount of physiologically active substances such as trans-resvaratrol, trans-viniferin, and cis-viniferin.
  • Malt ( Hordei Fructus Germinatus ) is a sprouted and dried barley ( Hordeum vulgare Linn, ⁇ ) of the Poaceae family.
  • the synonyms of malt include barley malt, barley wall, barley hair, and barley malt ( ⁇ ). ), grain maek ( ⁇ ), etc., and amylase, a malt enzyme, acts to convert starch into sugar, so it is also known as “malt”.
  • Malt contains diastase, invertase, glucose 6-phosphate dehydrogenase, a-amylase, b-amylase, protease, dextrin It contains a lot of enzymes involved in protein metabolism, such as maltose, glucose, and vitamin B. , it has been reported to be effective in hepatitis, etc.
  • Astragalus Astragali Radix
  • Astragalus is a perennial herb belonging to the leguminous family (Leguminosae), which digs up the roots of Astragalus membranaceus Bunge and peels and dries them.
  • Leguminosae leguminous family
  • it has been used for purposes such as diuresis, tonic, lowering blood pressure, anti-inflammatory, antipyretic, pain relief, etc.
  • Immunity, anticancer, antiviral, antibacterial, diuretic, anti-inflammatory, etc. are very diverse.
  • the saponin component contained in astragalus is known to exhibit effects such as antioxidant, anti-aging, and skin regeneration.
  • the extract may be extracted with water, C1 to C4 alcohol, or a mixed solvent thereof.
  • the extract may exhibit an ovarian protective effect against ovotoxicity through reactive oxygen species (ROS) production inhibitory activity, and the ovotoxicity is induced by 4-vinylcyclohexene diepoxide (VCD) can
  • the extract can inhibit apoptosis of ovarian cells.
  • the extract can activate the PI3K/Akt signaling pathway.
  • the pharmaceutical composition of the present invention is prepared in a unit dose form or in a multi-dose container by formulating using a pharmaceutically acceptable carrier according to a method that can be easily performed by those skilled in the art. It can be prepared by incorporating into
  • the pharmaceutically acceptable carrier is one commonly used in formulation, and includes lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like.
  • the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, and the like, in addition to the above components.
  • the content of the additives included in the pharmaceutical composition is not particularly limited and may be appropriately adjusted within the range of content used in conventional formulations.
  • the pharmaceutical composition may be formulated into an injectable formulation such as an aqueous solution, suspension, or emulsion, a pill, a capsule, a granule, a tablet, a cream, a gel, a patch, a spray, an ointment, a warning agent, a lotion, a liniment agent, a paste agent, and a cataplasma agent. It may be formulated in the form of one or more skin external preparations selected from the group consisting of, but is not limited thereto.
  • an injectable formulation such as an aqueous solution, suspension, or emulsion, a pill, a capsule, a granule, a tablet, a cream, a gel, a patch, a spray, an ointment, a warning agent, a lotion, a liniment agent, a paste agent, and a cataplasma agent. It may be formulated in the form of one or more skin external preparations selected from the group consisting of, but is not
  • the pharmaceutical composition of the present invention may additionally contain pharmaceutically acceptable carriers and diluents for formulation.
  • the pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose and hydroxypropylcellulose, gelatin, alginates, and polyvinyl pyrrolidone. binders such as talc, calcium stearate, lubricants such as hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone and crospovidone, surfactants such as polysorbates, cetyl alcohol, glycerol and the like, but are not limited thereto.
  • the pharmaceutically acceptable carrier and diluent may be biologically and physiologically compatible with the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents and/or dispersion media.
  • the pharmaceutical composition of the present invention may be administered orally or parenterally (eg, intravenous, subcutaneous, intraperitoneal or topical application) depending on the desired method.
  • parenterally eg, intravenous, subcutaneous, intraperitoneal or topical application
  • it may be formulated into tablets, troches, lozenges, aqueous suspensions, oily suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups, elixirs, and the like.
