KR102132873B1 - Composition for the prevention or treating of oral diseases comprising extract of indigo, Lindera Root, Madder Root and Psoraleae Semen - Google Patents

Abstract

The present invention relates to a composition for preventing or treating oral diseases, wherein the complex composition of Persicaria tinctoria, Lindera aggregate, Zanthoxylum piperitum, and Psoralea corylifolia has high antibacterial activity on causative bacteria of dental caries and causative bacteria of periodontal disease, and also has a significantly excellent anti-inflammatory effect, thereby being able to be used to prevent or treat oral diseases.

Description

Composition for the prevention or treating of oral diseases comprising extract of indigo, Lindera Root, Madder Root and Psoraleae Semen}

The present invention relates to a composition for preventing or treating oral diseases, and more particularly, to a composition for preventing or treating dental caries and periodontal disease, including cheongdae, stigma, cheoncho and pagoji.

Dental caries is a disease in which tooth enamel is damaged by acid generated when bacteria in the oral cavity decompose sucrose, starch, and the like, and is a chronic disease with high morbidity. The main cause of dental caries is plaque on the surface of the teeth, and the bacteria that make up it are caused by acid produced by using food residues or sugar left in the mouth after eating food.

In particular, Streptococcus mutans ( S. mutans ) is a bacterium that is widely involved in the onset of dental caries and demineralizes tooth enamel by releasing lactic acid as a metabolite. The glycosyltransferases (GTFase) produced by S. mutans catalyze the reaction of synthesizing sticky insoluble glucans using sucrose as a substrate.

This glucan attaches bacteria such as S. mutans and Streptococcus sobrinus to the surface of the teeth to enable multiplication. In particular, it is densely insoluble in water, so that saliva with acid diffusion or buffering action from the plaque forms a barrier that cannot penetrate into the plaque, and stagnates the produced acid locally to continue demineralization, causing dental caries. do. In order to prevent or treat this, it is necessary to inhibit the formation of metabolites of microorganisms in the oral cavity and inhibit plaque formation.

Periodontal disease is commonly referred to as qichi, and is divided into gingivitis and periodontitis depending on the severity of the disease. Gingivitis is a form in which inflammation is limited to soft tissue and is called periodontitis when it has progressed around the gums and around the gum bones. The direct cause of periodontal disease is that plaque formed continuously on the teeth is not removed, but hardens to form calculus, and calculus provides an environment in which plaque is easily formed, so that more bacteria grow.

Porphyromonas gingivalis is known to be the main causative agent of periodontal disease. As periodontal disease progresses, it penetrates the fissure epithelium, and in the process of attaching or penetrating host tissues and cells, it produces metabolites or toxins that not only directly harm the periodontal tissues, but also cytoplasm produced by cells that react with P. gingivalis. Cain (cytokine) and substances produced in host cells that respond to the cytokine further destroy periodontal tissue.

In the oral cavity, when an inflammatory reaction is induced by a specific bacterium, a reaction such as activating inactive collagenase or stimulating the secretion of matrix metalloproteinases (MMPs) occurs. Collagenase is a substance causing degeneration of gums by decomposing collagen, which is a substrate of periodontal tissue, and can progress to periodontal disease if left unattended.

MMPs are present in particularly high concentrations in areas with inflammatory periodontal disease, and are known to inhibit the regeneration and development of periodontal tissue and degrade collagen. Eating gum treatments are not very helpful for treatment and it is recommended to use ferns or antibiotics to kill special bacteria in the gums.

In the human body, the oral cavity is involved in the endocrine action of the salivary glands, the composition of breath and speech, in addition to various functions related to food intake, such as chewing, oral digestion, and taste. In other words, as a primary gateway through which all nutrients introduced by food intake and pathogens in the air enter the human body, organs such as teeth, gums, and tongue related to vocal, mastication, and aesthetic functions are connected organically. Institution. Currently, this important oral hygiene and health care relies on mouthwashes made of artificial compounds.

In particular, as products currently on the market have resistance to existing antibiotics to oral bacteria, they have strong activity by chemical components, so they have to worry about side effects such as toxicity. Therapeutic agents, such as pain relievers necessary for pain relief and antibiotics for inhibiting microflora in the oral cavity, have side effects on usage limitations and misuse, and oral cleaning agents used to prevent tooth decay, plaque and plaque, plaque, and bad breath are used even after use. It often remains within. Inflammation of the oral mucosa is caused by this residue, and in severe cases there is a risk of poisoning. In other words, various treatments and cleaners used for oral care will harm the oral and dental health.

There is a need to provide safer and more natural material-based products to consumers who have already been domesticated in various artificial compound-based mouthwashes for dental health and oral hygiene.

As a related art related to the present invention, in Korean Patent Publication No. 10-2018-0083242 (a composition for periodontal disease and a mouthwash containing the same), a composition for periodontal disease comprising hyunggae extract, sesin extract, peppermint extract and Angelica extract And mouthwashes comprising the same. In Korean Patent Publication No. 10-2014-0104331 (Oral fragrance composition comprising cypress extract and herbal extract and method for manufacturing the same), cypress extract extracted under reduced pressure using a solvent from cypress and cypress essential oil extracted by steam distillation ( essential oil), Chihwang, Omija, Gaza, Jinbeom, Yeongyo, Mokhyang, and Ohjaja are disclosed for oral perfume based on herbal extracts extracted under reduced pressure using a solvent from herbal medicines and methods for manufacturing the same. In Korean Patent Publication No. 10-2006-0002147 (Food composition effective for oral and throat system diseases and its manufacturing method), it has efficacy against oral and throat system diseases including confessional plaques, green onions, and ginseng and has side effects on the human body. Disclosed is a food composition composed of no medicinal herbs and a method for manufacturing the same.

