JP2022093452A - Oral composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide compositions for repairing and regenerating periodontal tissue damaged by gingivitis or alveolar pyorrhea.

SOLUTION: Prepared are a composition for promoting the regeneration and/or repair of periodontal tissue, a composition for promoting the activation and/or repair of gingival cells, a composition for the prevention and/or treatment of alveolar pyorrhea, as well as an anti-inflammatory composition, a barrier function-improving composition, and antibacterial activity-promoting composition, in the oral cavity, which are characterized by containing at least one or more selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, Sasa veitchii extract, and Malva mauritiana extract.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to a composition for promoting periodontal tissue regeneration and / or repair, a composition for activating gingival cells and / or promoting repair, a composition for preventing and / or treating alveolar pyorrhea, and a composition for oral anti-inflammatory. The present invention relates to a composition for improving the barrier function in the oral cavity and a composition for promoting antibacterial activity in the oral cavity.

Periodontal disease (also called periodontal disease) refers to a condition in which the healthy condition of periodontal tissue is impaired, including diseases such as alveolar pyorrhea and periodontitis. The periodontal tissue consists of gingiva (gingiva) and alveolar bone (bone tissue that supports the tooth), cement that covers the tooth root (root of the tooth), root membrane that connects the tooth root and the alveolar bone, etc., and firmly adheres and fixes the tooth in the correct position. It has a strong structure for use. However, when bacteria settle between the teeth and gums and plaque (dental plaque) accumulates, the health condition is impaired, and QOL such as tooth wobbling and bad breath occurs. The risk of periodontal disease increases due to deterioration of the oral environment such as a decrease in saliva with aging, lifestyle-related diseases, aging, and diseases such as diabetes. It is also known that periodontal disease affects immune cells, resulting in exacerbation of diabetes, cardiovascular disease and the like. For this reason, the rate of having periodontal disease tends to be very high in an aging society, and the development of effective treatment and prevention methods for periodontal disease is an important issue in maintaining and improving people's health and reducing medical costs. It has become.

Among periodontal diseases, for advanced alveolar pyorrhea, surgical treatment has been taken to remove dental plaque, tartar, etc. from the lesion to improve the disease. On the other hand, chemical approaches have also been used in combination with surgical procedures or alone to improve periodontal disease. Although periodontal disease progresses to the inside of the gums, the chemical approach has the advantage over surgical procedures in that it can be effective from the gap between the teeth and gums to the back. Among such chemical approaches, a means for suppressing or reducing bacteria causing inflammation with an antibacterial agent or a bactericidal agent by utilizing naturally derived components (Patent Document 1), a periodontal tissue regeneration promoting substance. (Patent Document 2) and the like have been reported so far.

Japanese Unexamined Patent Publication No. 2016-11460 Japanese Unexamined Patent Publication No. 2017-12188

However, continuous administration of fungicides and antibacterial agents may produce resistant strains, especially with single agent use. Moreover, these agents themselves cannot repair the periodontal tissue. On the other hand, although regeneration-promoting agents such as peptides derived from enamel proteins are naturally derived, they are complicated in manufacturing and quality control to ensure safety because they use gene recombination technology in the agents themselves and in the manufacturing process. Due to its high cost, it was not a component that could be widely applied to oral compositions.

Therefore, the present invention is a periodontal disease damaged by periodontitis, alveolar pyorrhea, etc. by enhancing the self-repairing ability inherent in the living body with a safe ingredient that has already been administered to humans and ingested for many years. It is an object of the present invention to provide a composition for repairing and regenerating tissue.

In oral tissues such as periodontal tissues, the present inventors promote hyaluronic acid, hyaluronic acid salts, kumazasa extract, and xenia oi extract to promote periodontal tissue regeneration and repair, and activate and repair gingival cells. The present invention has been newly found to have excellent effects such as promotion of periodontal disease, prevention and treatment of periodontal disease, suppression of inflammation, improvement of barrier function of gingival cells, and promotion of antibacterial activity.

That is, the present invention provides the following.
Item 1.
(A) For promoting periodontal tissue regeneration and / or promoting restoration, which comprises at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salt, Kumazasa extract, and mallow extract. Composition.
Item 2.
(A) A composition for promoting gingival cell activation and / or repair, which comprises at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, Kumazasa extract, and mallow extract. thing.
Item 3.
(A) A composition for preventing and / or treating periodontal disease, which comprises at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, a bamboo strip extract, and a mallow extract. ..
Item 4.
(A) An oral anti-inflammatory composition comprising at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salts, Kumazasa extract, and mallow extract.
Item 5.
(A) A composition for improving a barrier function in the oral cavity, which comprises at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, a bamboo strip extract, and a mallow extract.
Item 6.
(A) A composition for promoting antibacterial activity in the oral cavity, which comprises at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, a bamboo strip extract, and a mallow extract.
Item 7.
Item 6. The composition according to any one of Items 1 to 6, wherein the component (A) is hyaluronic acid and / or a salt thereof.

According to the composition of the present invention, inflammation is suppressed and a living body is contained by containing at least one selected from the group consisting of (A) hyaluronic acid, a salt of hyaluronic acid, a kumazasa extract, and a mallow extract. It is possible to enhance the self-repairing function that the mallow originally has. Then, the periodontal tissue damaged by periodontitis, alveolar pyorrhea, etc. can be effectively repaired and regenerated.

[Composition]
The composition for promoting periodontal tissue regeneration and / or repair, the composition for activating gingival cells and / or promoting repair, the composition for preventing and / or treating alveolar pyorrhea, and the composition for anti-inflammatory in the oral cavity of the present invention. The composition for improving the barrier function and the composition for promoting the antibacterial activity are
(A) Contains at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salt, Kumazasa extract, and mallow extract.

