WO2020204242A1 - Antimicrobial composition for inhibiting oral bacteria and orally disintegrating film - Google Patents

Antimicrobial composition for inhibiting oral bacteria and orally disintegrating film Download PDF

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Publication number
WO2020204242A1
WO2020204242A1 PCT/KR2019/004204 KR2019004204W WO2020204242A1 WO 2020204242 A1 WO2020204242 A1 WO 2020204242A1 KR 2019004204 W KR2019004204 W KR 2019004204W WO 2020204242 A1 WO2020204242 A1 WO 2020204242A1
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Prior art keywords
oral
extract
composition
sambaekcho
yolk powder
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PCT/KR2019/004204
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French (fr)
Korean (ko)
Inventor
조명행
김도형
Original Assignee
(주)지웰바이오
조명행
김도형
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Publication of WO2020204242A1 publication Critical patent/WO2020204242A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
    • 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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/78—Saururaceae (Lizard's-tail family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • 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
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/204—Animal extracts
    • A23V2250/2044—Egg yolk

Definitions

  • the present invention is an antibacterial composition for inhibiting oral bacteria capable of preventing, improving and treating oral diseases by inhibiting bacteria and oral inflammation causing oral diseases, pharmaceutical compositions for preventing or treating oral diseases, health functional food compositions and quasi-drug compositions. About.
  • the present invention relates to an oral disintegrating film for inhibiting oral bacteria.
  • More than 400 kinds of bacteria are proliferating in human oral cavity, and the number of bacteria reaches 10 billion, and it is known that there are bacteria at the level of 10 8 ⁇ 10 9 CFU/ml in saliva.
  • the teeth are perforated with a large number of microscopic holes, so bacteria that cause tooth decay enter the perforated hole and make the tooth sick. This is caries.
  • Dental caries and periodontal disease are infectious oral diseases, which prevent caries-causing bacteria such as Streptococcus mutans and/or periodontopathogenic bacteria such as Porphyromonas gingivalis. It is known to be associated with dental plaque.
  • Anti-plaque chemicals or antibiotics such as vancomycin are used to suppress the bacteria that cause such oral infections.
  • conventionally used materials are limited in clinical use due to problems such as unpleasant bitter taste, tooth discoloration, and resistance to antibiotics.
  • formulations administered orally include various oral dissolution formulations such as tablets, chewable tablets, sublingual tablets, capsules, and liquids.
  • general tablets and capsules have disadvantages of difficulty in taking drugs, such as animals, and liquid preparations have disadvantages of poor stability and inaccurate dosage.
  • an oral disintegrating tablet was recently developed in which a solid drug was developed in an oral disintegration form.
  • oral disintegrating tablets have the disadvantage of additionally drinking water, so there is a need for a new oral disintegrating film formulation.
  • the newly developed oral disintegrating film formulation has the advantage that it can be taken without water, and since it disintegrates in the oral cavity, it can be easily taken.
  • the present inventors were discussing a method to effectively inhibit oral bacteria and inhibit inflammation.When using a mixture of egg yolk powder, Sambaekcho extract, and Eoseongcho extract, it exhibits effective antibacterial activity against oral bacteria and prevents inflammation induced by oral cells. It was confirmed that it can be effectively suppressed and the present invention was completed. In addition, it was confirmed that the convenience of taking can be improved by preparing an oral disintegrating film containing them.
  • an object of the present invention is to provide an antibacterial composition for inhibiting oral bacteria including egg yolk powder, Eoseongcho extract and Sambaekcho extract, a pharmaceutical composition for preventing or treating oral diseases, a health functional food composition, a quasi-drug composition, and an oral disintegrating film containing them. To provide.
  • the present invention provides an antibacterial composition for inhibiting oral bacteria comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the present invention provides a pharmaceutical composition for preventing or treating oral diseases comprising yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the present invention provides a health functional food composition for preventing or improving oral diseases, including yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the present invention provides a quasi-drug composition for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the present invention provides a veterinary composition for preventing or improving oral diseases comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the present invention provides a composition for preparing an oral disintegrating film for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
  • the present invention provides an oral disintegrating film for preventing or improving oral diseases comprising egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
  • the egg yolk powder, Eoseongcho extract and Sambaekcho extract of the present invention inhibit inflammation induced by infection with periodontal disease-causing bacteria, and effectively inhibit Porphyromonas gingivalins or Porphyromonas canginibalis, which are representative oral bacteria, at low concentrations. Since it can, it can be usefully used in the prevention or treatment of various oral diseases.
  • the yolk powder, Eoseongcho extract, and Sambaekcho extract of the present invention are prepared as an oral disintegrating film to improve the convenience of taking the active ingredient in an individual, such as an animal, having difficulty in oral intake.
  • 1 is a diagram showing the results of confirming the change in cell proliferation rate in the normal control group and the inducing control in which inflammation was induced by Gingival LPS, and the experimental group treated with the test substance of the present invention by concentration through MTT analysis.
  • FIG. 2 is a diagram showing the results of confirming the PEG2 inhibitory activity through a change in the concentration of PGE2 in the normal control group, the trigger control in which inflammation was induced with Gingival LPS, and the experimental group treated with the test substance of the present invention by concentration.
  • FIG. 3 is a diagram showing a phenomenon in which a mother film and an original film are separated during a film casting process.
  • Figure 4 is a diagram showing an oral disintegrating film prepared including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the present invention relates to an antibacterial composition for inhibiting oral bacteria including egg yolk powder, Eoseongcho extract and Sambaekcho extract, and a composition for preparing an oral disintegrating film comprising them.
  • the present invention relates to a use of a composition comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract for use in inhibiting oral bacteria.
  • the present invention relates to a use for preparing an antibacterial composition for inhibiting oral bacteria including oral bacteria yolk powder, Eoseongcho extract, and Sambaekcho extract.
  • the antibacterial composition of the present invention can effectively inhibit the proliferation of harmful oral bacteria present in the oral cavity, and can suppress inflammation caused by oral bacteria.
  • the present invention is characterized in that it comprises egg yolk powder, Eoseongcho extract, and Sambaekcho extract as active ingredients in order to show the oral bacteria inhibitory effect.
  • the yolk powder of the present invention may be a sweetened yolk powder, and may include Egg yolk IgY (immunoglobulin Y).
  • the Eoseongcho extract or the Sambaekcho extract may be extracted and separated from Eoseongcho or Sambaekcho using a method known in the art for extraction and separation, and may be purchased from a company such as Dadang & Co., Ltd. Can be used.
  • The'extract' as defined in the present invention is extracted from Eoseongcho or Sambaekcho using an appropriate solvent, and includes, for example, a crude extract of Eoseongcho or Sambaekcho, a polar solvent-soluble extract, or a non-polar solvent-soluble extract.
  • all of the outposts, seeds, stems, leaves, and flowers of Eoseongcho or Sambaekcho can be used without limitation.
  • any solvent may be used as long as it is a pharmaceutically acceptable solvent, and water or an organic solvent may be used, but is not limited thereto, but the extract of the present invention includes water, 1 to 1 carbon atoms. It can be extracted with one type of extraction solvent selected from the group consisting of alcohol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, n-hexane, hydrochloric acid, formic acid, cyclohexane, and mixtures thereof. It can be extracted using water.
  • any one of methods such as hot water extraction, cold precipitation extraction, reflux cooling extraction, solvent extraction, steam distillation method, ultrasonic extraction method, elution method, compression method, etc. can be used.
  • the desired extract may be further subjected to a conventional fractionation process, or may be purified using a conventional purification method.
  • Eoseongcho or Sambaekcho extract of the present invention can be extracted, fractionated, and purified including, without limitation, methods known in the art. Therefore, in the present invention, the extract of Eoseongcho or Sambaekcho is a concept including all extracts, fractions and purified products obtained in each step of extraction, fractionation or purification, their dilutions, concentrates or dried products.
  • the active ingredients of the present invention egg yolk powder, Eoseongcho extract, and Sambaekcho extract can be included in the composition in a mass ratio of 1 to 10: 0.1 to 5: 1 in order to achieve the purpose of suppressing oral bacteria, preventing, treating, and improving oral diseases. And, preferably, it may be included in a mass ratio of 1 to 5: 0.3 to 0.8: 1, and in one embodiment of the present invention, the yolk powder: Eoseongcho extract: Sambaekcho extract is 3:0.5:1 mass ratio of 30mg, 5mg, 1mg A composition containing was used.
  • the antimicrobial composition for inhibiting oral bacteria including the yolk powder, Eoseongcho extract and Sambaekcho extract of the present invention is a variety of oral bacteria that can cause diseases in the oral cavity Streptococcus mutans , Streptococcus sanguinis ), Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus Actinobacillus actinomycetemcomitans , Tannerella forsythia , Treponemadenticola and Fusobacterium nucliatum nucleatum ), Porphyromonas gingivalins ( Porphyromonas gingivalis ) or Porphyromonas canginsivalis ( Porphyromonas cangingivalis ), and is preferably a bacterium that causes periodontal diseases including periodontitis or gingivitis in the oral cavity, Porphyromonas gingival
  • the antimicrobial composition for inhibiting oral bacteria of the present invention may additionally contain a component that enhances flavor for the purpose of enhancing the preference when administered orally, and may include, for example, beef flavor, chicken flavor, pork flavor, spices, etc. have.
  • the antimicrobial composition of the present invention can be prepared in any formulation commonly prepared in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, oral ointment, oral varnish, oral cavity Mouthwash, oral patch, oral disintegrating film, gum and gum massage cream, etc. may have formulations, but are not limited thereto, and preferably toothpaste, oral rinse, oral spray, oral ointment, oral patch, oral cavity It can be prepared in one type of formulation selected from the group consisting of a disintegrating film and a gum, more preferably an oral disintegrating film formulation.
  • the present invention is a pharmaceutical composition for preventing or treating oral diseases, including yolk powder, Eoseongcho extract and Sambaekcho extract, a health functional food composition for preventing or improving oral diseases, a quasi-drug composition for preventing or improving oral diseases, and preventing or improving oral diseases It relates to a veterinary composition for use.
  • oral disease refers to various diseases occurring in the oral region, and the oral region refers to a space in the mouth that is connected from the front lip to the posterior oral cavity to the pharynx.
  • the oral disease is a disease occurring in the oral cavity, it is a concept that includes all regardless of the condition, and preferably, one selected from the group consisting of plaque, bleeding gums, bad breath, aching teeth and dental caries, periodontitis and gingivitis It may be more than, more preferably periodontitis or periodontitis.
  • Gingivitis or periodontitis is a type of periodontal disease, which refers to a disease that causes inflammation in the gingiva, periodontal ligaments and bone tissues that support teeth.
  • Gingivitis is an inflammatory disease that is limited to soft tissues and gums, and is defined as periodontitis when the inflammation has progressed to around the gum bones other than the gums.
  • LPS Lipopolysaccharids
  • the yolk powder, Eoseongcho extract, and Sambaekcho extract of the present invention inhibit the proliferation of bacteria that cause periodontal disease, such as Porphyromonas gingivalins or Porphyromonas canginivalis, and can effectively inhibit the inflammatory LPS induced thereby .
  • Periodontal disease or periodontal disease, including gingivitis has the effect of preventing or treating, improving.
  • the egg yolk powder, Eoseongcho extract, and Sambaekcho extract are preferably contained in an amount of 0.01 to 95 parts by weight based on the total 100 parts by weight of the pharmaceutical composition, and more preferably 1 to 80 parts by weight. If the content is less than 0.01 parts by weight, the dosage efficiency may be deteriorated, and if it exceeds 95 parts by weight, there may be difficulties in formulation.
  • the pharmaceutical composition according to the present invention may contain a pharmaceutically effective amount of egg yolk powder, Eoseongcho extract, or Sambaekcho extract alone, or may contain one or more pharmaceutically acceptable carriers, excipients, or diluents.
  • the egg yolk powder, Eoseongcho extract, and Sambaekcho extract of the present invention may be included in a pharmaceutically effective amount, and "pharmaceutically effective amount" means, for example, porphyromonas gingivalins or porphyromonas canginivali, which are periodontal disease-causing bacteria. It refers to an amount sufficient to prevent, improve, or cure periodontal diseases that may occur by inhibiting the growth of S.
  • pharmaceutically acceptable refers to a composition that is physiologically acceptable and, when administered to an individual, does not usually cause allergic reactions such as gastrointestinal disorders, dizziness or similar reactions.
  • the pharmaceutical composition according to the present invention is preferably formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, and oral disintegrating films according to a conventional method.
  • oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, and oral disintegrating films according to a conventional method.
  • Suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently Mack Publishing Company, Easton PA.
  • Carriers, excipients and diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, mineral oil, and the like.
  • Solid preparations for oral administration include films, tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient in the composition, such as starch, calcium carbonate, and sucrose. , Lactose, gelatin, etc. are mixed to prepare.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included.
  • the pharmaceutical composition of the present invention is an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal, or human conceived by a researcher, veterinarian, doctor or other clinician, that is, the symptom of the disease or disorder being treated. It can be administered in a therapeutically effective amount, which is an amount that induces remission. It is apparent to those skilled in the art that the therapeutically effective dosage and frequency of administration of the pharmaceutical composition of the present invention will vary according to the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, and general health of the patient.
  • the pharmaceutical composition of the present invention may be administered in an amount of 1 to 10,000 mg/kg/day, preferably 1 to 200 mg/kg/day, and may be administered once a day or several times. It can also be administered separately.
