WO2023210880A1 - Composition comprising ginsenoside compound k or complex ginsenoside composition for preventing or treating periodontal disease - Google Patents
Composition comprising ginsenoside compound k or complex ginsenoside composition for preventing or treating periodontal disease Download PDFInfo
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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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- 229960000414 sodium fluoride Drugs 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
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- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Images
Classifications
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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
[Objective]: To provide a natural product-derived composition having little or no side effects and exhibiting activity to prevent, treat, or alleviate periodontal disease [Solution]: The present inventors found that ginsenoside compound K, derived from red ginseng or the like, or a complex ginsenoside composition, in which ginsenoside compound K, ginsenoside Rg3 (R+S), ginsenoside F2, ginsenoside Rh2, and ginsenoside Rb1 are mixed, exhibited a remarkable effect on the inhibition of causative bacteria of periodontal disease. The composition can be used as an oral composition including toothpaste and mouthwash, as well as a pharmaceutical composition for preventing or treating periodontal disease, and can also be applied to a food composition, such as gum, a beverage, or confectionery.
Description
본 발명은 홍삼에서 추출 및/또는 가공한 복합 진세노사이드 조성물 또는 진세노사이드 화합물 K를 포함하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.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.
잇몸 질환은 주로 30대 이후에 발생하여 중년에 들어서는 이가 빠지거나 다른 관련 질환을 일으키는 원인이 된다. 잇몸 질환은 치아를 떠받들고 있는 치아 주위 조직에 염증이 생기는 질환으로서, 치주질환에 이환되게 되면 임상적으로 치은출혈과 종창, 치주낭의 형성 및 치조골의 파괴 등으로 인하여 치아가 상실될 수 있다. 치주질환의 원인으로는 국소적요인과 전신적요인이 있는데, 국소적 요인으로 치태(dental plaque)가 치주낭 내에 기계적으로 축적되면 주변에 존재하는 세균들의 서식처가 되고, 서식하는 세균은 점차 호기성, 통기성, 그람 양성 세균에서 혐기성 그람음성 세균으로 점차 이행되며, 치주낭의 심부로 증식하게 된다. 이때 증식된 혐기성 그람음성 세균의 독소 및 산물이 직접 조직을 파괴하거나 면역계를 자극하여 자극된 면역계에서부터 여러 작용에 의하여 치주조직 파괴 및 염증을 유발하게 된다. 치태가 6개월 이상 경과하는 경우에는 칫솔로는 제거할 수 없는 딱딱한 치석으로 변하게 된다. 치태와 치석을 제거하지 않을 경우 치아의 잇몸 분리가 계속되어 음식물 찌꺼기가 모이는 공간이 형성되며 치아를 제자리에 고정시켜주는 주위조직의 파괴를 초래할 수 있다.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. At this time, 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.
본 발명에서는 위와 같은 과정으로 발생하는 잇몸 질환 또는 치주질환을 구강 내 염증을 유발하는 경우를 통칭하는 의미로 사용하였으며, 예컨대 치주염, 치은염, 풍치, 지치우위염, 치주농양, 치은증식증, 치근막염, 마모증 또는 교모증 등을 포함한다.In the present invention, 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.
비교적 발생빈도가 높은 치주질환은 만성치은염, 만성치주염, 소년치주염, 급성괴저성궤양성치은염을 예로 들 수 있다. 치주질환은 치아우식증과 마찬가지로 구강 내에 존재하는 세균에 의해 야기되는데, 치은연상 치면세균막(Supragingival plaque) 내에 있는 세균은 치은염(gingivitis)발생과 연관이 깊고, 치은연하 치면세균막(Subgingival plaque)의 세균은 치주염(Periodontitis)의 발생과 관련이 깊다고 알려져 있다. 치주염은 치은염과 함께 발생되나 모든 치은염이 치주염으로 진행되는 것은 아니다.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.
치아우식증을 일으키는 세균과 치주질환을 일으키는 세균은 종이 다른 것으로 알려져 있으며, 치아우식 원인균은 호기성 균인 반면, 치주질환을 일으키는 균은 혐기성균으로서, 대표적인 치주질환 원인균은 프로피로모나스 진지발리스 (Prophyromonas gingivalis), 프레보텔라 인테르메디아 (Prevotella intermedia), 악티노바실러스 악티노미세템코미탄스 (Actinobacillus actinomycetemcomitans), 에이케넬라 코로덴츠 (Eikenella corrodents), 푸소박테리움 누클레아툼 (Fusobacterium nucleatum), 박테리오이데스 포르시티우스 (Bacteroides forsythius), 캄피박테렉투스 트레포네마 (Campybacterrectus, Treponema (spirochetes)) 등인 것으로 보고되었다. 치주질환 중 특히 치은염은 대부분 치은의 염증성 변화에 의해서 발생되며, 이때 적절한 관리를 통해 원상태로 회복할 가능성이 있다.It is known that 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. Among periodontal diseases, 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.
