WO2019230996A1 - Composition permettant la prévention ou le traitement de maladies de la bouche - Google Patents

Composition permettant la prévention ou le traitement de maladies de la bouche Download PDF

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Publication number
WO2019230996A1
WO2019230996A1 PCT/KR2018/006033 KR2018006033W WO2019230996A1 WO 2019230996 A1 WO2019230996 A1 WO 2019230996A1 KR 2018006033 W KR2018006033 W KR 2018006033W WO 2019230996 A1 WO2019230996 A1 WO 2019230996A1
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WIPO (PCT)
Prior art keywords
oral
quasi
composition
drug composition
present
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PCT/KR2018/006033
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English (en)
Korean (ko)
Inventor
유정헌
이상화
Original Assignee
주식회사 엘지생활건강
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Priority to PCT/KR2018/006033 priority Critical patent/WO2019230996A1/fr
Application filed by 주식회사 엘지생활건강 filed Critical 주식회사 엘지생활건강
Priority to KR1020207037856A priority patent/KR102315355B1/ko
Priority to KR1020217033216A priority patent/KR102470030B1/ko
Priority to KR1020207034015A priority patent/KR102546767B1/ko
Priority to KR1020207037855A priority patent/KR102288921B1/ko
Priority to CN201880094107.3A priority patent/CN112236148A/zh
Priority to KR1020207037854A priority patent/KR102288920B1/ko
Priority to JP2020567022A priority patent/JP7206302B2/ja
Publication of WO2019230996A1 publication Critical patent/WO2019230996A1/fr
Priority to JP2022132595A priority patent/JP7321632B2/ja
Priority to JP2022132594A priority patent/JP7413465B2/ja
Priority to JP2022132596A priority patent/JP7412844B2/ja
Priority to JP2023217980A priority patent/JP2024038088A/ja

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Classifications

    • 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
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • 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 composition for preventing or treating oral diseases including natural compounds as an active ingredient, and more particularly, to a quasi-drug composition having the effect of preventing or improving dental caries, periodontal disease, toothache, syring and bad breath. will be.
  • the present invention also relates to pharmaceutical compositions, food compositions and compositions for oral cavity comprising natural compounds as active ingredients.
  • Healthy teeth are an important factor in determining quality of life, which is said to be one of the five folds.
  • dental diseases dental cavities and periodontal disease are high incidences worldwide, and various clinical symptoms such as pain, malignant dysfunction, destruction of periodontal tissue, bad breath and acute infections. It is known to be a major factor causing tooth loss and tooth loss, and the cause of oral disease is increasing due to changes in diet.
  • microorganisms exist in the human oral cavity, and these microorganisms are controlled by enzymes such as lysozyme secreted by saliva.
  • enzymes such as lysozyme secreted by saliva.
  • the oral environment rich in nutrients and water, is a good condition for microorganisms to grow, and the tongue and dental plaque provide an excellent habitat for microorganisms.
  • Some of these microorganisms are opportunistic bacteria and cause diseases such as dental caries, periodontal disease, and syphilis (dental hypersensitivity).
  • antibacterial method of inhibiting the proliferation of oral pathogens that cause dental caries, periodontal disease, bad breath and syring while living in plaque, and various kinds of antibacterial agents including antibiotics having bactericidal and bacteriostatic effects on oral pathogens, It has been developed as an inhibitor and treatment for periodontal disease, pulp and root canal infection.
  • antibacterial agents used in oral cleaning agents include Sangquinarine, Listerine, Peroxide, Chlorhexidine, etc., which have no clear effect on bacteria in the oral cavity.
  • the therapeutic effect on periodontal disease is less clear and the price is expensive
  • Listerin has a slight bacteriostatic effect with alcohol as the main ingredient, but it has a temporary effect in the oral cavity, and also has a harmful effect on tissues for long-term use. There are disadvantages that can appear.
  • chlorhexidine is known to be the best among the formulations known to date to prevent plaque formation and to prevent and treat periodontal disease.
