WO2023210880A1 - Composition comprenant un composé de ginsénoside k ou une composition de ginsénoside complexe permettant de prévenir ou de traiter une maladie parodontale - Google Patents

Composition comprenant un composé de ginsénoside k ou une composition de ginsénoside complexe permettant de prévenir ou de traiter une maladie parodontale Download PDF

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WO2023210880A1
WO2023210880A1 PCT/KR2022/012484 KR2022012484W WO2023210880A1 WO 2023210880 A1 WO2023210880 A1 WO 2023210880A1 KR 2022012484 W KR2022012484 W KR 2022012484W WO 2023210880 A1 WO2023210880 A1 WO 2023210880A1
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Prior art keywords
ginsenoside
composition
periodontal disease
preventing
complex
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PCT/KR2022/012484
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English (en)
Korean (ko)
Inventor
오진환
허율
김진희
이현철
하유진
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주식회사 비티진
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Publication of WO2023210880A1 publication Critical patent/WO2023210880A1/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
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • 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
    • A23V2200/312—Foods, ingredients or supplements having a functional effect on health having an effect on dental health

Definitions

  • the present invention relates to a composite ginsenoside composition extracted and/or processed from red ginseng or a composition for preventing or treating periodontal disease containing ginsenoside compound K.
  • Gum disease usually occurs after the age of 30 and causes tooth loss and other related diseases in middle age. Gum disease is a disease in which inflammation occurs in the tissues around the teeth that support the teeth. Clinically, periodontal disease can lead to tooth loss due to gingival bleeding and swelling, formation of periodontal pockets, and destruction of alveolar bone. The causes of periodontal disease include local and systemic factors. When dental plaque mechanically accumulates within the periodontal pockets due to local factors, it becomes a habitat for bacteria existing in the surrounding area, and the bacteria living there gradually become aerobic, breathable, and It gradually transitions from Gram-positive bacteria to anaerobic Gram-negative bacteria and proliferates deep into the periodontal pocket.
  • the toxins and products of the proliferated anaerobic Gram-negative bacteria directly destroy the tissue or stimulate the immune system, causing periodontal tissue destruction and inflammation through various actions, including the stimulated immune system. If plaque persists for more than 6 months, it turns into hard tartar that cannot be removed with a toothbrush. If plaque and tartar are not removed, the separation of the gums from the teeth will continue, forming a space where food particles can collect, and may result in the destruction of the surrounding tissue that holds the teeth in place.
  • gum disease or periodontal disease occurring through the above process is used to collectively refer to cases that cause inflammation in the oral cavity, such as periodontitis, gingivitis, gum disease, gingivitis, periodontal abscess, gingival hyperplasia, periodontal fasciitis, Includes attrition or gliosis.
  • Periodontal diseases with relatively high incidence include chronic gingivitis, chronic periodontitis, juvenile periodontitis, and acute gangrenous ulcerative gingivitis.
  • Periodontal disease like dental caries, is caused by bacteria present in the oral cavity. Bacteria in the supragingival plaque are closely related to the development of gingivitis, and bacteria in the subgingival plaque are closely related to the development of gingivitis. It is known to be closely related to the occurrence of periodontitis. Periodontitis occurs together with gingivitis, but not all gingivitis progresses to periodontitis.
  • the bacteria that cause dental caries and the bacteria that cause periodontal disease are of different species.
  • the bacteria that cause dental caries are aerobic bacteria, while the bacteria that cause periodontal disease are anaerobic bacteria.
  • the representative bacteria that causes periodontal disease is Prophyromonas gingivalis . ), Prevotella intermedia , Actinobacillus actinomycetemcomitans , Eikenella corrodents , Fusobacterium nucleatum , Bacterioides It was reported to be Bacteroides forsythius , Campybacterrectus, Treponema ( spirochetes ), etc.
  • gingivitis in particular is mostly caused by inflammatory changes in the gingiva, and there is a possibility that it can be restored to its original state through appropriate management.
  • periodontal disease is also an infectious disease and is caused by various factors. Periodontal disease progresses and recovers through cyclical stages over a certain period of time due to the action of pathogens and the host defense system. Dental caries Unlike the case, nutritional factors are known to play a more subtle role in the development of periodontal disease in this process. In other words, periodontal disease follows a series of processes that can prevent infection and promote wound healing through appropriate nutritional intake.
  • Republic of Korea Patent No. 2344605 is a partially hydrolyzed ginsenoside prepared by mixing ⁇ -glucanase with ginseng saponin extract containing mastic gum, and the partially hydrolyzed ginsenoside is F2, Rg1, F1, and Rf. and Rg2 and lipid nanoparticles containing phospholipids as a solvent as an active ingredient.
  • Republic of Korea Patent Publication No. 2016-124007 discloses a pharmaceutical composition for preventing or treating periodontitis containing as an active ingredient a complex extract of Panax ginseng and Rehmannia glutinosa with a weight ratio of ginsenoside Rg3 to ginsenoside Rb1 of 0.20 or more.