위와 같이, 치아우식증과 마찬가지로 치주질환 또한 감염성 질환으로서 다양한 요인에 의해 발생하게 되며, 치주질환은 병원균의 작용과 숙주방어체계에 의해 일정 기간 동안 질병의 진행과 회복이 순환단계를 거치게 되는데, 치아우식증의 경우와는 달리 이 과정에 영양요인이 치주병 발생에 좀 더 미묘한 역할을 담당하는 것으로 알려져 있다. 즉, 치주질환은 적절한 영양섭취를 통해 감염을 예방하고 상처치유를 촉진시킬 수 있는 일련의 과정을 따른다.As above, like dental caries, 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.
치주질환의 예방을 위하여 불소 화합물, 클로로헥시딘 글루코네이트, 트리클로산 등을 일반적으로 적용하고 있으나, 이 성분들은 부작용의 우려가 높고 내성 균주가 생기는 문제가 발생할 수 있다. 최근에는 이러한 문제점을 해결하기 위하여 치주질환의 예방 또는 치료에 생약재를 비롯한 천연 성분을 이용하려는 시도가 활발해지고 있으며, 다양한 천연 성분 추출물이 치주질환 예방 및/또는 치료용으로 구강조성물, 약학 조성물 등에 응용되고 있다.To prevent periodontal disease, fluorine compounds, chlorhexidine gluconate, triclosan, etc. are generally used, but these ingredients have a high risk of side effects and may cause problems with the development of resistant strains. Recently, in order to solve these problems, attempts to use natural ingredients, including herbal medicines, for the prevention or treatment of periodontal disease are becoming more active, and various natural ingredient extracts are applied to oral compositions, pharmaceutical compositions, etc. for the prevention and/or treatment of periodontal disease. It is becoming.
대한민국 특허 제2344605호는 매스틱 검이 포집된, 인삼 사포닌 추출물에 β-글루카나제를 혼합하여 제조된 부분가수분해 진세노사이드로서, 상기 부분가수분해 진세노사이드는 F2, Rg1, F1, Rf 및 Rg2를 포함하고 및 용제로서 인지질을 포함하는 지질나노입자를 유효성분으로 함유하는 잇몸 질환의 예방 또는 치료용 조성물을 개시한다.Republic of Korea Patent No. 2344605 is a partially hydrolyzed ginsenoside prepared by mixing β-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.
대한민국 공개특허 2016-124007호는 진세노사이드 Rg3의 진세노사이드 Rb1에 대한 중량비가 0.20 이상인 삼칠 및 숙지황의 복합 추출물을 유효성분으로 함유하는 치주염 예방 또는 치료용 약학적 조성물을 개시한다.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.
본 발명은 부작용이 적거나 없으며 좀 더 높은 치주질환의 예방 및/또는 치료 효과를 나타내는 천연 물질 유래 조성물을 제공하는 것을 목적으로 한다.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.
또한, 본 발명은 상기 천연 물질 유래 조성물을 함유하는 치주질환 예방 및/또는 치료용 약학 조성물을 제공하는 것을 목적으로 한다.In addition, the present invention aims to provide a pharmaceutical composition for preventing and/or treating periodontal disease containing the composition derived from the natural material.
또한, 본 발명은 상기 천연 물질 유래 조성물을 함유하는 치주질환 예방 및/또는 개선용 식품 조성물을 제공하는 것을 목적으로 한다.In addition, the present invention aims to provide a food composition for preventing and/or improving periodontal disease containing the composition derived from the natural material.
본 발명자들은 홍삼 또는 인삼으로부터 추출한 진세노사이드 화합물 K 또는 용매를 사용하여 홍삼 또는 인삼으로부터 복합 진세노사이드를 추출하고 이를 흡착수지에 흡착한 후 용매로 탈착하여 부분 정제하여 홍삼 농축물을 혼합한 복합 진세노사이드 조성물 (이하 본 발명의 설명, 도면에서 "BTEX-K"와 혼용함)이 농도별로 치주질환 원인균에 대한 항균력을 나타냄을 밝히고, 이 조성물들을 포함하는 치주질환 예방 또는 치료용 약학 조성물, 치주질환 예방 또는 개선용 치약 조성물, 치주질환 예방 또는 개선용 구강세척제 조성물 및 치주질환 예방 또는 개선용 식품 조성물을 발명하였다.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.
상기 치주질환은 구강 내 염증을 유발하는 경우라면 특별히 제한되지 않으며, 예를 들어, 치은염, 치주염, 풍치, 지치우위염(사랑니염), 치주농양, 치은증식증, 부정교합, 치근막염, 마모증 또는 교모증 등을 포함할 수 있다.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.