  • the pharmaceutical composition of the present invention can be administered to a subject by various routes. Any mode of administration can be expected, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater or by intracerebrovascular injection, but most preferred is oral administration.
  • the pharmaceutical composition according to the present invention may be used alone, but according to the choice of a person skilled in the art, other suitable treatment methods (e.g., surgery, radiation therapy, hormone therapy, chemotherapy and biological It can be used in combination with the method of using a reaction regulator, etc.).
  • other suitable treatment methods e.g., surgery, radiation therapy, hormone therapy, chemotherapy and biological It can be used in combination with the method of using a reaction regulator, etc.
  • prevention may mean any action of inhibiting or delaying the onset of oral diseases by administering the composition for preventing or treating oral diseases according to the present invention to an individual.
  • treatment may refer to any action in which the composition according to the present invention is administered to an individual suspected of oral disease to improve or benefit from symptoms related to oral disease.
  • the term "improvement” may mean any action that at least reduces the severity of a parameter related to the condition being treated, for example, symptoms.
  • the term "individual" may mean all animals including humans who have or are likely to develop oral disease.
  • the present invention relates to a method for preventing or treating oral diseases comprising the step of administering to an individual a composition comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  • the type of food is not particularly limited, and may include all foods in a conventional sense.
  • foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea , Drinks, alcoholic beverages, and vitamin complexes.
  • the composition may be added as it is or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method.
  • the term "food” refers to a natural product or processed product containing one or more nutrients, and preferably refers to a state that can be eaten directly through some degree of processing, and is a common meaning,
  • the food composition is intended to include all foods, food additives, health functional foods and beverages.
  • Foods to which the composition of the present invention can be added include, for example, various foods, beverages, gum, candy, tea, vitamin complexes, and functional foods.
  • food in the present invention includes special nutritional foods (e.g., formula, infant food, etc.), processed meat products, fish meat products, tofu, muk, noodles (e.g., ramen, noodles, etc.), health supplement food, seasoning food ( Example, soy sauce, miso, red pepper paste, mixed sauce, etc.), sauces, confectionery (eg, snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruit, vegetable beverages, soy milk, fermented beverages, ice cream, etc.), natural seasonings (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages, and other health supplements.
  • the food, beverage or food additive may be prepared by a conventional
  • the term "health functional food” refers to food manufactured and processed by extracting, concentrating, refining, mixing, or extracting, concentrating, refining, and mixing specific ingredients as raw materials for the purpose of supplementing health. It refers to foods designed and processed to sufficiently exert biological control functions such as biological defense, biological rhythm control, and disease prevention and recovery by the above ingredients, and related to the prevention of diseases or recovery of health, etc. It refers to something that can perform a function.
  • composition according to the present invention when used as a health functional food, it may be added as it is or may be used with other foods or food ingredients, which may be selected and used appropriately as needed.
  • the composition according to the present invention can be used.
  • Fermented milk health functional foods that may contain the composition of the present invention include, for example, yogurt, calpis, cheese, butter, and the like, and fermented products include tofu, miso, cheonggukjang, jelly, kimchi, and the like.
  • the composition according to the present invention may mix well-known additives and other suitable auxiliary ingredients that may be contained in a health functional food according to the choice of a person skilled in the art.
  • the composition of the present invention When using the composition of the present invention as a quasi-drug, the composition may be added as it is or may be used with other quasi-drug components, and may be appropriately used according to a conventional method.
  • the mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).
  • the present invention when used as a quasi-drug composition, it can be prepared and used in formulations such as toothpaste, oral cleansers, oral rinses, oral sprays, and oral disintegrating films as oral compositions.
  • the present invention relates to a composition for preparing an oral disintegrating film for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
  • the Orally Disintegrating Film of the present invention can be used interchangeably with an oral film, an oral dissolving film, etc., and can be taken without water, so not only the elderly who have difficulty in taking tablets or capsules, It is very useful for children, the handicapped, patients lying in bed, and busy modern people. It can also be used for veterinary purposes in animals that are difficult to ingest drugs.
  • the antimicrobial composition contained in the oral disintegrating film has the advantage of being directly applied to the oral cavity and staying there, and an individual who has difficulty in taking the drug can take it without reluctance to suppress oral bacteria.
  • the oral disintegrating film of the present invention has physical properties suitable for the film and can be formulated for the purpose of facilitating dissolution of the included antimicrobial composition, including a film forming agent, a disintegrant, a plasticizer, an emulsifier, a sweetener, etc. Can be formulated.
  • the film-forming agent refers to a water-soluble polymer for the purpose of facilitating film formation, and fluran, gelatin, pectin, low viscosity pectin, hydroxypropylmethylcellulose, low viscosity hydroxypropylmethylcellulose, and hydride Roxyethylcellulose, hydroxypropyl cellulose, carboxymethylcellulose, polyvinyl alcohol, polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, polyethylene glycol, alginic acid, low viscosity alginic acid, sodium alginate, carrageenan, modified starch, casein, Whey protein isolate, soy protein isolate, zein, leban, elcinan, gluten, acacia gum, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum, gellan gum, and at least one selected from the group consisting of agar It may be a water-soluble polymer.
  • fluran may be used as a film forming agent, and when fluran is used, it may be included in 35 to 60% by weight, preferably 45 to 55% by weight, based on the total solid content of the composition for film production. .
  • the composition for producing an oral disintegrating film of the present invention may contain the yolk powder, Eoseongcho extract and Sambaekcho extract in a mass ratio of 1 to 10: 0.1 to 5: 1 in the composition in order to achieve an oral bacteria inhibiting effect, preferably 1 to 5: may be included in a mass ratio of 0.3 to 0.8: 1.
  • composition for producing an oral disintegrating film of the present invention may further include flavoring flavor for the purpose of improving consumer preference, and preferably may include flavoring flavor in liquid form. If the flavoring flavor exceeds 6% by weight of the total solids of the composition for film production, oil may leak during the production of the oral disintegrating film, resulting in separation of the mother film and the original film, and disintegration may not be achieved when feeding the individual. Therefore, seasoning flavor is preferably included in a liquid form in the composition for producing a film, and may be included in 2 to 5% by weight, more preferably 2 to 4% by weight of the total solid content of the composition for film production.
  • the seasoning flavor may include, without limitation, various natural and synthetic flavoring flavors that can be used as food additives, most preferably beef flavor.
  • the composition for preparing an oral disintegrating film of the present invention may contain egg yolk powder, Eoseongcho extract, Sambaekcho extract and film forming agent to achieve oral disintegration, film formulation, and oral bacterial inhibitory effect upon oral disintegration, and to enhance preference It may further include a liquid seasoning flavor.
  • the liquid seasoning flavor is included in this way, the egg yolk powder, Eoseongcho extract, Sambaekcho extract, and liquid seasoning flavor may be included in the composition for oral disintegration film production in a mass ratio of preferably 1 to 5: 0.3 to 0.8: 1: 0.3 to 0.8. have.
  • composition for preparing an oral disintegrating film of the present invention may contain one or more surfactants selected from the group consisting of nonionic surfactants, cationic surfactants, anionic surfactants, and zwitterionic surfactants, and preferably Sodium lauryl sulfate (SLS), glycerin fatty acid ester, sucrose fatty acid ester, lecithin, enzyme-treated lecithin, polysorbate, sorbitan fatty acid ester and sucrose fatty acid ester may be one or more selected from the group consisting of, and more preferably lauryl Sodium sulfate (SLS) and/or polysorbate.
  • surfactants selected from the group consisting of nonionic surfactants, cationic surfactants, anionic surfactants, and zwitterionic surfactants, and preferably Sodium lauryl sulfate (SLS), glycerin fatty acid ester, sucrose fatty acid ester, lecithin, enzyme-treated lec
  • the polysorbate is polysorbate 20 (monolauric acid), 40 (monopalmitic acid), 60 (monostearic acid), 65 (tristearic acid), 80 (monooleic acid) can be used without limitation, Most preferably, it may be polysorbate 20.
  • the oral disintegrating film of the present invention may additionally contain a sweetener, and sorbitol solution, sucralose, sodium chloride, mannitol, aspartame, acesulfame salt, saccharin salt, neotime, cyclamate salt within the limit of not impairing the physical properties of the film It may be one or more selected from the group consisting of taumatin, nahan fruit extract, licorice extract and enzyme-treated stevia.
  • test substance that suppresses inflammation in the oral cavity and inhibits the proliferation of oral bacteria.
  • the activity of inhibiting oral bacteria was confirmed below.
  • Sweetened egg yolk powder was purchased from Adbiotech and used.
  • Eoseongcho was washed with purified water, and purified water 15 times the extraction concentration was added and extracted at 60°C for 2 hours.
  • the obtained Eoseongcho water extract was filtered through a filter cloth or a 0.45 ⁇ m stainless steel mesh net.
  • Sambaekcho extract was also obtained by water extraction in the same manner as Eoseongcho extract.
  • HGF-1 Human gingival fibroblasts (HGF-1) were purchased from ATCC and used to analyze the effect on the dental cell environment (ATCC CRL-2014, 63449675). These cells are known to be the most suitable cells for oral studies, and are known to be most suitable for measuring PGE2 after Gingival LPS treatment.
  • Gingival fibroblasts were cultured from April 24, 2018 to May 2, 2018 in an incubator set at 37°C, 95% humidity, and 5% CO 2 . During the incubation period, temperature, humidity, and CO 2 The concentration was checked every 8 hours. DMEM medium, 10% FBS, 2 mL L-glutamine, 50 U/mL penicillin, and 50 ⁇ g/mL streptomycin were used for this experiment. For cell culture, a 75 cm 2 flask was used. At this time, the cells were cultured at a density of 5 X 10 6 cells/flask and replaced with fresh medium every 48 hours. After observing the degree of cell proliferation, it was isolated when proliferating more than 70%.
  • MTT assay Thiazolyl Blue Tetrazolium Blue; Sigma, M5655 was performed to confirm whether the test substance prepared in Example 1 exhibits toxicity to oral cells.
  • Gingival LPS 1 ⁇ g/mL was treated as an inflammatory substance, and the test substance prepared in Example 1 was changed to 5 to 1000 ⁇ g/mL, treated on HGF-1 cells, and cultured for 24 hours, after which the cell proliferation rate and PGE2 concentration The change of was measured.
  • Table 2 shows the test groups used for the test.
  • the concentration of PGE 2 increased rapidly by Gingival LPS treatment, and significantly decreased in a concentration-dependent manner by treatment of the test substance. Therefore, it was confirmed that the test material prepared in Example 1 can effectively inhibit PGE 2 , a product of inducing gingival inflammation in oral cells.
  • Example 1 In order to determine whether the preparation material of Example 1 exhibits an inhibitory effect on oral bacteria, the oral bacteria Porphyromonas gingivalis (P. cangingivalis ) and Porphyromonas cangingivalis ( Porphyromonas cangingivalis, P. cangingivalis ) , followed by a MIC ( minimal inhibition concentration) test.
  • P. cangingivalis And P. gingivalis were cultured for 48 hours at 37 °C anaerobic conditions using a medium prepared by adding hemin, vitamin K 3 and 5% sheep blood to Tryptic soy broth.
  • the first cultured bacteria were smeared on Tryptic soy agar + hemin + vitamin K 3 + 5% sheep blood to measure the number of bacteria, and then diluted to a concentration of 2.5 X 10 5 CFU/mL and used for MIC test.
  • Each test substance prepared in Example 1 was diluted in 96 wells by the same dilution factor, and then the same amount of bacteria was inoculated. After incubation for 48 hours, the absorbance was measured using a wavelength of 600 nm (Biotek, Epoch 2), and n number of the dilution factor of each test substance was set to 3 for accurate measurement.
  • each bacterium was stably cultured in a medium suitable for proliferation, maintained at least 2.5 X 10 5 CFU/mL, and cultured for 48 hours in an anaerobic 37° C. culture condition.
  • the test substance was treated in an equal amount in each well (96 well plate), and then the same amount of bacteria was inoculated into each well and incubated for 48 hours under anaerobic conditions at 37°C.
  • the absorbance (optical density, 600 nm) of each well was measured through a microplate reader to confirm antimicrobial activity and MIC.
  • IC80 Inhibitory concentration 80% maximal
  • IC70 Inhibitory concentration 70% maximal
  • IC50 Inhibitory concentration 50% maximal
  • the oral disintegrating film formulation was prepared using the yolk powder, Eoseongcho extract, and Sambaekcho extract, which confirmed the effect of inhibiting gingivitis and oral bacteria through Examples 2 and 3.
  • Beef flavor was added to enhance the preference, and preparation was carried out while varying the form of addition in powder or liquid form, and different amounts of 2.5, 5, and 10 mg.
  • As a result of manufacturing the oral disintegrating film according to the form and amount of beef flavor added if the beef flavor is added in powder or liquid form over 10 mg and exceeds 6% of the total solid content, a lot of oil spills out and disintegrates well during film production. It was confirmed that it was not lost.
  • a phenomenon in which the mother film and the original film are separated as shown in FIG. 3 occurred during the film casting process.
  • the composition of the film solution and the size of the film were adjusted, and with a composition that can achieve both film casting and disintegration effects, sweetened egg yolk powder (from Adbiotech) 30 mg, Sambaekcho extract 10mg, Eoseongcho extract 5mg And 5 mg of liquid beef flavor was derived, and a final oral disintegrating film was prepared by setting the size of the film to 27 * 40 mm, and the prepared oral disintegrating film is shown in FIG. 4. Component information and film size information used in the preparation of the oral disintegrating film are shown in Table 7 below.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • tablets are prepared by tableting according to a conventional tablet preparation method.