[(A) component]
Among the components (A), as the hyaluronic acid, a known substance can be used, and examples thereof include hyaluronic acid, its derivatives, and salts thereof. Hyaluronic acid is a kind of acidic mucopolysaccharide, and is a polysaccharide containing a disaccharide of glucuronic acid and N-acetylglucosamine as a constituent unit. Hyaluronic acid can be extracted and recovered from chicken crowns, animal tissues such as shark skin, umbilical cord, eyeball, skin, and cartilage, hyaluronic acid-producing microorganisms such as Streptococcus microorganisms, and cultures of animal cells or plant cells. .. You can also purchase a commercial product.

The viscosity average molecular weight of hyaluronic acid is not particularly limited as long as the effect of the present invention is exhibited, but for example, the viscosity average molecular weight is 0.1 to 5 million. Here, the viscosity average molecular weight can be obtained by a known measuring method such as the method described in the 17th revised Japanese Pharmacopoeia general test method viscosity measuring method 1st method: capillary viscometer method.

The derivative of hyaluronic acid is not particularly limited as long as it is pharmacologically or physiologically acceptable, and for example, acetylated hyaluronic acid having an acetylated hydroxylation, sulfated hyaluronic acid having a hydroxylated sulfate, and cationization. Examples thereof include cationized hyaluronic acid, hydrophobized hydrolyzed hyaluronic acid (hydrolyzed alkyl hyaluronate (C12-13) glyceryl, etc.), hyaluronic acid crosspolymer, propylene glycol hyaluronate, and the like. As the derivative of hyaluronic acid, preferably acetylated hyaluronic acid, cationized hyaluronic acid, hydrolyzed hyaluronic acid, hyaluronic acid crosspolymer and / or propylene glycol hyaluronate are used.

The salt of hyaluronic acid or a derivative thereof is also not particularly limited as long as it is pharmacologically or physiologically acceptable, for example, alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, aluminum and the like. Examples include salt with metal. Preferably, a sodium salt or a potassium salt is used as the salt of hyaluronic acid or a derivative thereof. Specific salts of hyaluronic acid or its derivatives include, for example, sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, ammonium hyaluronate, monoethanolamine hyaluronate, and acetylated sodium hyaluronate. , Acetylized potassium hyaluronate, acetylated calcium hyaluronate, acetylated magnesium hyaluronate, acetylated zinc hyaluronate, acetylated ammonium hyaluronate, sodium hyaluronate crosspolymer, hydroxypropyltrimonium hyaluronate and the like. As the salt of hyaluronic acid or a derivative thereof, a sodium salt or a potassium salt is preferably used, and more preferably, a sodium salt is used.

Among the components (A), the Kumazasa extract is an extract obtained from Kumazasa (Sasa veitchii or Sasa veitchii (Carr.) REHD. (Gramineae)). Kumazasa is a plant of the Gramineae family, and can be used that grows naturally in the mountains of Japan. A polar solvent can be used as the extraction solvent, for example, lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene glycol. , Propylene glycol, dipropylene glycol, glycerin, diglycerin, ethylene glycol and other polyhydric alcohols having 2 to 5 carbon atoms; purified water or a mixture of at least two or more selected from these solvents. Among these, a lower alcohol, purified water, or a mixture of two or more selected from these solvents is preferable, and ethanol, purified water, or a mixture thereof is more preferable. The site that can be used as an extraction raw material is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include leaves, flowers, underground parts, bark, branches, above-ground parts, or mixtures thereof. Of these, leaves are preferable.

It is also possible to use a commercially available product for the Kumazasa extract. Examples of commercially available products of Kumazasa extract include trade name: Kumazasa extract (manufactured by Maruzen Pharmaceuticals Co., Ltd.) and trade name: Falcolex Kumazasa E (manufactured by Ichimaru Falcos Co., Ltd.).

Among the components (A), the mallow extract is an extract obtained from the Malvaceae mallow genus Cheeses (Malva silvestris Linne (Mallowaceae)) as a raw material. Cheeses is a perennial plant native to Europe and grows in the wild, but it is also cultivated for use as an herb and herbal medicine. A polar solvent can be used as the extraction solvent, and the polar solvent is, for example, a lower alcohol having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; and a lower aliphatic ketone such as acetone and methyl ethyl ketone. Polyhydric alcohol having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, diglycerin, ethylene glycol; purified water, or two or more selected from these solvents. Examples thereof include a mixture, preferably a lower alcohol, a polyhydric alcohol, purified water, or a mixture consisting of two or more selected from these solvents, and more preferably ethanol and 1,3-butylene glycol. , Propylene glycol, purified water, or a mixture of two or more selected from these solvents.

The site that can be used as an extraction raw material is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include leaves, flowers, stems, roots, above-ground parts, underground parts or mixtures thereof, and are preferable. Flowers and leaves.

Commercially available products can also be used as the mallow extract. Commercially available products of mallow extract include, for example, trade name: Usvenia oi extract LA, Usvenia oi extract BG, Mallow Moisture (both manufactured by Maruzen Pharmaceuticals Co., Ltd.), or trade name: Falcolex Zenia Oy B (manufactured by Ichimaru Falcos). Can be mentioned.

In the present invention, when an extract is obtained from Kumazasa or Usvenia oi, the extraction method is not particularly limited, but all or part of the dried product of Usvenia oi or Kumazasa, or a powder obtained by crushing and crushing the dried product. Is extracted with a solvent. The extract of Kumazasa or Usvenia oi may be used as it is, or may be diluted or concentrated. When the extract of Kumazasa or Usvenia oi is obtained, it is also possible to use Kumazasa or Usvenia oi preserved by freeze-drying.