본 발명의 진세노사이드 화합물 K 또는 복합 진세노사이드 조성물 BTEX-K는 치면 세균막 감소 및 치면 유기산 생성 억제 효과를 나타냈다.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.
도 1은 진세노사이드 화합물 K (Compound-K)와 복합 진세노사이드 조성물 BTEX-K 화합물 농도별 처리에 따른 항균력 결과 (페이퍼 디스크 방법)이다 ((좌) P.intermedia, (우) P.gingivalis).
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 ).
도 2는 진세노사이드 화합물 K와 복합 진세노사이드 조성물 BTEX-K 농도별 처리에 따른 항균력 결과 (광학 밀도 측정법)이다 (*p<0.05, **p<0.01, ***p<0.001은 EtOH 그룹과 비교함).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).
도 3은 P.gingivalis 에 대한 진세노사이드 화합물 K와 복합 진세노사이드 조성물 BTEX-K의 항균력 결과이다 (**p<0.01, ***p<0.001은 EtOH 그룹과 비교함).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).
본 발명은 This invention
(가) 진세노사이드 화합물 K; 또는(A) Ginsenoside compound K; or
(나) 진세노사이드 화합물 K 100중량부에 대하여 진세노사이드 Rg3(R+S), 진세노사이드 F2, 진세노사이드 Rh2 및 진세노사이드 Rb1이 각각 7 중량부 이상 함유된 복합 진세노사이드 조성물 (이하 명세서 및 도면에서 "BTEX-K"와 혼용함);을 유효성분으로 함유하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.(B) 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.
또한, 본 발명은 상기 나)의 복합 진세노사이드 조성물이In addition, the present invention relates to the complex ginsenoside composition of b) above.
1) 홍삼을 추출 및 농축하여 홍삼 농축물을 얻는 단계; 1) Extracting and concentrating red ginseng to obtain red ginseng concentrate;
2) 홍삼 농축물을 용해시킨 후 합성흡착수지 컬럼에 통과시켜 흡착한 후 에탄올로 탈착하여 진세노사이드 Rb1, Rb2, Rc 및 Rd를 포함하는 복합 진세노사이드를 얻는 단계;2) dissolving the red ginseng concentrate, passing it through a synthetic adsorption resin column, adsorbing it, and then desorbing it with ethanol to obtain complex ginsenosides containing ginsenosides Rb1, Rb2, Rc and Rd;
3) 복합 진세노사이드를 알파-갈락토시다제로 처리하여 발효 복합 진세노사이드를 얻는 단계; 및3) obtaining fermented complex ginsenosides by treating the complex ginsenosides with alpha-galactosidase; and
4) 상기 1) 단계에서 얻은 홍삼 농축물에 상기 3) 단계에서 얻은 발효 복합 진세노사이드를 가하여 복합 진세노사이드 조성물을 얻는 단계;를 거쳐 얻어지는 것을 특징으로 하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.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.
상기 합성흡착수지 컬럼은 특별한 제한은 없으나 다공성 흡착수지 컬럼이 바람직하며, 더욱 바람직하게는 HP2MG 또는 HP-20 중 하나 이상임을 특징으로 한다.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.
또한, 본 발명에서 상기 복합 진세노사이드 조성물은In addition, in the present invention, the complex ginsenoside composition is
a) 진세노사이드 화합물 K 100mg/g 이상이거나 또는 a) Ginsenoside compound K is 100mg/g or more, or
b) 진세노사이드 화합물 K 100mg/g 이상, 진세노사이드 Rg3(R+S), 진세노사이드 F2, 진세노사이드 Rh2 및 진세노사이드 Rb1이 각각 8mg/g 이상 함유되는 것을 특징으로 하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.b) 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.
또한, 본 발명에서 상기 진세노사이드 화합물 K 또는 상기 복합 진세노사이드 조성물은 치주질환을 일으키는 미생물의 생육을 억제하는 것을 특징으로 하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.In addition, in the present invention, 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.
또한, 본 발명에서 상기 진세노사이드 화합물 K는 100㎍/㎖ 내지 1mg/㎖ 또는 상기 복합 진세노사이드 조성물은 500㎍/㎖ 내지 5mg/㎖임을 특징으로 하는, 치주질환 예방 또는 치료용 조성물에 관한 것이다.In addition, in the present invention, the ginsenoside compound K is 100㎍/㎖ to 1mg/㎖ or the composite ginsenoside composition is 500㎍/㎖ to 5mg/㎖. will be.
또한, 본 발명에서 상기 1), 2) 및 4) 단계의 홍삼 농축물은 분말 상태 또는 액상임을 특징으로 하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.In addition, 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.