  • parenteral administration it may be formulated as an injection solution, suppository, powder for respiratory inhalation, aerosol for spray, ointment, powder for application, oil, cream, etc.
  • the dosage of the pharmaceutical composition of the present invention depends on the patient's condition, weight, age, sex, health condition, dietary constitution specificity, the nature of the preparation, the severity of the disease, the administration time of the composition, the administration method, the administration period or interval, the excretion rate and
  • the range may vary depending on the type of drug, and may be appropriately selected by a person skilled in the art. For example, it may range from about 0.1 to 10,000 mg/kg, but is not limited thereto, and may be divided and administered once or several times a day.
  • the pharmaceutical composition may be administered orally or parenterally (eg, intravenous, subcutaneous, intraperitoneal or topical application) depending on the desired method.
  • the pharmaceutically effective amount and effective dose of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, administration route, etc. of the pharmaceutical composition, and those skilled in the art can achieve effective treatment for the desired treatment.
  • the dosage can be easily determined and prescribed.
  • Administration of the pharmaceutical composition of the present invention may be administered once a day, or may be divided and administered several times.
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix )
  • Shin Magnoliae Flos
  • peony Paeoniae Radix
  • malt Hordei Fructus Germinatus
  • astragalus Astragali Radix
  • a health functional food composition for preventing or improving premature ovarian failure or early menopause containing at least one extract selected from the group consisting of as an active ingredient to provide.
  • the present invention can be generally used as a commonly used food.
  • the food composition of the present invention can be used as a health functional food.
  • health functional food refers to food manufactured and processed using raw materials or ingredients having useful functionalities for the human body in accordance with the Health Functional Food Act, and "functional” refers to food that is not related to the structure and function of the human body. It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients or physiological functions.
  • the health functional food composition may include conventional food additives, and the suitability as the "food additive" is determined in accordance with the General Rules and General Test Methods of Food Additives approved by the Ministry of Food and Drug Safety, unless otherwise specified. It is judged according to the specifications and standards for the item.
  • Items listed in the "Food Additive Code” include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigment, licorice extract, crystalline cellulose, goyang pigment, guar gum, and mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
  • chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid
  • natural additives such as dark pigment, licorice extract, crystalline cellulose, goyang pigment, guar gum
  • mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations.
  • the food composition of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like.
  • hard capsules can be prepared by mixing and filling a composition according to the present invention with additives such as excipients in a conventional hard capsule, and soft capsules contain the composition according to the present invention. It can be prepared by mixing with additives such as excipients and filling in a capsule base such as gelatin.
  • the soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative, and the like, if necessary.
  • prevention refers to any action that suppresses or delays the symptoms or diseases by administering the composition according to the present invention.
  • treatment refers to all activities that improve or beneficially change the symptoms of the symptoms or diseases by administration of the composition according to the present invention.
  • improvement means any action that improves the bad condition of the symptom or disease by administering or ingesting the composition of the present invention to a subject.
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix ) It provides a pharmaceutical composition for preventing or treating ovotoxicity, containing as an active ingredient one or more extracts selected from the group consisting of .
  • the present invention is Shin ( Magnoliae Flos ), peony ( Paeoniae Radix ), malt ( Hordei Fructus Germinatus ) and astragalus ( Astragali Radix ) Provides a health functional food composition for preventing or improving ovotoxicity containing at least one extract selected from the group consisting of as an active ingredient do.
  • MFMW Magnoliae 3.3 g of Flos macerated water and 4.94 g of Magnoliae Flos macerated ethanol (MFME) were obtained.
  • the scavenging activity for DPPH radicals was measured. 1mL of 1M DPPH solution and 450 ⁇ L of 50mM Tris-HCl buffer (pH 7.4) were added to 50 ⁇ l of the sample and mixed. After reacting the mixture at room temperature for 30 minutes, absorbance was measured at a wavelength of 517 nm using a microplate reader (VersaMax, Molecular Devices, USA). The scavenging activity of the DPPH radical was expressed as a concentration showing 50% scavenging ability (EC 50 ).
