KR102917254B1 - Composition for prevention or treatment of oral disease comprising Forsythiae Fructus extract - Google Patents

Abstract

The present invention relates to a composition for preventing or treating oral diseases, including a forsythia extract, and more particularly, to a composition having an effect of preventing or improving toothache, tooth sensitivity, and bad breath. The composition of the present invention has excellent antibacterial activity against bacteria causing dental caries and periodontal disease, and suppresses PGE2, a pain and inflammation marker, in a concentration-dependent manner, and has excellent effects of inhibiting gingivitis formation, suppressing tooth sensitivity symptoms, and eliminating bad breath, and thus has high utility as an quasi-drug composition for preventing or improving one or more oral diseases selected from the group consisting of toothache, tooth sensitivity, and bad breath. In addition, the composition of the present invention can be used as a pharmaceutical composition and a food composition.

Description

Composition for prevention or treatment of oral disease comprising Forsythiae Fructus extract

The present invention relates to a composition for preventing or treating oral diseases comprising a lotus root extract, and more particularly, to an over-the-counter drug composition having the effect of preventing or improving toothache, tooth sensitivity, and bad breath. The present invention also relates to a pharmaceutical composition comprising a lotus root extract, a food composition, and an oral composition comprising the extract.

Healthy teeth are considered one of the five blessings, a crucial factor in determining quality of life. Among oral diseases, dental caries (cavities) and periodontal disease (pyorrhea) have high incidence rates worldwide. They cause various clinical symptoms such as pain, masticatory dysfunction, periodontal tissue destruction, bad breath, and tooth sensitivity, and are known to be the main factors leading to tooth loss. Furthermore, changes in dietary habits are increasing the causative factors of oral disease.

The human oral cavity is known to harbor approximately 600 to 800 species of microorganisms, controlled by enzymes such as lysozyme secreted in saliva. However, the oral environment, rich in nutrients and moisture, fosters the growth of microorganisms, and the tongue and dental plaque provide excellent habitats for them. Some of these microorganisms are opportunistic pathogens, causing conditions such as dental caries, periodontal disease, dentin hypersensitivity, and bad breath.

Antibacterial agents are used to suppress the growth of oral pathogens that live in dental plaque and cause dental caries, periodontal disease, bad breath, and tooth sensitivity. Various types of antibacterial agents, including antibiotics with bactericidal and bacteriostatic effects on oral pathogens, have been developed as agents for suppressing and treating dental caries, periodontal disease, and pulp and periapical infections.

However, antibiotics have the disadvantage of being difficult to use long-term because they can cause systemic side effects, as well as the emergence of resistant bacteria and superinfection in the oral cavity, making them difficult to use and can only be used as a treatment. Furthermore, antibacterial agents used in mouthwashes include Sangquinarine, Listerine, peroxide, and chlorhexidine. Sangquinarine has unclear effects on bacteria in the oral cavity, and its effectiveness in treating periodontal disease is even more unclear. It is also expensive. Listerine, which is mainly composed of alcohol, has some bacteriostatic properties, but its effect in the oral cavity is only temporary. Long-term use can also cause tissue damage. Furthermore, pyroxide, which has recently been added for whitening effects, is toxic to bacteria but is also toxic to human tissue, raising safety concerns. Furthermore, pyroxide-resistant bacteria sometimes emerge. In addition, chlorhexidine is known to be the best agent among those known to date for preventing and treating periodontal disease as well as inhibiting plaque formation, but it has the problem of causing irritation, discoloration and degeneration of tissues, and especially showing side effects such as a strong irritating taste and a strong odor, and it can cause dysbiosis and is carcinogenic, so its use is restricted in pregnant women, and it has the disadvantage of not being able to be used for long-term treatment or especially preventive purposes.

Meanwhile, Forsythiae Fructus refers to the dried fruit of the Uiseong Forsythia or Dangeong Forsythia, which belongs to the Oleaceae family. In Japan, the same plant originating from Korea is used as a medicinal herb, but in China, only the dried fruit of Dangeong Forsythia is used, not the Uiseong Forsythia. Forsythiae fruit forms chambers similar to lotus flowers, has a unique smell, a bitter taste, and slightly cooling energy. Its medicinal effects include reducing fever and detoxifying, eliminating wind-heat, and reducing swelling such as boils. Its pharmacological effects include antibacterial, anti-inflammatory, hypotensive, hemostatic, liver-healing, emetic, and diuretic effects. Its main chemical components include forsythol, sterol compounds, saponins, and oleanolic acid.