  • the above ingredients are mixed and filled into gelatin capsules to prepare tablets.
  • Purified water was added and the total was adjusted to 1,00ml.
  • the above ingredients are mixed according to a conventional method for preparing a liquid, and then filled in a brown bottle and sterilized to prepare a liquid.
  • Vitamin A acetate 70 ⁇ g
  • Vitamin B6 0.5 mg
  • Vitamin B12 0.2 ⁇ g
  • composition ratio of the vitamin and mineral mixture is relatively suitable for the health functional food, but it is possible to arbitrarily modify the composition, and the above ingredients are mixed according to the general health functional food manufacturing method. Then, it can be used in the manufacture of a health functional food composition (eg, nutritional candy, etc.) according to a conventional method.
  • a health functional food composition eg, nutritional candy, etc.
  • the resulting solution is filtered and obtained in a sterilized 2 liter container, sealed and sterilized, and stored in a refrigerator. It is used to prepare the health functional beverage composition of the present invention.
  • composition ratio is composed of ingredients suitable for a relatively preferred beverage in a preferred embodiment, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the demand class, the country of demand, and the intended use.

Abstract

The present invention relates to: an antimicrobial composition for inhibiting oral bacteria which inhibits oral disease-causing bacteria and inflammation, and thus is able to prevent, ameliorate, and treat oral diseases; a pharmaceutical composition for preventing or treating oral diseases; a health functional food composition; and a quasi-drug composition. Yolk powder, a Houttuynia cordata extract, and a Saururus chinensis extract of the present invention inhibit inflammation induced by infections by periodontal disease-causing bacteria, and can effectively inhibit, at low concentrations, the typical oral bacteria of Porphyromonas gingivalis or Porphyromonas cangingivalis, and thus can be effectively used in the prevention or treatment of various oral diseases.

Description

구강 세균 억제용 항균 조성물 및 구강붕해필름Antibacterial composition and oral disintegrating film for inhibiting oral bacteria
본 발명은 구강 질환을 유발하는 세균 및 구강 염증을 억제하여 구강 질환을 예방, 개선 및 치료할 수 있는 구강 세균 억제용 항균 조성물, 구강 질환 예방 또는 치료용 약학적 조성물, 건강기능식품 조성물 및 의약외품 조성물에 관한 것이다. 또한 본 발명을 구강 세균 억제용 구강붕해필름에 관한 것이다. The present invention is an antibacterial composition for inhibiting oral bacteria capable of preventing, improving and treating oral diseases by inhibiting bacteria and oral inflammation causing oral diseases, pharmaceutical compositions for preventing or treating oral diseases, health functional food compositions and quasi-drug compositions. About. In addition, the present invention relates to an oral disintegrating film for inhibiting oral bacteria.
사람의 구강에는 400 종류 이상의 세균이 번식하고 있으며, 그 균수는 100억 개에 달하고 타액에는 10 8∼10 9 CFU/㎖ 수준의 균이 존재하는 것으로 알려져 있다. 치아는 미세한 구멍이 다수개 천공되어 있어서 충치를 일으키는 세균이 천공된 구멍으로 들어가 치아를 병들게 하는데 이것이 충치이다. More than 400 kinds of bacteria are proliferating in human oral cavity, and the number of bacteria reaches 10 billion, and it is known that there are bacteria at the level of 10 8 ~ 10 9 CFU/ml in saliva. The teeth are perforated with a large number of microscopic holes, so bacteria that cause tooth decay enter the perforated hole and make the tooth sick. This is caries.
충치(dental caries) 및 치주염(periodontal disease)은 감염 구강 질환으로서, 스트렙토코커스 뮤탄스(Streptococcus mutans)와 같은 충치원인균 및/또는 포르피로모나스 진지발리스(Porphyromonas gingivalis)와 같은 치주원인균(periodontopathogenic)을 포함하는 치태(dental plaque)와 관련이 있는 것으로 알려져 있다. Dental caries and periodontal disease are infectious oral diseases, which prevent caries-causing bacteria such as Streptococcus mutans and/or periodontopathogenic bacteria such as Porphyromonas gingivalis. It is known to be associated with dental plaque.
이와 같은 구강 내 감염을 유발하는 균을 억제하기 위하여 항치태 화학제제 또는 반코마이신(vancomycin)과 같은 항생물질을 사용하고 있다. 그러나 종래 사용되고 있는 물질들은 불쾌한 쓴맛, 치아 변색, 항생물질에 대한 내성 등의 문제가 지적되어 임상적으로 사용이 제한적이다. Anti-plaque chemicals or antibiotics such as vancomycin are used to suppress the bacteria that cause such oral infections. However, conventionally used materials are limited in clinical use due to problems such as unpleasant bitter taste, tooth discoloration, and resistance to antibiotics.
또한 구강에 발생하는 질환을 예방, 치료하기 위해서는 구강에 직접적으로 작용하는 것이 바람직한데 구강 내 투여 시 약 냄새에 대한 거부감에 의해 약물의 복용이 어려운 경우가 있어, 효과적인 치료에 어려움이 있다. 특히 구강에 약물을 오래도록 머무르도록 하기 어려운 노약자, 또는 수의학적 약물로 적용 시 후각이 예민한 동물의 경우 이와 같은 어려움이 매우 큰 실정이다. In addition, in order to prevent and treat diseases occurring in the oral cavity, it is desirable to act directly on the oral cavity. When administered orally, it is difficult to take the drug due to the rejection of the smell of the drug, so effective treatment is difficult. In particular, the situation is very difficult in the case of the elderly, it is difficult to keep the drug in the oral cavity for a long time, or the animal with a sensitive sense of smell when applied as a veterinary drug.
한편 경구에 투여되는 제형으로는 정제, 츄어블정, 설하정, 캡슐, 액제 등의 다양한 구강 용해 제제 등이 있다. 이 중 일반 정제나 캅셀제 등은 약물의 복용이 곤란한 개체, 예컨대 동물에게는 복용의 어려움이 있는 단점이 있으며 액제의 경우 안정성이 떨어지고 용량이 정확하지 않다는 단점이 있다. 이에 따라 쉽게 복용 유도할 수 있는 새로운 제제에 대한 필요성이 있으며, 최근 고형제를 구강 내 붕괴형태로 개발시킨 구강 붕해정이 개발되었다. 그러나 구강붕해정은 추가적으로 물을 마셔야 한다는 단점이 있어, 새로운 구강붕해필름 제형에 대한 필요성이 있었다. 이에 새롭게 개발된 구강붕해필름 제제는 물없이 복용할 수 있고, 구강 내에서 붕해되므로 복용을 용이하게 할 수 있다는 장점이 있다. 그러나 구강붕해필름의 경우 유효성분에 따라 약물의 용출, 붕해가 원활하게 이루어지는 조건을 설정하는 것이 까다로워 제제 개발의 걸림돌이 되고 있다. On the other hand, formulations administered orally include various oral dissolution formulations such as tablets, chewable tablets, sublingual tablets, capsules, and liquids. Among them, general tablets and capsules have disadvantages of difficulty in taking drugs, such as animals, and liquid preparations have disadvantages of poor stability and inaccurate dosage. Accordingly, there is a need for a new formulation that can be easily induced to take, and an oral disintegrating tablet was recently developed in which a solid drug was developed in an oral disintegration form. However, oral disintegrating tablets have the disadvantage of additionally drinking water, so there is a need for a new oral disintegrating film formulation. Accordingly, the newly developed oral disintegrating film formulation has the advantage that it can be taken without water, and since it disintegrates in the oral cavity, it can be easily taken. However, in the case of the oral disintegrating film, it is difficult to set the conditions in which the dissolution and disintegration of the drug is smoothly performed depending on the active ingredient, which is an obstacle to the development of the formulation.
따라서 구강 내 질환을 예방 또는 치료함에 있어서 종래의 항생제 사용 부작용을 해소함과 동시에 약물 복용의 문제점까지 해결할 수 있는 새로운 기술에 대한 필요성이 있다. Therefore, in preventing or treating oral diseases, there is a need for a new technology capable of solving the problems of taking drugs while solving the side effects of using conventional antibiotics.
이에 본 발명자들은 구강 세균을 효과적으로 억제하고 염증을 억제할 수 있는 방법을 논의하던 중, 난황분말, 삼백초 추출물, 어성초 추출물을 혼합하여 이용하는 경우 구강 세균에 효과적인 항균 활성을 나타내고 구강세포에서 유도되는 염증을 효과적으로 억제할 수 있음을 확인하고 본 발명을 완성하였다. 또한 이들을 포함하는 구강붕해필름을 제조하여 복용의 편의성을 증진시킬 수 있음을 확인하였다. Accordingly, the present inventors were discussing a method to effectively inhibit oral bacteria and inhibit inflammation.When using a mixture of egg yolk powder, Sambaekcho extract, and Eoseongcho extract, it exhibits effective antibacterial activity against oral bacteria and prevents inflammation induced by oral cells. It was confirmed that it can be effectively suppressed and the present invention was completed. In addition, it was confirmed that the convenience of taking can be improved by preparing an oral disintegrating film containing them.
따라서 본 발명의 목적은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강세균 억제용 항균 조성물, 구강질환 예방 또는 치료용 약학적 조성물, 건강기능식품 조성물, 의약외품 조성물 및 이들을 포함하는 구강붕해필름을 제공하는 것이다. Accordingly, an object of the present invention is to provide an antibacterial composition for inhibiting oral bacteria including egg yolk powder, Eoseongcho extract and Sambaekcho extract, a pharmaceutical composition for preventing or treating oral diseases, a health functional food composition, a quasi-drug composition, and an oral disintegrating film containing them. To provide.
상기 목적을 달성하기 위하여, 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강세균 억제용 항균 조성물을 제공한다. In order to achieve the above object, the present invention provides an antibacterial composition for inhibiting oral bacteria comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
또한 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 치료용 약학적 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing or treating oral diseases comprising yolk powder, Eoseongcho extract and Sambaekcho extract.
또한 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 개선용 건강기능식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for preventing or improving oral diseases, including yolk powder, Eoseongcho extract and Sambaekcho extract.
또한 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 개선용 의약외품 조성물을 제공한다. In addition, the present invention provides a quasi-drug composition for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
또한 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 개선용 수의학적 조성물을 제공한다. In addition, the present invention provides a veterinary composition for preventing or improving oral diseases comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
또한 본 발명은 난황분말, 어성초 추출물, 삼백초 추출물 및 필름 형성제를 포함하는 구강질환 예방 또는 개선용 구강붕해필름 제조용 조성물을 제공한다. In addition, the present invention provides a composition for preparing an oral disintegrating film for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
또한 본 발명은 난황분말, 어성초 추출물, 삼백초 추출물 및 필름 형성제를 포함하는 구강질환 예방 또는 개선용 구강붕해필름을 제공한다. In addition, the present invention provides an oral disintegrating film for preventing or improving oral diseases comprising egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
본 발명의 난황분말, 어성초 추출물 및 삼백초 추출물은 치주질환 유발균 감염에 의해 유도되는 염증을 억제하고, 대표적인 구강세균인 포르피로모나스 진지발린스 또는 포르피로모나스 칸진지발리스를 낮은 농도에서 효과적으로 억제할 수 있으므로, 다양한 구강 질환의 예방 또는 치료에 유용하게 활용될 수 있다. 또한 본 발명의 난황분말, 어성초 추출물 및 삼백초 추출물은 구강붕해필름으로 제조되어 유효성분의 구강 섭취가 어려운 개체, 예컨대 동물에서 복용 편의성을 개선할 수 있다. The egg yolk powder, Eoseongcho extract and Sambaekcho extract of the present invention inhibit inflammation induced by infection with periodontal disease-causing bacteria, and effectively inhibit Porphyromonas gingivalins or Porphyromonas canginibalis, which are representative oral bacteria, at low concentrations. Since it can, it can be usefully used in the prevention or treatment of various oral diseases. In addition, the yolk powder, Eoseongcho extract, and Sambaekcho extract of the present invention are prepared as an oral disintegrating film to improve the convenience of taking the active ingredient in an individual, such as an animal, having difficulty in oral intake.
도 1은 정상 대조군 및 Gingival LPS 로 염증이 유도된 유발 대조군, 본원 발명의 시험물질을 농도 별로 처리한 실험군에서의 세포 증식률의 변화를 MTT 분석을 통해 확인한 결과를 나타낸 도이다. 1 is a diagram showing the results of confirming the change in cell proliferation rate in the normal control group and the inducing control in which inflammation was induced by Gingival LPS, and the experimental group treated with the test substance of the present invention by concentration through MTT analysis.
도 2는 정상 대조군 및 Gingival LPS 로 염증이 유도된 유발 대조군, 본원 발명의 시험물질을 농도 별로 처리한 실험군에서 PGE2 의 농도 변화를 통해 PEG2 억제 활성을 확인한 결과를 나타낸 도이다. FIG. 2 is a diagram showing the results of confirming the PEG2 inhibitory activity through a change in the concentration of PGE2 in the normal control group, the trigger control in which inflammation was induced with Gingival LPS, and the experimental group treated with the test substance of the present invention by concentration.
도 3은 필름 캐스팅 과정에서 마더필름과 원필름이 분리되는 현상을 나타낸 도이다. 3 is a diagram showing a phenomenon in which a mother film and an original film are separated during a film casting process.
