WO2022255654A1 - Pharmaceutical composition for preventing or treating gingivitis or periodontitis comprising aucuba japonica extract - Google Patents
Pharmaceutical composition for preventing or treating gingivitis or periodontitis comprising aucuba japonica extract Download PDFInfo
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- WO2022255654A1 WO2022255654A1 PCT/KR2022/006334 KR2022006334W WO2022255654A1 WO 2022255654 A1 WO2022255654 A1 WO 2022255654A1 KR 2022006334 W KR2022006334 W KR 2022006334W WO 2022255654 A1 WO2022255654 A1 WO 2022255654A1
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- periodontitis
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—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)
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- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/312—Foods, ingredients or supplements having a functional effect on health having an effect on dental health
Definitions
- the present invention relates to a pharmaceutical composition for preventing or treating gingivitis or periodontitis, which is a soft tissue inflammatory disease in the oral cavity, containing a pine tree extract.
- the tooth consists of enamel, dentin, pulp, gingiva (gum), gingival fissure, periodontal ligament, and cementum.
- Enamel is the outermost part of the tooth and is the hardest, highly calcified tissue (96-97% inorganic) in the human body. It serves to chew, cut, grind, and withstand the force applied to the jaw.
- Dentin is located within enamel, which is weaker than enamel and is a part connected to nerves and occupies the largest part of tooth constituent tissues.
- tertiary dentin (reparative dentin), which is formed as a defense mechanism against
- the pulp is a soft tissue unique tissue located in the center of the tooth, composed of 25% organic matter and 75% water, and contains nerves, blood vessels and lymphatic vessels. The pulp is divided into the pulp, which corresponds to the crown, and the root canal, which corresponds to the root of the tooth.
- the gingiva refers to the part that looks red under the teeth and serves as a body that supports the teeth as a soft tissue located at the boundary between the teeth and the mouth. Gingival fissures, also known as gingival pockets, are gaps between teeth and gums and are the cause of most gum disease.
- the periodontal ligament is a fibrous tissue that connects the alveolar bone to the tooth and acts as a shock absorber to absorb forces applied to the tooth.
- Cementum is attached to the periodontal membrane that surrounds the root of the tooth and holds the tooth and gum bone in place. Cementum serves as an adhesive so that the periodontal ligament, which is a trabecular meshwork, can be well attached to the tooth, and it becomes thicker with age.
- Periodontal tissue which physically supports teeth, detects tooth movements, and supplies necessary blood flow to teeth, is composed of four types of tissues surrounding teeth, gingiva, cementum, periodontal ligament, and alveolar bone.
- the teeth are located in the alveolar bone and are held in place by the periodontal ligament.
- the periodontal ligament connects the cementum of the tooth and the alveolar bone, and although it is originally a soft tissue, the cementum or the alveolar bone and the direct bonding site are calcified so that the ligament and the bone are firmly bonded.
- the periodontal ligament absorbs external shocks applied to the teeth, transmits the force of chewing to the alveolar bone, and when chewing food, all teeth move little by little in one direction as a whole to help masticatory activities by adhering to each other, and to protect teeth and teeth from external inflammation and germs. It acts as a barrier to prevent the spread of inflammation to alveolar bone (Republic of Korea Patent Publication 10-2016-0122923).
- Chronic inflammatory diseases occurring in oral soft tissue include gingivitis and periodontitis.
- Complications of chronic diseases such as oral bacterial growth and diabetes are emerging as strong causes of chronic inflammatory diseases in oral soft tissues, and various antibacterial agents, anti-inflammatory agents, and antioxidants are effective in preventing or treating oral chronic inflammatory diseases. It is being used (Korean Registered Patent No. 10-1406106).
- japonica Aucuba japonica
- Kariya African aphid .
- It mainly grows as a garden tree in warm mountains, and is a representative type of temperate evergreen forest, which is distributed in southern Korea, especially in Ulleungdo.
- the fruit of the tree is beautiful and popular for ornamental purposes, and the leaves and bark are used for medicinal purposes.
- Oak trees have traditionally been used to treat inflammation such as neuralgia, arthritis and gout, but nothing is known about their use in the treatment of oral inflammation.
- the inventors of the present invention studied a novel material that can be used for the prevention or treatment of gingivitis or periodontitis, which is an inflammatory disease of oral soft tissue in natural products, while the hot water extract of pine tree improves inflammation such as swelling and redness of soft tissues in the gums,
- the present invention was completed by confirming that destruction of alveolar bone caused by gum inflammation can be effectively inhibited.
- An object of the present invention is to provide a pharmaceutical composition for preventing or treating gingivitis or periodontitis, which is a soft tissue inflammatory disease in the oral cavity, containing a pine extract.
- Another object of the present invention is to provide a health functional food composition for preventing or improving gingivitis or periodontitis containing a pine extract.
- Another object of the present invention is to provide an animal feed composition containing a pine tree extract.
- Another object of the present invention is to provide a method for treating oral soft tissue inflammatory diseases of non-human animals, comprising the step of administering or treating a pine tree extract to animals with oral soft tissue inflammatory symptoms other than humans.
- the present invention provides a pharmaceutical composition for preventing or treating gingivitis or periodontitis containing an extract of Aucuba japonica .
- the pine extract may be characterized in that it is a hot water extract.
- the pine extract may be characterized by extracting leaves, stems or mixtures thereof of pine trees.
- the present invention also provides a health functional food composition for preventing or improving gingivitis or periodontitis containing an extract of cedar.
- the present invention also provides an animal feed composition containing the pine tree extract.
- the present invention also provides a method for treating oral soft tissue inflammatory disease comprising the step of administering an extract of Aucuba japonica to a subject in need thereof.
- the present invention also provides the use of Aucuba japonica extract for the treatment of oral soft tissue inflammatory disease.
- the present invention also provides use of an extract of Aucuba japonica for the preparation of a drug for the treatment of oral soft tissue inflammatory diseases.
- the pine tree extract according to the present invention is a natural component and exhibits excellent therapeutic effects on oral soft tissue inflammatory diseases such as gingivitis or periodontitis without side effects on humans or animals, and is a pharmaceutical composition and food for preventing or treating oral soft tissue inflammatory diseases. It can be used as a composition for animal feed, or as a method for treating inflammatory diseases of soft tissues in the oral cavity of animals.
- 1 is a measurement of the degree of edema and redness of the gums when a beagle dog with gingivitis was treated with a cedar extract.
- Figure 2 is a result of measuring the degree of destruction of alveolar bone when cedar extract was administered to rats with periodontitis.
- the present invention in one aspect relates to a pharmaceutical composition for preventing or treating gingivitis or periodontitis containing an extract .
- the present invention relates to a method for treating oral soft tissue inflammatory disease comprising administering an extract of Aucuba japonica to a subject in need thereof.
- the present invention relates to the use of an extract of Aucuba japonica for the treatment of oral soft tissue inflammatory diseases.
- the present invention relates to the use of an extract of Aucuba japonica for the manufacture of a drug for the treatment of oral soft tissue inflammatory diseases.
- Aucuba japonica used in the present invention is a kind of evergreen subject of the dicotyledonous umbel dogwood family, and is mainly distributed in the southern part of Korea, especially in the Ulleungdo region. In other words, it is also called Doyeop Coral, Cheongakpan, or Blue Tree.
- extract refers to a liquid component obtained by immersing a desired substance in various solvents and then extracting at room temperature, low temperature or elevated temperature for a certain period of time, and removing the solvent from the liquid component. It means the result, such as the obtained solid content.
- it can be comprehensively interpreted as including all dilutions of the results, concentrates thereof, adjusted products, and purified products thereof.
- the pine tree extract may be an extract extracted from the whole aerial part of pine tree, a part thereof, or a material derived therefrom.
- the pine extract is preferably a hot water extract, but is not limited thereto.
- the part may be a stem, leaf, flower, petal or seed of an arboreal tree.
- the pine extract may be characterized by extracting leaves, stems or mixtures thereof of pine trees, but is not limited thereto.
- Whole, part of, or material derived therefrom used for extraction may be ground or shredded or suitably dried.
- the extraction solvent that can be used in the present invention is not particularly limited, and for example, water or an organic solvent may be used, and the organic solvent includes methanol, ethanol, propanol, and isopropanol. , alcohols having 1 to 4 carbon atoms, including butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, Various solvents such as hexane and cyclohexane may be used alone or in combination, but are not limited thereto.
- any one of methods such as hot water extraction, cold brew extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used, preferably hot water extraction.
- the desired extract may be additionally subjected to a conventional fractionation process or may be purified using a conventional purification method.
- any known method may be used.
- the pine extract may be a hot water extract of pine tree, and 3 to 20 times the weight of the medicinal material, preferably 5 to 15 times the water is added, and the temperature is 80 to 120 ° C., preferably 85 to 110 ° C.
- extraction may be performed at a temperature of 90 to 105° C. for 1 to 24 hours, preferably for 2 to 12 hours, and more preferably for 3 to 8 hours, but the hot water extraction method is not limited thereto.
- the extract according to the present invention may be subjected to additional processes such as filtration, concentration, and drying as necessary after the extraction.
- additional processes such as filtration, concentration, and drying as necessary after the extraction.
- the method and conditions of the additional process are not particularly limited, and may be performed by a method known in the art or under commonly performed conditions.
- the final concentration of the pine tree extract may be 10 to 1000 mg/kg, preferably 100 to 250 mg/kg, but is not limited thereto.
- the pharmaceutical composition may include only an effective amount of pine extract or one or more pharmaceutically acceptable carriers, excipients or diluents.
- the term "effective amount (or effective amount)” means an amount that is very sufficient to deliver desired effects but is small enough to sufficiently prevent serious side effects within the scope of medical judgment.
- the amount of the composition administered to the body by the composition of the present invention may be appropriately adjusted in consideration of the route of administration and the subject of administration.