  • chlorhexidine causes irritation to tissue, pigmentation and degeneration of tissues, and especially has a strong irritating taste and a bad smell.
  • myocerosis can be caused, there is a carcinogenic disadvantage that can not be used for a long time for the purpose of treatment or prevention, such as limited use in pregnant women.
  • artificially synthesized compounds through chemical reactions may cause side effects such as cytotoxicity or accumulation in the human body, and thus, studies on the pharmacological activity of natural compounds having a low possibility of side effects are required in terms of safety.
  • the present inventors conducted a study to derive a natural material excellent in preventing and improving oral diseases such as dental caries, periodontal disease, toothache, schizophrenia, and bad breath, without worrying about such side effects.
  • the natural compounds that can be used safely and safely in the body have antibacterial effects against dental caries and periodontal disease-inducing bacteria, toothache relieving effect through PGE2 inhibitory effect, gingivitis formation inhibitory effect, antiviral effect and bad breath removal effect.
  • the present invention was completed to complete the quasi-drug composition, the pharmaceutical composition, the food composition, and the composition for oral cavity using the same.
  • An object of the present invention is to provide a quasi-drug composition for the prevention or improvement of oral diseases comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases, including a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Still another object of the present invention is to provide a food composition for preventing or improving oral diseases including a natural compound or a food acceptable salt thereof as an active ingredient.
  • Still another object of the present invention is to provide a composition for oral cavity comprising a natural compound or an acceptable salt thereof as an active ingredient.
  • the quasi-drug composition comprising the natural compound of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient is excellent in preventing or improving oral disease.
  • the composition of the present invention is excellent in antimicrobial activity against dental caries and periodontal disease-inducing bacteria, concentration-dependent inhibition of pain and inflammation markers, inhibition of gingivitis formation, symptom suppression effect and bad breath removal effect It is excellent in utilization as a quasi-drug composition for the prevention or improvement of one or more oral diseases selected from the group consisting of dental caries, periodontal disease, syringe and bad breath.
  • the composition containing the natural compound of the present invention can be used as a pharmaceutical composition and a food composition.
  • the present invention solves the above problems and provides a quasi-drug composition for the prevention or improvement of oral disease comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient in order to achieve the object of the present invention.
  • a pharmaceutical composition for preventing or treating oral disease comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a food composition for preventing or improving oral disease comprising a natural compound or a food acceptable salt thereof as an active ingredient.
  • composition for oral cavity comprising a natural compound or an acceptable salt thereof as an active ingredient.
  • the present invention provides a quasi-drug composition
  • a quasi-drug composition comprising a natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the 'natural compound' refers to a substance which is directly made from organisms such as microorganisms, plants and animals, and can be extracted, separated or purified therefrom.
  • the natural compound albiflorin and astragalol Astragaloside I, Brassinolide, Eleutheroside E, Geniopicrin, Gramine, Liensinine, Macrantoidine B ( Macranthoidin B), Neohesperidin dihydrochalcone, Obacunone, Oxysophocarpine, Sclareolide, Sophoricoside, Sweroside , Synephrine and the like, but is not limited thereto.
  • the Albiflorin is an organic compound represented by the formula 1 and having a molecular formula C 23 H 28 O 11 , molecular weight 408.4.
  • the Astragaloside I is an organic compound represented by Chemical Formula 2 and having the molecular weight C 45 H 72 O 16 , molecular weight 869.0.
  • brassinolide is an organic compound represented by the formula (3) and having the molecular formula C 28 H 48 O 6 , molecular weight 480.6.
  • the Eleutheroside E is an organic compound represented by Chemical Formula 4 and having a molecular weight of C 34 H 46 O 18 , a molecular weight of 742.7.
  • the gentiopicrin is an organic compound represented by Chemical Formula 5 and having a molecular weight of C 16 H 20 O 9 , a molecular weight of 356.3.
  • the gramine is an organic compound represented by the formula 6 and having the molecular formula C 11 H 14 N 2 , molecular weight 174.