  • the scavenging activity for peroxide anion was measured using the NBT reduction method. 10 ⁇ L of 30 mM EDTA (ethylene-diamine-tetraacetic acid, pH 7.4), 1 ⁇ L of 30 mM hypoxanthine, and 200 ⁇ L of 1.42 mM NBT (nitroblue tetrazolium) were added to 30 ⁇ L of sample, followed by reaction at room temperature for 3 minutes, followed by oxidation of 1 U/mL xanthine 10 ⁇ L of enzyme (xanthine oxidase) was added, and the total volume was adjusted to 300 ⁇ L with 50 mM phosphate buffer (pH 7.4). After incubating the reaction solution at room temperature for 20 minutes, the absorbance was measured at a wavelength of 560 nm, and the results were expressed in terms of NBT reduction EC 50 values by superoxide radicals.
  • 10 ⁇ L of 30 mM EDTA ethylene-diamine-tetraacetic acid, pH
  • MTT 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide) assay method.
  • 1 ⁇ 10 4 cells/well of CHO-K1 cells were cultured in a 96-well plate, and after serum starvation for 4 hours, the four extracts were pretreated by concentration, respectively, and VCD 1.5mM was sequentially applied. treated and cultured for 24 hours under conditions of 37°C and 5% CO 2 .
  • 10 ⁇ L of MTT solution 2mg/mL per well was added and reacted for 2 hours in an incubator at 37°C and 5% CO 2 conditions.
  • the ROS activities of the four extracts were measured. After culturing CHO-K1 cells in a 6-well plate, the above four extracts were pre-treated for 1 hour, treated with VCD 1.5 mM, and further cultured for 18 hours.
  • DCFH-DA (2' 7-dichlorofluorescein diacetate) diluted with PBS (phosphate buffer saline) was added to the medium at a concentration of 1 ⁇ M, incubated for 30 minutes, and then the cells were washed twice with PBS. Thereafter, the fluorescence intensity was measured using a CytoFLEX flow cytometer (Beckman Coulter Inc., USA), and the increase rate of DCF fluorescence intensity was calculated as a percentage (%) compared to the control group.
  • CHO-K1 cells were pretreated with Shinyi and Astragalus extracts at various concentrations for 1 hour, respectively, and VCD 1.5 After treatment with mM, and incubation at 37° C. and 5% CO 2 for 24 hours, the cells were observed under an optical microscope (Nikon, Japan). To observe CHO-K1 cell nuclei, CHO-K1 cells were washed twice with PBS, fixed with 4% paraformaldehyde, and washed twice with PBS.
  • DAPI 4,6-diamidino-2-phenylindole
  • the membrane was treated with a blocking buffer (5% non-fat milk) for 1 hour, and then washed with a PBST solution containing 0.1% Tween 20. It was treated overnight at 4 ° C using the antibody of each protein to be reported, the secondary antibody was HRP-linked anti-rabbit (anti-rabbit) or anti-mouse (anti-mouse) was used, and enhanced chemiluminoescence solution (Amersham , Piscataway, NJ, USA), the expression level of each protein was observed in a Fusion Solo-2 image image analyzer (Vilber Lourmat, Paris, France), and images were acquired.
  • a blocking buffer 5% non-fat milk
  • mice 11-18 g B6C3F1 female mice were purchased from the central laboratory animals and used for experiments after being acclimatized to the laboratory environment while supplying sufficient food and water for one week.
  • the laboratory environment maintained a temperature of 22 ⁇ 2 ° C and continued day and night in 12-hour increments until the end of the experiment.