The oral disease treatment aids or cleaning compositions of the patent evaluated antibacterial activity against each of the three strains of S. mutans, S. sobrinus, and P. gingivalis , the major causative agents of dental caries and periodontal disease , but anti-inflammatory activity and oral cavity The toxicity evaluation of the cells has not been conducted, and there is a limitation that the oral cell toxicity evaluation for residuals is insufficient.

The present inventors have confirmed that the complex composition of Cheongdae, Cheoncho, Ohyeol and Pagoji has high antibacterial activity against the causative agent of dental caries and the causative agent of periodontal disease, and also has an excellent anti-inflammatory effect.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases, including at least one extract selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji.

Another object of the present invention is to provide an antimicrobial or anti-inflammatory composition comprising one or more extracts selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji.

Another object of the present invention is to provide a health functional food composition for improving oral disease, including at least one extract selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji.

Another object of the present invention is to prevent, treat or improve oral diseases of one or more extracts selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji, or to use antibacterial or anti-inflammatory agents against dental caries and periodontal disease causative bacteria. will be.

The present invention relates to a composition for preventing or treating oral diseases, and the complex composition of Cheongdae, Cheoncho, Ohyeol and Pagoji according to the present invention has high antibacterial activity against causative agents of dental caries and causative agent of periodontal disease, and also has excellent anti-inflammatory effects. Shows.

The present inventors prepared a composite composition including Cheongdae, Cheoncho, filth, and crest paper and treated them in oral cells to confirm the antibacterial and anti-inflammatory effects on oral disease causative bacteria.

Hereinafter, the present invention will be described in more detail.

An aspect of the present invention is a pharmaceutical composition for preventing or treating oral diseases, including at least one extract selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji.

In this specification, "Cheongdae ( Polygonum taintorium Lour. )" is said to kill bad insects in Donguibogam and dissolve it like water . It removes heat poison from the body, clears blood, and removes surprising symptoms. Is known. It treats a child's high fever, fever caused by a game, and a fever with a headache and chills due to an epidemic. In the original book, it is used when coughing through waste heat and sticky sputum comes out, and is said to be used for eczema and stomatitis. According to a recent study, it has antibacterial and anti-inflammatory effects, and is expected to be used for psoriasis treatment and cancer treatment.

In this specification, "Cheoncho ( Zanthoxylum piperitum AP Dc.)" is a traditional herbal material used to treat toothache. According to human resources, in general, toothache must be used for a thousand seconds to paralyze the pain, and according to distilled herbs, teeth and hair are strengthened and toothache is eliminated. According to a recent study, immunomodulation and anti-inflammatory activity have been reported.

In this specification, "Olea ( Lindera strichnifolia Fernandez-Villar )" is a herbal material known to treat all cavalry, and it is said that it is very easy to treat chest and abdominal chills , especially if you grind it with acupuncture and eat it little by little. According to Donguibogam, it has the effect of circulating the energy to rejuvenate the mind, stopping the pain, and killing the stomach worm in children. Recent studies have reported antioxidant enzyme activation.

In the present specification, "pagoji ( Psoralea corylifolia L.)" is also called bogolji , which means that the index ( 지수 ) in the bone (보). According to Donguibogam, it treats various symptoms caused by overwork, colds, etc. in the whole body, chills in the bone marrow, and cold and weak back and legs. Recent studies have reported antibacterial and antithrombotic action.

The pharmaceutical composition may include 0.1 to 7.0% by weight of Cheongdae, 0.1 to 3.0% by weight of cheoncho, 0.1 to 2.0% by weight of paste, and 0.1 to 2.0% by weight of crest paper, but is not limited thereto.

The cheongdae may be 0.1 to 4.0, 0.1 to 3.0, 1.0 to 7.0 or 1.0 to 4.0, for example, 1.0 to 3.0 wt%, but is not limited thereto.

The thousand seconds may be 0.1 to 3.0, 0.5 to 3.0 or 1.0 to 3.0, for example, 1.0 to 2.0 wt%, but is not limited thereto.

The stain may be 0.1 to 1.0 or 0.5 to 2.0, for example, 0.5 to 1.0 wt%, but is not limited thereto.

The crest paper may be 0.1 to 1.0 or 0.5 to 2.0, for example, 0.5 to 1.0 wt%, but is not limited thereto.

The pharmaceutical composition may further include one or more selected from the group consisting of peppermint, sesin, clove, celestial, milky white, rhubarb, and yellow lotus.

" Mentha ( Mentha canadensis )" in the present specification helps to activate saliva secretion and also promotes secretion of mucus in the lungs to filter out foreign substances entering the lungs. Also, according to Donguibogam, it sweats and releases poison, relieves fatigue and clears the head and eyes. In addition, menthol contained in peppermint is a strong and refreshing fragrance that prevents bad breath and relieves gum pain or swelling while suppressing the growth of bacteria in the oral cavity. It is also effective in relieving inflammation, improving inflammation such as tonsillitis and sore throat and helping relieve pain and preventing and improving bronchial diseases. In oriental medicine, it has been frequently used for otolaryngology diseases such as the tongue and throat.

In the present specification, "Sesin ( Asarum sieboldii Miq )" has been used to treat coughing, headaches, swelling of the bones of the body, and painful symptoms in the arms and legs. According to Donguibogam, it is used to warm the inside, lower the energy, brighten the eyes, and sweat. When the eyes or teeth hurt, the gums are swollen and sore. According to a recent study, it is effective in managing oral odor syndrome due to periodontal disease, and has been reported on anti-inflammatory, analgesic, and antibacterial effects against tooth decay.

In this specification, "scent ( Syzygium aromaticum )" is one of the world's leading fragrances and is most widely used as a fragrance treatment. In a book called Han Gwanui in the third century B.C.E., Jeonghyang was said to have been held by the court officials in order to get rid of bad breath when he realized the emperor. According to Donguibogam, it is used when the stomach is cold, the stomach is cold, aching, nausea, diarrhea, or lack of appetite, hiccups, digestive problems, knee and lower back pain and soreness. Recent studies have also demonstrated that it suppresses bad breath and has anti-inflammatory effects.