도 4는 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하여 제조된 구강붕해필름을 나타낸 도이다. Figure 4 is a diagram showing an oral disintegrating film prepared including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강세균 억제용 항균 조성물 및 이들을 포함하는 구강붕해필름 제조용 조성물에 관한 것이다. The present invention relates to an antibacterial composition for inhibiting oral bacteria including egg yolk powder, Eoseongcho extract and Sambaekcho extract, and a composition for preparing an oral disintegrating film comprising them.
또한 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 조성물의 구강세균 억제에 사용하기 위한 용도에 관한 것이다. In addition, the present invention relates to a use of a composition comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract for use in inhibiting oral bacteria.
또한 본 발명은 구강세균 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강세균 억제용 항균 조성물을 제조하기 위한 용도에 관한 것이다. In addition, the present invention relates to a use for preparing an antibacterial composition for inhibiting oral bacteria including oral bacteria yolk powder, Eoseongcho extract, and Sambaekcho extract.
본 발명의 항균 조성물은 특히 구강에 존재하는 유해 구강 세균의 증식을 효과적으로 저해할 수 있으며, 구강 세균에 의해 유발되는 염증을 억제할 수 있다. In particular, the antibacterial composition of the present invention can effectively inhibit the proliferation of harmful oral bacteria present in the oral cavity, and can suppress inflammation caused by oral bacteria.
이하, 본 발명을 더욱 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 구강 세균 억제 효과를 나타내기 위하여 난황분말, 어성초 추출물 및 삼백초 추출물을 유효성분으로 포함하는 것을 특징으로 한다. The present invention is characterized in that it comprises egg yolk powder, Eoseongcho extract, and Sambaekcho extract as active ingredients in order to show the oral bacteria inhibitory effect.
본 발명의 난황분말은 가당 난황분말일 수 있으며, Egg yolk IgY (immunoglobulin Y) 를 포함할 수 있다. The yolk powder of the present invention may be a sweetened yolk powder, and may include Egg yolk IgY (immunoglobulin Y).
본 발명에 있어, 어성초 추출물 또는 삼백초 추출물은 당업계에 공지된 추출 및 분리하는 방법을 사용하여 어성초 또는 삼백초로부터 추출 및 분리하여 수득한 것을 사용할 수 있으며 예컨대 다당앤 (주) 와 같은 회사로부터 구입하여 사용할 수 있다. 본 발명에서 정의된 '추출물'은 적절한 용매를 이용하여 어성초 또는 삼백초로부터 추출한 것이며, 예를 들어, 어성초 또는 삼백초의 조추출물, 극성용매 가용 추출물 또는 비극성용매 가용 추출물을 모두 포함한다. 본 발명의 추출에는 어성초 또는 삼백초의 전초, 종자, 줄기, 잎, 꽃을 모두 제한없이 사용할 수 있다. In the present invention, the Eoseongcho extract or the Sambaekcho extract may be extracted and separated from Eoseongcho or Sambaekcho using a method known in the art for extraction and separation, and may be purchased from a company such as Dadang & Co., Ltd. Can be used. The'extract' as defined in the present invention is extracted from Eoseongcho or Sambaekcho using an appropriate solvent, and includes, for example, a crude extract of Eoseongcho or Sambaekcho, a polar solvent-soluble extract, or a non-polar solvent-soluble extract. In the extraction of the present invention, all of the outposts, seeds, stems, leaves, and flowers of Eoseongcho or Sambaekcho can be used without limitation.
본 발명의 추출물을 추출하기 위한 용매로는 약학적으로 허용되는 용매라면 어느 것을 사용해도 무방하며, 물 또는 유기용매를 사용할 수 있고, 이에 제한되지는 않으나, 본 발명의 추출물은 물, 탄소수 1 내지 4의 알코올, 아세톤, 에테르, 벤젠, 클로로포름, 에틸아세테이트, 메틸렌클로라이드, n-헥산, 염산, 포름산, 사이클로헥산 및 이들의 혼합물로 이루어진 군에서 선택된 1종의 추출용매로 추출될 수 있으며, 가장 바람직하게는 물을 이용하여 추출될 수 있다. As a solvent for extracting the extract of the present invention, any solvent may be used as long as it is a pharmaceutically acceptable solvent, and water or an organic solvent may be used, but is not limited thereto, but the extract of the present invention includes water, 1 to 1 carbon atoms. It can be extracted with one type of extraction solvent selected from the group consisting of alcohol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, n-hexane, hydrochloric acid, formic acid, cyclohexane, and mixtures thereof. It can be extracted using water.
추출물을 제조하기 위한 추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법 중 어느 하나를 선택하여 사용할 수 있다. 또한, 목적하는 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다. 본 발명의 어성초 또는 삼백초 추출물은 당 분야의 공지된 방법을 제한없이 포함하여 추출, 분획, 정제될 수 있다. 따라서 본 발명에 있어서 어성초 또는 삼백초 추출물은 추출, 분획 또는 정제의 각 단계에서 얻어지는 모든 추출액, 분획 및 정제물, 그들의 희석액, 농축액 또는 건조물을 모두 포함하는 개념이다.As an extraction method for preparing the extract, any one of methods such as hot water extraction, cold precipitation extraction, reflux cooling extraction, solvent extraction, steam distillation method, ultrasonic extraction method, elution method, compression method, etc. can be used. In addition, the desired extract may be further subjected to a conventional fractionation process, or may be purified using a conventional purification method. Eoseongcho or Sambaekcho extract of the present invention can be extracted, fractionated, and purified including, without limitation, methods known in the art. Therefore, in the present invention, the extract of Eoseongcho or Sambaekcho is a concept including all extracts, fractions and purified products obtained in each step of extraction, fractionation or purification, their dilutions, concentrates or dried products.
본 발명의 유효성분인 난황분말, 어성초 추출물, 삼백초 추출물은 구강세균 억제, 구강 질환 예방, 치료, 개선을 위한 목적을 달성하기 위하여, 1 내지 10: 0.1 내지 5: 1 의 질량비로 조성물 내에 포함될 수 있고, 바람직하게는 1 내지 5: 0.3 내지 0.8: 1 의 질량비로 포함될 수 있고, 본 발명의 일 구현예서는 난황분말: 어성초 추출물: 삼백초 추출물을 3:0.5:1 질량비인 30mg, 5mg, 1mg 로 포함하는 조성물을 이용하였다. The active ingredients of the present invention, egg yolk powder, Eoseongcho extract, and Sambaekcho extract can be included in the composition in a mass ratio of 1 to 10: 0.1 to 5: 1 in order to achieve the purpose of suppressing oral bacteria, preventing, treating, and improving oral diseases. And, preferably, it may be included in a mass ratio of 1 to 5: 0.3 to 0.8: 1, and in one embodiment of the present invention, the yolk powder: Eoseongcho extract: Sambaekcho extract is 3:0.5:1 mass ratio of 30mg, 5mg, 1mg A composition containing was used.
본 발명의 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강세균 억제용 항균 조성물은 구강 내에서 질환을 유발할 수 있는 다양한 구강세균인 스트렙토코쿠스 뮤탄스( Streptococcus mutans), 스트렙토코커스 산구이니스( Streptococcus sanguinis), 스트렙토코커스 소브리누스( Streptococcus sobrinus), 스트렙토코커스 라티( Streptococcus ratti), 스트렙토코커스 크리세티( Streptococcus criceti), 스트렙토코커스 안지노서스( Streptococcus anginosus) 악티노바실루스 악티노마이세템코미탄스 ( Actinobacillusactinomycetemcomitans), 타네렐라 포르시시아( Tannerella forsythia), 트레포네마 덴티콜라 ( Treponemadenticola) 및 푸소박테리움 누클리아툼( Fusobacterium nucleatum), 포르피로모나스 진지발린스 ( Porphyromonas gingivalis) 또는 포르피로모나스 칸진지발리스 ( Porphyromonas cangingivalis) 를 억제할 수 있고, 바람직하게는 구강 내에서 치주염 또는 치은염을 포함하는 치주 질환을 유발하는 세균인 포르피로모나스 진지발린스 ( Porphyromonas gingivalis) 또는 포르피로모나스 칸진지발리스 ( Porphyromonas cangingivalis) 를 억제할 수 있다. The antimicrobial composition for inhibiting oral bacteria including the yolk powder, Eoseongcho extract and Sambaekcho extract of the present invention is a variety of oral bacteria that can cause diseases in the oral cavity Streptococcus mutans , Streptococcus sanguinis ), Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus Actinobacillus actinomycetemcomitans , Tannerella forsythia , Treponemadenticola and Fusobacterium nucliatum nucleatum ), Porphyromonas gingivalins ( Porphyromonas gingivalis ) or Porphyromonas canginsivalis ( Porphyromonas cangingivalis ), and is preferably a bacterium that causes periodontal diseases including periodontitis or gingivitis in the oral cavity, Porphyromonas gingivalins gingivalis ) or Porphyromonas cangingivalis .
본 발명의 구강 세균 억제용 항균 조성물은 구강으로 투여 시 기호도를 높이고자 하는 목적으로 풍미를 향상시키는 성분을 추가로 포함할 수 있으며, 예컨대 비프향, 치킨향, 포크향, 향신료 등을 포함할 수 있다. The antimicrobial composition for inhibiting oral bacteria of the present invention may additionally contain a component that enhances flavor for the purpose of enhancing the preference when administered orally, and may include, for example, beef flavor, chicken flavor, pork flavor, spices, etc. have.
본 발명의 항균 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 치약, 구강세정제, 구강청정제, 껌, 캔디류, 구강스프레이, 구강용 연고제, 구강용 바니쉬, 구강양치액, 구강용 패치, 구강붕해 필름, 검 및 잇몸 마사지 크림 등의 제형을 가질 수 있으나 이에 제한되는 것은 아니며, 바람직하게는 치약, 구강 세정제, 구강용 스프레이, 구강용 연고제, 구강용 패치, 구강붕해 필름 및 검으로 이루어지는 군에서 선택된 1 종의 제형, 더욱 바람직하게는 구강붕해 필름 제형으로 제조될 수 있다. The antimicrobial composition of the present invention can be prepared in any formulation commonly prepared in the art, for example, toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, oral ointment, oral varnish, oral cavity Mouthwash, oral patch, oral disintegrating film, gum and gum massage cream, etc. may have formulations, but are not limited thereto, and preferably toothpaste, oral rinse, oral spray, oral ointment, oral patch, oral cavity It can be prepared in one type of formulation selected from the group consisting of a disintegrating film and a gum, more preferably an oral disintegrating film formulation.
또한 본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 치료용 약학적 조성물, 구강질환 예방 또는 개선용 건강기능식품 조성물, 구강질환 예방 또는 개선용 의약외품 조성물 및 구강질환 예방 또는 개선용 수의학적 조성물에 관한 것이다. In addition, the present invention is a pharmaceutical composition for preventing or treating oral diseases, including yolk powder, Eoseongcho extract and Sambaekcho extract, a health functional food composition for preventing or improving oral diseases, a quasi-drug composition for preventing or improving oral diseases, and preventing or improving oral diseases It relates to a veterinary composition for use.
본 발명에 있어, 구강질환은 구강 영역에서 발생하는 여러 가지 질환을 말하며, 상기 구강 영역은 앞쪽 입술부터 뒤쪽 구협에서 인두와 연결되는 입 안의 공간을 의미한다. 본 발명에서 상기 구강질환은 구강에 발생하는 질환이라면 그 병증에 관계없이 모두 포함하는 개념이며, 바람직하게는 프라그, 잇몸 출혈, 구취, 시린이 및 치아 우식증, 치주염 및 치은염으로 이루어진 군에서 선택된 1종 이상일 수 있고, 더욱 바람직하게는 치주염 또는 치주염일 수 있다. In the present invention, oral disease refers to various diseases occurring in the oral region, and the oral region refers to a space in the mouth that is connected from the front lip to the posterior oral cavity to the pharynx. In the present invention, if the oral disease is a disease occurring in the oral cavity, it is a concept that includes all regardless of the condition, and preferably, one selected from the group consisting of plaque, bleeding gums, bad breath, aching teeth and dental caries, periodontitis and gingivitis It may be more than, more preferably periodontitis or periodontitis.
치은염 또는 치주염은 치주 질환의 일종으로, 치아를 받치고 있는 치은과 치주인대, 골조직에 염증이 생기는 질환을 말한다. 치은염은 연조직, 잇몸에만 국한된 형태로 나타나는 염증 질환이고, 염증이 잇몸 외 잇몸뼈 주변까지 진행된 경우 치주염으로 정의한다. 치은 (잇몸) 과 치아 사이의 틈에 구강세균이 침투하면서 염증의 원인이 되는 LPS (Lipopolysaccharids) 를 방출하고, 이는 결과적으로 잇몸이 붓고 출혈이 일어나는 염증을 유발시킨다. 본 발명의 난황분말, 어성초 추출물, 삼백초 추출물은 치주 질환을 일으키는 세균, 예컨대 포르피로모나스 진지발린스 또는 포르피로모나스 칸진지발리스의 증식을 억제하고 이에 의해 유도되는 염증성 LPS 를 효과적으로 억제할 수 있으므로, 치주염 또는 치은염을 포함하는 치주 질환을 예방 또는 치료, 개선하는 효과가 있다. Gingivitis or periodontitis is a type of periodontal disease, which refers to a disease that causes inflammation in the gingiva, periodontal ligaments and bone tissues that support teeth. Gingivitis is an inflammatory disease that is limited to soft tissues and gums, and is defined as periodontitis when the inflammation has progressed to around the gum bones other than the gums. As oral bacteria penetrate the gap between the gingival (gum) and teeth, it releases LPS (Lipopolysaccharids), which causes inflammation, which in turn causes inflammation in which the gums swell and bleed. Since the yolk powder, Eoseongcho extract, and Sambaekcho extract of the present invention inhibit the proliferation of bacteria that cause periodontal disease, such as Porphyromonas gingivalins or Porphyromonas canginivalis, and can effectively inhibit the inflammatory LPS induced thereby , Periodontal disease or periodontal disease, including gingivitis, has the effect of preventing or treating, improving.
