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WO2018230942A1 - Composition contenant un extrait ou une fraction d'extrait de reynoutria japonica pour prévenir et traiter le syndrome de l'œil sec - Google Patents

Composition contenant un extrait ou une fraction d'extrait de reynoutria japonica pour prévenir et traiter le syndrome de l'œil sec Download PDF

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Publication number
WO2018230942A1
WO2018230942A1 PCT/KR2018/006659 KR2018006659W WO2018230942A1 WO 2018230942 A1 WO2018230942 A1 WO 2018230942A1 KR 2018006659 W KR2018006659 W KR 2018006659W WO 2018230942 A1 WO2018230942 A1 WO 2018230942A1
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Prior art keywords
fraction
extract
dry eye
eye syndrome
alcohol
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PCT/KR2018/006659
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English (en)
Korean (ko)
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김진숙
김정현
김찬식
김영숙
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한국한의학연구원
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Publication of WO2018230942A1 publication Critical patent/WO2018230942A1/fr

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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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/35—Extraction with lipophilic solvents, e.g. Hexane or petrol ether

Definitions

  • the present invention is a pharmaceutical composition for the prevention or treatment of dry eye syndrome comprising esoteric muscle extract or fractions thereof as an active ingredient, health functional food for preventing or improving dry eye syndrome, esoteric extract or A method for preventing or treating dry eye syndrome, comprising the steps of administering to the subject a composition comprising a fraction thereof as an active ingredient, the purpose of preventing or treating dry eye syndrome of a composition comprising an extract of E. coli muscle extract or a fraction thereof as an active ingredient, and
  • the present invention relates to the use of a rhododendron extract or a fraction thereof for preparing a prophylactic or therapeutic agent.
  • Dry eye syndrome is not simply a lack of tears, but also causes eye discomfort, eye strain, decreased vision, and tear instability due to tears and inflammation of the ocular surface (cornea and conjunctiva).
  • the pathogenesis has not yet been fully understood, but studies have shown that inflammation plays an important role, such as invasion of inflammatory cells, increased immune activating molecule and adhesion molecule expression, Th1 and Th17 responses, apoptosis markers and abnormal changes in chemokines. have.
  • the global dry eye market is expected to grow at an average annual rate of 12.8% from $ 1.6 billion in 2012 ($ 1.88 trillion) in 2012 to $ 5.5 billion (6.46 trillion won) in 2011.
  • the Korea Health Insurance Review & Assessment Service the total medical expenses used to treat dry eye syndrome in Korea increased by 8.6% per year, up to KRW 51.5 billion in 2009 and KRW 72.2 billion in 2013, more than KRW 20 billion in five years (EToday, 2016. 06.27) .
  • dry eye syndrome is a common disease that occurs in about 20% of Korean adults.
  • dry eye syndrome continues to increase due to global temperature changes, especially Elino, and environmental pollution such as fine dust.
  • Polygonum Cuspidatum (Japanese Knotweed) is a perennial plant of the genus Madaceae , which grows in Sanya in Korea, and is distributed in Korea, Japan, Taiwan, and China.
  • Hojangeun has been used as a diuretic, analgesic, and sedative in the private sector, and pharmacological action of Hojangeun has been shown to inhibit lipid metabolism (Masaki H., et al., 1995, Biol. Pharm. Bull. 18: 162-166, 1995), protein tyrosine kinase inhibition (Jayatilake GS, et al., 1993, J. Nat. Prod. 56: 1805-1810), mutagenic inhibition (Su et al., 1995, Mutat. Res. 329: 205- 212).
  • the inventors of the present invention while searching for a composition for preventing and treating dry eye syndrome in natural products, confirming that E. coli muscle extract or fractions thereof can treat dry eye syndrome by increasing tear secretion, suppressing corneal morphology, and preventing eye fatigue, The present invention has been completed.
  • One object of the present invention to provide a pharmaceutical composition for the prevention or treatment of dry eye syndrome comprising E. coli muscle extract or fractions thereof as an active ingredient.
  • Another object of the present invention is to provide a method for preventing or treating dry eye syndrome, comprising administering to a subject a composition comprising Escherichia coli extract or a fraction thereof as an active ingredient.
  • Another object of the present invention is to provide a prophylactic or therapeutic use of dry eye composition of a composition comprising an extract of E. coli muscle or fractions thereof as an active ingredient.
  • Another object of the present invention is to provide the use of E. coli muscle extract or a fraction thereof for the manufacture of a medicament for the prevention or treatment of dry eye syndrome.
  • the extract of the present invention and its fractions can significantly inhibit the decrease of tear secretion and corneal morphology due to dry eye syndrome, it can be widely used in the development of pharmaceutical compositions for the prevention or treatment of eye fatigue and dry eye syndrome.
  • it can be widely used in the development of pharmaceutical compositions for the prevention or treatment of eye fatigue and dry eye syndrome.