또한, 본 발명에서 상기 진세노사이드 화합물 K 또는 복합 진세노사이드 조성물은 액상, 크림상, 페이스트상 또는 고체상임을 특징으로 하는 치주질환 예방 또는 치료용 조성물에 관한 것이다.In addition, 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.
또한, 본 발명은 상기 치주질환 예방 또는 치료용 조성물을 포함하는 치주질환 예방 또는 치료용 약학 조성물에 관한 것이다.In addition, the present invention relates to a pharmaceutical composition for preventing or treating periodontal disease, including the composition for preventing or treating periodontal disease.
상기 진세노사이드 화합물 K 및/또는 복합 진세노사이드 조성물 BTEX-K를 유효성분으로 함유하는 치주질환 예방 또는 치료용 약학 조성물은 약제학적 분야에서 통상적으로 허용되는 담체와 함께 배합하여 통상적인 방법에 의해 주사형태, 경구투여, 도포제 형태 등으로 제형화할 수 있다. 예를 들면 액제, 시럽제, 캡슐제, 과립제, 분말, 연고, 에멀젼, 겔, 크림 등으로 제제화할 수 있으며, 이를 여러 경로로 투여할 수 있다. 여러 가지 제형 중 예컨대, 주사용 조성물은 등장성 수용액 또는 현탁액이 바람직하고, 언급한 조성물은 멸균되고/되거나 보조제(예: 방부제, 안정화제, 습윤제 또는 유화제 용액 촉진제, 삼투압 조절을 위한 염/또는 완충제)를 함유한다. 또한, 이들은 기타 치료적으로 유용한 물질을 함유할 수 있다. 약제학적으로 허용 가능한 담체에는 유당, 포도당, 자당, 소르비톨, 마니톨, 전분, 검 아카시아, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미세결정 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 미네랄 오일 등이 포함된다. 상기 조성물에는 또한 윤활제, 웨팅제, 풍미제, 유화제 및 방부제 등이 더 포함될 수 있다. 본 발명의 조성물은 과립제, 산제, 액제, 정제, 캅셀제 또는 건조 시럽제 등의 경구용 제제 또는 주사제 등의 비경구용 제형으로 제제화할 수 있으나, 이러한 제형에 한정되는 것은 아니다.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. Among various dosage forms, for example, 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. 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.
이와 같이 제조된 약제학적 제제는 목적하는 바에 따라 피하 투여, 근육 투여 또는 경구투여, 정맥 투여, 구강 도포, 잇몸 도포 등으로 투여할 수 있으며, 용량은 일일 투여량이 0.001㎍/㎏~100㎎/㎏의 양을 1 내지 수회에 나누어 투여할 수 있다. 특정 환자에 대한 투여용량 수준은 환자의 체중, 연령, 성별, 건강상태, 투여시간, 투여방법, 질환의 중증도 등에 따라 변화될 수 있다.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㎍/㎏~100㎎/㎏. 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.
또한, 상기 진세노사이드 화합물 K 및/또는 복합 진세노사이드 조성물 BTEX-K를 유효성분으로 함유하는 치주질환 예방 또는 치료용 약학 조성물은 특히 잇몸 도포 또는 구강 도포용 외용제임을 특징으로 한다. 본 발명의 치주질환 예방 또는 치료용 조성물을 유효성분으로 하는 도포제는 통상적인 제조방법에 따라 어떤 형태로든 용이하게 제조할 수 있다. 일례로서 크림형 도포제를 제조함에 있어서는 일반적인 수중유형(O/W) 또는 유중수형(W/O)의 크림 베이스에 본 발명의 항염증 조성물을 함유시키고 여기에 향료, 킬레이트제, 색소, 산화방지제, 방부제 등을 필요에 따라 사용하는 한편, 물성개선을 목적으로 단백질, 미네랄, 비타민 등 합성 또는 천연소재를 병용할 수 있다.In addition, 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. As an example, in manufacturing a cream-type coating agent, 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.
또한, 본 발명은 상기 치주질환 예방 또는 치료용 조성물을 포함하는 치주질환 예방 또는 개선용 치약 조성물에 관한 것이다.In addition, the present invention relates to a toothpaste composition for preventing or improving periodontal disease, including the composition for preventing or treating periodontal disease.
또한, 본 발명은 상기 치주질환 예방 또는 치료용 조성물을 포함하는 치주질환 예방 또는 개선용 구강세척제 조성물에 관한 것이다.In addition, the present invention relates to an oral wash composition for preventing or improving periodontal disease, comprising the composition for preventing or treating periodontal disease.
또한, 본 발명은 상기 치주질환 예방 또는 치료용 조성물을 포함하는 치주질환 예방 또는 개선용 식품 조성물에 관한 것이다.In addition, the present invention relates to a food composition for preventing or improving periodontal disease, including the composition for preventing or treating periodontal disease.