- pharmaceutically acceptable refers to a composition that is physiologically acceptable and does not cause allergic reactions such as gastrointestinal disorders and dizziness or similar reactions when administered to humans.
- Carriers or media usable in the present invention include solvents, dispersants, coatings, absorption accelerators, controlled release agents (i.e. sustained release agents), and one or more inert excipients (starch, polyols, granules, microfine cellulose, microcrystalline cellulose (including, for example, cellspheres, cellphere beads, diluents, lubricants, binders, disintegrants, etc.), etc.
- Pharmaceutically acceptable carriers and pharmaceutical Excipients for use as acceptable inert carriers and examples of such additional ingredients include, but are not limited to, binders, fillers, disintegrants, lubricants, antimicrobial agents, and coating agents.
- the pharmaceutical composition according to the present invention is formulated in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively. and can be used.
- Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc.
- various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included.
- Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, flavor enhancers, preservatives or mucosal adhesives.
- Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
- injectable esters such as ethyl oleate
- a base for the suppository witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.
- the dosage form may be in the form of a powder, granule, tablet, emulsion, syrup, aerosol, soft or hard gelatin capsule, sterile injectable solution, or sterile powder.
- the composition for preventing or treating diseases according to the present invention can be administered through various routes including oral, transdermal, subcutaneous, intravenous or intramuscular, and the dosage of the active ingredient depends on the route of administration, the patient's age, sex, and body weight. And it can be appropriately selected according to various factors such as the severity of the patient, and can be administered in combination with a known compound having an effect of preventing, improving or treating symptoms of a disease.
- the amount of the extract according to the present invention may vary depending on the patient's age, sex, and weight, but may be administered once or several times a day at 10 to 1000 mg/kg.
- the dosage may be increased or decreased depending on the route of administration, severity of disease, sex, weight, age, and the like. Therefore, the dosage is not intended to limit the scope of the present invention in any way.
- the term 'treatment' relates to caring for a diseased subject in order to improve, cure, or reduce the symptoms of a disease or to reduce or halt the progression of a disease.
- the term 'prevention' relates to averting, delaying, impeding, or hindering reducing a disease.
- the pharmaceutical composition for treating or preventing gingivitis or periodontitis containing an extract of gingivitis according to the present invention can be used for the purpose of treating or preventing gingivitis and/or periodontitis in mammals, including humans, and is also applied to companion animals such as dogs and cats. this will be possible
- the present invention may be characterized in that it provides a pharmaceutical composition for preventing or treating oral soft tissue inflammatory diseases containing a pine tree extract, wherein the oral soft tissue inflammatory diseases may be gingivitis and/or periodontitis. .
- the present invention relates to a composition for food for preventing or improving soft tissue inflammation in the oral cavity containing an extract of Aucuba japonica, and specifically for preventing or improving gingivitis and/or periodontitis containing an extract of Aucuba japonica in some embodiments. It relates to a health functional food composition.
- the food may be a main ingredient, supplementary ingredient, food additive, health functional food or functional beverage of food, but is not limited thereto.
- Food to which the food composition according to the present invention can be added includes, for example, various foods, beverages, chewing gum, tea, vitamin complexes, health functional foods, and other functional foods.
- foods include special nutritional foods (eg, formula milk, infant/young child food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), breads, health supplements, seasonings Foods (eg, soy sauce, soybean paste, gochujang, mixed paste, etc.), sauces, confectionery (eg, snacks), candies, chocolates, chewing gum, ice cream, dairy products (eg, fermented milk, cheese, etc.), other processed foods, kimchi, It includes, but is not limited to, pickled foods (various types of kimchi, pickled vegetables, etc.), beverages (eg, fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.).
- the food includes, but is
- the health functional food refers to a food group or food composition that has added value so that the function of the food acts for a specific purpose by using physical, biochemical, or bioengineering methods, etc. It refers to food designed and processed to sufficiently express the body's regulatory function related to the living body.
- the functional food may include food additives that are acceptable in food science, and may further include one or more of appropriate carriers, additives, excipients, and diluents commonly used in the manufacture of functional foods.
- the health functional food may be formulated as one selected from the group consisting of tablets, pills, powders, granules, powders, capsules and liquid formulations by further including one or more of carriers, diluents, excipients and additives.
- carriers diluents, excipients and additives.
- examples of foods to which the extract of the present invention can be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gum, tea, vitamin complexes, health functional foods, and the like.
- Additives that may be further included in the present invention include natural carbohydrates, flavors, flavor enhancers, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors, etc.), colorants, fillers (cheese, chocolate) Etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation agents and at least one component selected from the group consisting of fruit flesh can be used
- natural carbohydrates examples include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol.
- natural flavoring agents thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
- the health functional food of the present invention is various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like.
- the composition according to the present invention may contain fruit flesh for preparing natural fruit juice and vegetable beverages. These components may be used independently or in combination.
- carrier examples include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium phosphate, calcium Silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methylcellulose, methyl hydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate And at least one selected from the group consisting of mineral oil is preferably used.
- the health functional food of the present invention When formulating the health functional food of the present invention, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
- diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
- the content of the extract according to the present invention as an active ingredient in the above-described formulation can be appropriately adjusted according to the type and purpose of use, the patient's condition, the type and severity of symptoms, etc., and is 0.001 to 99.9% by weight based on the solid content weight, preferably. It may be 0.01 to 50% by weight, but is not limited thereto.
- the content of the extract may be 1 to 10% by weight, for example about 2% by weight.
- the dosage of the health functional food of the present invention may vary depending on the patient's age, weight, sex, dosage form, state of health and degree of disease, and may be administered once or several times a day at regular time intervals according to the judgment of a doctor or pharmacist. Split doses may also be used.
- the daily dosage may be 10 to 1000 mg/kg based on the active ingredient content.
- the above dosage is an example of an average case, and the dosage may be higher or lower depending on individual differences. If the daily dose of the health functional food of the present invention is less than the above dose, a significant effect may not be obtained, and if it exceeds more than that, it is uneconomical and may cause undesirable side effects because it is out of the range of the usual dose. have.
- the functional beverage refers to a general term for drinking to quench thirst or enjoy the taste, and there are no particular restrictions on other components other than including a composition for improving or preventing the disease symptoms as an essential component in the indicated ratio.
- various flavoring agents or natural carbohydrates may be included as additional components.
- the food composition of the present invention contains various nutrients, vitamins, minerals (electrolytes), natural carbohydrates, flavors such as synthetic flavors and natural flavors, coloring agents and fillers (cheese, chocolate, etc.) ), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages and fruit flesh, etc. can be used independently or in combination.
- the present invention relates to an animal feed composition comprising a pine tree extract.
- the feed composition of the present invention includes a pine extract as an active ingredient in order to prevent, treat, improve, or alleviate oral soft tissue inflammatory diseases or symptoms, such as gingivitis and/or periodontitis, and can be used in any formulation conventionally prepared in the art. can be manufactured.
- the feed composition of the present invention may include auxiliary components such as amino acids, inorganic salts, vitamins, antibiotics, antimicrobial substances, antioxidants, antifungal enzymes, and other probiotic-type microorganism preparations; grains such as ground or crushed wheat, oats, barley, corn and rice; vegetable protein feeds such as those based on rape, soybean and sunflower; animal protein feed such as blood meal, meat meal, bone meal and fish meal; dry ingredients consisting of sugar and dairy products, such as various powdered milk and whey powder; main components such as lipids, for example, animal fats and vegetable fats optionally liquefied by heating; Additives such as nutritional supplements, digestion and absorption enhancers, growth promoters, and disease preventives may be further included.
- auxiliary components such as amino acids, inorganic salts, vitamins, antibiotics, antimicrobial substances, antioxidants, antifungal enzymes, and other probiotic-type microorganism preparations
- grains such as ground or crushed wheat, oats, barley
- the feed composition of the present invention may be in the form of a powder or liquid formulation, and may include an excipient for feed additives.
- Excipients for feed additives include, for example, calcium carbonate, horse powder, zeolite, jade powder or rice bran, but are not limited thereto.
- the present invention relates to a method for treating oral soft tissue inflammatory disease in an animal comprising administering an Aucuba japonica extract to an animal having oral soft tissue inflammatory symptoms.
- the soft tissue inflammation symptoms in the oral cavity may be gingivitis and/or periodontitis symptoms, but are not limited thereto.
- the animal may be a mammal, preferably a companion animal such as a dog or cat, but is not limited thereto, and a person skilled in the art has a dental structure similar to that of a dog or cat. It will be possible to easily apply the present technology to mammals that have it.
- the animal may be a human.
- the pine tree extract may be administered as an oral agent, oral spray or oral ointment, or treated with a liquid toothpaste or mouthwash, but is not limited thereto.
- the pine extract may be characterized in that it is administered in a daily dose of 0.1 to 10000 mg/kg, preferably 1 to 1000 mg/kg, but is not limited thereto.
- the pine extract may be administered in a daily dose of 10 to 300 mg/kg, for example, about 50 mg/kg, 100 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg. It can be administered in a daily dosage of a dose.
- the pine tree extract may be administered at a dosage of 1 to 100 mg/day, preferably 5 to 50 mg/day, but is not limited thereto.
- the leaves and stems of the cedar tree were collected from the forest in Jisepo-ri, Irun-myeon, Geoje-si, Gyeongsangnam-do in August 2020, and the evidence specimen is stored in the sample storage room of Chonbuk National University.
- 900 L of distilled water was added to 100 kg of pine tree, heated at 100 ° C. for 3 hours, concentrated under reduced pressure, and then dried to prepare a hot water extract of pine tree.