In the present invention, the total content of the component (A) is not particularly limited, but from the viewpoint of significantly exerting the effect of the present invention, it may be 0.000001 to 5% by mass based on the total amount of the composition. It is preferably 0.000005 to 2% by mass, more preferably 0.00001 to 1% by mass, and particularly preferably 0.00001 to 0.2% by mass. The above content is a solid content conversion amount.

In the present invention, the content of hyaluronic acid or a salt thereof alone among the components (A) is, for example, 0.00001 to 2 mass based on the total amount of the composition from the viewpoint of significantly exerting the effect of the present invention. %, More preferably 0.0001 to 1.5% by mass, further preferably 0.0001 to 0.5% by mass, and even more preferably 0.001 to 0.1% by mass. Is particularly preferred.

In the present invention, the content of the Kumazasa extract alone among the components (A) is, for example, 0.000001 or more in terms of solid content, based on the total mass of the composition, from the viewpoint of significantly exerting the effect of the present invention. It is preferably 1% by mass, more preferably 0.000003 to 0.5% by mass, further preferably 0.000005 to 0.3% by mass, and 0.00001 to 0.2% by mass. It is even more preferably 0.00001 to 0.1% by mass, and most preferably 0.00001 to 0.01% by mass.

In the present invention, the content of the Xenia oi extract alone of the component (A) is, for example, 0.000001 to 1 mass in terms of solid content, based on the total amount of the composition, from the viewpoint of significantly exerting the effect of the present invention. %, More preferably 0.000003 to 0.5% by mass, further preferably 0.000005 to 0.3% by mass, and even more preferably 0.000005 to 0.2% by mass. It is more preferably 0.00001 to 0.1% by mass, and most preferably 0.00001 to 0.01% by mass.

All of these components (A) may be used alone or in any combination of two or more. Although not limited, the component (A) is preferably at least hyaluronic acid or a salt thereof, or a kumazasa extract, and more preferably hyaluronic acid or a salt thereof, from the viewpoint of excellent periodontal tissue regeneration ability.

[Use]
As used herein, periodontal disease or periodontal lesion refers to a condition in which the healthy condition of the periodontal tissue consisting of gingiva (so-called gum), cementum, periodontal ligament and alveolar bone is impaired, and is infected with bacteria. Can be caused by.

Among the bacteria in the mouth, three types of bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are known as the cause of periodontal disease, are also called red complex, and are also called red complex. There is. In addition, Aggregatibacter actinomycetemcomitans and Prevotella intermedia are also known as causative bacteria of periodontal disease. Recent studies have shown that various bacteria are involved in a complex manner and are involved in the progression of periodontal disease. In periodontal disease, the growth of these causative bacteria may cause symptoms such as giving off a peculiar bad breath and making the mouth sticky when waking up.

Dental plaques release toxins such as lipopolysaccharide (LPS), proteolytic enzymes (proteases), and collagen degrading enzymes (collagenase) derived from oral bacteria. Proteases and collagenase damage the gums, and LPS acts on the cells of the gums to secrete inflammatory cytokines. This inflammatory cytokine causes inflammation of the gums, damaging the gums and periodontal ligament. This leads to bleeding and swelling of the gums, and the lowering of the gums, which makes the teeth look longer. In addition, inflammatory cytokines overactivate immune cells in the body, resulting in the release of RANKL, which stimulates osteoclasts, from the immune cells. As a result, the alveolar bone that supports the teeth melts, and tooth mobility (wobble) begins to be seen, and the teeth eventually fall out. Inflammation and excessive activation of immune cells cause tissue damage and destruction and further inflammation, resulting in a synergistic deterioration that can be described as a negative chain of periodontal tissue destruction.

Periodontal disease can be broadly divided into two types, gingival inflammation (gingival inflammation) and alveolar pyorrhea (periodontitis), depending on the progression of the condition.

Periodontitis (gingival inflammation) refers to a condition in which the cementum, periodontal ligament, and alveolar bone are not destroyed but the gums are damaged. Symptoms of gum inflammation (gingiva inflammation) include, for example, redness of the gums (the gums look red, red-black, blackish, or dark black), swelling (the gingiva is round and swollen), and edema (there is no firmness of the gums). , Feeling buoyant), bleeding (bleeding from the gums due to brushing teeth, etc.), pain, itchy gums, white pus-like appearance when pressing the gums, hypersensitivity (temperature changes and physics) (I feel the gums squeaky or the gums hurt due to the stimulus).

Alveolar pyorrhea refers to a condition in which the initial inflammation of the gingiva spreads to deep periodontal tissues such as cementum, periodontal ligament, and alveolar bone, and is damaged and destroyed. Symptoms of alveolar pyorrhea include, for example, lowering of the teeth, thinning of the teeth, and gaps between teeth, in addition to the above-mentioned symptoms caused by periodontal disease bacteria and symptoms of periodontitis (gingival inflammation). These include the appearance of long teeth, the tendency for objects to get caught in the gaps between teeth, the feeling of floating teeth, the shaking of teeth, and the wobbling of teeth.

In healthy gums that are not affected by alveolar pyorrhea, the roots of the teeth buried in the gums are covered with cementum, which is further covered by the periodontal ligament. The periodontal ligament plays a very important role in connecting the alveolar bone, which is the bone that supports the tooth, to the tooth. The gums are originally light pink, firm, strong, and have a "fluffy" appearance, and almost no bleeding occurs even when cleaned with a toothpaste or an interdental brush.