본 발명에서 사용된 용어 "식품"이란 영양소를 한 가지 또는 그 이상 함유하고 있는 천연물 또는 가공품을 의미하며, 바람직하게는 어느 정도의 가공 공정을 거쳐 직접 먹을 수 있는 상태가 된 것을 의미하며, 통상적인 의미로서, 식품, 식품 첨가제, 기능성식품, 건강기능식품, 건강보조식품 및 음료 등을 모두 포함할 수 있다. 본 발명의 식품 조성물은, 비제한적으로 각종 음료, 껌, 차, 과자, 비타민 복합체, 건강 보조식품 등의 형태로 제조될 수 있다. 본 발명의 식품 조성물의 바람직한 섭취량은 섭취하는 사람의 상태, 체중, 증상의 정도, 식품 형태, 섭취 기간에 따라 다르며, 적절하게 선택될 수 있다. 본 발명의 식품 조성물은 유효 성분이 1일 0.2㎎/㎏ 내지 200㎎/㎏으로 섭취되도록 하는 것이 최적의 효과를 위해 바람직하다.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.
또한, 본 발명은 상기 진세노사이드 화합물 K 또는 복합 진세노사이드 조성물을 유효성분으로 함유하는 치약 조성물에 관한 것이다. 메스틱오일, 프로폴리스 추출물, 피로인산나트륨, 플루오르화나트륨, 토코페롤아세테이트, 하이드록시아파타이트, 감미제, 점증제, 연마제, 습윤제 또는 계면활성제 등을 필요에 따라 부가하여 통상의 치약 조성물 제조 방법으로 제형화할 수 있다.Additionally, 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.
또한, 본 발명은 상기 진세노사이드 화합물 K 또는 복합 진세노사이드 조성물을 유효성분으로 함유하는 구강세척제 조성물에 관한 것이다. 가용화제, 습윤제, 계면활성제, 윤활제, 향료, 감미제, 방부제 또는 약효제 등을 필요에 따라 부가하여 통상의 구강세척제 조성물 제조방법에 따라 제형화할 수 있으며, 껌(gum), 구강 세정제, 구강 청결제, 구강용 스프레이, 구강용 연고제, 구강용 패치 또는 이들의 조합으로 이루어진 군에서 선택되는 제형으로 제조할 수 있다.Additionally, 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.
이하, 본 발명의 구체적인 방법을 실시예를 들어 좀 더 자세히 설명한다. 그러나 본 발명의 범위가 이들 실시예의 기재에만 한정되는 것이 아님은 본 발명이 속한 기술분야에서 통상의 지식을 가진 자에게 자명하다.Hereinafter, the specific method of the present invention will be described in more detail through examples. However, it is obvious to those skilled in the art that the scope of the present invention is not limited to the description of these embodiments.
시험 방법Test Methods
1.1 치주균 성장억제 (페이퍼 디스크 법)1.1 Inhibition of periodontal fungal growth (paper disk method)
① 균수가 105가 되도록 프로피로모나스 진지발리스 (P.gingivalis), 프레보텔라 인테르메디아 (P.intermedia)를 KCOM medium 1에서 혐기 조건으로 배양하였다.① Propyromonas gingivalis so that the number of bacteria reaches 10 5 ( P. gingivalis ), Prevotella intermedia ( P. intermedia ) Cultured under anaerobic conditions in KCOM medium 1.
② 위와 같이 배양된 균 일정량을 KCOM medium 1 고체배지에 접종 후 멸균된 면봉으로 배지 전체에 고르게 도말하였다.② A certain amount of bacteria cultured as above was inoculated into KCOM medium 1 solid medium and then evenly smeared over the entire medium with a sterilized cotton swab.
③ 아래 표 1의 화합물 K 또는 복합 진세노사이드 조성물 "BTEX-K"를 에탄올에 녹여 희석한 후 40 ul를 분취하여 페이퍼 디스크에 점적하여 말린 후 균이 도말된 고체배지의 일정한 구획에 올려놓았다. 대조군은 시료 추출물 대신 에탄올을 점적하였다.③ Compound K or the complex ginsenoside composition "BTEX-K" of Table 1 below was dissolved and diluted in ethanol, then 40 ul was aliquoted, spotted on a paper disk, dried, and placed on a certain section of the solid medium on which the bacteria had been spread. In the control group, ethanol was instilled instead of the sample extract.
번호number | 시료sample | 농도density |
1One | Compound KCompound K | 25 mg25mg |
22 | BTEX-K1BTEX-K1 | 200 mg200mg |
④ 37℃의 혐기성 배양기에서 24시간 동안 혐기 조건으로 배양하였다.④ Cultured under anaerobic conditions in an anaerobic incubator at 37°C for 24 hours.