  • the liensinine is an organic compound represented by Chemical Formula 7 and having a molecular formula C 37 H 42 N 2 O 6 , molecular weight 610.7.
  • the macronoidin B (Macranthoidin B) is an organic compound represented by the formula (8) and has a molecular formula C 65 H 106 O 32 , molecular weight 1399.5.
  • the neohesperidin dihydrochalcone (Neohesperidin dihydrochalcone) is an organic compound represented by the formula 9 and having a molecular formula C 28 H 36 O 15 , molecular weight 612.5.
  • the Obacunone is an organic compound represented by Chemical Formula 10 and having a molecular weight of C 25 H 30 O 7 , a molecular weight of 455.
  • the Oxysophocarpine is an organic compound represented by Chemical Formula 11 and having a molecular weight of C 15 H 22 N 2 O 2 , a molecular weight of 262.4.
  • the Sclareolide is an organic compound represented by Chemical Formula 12 and having molecular formula C 16 H 26 O 2 , molecular weight 250.3.
  • the sophoricoside is an organic compound represented by Chemical Formula 13 and having molecular formula C 21 H 20 O 10 , molecular weight 432.
  • Sweroside is an organic compound represented by Chemical Formula 14 and having molecular formula C 16 H 22 O 9 , molecular weight 358.3.
  • the cinephrine (Synephrine) is an organic compound represented by the formula 15 and having a molecular formula C 9 H 13 NO 2 , molecular weight 167.2.
  • the present invention is not particularly limited to the method of obtaining the compound, and chemically synthesized by a method known in the art, or a commercially available material may be used.
  • the compounds of the present invention may exist in unsolvated as well as solvated forms.
  • the compounds of the present invention may exist in crystalline or amorphous form, and all such physical forms are included in the scope of the present invention.
  • the present invention provides a quasi-drug composition for preventing or ameliorating oral diseases, including the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention specifically comprises at least one oral cavity selected from the group consisting of dental caries, periodontal disease (periodonitis or gingivitis), toothache, syringe and bad breath comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the quasi-drug composition for disease prevention or improvement can be provided.
  • the 'natural compound' is as described above.
  • oral disease refers to various diseases occurring in the oral cavity, and the oral cavity refers to a space in the mouth connected to the pharynx from the anterior lip to the posterior bulb.
  • the oral disease is a disease occurring in the oral cavity is a concept including all irrespective of the condition, non-limiting examples of the oral disease is dental caries, periodontal disease (periodonitis or gingivitis), toothache, ache, bad breath Etc. can be mentioned.
  • tooth cavities is an infectious disease caused by bacteria inhabiting the tooth surface, also called tooth decay, and shows signs of erosion due to erosion of hard tissues of the tooth.
  • tooth enamel or enamel the milky white translucent and hard substance covering the surface of the head of the tooth and protecting the dentin of teeth. It is caused by the acid produced by the decomposition of sugar and starch by the oral pathogens in the mouth. Tooth decay of the tooth is damaged by tooth decay.
  • dental plaque plaque
  • Saliva forms a thin, sticky membrane on the teeth, and streptococcus sobrinus, a type of streptococci, on it.
  • Oral microorganisms such as Streptococcus sobrinus and Streptococcus mutans , attach to form biofilms, making dental plaques and thicker by Fusobacterium . Lose.
  • the dental caries of the present invention include all irrespective of the species causing the dental caries, specifically, Streptococcus mutans ( Streptococcus mutans ), Streptococcus sanguinis , Streptococcus sobrinus ( Streptococcus sobrinus ), Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus and one or more selected from the group consisting of lactic acid bacteria, more specifically Streptococcus It can be a mutans.
  • Streptococcus mutans is a type of streptococcus gram-positive bacteria, also called cavities.
  • the Streptococcus mutans proliferate only on the surface of the tooth, but the induction is not completed until about 30 months of age. Therefore, until this time, mutans bacteria are difficult to grow, as in infancy. If other oral bacteria settle in the mouth because they are not infected with mutans from the adult's mouth during infancy, it is difficult for new mutans to enter the already well-balanced oral ecosystem. Will be lowered. If you are already infected with the causative organism through the mouth of the adult, often brush your teeth and keep your mouth clean to help prevent tooth decay. However, once the mutans bacteria are established in the oral cavity, it is impossible to eradicate the mutans bacteria.