약학적 조성물의 경우, 상기 난황분말, 어성초 추출물, 삼백초 추출물은 약학적 조성물 총 100 중량부에 대하여 0.01~95 중량부로 포함되는 것이 바람직하며, 더욱 바람직하게는 1~80 중량부로 포함될 수 있다. 그 함량이 0.01 중량부 미만일 경우에는 복용 효율성이 떨어질 수 있으며, 95 중량부를 초과할 경우에는 제형화에 어려움이 있을 수 있다.In the case of a pharmaceutical composition, the egg yolk powder, Eoseongcho extract, and Sambaekcho extract are preferably contained in an amount of 0.01 to 95 parts by weight based on the total 100 parts by weight of the pharmaceutical composition, and more preferably 1 to 80 parts by weight. If the content is less than 0.01 parts by weight, the dosage efficiency may be deteriorated, and if it exceeds 95 parts by weight, there may be difficulties in formulation.
본 발명에 따른 약학적 조성물은 약학적으로 유효한 양의 난황분말, 어성초 추출물, 삼백초 추출물을 단독으로 포함하거나 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제를 포함할 수 있다. The pharmaceutical composition according to the present invention may contain a pharmaceutically effective amount of egg yolk powder, Eoseongcho extract, or Sambaekcho extract alone, or may contain one or more pharmaceutically acceptable carriers, excipients, or diluents.
본 발명의 난황분말, 어성초 추출물, 삼백초 추출물은 약학적으로 유효한 양으로 포함될 수 있으며, "약학적으로 유효한 양"이란, 예컨대 치주질환 유발 세균인 포르피로모나스 진지발린스 또는 포르피로모나스 칸진지발리스의 생육을 억제하여 이로 인해 발생할 수 있는 치주질환의 예방, 개선 또는 치료 효과를 발휘하기에 충분한 양을 말한다. 상기 "약학적으로 허용되는"이란, 생리학적으로 허용되고 개체에게 투여될 때, 통상적으로 위장 장애, 현기증과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다.The egg yolk powder, Eoseongcho extract, and Sambaekcho extract of the present invention may be included in a pharmaceutically effective amount, and "pharmaceutically effective amount" means, for example, porphyromonas gingivalins or porphyromonas canginivali, which are periodontal disease-causing bacteria. It refers to an amount sufficient to prevent, improve, or cure periodontal diseases that may occur by inhibiting the growth of S. The term "pharmaceutically acceptable" refers to a composition that is physiologically acceptable and, when administered to an individual, does not usually cause allergic reactions such as gastrointestinal disorders, dizziness or similar reactions.
또한 본 발명에 따른 약학적 조성물은 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸, 구강붕해필름 등의 경구형 제형의 형태로 제형화하여 사용하는 것이 바람직하다. 당해 기술 분야에 알려진 적합한 제제는 문헌(Remington's Pharmaceutical Science, 최근, Mack Publishing Company, Easton PA)에 개시되어 있는 것을 사용하는 것이 바람직하다. 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 소르비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트, 광물유 등이 있다. 상기 약학적 조성물을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 필름제, 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 조성물에 적어도 하나 이상의 부형제, 예를 들면 전분, 칼슘 카보네이트(calcium carbonate), 수크로오스, 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다In addition, the pharmaceutical composition according to the present invention is preferably formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, and oral disintegrating films according to a conventional method. Do. Suitable formulations known in the art are preferably those disclosed in Remington's Pharmaceutical Science, recently Mack Publishing Company, Easton PA. Carriers, excipients and diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, mineral oil, and the like. When formulating the pharmaceutical composition, it is prepared by using a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, and surfactant. Solid preparations for oral administration include films, tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient in the composition, such as starch, calcium carbonate, and sucrose. , Lactose, gelatin, etc. are mixed to prepare. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included.
본 발명의 약학적 조성물은 연구자, 수의사, 의사 또는 기타 임상에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학적 조성물의 양, 즉 치료되는 질환 또는 장애의 증상의 완화를 유도하는 양인 치료상 유효량으로 투여할 수 있다. 본 발명의 약학적 조성물에 대한 치료상 유효 투여량 및 투여횟수는 원하는 효과에 따라 변화될 것임은 당업자에게 자명하다. 그러므로, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 질환의 종류, 질환의 중증도, 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 바람직한 효과를 위해서, 본 발명의 약학적 조성물은 1~10,000㎎/㎏/day, 바람직하게는 1~200㎎/㎏/day의 양으로 투여할 수 있으며, 하루에 한번 투여할 수도 있고, 수 회에 나누어 투여할 수도 있다. The pharmaceutical composition of the present invention is an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal, or human conceived by a researcher, veterinarian, doctor or other clinician, that is, the symptom of the disease or disorder being treated. It can be administered in a therapeutically effective amount, which is an amount that induces remission. It is apparent to those skilled in the art that the therapeutically effective dosage and frequency of administration of the pharmaceutical composition of the present invention will vary according to the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, and general health of the patient. It can be adjusted according to various factors including condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and drugs used simultaneously. For a desirable effect, the pharmaceutical composition of the present invention may be administered in an amount of 1 to 10,000 mg/kg/day, preferably 1 to 200 mg/kg/day, and may be administered once a day or several times. It can also be administered separately.
본 발명의 약학적 조성물은 개체에게 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 구강, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사에 의해 투여될 수 있으나, 구강 내 투여되는 것이 가장 바람직하다. The pharmaceutical composition of the present invention can be administered to a subject by various routes. Any mode of administration can be expected, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater or by intracerebrovascular injection, but most preferred is oral administration.
본 발명에 따른 약학적 조성물은 단독으로 사용될 수 있으나, 통상의 기술자의 선택에 따라 통상적으로 구강질환의 치료 증강 효과가 있는 적절한 기타 치료 방법(예컨대, 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제 이용 방법 등)과 병용하여 사용할 수 있다.The pharmaceutical composition according to the present invention may be used alone, but according to the choice of a person skilled in the art, other suitable treatment methods (e.g., surgery, radiation therapy, hormone therapy, chemotherapy and biological It can be used in combination with the method of using a reaction regulator, etc.).
본 발명에서 용어, "예방"이란, 본 발명에 따른 구강 질환의 예방 또는 치료용 조성물을 개체에 투여하여 구강 질환의 발병을 억제하거나 지연시키는 모든 행위를 의미할 수 있다.In the present invention, the term "prevention" may mean any action of inhibiting or delaying the onset of oral diseases by administering the composition for preventing or treating oral diseases according to the present invention to an individual.
본 발명에서 용어, "치료"란, 본 발명에 따른 조성물을 구강 질환의 의심 개체에 투여하여 구강 질환의 관련 질환의 증세가 호전되도록 하거나 이롭게 되도록 하는 모든 행위를 의미할 수 있다.In the present invention, the term "treatment" may refer to any action in which the composition according to the present invention is administered to an individual suspected of oral disease to improve or benefit from symptoms related to oral disease.
본 발명에서 용어, "개선"은 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미할 수 있다.In the present invention, the term "improvement" may mean any action that at least reduces the severity of a parameter related to the condition being treated, for example, symptoms.
본 발명에서 용어, "개체"란, 구강 질환이 발병되었거나 발병할 가능성이 있는 인간을 포함한 모든 동물을 의미할 수 있다.In the present invention, the term "individual" may mean all animals including humans who have or are likely to develop oral disease.
본 발명은 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 조성물을 개체에 투여하는 단계를 포함하는 구강질환 예방 또는 치료 방법에 관한 것이다. The present invention relates to a method for preventing or treating oral diseases comprising the step of administering to an individual a composition comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
본 발명에 따른 식품 조성물에서, 상기 식품의 종류는 특별히 제한되지 아니하며, 통상적인 의미에서의 식품을 모두 포함할 수 있다. 상기 물질을 첨가할 수 있는 식품의 비제한적인 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등을 들 수 있다. 상기 조성물을 식품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다.In the food composition according to the present invention, the type of food is not particularly limited, and may include all foods in a conventional sense. Non-limiting examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea , Drinks, alcoholic beverages, and vitamin complexes. When using the composition as a food additive, the composition may be added as it is or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method.
본 명세서에서 식품이란 함은 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 의미이고, 상기 식품 조성물은 식품, 식품 첨가제, 건강 기능성 식품 및 음료를 모두 포함하는 의도이다.In the present specification, the term "food" refers to a natural product or processed product containing one or more nutrients, and preferably refers to a state that can be eaten directly through some degree of processing, and is a common meaning, The food composition is intended to include all foods, food additives, health functional foods and beverages.
본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 캔디, 차, 비타민 복합제, 기능성 식품 등이 있다. 추가로, 본 발명에서 식품에는 특수영양식품(예, 조제유류, 영, 유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류(예, 라면류, 국수류 등), 건강보조식품, 조미식품(예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류(예, 스넥류), 유가공품(예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임 식품(각종 김치류, 장아찌 등), 음료(예, 과실, 채소류 음료, 두유류, 발효음료류, 아이스크림류 등), 천연조미료(예, 라면 스프 등), 비타민 복합제, 알코올 음료, 주류 및 그 밖의 건강보조식품류를 포함하나 이에 한정되지 않는다. 상기 식품, 음료 또는 식품첨가제는 통상의 제조방법으로 제조될 수 있다.Foods to which the composition of the present invention can be added include, for example, various foods, beverages, gum, candy, tea, vitamin complexes, and functional foods. In addition, food in the present invention includes special nutritional foods (e.g., formula, infant food, etc.), processed meat products, fish meat products, tofu, muk, noodles (e.g., ramen, noodles, etc.), health supplement food, seasoning food ( Example, soy sauce, miso, red pepper paste, mixed sauce, etc.), sauces, confectionery (eg, snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruit, vegetable beverages, soy milk, fermented beverages, ice cream, etc.), natural seasonings (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages, and other health supplements. The food, beverage or food additive may be prepared by a conventional manufacturing method.
본 발명에 따른 건강기능식품 조성물에서 "건강기능식품"이란 건강보조의 목적으로 특정성분을 원료로 하거나 식품 원료에 들어있는 특정성분을 추출, 농축, 정제, 혼합 등의 방법으로 제조, 가공한 식품을 말하며, 상기 성분에 의해 생체 방어, 생체리듬의 조절, 질병의 방지와 회복 등 생체조절기능을 생체에 대하여 충분히 발휘할 수 있도록 설계되고 가공된 식품을 말하는 것으로서, 질병의 예방 또는 건강의 회복 등과 관련된 기능을 수행할 수 있는 것을 말한다.In the health functional food composition according to the present invention, the term "health functional food" refers to food manufactured and processed by extracting, concentrating, refining, mixing, or extracting, concentrating, refining, and mixing specific ingredients as raw materials for the purpose of supplementing health. It refers to foods designed and processed to sufficiently exert biological control functions such as biological defense, biological rhythm control, and disease prevention and recovery by the above ingredients, and related to the prevention of diseases or recovery of health, etc. It refers to something that can perform a function.
본 발명에 따른 조성물을 건강기능식품으로 사용하는 경우, 이를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 이는 필요에 따라 선택하여 적절하게 사용될 수 있다. When the composition according to the present invention is used as a health functional food, it may be added as it is or may be used with other foods or food ingredients, which may be selected and used appropriately as needed.
또한, 본 발명에 따른 조성물이 사용될 수 있는 건강기능식품의 종류에는 특별한 제한이 없다. 예컨대, 라면, 기타 면류, 음료수, 차, 드링크제, 알콜 음료, 각종 스프, 육류, 소세지, 빵, 초코렛, 캔디류, 과자류, 피자, 껌류, 아이스크림류를 포함한 낙농제품, 또는 비타민 복합제 등이 있다. 특히, 본 발명에 따른 치주염균에 대한 억제 효과가 우수하므로, 다양한 건강기능식품으로 제조하기 적합하다. 본 발명의 조성물이 포함될 수 있는 발효유 건강기능식품으로는 예컨대, 요구르트, 칼피스, 치즈, 버터 등을 들 수 있고, 발효 제품으로는 두부, 된장, 청국장, 젤리, 김치 등을 들 수 있다. 또한, 본 발명에 따른 조성물은 통상의 기술자의 선택에 따라 통상적으로 건강기능식품에 함유될 수 있는 적절한 기타 보조성분과 공지의 첨가제를 혼합할 수 있다. In addition, there is no particular limitation on the kind of health functional food in which the composition according to the present invention can be used. For example, ramen, other noodles, beverages, tea, drinks, alcoholic beverages, various soups, meat, sausage, bread, chocolate, candy, confectionery, pizza, gum, dairy products including ice cream, or vitamin complexes. In particular, since the inhibitory effect against periodontitis according to the present invention is excellent, it is suitable for manufacturing various health functional foods. Fermented milk health functional foods that may contain the composition of the present invention include, for example, yogurt, calpis, cheese, butter, and the like, and fermented products include tofu, miso, cheonggukjang, jelly, kimchi, and the like. In addition, the composition according to the present invention may mix well-known additives and other suitable auxiliary ingredients that may be contained in a health functional food according to the choice of a person skilled in the art.