The composition for promoting periodontal tissue regeneration or restoration of the present invention can regenerate or repair periodontal tissue that has collapsed due to periodontal disease or the like. In the present specification, "promotion" of regeneration or restoration directly enhances the inherent regeneration or restoration ability of periodontal tissue, as well as through improvement of damage and inflammation of shallow periodontal tissue to deep teeth. Includes enhancing the ability of periodontium to regenerate or repair. Promoting periodontal tissue regeneration or restoration is, for example, rejuvenating, repairing, repairing, rejuvenating, rejuvenating, restoring, reborn, healthy periodontal tissue (eg, gums and roots of teeth). It can also be expressed as recovering or healing toward the condition. In addition, expressions such as "gingival care" that indicate improvement of the condition of the periodontal tissue can also be used. By promoting the regeneration or repair of periodontal tissue, the above-mentioned symptoms of periodontitis and alveolar pyorrhea can be prevented, treated or ameliorated.

The periodontal tissue targeted by the composition for promoting periodontal tissue regeneration or restoration of the present invention is, for example, periodontal ligament, gingiva, gingival epithelium (surface or mucous membrane of gingiva), or periodontal ligament, preferably periodontal ligament. , Gingiva, or gingival epithelium (surface or mucosa of the gingiva), more preferably periodontal ligament.

The cells of the periodontal tissue that are the target of the composition for promoting periodontal tissue regeneration or restoration of the present invention are, for example, cells that form gingiva or periodontal ligament, and are preferably gingival epithelial cells, gingival fibroblasts, or gingival fibroblasts. Periodontal ligament fibroblasts, more preferably periodontal ligament fibroblasts.

Dental fibroblasts are similar in morphology to gingival fibroblasts and are thought to be cells responsible for the maintenance of root membrane tissue, from cell populations of pluripotent cells and cells with different functions. It is configured. Therefore, it is considered to be an important cell for the maintenance and regeneration of periodontal tissue.

The composition for activating gingival cells of the present invention activates cells forming periodontal tissue. Here, "activation" of a cell means improving the state of the cell by, for example, increasing the expression level of a gene or the ability of the cell to proliferate. To express "activating" a cell, for example, "reviving a weakened cell", "activating a cell", "revitalizing a cell", "energizing a cell", or "activating a cell" Expressions such as "revitalize", "revive", "revive", "revive", "reborn", and "make healthy" can be used. By activating gingival cells, the above-mentioned symptoms of periodontitis and alveolar pyorrhea can be prevented or ameliorated.

The periodontal tissue targeted by the composition for activating gingival cells of the present invention is, for example, periodontal ligament, gingiva, gingival epithelium (surface or mucous membrane of gingiva), or alveolar bone, preferably periodontal ligament, gingiva, and the like. Alternatively, it is the gingival epithelium (the surface of the gingiva or the mucous membrane), more preferably the periodontal ligament.

The periodontal tissue cells targeted by the composition for activating gingival cells of the present invention are, for example, cells forming gingiva or periodontal ligament, preferably oral keratinocytes, gingival fibroblasts, or periodontal ligament fibroblasts. It is a cell, more preferably a periodontal ligament fibroblast.

The composition for preventing alveolar pyorrhea of the present invention can prevent the above-mentioned symptoms of alveolar pyorrhea, and can be used for preventing or ameliorating the symptoms of periodontal disease including alveolar inflammation and alveolar pyorrhea. Further, it can be more preferably used for prevention or improvement of symptoms of alveolar pyorrhea. For example, the composition for preventing alveolar pyorrhea of the present invention can also be applied to healthy gums. In order to express the prevention of the symptoms of gum inflammation and alveolar pyorrhea, the expression with the addition of words indicating prevention against various symptoms caused by the above-mentioned gingival inflammation, alveolar pyorrhea and periodontal disease (for example). , Preventing bleeding from the gums, Preventing bad breath and stickiness in the mouth, Preventing swelling and bleeding of the gums, etc.); , Strong gums, plump gums, etc. can be used to describe changes to healthy gums; to prevent teeth from squeezing (with cold things, etc.), for clean / refreshing breath, etc. ..

The composition for treating alveolar pyorrhea of the present invention can improve the above-mentioned symptoms of alveolar pyorrhea. In order to express the improvement of the symptom, an expression to improve a specific part of the periodontal tissue such as "gingival care" can also be used.

The composition for preventing and / or treating periodontal pyorrhea of the present invention enhances the barrier function and antibacterial function on the surface of periodontal tissue, and at the same time suppresses inflammation to prevent exacerbation of symptoms, and cells in deep tissues such as periodontal membrane. As a result of promoting tissue regeneration through activation, it has an excellent effect in preventing and / or treating periodontal disease.

The oral anti-inflammatory composition of the present invention suppresses an increase in the expression level of inflammatory cytokine genes such as IL-1α and IL-8 when the cells forming the periodontal tissue are stimulated by LPS or the like. .. Inflammation of periodontal tissue can be suppressed, and the negative chain of tissue damage and destruction can be stopped. As a result, the above-mentioned symptoms of periodontitis and alveolar pyorrhea, particularly the symptoms of periodontitis, can be prevented or ameliorated.

The periodontal tissue targeted by the oral anti-inflammatory composition of the present invention is, for example, periodontal ligament, gingiva, gingival epithelium, or alveolar bone, preferably periodontal ligament, gingiva, or gingival epithelium, more preferably. Is the periodontal ligament.

The cells of the periodontal tissue targeted by the anti-inflammatory composition in the oral cavity of the present invention are, for example, cells forming gingiva or gingival membrane, preferably oral keratinocytes, gingival fibroblasts, or gingival fibroblasts. It is a cell, more preferably an oral keratinocyte.