- Example 2 Inflammation improvement efficacy test, such as gum swelling and redness inhibition in beagle dogs with gingivitis (gingivitis)
- composition of oral ointment containing pine tree extract ingredient Content consists of 2% cedar extract oral ointment Vehicle oral ointment without cedar extract cedar extract 400 mg - Sodium polyacrylate (PAA, mucoadhesive) 300mg 300mg Mannitol (flavor enhancer) 100 mg 100 mg Methyl paraben (preservative) 18mg 18mg Poly parabens (preservative) 2mg 2 mg
- 1.0 g/day of the prepared oral ointment was applied to the gingival region of the upper molars on both sides of the maxilla twice a day for 4 weeks.
- the content of the active ingredient contained in 1.0 g/day was 20 mg/day.
- the gingivitis index of the gums of the beagle dog treated with the vehicle oral ointment without the pine extract was deteriorated over time, whereas the beagle administered the oral ointment containing the pine extract.
- the gingivitis index decreased by about 15%.
- the day of inducing periodontitis was set as day 0, and the rats were sacrificed 2 weeks after the day of inducing periodontitis.
- pine extract was orally administered at concentrations of 50, 100, and 250 mg/kg once a day, and only vehicle (DW) was orally administered to the control group. It was confirmed whether the suture was maintained from the day periodontitis was induced to the day the rat was sacrificed.
- the rats were sacrificed and their mandibles were removed. Thereafter, all soft tissues were removed by treatment with 1M NaOH for about 1 hour, and then the degree of alveolar bone loss was quantified by measuring the length from the cemento-enamel junction to the crest of the alveolar bone.
- the pine tree extract according to the present invention is a natural ingredient and exhibits excellent therapeutic effects on oral soft tissue inflammatory diseases such as gingivitis or periodontitis without side effects on humans or animals, and is a pharmaceutical composition and food for preventing or treating oral soft tissue inflammatory diseases. It can be used as a composition for animal feed, or as a method for treating inflammatory diseases of soft tissues in the oral cavity of animals.
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Abstract
The present invention relates to a pharmaceutical composition for the prevention or treatment of gingivitis or periodontitis, comprising an Aucuba japonica extract as an active ingredient. The Aucuba japonica extract according to the present invention is a natural ingredient and exhibits an excellent effect of treating inflammatory diseases of soft tissues in the oral cavity, such as gingivitis or periodontitis, without side effects in humans or animals, and thus can be used as a pharmaceutical composition and food composition for the prevention or treatment of gingivitis, periodontitis, or the like and can be used in an animal feed composition or a method for treating inflammatory diseases of soft tissues in the oral cavity of animals.
Description
본 발명은 식나무 추출물을 포함하는 구강 내 연조직 염증 질환인 치은염 또는 치주염의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing or treating gingivitis or periodontitis, which is a soft tissue inflammatory disease in the oral cavity, containing a pine tree extract.
치아는 법랑질, 상아질, 치수, 치은(잇몸), 치은열구, 치주인대 및 백악질로 이루어져 있다. 법랑질은 치아의 가장 바깥쪽을 구성하는 부분이며 인체에서 가장 단단한, 고도로 석회화된 조직(무기질 96~97%)으로 음식물을 씹고, 끊고, 갈고, 턱에 가해지는 힘을 견디는 역할을 한다. 법랑질 안에는 상아질이 위치하는데, 상아질은 법랑질 보다 약하고 신경으로 연결되는 부위이며 치아 구성 조직 중 가장 많은 부분을 차지한다. 70%의 무기질, 18%의 유기질 및 12%의 수분으로 구성되어 있고, 일생동안 계속해서 형성되며 형성 시기에 따라 치근형성 전 형성되는 1차상아질과 치근형성 후 형성되는 2차 상아질, 이물질의 칩입에 대해 방어기전으로 형성되는 3차상아질(수복상아질)로 구분된다. 치수(pulp)는 치아 중심부에 위치한 연조직성 고유조직으로 25%의 유기질과 75%의 수분으로 구성되며 신경, 혈관 및 림프관이 존재한다. 치수는 치관에 해당되는 수실과 치근에 해당되는 치근관으로 구분되며 상아질을 형성하고 치아의 영양공급과 지각을 담당하는 역할을 한다. 치은(잇몸)은 치아 아래로 붉게 보이는 부분을 말하며 치아와 입안이 연결되는 경계부위에 있는 연조직으로 치아를 지탱해주는 몸체 역할을 한다. 치은열구는 치은낭이라고도 하며 치아와 잇몸 사이의 벌어진 틈을 말하며 대부분의 잇몸병이 발생하는 원인이 되는 부위이다. 치주인대는 치조골과 치아를 연결하는 섬유조직으로 치아에 가해지는 힘을 흡수하는 완충역할을 한다. 백악질은 치아의 뿌리 부분을 둘러싸고 있는, 치아와 잇몸 뼈를 고정하는 치근막에 부착되어 있다. 백악질은 섬유주인 치주인대가 치아에 잘 붙어있을 수 있도록 접착제 역할을 하며 나이가 들수록 두꺼워지는데, 나이가 들어 법랑질 부분이 닳게 되면 뿌리 끝 부분의 백악질이 두꺼워지면서 치아의 높이를 메우기 때문이다.The tooth consists of enamel, dentin, pulp, gingiva (gum), gingival fissure, periodontal ligament, and cementum. Enamel is the outermost part of the tooth and is the hardest, highly calcified tissue (96-97% inorganic) in the human body. It serves to chew, cut, grind, and withstand the force applied to the jaw. Dentin is located within enamel, which is weaker than enamel and is a part connected to nerves and occupies the largest part of tooth constituent tissues. Composed of 70% inorganic matter, 18% organic matter, and 12% water, it is continuously formed throughout life, and depending on the period of formation, primary dentin formed before root formation and secondary dentin formed after root formation, intrusion of foreign matter It is divided into tertiary dentin (reparative dentin), which is formed as a defense mechanism against The pulp is a soft tissue unique tissue located in the center of the tooth, composed of 25% organic matter and 75% water, and contains nerves, blood vessels and lymphatic vessels. The pulp is divided into the pulp, which corresponds to the crown, and the root canal, which corresponds to the root of the tooth. The gingiva (gum) refers to the part that looks red under the teeth and serves as a body that supports the teeth as a soft tissue located at the boundary between the teeth and the mouth. Gingival fissures, also known as gingival pockets, are gaps between teeth and gums and are the cause of most gum disease. The periodontal ligament is a fibrous tissue that connects the alveolar bone to the tooth and acts as a shock absorber to absorb forces applied to the tooth. Cementum is attached to the periodontal membrane that surrounds the root of the tooth and holds the tooth and gum bone in place. Cementum serves as an adhesive so that the periodontal ligament, which is a trabecular meshwork, can be well attached to the tooth, and it becomes thicker with age.
치아를 물리적으로 지지하고, 치아의 움직임을 감지하며 치아에 필요한 혈류 등을 공급하는 치주조직은 치아를 둘러싸고 있는 4종류의 조직, 치은, 백악질, 치주인대 및 치조골으로 구성된다. 치아는 치조골 안에 위치하며 치주인대에 의해 고정된다. 치주인대는 치아의 백악질과 치조골을 연결하며, 본디 부드러운 조직(soft tissue)이지만 백악질 또는 치조골과 직접 결합하는 부위는 석회화되어 인대와 뼈가 단단히 결합하도록 한다. 또한 치주인대는 치아에 가해지는 외부 충격을 흡수하고, 씹는 힘을 치조골에 전달하며 음식물을 씹을 때 모든 치아가 전체적으로 한 방향으로 조금씩 움직이게 하여 서로를 밀착시킴으로써 저작활동을 도우며 외부염증과 세균으로부터 치아 및 치조골로의 염증확산을 막는 방어벽 역할을 한다 (대한민국 공개특허 10-2016-0122923). Periodontal tissue, which physically supports teeth, detects tooth movements, and supplies necessary blood flow to teeth, is composed of four types of tissues surrounding teeth, gingiva, cementum, periodontal ligament, and alveolar bone. The teeth are located in the alveolar bone and are held in place by the periodontal ligament. The periodontal ligament connects the cementum of the tooth and the alveolar bone, and although it is originally a soft tissue, the cementum or the alveolar bone and the direct bonding site are calcified so that the ligament and the bone are firmly bonded. In addition, the periodontal ligament absorbs external shocks applied to the teeth, transmits the force of chewing to the alveolar bone, and when chewing food, all teeth move little by little in one direction as a whole to help masticatory activities by adhering to each other, and to protect teeth and teeth from external inflammation and germs. It acts as a barrier to prevent the spread of inflammation to alveolar bone (Republic of Korea Patent Publication 10-2016-0122923).
구강내 연조직에서 발생하는 대표적인 만성 염증성 질환으로는 치은염과 치주염 있다. 구강내 상제하는 세균의 증식 및 당뇨병 등과 같은 만성질환의 합병증이 구강내 연조직에서 만성염증성 질환의 강력한 병인으로 부각되고 있으며 다양한 항균제, 항염제, 항산화제 등이 이들 구강내 만성염증성 질환의 예방이나 치료에 사용되고 있다 (대한민국 등록특허 10-1406106). Representative chronic inflammatory diseases occurring in oral soft tissue include gingivitis and periodontitis. Complications of chronic diseases such as oral bacterial growth and diabetes are emerging as strong causes of chronic inflammatory diseases in oral soft tissues, and various antibacterial agents, anti-inflammatory agents, and antioxidants are effective in preventing or treating oral chronic inflammatory diseases. It is being used (Korean Registered Patent No. 10-1406106).