Against this backdrop, the inventors of the present invention conducted research to derive a natural material that is highly effective in preventing and improving oral diseases such as dental caries, periodontal disease, toothache, sensitivity, and bad breath, without concerns about the above-mentioned side effects. As a result, it was discovered that the extract of Forsythia japonica, a natural composition that is safe for the body and can be used with confidence, exhibits an antibacterial effect against bacteria that cause dental caries and periodontal disease, a PGE2 inhibitory effect, a gingivitis formation inhibitory effect, a sensitivity inhibitory effect, and a bad breath elimination effect, and thus completed a quasi-drug composition utilizing the extract, a pharmaceutical composition, a food composition, and an oral composition comprising the extract.

Korean Patent Publication No. 10-2015-0050239 Korean Patent Publication No. 10-2009-0117448

The purpose of the present invention is to provide a pharmaceutical composition for preventing or improving oral diseases, which contains a lotus root extract as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating oral diseases, which contains a lotus root extract as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving oral diseases, which contains a lotus root extract as an effective ingredient.

Another object of the present invention is to provide an oral composition comprising a lotus root extract as an active ingredient.

The present invention provides a pharmaceutical composition for preventing or improving oral diseases, which contains a lotus root extract as an effective ingredient, to solve the above-mentioned problems and achieve the purpose of the present invention.

In another aspect of the present invention, a pharmaceutical composition for preventing or treating oral diseases is provided, which comprises a lotus root extract as an active ingredient.

As another aspect of the present invention, a food composition for preventing or improving oral diseases is provided, which comprises a lotus root extract as an effective ingredient.

As another aspect of the present invention, an oral composition comprising a lotus root extract as an active ingredient is provided.

The present invention provides a pharmaceutical composition containing a lotus root extract as an active ingredient.

In the present invention, “Yeon-gyo (Forsythiae Fructus)” refers to the dried fruit of Uiseong Forsythia or Danggyo, which belongs to the Oleaceae family. When the fruit is just beginning to ripen and still green, it is picked, steamed, and dried. When it is picked and dried when fully ripe, it is called Cheong-gyo (靑翹). The shape is an oval or long oval capsule with both ends pointed, and some have the stem remaining at the base. The outer surface is light brown or dark brown, and there are small light gray raised dots scattered on it and two vertical grooves. When fully ripe, the fruit is split along the vertical grooves and the ends are twisted. The inside of the split pericarp is yellowish brown and has a septum in the center. The seeds have thin, long oval wings. The fruit is oblong or ovoid, slightly flattened, 1.5–2.5 cm long and 0.5–1.3 cm in diameter.

In the present invention, the term "extract" includes the extract itself and all formulations that can be formed using the extract, such as an extract obtained by the extraction treatment of the above-mentioned lotus root, a diluted or concentrated extract, a dried product obtained by drying the extract, a controlled or purified product of the extract, or a mixture thereof.

The extract of the present invention can be extracted from a natural, hybrid or mutant plant of the above-mentioned plant, and can also be extracted from a plant tissue culture.

In the extraction of the above-mentioned yeokgyo of the present invention, the extraction method is not particularly limited, and extraction can be performed according to a method commonly used in the relevant technical field. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, and reflux extraction, and these may be performed alone or in combination of two or more methods.

In the present invention, the type of extraction solvent used to extract the above-described lotus root is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent include water; lower alcohols having C ₁ to C ₄ such as methanol, ethanol, propyl alcohol, butyl alcohol, etc.; polyhydric alcohols such as glycerin, butylene glycol, propylene glycol, etc.; and hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether, dichloromethane, etc.; or mixtures thereof. Specifically, water, lower alcohols, 1,3-butylene glycol, and ethyl acetate can be used alone or in combination of two or more. In the present invention, the solvent for extracting the lotus root may be more specifically water (or distilled water), 1,3-butylene glycol, or a mixed solvent thereof, and more specifically, a solvent in which water (or distilled water): 1,3-butylene glycol is mixed in a weight ratio of about 7:3 may be used. Even more specifically, a solvent in which water (or distilled water): 1,3-butylene glycol is mixed in a weight ratio of about 6:4 may be used. The solvent may be used to extract the lotus root one or more times to prepare a solvent extract, and the solvent extract may be distilled under reduced pressure and then freeze-dried or spray-dried to prepare a dried extract. In a specific embodiment of the present invention, the lotus root extract was prepared using ethanol (Example 1).

In the present invention, the extract extracted by hot water or cold immersion can be used as is after filtering, for example, filtering out particles using nylon or the like, or filtering using a cryofiltration method, etc., to remove floating solid particles, or can be used after drying using freeze drying, hot air drying, spray drying, etc.

The present invention provides a pharmaceutical composition for preventing or improving oral diseases, comprising a lotus root extract as an active ingredient.

In addition, specifically, the present invention can provide an over-the-counter pharmaceutical composition for preventing or improving one or more oral diseases selected from the group consisting of toothache, sensitivity, and bad breath, which contains a lotus root extract as an active ingredient.