⑤ 페이퍼 디스크 주위의 억제환을 측정하였다.⑤ The inhibition ring around the paper disk was measured.
1.2 치주균 성장억제 (광학 밀도 측정법)1.2 Inhibition of periodontal bacteria growth (optical densitometry)
① 균수가 105가 되도록 프로피로모나스 진지발리스 (P.gingivalis), 프레보텔라 인테르메디아 (P.intermedia)를 KCOM medium 1에서 혐기 조건으로 배양하였다.① Propyromonas gingivalis so that the number of bacteria reaches 10 5 ( P. gingivalis ), Prevotella intermedia ( P. intermedia ) Cultured under anaerobic conditions in KCOM medium 1.
② 배양된 균 일정량을 KCOM medium 1 액체배지에 접종하였다.② A certain amount of cultured bacteria was inoculated into KCOM medium 1 liquid medium.
③ 아래 표 2의 농도가 되도록 화합물 K 또는 복합 진세노사이드 조성물 "BTEX-K"를 액체 배양 배지에 첨가하였다. 대조군은 시료 추출물 대신 에탄올을 첨가하였다.③ 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.
번호number | 시료sample | 농도density |
1One |
Compound K |
200 ug/ml, 400 ug/ml200 ug/ml, 400 ug/ml |
22 | BTEX-K1BTEX-K1 | 1 mg/ml, 2 mg/ml1 mg/ml, 2 mg/ml |
④ 37℃의 혐기성 배양기에서 24시간 동안 혐기적으로 배양하였다.④ Cultured anaerobically in an anaerobic incubator at 37°C for 24 hours.
⑤ OD660 nm에서 흡광도를 측정하였다.⑤ Absorbance was measured at OD 660 nm .
2. 시험결과2. Test results
2.1 페이퍼 디스크 방법을 이용한 항균력 시험 결과2.1 Antibacterial activity test results using the paper disk method
KCOM medium 1 배지에서 혐기적으로 배양된 프로피로모나스 진지발리스 (P.gingivalis), 프레보텔라 인테르메디아 (P.intermedia)를 KCOM medium 1 고체배지에 도말한 후 화합물 K를 각 1, 5, 10, 20 ug씩 점적한 페이퍼 디스크를 올려놓은 다음 24시간 37℃ 혐기성 배양기에서 혐기적으로 배양한 결과, 억제환이 나타나지 않았다. BTEX-K 역시 페이퍼 디스크에 각 5, 10, 20, 50, 100 ug씩 점적한 후 말린 다음 균주를 도말한 배지에 올려놓고 24시간 배양하였으나, 억제환이 나타나지 않았다 (데이터 나타내지 않음).Propyromonas gingivalis cultured anaerobically in KCOM medium 1 medium ( P. gingivalis ), Prevotella intermedia ( P. intermedia ) After plating on KCOM medium 1 solid medium, paper disks onto which 1, 5, 10, and 20 ug of compound K were added were placed and then cultured anaerobically in an anaerobic incubator at 37°C for 24 hours. As a result, no inhibitory rings appeared. BTEX-K was also dropped on paper disks at 5, 10, 20, 50, and 100 ug each, dried, placed on the culture medium on which the strain was plated, and cultured for 24 hours, but no inhibitory ring appeared (data not shown).
결론적으로 시료의 농도가 너무 낮아 억제환이 나타나지 않은 것으로 판단하였다. 그리하여 페이퍼 디스크 방법이 아닌 광학 밀도 측정방법을 사용하여 항균력을 측정하기로 하였다.In conclusion, it was determined that the concentration of the sample was so low that no inhibitory ring appeared. Therefore, it was decided to measure antibacterial activity using the optical density measurement method rather than the paper disk method.
2.2 광학 밀도 측정방법을 이용한 항균력 시험 결과2.2 Antibacterial activity test results using optical density measurement method
프로피로모나스 진지발리스 (P.gingivalis), 프레보텔라 인테르메디아 (P.intermedia)의 경우 KCOM medium 1 배지에서 혐기적으로 배양된 균주들을 화합물 K가 200 ug/ml 의 농도로 맞춰진 KCOM medium 1 액체배지에 접종 후 37℃ 혐기성 인큐베이터에서 24시간 배양한 다음, 660 nm에서 흡광도를 측정하여 동량의 에탄올만을 넣은 배양액과 비교하였다. BTEX-K 역시 배양배지에 1 mg/ml 의 농도로 넣고 일정량의 배양된 프로피로모나스 진지발리스 (P.gingivalis), 프레보텔라 인테르메디아 (P.intermedia)를 접종하여 위에 언급한 방법으로 배양 후 흡광도를 측정하여 대조군과 비교하여 상대적인 항균력을 판단하였다.Propyromonas gingivalis ( P. gingivalis ) and 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 ℃ 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 ) were inoculated and cultured using the above-mentioned method, and then the absorbance was measured to determine the relative antibacterial activity compared to the control group.