한편, 식나무 (Aucuba japonica)는 우리나라 남해 및 제주 일대에서 자라는 가리야과 활엽관목으로 주로 따뜻한 산지에서 정원수로 자라며, 온대 조엽수림을 이루는 대표적인 종류로서 한국 남부, 특히 울릉도 지역에 분포하고 있다. 식나무의 열매는 아름다워 관상용으로 인기가 있고 잎과 수피는 약용에 사용하는데 생약명을 도엽산호(桃葉珊瑚), 천각판(天脚板) 혹은 청목(靑木)이라고 한다. 식나무는 전통적으로 신경통이나 관절염, 통풍과 같은 염증을 치료하는데 사용되어 왔으나 구강 염증 치료 용도에 대해서는 아직 알려진 바 없다.On the other hand, japonica ( Aucuba japonica ) is a broad-leaved shrub of the family Kariya that grows in the southern seas and Jeju of Korea. It mainly grows as a garden tree in warm mountains, and is a representative type of temperate evergreen forest, which is distributed in southern Korea, especially in Ulleungdo. The fruit of the tree is beautiful and popular for ornamental purposes, and the leaves and bark are used for medicinal purposes. Oak trees have traditionally been used to treat inflammation such as neuralgia, arthritis and gout, but nothing is known about their use in the treatment of oral inflammation.
이에, 본 발명자들은 천연물에서 구강내 연조직 염증질환인 치은염 또는 치주염의 예방이나 치료에 사용할 수 있는 신규한 물질에 대해 연구하던 중, 식나무 열수 추출물이 잇몸 연조직의 부종 및 발적과 같은 염증을 개선하며, 잇몸의 염증에 의한 치조골의 파괴를 효과적으로 억제할 수 있음을 확인하여 본 발명을 완성하였다. Accordingly, the inventors of the present invention studied a novel material that can be used for the prevention or treatment of gingivitis or periodontitis, which is an inflammatory disease of oral soft tissue in natural products, while the hot water extract of pine tree improves inflammation such as swelling and redness of soft tissues in the gums, The present invention was completed by confirming that destruction of alveolar bone caused by gum inflammation can be effectively inhibited.
본 발명의 목적은 식나무 추출물을 포함하는 구강내 연조직 염증 질환인 치은염 또는 치주염의 예방 또는 치료용 약학적 조성물을 제공하는데 있다.An object of the present invention is to provide a pharmaceutical composition for preventing or treating gingivitis or periodontitis, which is a soft tissue inflammatory disease in the oral cavity, containing a pine extract.
본 발명의 다른 목적은 식나무 추출물을 포함하는 치은염 또는 치주염 예방 또는 개선용 건강기능식품 조성물을 제공하는데 있다.Another object of the present invention is to provide a health functional food composition for preventing or improving gingivitis or periodontitis containing a pine extract.
본 발명의 또 다른 목적은 식나무 추출물을 포함하는 동물용 사료 조성물을 제공하는데 있다.Another object of the present invention is to provide an animal feed composition containing a pine tree extract.
본 발명의 또 다른 목적은 인간을 제외한 구강내 연조직 염증 증상이 있는 동물에게 식나무 추출물을 투여하거나 처리하는 단계를 포함하는 인간을 제외한 동물의 구강내 연조직 염증 질환 치료방법을 제공하는데 있다. Another object of the present invention is to provide a method for treating oral soft tissue inflammatory diseases of non-human animals, comprising the step of administering or treating a pine tree extract to animals with oral soft tissue inflammatory symptoms other than humans.
상기 목적을 달성하기 위하여 본 발명은 식나무(Aucuba japonica) 추출물을 포함하는 치은염 또는 치주염의 예방 또는 치료용 약학적 조성물을 제공한다. In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating gingivitis or periodontitis containing an extract of Aucuba japonica .
본 발명에 있어서, 상기 식나무 추출물은 열수 추출물인 것을 특징으로 할 수 있다.In the present invention, the pine extract may be characterized in that it is a hot water extract.
본 발명에 있어서, 상기 식나무 추출물은 식나무의 잎, 줄기 또는 이의 혼합물을 추출한 것을 특징으로 할 수 있다.In the present invention, the pine extract may be characterized by extracting leaves, stems or mixtures thereof of pine trees.
본 발명은 또한 식나무 추출물을 포함하는 치은염 또는 치주염 예방 또는 개선용 건강기능식품 조성물을 제공한다. The present invention also provides a health functional food composition for preventing or improving gingivitis or periodontitis containing an extract of cedar.
본 발명은 또한 식나무 추출물을 포함하는 동물용 사료 조성물을 제공한다.The present invention also provides an animal feed composition containing the pine tree extract.
본 발명은 또한 식나무(Aucuba japonica) 추출물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는 구강내 연조직 염증 질환 치료방법을 제공한다.The present invention also provides a method for treating oral soft tissue inflammatory disease comprising the step of administering an extract of Aucuba japonica to a subject in need thereof.
본 발명은 또한 구강내 연조직 염증 질환 치료를 위한 식나무(Aucuba japonica) 추출물의 용도를 제공한다.The present invention also provides the use of Aucuba japonica extract for the treatment of oral soft tissue inflammatory disease.
본 발명은 또한 구강내 연조직 염증 질환 치료를 위한 약물의 제조를 위한 식나무(Aucuba japonica) 추출물의 용도를 제공한다.The present invention also provides use of an extract of Aucuba japonica for the preparation of a drug for the treatment of oral soft tissue inflammatory diseases.
본 발명에 따른 식나무 추출물은 천연 성분으로 인간이나 동물에 부작용 없이 치은염 또는 치주염과 같은 구강내 연조직 염증 질환에 우수한 치료 효과를 발휘하는 바, 구강내 연조직 염증 질환의 예방 또는 치료용 약학적 조성물과 식품용 조성물로 활용할 수 있고, 동물의 사료 조성물이나 동물의 구강내 연조직 염증 질환 치료방법으로의 활용이 가능하다. The pine tree extract according to the present invention is a natural component and exhibits excellent therapeutic effects on oral soft tissue inflammatory diseases such as gingivitis or periodontitis without side effects on humans or animals, and is a pharmaceutical composition and food for preventing or treating oral soft tissue inflammatory diseases. It can be used as a composition for animal feed, or as a method for treating inflammatory diseases of soft tissues in the oral cavity of animals.
도 1은 치은염(gingivitis)을 가진 비글견 (beagle dog)에 식나무 추출물을 처리했을 때 잇몸의 부종 및 발적 정도를 측정한 것이다.1 is a measurement of the degree of edema and redness of the gums when a beagle dog with gingivitis was treated with a cedar extract.
도 2는 치주염(periodontitis)을 유발한 쥐에 식나무 추출물을 투여했을 때, 치조골의 파괴 정도를 측정한 결과이다. Figure 2 is a result of measuring the degree of destruction of alveolar bone when cedar extract was administered to rats with periodontitis.
다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술분야에서 숙련된 전문가에 의해서 통상적으로 이해되는 것과 동일한 의미를 갖는다. 일반적으로 본 명세서에서 사용된 명명법은 본 기술 분야에서 잘 알려져 있고 통상적으로 사용되는 것이다.Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is one well known and commonly used in the art.
본 발명에서는 치은염을 가지는 비글견 (beagle dog)에 식나무 추출물을 4 주간 투여한 결과 잇몸의 부종 및 발적과 같은 잇몸의 만성염증에 의한 치은염 증상이 개선되고 (도 1), 나아가 치주염 동물 모델(ligature-induced periodontitis rat)에 식나무 추출물을 2주간 투여한 결과, 농도 의존적으로 잇몸 염증에 의한 치조골 파괴를 억제하는 효과가 있음을 확인하였다 (도 2). In the present invention, as a result of administering cedar extract to a beagle dog with gingivitis for 4 weeks, symptoms of gingivitis caused by chronic inflammation of the gums, such as swelling and redness of the gums, are improved (FIG. 1), and furthermore, a periodontitis animal model (ligature -induced periodontitis rats), as a result of administering the pine extract for 2 weeks, it was confirmed that there was an effect of suppressing alveolar bone destruction caused by gum inflammation in a concentration-dependent manner (FIG. 2).
따라서, 본 발명은 일 관점에서 식나무(Aucuba japonica) 추출물을 포함하는 치은염 또는 치주염 예방 또는 치료용 약학적 조성물에 관한 것이다.Accordingly, the present invention in one aspect relates to a pharmaceutical composition for preventing or treating gingivitis or periodontitis containing an extract .
다른 관점에서, 본 발명은 본 발명은 식나무(Aucuba japonica) 추출물을 이를 필요로 하는 개체에 투여하는 단계를 포함하는 구강내 연조직 염증 질환 치료방법에 관한 것이다.In another aspect, the present invention relates to a method for treating oral soft tissue inflammatory disease comprising administering an extract of Aucuba japonica to a subject in need thereof.
또 다른 관점에서, 본 발명은 구강내 연조직 염증 질환 치료를 위한 식나무(Aucuba japonica) 추출물의 용도에 관한 것이다.In another aspect, the present invention relates to the use of an extract of Aucuba japonica for the treatment of oral soft tissue inflammatory diseases.
또 다른 관점에서, 본 발명은 구강내 연조직 염증 질환 치료를 위한 약물의 제조를 위한 식나무(Aucuba japonica) 추출물의 용도에 관한 것이다.In another aspect, the present invention relates to the use of an extract of Aucuba japonica for the manufacture of a drug for the treatment of oral soft tissue inflammatory diseases.
본 발명에서 사용되는 "식나무(Aucuba japonica)"는 쌍떡잎식물 산형화목 층층나무과의 상록과목의 일종으로서, 한국 남부, 특히 울릉도 지역에 주로 분포하고 있다. 다른 말로 도엽산호(桃葉珊瑚), 천각판(天脚板) 혹은 청목(靑木)이라고도 부르기도 한다." Aucuba japonica " used in the present invention is a kind of evergreen subject of the dicotyledonous umbel dogwood family, and is mainly distributed in the southern part of Korea, especially in the Ulleungdo region. In other words, it is also called Doyeop Coral, Cheongakpan, or Blue Tree.