In the present invention, "oral disease" refers to various diseases occurring in the oral cavity, and the oral cavity refers to the space inside the mouth connecting the front lips to the back palate and the pharynx. In the present invention, the oral disease is a concept that includes all diseases occurring in the oral cavity regardless of their symptoms, and non-limiting examples of the oral disease include dental caries, periodontal disease (periodontitis or gingivitis), toothache, sensitivity, bad breath, etc.

In the present invention, “dental caries” refers to an infectious disease caused by bacteria living on the tooth surface, also called tooth decay, and exhibits symptoms of erosion and loss of the tooth’s hard tissue. Specifically, the milky-white, translucent, and hard substance that covers the crown surface of the tooth and protects the tooth dentin is called tooth enamel, and tooth decay occurs when the tooth enamel is damaged by acids generated when sugar, starch, etc. are broken down by oral pathogens living in the mouth. The main cause of dental caries is dental plaque, a bacterial film formed on the surface of teeth. Saliva forms a thin, sticky film on the teeth, and oral microorganisms such as Streptococcus sobrinus and Streptococcus mutans , which are types of streptococci, attach to it to form a biofilm, creating dental plaque, which is further thickened by Fusobacterium . The dental caries of the present invention includes all types of bacteria that cause dental caries, but specifically, it may be at least one selected from the group consisting of Streptococcus mutans , Streptococcus sanguinis , Streptococcus sobrinus , Streptococcus ratti , Streptococcus criceti , Streptococcus anginosus , and lactic acid bacteria, and more specifically, it may be Streptococcus mutans.

Streptococcus mutans, a type of streptococcus, is a Gram-positive bacterium and is also known as a cariogenic bacteria. Streptococcus mutans only proliferates on the surface of teeth, and primary teeth do not fully develop until around 30 months of age. Therefore, it is difficult for mutans bacteria to proliferate until this time, as they do in infancy. If mutans bacteria are not infected with mutans bacteria from adults during infancy, allowing other oral bacteria to establish themselves in the mouth, it will be difficult for mutans bacteria to enter the already balanced oral ecosystem, significantly reducing the risk of developing cavities throughout life. If the causative bacteria have already been transmitted through the mouths of adults, brushing frequently and maintaining a clean mouth can help prevent cavities. However, once mutans bacteria have established themselves in the oral cavity, eradication is impossible.

In one embodiment of the present invention, after inoculating a disk containing a forsythia extract into a medium on which Streptococcus mutans was spread, the size of the growth inhibition zone was measured, and it was confirmed that the experimental group containing the forsythia extract had a growth inhibition zone diameter of 10.0 mm or more, indicating significantly excellent antibacterial activity against Streptococcus mutans (Table 2).

In the present invention, "periodontal disease" refers to a disease in which inflammation occurs in the gingiva, periodontal ligament, and bone tissue supporting the teeth, commonly referred to as pyorrhea. Depending on the severity of the disease, it is divided into gingivitis and periodontitis. It is a relatively mild and quickly recovering form of periodontal disease. When the inflammation is limited to the gums, i.e., soft tissue, it is called gingivitis. When this inflammation progresses to the gums and the surrounding alveolar bone, it is called periodontitis. There is a V-shaped gap between the gingiva (gums) and the teeth. When oral pathogens attack the area below the gum line in this groove (sulcus), they release lipopolysaccharide (LPS), an inflammatory stimulant. This causes inflammation, including swelling and bleeding of the gums, and damages the periodontal ligament and adjacent tissues. As periodontitis progresses, it damages the periodontal ligament and even the alveolar bone, ultimately leading to tooth loss. Nutritional deficiencies such as protein and vitamins, pregnancy or hormonal disorders such as diabetes, smoking, and acquired immunodeficiency syndrome (AIDS) can worsen the disease. In addition, dental plaque and tartar can be cited as other causes of periodontal disease. The periodontal disease of the present invention includes all types of bacteria that cause periodontal disease, but specifically, Actinobacillus actinomycetemcomitans actinomycetemcomitans ), Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola The bacterium may be at least one species selected from the group consisting of Porphyromonas gingivalis, Porphyromonas denticola , and Fusobacterium nucleatum , and more specifically, Porphyromonas gingivalis.

The above Porphyromonas gingivalis is a type of bacterium in the genus Bacteroidetes, a Gram-negative anaerobic bacterium. Porphyromonas gingivalis is found in the oral cavity where periodontal disease has occurred, and is also found in the upper gastrointestinal tract, respiratory tract, and colon. In patients with chronic periodontal disease, collagen is degraded by the bacterium's collagenase enzyme, and the bacterium can invade gingival fibroblasts and survive even under high concentrations of antibiotics. Furthermore, the bacterium can invade gingival epithelial cells and survive for extended periods of time.