  • the control group was intraperitoneally injected with sesame oil (Sigma-Aldrich, USA), and the control (VCD) and experimental groups (VCD+MFMW 100mg/kg, VCD+MFMW 300mg/kg) were injected with VCD (Sigma-Aldrich, USA). , USA) was dissolved in sesame oil and intraperitoneally injected at a concentration of 160 mg/kg/day 5 times a week for a total of 2 weeks to induce premature ovarian failure.
  • mice were sacrificed on the last day of the experiment, the entire uterus and ovaries were removed, observed with the naked eye, and their weights were measured.
  • CHO-K1 cells were pretreated with the above four extracts at various concentrations (1, 10, 100, and 200 ⁇ g/mL) for 1 hour, and after inducing ovotoxicity with VCD 1.5mM, protective effect against ovotoxicity.
  • the Shinyi extract showed a concentration-dependent protective effect against dyslexia in MFMW, and showed a survival rate almost similar to that of the control group not treated with VCD at a concentration of 100 ⁇ g / mL or more
  • MFME showed a protective effect against dyslexia at concentrations of 1 and 10 ⁇ g/mL.
  • peony, malt and astragalus extracts showed a concentration-dependent protective effect against dyslexia.
  • the normal group (Con) maintains normal size of both the uterine and ovarian tissues
  • the VCD-treated group (V) confirmed that the tissues of the uterus and ovaries were significantly atrophied.
  • the Shinyi extract and VCD treated groups (V+ML and V+MH) exhibited similar uterine and ovarian tissue sizes to those of the normal group.
  • Example 9 Analysis of the ovarian/uterine protection effect by comparing the weight of the entire uterus and ovary with the weight of the ovary

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  • Alternative & Traditional Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Reproductive Health (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Polymers & Plastics (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Endocrinology (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

La présente invention concerne une composition permettant d'améliorer la fonction ovarienne ou de prévenir ou traiter l'ovotoxicité. Au moyen d'extraits de bouton de Magnolia Liliflora, de Paeonia Lactiflora, de malt et d'Astragalus Membranaceus inhibant la production d'oxygène actif, il est confirmé que la présente invention présente un effet de protection de cellules ovariennes, d'inhibition de l'apoptose et d'activation de la voie de signalisation PI3K/Akt contre l'ovotoxicité induite par VCD, et la présente invention peut ainsi être utilisée pour améliorer la fonction ovarienne ou prévenir, traiter ou améliorer l'ovotoxicité.
PCT/KR2023/001830 2022-02-14 2023-02-08 Composition pour améliorer la fonction ovarienne ou prévenir ou traiter l'ovotoxicité WO2023153794A1 (fr)

Applications Claiming Priority (16)

Application Number Priority Date Filing Date Title
KR10-2022-0018605 2022-02-14
KR10-2022-0018606 2022-02-14
KR10-2022-0018607 2022-02-14
KR20220018606 2022-02-14
KR10-2022-0018608 2022-02-14
KR20220018607 2022-02-14
KR20220018608 2022-02-14
KR20220018605 2022-02-14
KR10-2022-0076617 2022-06-23
KR1020220076616A KR20230122505A (ko) 2022-02-14 2022-06-23 작약 추출물을 유효성분으로 포함하는 난독성 예방 또는 치료용 약학 조성물
KR1020220076618A KR20230122507A (ko) 2022-02-14 2022-06-23 황기 추출물을 유효성분으로 포함하는 난독성 예방 또는 치료용 약학 조성물
KR10-2022-0076615 2022-06-23
KR10-2022-0076616 2022-06-23
KR1020220076617A KR20230122506A (ko) 2022-02-14 2022-06-23 맥아 추출물을 유효성분으로 포함하는 난소 기능 강화용 조성물
KR10-2022-0076618 2022-06-23
KR1020220076615A KR20230122504A (ko) 2022-02-14 2022-06-23 신이 추출물을 유효성분으로 포함하는 난소 기능 강화용 조성물

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WO2023153794A1 true WO2023153794A1 (fr) 2023-08-17

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