본 발명의 조성물을 의약외품으로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 의약외품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 본 발명이 의약외품 조성물로 사용되는 경우, 구강 조성물인 치약류, 구강청결제류, 구강세정제류 구강 스프레이류, 구강 붕해 필름 등의 제형으로 제조하여 사용할 수 있다. When using the composition of the present invention as a quasi-drug, the composition may be added as it is or may be used with other quasi-drug components, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). When the present invention is used as a quasi-drug composition, it can be prepared and used in formulations such as toothpaste, oral cleansers, oral rinses, oral sprays, and oral disintegrating films as oral compositions.
또한 본 발명은 난황분말, 어성초 추출물, 삼백초 추출물 및 필름 형성제를 포함하는 구강질환 예방 또는 개선용 구강붕해필름 제조용 조성물에 관한 것이다. In addition, the present invention relates to a composition for preparing an oral disintegrating film for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
본 발명의 구강 붕해 필름 (Orally Disintegrating Film) 은 구강 속용 필름, 구강 용해 필름 등과 상호 교환적으로 사용될 수 있고, 물이 없이도 복용할 수 있으므로, 정제나 캅셀제를 복용하기에 어려움을 겪는 노인뿐만 아니라, 어린이, 장애자, 침대에 누워 있는 환자, 그리고 바쁜 현대인들에게도 매우 유용하며, 또한 약물의 섭취가 어려운 동물에 수의학적 목적으로 유용하게 사용될 수 있다. 구강 붕해 필름에 포함된 항균 조성물은 구강에 직접적으로 적용되어 머무를 수 있는 장점이 있고, 약을 먹기 어려운 개체가 거부감없이 복용하여 구강 세균을 억제할 수 있다. 본 발명의 구강붕해 필름은 필름에 적합한 물성을 갖고, 포함된 항균 조성물 용출을 원활하게 할 수 있는 목적으로 제형화될 수 있고, 필름 형성제, 붕해제, 가소제, 유화제, 감미제 등을 포함하여 제형화 될 수 있다. The Orally Disintegrating Film of the present invention can be used interchangeably with an oral film, an oral dissolving film, etc., and can be taken without water, so not only the elderly who have difficulty in taking tablets or capsules, It is very useful for children, the handicapped, patients lying in bed, and busy modern people. It can also be used for veterinary purposes in animals that are difficult to ingest drugs. The antimicrobial composition contained in the oral disintegrating film has the advantage of being directly applied to the oral cavity and staying there, and an individual who has difficulty in taking the drug can take it without reluctance to suppress oral bacteria. The oral disintegrating film of the present invention has physical properties suitable for the film and can be formulated for the purpose of facilitating dissolution of the included antimicrobial composition, including a film forming agent, a disintegrant, a plasticizer, an emulsifier, a sweetener, etc. Can be formulated.
본 발명에 있어 필름 형성제는 필름 형성이 원활하게 이루어지도록 하는 목적의 수용성 고분자를 의미하며, 플루란, 젤라틴, 펙틴, 저점도 펙틴, 하이드록시프로필메틸셀룰로오스, 저점도 하이드록시프로필메틸셀룰로오스, 하이드록시에틸셀룰로오스, 하이드록시프로필 셀룰로오스, 카르복시메틸셀룰로오스, 폴리비닐알콜, 폴리아크릴산, 메틸메타크릴레이트 공중합체, 카르복시비닐 중합체, 폴리에틸렌글리콜, 알긴산, 저점도 알긴산, 알긴산 나트륨, 카라기난, 변성 전분, 카제인, 유장단백분리물, 콩단백분리물, 제인, 레반, 엘시난, 글루텐, 아카시아검, 카라기난, 아라비아 검, 구아 검, 로커스트빈 검, 잔탄 검, 겔란 검 및 아가로 이루어진 군으로부터 선택되는 1종 이상의 수용성 고분자일 수 있다. 본 발명에 있어 가장 바람직하게는 플루란을 필름 형성제로 사용할 수 있으며, 플루란을 사용하는 경우, 필름 제조용 조성물의 고형분 합계 대비 35 내지 60 중량%, 바람직하게는 45 내지 55 중량% 로 포함될 수 있다. In the present invention, the film-forming agent refers to a water-soluble polymer for the purpose of facilitating film formation, and fluran, gelatin, pectin, low viscosity pectin, hydroxypropylmethylcellulose, low viscosity hydroxypropylmethylcellulose, and hydride Roxyethylcellulose, hydroxypropyl cellulose, carboxymethylcellulose, polyvinyl alcohol, polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, polyethylene glycol, alginic acid, low viscosity alginic acid, sodium alginate, carrageenan, modified starch, casein, Whey protein isolate, soy protein isolate, zein, leban, elcinan, gluten, acacia gum, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum, gellan gum, and at least one selected from the group consisting of agar It may be a water-soluble polymer. In the present invention, most preferably, fluran may be used as a film forming agent, and when fluran is used, it may be included in 35 to 60% by weight, preferably 45 to 55% by weight, based on the total solid content of the composition for film production. .
본 발명의 구강붕해필름 제조용 조성물은 구강세균 억제 효과를 달성하기 위하여 상기 난황분말, 어성초 추출물 및 삼백초 추출물을 1 내지 10: 0.1 내지 5: 1 의 질량비로 조성물 내에 포함할 수 있고, 바람직하게는 1 내지 5: 0.3 내지 0.8: 1 의 질량비로 포함할 수 있다. The composition for producing an oral disintegrating film of the present invention may contain the yolk powder, Eoseongcho extract and Sambaekcho extract in a mass ratio of 1 to 10: 0.1 to 5: 1 in the composition in order to achieve an oral bacteria inhibiting effect, preferably 1 to 5: may be included in a mass ratio of 0.3 to 0.8: 1.
또한 본 발명의 구강붕해필름 제조용 조성물은 수요자의 기호도를 향상시키기 위한 목적으로 조미향을 더 포함할 수 있고, 바람직하게는 액상 형태의 조미향을 포함할 수 있다. 조미향이 필름 제조용 조성물 총 고형분 합계의 6 중량% 를 초과하는 경우 구강붕해필름 제작 시 기름이 유출되어 마더필름과 원필름의 분리가 일어날 수 있으며, 개체 급여시 붕해가 달성되지 않을 수 있다. 따라서 조미향은 필름 제조용 조성물 내 액상 형태로 포함되는 것이 바람직하며, 필름 제조용 조성물 총 고형분 합계의 2 내지 5 중량%, 더욱 바람직하게는 2 내지 4 중량%로 포함될 수 있다. In addition, the composition for producing an oral disintegrating film of the present invention may further include flavoring flavor for the purpose of improving consumer preference, and preferably may include flavoring flavor in liquid form. If the flavoring flavor exceeds 6% by weight of the total solids of the composition for film production, oil may leak during the production of the oral disintegrating film, resulting in separation of the mother film and the original film, and disintegration may not be achieved when feeding the individual. Therefore, seasoning flavor is preferably included in a liquid form in the composition for producing a film, and may be included in 2 to 5% by weight, more preferably 2 to 4% by weight of the total solid content of the composition for film production.
본 발명에 있어 상기 조미향은 식품 첨가제로 사용될 수 있는 다양한 천연, 합성 조미향을 제한없이 포함할 수 있으나, 가장 바람직하게는 비프향일 수 있다. In the present invention, the seasoning flavor may include, without limitation, various natural and synthetic flavoring flavors that can be used as food additives, most preferably beef flavor.
본 발명의 구강붕해필름 제조용 조성물은 구강붕해, 필름 제형화, 구강 붕해 시 구강 세균 억제 효과달성을 위하여 난황분말, 어성초 추출물, 삼백초 추출물 및 필름 형성제를 포함할 수 있으며, 기호도 증진을 위해 액상 조미향을 더 포함할 수 있다. 이와 같이 액상 조미향이 포함되는 경우, 난황분말, 어성초 추출물, 삼백초 추출물 및 액상 조미향은 바람직하게는 1 내지 5: 0.3 내지 0.8 : 1: 0.3 내지 0.8의 질량비로 구강붕해필름 제조용 조성물에 포함될 수 있다. The composition for preparing an oral disintegrating film of the present invention may contain egg yolk powder, Eoseongcho extract, Sambaekcho extract and film forming agent to achieve oral disintegration, film formulation, and oral bacterial inhibitory effect upon oral disintegration, and to enhance preference It may further include a liquid seasoning flavor. When the liquid seasoning flavor is included in this way, the egg yolk powder, Eoseongcho extract, Sambaekcho extract, and liquid seasoning flavor may be included in the composition for oral disintegration film production in a mass ratio of preferably 1 to 5: 0.3 to 0.8: 1: 0.3 to 0.8. have.
본 발명의 구강붕해필름 제조용 조성물은 비이온성 계면활성제, 양이온성 계면활성제, 음이온성 계면활성제 및 양쪽성 이온계 계면활성제로 이루어진 군에서 선택된 1종 이상의 계면활성제를 포함할 수 있으며, 바람직하게는 라우릴황산나트륨(SLS), 글리세린지방산에스테르, 수크로오스 지방산에스테르, 레시틴, 효소처리 레시틴, 폴리소르베이트, 솔비탄지방산에스테르 및 자당 지방산에스테르로 이루어진 군으로부터 선택된 1종 이상일 수 있고, 더욱 바람직하게는 라우릴황산나트륨(SLS) 및/또는 폴리소르베이트일 수 있다. 상기 폴리소르베이트는 폴리소르베이트 20(모노라우르산), 40(모노팔미트산), 60(모노스테아르산), 65(트리스테아르산), 80(모노올레산)을 제한없이 사용 가능하나, 가장 바람직하게는 폴리소르베이트 20일 수 있다. The composition for preparing an oral disintegrating film of the present invention may contain one or more surfactants selected from the group consisting of nonionic surfactants, cationic surfactants, anionic surfactants, and zwitterionic surfactants, and preferably Sodium lauryl sulfate (SLS), glycerin fatty acid ester, sucrose fatty acid ester, lecithin, enzyme-treated lecithin, polysorbate, sorbitan fatty acid ester and sucrose fatty acid ester may be one or more selected from the group consisting of, and more preferably lauryl Sodium sulfate (SLS) and/or polysorbate. The polysorbate is polysorbate 20 (monolauric acid), 40 (monopalmitic acid), 60 (monostearic acid), 65 (tristearic acid), 80 (monooleic acid) can be used without limitation, Most preferably, it may be polysorbate 20.
본 발명의 구강붕해필름에는 추가적으로 감미제가 포함될 수 있으며, 필름의 물성을 저해하지 않는 한도 내에서 소르비톨액, 수크랄로스, 염화나트륨, 만니톨, 아스파탐, 아세설팜염, 사카린염, 네오타임, 사이클라메이트염, 타우마틴, 나한과 추출물, 감초 추출물 및 효소처리 스테비아로 이루어진 군에서 선택되는 1종 이상일 수 있다. The oral disintegrating film of the present invention may additionally contain a sweetener, and sorbitol solution, sucralose, sodium chloride, mannitol, aspartame, acesulfame salt, saccharin salt, neotime, cyclamate salt within the limit of not impairing the physical properties of the film It may be one or more selected from the group consisting of taumatin, nahan fruit extract, licorice extract and enzyme-treated stevia.
명세서 기재의 복잡성을 피하기 위해 중복되는 내용에 대한 추가적인 서술은 생략한다. In order to avoid the complexity of describing the specification, additional descriptions of overlapping content will be omitted.
이하 본 발명의 이해를 돕기 위하여 바람직한 실시예 및 제제예를 제시한다. 그러나 하기 실시예 및 제제예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 이에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred examples and formulation examples are presented to aid in understanding the present invention. However, the following examples and formulation examples are provided for easier understanding of the present invention, and the contents of the present invention are not limited thereby.
실시예Example 1. 시험 물질의 제조 1. Preparation of test substance
구강 내 염증을 억제하고, 구강 세균의 증식을 억제하는 시험물질을 제조하기 위하여, 하기 표 1 과 같은 조성의 시험물질을 제조하였다. In order to produce a test substance that suppresses inflammation in the oral cavity and inhibits the proliferation of oral bacteria, a test substance having the composition shown in Table 1 was prepared.
Figure PCTKR2019004204-appb-img-000001
Figure PCTKR2019004204-appb-img-000001
상기와 같이 제조된 혼합 조성물을 이용하여 이하 구강세균 억제 활성을 확인하였다. 가당난황분말은 애드바이오텍으로부터 구입하여 사용하였다. 어성초는 정제수로 세척하였으며, 추출농도의 15배 정제수를 투입하여 60℃ 에서 2시간 동안 추출하였다. 수득된 어성초 수 추출물을 여과포 또는 0.45μm 스테인레스 매쉬망으로 여과하였다. 삼백초 추출물도 어성초 추출물과 동일한 방법으로 수 추출하여 수득하였다. By using the mixed composition prepared as described above, the activity of inhibiting oral bacteria was confirmed below. Sweetened egg yolk powder was purchased from Adbiotech and used. Eoseongcho was washed with purified water, and purified water 15 times the extraction concentration was added and extracted at 60°C for 2 hours. The obtained Eoseongcho water extract was filtered through a filter cloth or a 0.45 μm stainless steel mesh net. Sambaekcho extract was also obtained by water extraction in the same manner as Eoseongcho extract.