In one embodiment of the present invention, after inoculating a disk containing a lotus root extract onto a medium on which Porphyromonas gingivalis was spread, the size of the growth inhibition zone was measured. As a result, it was confirmed that the experimental group including the lotus root extract had a growth inhibition zone diameter of 10.0 mm or more, indicating significantly excellent antibacterial activity against Porphyromonas gingivalis (Table 2).

In addition, in one embodiment of the present invention, a clinical trial was conducted by selecting experimental subjects with gingivitis, and it was confirmed that the experimental group using the experimental toothpaste containing the extract of the forsythia was excellent in suppressing gingivitis and that the effect was sustained (Table 4).

In the present invention, "toothache" refers to pain in the tooth when eating sweet foods, or very cold or hot foods. Generally, it includes not only pain in the tooth itself, but also pain in the periodontal tissue that supports the tooth to the jawbone. Pain usually occurs when chewing, the gums swell, and a foul-smelling discharge is produced. Toothache manifests slightly differently depending on the underlying disease. Specifically, pain due to dental caries is initially painless, but gradually progresses and pain appears when the decay deepens to the nerve inside the tooth. Pain is caused by inflammation of the tissues surrounding the tooth in the case of an impacted tooth. Pain occurs when a tooth is broken or cracked, or when the tooth cracks when exposed to cold foods or when biting hard, irritating the nerve. In the case of pulpitis, pain is initially felt when exposed to cold foods, and as the condition progresses, pain is felt when exposed to hot foods. As the inflammation progresses and the pulp tissue dies, there is no response to cold or heat, and pain occurs due to inflammation of the periapical region (the tip of the tooth root).

In one embodiment of the present invention, as a result of confirming the PGE2 inhibitory effect known as a pain and inflammation marker, the experimental group including the forsythia extract showed the effect of inhibiting PGE2 in a concentration-dependent manner, confirming that a composition including the forsythia extract can be used for the purpose of preventing or alleviating toothache (Fig. 1).

In the present invention, “sensitive dentine” refers to hypersensitive dentine, and the symptom of sensitive dentine refers to dentine hyperesthesia. Sensitivity refers to the sensitivity of the exposed dentine part of the tooth when it comes into contact with cold air or irritating food, and 60 to 98% of adults with periodontal disease show symptoms. Sensitivity symptoms can appear when the tooth is receded toward the gums due to poor brushing habits, excessive occlusal force, acid dissolution, poor oral hygiene, after periodontal treatment, after restorative treatment, or when the tooth is dissolved due to acidification. The fundamental cause of the symptom of sensitive dentine is the exposure of many tubules in the tooth’s dentine to the outside. Due to the exposure, all stimuli are transmitted directly to the nerves in the pulp, making the same stimulus more sensitive than usual and causing pain. Sensitivity symptoms can range from mild to severe and persistent. Because teeth do not regenerate, painkillers or anti-inflammatory medications are not a fundamental solution. Sensitivity can affect the entire tooth or be localized to specific areas, such as the upper or lower jaw, or the right or left side. The most common site of sensitivity varies depending on the cause, but is most commonly the canine or premolars. The most severe area of pain, in over 90% of cases, is the cervical region, the area between the gums and the tooth.

In one embodiment of the present invention, a clinical trial was conducted by selecting test subjects having teeth with dentin hypersensitivity, and as a result, the test group that used the test group toothpaste containing the forsythia extract had an excellent effect in suppressing dentin symptoms, confirming that a composition containing the forsythia extract can be used for the purpose of preventing or improving dentin sensitivity (Table 6).

In the present invention, "bad breath" refers to an odor originating from the oral cavity and adjacent organs, with 85-90% of bad breath originating from the oral cavity, particularly from the back of the tongue. The main components of bad breath are volatile sulfur compounds, of which 90% are hydrogen sulfide, which is produced from cysteine, and methyl mercaptan and dimethyl sulfide, which are produced from methionine. These components are mainly produced by protein enzymes secreted by anaerobic bacteria, and the back of the tongue is the most important habitat. This area is not well cleansed by saliva, and many small depressions provide a place where bacteria continuously reside. The production of volatile sulfur compounds by anaerobic bacteria is the most important cause of bad breath, but it is also caused by oral diseases such as dental caries, periodontitis, and dry mouth. Many types of anaerobic bacteria are involved in causing bad breath, and a non-limiting example of a bad breath-causing bacteria is Porphyromonas gingivalis, which secretes many types and quantities of enzymes.

In one embodiment of the present invention, as a result of conducting a clinical trial on test subjects without dental caries, the test group that used the test group toothpaste containing the forsythia extract had an excellent bad breath removal effect, confirming that a composition containing the forsythia extract can be used for the purpose of preventing or improving bad breath (Table 7).