The composition for improving the barrier function in the oral cavity of the present invention improves, strengthens or promotes the "barrier function" of the cells forming the periodontal tissue. Here, the "barrier function" refers to a function of the vicinity of the surface of a living tissue to prevent foreign substances from the outside world from invading the inside of the tissue. For example, by promoting the expression of a gene related to tight junction construction such as Claudin-1 and increasing the amount of the protein, the barrier function of cells forming periodontal tissue can be improved. In order to express the promotion of the barrier function in the oral cavity, expressions such as blocking toxins and foreign substances, enhancing the protective function of the gums, improving or protecting the surface of the gums, strengthening the surface of the gums or gums, etc. Can be used. By improving the barrier function, toxins such as LPS and proteolytic enzymes can invade the inside of the periodontium, and nutrients and physiologically active substances that are important for maintaining the healthy state of the tissue from the periodontium. Outflow can be prevented and further damage to the periodontal tissue can be prevented. Furthermore, the natural healing power of the periodontal tissue can be improved. As a result, the above-mentioned symptoms of periodontitis and alveolar pyorrhea, particularly the symptoms of periodontitis, can be prevented or ameliorated.

The periodontal tissue targeted by the composition for improving the barrier function in the oral cavity of the present invention is, for example, epithelial tissue in the oral cavity, preferably gingival epithelium.

The cells of the periodontal tissue that are the target of the composition for improving the barrier function in the oral cavity of the present invention are, for example, oral keratinocytes.

The composition for promoting antibacterial activity in the oral cavity of the present invention promotes antibacterial activity against foreign bacteria and fungi (molds) originally possessed by cells forming periodontium. For example, it promotes the expression of the gene for β-defensin-1, which is an antibacterial substance secreted from cells and is a kind of protein, and promotes the production of β-defenssin-1. In order to express the promotion of such antibacterial activity, for example, the causative bacteria of periodontal disease including the bacteria exemplified above, which enhance the defense function of the gums, enhance the defense power inherent in the living body, and enhance the immunity. Expressions such as suppressing, reducing, or suppressing proliferation can be used. By promoting the antibacterial activity, the symptoms caused by the causative bacteria of periodontal disease, the symptoms of periodontitis, and the symptoms of alveolar pyorrhea, particularly the symptoms caused by the causative bacteria of periodontal disease, can be prevented or ameliorated.

Further, the composition for promoting antibacterial activity in the oral cavity of the present invention is an antibacterial agent or a bactericidal agent that directly inhibits or sterilizes the action of bacteria or the like from the viewpoint of suppressing the amount of the antibacterial agent or the bactericidal agent used and suppressing the appearance of resistant bacteria. Can be used in combination with agents.

The periodontal tissue targeted by the composition for promoting antibacterial activity in the oral cavity of the present invention is, for example, epithelial tissue in the oral cavity, preferably gingival epithelium.

The cells of the periodontal tissue that are the target of the composition for promoting antibacterial activity in the oral cavity of the present invention are, for example, oral keratinocytes.

The composition of the present invention increases the expression of the hyaluronic acid synthase genes HAS1 and HAS3, and increases the amount of hyaluronic acid produced in the oral tissue. Therefore, the composition of the present invention can be used, for example, as a composition for promoting hyaluronic acid production in the oral cavity, a composition for enhancing the water retention capacity of the oral cavity tissue, and a composition for enhancing the moisturizing power of the oral cavity tissue. Such promotion of hyaluronic acid production in the oral cavity, enhancement of the water retention capacity of the oral tissue, and enhancement of the moisturizing power of the oral tissue are the tissues associated with the increase in the water content of the oral tissue, such as making the gums fresh and plump. It can also be expressed as a change in. The periodontal tissue targeted by these compositions is, for example, the epithelial tissue in the mouth, preferably the gingival epithelium. The cells of the periodontal tissue that are the target of these compositions are, for example, periodontal ligament fibroblasts, gingival fibroblasts, or oral keratinosites, preferably oral keratinosites.

The composition for promoting periodontal tissue regeneration and / or promoting restoration of the present invention, the composition for activating gingival cells and / or promoting repair, and the composition for preventing and / or treating alveolar pyorrhea, and for anti-inflammatory in the oral cavity. The composition, the composition for improving the barrier function, and the composition for promoting antibacterial activity exert a direct or indirect improving effect in any classification (stage) of periodontitis (gingival inflammation) and periodontal disease.

As used herein, "prevention" means preventing or delaying the onset of a disease or symptom, or reducing the risk of developing a disease or symptom.

As used herein, the term "improvement" means improvement or alleviation of a disease, symptom or health condition, prevention or delay of deterioration of the disease, symptom or health condition, or reversal, prevention or delay of progression of the disease or symptom.

As used herein, "treatment" means improving or alleviating a disease, symptom or health condition, or preventing or delaying the deterioration of a disease, symptom or health condition, or reversing or preventing the progression of the disease or symptom. Or it refers to the act of delaying.
[Applicable site]
Although periodontal disease is known to occur in some or all of the teeth in the oral cavity, the compositions of the present invention can be used either locally or in whole in the oral cavity.

[Applicable person]
The age group of the subject to which the composition of the present invention is applied is not particularly limited, but is preferably an adult, more preferably, from the viewpoint that the number of persons who have or may have alveolar pyorrhea increases with aging. It is 30 years old or older, more preferably middle-aged people (45 years old or older) to elderly people (55 years old or older).