본 발명에서의 용어, "추출물(extract)"이란, 목적하는 물질을 다양한 용매에 침지한 다음, 상온, 저온 또는 가온 상태에서 일정시간 동안 추출하여 수득한 액상성분, 상기 액상성분으로부터 용매를 제거하여 수득한 고형분 등의 결과물을 의미한다. 뿐만 아니라, 상기 결과물에 더하여, 상기 결과물의 희석액, 이들의 농축액, 이들의 조정제물, 정제물 등을 모두 포함하는 것으로 포괄적으로 해석될 수 있다.As used herein, the term "extract" refers to a liquid component obtained by immersing a desired substance in various solvents and then extracting at room temperature, low temperature or elevated temperature for a certain period of time, and removing the solvent from the liquid component. It means the result, such as the obtained solid content. In addition, in addition to the above results, it can be comprehensively interpreted as including all dilutions of the results, concentrates thereof, adjusted products, and purified products thereof.
본 발명에 있어서, 상기 식나무 추출물은 식나무의 지상부의 전체, 그 일부분, 또는 이들로부터 유래된 재료로부터 추출된 추출물일 수 있다. 본 발명에 있어서, 상기 식나무 추출물은 열수 추출물인 것이 바람직하나, 이에 한정되지는 않는다. In the present invention, the pine tree extract may be an extract extracted from the whole aerial part of pine tree, a part thereof, or a material derived therefrom. In the present invention, the pine extract is preferably a hot water extract, but is not limited thereto.
본 발명에 있어서, 상기 일부분은 식나무의 줄기, 잎, 꽃, 꽃잎 또는 종실일 수 있다. 바람직하게는, 상기 식나무 추출물은 식나무의 잎, 줄기 또는 이의 혼합물을 추출한 것을 특징으로 할 수 있으나, 이에 한정되지는 않는다.In the present invention, the part may be a stem, leaf, flower, petal or seed of an arboreal tree. Preferably, the pine extract may be characterized by extracting leaves, stems or mixtures thereof of pine trees, but is not limited thereto.
추출에 사용된 상기 식나무의 전체, 그 일부분, 또는 이들로부터 유래된 재료는 분쇄 또는 세절되거나 적당하게 건조된 것일 수 있다. Whole, part of, or material derived therefrom used for extraction may be ground or shredded or suitably dried.
본 발명에서 사용될 수 있는 추출 용매는 특별히 한정되지 않으며, 예를 들면, 물 또는 유기용매를 사용할 수 있고, 유기용매로는 메탄올 (methanol), 에탄올(ethanol), 프로판올(propanol), 이소프로판올(isopropanol), 부탄올(butanol) 등을 포함하는 탄소수 1 내지 4의 알코올, 아세톤(acetone), 에테르(ether), 벤젠(benzene), 클로로포름(chloroform), 에틸아세테이트(ethyl acetate), 메틸렌클로라이드(methylene chloride), 헥산(hexane) 및 시클로헥산 (cyclohexane) 등의 각종 용매를 단독으로 혹은 혼합하여 사용할 수 있으나, 이에 한정되지는 않는다.The extraction solvent that can be used in the present invention is not particularly limited, and for example, water or an organic solvent may be used, and the organic solvent includes methanol, ethanol, propanol, and isopropanol. , alcohols having 1 to 4 carbon atoms, including butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, Various solvents such as hexane and cyclohexane may be used alone or in combination, but are not limited thereto.
추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법 중 어느 하나를 선택하여 사용할 수 있으며, 바람직하게는 열수추출법일 수 있다. 또한, 목적하는 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다. 본 발명에 따른 추출물의 제조방법에는 제한이 없으며, 공지되어 있는 어떠한 방법도 이용될 수 있다.As an extraction method, any one of methods such as hot water extraction, cold brew extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used, preferably hot water extraction. In addition, the desired extract may be additionally subjected to a conventional fractionation process or may be purified using a conventional purification method. There is no limitation on the preparation method of the extract according to the present invention, and any known method may be used.
본 발명의 바람직한 일 양태로, 식나무 추출물은 식나무 열수 추출물일 수 있으며, 약재 중량의 3 내지 20배, 바람직하게는 5 내지 15배의 물을 가하여, 80 내지 120℃바람직하게는 85 내지 110℃보다 바람직하게는 90 내지 105℃의 온도로, 1 내지 24시간, 바람직하게는 2 내지 12 시간, 보다 바람직하게는 3 내지 8 시간 추출할 수 있으나, 열수 추출방법이 이에 한정되지는 않는다.In a preferred aspect of the present invention, the pine extract may be a hot water extract of pine tree, and 3 to 20 times the weight of the medicinal material, preferably 5 to 15 times the water is added, and the temperature is 80 to 120 ° C., preferably 85 to 110 ° C. Preferably, extraction may be performed at a temperature of 90 to 105° C. for 1 to 24 hours, preferably for 2 to 12 hours, and more preferably for 3 to 8 hours, but the hot water extraction method is not limited thereto.
본 발명에 따른 추출물은 상기 추출 이후에 필요에 따라 여과, 농축, 건조 등의 추가 공정을 행한 것일 수 있다. 상기 추가 공정의 방법과 조건은 특별히 한정되지 않으며, 본 기술분야에 공지된 방법이나 통상적으로 행해지는 조건으로 수행될 수 있을 것이다.The extract according to the present invention may be subjected to additional processes such as filtration, concentration, and drying as necessary after the extraction. The method and conditions of the additional process are not particularly limited, and may be performed by a method known in the art or under commonly performed conditions.
상기 식나무 추출물의 최종 농도는 10 내지 1000 mg/kg일 수 있고, 바람직하게는 100 내지 250 mg/kg일 수 있으나, 이에 한정되지는 않는다.The final concentration of the pine tree extract may be 10 to 1000 mg/kg, preferably 100 to 250 mg/kg, but is not limited thereto.
본 발명에 있어서, 상기 약학적 조성물은 식나무 추출물 만을 유효량 포함하거나 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제를 포함할 수 있다.In the present invention, the pharmaceutical composition may include only an effective amount of pine extract or one or more pharmaceutically acceptable carriers, excipients or diluents.
본 발명에서, 용어 "유효량(또는, 유효한 양)"은 바람직한 효과를 전달하기에는 매우 충분하지만 의학적 판단 범위 내에서 심각한 부작용을 충분히 방지할 정도로 적은 양을 의미한다. 본 발명의 조성물에 의하여 체내에 투여되는 조성물의 양은 투여 경로, 투여 대상을 고려하여 적절하게 조정될 수 있다.In the present invention, the term "effective amount (or effective amount)" means an amount that is very sufficient to deliver desired effects but is small enough to sufficiently prevent serious side effects within the scope of medical judgment. The amount of the composition administered to the body by the composition of the present invention may be appropriately adjusted in consideration of the route of administration and the subject of administration.
또한, 상기에서 "약학적으로 허용되는"이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장 장애, 현기증과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다.In addition, "pharmaceutically acceptable" as used herein refers to a composition that is physiologically acceptable and does not cause allergic reactions such as gastrointestinal disorders and dizziness or similar reactions when administered to humans.
본 발명에서 이용 가능한 담체 혹은 매체는 용매, 분산제, 코팅, 흡수 촉진제, 제어된 방출제(즉, 서방제), 및 1종 이상의 불활성 부형제(전분, 폴리올, 과립제, 극미세 셀룰로스(microfine cellulose), 미세결정형 셀룰로스(예컨대, 셀피어, 셀피어 비즈(Celphere beads), 희석제, 윤활제, 결착제(binder), 붕해제 등을 포함함) 등을 포함할 수 있다. 약학적으로 허용가능한 담체 및 약학적으로 허용가능한 불활성 담체로서 이용하기 위한 부형제 그리고 상기 추가의 성분의 예로는, 결착제, 충전제, 붕해제, 윤활제, 항미생물제 및 코팅제를 들 수 있지만, 이에 한정되는 것은 아니다.Carriers or media usable in the present invention include solvents, dispersants, coatings, absorption accelerators, controlled release agents (i.e. sustained release agents), and one or more inert excipients (starch, polyols, granules, microfine cellulose, microcrystalline cellulose (including, for example, cellspheres, cellphere beads, diluents, lubricants, binders, disintegrants, etc.), etc. Pharmaceutically acceptable carriers and pharmaceutical Excipients for use as acceptable inert carriers and examples of such additional ingredients include, but are not limited to, binders, fillers, disintegrants, lubricants, antimicrobial agents, and coating agents.
본 발명에 따른 상기 약학적 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention is formulated in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively. and can be used.
경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제, 향미증진제, 보존제 또는 점막부착제 등이 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, flavor enhancers, preservatives or mucosal adhesives. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.
제형은 분말, 과립, 정제, 에멀젼, 시럽, 에어로졸, 연질 또는 경질 젤라틴캅셀, 멸균 주사용액, 멸균 분말의 형태일 수 있다. 또한, 본 발명에 따른 질환의 예방 또는 치료용 조성물은 경구, 경피, 피하, 정맥 또는 근육을 포함한 여러 경로를 통해 투여될 수 있으며, 활성 성분의 투여량은 투여 경로, 환자의 연령, 성별, 체중 및 환자의 중증도 등의 여러 인자에 따라 적절히 선택될 수 있고, 질환의 증상을 예방, 개선 또는 치료하는 효과를 가지는 공지의 화합물과 병용하여 투여할 수 있다.The dosage form may be in the form of a powder, granule, tablet, emulsion, syrup, aerosol, soft or hard gelatin capsule, sterile injectable solution, or sterile powder. In addition, the composition for preventing or treating diseases according to the present invention can be administered through various routes including oral, transdermal, subcutaneous, intravenous or intramuscular, and the dosage of the active ingredient depends on the route of administration, the patient's age, sex, and body weight. And it can be appropriately selected according to various factors such as the severity of the patient, and can be administered in combination with a known compound having an effect of preventing, improving or treating symptoms of a disease.