The quasi-drug composition of the present invention may include an oral quasi-drug. The components included in the quasi-drug composition of the present invention may include, in addition to the effective ingredient, components commonly used in oral quasi-drug compositions, such as an abrasive, a humectant, a binder, a foaming agent, a sweetener, a preservative, a medicinal ingredient, a flavoring agent, a coloring agent, a solvent, a whitening agent, a solubilizer, or a pH adjusting agent.

The oral pharmaceutical composition of the present invention can be manufactured in any formulation commonly manufactured in the art, and may have formulations such as toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, oral ointment, oral varnish, mouthwash, and gum massage cream, but is not limited thereto.

As an example, when the oral pharmaceutical composition of the present invention is in the form of a toothpaste, it may include a wetting agent, an abrasive, a binder, a foaming agent, a flavoring agent, a sweetener, a coloring agent, a preservative, a medicinal ingredient, a solvent, a pH regulator, etc.

The above humectant is used to make the powder among the toothpaste ingredients into a paste and to prevent the toothpaste from hardening in the air. Glycerin, sorbitol, propylene glycol, polyethylene glycol, etc. may be used alone or in a mixture of two or more thereof, in an amount of 1 to 60 wt%, specifically 10 to 50 wt%, of the total weight of the composition.

The foaming agent increases the cleaning effect by spreading the toothpaste in the oral cavity and acts as a surfactant to clean oral contamination. Surfactants such as sodium lauryl sulfate, sodium lauryl sarcosinate, sodium alkyl sulfosuccinate, and sucrose fatty acid ester may be used alone or in combination of two or more thereof, in an amount of 0.5 to 10 wt%, specifically 0.5 to 5 wt%, of the total weight of the composition.

The above binder prevents separation between the powder and liquid components in the toothpaste, and can be used alone or in combination of two or more kinds of cellulose derivatives such as sodium carboxymethyl cellulose, methyl cellulose, and hydroxypropyl cellulose, and sodium alginate, carrageenan, and xanthan gum, in an amount of 0.1 to 5 wt%, specifically 0.3 to 2 wt%, of the total weight of the composition.

The above abrasive removes attachments on the tooth surface without damaging the tooth surface and allows the tooth to have its original gloss. Calcium carbonate (CaCO ₃ ), dibasic calcium phosphate (CaHPO ₄ , CaHPO ₄ 2H ₂ O), anhydrous silicic acid (SiO ₂ 2H ₂ O), aluminum hydroxide (Al(OH) ₃ ), potassium pyrophosphate, magnesium carbonate, etc. may be used alone or in combination of two or more thereof in an amount of 1 to 60 wt%, specifically 10 to 50 wt%, of the total weight of the composition.

The above flavoring agent is intended to improve the feeling of use by providing a refreshing feeling and smell to the toothpaste, and may be used alone or in combination of two or more kinds, such as peppermint oil, spearmint oil, and menthol, in an amount of 1 to 60 wt%, specifically 0.01 to 5 wt%, of the total weight of the composition.

The above sweetener is used to remove unpleasant tastes caused by toothpaste raw materials and to improve the refreshing feeling. Saccharic acid, aspartame, xylitol, licorice acid, etc. can be used alone or in combination of two or more kinds, in an amount of 1 to 60 wt%, specifically 0.01 to 5 wt%, of the total weight of the composition.

The medicinal ingredients are for the purpose of preventing dental caries, preventing periodontal disease, preventing toothache, preventing sensitivity, and eliminating bad breath, and may include fluoride, zinc chloride, chlorhexidine, aminocaproic acid, tranexamic acid, cetylpyridium chloride, pyridoxine chloride, triclosan, tocopheryl acetate, sodium monofluorophosphate, etc., either alone or in combination of two or more. In the present invention, forsythia extract may be used as an additional medicinal ingredient.

The oral pharmaceutical composition of the present invention may be used alone or in combination, or may be used in combination with other oral pharmaceutical compositions other than the present invention.

In another aspect of the present invention, a pharmaceutical composition comprising a lotus root extract as an active ingredient is provided. In addition, specifically, the present invention can provide a pharmaceutical composition for the prevention or treatment of one or more oral diseases selected from the group consisting of toothache, sensitivity, and bad breath, comprising a lotus root extract as an active ingredient. The lotus root extract, oral diseases, toothache, sensitivity, and bad breath are as described above.

The pharmaceutical composition of the present invention can be formulated in the form of tablets, pills, powders, granules, capsules, suspensions, oral solutions, emulsions, syrups, aerosols, sterile injection solutions, etc. according to conventional methods for preventing and treating oral diseases.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations can be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, etc., and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives can be used.

Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, suppositories, etc. Non-aqueous solutions and suspensions may include vegetable oils such as propylene glycol, polyethylene glycol, olive oil, and injectable esters such as ethyl oleate.