실시예 2. 치은 섬유아세포에 대한 치은염증 억제 효과 확인Example 2. Checking the effect of inhibiting gingival inflammation on gingival fibroblasts
치아 세포 환경에 미치는 영향을 분석하기 위하여 인간 치은 섬유아세포 (Gingival Fibroblast (HGF-1)) 를 ATCC 로부터 구입하여 사용하였다 (ATCC CRL-2014, 63449675). 상기 세포는 구강 연구에 가장 적합한 세포로 알려져 있으며, Gingival LPS 를 처리한 후 PGE2 를 측정하는데 가장 적합한 것으로 알려져 있는 세포이다. Human gingival fibroblasts (HGF-1) were purchased from ATCC and used to analyze the effect on the dental cell environment (ATCC CRL-2014, 63449675). These cells are known to be the most suitable cells for oral studies, and are known to be most suitable for measuring PGE2 after Gingival LPS treatment.
치은 섬유아세포를 온도 37 ℃, 습도 95 %, CO 2 5 % 조건으로 설정된 배양기 안에서 2018년 4월 24일에서 2018년 5월 2일에 걸쳐 배양하였으며, 배양기간 동안 배양기의 온도, 습도, CO 2 농도를 8시간 단위로 확인하였다. 본 실험에는 DMEM 배지, 10% FBS, 2mL L-글루타민, 50U/mL 페니실린, 50 μg/mL 스트렙토마이신을 이용하였다. 세포 배양은 75 cm 2 플라스크를 사용하였다. 이 때 세포의 밀도는 5 X 10 6 cells/flask로 배양하였고, 48 시간 마다 신선한 배지로 교환하였다. 세포 증식 정도를 관찰한 후 70% 이상 증식 시 분리하였다. Gingival fibroblasts were cultured from April 24, 2018 to May 2, 2018 in an incubator set at 37°C, 95% humidity, and 5% CO 2 .During the incubation period, temperature, humidity, and CO 2 The concentration was checked every 8 hours. DMEM medium, 10% FBS, 2 mL L-glutamine, 50 U/mL penicillin, and 50 μg/mL streptomycin were used for this experiment. For cell culture, a 75 cm 2 flask was used. At this time, the cells were cultured at a density of 5 X 10 6 cells/flask and replaced with fresh medium every 48 hours. After observing the degree of cell proliferation, it was isolated when proliferating more than 70%.
2.1 세포 독성 확인2.1 Cytotoxicity check
실시예 1에서 제조한 시험 물질이 구강 세포에 독성을 나타내는지 확인하기 위해 MTT 어세이(Thiazolyl Blue Tetrazolium Blue; Sigma, M5655)를 수행하였다. 염증 물질로 Gingival LPS 1μg/mL 을 처리하고, 실시예 1 에서 제조한 시험물질을 5 내지 1000 μg/mL 로 변화시키면서 HGF-1 세포에 처리한 후 24 시간 배양하였으며, 이 후 세포 증식률 및 PGE2 농도의 변화를 측정하였다. 시험에 사용한 시험군을 표 2에 나타내었다. MTT assay (Thiazolyl Blue Tetrazolium Blue; Sigma, M5655) was performed to confirm whether the test substance prepared in Example 1 exhibits toxicity to oral cells. Gingival LPS 1μg/mL was treated as an inflammatory substance, and the test substance prepared in Example 1 was changed to 5 to 1000 μg/mL, treated on HGF-1 cells, and cultured for 24 hours, after which the cell proliferation rate and PGE2 concentration The change of was measured. Table 2 shows the test groups used for the test.
Figure PCTKR2019004204-appb-img-000002
Figure PCTKR2019004204-appb-img-000002
시험물질과 함께 처리한 세포 배양 배지를 모두 제거한 뒤, 무혈청 DEME 을 이용하여 조심스럽게 세척하였다. 이 후 무혈청 DMEM 을 제거하고 무혈청 배지에 10% Blue Tetrazolium Blue (5 mg/mL) 를 혼합하고, 그 혼합액을 각 웰에 200 μL 동량으로 처리하였다. 5 % CO 2, 37 ℃ 조건에서 120 분간 배양하고, 상층액을 조심스럽게 제거하고 DMSO 를 처리하였다. 마이크로 플레이트 리더의 550nM 파장을 이용하여 흡광도를 측정하였으며 그 결과를 도 1에 나타내었다. After removing all of the cell culture medium treated with the test substance, it was carefully washed with serum-free DEME. Thereafter, the serum-free DMEM was removed, 10% Blue Tetrazolium Blue (5 mg/mL) was mixed in a serum-free medium, and the mixture was treated with an equal amount of 200 μL in each well. 5% CO 2 , Incubated at 37° C. for 120 minutes, and the supernatant was carefully removed and treated with DMSO. The absorbance was measured using the 550nM wavelength of the microplate reader, and the results are shown in FIG. 1.
도 1에 나타낸 바와 같이, 정상 대조군 대비 모든 시험군에서 유의성이 확인되지 않았으며, 모든 농도의 시험물질이 세포 증식에 영향을 미치지 않는 것을 확인하였다.As shown in FIG. 1, significance was not confirmed in all test groups compared to the normal control, and it was confirmed that all concentrations of test substances did not affect cell proliferation.
2.2 PGE 2 (prostaglandin E 2) 억제 어세이 2.2 PGE 2 (prostaglandin E 2 ) inhibition assay
MTT assay와는 별도로 HGF-1 세포에 실시예 1의 시험물질 투여 1 시간 후, Gingival LPS (1 μg/mL)을 처리하였다. 처리 24 시간 후, PGE 2 ELISA Kit (Abcam, USA)를 이용하여 PGE 2의 함량을 확인하였다. 자료의 정규성을 가정하고, 모수적 일원분산분석 (One-way ANOVA)을 이용하여 시험군간의 유의성을 검정하였으며, 유의성이 인정되었을 경우, Dunnett’s multiple comparison test를 이용하여 사후검정을 실시하였다. 통계학적 분석은 Prism 5.03 (GraphPad Software Inc., San Diego, CA, USA)을 이용하여 실시하였으며, p값이 0.05 미만일 경우, 통계학적으로 유의한 것으로 판정하였다. 치은섬유아세포 (HGF-1)에 시험물질 투여 1 시간 뒤, Gingival LPS를 1 μg/mL의 농도로 처리하고 PGE 2 의 발현을 확인하였다. PGE 2 억제 어세이에 사용한 시험군을 표 3에 나타내었고, PGE 2 억제 어세이 결과를 표 4 및 도 2에 나타내었다. Apart from the MTT assay, 1 hour after administration of the test substance of Example 1 to HGF-1 cells, Gingival LPS (1 μg/mL) was treated. After treatment 24 hours, using the PGE 2 ELISA Kit (Abcam, USA ) confirmed the amount of PGE 2. Assuming the normality of the data, the significance between the test groups was tested using a parametric one-way ANOVA, and if the significance was recognized, a post-test was performed using Dunnett's multiple comparison test. Statistical analysis was performed using Prism 5.03 (GraphPad Software Inc., San Diego, CA, USA), and a p value of less than 0.05 was determined to be statistically significant. 1 hour after administration of the test substance to gingival fibroblasts (HGF-1), Gingival LPS was treated at a concentration of 1 μg/mL and PGE 2 The expression of was confirmed. PGE 2 The test groups used in the inhibition assay are shown in Table 3, and the results of the PGE 2 inhibition assay are shown in Table 4 and FIG. 2.
Figure PCTKR2019004204-appb-img-000003
Figure PCTKR2019004204-appb-img-000003
Figure PCTKR2019004204-appb-img-000004
Figure PCTKR2019004204-appb-img-000004
도 2 에 나타낸 바와 같이, PGE 2 의 농도는 Gingival LPS 처리에 의하여 급격하게 증가하였고, 시험물질의 처리에 의하여 농도 의존적으로 유의하게 감소하였다. 따라서 실시예 1에서 제조한 시험물질이 구강세포에서 치은염증 유도산물인 PGE 2 를 효과적으로 억제할 수 있음을 확인하였다. As shown in Fig. 2, the concentration of PGE 2 increased rapidly by Gingival LPS treatment, and significantly decreased in a concentration-dependent manner by treatment of the test substance. Therefore, it was confirmed that the test material prepared in Example 1 can effectively inhibit PGE 2 , a product of inducing gingival inflammation in oral cells.
실시예 3. 구강 질환 유발 세균 억제 효과 확인Example 3. Confirmation of oral disease-causing bacteria inhibition effect
실시예 1 의 제조물질이 구강 세균에 대한 억제 효과를 나타내는지 여부를 확인하기 위하여 구강 세균인 포르피로모나스 진지발린스 ( Porphyromonas gingivalis, P. cangingivalis) 및 포르피로모나스 칸진지발리스 ( Porphyromonas cangingivalis, P. cangingivalis ) 에 처리 후 MIC (Minimal inhibition concentration) 테스트를 수행하였다. P. cangingivalis 및 P. gingivalis를 Tryptic soy broth에 hemin, vitamin K 3 그리고 5 % sheep blood를 첨가하여 만든 배지를 이용하여 37 ℃ 혐기 조건에서 48 시간 동안 배양하였다. 최초 배양된 균을 Tryptic soy agar + hemin + vitamin K 3 + 5 % sheep blood에 도말하여 균수를 측정한 뒤, 2.5 X 10 5 CFU/mL 농도로 희석하여 MIC test에 이용하였다. 96 well에 각각의 실시예 1에서 제조한 시험물질을 동일한 희석배수로 희석한 뒤, 동량의 균을 접종하였다. 48 시간 배양 후 600 nm의 파장을 이용하여 흡광도를 측정하였고 (Biotek, Epoch 2) 정확한 측정을 위하여 각 시험물질의 희석배수의 n 수를 3으로 진행하였다. 구체적으로 각 세균을 증식에 맞는 배지에 안정 배양하여 2.5 X 10 5 CFU/mL 이상 유지하고 혐기 37 ℃ 배양 조건에서 48 시간 배양하였다. 시험물질을 희석배수에 의존하여 각 웰 (96 well plate)에 동량 처리한 후, 각 웰에 동량의 균을 접종하여 37 ℃ 혐기 조건에서 48 시간 동안 배양하였다. Microplate reader를 통해 각 웰의 흡광도 (optical density, 600 nm)를 측정하여 항균성 및 MIC를 확인하였다. IC80 (Inhibitory concentration 80 % maximal), IC70 (Inhibitory concentration 70 % maximal), 및 IC50 (Inhibitory concentration 50 % maximal) 를 하기와 같은 계산식을 이용하여 구하고 그 효과를 확인하였다. In order to determine whether the preparation material of Example 1 exhibits an inhibitory effect on oral bacteria, the oral bacteria Porphyromonas gingivalis (P. cangingivalis ) and Porphyromonas cangingivalis ( Porphyromonas cangingivalis, P. cangingivalis ) , followed by a MIC ( minimal inhibition concentration) test. P. cangingivalis And P. gingivalis were cultured for 48 hours at 37 ℃ anaerobic conditions using a medium prepared by adding hemin, vitamin K 3 and 5% sheep blood to Tryptic soy broth. The first cultured bacteria were smeared on Tryptic soy agar + hemin + vitamin K 3 + 5% sheep blood to measure the number of bacteria, and then diluted to a concentration of 2.5 X 10 5 CFU/mL and used for MIC test. Each test substance prepared in Example 1 was diluted in 96 wells by the same dilution factor, and then the same amount of bacteria was inoculated. After incubation for 48 hours, the absorbance was measured using a wavelength of 600 nm (Biotek, Epoch 2), and n number of the dilution factor of each test substance was set to 3 for accurate measurement. Specifically, each bacterium was stably cultured in a medium suitable for proliferation, maintained at least 2.5 X 10 5 CFU/mL, and cultured for 48 hours in an anaerobic 37° C. culture condition. Depending on the dilution factor, the test substance was treated in an equal amount in each well (96 well plate), and then the same amount of bacteria was inoculated into each well and incubated for 48 hours under anaerobic conditions at 37°C. The absorbance (optical density, 600 nm) of each well was measured through a microplate reader to confirm antimicrobial activity and MIC. IC80 (Inhibitory concentration 80% maximal), IC70 (Inhibitory concentration 70% maximal), and IC50 (Inhibitory concentration 50% maximal) were calculated using the following calculation formula and the effects were confirmed.
식: 100 - [O.D value (시험물질 + 균체) - O.D value (시험물질 Blank 값) / O.D value (PBS + 균체) X 100]Formula: 100-[O.D value (test substance + cells)-O.D value (test substance blank value) / O.D value (PBS + cells) X 100]
각 희석배수에 따른 MIC 결과를 표 5 및 표 6 에 나타내었다. The MIC results according to each dilution factor are shown in Tables 5 and 6.