In the present specification, " Levisticum officinale " has an effect of promoting blood circulation and relieving pain. In addition, it has anti-ulcer, lowering blood pressure, and antibacterial effects. According to Donguibogam, it is known that the zodiac is indispensable for the treatment of headaches, and when the parietal and the brain hurts, the zodiac must be used. According to a recent study, antimicrobial effects against various cavities were reported as a result of cytotoxicity (MTT assay) and MIC (minimum inhibitory concentration) investigations. In Oriental medicine, it is also used to treat diseases such as the tongue and throat along with peppermint.

As used herein, " Ulmus macrocarpa Hance " is used to treat insomnia by making a person fall asleep and urinating urinary tract stones according to Donguibogam. According to a recent study, it plays a role in strongly inhibiting matrix metalloproteinases (MMPs) and bacterial protease (MMPs), which are involved in the destruction of gum tissue due to periodontitis.

In this specification, "rhubarb ( Rheum rhabarbarum )" is a medicine used mainly to help bowel movements and to treat constipation, and is also called general genera in Donguibogam, which has excellent medicinal properties. The name was given because it seemed to be watching the general lead the military and advance as the efficacy of healing the fever and the like did not pass. According to a recent study, it has been reported that it has excellent anti-inflammatory and antipyretic effect, has antioxidant activity, and also has antiviral activity by inhibiting antibacterial activity against the causative agent of infection or various inflammations and viral protein synthesis. In particular, it has been reported that the antiviral activity is superior to the commonly used interferon agents.

In the present specification, "Hwangnyeon ( Coptis chinesis Franch )" is a medicine that is used to treat the stuffiness and swelling of Myeongchi according to Donguibogam. It is effective in antipyretic and blood pressure drop, and is a medicine used for stomatitis, glossitis and stomatitis caused by heat. The antibacterial action is remarkable, so it is widely used for skin infections, conjunctivitis, etc., and is effective for dysentery and diarrhea.

The pharmaceutical composition is 15.0 to 30.0% by weight of peppermint, 1.0 to 15.0% by weight of sesins, 5.0 to 15.0% by weight of cloves, 5.0 to 15.0% by weight of celestial body, 5.0 to 15.0% by weight of milkweed, 2.0 to 10.0% by weight of rhubarb and 0.1% by weight It may be to further include to 3.0% by weight, but is not limited thereto.

The mint may be 15.0 to 25.0 or 20.0 to 30.0, for example, 20.0 to 25.0 wt%, but is not limited thereto.

The sessin may be 1.0 to 10.0, 1.0 to 5.0, 4.0 to 15.0 or 4.0 to 10.0, for example, 4.0 to 5.0% by weight, but is not limited thereto.

The clove may be, for example, 5.0 to 12.0, 5.0 to 10.0, or 5.0 to 8.0, for example, 5.0 to 6.0% by weight, but is not limited thereto.

The archery may be 5.0 to 12.0, 5.0 to 8.0, 6.0 to 15.0 or 6.0 to 12.0, for example, 6.0 to 8.0% by weight, but is not limited thereto.

The milky skin may be 5.0 to 12.0, 5.0 to 10.0 or 5.0 to 8.0, for example, 5.0 to 6.0% by weight, but is not limited thereto.

The rhubarb may be 2.0 to 8.0, 2.0 to 6.0, 4.0 to 10.0 or 4.0 to 8.0, for example, 4.0 to 6.0 wt%, but is not limited thereto.

The hwangnyeon may be 0.1 to 2.0, 0.1 to 1.0, 0.2 to 3.0 or 0.2 to 2.0, for example, 0.2 to 1.0% by weight, but is not limited thereto.

The term "extract" herein refers to a solvent crude extract, a specific solvent soluble extract (solvent fraction) and a solvent fraction of the solvent crude extract, and the extract may be in solution, concentrate or powder form.

The extract may be a crude extract obtained by extraction with water and one or more solvents selected from the group consisting of straight or branched alcohols having 1 to 4 carbon atoms, and water, ethanol, methanol, butanol, ethyl acetate or mixtures thereof. It may be extracted with a solvent, for example, water may be extracted with a solvent, but is not limited thereto.

When using a mixture of water and alcohol in one solvent used for the preparation of the crude extract, 10% or more to less than 100% (v/v), 20% or more to less than 100% (v/v), 30% or more 100% (v/v) or less, 40% or more to 100% (v/v) or less, 50% or more to 100% (v/v) or less, 60% or more to 100% (v/v) or less, 70% Above to 100% (v/v), above 10% to below 90% (v/v), above 20% to below 90% (v/v), above 30% to below 90% (v/v), 40% to 90% (v/v), 50% to 90% (v/v), 60% to 90% (v/v) or 70% to 90% (v/v) It may be a straight or branched alcohol aqueous solution having 1 to 4 carbon atoms, for example, 80% (v/v) straight chain or branched alcohol aqueous solution having 1 to 4 carbon atoms.

In addition, the aqueous alcohol solution may be one or more selected from the group consisting of a methanol aqueous solution, an ethanol aqueous solution, a propanol aqueous solution, and a butanol aqueous solution, and may be, for example, an ethanol aqueous solution, but is not limited thereto.

The extract according to the present invention may be a solvent fraction obtained by fractionating the solvent crude extract with an additional solvent, for example, a solvent using at least one solvent selected from the group consisting of ethyl ether, ethyl acetate, and butanol in the solvent crude extract. It can be a fraction.

For example, a solvent crude extract extracted with one or more solvents selected from the group consisting of water and a straight chain or branched alcohol having 1 to 4 carbon atoms is used using at least one solvent selected from the group consisting of ethyl ether, ethyl acetate, and butanol. It can be a solvent fraction.

One aspect of the invention relates to a method of preparing an extract. The extract includes a crude solvent extract and a solvent fraction and is as described above.