Diabetes mellitus, cardiovascular disease, cerebral infarction, or a pre-stage state of these diseases, in which the use of the drug is restricted due to administration or ingestion of another drug due to the high safety of the components of the composition of the present invention. Alternatively, it is also preferably used for persons with osteoporosis. Among them, diabetes is clearly associated with alveolar pyorrhea, and osteoporosis is contraindicated in some of the pharmaceutical ingredients for alveolar pyorrhea, so these diseases are combined with alveolar pyorrhea. Those who have it are suitable objects of the composition of the present invention.

[PH]
The pH of the composition of the present invention is appropriately set according to the type of the component (A), the type and content of other compounding components, the pharmaceutical form, the method of use, etc., and is within a physiologically or pharmaceutically acceptable range. However, from the viewpoint of improving the usability, the pH is preferably 3 to 9, more preferably 4 to 8.5, still more preferably 4.5 to 7.5, and on the other hand, the dissolution of the tooth ( From the viewpoint of reducing the risk of acid erosion), the pH is preferably 5.5 to 6.0.

[Dosage form / form]
The dosage form of the composition of the present invention is not particularly limited as long as it is in a form known as a pharmaceutical product, a non-medicinal product, or a cosmetic product, and is, for example, a liquid agent, a foam agent, a cream agent, a paste agent, a spray agent, or a pasta agent. , Gels, films, tablets (troches, etc.), etc., but liquids, foams are preferable from the viewpoint of allowing a small amount of composition to stay for a long time and acting on periodontal tissues and causative bacteria of periodontal disease. Agents, creams, pastes or sprays, more preferably liquids, foams, creams or pastes.

The form of the composition of the present invention is not particularly limited as long as it is a form known as a pharmaceutical, a non-medicinal product, a cosmetic, or a food, and for example, a mouthwash, an oral cleaning agent such as mouthwash, and a dentifrice (toothpaste). Toothpaste, liquid toothpaste, foam toothpaste, powdered toothpaste, etc.), beauty liquid applied to toothpaste, troches, lozenges, candies, chewing gum, etc. From the viewpoint of acting on the dentifrice, it is preferably a mouthwash, an oral dentifrice, or a dentifrice, and more preferably a mouthwash, an oral dentifrice, a liquid dentifrice, or a foam-like dentifrice.

The composition of the present invention may be used in combination with antibacterial or bactericidal components as long as the effects of the present invention are not impaired. For example, benzethonium chloride, chlorhexidine gluconate, chlorhexidine hydrochloride, cetylpyridinium chloride, benzalkonium chloride, zinc citrate, sanginaline, delmopinol, sodium lauroyl sarcosin (LSS), alkyldiaminoethylglycine, triclosan, isopropylmethylphenol, hinokithiol, thymol. , Catechin, lactoferrin, lactoperoxidase, dextranase, lysoteam, protease, manuka honey extract, nycin, triclosan and the like can be used alone or in combination of two or more.

In the composition of the present invention, glycyrrhizic acid, β-glycyrrhetinic acid, ε-aminocaproic acid and salts or derivatives thereof can be used in combination as an anti-inflammatory agent as long as the effects of the present invention are not impaired.

In the composition of the present invention, tranexamic acid and a salt thereof can be used in combination as a bleeding improving agent as long as the effects of the present invention are not impaired.

The composition of the present invention can be used in combination with allantoin or the like as a tissue repair agent as long as the effects of the present invention are not impaired.

The composition of the present invention contains a fluorine compound such as sodium fluoride, sodium monofluorophosphate (MFP), tin fluoride, etc. as a remineralizing agent or a remineralization promoting substance as long as the effects of the present invention are not impaired. , Hydroxyapatite, Xylitol and the like can be used alone or in combination of two or more.

The composition of the present invention contains, as other medicinal ingredients, chlorophyll, sodium polyphosphate, sodium oxalis extract, tocopherol acetate (vitamin E), sodium pyrophosphate, polyethylene glycol, zinc chloride, as long as the effects of the present invention are not impaired. Sodium chloride, potassium nitrate, aluminum lactate, sodium hydrogen phosphate hydrate and the like can be used alone or in combination of two or more.

The composition of the present invention is a wetting agent such as glycerin, polyethylene glycol, 1,3-butylene glycol, dipropylene glycol; a sweetening agent such as sodium saccharin, sucralose; a cooling agent such as menthol, as long as the effect of the present invention is not impaired. Agents; Fragrances such as anetol; Nonionic surfactants such as glycerin fatty acid ester and polyoxyethylene hydrogenated castor oil; Anionic surfactants such as sodium lauryl sulfate; pH adjusters and bactericides other than the above components , Anti-inflammatory agents, preservatives, colorants, abrasives, vitamins, solvents (ethanol, etc.) and the like, which can contain components conventionally used in oral compositions.

The composition of the present invention is divided into 1 to several times a day, and is usually ingested or administered 1 to 6 times a day, 1 to 3 times a day, or 1 to 2 times a day or at arbitrary periods and intervals. sell.

Next, the present invention will be specifically described with reference to Examples and Test Examples, but the present invention is not limited to the following Examples and Test Examples.

The concentrations of the sodium hyaluronate, the kumazasa extract, and the mallow extract of the test examples of the present specification are all expressed by the mass of the component converted into solid content divided by the solution volume. Unless otherwise specified, the operation and measurement method using a commercially available kit followed the manual attached to the kit.

[Cell / medium]
As human oral keratinocytes (epithelial cells), Human Oral Keratinocyte: HOK (manufactured by Kurabo Industries, Ltd., Lot No. 12685) was used. Unless otherwise specified, the culture of human oral keratinocytes was carried out using an Oral keratinocyte medium (Ciencell, No. 2611) in an environment of 37 ° C., 5% carbon dioxide gas and 95% air.