Figure PCTKR2019004204-appb-img-000005
Figure PCTKR2019004204-appb-img-000005
Figure PCTKR2019004204-appb-img-000006
Figure PCTKR2019004204-appb-img-000006
표 5 에서 P. gingivalis에 대한 시험물질의 항균 능력을 확인한 결과, IC80은 1/128 희석배수에서 확인되었고, IC50은 1/4096 희석배수에서 확인하였다. 표 6에서 P. cangingivalis에 대한 시험물질의 항균 능력을 평가한 결과, IC70은 1/64 희석배수에서 확인되었고, IC50은 1/128 희석배수에서 확인하였다. 상기 결과를 통해 난황분말, 어성초 추출물, 삼백초 추출물을 포함하는 조성물이 구강 세균에 대한 항균 효과를 매우 낮은 희석배수에서도 나타낼 수 있음을 확인하였다. As a result of checking the antibacterial ability of the test substance against P. gingivalis in Table 5, IC80 was confirmed at 1/128 dilution factor, and IC50 was confirmed at 1/4096 dilution factor. As a result of evaluating the antimicrobial ability of the test substance against P. cangingivalis in Table 6, IC70 was confirmed at 1/64 dilution factor, and IC50 was confirmed at 1/128 dilution factor. Through the above results, it was confirmed that the composition including egg yolk powder, Eoseongcho extract, and Sambaekcho extract can exhibit an antibacterial effect against oral bacteria even at a very low dilution factor.
실시예 4. 구강붕해필름 제형의 제조Example 4. Preparation of oral disintegrating film formulation
실시예 2 및 3을 통해 치은염증 억제 및 구강세균억제 효과를 확인한 난황분말, 어성초 추출물 및 삼백초 추출물을 이용하여 구강붕해필름 제형을 제조하였다. 난황분말, 어성초 추출물 및 삼백초 추출물, 글리세린, 폴리소르베이트 20, 폴리소르베이트 80, 효소 처리 분말 스테비아, 비프향 액상, 비프향 합성 착향려, 변성전분, 플루란을 포함하여 필름액을 제조하였다. The oral disintegrating film formulation was prepared using the yolk powder, Eoseongcho extract, and Sambaekcho extract, which confirmed the effect of inhibiting gingivitis and oral bacteria through Examples 2 and 3. A film solution including egg yolk powder, Eoseongcho extract and Sambaekcho extract, glycerin, polysorbate 20, polysorbate 80, enzyme-treated powder stevia, beef flavor liquid, beef flavor synthetic flavor, modified starch, and fluran was prepared.
비프향은 기호도를 높이기 위하여 추가하였으며 분말 또는 액상 형태로 첨가형태를 달리하고 첨가량 2.5, 5, 10mg 으로 달리하면서 제조를 수행하였다. 비프향 첨가 형태 및 양에 따른 구강붕해필름 제조 결과, 비프향을 분말 또는 액상 형태로 10mg 이상, 전체 고형분 합계의 6% 를 초과하여 첨가하는 경우 필름 제작 시 기름이 많이 유출되었으며 붕해가 잘 이루어지지 않음을 확인하였다. 또한 필름 캐스팅 과정에서 도 3과 같이 마더필름과 원필름이 분리되는 현상이 발생하였다. 이러한 조건을 종합적으로 고려하여 필름액의 조성 및 필름의 크기를 조절하였고, 필름 캐스팅, 붕해 효과를 모두 달성할 수 있는 조성으로 가당난황분말 (구입처 애드바이오텍) 30 mg, 삼백초 추출물 10mg, 어성초 추출물 5mg 및 액상 비프향 5mg 을 도출하고 필름의 크기를 27*40mm 로 하여 최종 구강붕해 필름을 제조하였으며, 제조된 구강붕해 필름을 도 4에 나타내었다. 구강붕해 필름의 제조에 사용된 성분 정보 및 필름 사이즈 정보는 하기 표 7 과 같다. Beef flavor was added to enhance the preference, and preparation was carried out while varying the form of addition in powder or liquid form, and different amounts of 2.5, 5, and 10 mg. As a result of manufacturing the oral disintegrating film according to the form and amount of beef flavor added, if the beef flavor is added in powder or liquid form over 10 mg and exceeds 6% of the total solid content, a lot of oil spills out and disintegrates well during film production. It was confirmed that it was not lost. In addition, a phenomenon in which the mother film and the original film are separated as shown in FIG. 3 occurred during the film casting process. In consideration of these conditions, the composition of the film solution and the size of the film were adjusted, and with a composition that can achieve both film casting and disintegration effects, sweetened egg yolk powder (from Adbiotech) 30 mg, Sambaekcho extract 10mg, Eoseongcho extract 5mg And 5 mg of liquid beef flavor was derived, and a final oral disintegrating film was prepared by setting the size of the film to 27 * 40 mm, and the prepared oral disintegrating film is shown in FIG. 4. Component information and film size information used in the preparation of the oral disintegrating film are shown in Table 7 below.
Figure PCTKR2019004204-appb-img-000007
Figure PCTKR2019004204-appb-img-000007
표 7과 같이 필름을 제조하는 경우 마더필름과 원필름의 분리 현상이 관찰되지 않았으며, 제작시 기름이 유출되는 문제가 해소되었다. 또한 제조된 구강붕해필름을 강아지에 급여한 결과 빠른 붕해가 달성됨을 확인하였다. In the case of manufacturing the film as shown in Table 7, the separation phenomenon of the mother film and the original film was not observed, and the problem of oil leakage during production was solved. In addition, it was confirmed that rapid disintegration was achieved as a result of feeding the prepared oral disintegrating film to dogs.
제제예Formulation example 1. 의약품의 제조 1. Manufacturing of pharmaceuticals
1.1 1.1 산제의Powdery 제조 Produce
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
유당 100mg100mg lactose
탈크 10mg10mg talc
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
1.2 정제의 제조1.2 Preparation of tablets
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
옥수수전분 100mg100mg corn starch
유당 100mg100mg lactose
스테아린산 마그네슘 2mg2mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet preparation method.
1.3 캡슐제의 제조1.3 Preparation of capsules
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
옥수수전분 100mg100mg corn starch
유당 100mg100mg lactose
스테아린산 마그네슘 2mg2mg magnesium stearate
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 정제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare tablets.
1.4 주사제의 제조1.4 Preparation of injection
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
주사용 멸균 증류수 적량Suitable amount of sterile distilled water for injection
pH 조절제 적량proper amount of pH adjuster
통상의 주사제의 제조방법에 따라 1 앰플당(2ml) 상기의 성분 함량으로 제조한다.It is prepared with the above ingredients per ampoule (2 ml) according to a conventional injection preparation method.
1.5 1.5 액제의Liquid 제조 Produce
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
설탕 20g20 g sugar
이성화당 20g20g isomerized sugar
레몬향 적량Lemon flavor appropriate amount
정제수를 가하여 전체 1,00ml로 맞추었다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합한 다음, 갈색병에 충전하고 멸균시켜 액제를 제조한다.Purified water was added and the total was adjusted to 1,00ml. The above ingredients are mixed according to a conventional method for preparing a liquid, and then filled in a brown bottle and sterilized to prepare a liquid.
제제예Formulation example 2. 식품의 제조 2. Manufacture of food
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
비타민 혼합물 적량Vitamin mixture right amount
비타민 A 아세테이트 70 ㎍Vitamin A acetate 70 ㎍
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍Vitamin B12 0.2 ㎍
비타민 C 10 ㎎Vitamin C 10 mg
비오틴 10 ㎍Biotin 10 ㎍
니코틴산아미드 1.7 ㎎Nicotinic acid amide 1.7 mg
엽산 50 ㎍ Folic acid 50 ㎍
판토텐산 칼슘 0.5 ㎎0.5 mg of calcium pantothenate
무기질 혼합물 적량Suitable amount of inorganic mixture
황산제1철 1.75 ㎎Ferrous sulfate 1.75 mg
산화아연 0.82 ㎎Zinc oxide 0.82 mg
탄제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dicalcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎100 mg of calcium carbonate
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강기능식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합한 다음, 통상의 방법에 따라 건강기능식품 조성물 제조(예, 영양캔디 등)에 사용할 수 있다.The composition ratio of the vitamin and mineral mixture is relatively suitable for the health functional food, but it is possible to arbitrarily modify the composition, and the above ingredients are mixed according to the general health functional food manufacturing method. Then, it can be used in the manufacture of a health functional food composition (eg, nutritional candy, etc.) according to a conventional method.
제제예Formulation example 3. 음료의 제조 3. Manufacturing of beverages
난황분말, 어성초 추출물 및 삼백초 추출물 100mg100mg of egg yolk powder, Eoseongcho extract and Sambaekcho extract
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 ㎖Total 900 ml by adding purified water
통상의 건강기능성 음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강기능성 음료 조성물 제조에 사용한다. After mixing the above ingredients according to the normal health functional beverage manufacturing method, after stirring and heating at 85°C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 liter container, sealed and sterilized, and stored in a refrigerator. It is used to prepare the health functional beverage composition of the present invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용 용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The composition ratio is composed of ingredients suitable for a relatively preferred beverage in a preferred embodiment, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the demand class, the country of demand, and the intended use.

Claims (13)

  1. 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강세균 억제용 항균 조성물.Antibacterial composition for inhibiting oral bacteria comprising egg yolk powder, Eoseongcho extract, and Sambaekcho extract.
  2. 제1항에 있어서, 상기 어성초 추출물 또는 삼백초 추출물은 물, 탄소수 1 내지 4의 알코올, 아세톤, 에테르, 벤젠, 클로로포름, 에틸아세테이트, 메틸렌클로라이드, n-헥산, 염산, 포름산, 사이클로헥산 및 이들의 혼합물로 이루어진 군에서 선택된 1종의 추출용매에 의해 추출된 것인, 구강세균 억제용 항균 조성물. The method of claim 1, wherein the Eoseongcho extract or Sambaekcho extract is water, alcohol having 1 to 4 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, n-hexane, hydrochloric acid, formic acid, cyclohexane, and mixtures thereof. The antibacterial composition for inhibiting oral bacteria that is extracted by one type of extraction solvent selected from the group consisting of.
  3. 제1항에 있어서, 상기 난황분말, 어성초 추출물 및 삼백초 추출물은 1 내지 5: 0.3 내지 0.8 : 1 의 질량비로 포함되는 것을 특징으로 하는, 구강세균 억제용 항균 조성물. The antibacterial composition of claim 1, wherein the egg yolk powder, Eoseongcho extract and Sambaekcho extract are contained in a mass ratio of 1 to 5: 0.3 to 0.8:1.
  4. 제1항에 있어서, 상기 구강세균은 포르피로모나스 진지발린스 ( Porphyromonas gingivalis) 또는 포르피로모나스 칸진지발리스 ( Porphyromonas cangingivalis) 인, 구강세균 억제용 항균 조성물. The method of claim 1, wherein the oral bacteria are Porphyromonas gingivalis or Porphyromonas cangingivalis . Phosphorus, antibacterial composition for inhibiting oral bacteria.
  5. 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 치료용 약학적 조성물. A pharmaceutical composition for preventing or treating oral diseases comprising egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  6. 제5항에 있어서, 상기 구강질환은 프라그, 잇몸 출혈, 구취, 시린이 및 치아 우식증, 치주염 및 치은염으로 이루어진 군에서 선택된 1종 이상인, 구강질환 예방 또는 치료용 약학적 조성물.The pharmaceutical composition for preventing or treating oral diseases according to claim 5, wherein the oral disease is at least one selected from the group consisting of plaque, bleeding gums, bad breath, aching teeth and dental caries, periodontitis and gingivitis.
  7. 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 개선용 건강기능식품 조성물. Health functional food composition for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  8. 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 개선용 의약외품 조성물. A quasi-drug composition for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  9. 난황분말, 어성초 추출물 및 삼백초 추출물을 포함하는 구강질환 예방 또는 개선용 수의학적 조성물.A veterinary composition for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract and Sambaekcho extract.
  10. 난황분말, 어성초 추출물, 삼백초 추출물 및 필름 형성제를 포함하는 구강질환 예방 또는 개선용 구강붕해필름 제조용 조성물. Composition for producing an oral disintegrating film for preventing or improving oral diseases, including egg yolk powder, Eoseongcho extract, Sambaekcho extract, and film forming agent.
  11. 제10항에 있어서, 액상 조미향을 더 포함하는 구강붕해 필름 제조용 조성물. The composition for manufacturing an oral disintegrating film according to claim 10, further comprising a liquid flavoring flavor.
  12. 제11항에 있어서, 상기 난황분말, 어성초 추출물, 삼백초 추출물 및 액상 조미향은 1 내지 5: 0.3 내지 0.8 : 1: 0.3 내지 0.8의 질량비로 포함되는 것을 특징으로 하는, 구강붕해 필름 제조용 조성물.The composition for preparing an oral disintegrating film according to claim 11, wherein the egg yolk powder, Eoseongcho extract, Sambaekcho extract, and liquid seasoning flavor are included in a mass ratio of 1 to 5: 0.3 to 0.8: 1: 0.3 to 0.8.
  13. 제11항에 있어서, 상기 액상 조미향은 구강붕해 필름 제조용 조성물 총 고형분 합계의 2 내지 5 중량%로 포함되는 것을 특징으로 하는, 구강붕해 필름 제조용 조성물.The composition for producing an oral disintegrating film according to claim 11, wherein the liquid seasoning is contained in an amount of 2 to 5% by weight of the total solid content of the composition for producing an oral disintegrating film.
PCT/KR2019/004204 2019-04-04 2019-04-09 Antimicrobial composition for inhibiting oral bacteria and orally disintegrating film WO2020204242A1 (en)

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KR20120093607A (en) * 2011-02-15 2012-08-23 (주)한일제약 Oral liquid-type composition
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KR101843750B1 (en) * 2016-11-23 2018-04-05 주식회사 케이원 Orally disintegrating film for removing oral smell comprising wild ginseng concentrate and manufacturing method thereof

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