  • the purpose of the present invention is to provide a composition derived from natural substances that has little or no side effects and exhibits a higher prevention and/or treatment effect of periodontal disease.
  • the present invention aims to provide a pharmaceutical composition for preventing and/or treating periodontal disease containing the composition derived from the natural material.
  • the present invention aims to provide a food composition for preventing and/or improving periodontal disease containing the composition derived from the natural material.
  • the present inventors extracted complex ginsenosides from red ginseng or ginseng using ginsenoside compound K or a solvent, adsorbed them on an adsorption resin, desorbed them with a solvent, partially purified them, and mixed them with red ginseng concentrate. It was revealed that the ginsenoside composition (hereinafter used interchangeably with "BTEX-K" in the description and drawings of the present invention) exhibits antibacterial activity against periodontal disease-causing bacteria at different concentrations, and a pharmaceutical composition for preventing or treating periodontal disease containing these compositions, A toothpaste composition for preventing or improving periodontal disease, a mouthwash composition for preventing or improving periodontal disease, and a food composition for preventing or improving periodontal disease were invented.
  • the periodontal disease is not particularly limited as long as it causes inflammation in the oral cavity, for example, gingivitis, periodontitis, gum disease, gingivitis (wisdom toothitis), periodontal abscess, gingival hyperplasia, malocclusion, periodontitis, attrition, or pyopilosis. May include proof, etc.
  • Ginsenoside compound K or complex ginsenoside composition BTEX-K of the present invention showed the effect of reducing bacterial film on dental surfaces and inhibiting the production of organic acids on dental surfaces.
  • Figure 1 shows the antibacterial activity results (paper disk method) according to the treatment of ginsenoside compound K (Compound-K) and complex ginsenoside composition BTEX-K compound concentration ((left) P. intermedia, (right) P. gingivalis ).
  • Figure 2 shows the results of antibacterial activity (optical density measurement) according to treatment at different concentrations of ginsenoside compound K and complex ginsenoside composition BTEX-K (*p ⁇ 0.05, **p ⁇ 0.01, ***p ⁇ 0.001 for EtOH compared to the group).
  • Figure 3 shows P. Results of antibacterial activity of ginsenoside compound K and complex ginsenoside composition BTEX-K against gingivalis ( **p ⁇ 0.01, ***p ⁇ 0.001 compared with EtOH group).
  • a complex ginsenoside composition containing 7 parts by weight or more of ginsenoside Rg3 (R+S), ginsenoside F2, ginsenoside Rh2, and ginsenoside Rb1 based on 100 parts by weight of ginsenoside compound K (hereinafter used interchangeably with “BTEX-K” in the specification and drawings); relates to a composition for preventing or treating periodontal disease containing as an active ingredient.
  • the present invention relates to the complex ginsenoside composition of b) above.
  • step 4) adding the fermented complex ginsenoside obtained in step 3) to the red ginseng concentrate obtained in step 1) above to obtain a complex ginsenoside composition; will be.
  • the synthetic adsorption resin column is not particularly limited, but is preferably a porous adsorption resin column, and more preferably is at least one of HP2MG or HP-20.
  • the complex ginsenoside composition is
  • Ginsenoside compound K is 100mg/g or more, or
  • Periodontal disease characterized by containing more than 100 mg/g of ginsenoside compound K and more than 8 mg/g of ginsenoside Rg3 (R+S), ginsenoside F2, ginsenoside Rh2, and ginsenoside Rb1, respectively. It relates to a composition for prevention or treatment.
  • the ginsenoside compound K or the composite ginsenoside composition relates to a composition for preventing or treating periodontal disease, characterized in that it inhibits the growth of microorganisms that cause periodontal disease.
  • the ginsenoside compound K is 100 ⁇ g/ml to 1mg/ml or the composite ginsenoside composition is 500 ⁇ g/ml to 5mg/ml. will be.
  • the present invention relates to a composition for preventing or treating periodontal disease, wherein the red ginseng concentrate in steps 1), 2) and 4) is in powder or liquid form.
  • the present invention relates to a composition for preventing or treating periodontal disease, wherein the ginsenoside compound K or the complex ginsenoside composition is in the form of liquid, cream, paste or solid.
  • the present invention relates to a pharmaceutical composition for preventing or treating periodontal disease, including the composition for preventing or treating periodontal disease.
  • the pharmaceutical composition for preventing or treating periodontal disease containing the ginsenoside compound K and/or the complex ginsenoside composition BTEX-K as an active ingredient is prepared by a conventional method by mixing it with a carrier commonly accepted in the pharmaceutical field. It can be formulated in the form of injection, oral administration, or liniment. For example, it can be formulated into liquid, syrup, capsule, granule, powder, ointment, emulsion, gel, cream, etc., and can be administered through various routes.
  • compositions for injection isotonic aqueous solutions or suspensions are preferred, and the compositions mentioned are sterilized and/or contain auxiliaries (e.g., preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, salts/or buffers for adjusting osmotic pressure). ) contains. Additionally, they may contain other therapeutically useful substances.
  • auxiliaries e.g., preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, salts/or buffers for adjusting osmotic pressure.