  • Figure 1 is a schematic diagram showing the step of stepwise sequential fractionation using n-hexane (n-hexane), ethyl acetate (EtOAc), n-butanol (n-BuOH) with respect to the extract ethanol.
  • n-hexane n-hexane
  • EtOAc ethyl acetate
  • n-BuOH n-butanol
  • Figure 2 is a graph showing the changes in tear secretion of rats following administration of the elongated muscle butanol fraction (*: p ⁇ 0.05 vs. Nor; #: p ⁇ 0.05 vs. DED).
  • Figure 3 is a photograph showing the changes in the corneal morphology of rats following the administration of the E. coli butanol fraction.
  • Figure 4 is a graph showing the corneal smoothness score (corneal smoothness score) of rats following administration of the elongated muscle butanol fraction.
  • the corneal smoothness score was evaluated by measuring the corneal morphology by scoring the degree of distortion in a round circle from 0 to 5 (0 points: no distortion, 1 point: crushed at 1/4 site, 2 points: 2/4 site) Dentification, 3 points: dent at 3/4 site, 4 points: dent at all site, 5 points: severe crushing, no rounded shape; #: p ⁇ 0.05 vs. DED).
  • the inventors of the present invention while developing various therapeutic agents that can effectively treat dry eye syndrome, found that E. coli extract or fractions thereof had an effect of treating dry eye syndrome.
  • the extracts or fractions of K. koji significantly inhibited the decrease in tear secretion and changes in corneal morphology due to dry eye, and also showed similar effects to commercially available drugs used for the treatment of dry eye syndrome.
  • the technique for treating dry eye syndrome using the E. coli extract or fraction is not known at all, and was first developed by the present inventors.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of dry eye syndrome comprising E. coli muscle extract or a fraction thereof as an active ingredient.
  • the present invention comprises the step of administering to a subject a composition comprising an extract of E. coli or fractions thereof as an active ingredient, dry eye prevention or treatment method; Preventing or treating dry eye syndrome of a composition comprising an extract of E. coli or a fraction thereof as an active ingredient; Or the use of E. coli muscle extract or fractions thereof for the manufacture of a medicament for the prevention or treatment of dry eye syndrome.
  • the extract of K. koji with the prophylactic and therapeutic activity of dry eye syndrome can be extracted from various organs of natural, hybrid, and mutant plants, for example, roots, stems, leaves, flowers, trunks of berries, peels of berries as well as plants Extractable from tissue culture.
  • the term "hojanggeun” used in the present invention is a perennial plant of the genus Madipulaceae which grows in Sanya in Korea, the root stem is thick, and the stem is about 1.5 m in height. Leaves are alternate, egg-shaped, 6-12 cm long, with sharp tips, petioles long. As a child, the appearance of the stem resembles Hopi, so it was named Ho Jang-geun. Ho Jang-geun has been used as a diuretic, pain economy, and sedative in the private sector, and in traditional medicine in Korea and other Asian regions Has been used.
  • the extract may be extracted from the roots, stems, leaves, flowers, or fruit of the roots, but is not particularly limited thereto.
  • the extract of Keunjangeun is extracted with a solvent selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms and mixed solvents thereof, but is not limited thereto.
  • the extract may include an extract obtained by an extraction treatment, a diluent or concentrate of the extract, a dried product obtained by drying the extract, or any one of these modifiers or purified products.
  • the alcohol may be butyl alcohol, ethyl alcohol, methyl alcohol or a water soluble alcohol thereof.
  • the water-soluble alcohol may be an alcohol containing 0.1 to 100% by weight
  • the butyl alcohol may be a saturated butyl alcohol.
  • the saturated butyl alcohol refers to butanol containing water with maximum mixing water and butyl alcohol, the amount of water may be the same amount or more.
  • the polar solvent of a lower alcohol having a carbon number of 1 (C 1 ) to a carbon number (C 4 ), such as ethanol is repeatedly extracted at room temperature in an extraction container, and then, at a temperature of 40 ° C. Concentration under reduced pressure in ethanol to obtain an extract (Fig. 1). In addition, the extract was filtered and then maintained at a temperature of 40 to 45 ° C. or lower during concentration to prevent decomposition and hydrolysis of the components, and concentrated under reduced pressure.
  • fraction refers to the result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture comprising several different components.
  • the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art.
  • a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting ephedra root is not particularly limited, and may be performed according to a method commonly used in the art.
  • a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting ephedra root is not particularly limited, and may be performed according to a method commonly used in the art.
  • a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting ephedra root.
  • the fraction may be a hexane fraction, ethyl acetate fraction, butanol fraction or water fraction of the extract of the extract.
  • the fractions may each comprise 0.01 to 100% by weight, more specifically 1 to 80% by weight relative to the total weight of the pharmaceutical composition.