  • the size of the growth inhibition ring was measured, and in the case of the experimental group containing the compound, growth inhibition
  • the ring diameter of 10.0 mm or more exhibits a very good antimicrobial activity against Streptococcus mutans, confirming that the composition comprising the natural compound can be used for preventing or improving dental caries (Table 2).
  • gingival disease is a disease in which the gingival, periodontal ligament and bone tissue supporting the teeth are inflamed, which is also commonly referred to as vertigo, gingivitis and periodontitis depending on the severity of the disease. Divided into It is a relatively light and fast-recovering form of periodontal disease that is limited to the gums, ie soft tissues, is called gingivitis, and when this inflammation progresses to the gums and around the gum bone, it is called periodontitis.
  • the periodontal disease of the present invention includes all irrespective of the species causing the periodontal disease, specifically, Actinobacillus actinomycetem comitans, Porphyromonas gingivalis , Tanene At least one homogeneous selected from the group consisting of Tannerella forsythia , Treponema denticola , and Fusobacterium nucleatum , and more specifically, porphyromonas It may be a ballis.
  • the Pyromonas jinjivalis is a bacteroid (Bacteroide) flexible bacteria, gram-negative bacteria, anaerobic bacteria.
  • the porphyromonas gingivalis is found in the oral cavity in which periodontal disease has occurred, as well as in the upper gastrointestinal tract, respiratory tract and colon.
  • collagen is degraded by the bacteria's collagenase enzyme, which can invade gingival fibroblasts and survive under significant concentrations of antibiotics.
  • the fungus can invade gingival epithelial cells to survive for a long time.
  • the ring-ring diameter of 10.0 mm or more exhibits a very good antimicrobial activity against Porphyromonas gingivalis, confirming that the composition comprising the compound can be used for preventing or improving periodontal disease (Table 2).
  • the experimental group using the experimental group toothpaste containing the compound is excellent in the gingival inflammation inhibitory effect, even after 6 months It was confirmed that the bleeding inhibitory effect was maintained by maintaining a normal bleeding state, and the composition containing the natural compound could be used for preventing or improving periodontal disease including gingivitis (Table 4).
  • the “toothache” refers to pain in teeth when eating sweet foods or very cold or hot foods. Generally, not only the pain of teeth itself but also the periodontal tissues supporting the teeth on the jawbone Pain is also included. Pain usually occurs when chewing, swelling gums, and secretive smell. Toothache is a slightly different pain depending on the causative disease.In particular, the pain caused by dental caries is initially painless, but gradually progresses to deep nerve decay to the nerves in the tooth. Pain can be triggered, and if a tooth breaks or cracks, it can cause pain by stimulating the nerves as the teeth crack when touching or biting cold food.
  • a symptom refers to dentin hyperesthesia.
  • Sirin's symptoms are sensitive when the dentin of exposed teeth comes in contact with cold air or irritating foods, and is present in 60 to 98% of adults with periodontal disease. This symptom is caused by a tooth decay on the gum side due to incorrect brushing habits, excessive occlusal force, or acid dissolution, poor oral hygiene conditions, periodontal treatment, restorative treatment, and acidification of the tooth. May appear.
  • many of the tubules present in the dentin of the tooth are exposed to the outside. By exposing all the stimuli to the nerves in the pulp, they are more sensitive to the same stimulus and can cause pain.
  • Syringe symptoms can range from mild to intense, painful pain, and because of the nature of the teeth do not regenerate, painkillers and anti-inflammatory drugs are not a fundamental solution to the symptoms. Shirini symptoms can be seen throughout the entire tooth and may be confined to a specific area, such as the maxilla or mandible, or right or left. The most common areas are different depending on the cause, but mainly the fangs and small molar areas, the most severe pain area is more than 90% of the cervical area, the boundary between the gum and teeth.