As human periodontal ligament fibroblasts, Human Periodontal Fibroblast: HPDLF (manufactured by ScienCell) was used. Unless otherwise specified, human periodontal ligament fibroblasts are cultured in DMEM medium (Gibco, Product No. 11995073) with 10% (v / v) fetal bovine serum (FBS) and Antimycotic (Gibco). , Product No. 15240062) was added to 1% (v / v) and used in an environment of 37 ° C., 5% carbon dioxide gas and 95% air.

[Test Example 1. Anti-inflammatory effect on oral keratinocyte inflammation (gene expression analysis)]
Human oral keratinocytes (epithelial cells) were seeded on a 24-well plate (CellBind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, each component shown in Table 1 was replaced with a medium in which each component was dissolved at each concentration and cultured.
The next day, Escherichia coli-derived lipopolysaccharide (Lipopolysaccharides from Escherichia coli: LPS, manufactured by Sigma) was replaced with a medium in which each component shown in Table 1 was dissolved at each concentration, and the cells were further cultured for 6 hours. In addition, in order to calculate the gene expression level in the background, a group treated with LPS and a medium to which each component was not added was also provided. After culturing, the cells were washed twice with PBS (-), RNA was extracted using RNeasy (registered trademark) Mini Kit (manufactured by Qiagen), and then TOYOBO RiverTra Ace qPCR RT Master Mix with gDNA Remover (manufactured by TOYOB) was used. CDNA was made using. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq. As Taqman Probe, GAPDH (Hs02758991_g1), IL-8 (Hs00174103_m1), and IL-1A (Hs00174092_m1) purchased from Applied Biosystems were used.

From the measurement results, the gene expression levels of IL-1α and IL-8 in the group treated with the medium to which only LPS (100 μg / mL) was added (Comparative Example 1-2), and the medium to which LPS and each component were not added were used. Based on the difference between the gene expression levels of IL-1α and IL-8 in the treated group (Comparative Example 1-1), the gene expression levels of IL-1α and IL-8 in each example, LPS and From the difference between the gene expression levels of IL-1α and IL-8 in the group treated with the medium without adding each component (Comparative Example 1-1), IL-1α and IL-8 with each component added, respectively. The expression reduction rate of was calculated. The results are shown in Table 1. Here, the expression reduction rate is calculated as follows.
<Expression reduction rate (%)>
= (1-((Gene expression level in each example-Gene expression level in Comparative Example 1-1) /
(Gene expression level in Comparative Example 1-2-Gene expression level in Comparative Example 1-1))) × 100

From this result, by stimulating oral keratinocytes with LPS, which is a toxin derived from bacteria, the expression of IL-1α and IL-8, which are inflammatory cytokines, is enhanced (Comparative Example 1-2), but sodium hyaluronate. It was confirmed that the expression was reduced by adding the Keratinocyte extract and the mallow extract (Examples 1-1 to 1-6).

[Test Example 2. Anti-inflammatory effect on oral keratinocyte inflammation (expression analysis at protein level)]
Human oral keratinocytes were seeded on a 96-well plate (Cell Lind, manufactured by Corning) at a cell number of 5600 cells / well. After culturing for 24 hours, each component shown in Table 2 was replaced with a medium in which each component was dissolved at each concentration and cultured.
The next day, 100 μg of LPS and each component shown in Table 2 were replaced with a medium in which they were dissolved at their respective concentrations, and the cells were further cultured for one day. After culturing, the culture medium supernatant (sample for ELISA) was collected, and the expression level of IL-1α was measured by Human IL-1 alpha / IL-1F1 DuoSet ELISA (manufactured by R & D Systems). In addition, the culture plate from which the supernatant had been removed was washed twice with PBS, and Hoechst 33342 was diluted 1000-fold with medium and replaced with the medium in well. After culturing for 10 minutes, images were taken with Image Xpress ((Molecular Devices) (16 fields / well). Cell count was measured by analysis with a dedicated cell counting program (MetaXpress) of the instrument. Each group obtained by ELISA. The expression level of IL-1α was divided by the value of the number of cells obtained by Hoechst staining to obtain the expression level of IL-1α protein per cell number, and the mixture was treated only with a medium to which LPS or each component was not added. (Comparative Example 2-1), the IL-1α protein expression level per cell was set to 1, and the relative protein expression level when LPS or each component was added was calculated.

Based on the difference in the expression level between IL-1α (Comparative Example 2-2) in the control to which LPS (100 μg / mL) was added and the culture medium to which LPS or each component was not added (Comparative Example 2-1). Table 2 shows the results of calculating the IL-1α expression reduction rate when each component was added. Here, the IL-1α expression reduction rate (%) is calculated as follows.
<IL-1α expression reduction rate (%)>
= (1-((Protein expression level in each example-Protein expression level in Comparative Example 2-1) / (Protein expression level in Comparative Example 2-2-Protein expression level in Comparative Example 2-1))) x 100

From this result, even in the expression analysis at the protein level using ELISA, the expression of IL-1α protein, which is an inflammatory cytokine, is enhanced by LPS (Comparative Example 2-1), but sodium hyaluronate, Kumazasa extract, Alternatively, it was confirmed that the expression was reduced by adding the Xenia oi extract (Examples 2-1 to 2-6).