  • Pharmaceutically acceptable carriers include lactose, glucose, sucrose, sorbitol, mannitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, These include methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • the composition may further include lubricants, wetting agents, flavoring agents, emulsifiers, and preservatives.
  • the composition of the present invention can be formulated into oral preparations such as granules, powders, solutions, tablets, capsules, or dry syrups, or parenteral dosage forms such as injections, but is not limited to these dosage forms.
  • the pharmaceutical preparation prepared in this way can be administered subcutaneously, intramuscularly, orally, intravenously, orally, or gumally, depending on the purpose, and the daily dose is 0.001 ⁇ g/kg ⁇ 100mg/kg.
  • the amount can be administered in one to several divided doses.
  • the dosage level for a specific patient may vary depending on the patient's weight, age, gender, health status, administration time, administration method, and severity of the disease.
  • the pharmaceutical composition for preventing or treating periodontal disease containing the ginsenoside compound K and/or the complex ginsenoside composition BTEX-K as an active ingredient is characterized as an external preparation for application to the gums or oral cavity.
  • the coating agent containing the composition for preventing or treating periodontal disease of the present invention as an active ingredient can be easily manufactured in any form according to a conventional manufacturing method.
  • the anti-inflammatory composition of the present invention is contained in a general oil-in-water (O/W) or water-in-oil (W/O) cream base, and fragrance, chelating agent, pigment, antioxidant, Preservatives, etc. can be used as needed, while synthetic or natural materials such as proteins, minerals, and vitamins can be used together to improve physical properties.
  • the present invention relates to a toothpaste composition for preventing or improving periodontal disease, including the composition for preventing or treating periodontal disease.
  • the present invention relates to an oral wash composition for preventing or improving periodontal disease, comprising the composition for preventing or treating periodontal disease.
  • the present invention relates to a food composition for preventing or improving periodontal disease, including the composition for preventing or treating periodontal disease.
  • the term "food” used in the present invention refers to a natural product or processed product containing one or more nutrients, preferably in a state ready to be eaten directly after a certain degree of processing, and By definition, it can include food, food additives, functional foods, health functional foods, health supplements, and beverages.
  • the food composition of the present invention can be manufactured in the form of, but not limited to, various beverages, gum, tea, snacks, vitamin complexes, health supplements, etc.
  • the preferred intake amount of the food composition of the present invention varies depending on the condition of the person consuming it, body weight, severity of symptoms, food type, and intake period, and can be selected appropriately. For the optimal effect, the food composition of the present invention is preferably ingested with an active ingredient of 0.2 mg/kg to 200 mg/kg per day.
  • the present invention relates to a toothpaste composition containing the ginsenoside compound K or the complex ginsenoside composition as an active ingredient. It can be formulated using a conventional toothpaste composition manufacturing method by adding mestic oil, propolis extract, sodium pyrophosphate, sodium fluoride, tocopherol acetate, hydroxyapatite, sweetener, thickener, abrasive, wetting agent or surfactant as necessary. You can.
  • the present invention relates to a mouthwash composition containing the ginsenoside compound K or the complex ginsenoside composition as an active ingredient.
  • Solubilizers, humectants, surfactants, lubricants, flavorings, sweeteners, preservatives or medicinal agents can be added as needed to formulate the mouthwash composition according to a conventional oral wash composition manufacturing method.
  • Gum, mouthwash, mouthwash, It can be prepared as a formulation selected from the group consisting of oral spray, oral ointment, oral patch, or a combination thereof.
  • Compound K or complex ginsenoside composition “BTEX-K” was added to the liquid culture medium to achieve the concentration shown in Table 2 below. In the control group, ethanol was added instead of the sample extract.
  • Propyromonas gingivalis P. gingivalis
  • Prevotella intermedia P. intermedia
  • strains cultured anaerobically in KCOM medium 1 medium were inoculated into KCOM medium 1 liquid medium with compound K at a concentration of 200 ug/ml, and then 37 After culturing in an anaerobic incubator at °C for 24 hours, the absorbance was measured at 660 nm and compared with the culture containing only the same amount of ethanol.
  • BTEX-K was also added to the culture medium at a concentration of 1 mg/ml and a certain amount of cultured Propyromonas gingivalis was added to the culture medium.
  • P. gingivalis and Prevotella intermedia P. intermedia
  • Compound K showed an antibacterial activity of about 55% compared to the control group, and BTEX-K showed an antibacterial activity of 34%. In addition, it was confirmed that the antibacterial activity increased as the concentration of red ginseng extract increased.
  • the optical density measurement method was more suitable for measuring antibacterial activity than the paper disk method.
  • Ginsenoside K or complex ginsenoside composition of the present invention can be used in oral compositions including pharmaceutical compositions for treating gum disease, toothpaste, and mouthwash, and can also be used in gum, beverages, confectionery, etc. for preventing or improving gum disease. It can also be applied to food compositions.