The manufacturing process of the extract according to the present invention will be described in more detail as follows: About 10 to 100 times based on the weight of the material, preferably at room temperature with an extraction solvent having a weight of 10 to 20 times. After extraction, the filtrate is collected by filtration. The extraction temperature is not particularly limited, but is preferably 60 to 120°C, 60 to 100°C, 80 to 120°C, preferably 80 to 100°C.

The extraction process may be repeated once or several times, and in one preferred example of the present invention, a method of re-extraction after the primary extraction may be adopted, which, even when effectively filtering large quantities of herbal extracts, is performed even if the herbal extracts are filtered effectively. This is to prevent the loss due to the high moisture content, and the extraction efficiency is reduced only by the first extraction. In addition, as a result of verifying the extraction efficiency at each step, it was found that about 80 to 90% of the total extraction amount is extracted by secondary extraction.

In one example of the present invention, when the extraction process is repeated twice, the obtained residue is refluxed again with an extraction solvent, about 5 to 15 volume times, preferably 8 to 12 volume times. After extraction, it is filtered and combined with the filtrate obtained previously, and concentrated under reduced pressure to prepare an extract. Thus, the extraction efficiency can be increased by mixing the extract obtained over the second time and the filtrate obtained after each extraction, but the extract of the present invention is not limited to the number of extractions.

When the amount of the solvent used in the preparation of the extract is too small, stirring becomes difficult and the solubility of the extract is lowered to lower the extraction efficiency. In the case of excessively large amount, the amount of the solvent used in the next purification step is increased, so it is not economical and handled. Since a phase problem may occur, the amount of the solvent used is preferably within the above range.

The filtered extract obtained in this way is about 10 to 30 times the total amount of concentrate, preferably 15 to 25 times, more preferably about to adjust the content of the lower alcohol remaining to be suitable for use as a pharmaceutical raw material. After azeotropic concentration of 1 to 5 times, preferably 2 to 3 times, with 20 times the weight of water, and homogeneous suspension by adding the same amount of water again, lyophilization can be prepared as an extract in powder form.

The extract may be extracted for 3 to 7 hours, preferably 4 to 6 hours, but is not limited thereto.

The extraction method used in the present invention may be any method commonly used, for example, room temperature extraction, cold extraction, hot water extraction, ultrasonic extraction, steam extraction, or reflux cooling extraction, and may be a reduced pressure or pressure extraction method. , But is not limited thereto.

The pharmaceutical composition may further include one or more selected from the group consisting of allantoin and xylitol, and may further include allantoin 0.1 to 1.0 wt% and xylitol 2.0 to 8.0 wt%, but is not limited thereto. no.

In the present specification, "Allantoin" is a natural ingredient widely used in oral products such as mouthwashes and toothpastes, and is also used in skin conditioning agents and skin protection agents. The Korea Food and Drug Administration and the US FDA also said that it is safe for use as a treatment for oral wounds. It has excellent anti-inflammatory and anti-allergic effects, and is also effective at low concentrations. In addition, it promotes cell growth and is effective in healing and rebuilding damaged skin.

In the present specification, "xylitol" is a natural material that is also called birch sugar, and has a sugar similar to sucrose, and is a sugar alcohol that is not readily degraded by bacteria in the oral cavity and has a great effect on preventing dental caries. In addition, the Ministry of Food and Drug Safety (KFDA) announced that it helps reduce the risk of tooth decay, and several studies have shown that xylitol is effective in reducing S. mutans in oral saliva and plaque.

The allantoin may be 0.1 to 0.8, 0.1 to 0.6, 0.1 to 0.4, 0.2 to 1.0, 0.2 to 0.8 or 0.2 to 0.6, for example, 0.2 to 0.4% by weight, but is not limited thereto.

The xylitol may be 2.0 to 6.0, 4.0 to 8.0 or 4.0 to 6.0, for example, 4.0 to 5.0% by weight, but is not limited thereto.

The pharmaceutical composition of the present invention may be used as a pharmaceutical composition comprising a pharmaceutically effective amount of extract and/or a pharmaceutically acceptable carrier.

The term "pharmaceutically effective amount" as used herein means an amount sufficient to achieve the efficacy or activity of the aforementioned extract.

The pharmaceutically acceptable carrier included in the pharmaceutical composition of the present invention is commonly used in formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, etc. It does not work. The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.

The pharmaceutical composition according to the present invention can be administered to various mammals, including humans, by various routes. The mode of administration may be any of the commonly used modes, for example, oral, skin, intravenous, intramuscular, subcutaneous, and the like, and may be administered, preferably, orally.

Suitable dosages of the pharmaceutical compositions of the present invention vary by factors such as formulation method, mode of administration, patient's age, weight, gender, morbidity, food, time of administration, route of administration, rate of excretion, and response sensitivity, Usually, a skilled physician can easily determine and prescribe a dose effective for the desired treatment or prevention.

The pharmaceutical composition of the present invention is prepared in a unit dose form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by those skilled in the art to which the present invention pertains. Or it can be manufactured by incorporating into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of ex-agent, powder, granule, tablet, capsule or gel (eg, hydrogel), and may further include a dispersant or stabilizer. .

In one embodiment of the present invention, 2.0% by weight of Cheongdae, 2.0% by weight of Cheoncho, 0.5% by weight of Peaches, 0.5% by weight of Pagoji, 25.0% by weight of peppermint, 4.0% by weight of Sesins, 5.0% by weight of cloves, 6.0% by weight of Cheongung, Yubaekpi A pharmaceutical composition for preventing or treating oral diseases including 5.0% by weight, 4.0% by weight of rhubarb, 0.2% by weight of hwangnyeon, 0.2% by weight of allantoin, and 4.5% by weight of xylitol was prepared.

The oral disease may be selected from the group consisting of dental caries, periodontal disease, gingivitis, periodontitis, chronic periodontitis, peri-implantitis, pulp, root canal disease, and maxillary osteomyelitis, for example, dental caries or periodontal disease. Can.