  • compositions comprising natural compounds have confirmed that the sirin can be used for prophylactic or ameliorative purposes (Table 7).
  • oral breath is an odor derived from the oral cavity and adjacent organs, and 85 to 90% of the bad breath is derived from the oral cavity, particularly from the back of the tongue.
  • the main components of bad breath are volatile sulfur compounds, of which 90% of the total volatile sulfur compounds are hydrogen sulfide made from cysteine and methyl mercaptan and dimethyl sulfide made from methionine. These components are mainly produced by protein enzymes secreted by anaerobic bacteria, and the back of the tongue is the most important habitat. This area is not well cleaned by saliva, and there are many small depressions, which is a place where bacteria continue to live.
  • anaerobic bacteria The generation of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, but is also caused by oral diseases such as dental caries, periodontitis and dry mouth. Many types of anaerobic bacteria are involved in the development of bad breath, and non-limiting examples of the cause of bad breath include Porphyromonas gingivalis , which secrete many types and large amounts of enzymes.
  • the experimental group using the experimental group toothpaste containing the natural compound of the present invention is excellent in removing bad breath, the compound It was confirmed that the composition containing can be used for the prevention or improvement of bad breath (Table 8).
  • the quasi-drug composition of the present invention may include an oral quasi-drug.
  • Ingredients included in the quasi-drug composition of the present invention may include components commonly used in the quasi-drug composition for oral cavity as an active ingredient, for example, abrasives, wetting agents, binders, foaming agents, sweeteners, preservatives, medicinal ingredients, flavors Agents, dyes, solvents, brighteners, solubilizers or pH adjusters.
  • Oral quasi-drug composition of the present invention can be prepared in any formulation commonly prepared in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, oral spray, oral ointment, oral varnish It may have a formulation such as mouthwash, gum massage cream, but is not limited thereto.
  • the oral quasi-drug composition of the present invention when the oral quasi-drug composition of the present invention is a toothpaste formulation, it may include a humectant, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetening agent, a coloring agent, a preservative, an active ingredient, a solvent, a pH adjusting agent, and the like.
  • the wetting agent is a powder of the dentifrice component to prevent the toothpaste from being hardened in the air and glycerin, sorbet solution, propylene glycol, polyethylene glycol, etc. by mixing one or two or more of the total weight of the composition 1 to 60 weight %, Specifically 10 to 50% by weight can be used.
  • the foaming agent enhances the cleaning effect by dispersing the toothpaste in the oral cavity, and acts as a surfactant to clean the oral contamination.
  • Surfactants such as sodium lauryl sulfate, sodium lauryl sodium succinate, sodium alkyl sulfovacate, and sucrose fatty acid ester are used alone. Or by mixing two or more kinds of 0.5 to 10% by weight, specifically 0.5 to 5% by weight of the total weight of the composition can be used.
  • the binder is to prevent separation between the powder and the liquid component in the toothpaste, cellulose derivatives such as carboxymethyl cellulose sodium, methyl cellulose, hydroxy propyl cellulose and sodium alginate, carrageenan, xanthan gum and the like alone or in combination of two or more 0.1 to 5% by weight, specifically 0.3 to 2% by weight of the total weight of the composition can be used.
  • cellulose derivatives such as carboxymethyl cellulose sodium, methyl cellulose, hydroxy propyl cellulose and sodium alginate, carrageenan, xanthan gum and the like alone or in combination of two or more 0.1 to 5% by weight, specifically 0.3 to 2% by weight of the total weight of the composition can be used.
  • the abrasive is to remove the adhesion of the tooth surface without hurting the tooth surface and to polish the original teeth, calcium carbonate (CaCO 3 ), dicalcium phosphate (CaHPO 4 , CaHPO 4 2H 2 O), silicic anhydride (SiO 2 2H 2 O), aluminum hydroxide (Al (OH) 3 ), carium pyrophosphate, magnesium carbonate or the like alone or in combination of two or more of 1 to 60% by weight, specifically 10 to 50% by weight of the total weight of the composition Can be used.