  • the solvent fractions of the extract of the extract Kwon Keun-Geun are separated by using a non-polar solvent, such as n-hexane (n-hexane), ethyl acetate (EtOAc) or n-butanol (n-BuOH) after suspending the extract
  • a non-polar solvent such as n-hexane (n-hexane), ethyl acetate (EtOAc) or n-butanol (n-BuOH) after suspending the extract
  • polar solvent fractions and nonpolar solvent fractions can be obtained, respectively.
  • the solvent fraction is provided with water fraction, n-hexane fraction, ethyl acetate fraction or n-butanol fraction.
  • the kind of the fractionation solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols; And nonpolar solvents such as hexane, ethyl acetate, chloroform, dichloromethane, and the like. These may be used alone or in combination of two or more thereof.
  • alcohol in the fractionation solvent specifically, alcohols of C1 to C4 may be used.
  • Suspension root ethanol extract extracted by the manufacturing method of Example 1 was suspended in distilled water and then sequentially with n-hexane (n-hexane), ethyl acetate (EtOAc) or n-butanol (n-BuOH) Lineage fractions were obtained as above fractions of the extract of Kwon Keun-geun (Fig. 1).
  • dry eye syndrome refers to dry eye syndrome in which tear secretion is suppressed due to inflammation of the tear glands and denervation of the cornea, or meibomian gland dysfunction or eyelid dysfunction. It may be a disease caused by abnormal tear evaporation, etc., and may be a corneal conjunctival epithelial disorder represented by scarring of the cornea due to excessive dryness of the tear due to dry eye.
  • prevention refers to any action that inhibits or delays the symptoms of dry eye with the administration of a composition comprising E. coli muscle extract or a fraction thereof.
  • treatment refers to any action in which the symptoms of dry eye symptoms are improved or beneficially altered by administration of a composition comprising an extract of E. coli muscle extract or a fraction thereof.
  • the composition may be to increase the amount of tear secretion or to suppress the morphological changes of the cornea.
  • the change in the shape of the cornea is because the surface of the cornea is uneven due to the excessive drying of tears, and the rounded shape is bent and crushed.
  • the composition of the present invention may be to improve it smoothly and flatly.
  • the butanol fraction of ephedra muscle is administered, and in the high concentration group (1.0 mg / mL) three days after administration, the low concentration group (0.5 mg / mL) and the high concentration group (1.0 mg / mL) after 5 days of administration In tears), tear secretion was significantly increased, which was found to be similar to the drug used most often for dry eye syndrome (FIG. 2).
  • the term "pharmaceutical composition” means that is prepared for the purpose of preventing or treating a disease, and can be used by formulating in various forms according to each conventional method.
  • it may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, and the like, and may be used in the form of external preparations, suppositories, and sterile injectable solutions.
  • it may be used in a form suitable for eye drop administration, for example, eye drops, creams, ointments, gels or lotions.
  • composition of the present invention may be prepared in the form of a pharmaceutical composition for preventing or treating dry eye syndrome further comprising a suitable carrier, excipient or diluent commonly used in the manufacture of a pharmaceutical composition, the carrier is an unnatural carrier (non-naturally occuring carrier).
  • carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, and the like in the above extracts and fractions thereof.
  • excipients such as starch, calcium carbonate, and the like in the above extracts and fractions thereof.
  • Sucrose or lactose, gelatin and the like are mixed and prepared.
  • lubricants such as magnesium styrate and talc are also used.
  • Liquid preparations for oral use may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are commonly used to include suspensions, solutions, emulsions, and syrups. have.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • the dosage of the pharmaceutical composition of the present invention can be determined by those skilled in the art in consideration of the purpose of use, the degree of addiction of the disease, the age, weight, sex, history, or type of substance used as an active ingredient of the patient.
  • the pharmaceutical composition of the present invention may be administered at about 0.1 ng to about 1,000 mg / kg, specifically 1 ng to about 1,000 mg / kg, per adult, and the frequency of administration of the composition of the present invention is particularly limited thereto. However, it may be administered once a day or several times in divided doses. The dosage does not limit the scope of the invention in any aspect.
  • the present invention provides a method for treating dry eye syndrome comprising administering the pharmaceutical composition to a subject other than a human suffering from dry eye syndrome in a pharmaceutically effective amount.
  • the term "individual” may include, without limitation, mammals including mice, livestock, and the like having dry eye.
  • the "individual” may include a companion animal.
  • the companion animal refers to an animal that lives together with a human, and includes, but is not limited to, a mammal such as a dog, a cat, a hamster, and a guinea pig, a bird such as a parrot, a canary, and the like.