The oral diseases are Streptococcus mutans , Streptococcus sanguinis , Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti, Streptococcus crice Streptococcus anginosus , Streptococcus gordonii , Actinobacillus actinomycetemcomitans , Fusobacterium nucleatum , Prevotella Interpreta intermedia ) and one or more selected from the group consisting of Porphylomonas gingivalis , but is not limited thereto.

Another aspect of the present invention is an antimicrobial or anti-inflammatory composition comprising at least one extract selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji.

The antimicrobial or anti-inflammatory composition may be one or more selected from the group consisting of peppermint, sesin, cloves, celestial, milky white, rhubarb, and yellow lotus, but is not limited thereto.

The antibacterial or anti-inflammatory composition may be one or more selected from the group consisting of allantoin and xylitol, but is not limited thereto.

The antimicrobial or anti-inflammatory composition is Streptococcus mutans, Streptococcus sanguinis, Streptococcus sobrinus, Streptococcus latina, Streptococcus crisseti, Streptococcus angiosus, Streptococcus Gordony, Actinobacillus actinomistem Commitans, Fusobacterium nuclitum, Pribotela intermedia, and Popillomonas gingivalis may inhibit growth or inhibit inflammation induced by one or more selected from the group consisting of, but are not limited to no.

In one embodiment of the present invention, the composition of the present invention may be provided as a fern or mouthwash.

Another aspect of the present invention is a health functional food composition for improving oral disease, comprising at least one extract selected from the group consisting of Cheongdae, Cheoncho, Ohyeol and Pagoji.

The health functional food composition may further include one or more selected from the group consisting of peppermint, sessin, cloves, cheonggung, yubaekpi, rhubarb, and hwangnyeon, but is not limited thereto.

The health functional food composition may further include one or more selected from the group consisting of allantoin and xylitol, but is not limited thereto.

The oral diseases include streptococcus mutans, streptococcus sanguinis, streptococcus sobrinus, streptococcus latina, streptococcus criceti, streptococcus anginosus, streptococcus gordoni, actinobacillus actinomicetemcommitans, One or more selected from the group consisting of Fusobacterium nuclitum, Pribotela intermedia, and Popillomonas zincivalis may be used as causative bacteria, but are not limited thereto.

When the health functional food composition of the present invention is used as a food additive, the health functional food composition may be added as it is or used together with other food or food ingredients, and may be suitably used according to a conventional method. In general, the health functional food composition of the present invention in the manufacture of a food or beverage may be added in an amount of 15% by weight or less, preferably 10% by weight or less based on the raw material.

There are no particular restrictions on the type of food. Examples of foods to which the above substances can be added are meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, dairy products including gums, ice creams, various soups, beverages, teas, drinks, Alcoholic beverages, vitamin complexes, and the like, and include all foods in the ordinary sense.

The beverage may contain various flavoring agents or natural carbohydrates as an additional component. The natural carbohydrates described above may include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharin and aspartame. . The proportion of the natural carbohydrate can be appropriately determined by the choice of those skilled in the art.

In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin , Carbonic acid used in alcoholic beverages, carbonated beverages, and the like. In addition, the health functional food composition of the present invention may contain flesh for the preparation of natural fruit juice, fruit juice beverage and vegetable beverage. These ingredients can be used independently or in combination. The proportions of these additives can also be appropriately selected by those skilled in the art.

The present invention relates to a composition for the prevention or treatment of oral diseases, wherein the complex composition of Cheongdae, Cheoncho, Ohyeol and Pagoji has high antibacterial activity against the causative agent of dental caries and the causative agent of periodontal disease, and also has excellent anti-inflammatory effects, thereby effectively It can be used to prevent or treat oral diseases.

1 is a flow chart showing a method of manufacturing a composite composition for the prevention, treatment or improvement of oral diseases of the present invention.
Figure 2a is a graph showing the antibacterial activity against Streptococcus mutans ( Streptococcus mutans ) of the composite composition prepared according to the present invention.
Figure 2b is a graph showing the antibacterial activity against Streptococcus sobrinus ( Streptococcus sobrinus ) of the composite composition prepared according to the present invention.
Figure 2c is a graph showing the antibacterial activity against Porphylomonas gingivalis of the composite composition prepared according to the present invention.
Figure 3a is a graph showing the minimum inhibitory concentration for Streptococcus mutans of the composite composition prepared according to the present invention.
Figure 3b is a graph showing the minimum inhibitory concentration for streptococcus sobrinus of the composite composition prepared according to the present invention.
Figure 3c is a graph showing the minimum inhibitory concentration for Popillomonas gingivalis of the composite composition prepared according to the present invention.
Figure 4 is a graph showing the anti-inflammatory activity for the inflammation-causing substances isolated from Popillomonas zinvalis of the composite composition prepared according to the present invention.
Figure 5 is a graph evaluating the toxicity to the oral cells of the composite composition prepared according to the present invention compared to the existing oral cleaning agent.

Hereinafter, the present invention will be described in more detail by the following examples. However, these examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

Throughout this specification, "%" used to indicate the concentration of a specific substance, unless otherwise specified, solids/solids (weight/weight)%, solids/liquids (weight/volume)%, and The liquid/liquid is (volume/volume)%.

Example 1: Preparation of composition for oral treatment

41.1% by weight of purified water based on the total weight, 2.0% by weight of Cheongdae, 2.0% by weight of cheoncho, 0.5% by weight of sage, 0.5% by weight of clove paper, 25.0% by weight of peppermint, 4.0% by weight of sesins, 5.0% by weight of clove, 6.0% by weight of archery, A composite composition was prepared comprising 5.0% by weight of milk white skin, 4.0% by weight of rhubarb, 0.2% by weight of hwangnyeon, 0.2% by weight of allantoin, and 4.5% by weight of xylitol. The Cheongdae, Cheoncho, Oak, Pagoji, Peppermint, Sesin, Clove, Cheongung, Yubaekpi, Rhubarb and Hwangnyeon were used by filtering the extracted hot water at 100℃ for 5 hours after adding 10 times of purified water.