그 결과, 프로피로모나스 진지발리스 (P.gingivalis)와 프레보텔라 인테르메디아 (P.intermedia)에서 화합물 K와 BTEX-K에 대한 항균력을 확인할 수 있었다. BTEX-K보다는 화합물 K에 대한 항균력이 두 균 모두 상대적으로 크게 나타났다. 특히, 프레보텔라 인테르메디아 (P.intermedia)에 대한 화합물 K의 항균력은 76%이며 BTEX-K의 항균력은 52%로 나타났다 (***p<0.001). 프로피로모나스 진지발리스 (P.gingivalis)에 대한 화합물 K와 BTEX-K의 항균력은 각각 29% (***p<0.01)와 9%로 나타났다.As a result, Propyromonas gingivalis ( P. gingivalis ) and Prevotella intermedia ( P. intermedia ), the antibacterial activity of compounds K and BTEX-K was confirmed. The antibacterial activity against Compound K was relatively greater for both bacteria than for BTEX-K. In particular, the antibacterial activity of Compound K against Prevotella intermedia ( P. intermedia ) was 76%, and that of BTEX-K was 52% ( ***p <0.001). Propyromonas gingivalis The antibacterial activity of compounds K and BTEX-K against ( P. gingivalis ) was 29% ( ***p <0.01) and 9%, respectively.
치주질환의 주요균인 프로피로모나스 진지발리스 (P.gingivalis)에 대한 고농도 홍삼 추출물의 항균력 확인을 위해 화합물 K는 400 ug/ml의 농도에서 항균력을 측정하였고 BTEX-K는 2 mg/ml의 농도에서 항균력을 재측정하였다.Propyromonas gingivalis, the main bacteria causing periodontal disease To confirm the antibacterial activity of high-concentration red ginseng extract against ( P. gingivalis ), the antibacterial activity of compound K was measured at a concentration of 400 ug/ml, and the antibacterial activity of BTEX-K was re-measured at a concentration of 2 mg/ml.
그 결과, 화합물 K의 경우 대조군 대비 약 55%의 항균력을 보였고, BTEX-K의 경우 34%의 항균력을 보였다. 또한, 홍삼 추출물의 농도가 높을수록 항균력이 증가함을 확인하였다.As a result, 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.
3. 고찰3. Considerations
치주 원인균에 대한 홍삼 추출물 화합물 K와 BTEX-K의 항균력을 확인한 결과 치주균 중 프레보텔라 인테르메디아 (P.intermedia)의 성장 억제력 (항균력)이 다른 치주균에 비해 우수하게 나타났다.As a result of confirming the antibacterial activity of red ginseng extract compound K and BTEX-K against periodontal pathogens, the growth inhibition (antibacterial activity) of Prevotella intermedia ( P. intermedia ) among periodontal bacteria was found to be superior to that of other periodontal bacteria.
치주질환의 주요균인 프로피로모나스 진지발리스 (P.gingivalis)의 경우 홍삼 추출물의 농도가 높일수록 큰 항균력을 보이는 것을 알 수 있었다.Propyromonas gingivalis, the main bacteria causing periodontal disease In the case of ( P. gingivalis ), it was found that the higher the concentration of red ginseng extract, the greater the antibacterial activity.
본 치주균 억제 실험을 위해 두 가지 방법이 사용되었으며, 페이퍼 디스크 방법과 광학 밀도 측정방법을 사용한 결과 페이퍼 디스크 방법보다 광학 밀도 측정방법이 항균력을 측정하는데 더 적합하였다.Two methods were used for this periodontal bacteria inhibition experiment, and as a result of using the paper disk method and the optical density measurement method, the optical density measurement method was more suitable for measuring antibacterial activity than the paper disk method.
본 발명의 진세노사이드 K 또는 복합 진세노사이드 조성물은 잇몸 질환 치료용 약학 조성물, 치약, 구강세척제를 비롯한 구강용 조성물로 이용 가능하며, 그 외에도 잇몸 질환 예방 또는 개선 용도로 껌, 음료, 과자 등의 식품 조성물에도 응용할 수 있다.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.
Claims (11)
- (가) 진세노사이드 화합물 K; 또는(A) Ginsenoside compound K; or(나) 진세노사이드 화합물 K 100중량부에 대하여 진세노사이드 Rg3(R+S), 진세노사이드 F2, 진세노사이드 Rh2 및 진세노사이드 Rb1이 각각 7 중량부 이상 함유된 복합 진세노사이드 조성물;을 유효성분으로 함유하는 치주질환 예방 또는 치료용 조성물.(B) 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 A composition for preventing or treating periodontal disease containing as an active ingredient.