  • composition may be administered in single or multiple amounts in a pharmaceutically effective amount.
  • the route of administration of the pharmaceutical composition for preventing or treating dry eye syndrome of the present invention may be administered through any general route as long as it can reach the target tissue.
  • the pharmaceutical composition of the present invention is not particularly limited, but as desired, eye drops, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, transdermal patch administration, oral administration, intranasal administration, intrapulmonary administration, It may be administered through a route such as rectal administration, and specifically, may be administered through a route of eye drop administration.
  • the present invention provides a health functional food for preventing or improving dry eye syndrome comprising an extract of E. coli muscle or a fraction thereof as an active ingredient.
  • Kwon Keun-Geun In the health functional food of the present invention, the definition of Kwon Keun-Geun, fractions, and dry eye is as defined above.
  • the term "improvement” refers to any action in which dry eye syndrome improves or advantageously changes by oral administration of the composition.
  • the term "functional" means to obtain a useful effect in health applications such as nutrient control or physiological action on the structure and function of the human body.
  • the health functional food of the present invention can be prepared by a method commonly used in the art, and the preparation can be prepared by adding raw materials and ingredients commonly added in the art.
  • the formulation of the health functional food can also be prepared without limitation as long as the formulation is recognized as a health functional food.
  • the health functional food of the present invention can be prepared in various forms of formulation, unlike the general medicine has a merit and excellent portability, such as no side effects that can occur when taking a long-term use of the drug as a raw material, the present invention Dietary supplements are available as supplements to enhance the effect of preventing or improving dry eye syndrome.
  • the health functional food is added to the food material, such as beverages, teas, spices, gums, confections, etc., or the food prepared by encapsulation, powdered, suspension, etc. If you mean to bring a specific effect on health, unlike general medicine has the advantage that there is no side effect that can occur when taking long-term use of the drug as a raw material.
  • the butanol fraction of K. koji muscle is administered, in the high concentration group (1.0 mg / mL) three days after administration, the low concentration group (0.5 mg / mL) and the high concentration group (1.0 mg / mL) 5 days after administration.
  • tear secretion was significantly increased, which was found to be similar to the drug used most often for dry eye syndrome (FIG. 2).
  • the extract Kho Keun-Geun or fractions thereof may be usefully used as a health functional food for preventing or improving dry eye or eye fatigue.
  • Ethanol was added to the dried and fine spaghetti in the shade, and extracted repeatedly at room temperature in an extraction container, and then concentrated under reduced pressure at 40 ° C. to obtain an ethanol extract.
  • the extract was filtered and concentrated under reduced pressure. At this time, the temperature was maintained at about 40 °C concentration to prevent decomposition and hydrolysis of the components.
  • NOR non-surgical normal group
  • POCU7B elongated muscle butanol fraction
  • POCU7b low concentration
  • POCU7b-0.5 drug administration group administered 1.0 mg / ml of the butanol fraction
  • the control drug is hyaluronic acid (Haluronic acid; HL 1 mg / ml, Hallim Pharmaceutical, Korea) and carboxymethyl cellulose (CC 5 mg / ml), the most commonly used drug for dry eye , DI Clear, DIH Korea, Korea) consisted of a control group 1 administration group using two drugs, a control group 2 administration group.
  • the drug containing the E. coli butanol fraction of the present invention was prepared by dissolving at the above concentration in sterile saline containing 0.5% DMSO, and dropping 1 drop (drop) on both eyes every morning and afternoon. Each drug was applied twice a day to the control group, and only vehicle was applied to the normal and disease groups. After 3 and 5 days of drug administration, the tear amount was measured by the same tear amount measurement method as that described in Example 2.1.
  • the tear secretion was measured after instillation of POCU7B and the reference drug for 3 days. A significant increase in tear secretion was observed in the concentration administration group.
  • the control drug HL and CC also showed a significant increase in tear secretion and the efficacy was similar to the drug administration high concentration group (Fig. 2).
  • composition of the experimental group and the administration of the drug were performed in the same manner as in Example 2.2.
  • the cornea was anesthetized and photographed using a stereoscopic microsope (Olympus, Japan) with a fiberoptic ring illuminator.
  • the morphological changes of the corneas were evaluated by scoring the circular illuminators reflected from the corneal epithelial cells from 0 to 5 for the degree of distortion of round circles. 0 points: no distortion, 1 point: dent at 1/4 area, 2 points: dent at 2/4 area, 3 points: dent at 3/4 area, 4 points: dent at all parts, 5 points: severe dent Unable to recognize the shape of a round circle.