A composition was prepared by weighing 0.2% by weight of allantoin and 4.5% by weight of xylitol in the filtered extract and adding it as a powder to perform homogenization. The step of homogenizing by adding allantoin and xylitol was performed with a homogenizer.

Comparative Example 1: Preparation of oral treatment composition

Prepared in the same manner as in Example 1, 26.8% by weight of purified water, 20.0% by weight of peppermint, 10.0% by weight of sesins, 8.0% by weight of cloves, 10.0% by weight of archery, 7.0% by weight of milk white skin, 6.0% by weight of rhubarb, 2.0% by weight of Hwangnyeon , Allantoin 0.2 wt% and xylitol 5.0 wt%.

Comparative Example 2: Preparation of composition for oral treatment

Prepared in the same manner as in Example 1, but does not include Cheongdae, Cheoncho, Peony and Pagoji, 25.6% by weight of purified water, 20.0% by weight of peppermint, 10.0% by weight of sesins, 10.0% by weight of cloves, 10.0% by weight of celestial cord, 10.0% by milk Weight%, rhubarb 8.0% by weight, hwangnyeon 1.0% by weight, allantoin 0.4% by weight and xylitol was applied to 5.0% by weight.

Comparative Example 3: Preparation of composition for oral treatment

Prepared in the same manner as in Example 1, 28.1% by weight of purified water, 4.0% by weight of Cheongdae, 0.5% by weight of vinegar, 0.1% by weight of paste, 0.1% by weight of pagoji, 20.0% by weight of mint, 10.0% by weight of sessin, 8.0% by weight of cloves, It was applied with 10% by weight of the archery, 7.0% by weight of milk white skin, 6.0% by weight of rhubarb, 1.0% by weight of the yellow lotus, 0.2% by weight of allantoin and 5.0% by weight of xylitol.

Comparative Example 4: Preparation of composition for oral treatment

Prepared in the same manner as in Example 1, but does not include Cheongdae, Cheoncho, Peony and Pagoji, 46.1% by weight of purified water, 25.0% by weight of peppermint, 4.0% by weight of sesins, 5.0% by weight of cloves, 6.0% by weight of Cheongung, Yubaekpi 5.0 Weight %, rhubarb 4.0 wt %, hwangnyeon 0.2 wt %, allantoin 0.2 wt% and xylitol 4.5 wt% were applied.

The compositions of Example 1 and Comparative Examples 1 to 4 were prepared as shown in Table 1 below.

(weight%) Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Cheongdae 2.0 2.0 - 4.0 - Thousand seconds 2.0 2.0 - 0.5 - Filthy 0.5 0.5 - 0.1 - Crest 0.5 0.5 - 0.1 - mint 25.0 20.0 20.0 20.0 25.0 Seshin 4.0 10.0 10.0 10.0 4.0 cloves 5.0 8.0 10.0 8.0 5.0 Heaven 6.0 10.0 10.0 10.0 6.0 Milky white 5.0 7.0 10.0 7.0 5.0 rhubarb 4.0 6.0 8.0 6.0 4.0 goldthread 0.2 2.0 1.0 1.0 0.2 Allantoin 0.2 0.2 0.4 0.2 0.2 Xylitol 4.5 5.0 5.0 5.0 4.5 Purified water 41.1 26.8 25.6 28.1 46.1

Test Example 1: Measurement of antimicrobial activity of the composite composition

1-1. Comparison of antimicrobial activity of the composite composition

In order to compare the antimicrobial activity between the composite compositions prepared according to each Example and Comparative Example, the antimicrobial activity against the causative agent of each disease was tested through a minimum inhibitory concentration (MIC) test method.

The test organisms include Streptococcus mutans ( S. mutans ), Streptococcus sobrinus ( S. sobrinus ), and causative agent of periodontal disease, Porphyromonas gingivalis ; P. gingivalis ) was inoculated into a BHI (Brain Heart Infusion) broth liquid medium and incubated at 37°C for 48 hours.

The cultured bacterial culture solution was confirmed by measuring the absorbance at a wavelength of 650 nm using a spectrophotometer. For 10 ml of the bacterial culture solution prepared at a concentration of 1x10 ⁷ CFU/ml, the composite compositions corresponding to Examples 1 and Comparative Examples 1 to 4 were treated by 6.25% (v/v) of the total volume, respectively, and 5% (v/ v) The case where xylitol solution was treated was used as a control. After incubating at 37° C. for 24 hours, 200 ul was dispensed into a 96-well plate, and absorbance was measured at a wavelength of 650 nm. Thereafter, the measured absorbance values were compared to select the most active combination.

As can be seen in Figures 2a to 2c and Table 2, xylitol (control), Example 1 and Comparative Examples 1 to 4 as a result of comparing the antibacterial activity against the oral bacteria described above Example 1 and Comparative Examples 1 to 4 Showed a better antibacterial activity than 5% xylitol.

Xylitol Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 S. mutans 0.368±0.028 0.131±0.06 0.254±0.013 0.361±0.016 0.247±0.031 0.331±0.026 S. sobrinus 0.389±0.01 0.294±0.02 0.342±0.02 0.351±0.016 0.331±0.027 0.341±0.013 P. gingivalis 0.177±0.018 0.102±0.01 0.072±0.041 0.123±0.035 0.128±0.014 0.141±0.021

In particular, Example 1 showed significantly higher antimicrobial activity on S. mutans and S. sobrinus than Comparative Examples 1 to 4, and there was no significant difference from Comparative Example 1 to P. gingivalis , but Comparative Examples 2 to 4 And showed significantly high antibacterial activity. Therefore, it was confirmed that Example 1 is a composite having the most excellent antibacterial activity.