- 청구항 1에 있어서,In claim 1,상기 나)의 복합 진세노사이드 조성물은The complex ginsenoside composition of b) above is1) 홍삼을 추출 및 농축하여 홍삼 농축물을 얻는 단계; 1) Extracting and concentrating red ginseng to obtain red ginseng concentrate;2) 홍삼 농축물을 용해시킨 후 합성흡착수지 컬럼에 통과시켜 흡착한 후 에탄올로 탈착하여 진세노사이드 Rb1, Rb2, Rc 및 Rd를 포함하는 복합 진세노사이드를 얻는 단계;2) dissolving the red ginseng concentrate, passing it through a synthetic adsorption resin column, adsorbing it, and then desorbing it with ethanol to obtain complex ginsenosides containing ginsenosides Rb1, Rb2, Rc and Rd;3) 복합 진세노사이드를 알파-갈락토시다제로 처리하여 발효 복합 진세노사이드를 얻는 단계; 및3) obtaining fermented complex ginsenosides by treating the complex ginsenosides with alpha-galactosidase; and4) 상기 1) 단계에서 얻은 홍삼 농축물에 상기 3) 단계에서 얻은 발효 복합 진세노사이드를 가하여 복합 진세노사이드 조성물을 얻는 단계;를 거쳐 얻은 것을 특징으로 하는 치주질환 예방 또는 치료용 조성물.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; A composition for preventing or treating periodontal disease, characterized in that obtained through the following steps.
- 청구항 1에 있어서,In claim 1,상기 복합 진세노사이드 조성물은 The complex ginsenoside composition isa) 진세노사이드 화합물 K 100mg/g 이상이거나 또는 a) Ginsenoside compound K is 100mg/g or more, orb) 진세노사이드 화합물 K 100mg/g 이상, 진세노사이드 Rg3(R+S), 진세노사이드 F2, 진세노사이드 Rh2 및 진세노사이드 Rb1이 각각 8mg/g 이상 함유되는 것을 특징으로 하는 치주질환 예방 또는 치료용 조성물.b) 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. Composition for prevention or treatment.
- 청구항 1에 있어서,In claim 1,상기 진세노사이드 화합물 K 또는 상기 복합 진세노사이드 조성물은 치주질환을 일으키는 미생물의 생육을 억제하는 것을 특징으로 하는 치주질환 예방 또는 치료용 조성물.The ginsenoside compound K or the composite ginsenoside composition is a composition for preventing or treating periodontal disease, characterized in that it inhibits the growth of microorganisms that cause periodontal disease.
- 청구항 1에 있어서,In claim 1,상기 진세노사이드 화합물 K는 100㎍/㎖ 내지 1mg/㎖ 또는 상기 복합 진세노사이드 조성물은 500㎍/㎖ 내지 5mg/㎖임을 특징으로 하는, 치주질환 예방 또는 치료용 조성물.A composition for preventing or treating periodontal disease, characterized in that the ginsenoside compound K is 100㎍/㎖ to 1mg/㎖ or the composite ginsenoside composition is 500㎍/㎖ to 5mg/㎖.
- 청구항 2에 있어서,In claim 2,1), 2) 및 4) 단계의 홍삼 농축물은 분말 상태 또는 액상임을 특징으로 하는 치주질환 예방 또는 치료용 조성물.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.
- 청구항 1 또는 청구항 2에 있어서,In claim 1 or claim 2,상기 진세노사이드 K 또는 복합 진세노사이드 조성물은 액상, 크림상, 페이스트상 또는 고체상임을 특징으로 하는 치주질환 예방 또는 치료용 조성물.The ginsenoside K or complex ginsenoside composition is a composition for preventing or treating periodontal disease, characterized in that it is in the form of liquid, cream, paste or solid.
- 청구항 1의 치주질환 예방 또는 치료용 조성물을 포함하는 치주질환 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating periodontal disease, comprising the composition for preventing or treating periodontal disease of claim 1.
- 청구항 1의 치주질환 예방 또는 치료용 조성물을 함유하는 치주질환 예방 또는 개선용 치약 조성물.A toothpaste composition for preventing or improving periodontal disease containing the composition for preventing or treating periodontal disease of claim 1.
- 청구항 1의 치주질환 예방 또는 치료용 조성물을 함유하는 치주질환 예방 또는 개선용 구강세척제 조성물.An oral wash composition for preventing or improving periodontal disease containing the composition for preventing or treating periodontal disease of claim 1.
- 청구항 1의 치주질환 예방 또는 치료용 조성물을 함유하는 치주질환 예방 또는 개선용 식품 조성물.A food composition for preventing or improving periodontal disease containing the composition for preventing or treating periodontal disease of claim 1.
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