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Abstract

La présente invention concerne une composition pharmaceutique contenant un extrait ou une fraction d'extrait de Reynoutria japonica à titre de principe actif pour prévenir ou traiter le syndrome de l'œil sec, et un aliment fonctionnel pour la santé qui contient ledit extrait ou fraction d'extrait de Reynoutria japonica à titre de principe actif pour prévenir ou soulager le syndrome de l'œil sec. L'extrait ou la fraction d'extrait de Reynoutria japonica selon la présente invention peut significativement supprimer la réduction de la quantité de larmes sécrétées et le changement de forme de la cornée résultant du syndrome de l'œil sec, et peut par conséquent être largement utilisé dans le développement d'une composition pharmaceutique destinée à prévenir ou à traiter la fatigue oculaire et le syndrome de l'œil sec.
PCT/KR2018/006659 2017-06-13 2018-06-12 Composition contenant un extrait ou une fraction d'extrait de reynoutria japonica pour prévenir et traiter le syndrome de l'œil sec WO2018230942A1 (fr)

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KR1020170074403A KR20180136039A (ko) 2017-06-13 2017-06-13 호장근 추출물 또는 이의 분획물을 포함하는 안구건조증 예방 및 치료용 조성물
KR10-2017-0074403 2017-06-13

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WO2020111788A1 (fr) * 2018-11-28 2020-06-04 삼일제약주식회사 Préparation solide contenant un extrait de polygonum cuspidatum pour administration orale et ayant une stabilité améliorée, et son procédé de préparation
KR102310990B1 (ko) * 2019-10-16 2021-10-13 한국한의학연구원 호장근 지상부 추출물을 유효성분으로 포함하는 전안부질환의 예방 또는 치료용 조성물

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KR101764786B1 (ko) * 2015-12-30 2017-08-07 한국 한의학 연구원 호장근 추출물 또는 이의 분획물을 포함하는 안구건조증 예방 및 치료용 조성물

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