In addition, the pharmaceutical composition of the present invention may further comprise a carrier, excipient or diluent. As the carrier, excipient or diluent, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, hydroxypropyl methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, mineral oil such as silicon dioxide, etc. may be used.

The specific dosage of the pharmaceutical composition according to the present invention can be variously selected by those skilled in the art according to factors such as the formulation method, the patient's condition and weight, the patient's sex, age, degree of disease, drug form, administration route and period, excretion rate, and response sensitivity, and the dosage and frequency of administration do not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans via various routes. Any route of administration is conceivable, and can be administered, for example, orally, intravenously, intramuscularly, or subcutaneously.

In another aspect of the present invention, a food composition comprising a lotus root extract as an active ingredient is provided. In addition, specifically, the present invention can provide a food composition for preventing or improving one or more oral diseases selected from the group consisting of toothache, sensitivity, and bad breath, comprising a lotus root extract as an active ingredient. The lotus root extract, oral diseases, toothache, sensitivity, and bad breath are as described above. The food composition may be used in the form of a health functional food, but is not limited thereto.

The forsythia extract or a food-scientifically acceptable salt thereof included in the food composition of the present invention may be included in the form of forsythia extract, a fraction thereof, or a processed product thereof. In addition, the composition may include a food-scientifically acceptable food additive in addition to the active ingredient.

In the present invention, "food supplement additive" means a component that can be added to food as an auxiliary, and can be appropriately selected and used by those skilled in the art as added in the manufacture of health functional foods of each formulation. Examples of food supplement additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc., but the types of food supplement additives of the present invention are not limited by the above examples.

The food composition of the present invention may include a health functional food. In the present invention, "health functional food" refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients that have functionality useful to the human body. Here, "functionality" means obtaining a beneficial effect for health purposes, such as regulating nutrients for the structure and function of the human body or physiological functions. The health functional food of the present invention can be manufactured by a method commonly used in the art, and during the manufacturing process, raw materials and ingredients commonly added in the art can be added. In addition, the formulation of the health functional food can be manufactured without limitation as long as it is a formulation recognized as a health functional food. The food composition of the present invention can be manufactured in various forms of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur with long-term administration of drugs because it uses food as a raw material, and is highly portable, so the health functional food of the present invention can be consumed as a supplement for preventing or improving oral diseases.

There is no limitation on the form that the health functional food of the present invention can take, and it can include all foods in the conventional sense, and can be used interchangeably with terms known in the art such as functional food. In addition, the health functional food of the present invention can be manufactured by mixing other appropriate auxiliary ingredients that can be included in foods and known additives according to the choice of a person skilled in the art. Examples of foods that can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and it can be manufactured by adding it to juice, tea, jelly, and juice manufactured using the lotus root extract according to the present invention as a main ingredient. It also includes foods used as feed for animals.

The quasi-drug composition comprising the forsythia extract of the present invention as an active ingredient has an excellent effect in preventing or improving oral diseases. Specifically, the composition of the present invention has excellent antibacterial activity against bacteria causing dental caries and periodontal disease, and suppresses PGE2, a pain and inflammation marker, in a concentration-dependent manner, and has an excellent effect in inhibiting gingivitis formation, suppressing tooth sensitivity symptoms, and eliminating bad breath, and thus has high utility as a quasi-drug composition for preventing or improving one or more oral diseases selected from the group consisting of toothache, tooth sensitivity, and bad breath. In addition, the composition comprising the forsythia extract of the present invention can be used as a pharmaceutical composition and a food composition.

The following drawings attached to this specification illustrate preferred embodiments of the present invention, and serve to further understand the technical idea of the present invention together with the contents of the invention described above, and therefore the present invention should not be interpreted as being limited to matters described in such drawings.
Figure 1 shows the results of confirming the PGE2 inhibitory effect by treating macrophages with LPS (control group), an inflammatory stimulus, and LPS and forsythia extract (experimental group).

Hereinafter, the composition and effects of the present invention will be described in more detail through examples and experimental examples. These examples and experimental examples are intended solely to illustrate the present invention and are not intended to limit the scope of the present invention.

Example 1: Yeongyo Preparation of extracts

The lotus root was cut into small pieces, soaked in a 95% ethanol solution, and extracted at room temperature for 48 hours to prepare a lotus root extract.

Experimental example 1: dental caries and antibacterial effect against periodontitis-causing bacteria

In order to confirm the preventive or therapeutic effect of the extract of the forsythia japonica prepared in Example 1 on dental caries and periodontitis, an antibacterial activity experiment was conducted. In order to confirm the effect of inhibiting the growth of oral pathogens, an antibacterial test was conducted using the paper disk assay method using Streptococcus mutans , a representative bacterium causing dental caries, and Porphyromonas gingivalis , a representative bacterium causing periodontal disease.