본 발명에 따른 추출물의 사용량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 10 내지 1000 mg/kg으로 일일 1회 내지 수회 투여할 수 있다. 또한 그 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The amount of the extract according to the present invention may vary depending on the patient's age, sex, and weight, but may be administered once or several times a day at 10 to 1000 mg/kg. In addition, the dosage may be increased or decreased depending on the route of administration, severity of disease, sex, weight, age, and the like. Therefore, the dosage is not intended to limit the scope of the present invention in any way.
본 발명에서, 용어 '치료'는 질병의 증상을 개선, 치유 또는 감소 또는 질병의 진행을 감소 또는 정지시키기 위해 질병에 걸린 피험자를 돌보는 것과 관련된 것이다.In the present invention, the term 'treatment' relates to caring for a diseased subject in order to improve, cure, or reduce the symptoms of a disease or to reduce or halt the progression of a disease.
본 발명에서, 용어 '예방'은 질병을 축소시키는 방지(averting), 지연(delaying), 방해(impeding) 또는 저해(hindering)와 관련된 것이다.In the present invention, the term 'prevention' relates to averting, delaying, impeding, or hindering reducing a disease.
본 발명에 따른 식나무 추출물을 포함하는 치은염 또는 치주염 치료 또는 예방용 약학적 조성물은 인간을 비롯한 포유동물의 치은염 및/또는 치주염 치료 또는 예방의 목적으로 사용할 수 있으며, 예컨대 개나 고양이와 같은 반려동물에도 적용이 가능할 것이다. The pharmaceutical composition for treating or preventing gingivitis or periodontitis containing an extract of gingivitis according to the present invention can be used for the purpose of treating or preventing gingivitis and/or periodontitis in mammals, including humans, and is also applied to companion animals such as dogs and cats. this will be possible
본 발명은 식나무 추출물을 포함하는 구강내 연조직 염증 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것을 특징으로 할 수 있고, 상기 구강내 연조직 염증 질환은 치은염 및/또는 치주염인 것을 특징으로 할 수 있다.The present invention may be characterized in that it provides a pharmaceutical composition for preventing or treating oral soft tissue inflammatory diseases containing a pine tree extract, wherein the oral soft tissue inflammatory diseases may be gingivitis and/or periodontitis. .
본 발명은 다른 관점에서, 식나무(Aucuba japonica) 추출물을 포함하는 구강내 연조직 염증의 예방 또는 개선용 식품용 조성물에 관한 것으로, 구체적 일부 양태로 식나무 추출물을 포함하는 치은염 및/또는 치주염 예방 또는 개선용 건강기능식품 조성물에 관한 것이다. In another aspect, the present invention relates to a composition for food for preventing or improving soft tissue inflammation in the oral cavity containing an extract of Aucuba japonica, and specifically for preventing or improving gingivitis and/or periodontitis containing an extract of Aucuba japonica in some embodiments. It relates to a health functional food composition.
본 발명에 있어서, 상기 식품은 식품의 주원료, 부원료, 식품 첨가제, 건강기능식품 또는 기능성 음료일 수 있으나, 이에 한정되지는 않는다.In the present invention, the food may be a main ingredient, supplementary ingredient, food additive, health functional food or functional beverage of food, but is not limited thereto.
본 발명에 따른 상기 식품용 조성물을 첨가할 수 있는 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능식품, 기타 기능성 식품 등이 있다. 추가로, 본원발명에서 식품에는 특수영양식품(예, 조제유류, 영·유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류(예, 라면류, 국수류 등), 빵류, 건강보조식품, 조미식품(예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류(예, 스넥류), 캔디류, 쵸코렛류, 껌류, 아이스크림류, 유가공품(예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임식품(각종 김치류, 장아찌 등), 음료(예, 과실 음료, 채소류 음료, 두유류, 발효음료류 등), 천연조미료(예, 라면 스프 등)를 포함하나 이에 한정되지 않는다. 상기 식품, 음료 또는 식품첨가제는 통상의 제조방법으로 제조될 수 있다.Food to which the food composition according to the present invention can be added includes, for example, various foods, beverages, chewing gum, tea, vitamin complexes, health functional foods, and other functional foods. In addition, in the present invention, foods include special nutritional foods (eg, formula milk, infant/young child food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), breads, health supplements, seasonings Foods (eg, soy sauce, soybean paste, gochujang, mixed paste, etc.), sauces, confectionery (eg, snacks), candies, chocolates, chewing gum, ice cream, dairy products (eg, fermented milk, cheese, etc.), other processed foods, kimchi, It includes, but is not limited to, pickled foods (various types of kimchi, pickled vegetables, etc.), beverages (eg, fruit drinks, vegetable drinks, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.). The food, beverage or food additive may be prepared by a conventional manufacturing method.
상기 건강기능식품이란 식품에 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체내조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 식품을 의미한다. 상기 기능성 식품에는 식품학적으로 허용 가능한 식품 보조 첨가제를 포함할 수 있으며, 기능성 식품의 제조에 통상적으로 사용되는 적절한 담체, 첨가제, 부형제 및 희석제 중 하나 이상을 더 포함할 수 있다.The health functional food refers to a food group or food composition that has added value so that the function of the food acts for a specific purpose by using physical, biochemical, or bioengineering methods, etc. It refers to food designed and processed to sufficiently express the body's regulatory function related to the living body. The functional food may include food additives that are acceptable in food science, and may further include one or more of appropriate carriers, additives, excipients, and diluents commonly used in the manufacture of functional foods.
상기 건강기능식품은 담체, 희석제, 부형제 및 첨가제 중 하나 이상을 더 포함하여 정제, 환제, 산제, 과립제, 분말제, 캡슐제 및 액제 제형으로 이루어진 군에서 선택된 하나로 제형될 수 있다. 본 발명의 추출물을 첨가할 수 있는 식품으로는, 각종 식품류, 분말, 과립, 정제, 캡슐, 시럽제, 음료, 껌, 차, 비타민 복합제, 건강기능성 식품류 등이 있다.The health functional food may be formulated as one selected from the group consisting of tablets, pills, powders, granules, powders, capsules and liquid formulations by further including one or more of carriers, diluents, excipients and additives. Examples of foods to which the extract of the present invention can be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gum, tea, vitamin complexes, health functional foods, and the like.
상기 본 발명에 더 포함될 수 있는 첨가제로는, 천연 탄수화물, 향미제, 향미증진제, 영양제, 비타민, 광물(전해질), 풍미제 (합성 풍미제, 천연 풍미제 등), 착색제, 충진제(치즈, 초콜렛 등), 팩트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH조절제, 안정화제, 방부제, 산화 방지제, 글리세린, 알콜, 탄산화제 및 과육으로 이루어진 군으로부터 선택된 1종 이상의 성분을 사용할 수 있다.Additives that may be further included in the present invention include natural carbohydrates, flavors, flavor enhancers, nutrients, vitamins, minerals (electrolytes), flavors (synthetic flavors, natural flavors, etc.), colorants, fillers (cheese, chocolate) Etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation agents and at least one component selected from the group consisting of fruit flesh can be used
상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상기 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
상기 외에 본 발명의 건강기능식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명에 따른 조성물은 천연 과일 쥬스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다.In addition to the above, the health functional food of the present invention is various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. In addition, the composition according to the present invention may contain fruit flesh for preparing natural fruit juice and vegetable beverages. These components may be used independently or in combination.
상기 담체, 부형제, 희석제 및 첨가제의 구체적인 예로는 이에 한정하는 것은 아니나, 락토즈, 덱스트로즈, 슈크로즈, 솔비톨, 만니톨, 에리스리톨, 전분, 아카시아 고무, 인산칼슘, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 미세결정성 셀룰로즈, 폴리비닐피롤리돈, 셀룰로즈, 폴리비닐피롤리돈, 메틸셀룰로즈, 물, 설탕시럽, 메틸셀룰로즈, 메틸 하이드록시 벤조에이트, 프로필하이드록시 벤조에이트, 활석, 스테아트산 마그네슘 및 미네랄 오일로 이루어진 그룹으로부터 선택된 1종 이상이 사용되는 것이 바람직하다.Specific examples of the carrier, excipient, diluent, and additive include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, erythritol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium phosphate, calcium Silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, sugar syrup, methylcellulose, methyl hydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate And at least one selected from the group consisting of mineral oil is preferably used.
본 발명의 건강기능식품을 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.When formulating the health functional food of the present invention, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
상기 상술한 제형 내 유효성분으로서의 본 발명에 따른 추출물의 함량은 사용 형태 및 목적, 환자 상태, 증상의 종류 및 경중 등에 의하여 적절하게 조절할 수 있으며, 고형분 중량 기준으로 0.001 내지 99.9 중량%, 바람직하게는 0.01 내지 50 중량%일 수 있으나, 이에 한정되지 않는다. 예컨대, 상기 추출물의 함량은 1 내지 10 중량%, 예를 들어 약 2 중량% 일 수 있다. The content of the extract according to the present invention as an active ingredient in the above-described formulation can be appropriately adjusted according to the type and purpose of use, the patient's condition, the type and severity of symptoms, etc., and is 0.001 to 99.9% by weight based on the solid content weight, preferably. It may be 0.01 to 50% by weight, but is not limited thereto. For example, the content of the extract may be 1 to 10% by weight, for example about 2% by weight.