  • the flavoring agent is to enhance the feeling of use by providing a refreshing and odor to the toothpaste, peppermint oil, spearmint oil, menthol, etc. alone or in combination of two or more of 1 to 60% by weight of the total weight of the composition, specifically 0.01 ⁇ 5% by weight can be used.
  • the sweetener is to remove the unpleasant taste caused by the raw material of the dentifrice and to improve the refreshing feeling, 1 to 60% by weight of the total weight of the composition alone, or by mixing two or more types of saccharic acid, aspartame, xylitol, licoriceic acid, and the like. 0.01 to 5% by weight can be used.
  • the active ingredient is for prevention of dental caries, prevention of periodontal disease, prevention of toothache, prevention of syringes and elimination of bad breath, fluoride, zinc chloride, chlorhexidine, aminocapronic acid, tranexamic acid, cetylpyrididium chloride, pyridoxine, Triclosan, tocopherol acetate, sodium monofluorophosphate, etc. can be used individually or in mixture of 2 or more types. In the present invention, the compound may be used as an additional active ingredient.
  • the quasi-drug composition of the present invention can be used alone or in duplicate, or can be used in combination with other quasi-drug compositions other than the present invention.
  • a pharmaceutical composition comprising the natural compound or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention is a pharmaceutical composition for preventing or treating at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodonitis or gingivitis), toothache, syringe and bad breath comprising the natural compound as an active ingredient Can be provided.
  • the natural compound, oral disease, dental caries, periodontal disease, toothache, siryi and bad breath are as described above.
  • composition of the present invention in the form of tablets, pills, powders, granules, capsules, suspensions, solvents, emulsions, syrups, aerosols, sterile injectable solutions and the like according to conventional methods for preventing and treating oral diseases Formulation is possible.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, gelatin, and the like. Can be. In addition to the simple excipients, lubricants such as magnesium stearate, talc can also be used.
  • Liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups, and various excipients, for example, wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Can be used.
  • Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories, and the like.
  • non-aqueous solvent and the suspension solvent vegetable oils such as propylene glycol, polyethylene glycol, olive oil, etc., injectable esters such as ethyl oleate, and the like can be used.
  • compositions of the present invention may further comprise a carrier, excipient or diluent.
  • Carriers, excipients or diluents include lactose, textose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxy Mineral oils such as propyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, flophyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, silicon dioxide and the like can be used. have.
  • the specific dosage of the pharmaceutical composition according to the present invention depends on factors such as the formulation method, the condition and weight of the patient, the sex of the patient, the age, the extent of the disease, the form of the drug, the route and duration of the administration, the rate of excretion, the sensitivity of the reaction, and the like. It can be variously selected by those skilled in the art, and the dosage and frequency do not limit the scope of the present invention in any aspect.
  • the pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. through various routes. All modes of administration can be expected and can be administered, for example, by oral, intravenous, intramuscular or subcutaneous injection.
  • the present invention provides a food composition comprising the natural compound or a food acceptable salt thereof as an active ingredient.
  • the present invention specifically provides a food composition for preventing or ameliorating at least one oral disease selected from the group consisting of dental caries, periodontal disease (periodonitis or gingivitis), toothache, syring and bad breath comprising the compound as an active ingredient. can do.
  • the natural compound, oral disease, dental caries, periodontal disease, toothache, siryi and bad breath are as described above.
  • the food composition may be used in the form of health functional food, but is not limited thereto.
  • the natural compound or food acceptable salt thereof contained in the food composition of the present invention may be included in the form of an animal or plant comprising the compound, an extract thereof, a fraction thereof, or a processed product thereof.
  • the composition may contain a food supplement acceptable food additives in addition to the active ingredient.
  • the "food supplement” means a component that can be added to food supplements, and can be appropriately selected and used by those skilled in the art as being added to prepare the health functional food of each formulation.
  • food additives include flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and fillers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners. , pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like, but is not limited to the kind of food additives of the present invention by the above examples.