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Abstract

L'objectif de la présente invention consiste : à fournir une composition dérivée d'un produit naturel ayant peu ou pas d'effets secondaires et présentant une activité de prévention, de traitement, ou de soulagement d'une maladie parodontale. À cet effet, les présents inventeurs ont découvert qu'un composé de ginsénoside K, dérivé de ginseng rouge ou similaire, ou qu'une composition de ginsénoside complexe, dans laquelle un composé de ginsénoside K, de ginsénoside Rg3 (R+S), de ginsénoside F2, de ginsénoside Rh2, et de ginsénoside Rb1 sont mélangés, présentait un effet remarquable sur l'inhibition de bactéries responsables de maladie parodontale. La composition peut être utilisée comme composition par voie orale, y compris un dentifrice et un bain de bouche, ainsi qu'une composition pharmaceutique de prévention ou de traitement d'une maladie parodontale, et peut également être appliquée à une composition alimentaire, telle qu'une gomme, une boisson, ou une confiserie.
PCT/KR2022/012484 2022-04-25 2022-08-22 Composition comprenant un composé de ginsénoside k ou une composition de ginsénoside complexe permettant de prévenir ou de traiter une maladie parodontale WO2023210880A1 (fr)

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KR1020220050792A KR20230151286A (ko) 2022-04-25 2022-04-25 진세노사이드 화합물 k 또는 복합 진세노사이드 조성물을 포함하는 치주질환 예방 또는 치료용 조성물
KR10-2022-0050792 2022-04-25

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20090087709A (ko) * 2008-02-13 2009-08-18 주식회사 한국인삼공사 사포닌을 유효성분으로 포함하는 치주질환의 치료용 조성물
KR101915058B1 (ko) * 2017-07-21 2018-11-06 건국대학교 산학협력단 신규 류코노스톡 메센테로이데스 균주 및 이를 이용한 염증성 질환 예방 또는 치료용 조성물
KR20190110283A (ko) * 2018-03-20 2019-09-30 (재) 순천천연물의약소재개발연구센터 새싹인삼을 이용한 컴파운드 k의 제조방법 및 이에 따라 제조된 컴파운드 k를 포함하는 항산화 및 항균용 조성물
KR20200019358A (ko) * 2018-08-14 2020-02-24 주식회사 비티진 충치균의 생육억제 작용을 갖는 진세노사이드 및 조성물

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20090087709A (ko) * 2008-02-13 2009-08-18 주식회사 한국인삼공사 사포닌을 유효성분으로 포함하는 치주질환의 치료용 조성물
KR101915058B1 (ko) * 2017-07-21 2018-11-06 건국대학교 산학협력단 신규 류코노스톡 메센테로이데스 균주 및 이를 이용한 염증성 질환 예방 또는 치료용 조성물
KR20190110283A (ko) * 2018-03-20 2019-09-30 (재) 순천천연물의약소재개발연구센터 새싹인삼을 이용한 컴파운드 k의 제조방법 및 이에 따라 제조된 컴파운드 k를 포함하는 항산화 및 항균용 조성물
KR20200019358A (ko) * 2018-08-14 2020-02-24 주식회사 비티진 충치균의 생육억제 작용을 갖는 진세노사이드 및 조성물

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SHARMA ANSHUL, LEE HAE-JEUNG: "Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities", BIOMOLECULES, vol. 10, no. 7, pages 1028, XP093102512, DOI: 10.3390/biom10071028 *

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