After increasing the activity of each of the above oral pathogens under the optimal culture conditions in Table 1 below, they were cultured for 4 to 6 hours in the optimal medium for each bacteria to adjust the turbidity of the culture solution to Macfarland turbidity No. 0.5 (1.5 X 10 ⁸ ), and 0.1 ml of each oral pathogen was evenly spread on the plate medium. After that, the extract of Forsythia japonica was inoculated at a concentration of 10 mg/disc onto a sterilized paper disc (Whatman no. 5 paper, 8 mm diameter) and dried by absorption for 1 hour. Then, after culturing for 24 to 48 hours at the optimal temperature for each of the above oral pathogens, the size of the growth inhibition zone (diameter mm) was measured, and the results are shown in Table 2 below.

strains Optimal conditions Gram stain
(Gram staining) Strain name temperature badge characteristics Gram (+) Streptococcus mutans 37 BHI Facultative anaerobic Gram (-) Porphyromonas gingivalis 37 TSA Hemin Menadione Badge anaerobic

Results of measurement of antibacterial activity of lotus root extract against oral pathogens Growth inhibition ring diameter (mm) Streptococcus mutans Porphyromonas gingivalis Unprocessed - (Growth is not inhibited) - (Growth is not inhibited) Treatment with lotus root extract 10.7 10.7

As shown in Table 2 above, compared to the untreated group that was not treated with the extract of the lotus root, the group treated with the extract of the lotus root showed significantly superior antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis, with a growth inhibition zone diameter of 10.0 mm or more for the two types of oral pathogens.

Experimental example 2: Effect of inhibiting gingivitis formation

In order to confirm the gingivitis prevention or treatment effect of the extract of the lotus root prepared in Example 1 above, a clinical trial was conducted by selecting a test subject group.

First, a control toothpaste was prepared using sodium carboxymethylcellulose, sodium lauryl sulfate, glycerin, colloidal silicon dioxide, silica, sodium cocoyl isethionate, dodicin, and sweeteners, fragrances, and coloring agents commonly used in the manufacture of toothpaste. An experimental toothpaste was prepared by adding 0.01 wt% of the forsythia extract prepared in Example 1 to the control toothpaste.

In order to select experimental subjects, a detailed oral examination was conducted on patients with gingivitis who had even teeth and no missing teeth, 30 patients by gender at 10-year intervals from 30 to 50 years of age. Then, 120 experimental subjects were selected and divided into groups of 60 each, and a clinical trial on the treatment effect of gingivitis was conducted as follows.

Specifically, the experimental subjects were divided into a control group and an experimental group, and the control group was instructed to use the control group toothpaste manufactured above three times a day, two hours after meals and before going to bed, and the experimental group was instructed to use the experimental group toothpaste manufactured above three times a day at the same time. Afterwards, dental floss was performed to score the initial gingivitis index, and the control group used the control group toothpaste manufactured above, and the experimental group used the experimental group toothpaste manufactured above. After 1 week, 1 month, 3 months, and 6 months, an oral examination was performed to examine the gingivitis index. The gingivitis index was measured by inserting a periodontal probe into the gingival sulcus, burning the area around each tooth without applying force, and measuring the bleeding after 30 seconds, and recording the score according to the criteria shown in Table 3 below, and the results are shown in Table 4.

Gingivitis index standard score detail 0 points Bleeding-free state 1 point Normal bleeding condition 2 points bleeding on the line 3 points Interdental triangular bleeding condition 4 points Bleeding condition of entire gums

Anti-gingival inflammation effect hour
control group experimental group 0 weeks 1.04 1.05 1 week 1.55 1.06 1 month 2.61 1.07 3 months 2.79 1.09 6 months 2.89 1.10

As shown in Table 4 above, compared to the control group, the experimental group that used toothpaste containing the extract of the lotus root maintained a normal bleeding state even after 6 months, indicating that the effect of suppressing gingival inflammation was sustained.

Experimental example 3: Pain and inflammation Marker PGE2 Inhibitory effect

In order to confirm the effect of the extract of the lotus root prepared in Example 1 on preventing or treating toothache, the inhibitory effect of PGE2, known as a pain and inflammation marker, was confirmed.

First, macrophages were seeded at a concentration of 1.5 X 10 ⁵ cells/ml in DMEM medium containing 10% FBS and cultured in a 24-well plate at 37°C and 5% CO ₂ for 24 hours. Then, 1 ㎍/ml of LPS, an inflammation-inducing stimulus, and the forsythia extract prepared in Example 1 were treated at various concentrations and cultured for an additional 24 hours. Then, a PGE2 ELISA assay kit (Thermo SCIENTIFIC) was purchased and the supernatant was used to analyze the PGE2 inhibitory ability according to the concentration of the forsythia extract (Fig. 1).