  • the food composition of the present invention may include a health functional food.
  • the "health functional food” refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body.
  • the term “functionality” means obtaining useful effects on health purposes such as nutrient control or physiological effects 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.
  • Food composition of the present invention can be prepared in various forms of formulation, unlike the general medicine has the advantage that there is no side effect that can occur when taking a long-term use of the drug as a food raw material, excellent portability, Health functional foods can be taken as a supplement to prevent or improve oral disease.
  • the health functional food of the present invention can take, and may include all foods in a general sense, and may be mixed with terms known in the art such as functional foods.
  • the health functional food of the present invention may be prepared by mixing known additives with other appropriate auxiliary ingredients that may be included in the food according to the choice of those skilled in the art. Examples of foods that can be added include meat, sausages, breads, chocolates, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products, including ice cream, various soups, beverages, teas, drinks, alcoholic beverages and Vitamin complexes, and the like, can be prepared by adding to the juice, tea, jelly and juice prepared with the compound according to the present invention as a main component. It also includes foods used as feed for animals.
  • an antimicrobial activity experiment was performed. To determine the effect of inhibiting the growth of oral pathogens, the antimicrobial activity test was performed by using a paper disk test using Streptococcus mutans , a representative dental caries, and Porphyromonas gingivalis , a representative bacteria of periodontal disease. Was carried out.
  • the culture medium was incubated for 4 to 6 hours in the optimum medium of each bacterium to increase the turbidity of the culture medium.
  • 0.5 (1.5 ⁇ 10 8 ) was adjusted and 0.1 ml of each oral pathogen was evenly spread on a plate medium.
  • each of the compounds of Formulas 1 to 15 was inoculated at a sterilized paper disc (Whatman no. 5 paper, 8 mm diameter) at a concentration of 10 mg / disc, and then dried for 1 hour. Then, after culturing for 24 to 48 hours at the optimum temperature of each oral pathogen, the size (diameter mm) of growth-lowering ring was measured, and the results are shown in Table 2 below.
  • the group treated with the compounds of Formulas 1 to 15 has Streptococcus mutans and foreskin with a growth-lowering ring diameter of 9.5 mm or more for the two oral pathogens It showed fairly good antimicrobial activity against Lomonas gingivalis. Therefore, it was found that the compounds of Formulas 1 to 15 can be used for preventing or treating dental caries or periodontal disease.
  • sodium carboxymethylcellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silicas, sodium cocoyl isocyanate, dodysine and sweeteners, fragrances, coloring agents, and the like, which are generally used in preparing toothpaste, are used.
  • a control toothpaste was prepared, and an experimental toothpaste was prepared by containing 0.01 wt% of one compound of the compounds of Formulas 1 to 15 in the control toothpaste.
  • test subjects were divided into a control group and a test group, and the control group was trained to use the prepared control toothpaste three times a day before going to sleep 2 hours after eating, and the experimental group used the prepared test toothpaste three times a day at the same time.
  • the control group was trained to use the prepared control toothpaste three times a day before going to sleep 2 hours after eating
  • the experimental group used the prepared test toothpaste three times a day at the same time.
  • the gingivitis index was checked.
  • the gingivitis index is measured by inserting a periodontal probe into the gingival bulb and burning the probe around each tooth without applying force and measuring the bleeding state after 30 seconds. Scores were recorded according to the results shown in Table 4.
  • macrophages were inoculated at a concentration of 1.5 X 10 5 cells / ml in DMEM medium containing 10% FBS and incubated in a 24 well plate at 37 ° C. and 5% CO 2 for 24 hours. Then, after incubating for 24 hours by treating each of the concentration of LPS 1 ⁇ g / ml and the compounds of Formula 1 to 15 as an inflammation induction stimulator, PGE2 ELISA assay kit (Thermo SCIENTIFIC) was purchased and the supernatant PGE2 inhibitory ability was analyzed according to the concentrations of compounds of 1 to 15 (Table 5).