본 발명의 건강기능식품의 투여 용량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 및 질환 정도에 따라 달라질 수 있으며, 의사 또는 약사의 판단에 따라 일정 시간간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다. 예컨대, 유효성분 함량을 기준으로 1일 투여량이 10 내지 1000 ㎎/kg일 수 있다. 상기한 투여량은 평균적인 경우를 예시한 것으로서 개인적인 차이에 따라 그 투여량이 높거나 낮을 수 있다. 본 발명의 건강기능식품의 1일 투여량이 상기 투여 용량 미만이면 유의성 있는 효과를 얻을 수 없을 수 있으며, 그 이상을 초과하는 경우 비경제적일 뿐만 아니라 상용량의 범위를 벗어나므로 바람직하지 않은 부작용이 나타날 수 있다.The dosage of the health functional food of the present invention may vary depending on the patient's age, weight, sex, dosage form, state of health and degree of disease, and may be administered once or several times a day at regular time intervals according to the judgment of a doctor or pharmacist. Split doses may also be used. For example, the daily dosage may be 10 to 1000 mg/kg based on the active ingredient content. The above dosage is an example of an average case, and the dosage may be higher or lower depending on individual differences. If the daily dose of the health functional food of the present invention is less than the above dose, a significant effect may not be obtained, and if it exceeds more than that, it is uneconomical and may cause undesirable side effects because it is out of the range of the usual dose. have.
본 발명에서 상기 기능성 음료란 갈증을 해소하거나 맛을 즐기기 위하여 마시는 것의 총칭을 의미하며, 지시된 비율로 필수 성분으로서 상기 질환 증상의 개선 또는 예방용 조성물을 포함하는 것 외에 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.In the present invention, the functional beverage refers to a general term for drinking to quench thirst or enjoy the taste, and there are no particular restrictions on other components other than including a composition for improving or preventing the disease symptoms as an essential component in the indicated ratio. As with conventional beverages, various flavoring agents or natural carbohydrates may be included as additional components.
나아가 상기 기술한 것 이외에 본 발명의 식품 조성물이 함유하는 식품은 여러 가지 영양제, 비타민, 광물(전해질), 천연 탄수화물, 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 및 과육 등을 함유할 수 있으며, 상기 성분은 독립적으로 또는 조합하여 사용할 수 있다.Furthermore, in addition to the above, the food composition of the present invention contains various nutrients, vitamins, minerals (electrolytes), natural carbohydrates, flavors such as synthetic flavors and natural flavors, coloring agents and fillers (cheese, chocolate, etc.) ), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages and fruit flesh, etc. can be used independently or in combination.
또 다른 관점에서, 본 발명은 식나무 추출물을 포함하는 동물용 사료 조성물에 관한 것이다.In another aspect, the present invention relates to an animal feed composition comprising a pine tree extract.
본 발명의 사료 조성물은 구강내 연조직 염증 질환이나 증상, 예컨대 치은염 및/또는 치주염을 예방, 치료, 개선 또는 완화하기 위하여 식나무 추출물을 유효성분으로 포함하며, 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있다. 예를 들어, 본 발명의 사료 조성물은 아미노산, 무기염류, 비타민, 항생물질, 항균물질, 항산화, 항곰팡이 효소, 다른 생균 형태의 미생물 제제 등과 같은 보조제 성분; 곡물, 예를 들면 분쇄 또는 파쇄된 밀, 귀리, 보리, 옥수수 및 쌀; 식물성 단백질 사료, 예를 들면 평지, 콩 및 해바라기를 주성분으로 하는 것; 동물성 단백질 사료, 예를 들면 혈분, 육분, 골분 및 생선분; 당분 및 유제품, 예를 들면 각종 분유 및 유장 분말로 이루어지는 건조성분; 지질, 예를 들면 가열에 의해 임의로 액화시킨 동물성 지방 및 식물성 지방 등과 같은 주성분; 영양보충제, 소화 및 흡수향상제, 성장촉진제, 질병 예방제와 같은 첨가제가 추가로 포함될 수 있다.The feed composition of the present invention includes a pine extract as an active ingredient in order to prevent, treat, improve, or alleviate oral soft tissue inflammatory diseases or symptoms, such as gingivitis and/or periodontitis, and can be used in any formulation conventionally prepared in the art. can be manufactured. For example, the feed composition of the present invention may include auxiliary components such as amino acids, inorganic salts, vitamins, antibiotics, antimicrobial substances, antioxidants, antifungal enzymes, and other probiotic-type microorganism preparations; grains such as ground or crushed wheat, oats, barley, corn and rice; vegetable protein feeds such as those based on rape, soybean and sunflower; animal protein feed such as blood meal, meat meal, bone meal and fish meal; dry ingredients consisting of sugar and dairy products, such as various powdered milk and whey powder; main components such as lipids, for example, animal fats and vegetable fats optionally liquefied by heating; Additives such as nutritional supplements, digestion and absorption enhancers, growth promoters, and disease preventives may be further included.
본 발명의 사료 조성물은 분말 또는 액체 상태의 제제 형태일 수 있으며, 사료첨가용 부형제를 포함할 수 있다. 사료첨가용 부형제로는 예를 들어, 탄산칼슘, 말분, 제올라이트, 옥분 또는 미강 등을 들 수 있으나, 이에 제한되지 않는다.The feed composition of the present invention may be in the form of a powder or liquid formulation, and may include an excipient for feed additives. Excipients for feed additives include, for example, calcium carbonate, horse powder, zeolite, jade powder or rice bran, but are not limited thereto.
본 발명은 또 다른 관점에서, 구강내 연조직 염증 증상이 있는 동물에게 식나무(Aucuba japonica) 추출물을 투여하는 단계를 포함하는 동물의 구강내 연조직 염증 질환 치료방법에 관한 것이다. In another aspect, the present invention relates to a method for treating oral soft tissue inflammatory disease in an animal comprising administering an Aucuba japonica extract to an animal having oral soft tissue inflammatory symptoms.
본 발명에 있어서, 상기 구강내 연조직 염증 증상은 치은염 및/또는 치주염 증상일 수 있으나, 이에 한정되지는 않는다. In the present invention, the soft tissue inflammation symptoms in the oral cavity may be gingivitis and/or periodontitis symptoms, but are not limited thereto.
본 발명에 있어서, 상기 동물은 포유동물일 수 있으며, 바람직하게는 개 또는 고양이와 같은 반려동물일 수 있으나, 이에 한정되지는 않으며, 본 기술분야의 통상의 기술자는 개 또는 고양이와 유사한 치아 구조를 가지고 있는 포유동물에 용이하게 본 기술분야를 적용할 수 있을 것이다. 본 발명에 있어서, 상기 동물은 인간일 수 있다. In the present invention, the animal may be a mammal, preferably a companion animal such as a dog or cat, but is not limited thereto, and a person skilled in the art has a dental structure similar to that of a dog or cat. It will be possible to easily apply the present technology to mammals that have it. In the present invention, the animal may be a human.
본 발명에 있어서, 상기 식나무 추출물은 경구제, 구강 스프레이 또는 구강 연고제로 투여하거나, 액상치약 또는 구강청정제로 처리하는 것을 특징으로 할 수 있으나, 이에 한정되지는 않는다.In the present invention, the pine tree extract may be administered as an oral agent, oral spray or oral ointment, or treated with a liquid toothpaste or mouthwash, but is not limited thereto.
본 발명에 있어서, 상기 식나무 추출물은 0.1 내지 10000 ㎎/kg, 바람직하게는 1 내지 1000 mg/kg의 용량의 1일 투여량으로 투여되는 것을 특징으로 할 수 있으나, 이에 한정되는 것은 아니다. 예컨대, 상기 식나무 추출물은 10 내지 300 mg/kg의 용량의 1일 투여량으로 투여될 수 있으며, 예를 들면 약 50mg/kg, 100mg/kg, 150mg/kg, 200mg/kg, 250 mg/kg의 용량의 1일 투여량으로 투여될 수 있다.In the present invention, the pine extract may be characterized in that it is administered in a daily dose of 0.1 to 10000 mg/kg, preferably 1 to 1000 mg/kg, but is not limited thereto. For example, the pine extract may be administered in a daily dose of 10 to 300 mg/kg, for example, about 50 mg/kg, 100 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg. It can be administered in a daily dosage of a dose.
또 다른 양태로서, 상기 식나무 추출물은 1 내지 100 mg/day, 바람직하게는 5 내지 50 mg/day의 투여량으로 투여되는 것을 특징으로 할 수 있으나, 이에 한정되지는 않는다.In another aspect, the pine tree extract may be administered at a dosage of 1 to 100 mg/day, preferably 5 to 50 mg/day, but is not limited thereto.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예 1. 식나무 추출물의 제조Example 1. Preparation of cedar extract
식나무 잎과 줄기는 2020년 8월에 경남 거제시 일운면 지세포리 임야에서 채집하였으며, 증거표본은 전북대학교 시료보관실에 보관 중이다. 식나무 100kg에 900L의 증류수를 가한 다음 100℃에서 3시간 전탕하여 감압 농축한 후 건조하여 식나무 열수 추출물을 제조하였다.The leaves and stems of the cedar tree were collected from the forest in Jisepo-ri, Irun-myeon, Geoje-si, Gyeongsangnam-do in August 2020, and the evidence specimen is stored in the sample storage room of Chonbuk National University. 900 L of distilled water was added to 100 kg of pine tree, heated at 100 ° C. for 3 hours, concentrated under reduced pressure, and then dried to prepare a hot water extract of pine tree.