1-2. Measurement of minimum inhibitory concentration (MIC) using a step dilution test

In order to measure the MIC, experiments were performed with reference to the method described in the literature (Lee Sung-lim et al., Korean Journal of Environmental Health, 32; pp.192-197, 2006).

Specifically, the cultured bacterial culture solution was confirmed by measuring the absorbance at a wavelength of 650 nm using a spectrophotometer. Prepared at a concentration of 1x10 ⁷ CFU/ml, a sample obtained by dispensing 200 ul of only the bacterial culture solution in a 96-well plate was set to 0% of the composite composition, and the highest concentration of the composite composition compared to the bacterial culture solution was set to 50%.

Thereafter, the concentration was diluted stepwise 2-fold dilution over a total of 7 times starting from 50% to 0.78%. The mixture of the diluted composite composition and the bacterial culture solution was further incubated at 37°C for 48 hours, and absorbance was measured at 650 nm with a spectrophotometer. The lowest concentration at which the growth of the test strain was suppressed was determined as the minimum inhibitory concentration, and this is shown in Table 3 and FIGS. 3A to 3C.

Strain Minimum inhibitory concentration (%) Streptococcus mutans 6.25 Streptococcus sobrinus 12.50 Porphyromonas gingivalis 6.25

As a result of comparing the antibacterial activity against oral bacteria described above by concentration of 5% xylitol, Examples 1 and Comparative Examples 1 to 4, the minimum inhibitory concentration of the composite composition for S. mutans and P. gingivalis was 6.25%. , The minimum inhibitory concentration of the composite composition for S. sobrinus was 12.5%. Both the composite compositions of Example 1 and Comparative Examples 1 to 4 showed better antibacterial activity than comparative 5% xylitol (control), and in particular, Example 1 showed excellent antibacterial activity even at lower concentrations than Comparative Examples 1 to 4 composite composition. . Therefore, it is considered that the antibacterial activity of the composite composition according to Example 1 of the present invention can reduce bacteria in the oral cavity and suppress plaque formation, thereby preventing dental caries and periodontal disease.

Test Example 2. Measurement of anti-inflammatory activity of the composite composition

In order to confirm the anti-inflammatory activity of the composite composition of Example 1, it was confirmed that the anti-inflammatory activity against inflammation caused by oral cells.

As normal oral cells, gingival fibroblasts (HGF-1; human gingival fibroblast) were added using 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin DMEM (Dulbecco's modified Eagle's medium) medium at 37°C, 5 % CO2 was incubated in an incubator, and the experiment was performed by dispensing into a 3.5 x 10 ⁵ cell/well in a 24 well-plate.

P. gingivalis , the causative agent of periodontal disease, was prepared by culturing in BHI broth medium, and complex lipid polysaccharide Pg-LPS separated from endotoxin secreted by P. gingivalis was gingival fibroblasts in gingival fibroblasts. Inflammation was caused by treatment at a concentration of 100 ng/ml. Thus, the complex composition of Example 1 was treated with 150 ul based on 250 ul of liquid medium to the oral cells in which inflammation was induced.

In order to compare the anti-inflammatory activity of Example 1, the expression level of the inflammatory cytokine IL-17 gene in normal oral cells, oral cells that induces inflammation through Pg-LPS treatment, and oral cells that induce inflammation and treat the composite composition Significant decreases were measured by analysis by RT-PCR (real-time polymerase chain reaction).

4 and Table 4, the expression level of IL-17 gene in oral cells induced inflammation with Pg-LPS was significantly increased compared to the expression level of IL-17 gene in normal oral cells. On the other hand, when the composite composition of Example 1 was treated with oral cells inducing inflammation with Pg-LPS, the expression level of IL-17 gene rapidly decreased, indicating a significantly lower expression level, compared with normal oral cells. Even when it did.

Control Pg-LPS Example 1 IL-17 gene expression level 1.0±0.10 1.32±0.11 0.73±0.16

Therefore, it was confirmed that the complex composition of Example 1 has an anti-inflammatory activity because the inflammatory cytokine IL-17 decreases when treated with oral cells. It is considered that the composite composition of Example 1 can inhibit inflammatory activity in the oral cavity by anti-inflammatory activity, thereby preventing periodontal disease.

Test Example 3: Evaluation of the cytotoxicity of the composite composition

Toxicity to the oral cells of the mouthwash comprising the composite composition of Example 1 and a commercially available artificial compound was evaluated.

Specifically, as a method for evaluating the toxicity to gingival fibroblasts, which are oral cells, cell viability was measured using an MTT assay. In general, various experiments were conducted from 1 minute to 30 minutes, which is a time when using a mouthwash and a time when using it, which is highly likely to remain, to measure cell viability and to confirm cytotoxicity and sensitivity.

The gingival fibroblasts were prepared by culturing at a concentration of 3.5 x 10 ⁵ cells/well as in Test Example 2, and Example 1 and the mouthwash were treated with 250 ul per well as a stock solution.

As can be seen in Figure 5, when treated with a conventional oral cleanser based on the number of cells in the control group, the survival rate was reduced to about 20% even after only 1 minute treatment, and gradually decreased as the treatment time increased. On the other hand, the oral cells treated with the composite composition of Example 1 of the present invention showed little change at the treatment time of 1 minute, 3 minutes, and 5 minutes, and showed a slightly increased result from the first cells from 15 minutes.

Therefore, the composite composition of the present invention has significantly lower toxicity to the oral cells than the chemical oral cleaning agents sold on the market, and is safe from natural herbal material-based oral diseases because it does not affect the oral cells when it remains in the oral cavity. It was confirmed that it can be used as a composite composition for prevention or treatment.