  • Subjects were 40 volunteers who had dentin hypersensitivity teeth and agreed to participate in the trial, with a total of 80 subjects. In addition, 20 males and 20 females were 20 to 50 years old. The subjects were not aware of the toothpaste contents and the total duration of the experiment was 2 weeks.
  • the experiment was performed by measuring the response of the subject after applying a temperature stimulus. Before conducting the experiment, check the sensitive areas of the dentin hypersensitivity teeth of each subject in advance, and drop the cold water of about 5 ° C. with a dropper on the aerobic area of the tooth, and then score the test according to the criteria shown in Table 6 below.
  • the experimental group was allowed to use the experimental toothpaste three times a day for two weeks, and after two weeks, drop the cold water of about 5 ° C with an eyedropper to score.
  • Statistical treatment was tested before and after the experiment 2 weeks stimulation scores by paired Student T test (paired Student-t test), the response scores after 2 weeks for temperature stimulation is shown in Table 7 below.
  • Score criteria for subjects after stimulation score Contents 0 points There is no discomfort. 1 point Slightly uncomfortable or cold 2 points Sour 3 points pain.
  • test subjects were selected and clinical trials were carried out. Prepared.

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Abstract

La présente invention concerne une composition pour prévenir ou traiter des maladies de la bouche comprenant un composé naturel, et, plus spécifiquement, une composition de quasi-médicament ayant pour effet de prévenir ou de soulager les caries dentaires, la maladie parodontale, les douleurs dentaires, la sensibilité dentaire, et l'halitose. La composition de la présente invention a une excellente activité antimicrobienne contre les bactéries à l'origine des caries dentaires et de la maladie parodontale ; inhibe la douleur et le marqueur d'inflammation PGE2, d'une manière dépendante de la concentration ; et est très efficace pour empêcher l'apparition de gingivite, supprimer les symptômes de la sensibilité dentaire et éliminer l'halitose, et offre ainsi un important potentiel d'utilisation en tant que composition quasi-médicamenteuse pour prévenir ou soulager une ou plusieurs maladies de la bouche appartenant au groupe constitué par les caries dentaires, la maladie parodontale, les douleurs dentaires, la sensibilité dentaire, et l'halitose. En outre, la composition de la présente invention peut être utilisée comme composition pharmaceutique et comme composition alimentaire.
PCT/KR2018/006033 2018-05-28 2018-05-28 Composition permettant la prévention ou le traitement de maladies de la bouche WO2019230996A1 (fr)

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CN201880094107.3A CN112236148A (zh) 2018-05-28 2018-05-28 口腔疾病预防或治疗用组合物
KR1020207037856A KR102315355B1 (ko) 2018-05-28 2018-05-28 구강질환 예방 또는 치료용 조성물
KR1020217033216A KR102470030B1 (ko) 2018-05-28 2018-05-28 구강질환 예방 또는 치료용 조성물
KR1020207034015A KR102546767B1 (ko) 2018-05-28 2018-05-28 구강질환 예방 또는 치료용 조성물
KR1020207037855A KR102288921B1 (ko) 2018-05-28 2018-05-28 구강질환 예방 또는 치료용 조성물
PCT/KR2018/006033 WO2019230996A1 (fr) 2018-05-28 2018-05-28 Composition permettant la prévention ou le traitement de maladies de la bouche
KR1020207037854A KR102288920B1 (ko) 2018-05-28 2018-05-28 구강질환 예방 또는 치료용 조성물
JP2020567022A JP7206302B2 (ja) 2018-05-28 2018-05-28 口腔疾患の予防又は治療用組成物
JP2022132595A JP7321632B2 (ja) 2018-05-28 2022-08-23 口腔疾患の予防又は治療用組成物
JP2022132594A JP7413465B2 (ja) 2018-05-28 2022-08-23 口腔疾患の予防又は治療用組成物
JP2022132596A JP7412844B2 (ja) 2018-05-28 2022-08-23 口腔疾患の予防又は治療用組成物
JP2023217980A JP2024038088A (ja) 2018-05-28 2023-12-25 口腔疾患の予防又は治療用組成物

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