실시예 2. 치은염 (gingivitis)을 가진 비글견에서 잇몸 부종 및 발적 억제 등 염증개선 효능 검사Example 2. Inflammation improvement efficacy test, such as gum swelling and redness inhibition in beagle dogs with gingivitis (gingivitis)
9~13kg의 비글견 (beagle dog)을 이용하여 2주 이상의 휴약기를 가진 후 식나무 추출물을 투여하기 전 구강상태를 평가하고 이후 식나무 추출물이 2% 함유되어 있는 구강연고와 식나무 추출물이 포함되어 있지 않은 대조군 (vehicle only) 구강연고를 표 1과 같은 조성으로 제조하였다.Using a beagle dog weighing 9 to 13 kg, after taking a break of more than 2 weeks, the oral condition was evaluated before administering the pine tree extract, and then oral ointment containing 2% of the pine tree extract and pine tree extract were not included. A control (vehicle only) oral ointment was prepared with the composition shown in Table 1.
| 성분ingredient | 함량 (10ml 기준)Content (based on 10ml) | |
|
2% 식나무 추출물 함유 구강연고Contains 2% cedar extract oral ointment |
식나무 추출물 미포함 vehicle 구강연고Vehicle oral ointment without cedar extract | |
|
식나무 추출물 cedar extract |
400 mg400 mg | -- |
|
Sodium polyacrylate (PAA, 점막부착제)Sodium polyacrylate (PAA, mucoadhesive) |
300 mg300mg | 300 mg300mg |
|
Mannitol (향미증진제)Mannitol (flavor enhancer) |
100 mg100 |
100 mg100 mg |
|
Methyl paraben (보존제)Methyl paraben (preservative) |
18 mg18mg | 18 mg18mg |
|
Poly paraben (보존제)Poly parabens (preservative) |
2 mg2mg | 2 mg2 mg |
제조된 구강연고는 1일 2회 4주 동안 상악 양쪽 대구치 치은 부위에 0.5g씩 1.0g/day를 도포하였다. 1.0g/day에 함유된 식나무 유효성분의 함량은 20 mg/day였다. 4주 간의 식나무 추출물 투여 후 구강검사를 실시하여 다음의 기준으로 치은염 지수 (gingivitis index)를 평가하였다. 1.0 g/day of the prepared oral ointment was applied to the gingival region of the upper molars on both sides of the maxilla twice a day for 4 weeks. The content of the active ingredient contained in 1.0 g/day was 20 mg/day. After administration of the cedar extract for 4 weeks, an oral examination was conducted, and the gingivitis index was evaluated according to the following criteria.
| 점수score | 평가방법Assessment Methods |
| 00 | 질환 없음 no disease |
| 1One |
경미한 치은염 - 잇몸 : 약간의 발적 - 치아 : 약간의 치태 minor gingivitis - Gums: Slight redness - Teeth: Some plaque |
| 22 |
초기 치주염 - 잇몸 : 발적과 부종 - 치아 : 잇몸아래 치태, 약간의 치석 early periodontitis - Gums: redness and swelling - Teeth: Plaque under the gums, some tartar |
| 33 |
중등도 치주염 - 잇몸 : 발적, 부종, 출혈이 있을 수 있고, 단열 또는 증생 - 치아 : 중등도에서 심한 양의 치석, 잇몸하 치석, 치아가 흔들리거나 소실moderate periodontitis - Gums: May have redness, swelling, bleeding, adiabatic or hyperplasia - Teeth: Moderate to severe amounts of calculus, subgingival calculus, tooth loosening or loss |
| 44 |
심한 치주염 - 잇몸 : 심한 발적, 염증, 출혈, 치아 주변 pocket형성, 농이 있을 수 있음 - 치아 : 많은 양의 잇몸하 치석, 치아가 흔들리거나 소실severe periodontitis - Gums: Severe redness, inflammation, bleeding, pocket formation around teeth, pus may be present - Teeth: A large amount of subgingival calculus, teeth are loose or lost |
그 결과, 도 1과 같이 식나무 추출물이 미포함된 vehicle 구강연고를 처치한 비글견의 잇몸의 치은염 지수 (gingivitis index)는 시간이 경과하면서 더 악화된데 반해 식나무 추출물이 포함된 구강연고를 투여한 비글견에서 잇몸의 부종이 감소하고 발적이 감소하였으며, 결과적으로 치은염 지수가 약 15%가량 감소하는 것을 확인할 수 있었다.As a result, as shown in FIG. 1, the gingivitis index of the gums of the beagle dog treated with the vehicle oral ointment without the pine extract was deteriorated over time, whereas the beagle administered the oral ointment containing the pine extract. In dogs, it was confirmed that edema and redness of the gums decreased, and as a result, the gingivitis index decreased by about 15%.
실시예 3. Example 3.
in vivo in vivo
노화쥐에서 치조골 파괴 억제 효과 확인Confirmation of inhibitory effect on alveolar bone destruction in aging rats
6주령된 수컷 SD rat (다물사이언스, 대전, 대한민국)를 이용하였으며 1주일간 적응시키고 물과 음식은 자유롭게 섭취시켰다. 순화과정이 끝난 쥐에 졸레틴과 케타민을 1:2 비율 (1.5ml/kg)로 섞어 복강내 주사하여 마취를 유도하였다. 마취 후 아래턱 왼쪽 제2 대구치 치경부에 silk 봉합사 (0.5mm)를 결찰시켜 치주염을 유발하였다. 치실을 묶지 않은 하악 오른쪽 제2 대구치를 대조군으로 설정하였다. 치주염을 유발시킨 날을 0일로 하였으며, 치주염을 유발한 날부터 2주 후에 쥐를 희생하였다. 시험기간 동안 식나무 추출물을 50, 100, 250 mg/kg의 농도로 1일 1회씩 경구투여 하였으며, 대조군에는 vehicle (DW)만 경구투여하였다. 치주염을 유발한 날로부터 쥐를 희생시킨 날까지 봉합사가 유지되어 있는지 확인하였다. 2주 간의 식나무 추출물 투여 후 쥐를 희생시킨 후 하악을 적출하였다. 이후 1M NaOH에 1시간 정도 처리하여 연조직(soft tissue)을 모두 제거한 후 백악법랑경계(cemento-enamel junction)에서 치조골의 치조능(crest)까지 길이를 측정하여 치조골 소실 정도를 정량화 하였다. Six-week-old male SD rats (Damul Science, Daejeon, Republic of Korea) were used and allowed to acclimatize for one week, with free access to water and food. Anesthesia was induced by intraperitoneal injection of a mixture of zoletine and ketamine at a ratio of 1:2 (1.5ml/kg) to the rats after the acclimatization process was completed. After anesthesia, periodontitis was induced by ligating a silk suture (0.5 mm) to the cervical area of the left second molar of the lower jaw. The mandibular right second molar tooth, which was not flossed, was set as a control group. The day of inducing periodontitis was set as day 0, and the rats were sacrificed 2 weeks after the day of inducing periodontitis. During the test period, pine extract was orally administered at concentrations of 50, 100, and 250 mg/kg once a day, and only vehicle (DW) was orally administered to the control group. It was confirmed whether the suture was maintained from the day periodontitis was induced to the day the rat was sacrificed. After administering the cedar extract for 2 weeks, the rats were sacrificed and their mandibles were removed. Thereafter, all soft tissues were removed by treatment with 1M NaOH for about 1 hour, and then the degree of alveolar bone loss was quantified by measuring the length from the cemento-enamel junction to the crest of the alveolar bone.
그 결과, 도 2에서와 같이, 치주염이 발생한 쥐에서는 치아의 뿌리가 외부로 노출될 정도로 치조골의 파괴가 심하게 발생하였으나, 식나무 추출물을 투여한 쥐에서는 농도 의존적으로 치조골의 파괴가 억제되는 것을 확인할 수 있었다.As a result, as shown in FIG. 2, in rats with periodontitis, destruction of alveolar bone was severe enough to expose the roots of teeth to the outside, but in rats administered with cedar extract, it was confirmed that destruction of alveolar bone was suppressed in a concentration-dependent manner. there was.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.As above, specific parts of the present invention have been described in detail, and for those skilled in the art, it is clear that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. something to do. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
본 발명에 따른 식나무 추출물은 천연 성분으로 인간이나 동물에 부작용 없이 치은염 또는 치주염과 같은 구강내 연조직 염증 질환에 우수한 치료 효과를 발휘하는 바, 구강내 연조직 염증 질환의 예방 또는 치료용 약학적 조성물과 식품용 조성물로 활용할 수 있고, 동물의 사료 조성물이나 동물의 구강내 연조직 염증 질환 치료방법으로의 활용이 가능하다. The pine tree extract according to the present invention is a natural ingredient and exhibits excellent therapeutic effects on oral soft tissue inflammatory diseases such as gingivitis or periodontitis without side effects on humans or animals, and is a pharmaceutical composition and food for preventing or treating oral soft tissue inflammatory diseases. It can be used as a composition for animal feed, or as a method for treating inflammatory diseases of soft tissues in the oral cavity of animals.
Claims (6)
- 식나무(Aucuba japonica) 추출물을 포함하는 치은염 또는 치주염 예방 또는 치료용 약학적 조성물.A pharmaceutical composition for preventing or treating gingivitis or periodontitis, containing an extract of Aucuba japonica .
- 제1항에 있어서, 상기 식나무 추출물은 열수 추출물인 것을 특징으로 하는 약학적 조성물.The pharmaceutical composition according to claim 1, wherein the pine extract is a hot water extract.
- 제1항에 있어서, 상기 식나무 추출물은 식나무의 잎, 줄기 또는 이의 혼합물을 추출한 것을 특징으로 하는 약학적 조성물.The pharmaceutical composition according to claim 1, wherein the pine extract is obtained by extracting leaves, stems or mixtures thereof of pine tree.
- 식나무 추출물을 포함하는 치은염 또는 치주염 예방 또는 개선용 건강기능식품 조성물.Health functional food composition for preventing or improving gingivitis or periodontitis containing an extract of cedar tree.
- 식나무 추출물을 포함하는 동물용 사료 조성물.An animal feed composition comprising a pine tree extract.
- 인간을 제외한 구강내 연조직 염증 증상이 있는 동물에게 식나무 추출물을 투여하거나 처리하는 단계를 포함하는 인간을 제외한 동물의 구강내 연조직 염증 질환 치료방법. A method for treating inflammatory diseases of soft tissues in the oral cavity of animals other than humans, comprising the step of administering or treating a cedar extract to animals having symptoms of oral soft tissue inflammation other than humans.
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