As shown in Figure 1, compared to the group treated with only LPS, the 50 ppm concentration of the lotus root extract had an effect of inhibiting PGE2 by approximately 40%, and the 100 ppm concentration of the lotus root extract had an effect of inhibiting PGE2 by approximately 70%. Therefore, it was found that the lotus root extract can be used for the prevention or treatment of toothache.

Experimental example 4: Sirin Inhibitory effect

In order to confirm the preventive or therapeutic effect of the extract of the lotus root prepared in Example 1 above, a clinical trial was conducted by selecting experimental subjects, and the control group toothpaste and experimental group toothpaste used in the clinical trial were each prepared using the same method as the toothpaste of Experimental Example 2 above.

The subjects were 40 volunteers with dentin hypersensitivity who agreed to participate in this experiment, and a total of 80 teeth were tested. The subjects included 20 men and 20 women, and ranged in age from 20 to 50. The subjects were unaware of the toothpaste contents, and the total experimental period was two weeks.

The experiment was conducted by measuring the reaction of the experimental subjects after applying a temperature stimulus. Before conducting the experiment, the hypersensitive area of the tooth with dentin hypersensitivity of each experimental subject was checked in advance, and cold water of about 5℃ was dropped on the sensitive area of the tooth with a dropper, and a score was given according to the criteria shown in Table 5 below. The control group used the control toothpaste, and the experimental group used the experimental toothpaste three times a day for two weeks. After two weeks, cold water of about 5℃ was dropped with a dropper again, and a score was given. Statistical analysis was performed using a paired Student-t test on the stimulation scores before and after the experiment, and the reaction scores to the temperature stimulus two weeks later are shown in Table 6 below.

Post-stimulation subject rating criteria score detail 0 points There is no discomfort whatsoever. 1 point It's a little uncomfortable or itchy. 2 points It's very cold. 3 points sick.

The degree of suppression of the siren hour
control group experimental group 0 weeks 2.14±0.13 2.14±0.09 2 weeks 2.13±0.10 1.80±0.11 p>0.05 *p<0.05

※ p>0.05: 95% confidence, no statistically significant difference. *p<0.05: 95% confidence, statistically significant difference.

As shown in Table 6 above, compared to the control group, the experimental group using toothpaste containing forsythia extract showed a reduction in tooth sensitivity after two weeks. Therefore, forsythia extract can be used to prevent or treat tooth sensitivity.

Experimental example 5: Bad breath removal effect

In order to confirm the effect of the extract of the lotus root prepared in Example 1 on preventing or treating bad breath, a clinical trial was conducted by selecting experimental subjects, and the control group toothpaste and experimental group toothpaste used in the clinical trial were each prepared using the same method as the toothpaste of Experimental Example 2.

Fifty men and women without dental caries were selected as experimental subjects, and a cross-over test was conducted on the control and experimental toothpastes. Commercially available garlic powder was dispersed in water, left for 24 hours, and then diluted to a Halimeter reading of 700 ppb or higher. The diluted solution was used as a bad breath inducer. The subjects gargled with 15 ml of the diluted garlic powder solution for 30 seconds, and after 1 minute, the degree of bad breath was measured with a Halimeter. The control group used the control toothpaste, and the experimental group used the experimental toothpaste, respectively, and brushed their teeth for 30 seconds to 1 minute. The degree of bad breath was measured with a Halimeter 1, 5, and 30 minutes after brushing to determine the persistence of bad breath suppression, and the results are shown in Table 7 below.

Bad breath removal effect hour
control group experimental group 1 minute 54.2% 96.0% 5 minutes 45.8% 91.2% 30 minutes 39.5% 86.6%

As shown in Table 7 above, compared to the control group, the experimental group that used toothpaste containing forsythia extract had over 96% of bad breath eliminated after brushing, and even after 30 minutes had passed since brushing, the bad breath removal rate was over 86%, showing a significantly superior bad breath removal effect compared to the control group. It was found that forsythia extract can be used for the prevention or treatment of bad breath.

Claims (9)

A pharmaceutical composition for preventing or improving oral diseases containing Forsythiae Fructus extract as an active ingredient,
The above oral diseases are sensitive teeth or toothache,
The above-mentioned quasi-drug composition is for oral use.
A pharmaceutical composition according to claim 1, wherein the oral disease further includes dental caries, periodontal disease, or bad breath.
A pharmaceutical composition for preventing or treating oral diseases, comprising an extract of Forsythiae Fructus as an active ingredient,
A pharmaceutical composition wherein the oral disease is a sensitivity or toothache.
delete delete In claim 1, the non-medical composition is at least one selected from the group consisting of toothpaste, mouthwash, mouthwash, gum, candy, mouth spray, oral ointment, oral varnish, mouthwash, and gum massage cream.
A pharmaceutical composition according to claim 3, wherein the oral disease further includes dental caries, periodontal disease, or bad breath.
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