Claims (13)

Cheongdae extract 1.0 to 3.0 wt%; Cheoncho extract 1.0 to 3.0% by weight; 0.5 to 2.0% by weight of the extract of the ointment; Crest 0.5 to 2.0% by weight of extract; Peppermint extract 25.0 wt%; Secine extract 1.0-5.0 wt%; Clove extract 5.0 to 6.0% by weight; Cnidium extract 5.0-8.0 wt%; 5.0 to 6.0% by weight of milky white extract; Rhubarb extract 4.0 wt%; 0.1 to 1.0% by weight of Hwangnyeon extract; Allantoin 0.1-1.0 wt%; And xylitol 4.5% by weight; Oral disease prevention or treatment selected from the group consisting of dental caries, periodontal disease, gingivitis, periodontitis, chronic periodontitis, implant peritonitis, pulp, root canal disease and jaw osteomyelitis. According to claim 1, wherein the pharmaceutical composition is 2.0% by weight of Cheongdae extract; Cheoncho extract 2.0 wt%; 0.5% by weight of the extract of the pill; 0.5% by weight of pagoji extract; Peppermint extract 25.0 wt%; Secine extract 4.0 wt%; Clove extract 5.0 wt%; Cheongung extract 6.0% by weight; 5.0% by weight of Yubaekpi extract; Rhubarb extract 4.0 wt%; 0.2% by weight of hwangnyeon extract; Allantoin 0.2 wt%; And xylitol 4.5% by weight; which will include, oral disease prevention or treatment pharmaceutical composition.
delete delete The method according to claim 1, wherein the oral disease is Streptococcus mutans , Streptococcus sanguinis , Streptococcus sobrinus , Streptococcus sobrinus , Streptococcus ratti , Streptococcus ratti ( Streptococcus criceti ), Streptococcus anginosus , Streptococcus gordonii , Actinobacillus actinomycetemcomitans , Fusobacterium nucleum , Fusobac Prevotella intermedia ( Prevotella intermedia ) and one or more selected from the group consisting of Porphylomonas gingivalis ( Popphylomonas gingivalis ) as a causative bacteria, oral disease prevention or treatment pharmaceutical composition.
Cheongdae extract 1.0 to 3.0 wt%; Cheoncho extract 1.0 to 3.0% by weight; 0.5 to 2.0% by weight of the extract of the ointment; Crest 0.5 to 2.0% by weight of extract; Peppermint extract 25.0 wt%; Secine extract 1.0-5.0 wt%; Clove extract 5.0 to 6.0% by weight; Cnidium extract 5.0-8.0 wt%; 5.0 to 6.0% by weight of milky white extract; Rhubarb extract 4.0 wt%; 0.1 to 1.0% by weight of Hwangnyeon extract; Allantoin 0.1-1.0 wt%; And Xylitol 4.5% by weight; Antibacterial or anti-inflammatory composition comprising a.
According to claim 6, wherein the antibacterial or anti-inflammatory composition is 2.0% by weight of Cheongdae extract; Cheoncho extract 2.0 wt%; 0.5% by weight of the extract of the ointment; 0.5% by weight of pagoji extract; Peppermint extract 25.0 wt%; Secine extract 4.0 wt%; Clove extract 5.0 wt%; Cheongung extract 6.0% by weight; 5.0% by weight of Yubaekpi extract; Rhubarb extract 4.0 wt%; 0.2% by weight of hwangnyeon extract; Allantoin 0.2 wt%; And xylitol 4.5% by weight; containing, antimicrobial or anti-inflammatory composition.
delete The method of claim 6, wherein the antibacterial or anti-inflammatory composition is Streptococcus mutans , Streptococcus sanguinis , Streptococcus sobrinus , Streptococcus sobrinus , Streptococcus ratti , Streptococcus ratti Streptococcus criceti , Streptococcus anginosus , Streptococcus gordonii , Actinobacillus actinomycetemcomitans , Fusobacterium Fubacterium nucleatum ), Prevotella intermedia and Porphylomonas gingivalis , which inhibit growth or inhibit inflammation caused by or against one or more selected from the group consisting of Porphylomonas gingivalis . Composition. Cheongdae extract 1.0 to 3.0 wt%; Cheoncho extract 1.0 to 3.0% by weight; 0.5 to 2.0% by weight of the extract of the ointment; Crest 0.5 to 2.0% by weight of extract; Peppermint extract 25.0 wt%; Secine extract 1.0-5.0 wt%; Clove extract 5.0 to 6.0% by weight; Cnidium extract 5.0-8.0 wt%; 5.0 to 6.0% by weight of milky white extract; Rhubarb extract 4.0 wt%; 0.1 to 1.0% by weight of Hwangnyeon extract; Allantoin 0.1-1.0 wt%; And xylitol 4.5% by weight; dental caries, periodontal disease, gingivitis, periodontitis, chronic periodontitis, peri-implantitis, pulp, root canal disease and osteomyelitis selected from the group consisting of health functional food composition for improving oral disease. 11. The method of claim 10, The health functional food composition is 2.0% by weight of Cheongdae extract; Cheoncho extract 2.0 wt%; 0.5% by weight of the extract of the ointment; 0.5% by weight of pagoji extract; Peppermint extract 25.0 wt%; Secine extract 4.0 wt%; Clove extract 5.0 wt%; Cheongung extract 6.0% by weight; 5.0% by weight of Yubaekpi extract; Rhubarb extract 4.0 wt%; 0.2% by weight of hwangnyeon extract; Allantoin 0.2 wt%; And xylitol 4.5% by weight; containing, will improve the oral health functional food composition.
delete The method of claim 10, wherein the oral disease is Streptococcus mutans , Streptococcus sanguinis , Streptococcus sobrinus , Streptococcus sobrinus , Streptococcus ratti , Streptococcus ratti (Streptococcus criceti), Streptococcus anginosus , Streptococcus gordonii , Actinobacillus actinomycetemcomitans , Fusobacterium nucleatum , Fusobac Prevotella intermedia ( Prevotella intermedia ) and one or more selected from the group consisting of Porphylomonas gingivalis as a causative bacterium, health functional food composition for improving oral disease.

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