[Test Example 3. Antibacterial function improving effect of oral keratinocytes (gene expression analysis)]
Human oral keratinocytes were seeded on a 24-well plate (CellBind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, each component shown in Table 3 was replaced with a medium in which each component was dissolved at each concentration, and the cells were cultured for 6 hours. After culturing, the cells were washed twice with PBS (-), RNA was extracted using RNeasy Mini Kit (manufactured by Qiagen), and then TOYOBO RiverTra Ace qPCR RT Master Mix with gDNA Remember (manufactured by TOYOBO) was used. Made. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq (manufactured by Takara Bio Inc.). As Taqman Probe, GAPDH (Hs02758991_g1) and Defensin-1 (Hs00608345_m1) purchased from Applied Biosystems were used.

From the measurement results, the expression promotion rate when each component was added was calculated based on the expression level of β-Defensin-1 when treated with only the medium (Comparative Example 3-1). (Table 3). Here, the β-Defensin-1 expression promotion rate (%) is calculated as follows.
<Β-Defensin-1 expression promotion rate (%)>
= ((Gene expression level in each example / Gene expression level in Comparative Example 3-1) -1) × 100

From this result, the addition of sodium hyaluronate, Kumazasa extract, or mallow extract enhances the expression of β-Defensin-1, which is known as a cell-derived antibacterial factor, and sodium hyaluronate is particularly remarkable. It was clarified that the expression was enhanced (Examples 3-1 to 3-6).

[Test Example 4. Barrier function improving effect of oral keratinocytes (gene expression analysis)]
Human oral keratinocytes were seeded on a 24-well plate (CellBind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, each component shown in Table 4 was replaced with a medium in which each component was dissolved at each concentration, and the cells were cultured for 6 hours. After culturing, the cells were washed twice with PBS (-), RNA was extracted using RNeasy Mini Kit (manufactured by Qiagen), and then TOYOBO RiverTra Ace qPCR RT Master Mix with gDNA Remember (manufactured by TOYOBO) was used. Made. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq (manufactured by Takara Bio Inc.). As Taqman Probe, GAPDH (Hs02758991_g1) and Claudin-1 (Hs00221623_m1) purchased from Applied Biosystems were used.

From the measurement results, the expression promotion rate when each component was added was calculated based on the expression level of Claudin-1 in the control treated with only the medium (Comparative Example 4-1) (Table 4). Here, the Claudin-1 expression promotion rate (%) is calculated as follows.
<Claudin-1 expression promotion rate (%)>
= ((Gene expression level in each example / Gene expression level in Comparative Example 4-1) -1) × 100

From this result, the addition of sodium hyaluronate, Kumazasa extract or mallow extract promotes the expression of Claudin-1, which is known as a core protein for tight junction construction that contributes to the barrier function. Was clarified (Examples 4-1 to 4-5).

[Test Example 5 Barrier function improving effect of oral keratinocytes (electrical resistance value)]
Human oral keratinocytes were seeded at 96000 cells / well in a 12-well plate (12 mm Transwell® with 0.4 μm Polyester Membrane Insert, Sterile, Corning) insert. After culturing for 3 days, the cells were replaced with a differentiation-inducing medium (2 mM Ca 2 ⁺ added Oral Keratinocyte medium) in which TNFα and sodium hyaluronate were dissolved at the concentrations shown in Table 5, and the cells were cultured for 5 days. Then, the electric resistance value (TER value) of the insert was measured by Millicell (registered trademark) ERS-2 Voltohmmeter (manufactured by Millipore).

From the measurement results, the difference between the TER value in the differentiation-inducing medium alone (control) and the TER value when only TNF-α was added (Comparative Example 5-1) was used as a reference, and the TER value in Examples and Comparative Example 5- From the difference in TER value in No. 1, the barrier function improvement rate when sodium hyaluronate was added was calculated (Table 5). That is, the barrier function improvement rate (%) is calculated as follows.
<Barrier function improvement rate (%)>
= ((TER value in Example 5-1-TER value in Comparative Example 5-1) / (TER value in control-TER value in Comparative Example 5-1)) × 100

From this result, it was confirmed that the barrier function was lowered by the addition of TNF-α to oral keratinocytes (Comparative Example 5-1), but the barrier function was significantly improved by the addition of sodium hyaluronate (implementation). Example 5-1).

[Test Example 6 Cell proliferation effect of periodontal ligament fibroblasts (measurement of intracellular enzyme)]
Human periodontal ligament fibroblasts were seeded on a 96-well plate (Cell Bond, Corning) so that the number of cells was 3000 cells / well. After culturing for 6 hours, the concentration of fetal bovine serum (FBS) (MP Biomedicals, Lot No. A15035) was changed from 10% to 0.2% and cultured overnight. Twenty-four hours after cell seeding, sodium hyaluronate, Kumazasa extract, and mallow extract were replaced with a 0.2% FBS-containing medium in which the concentrations shown in Table 6 were dissolved, and the cells were cultured for 48 to 72 hours. After culturing, the cells were washed once with a serum-free medium, and the number of cells was measured by Cell Counting Kit-8 (CCK-8, Dojindo).

The cell proliferation promotion rate was calculated from the number of cells based on the number of cells in the 0.2% FBS-containing medium-treated group (Comparative Example 6-1) (Table 6). Here, the CCK-8 cell proliferation rate is calculated as follows.
<Cell proliferation promotion rate by CCK-8 (%)>
= ((Number of cells in each example / Number of cells in Comparative Example 6-1) -1) × 100

Proliferation and migration of periodontal ligament fibroblasts are important in the regeneration or repair of periodontal tissue. From the results shown in Table 6, it was confirmed that the addition of sodium hyaluronate or Kumazasa extract to periodontal ligament fibroblasts increased the enzymatic activity indicating cell proliferation and cell activation (Example 6-1). -Example 6-6).

[Test Example 7 intracellular hyaluronic acid production promoting effect of oral keratinocytes (gene expression analysis)]
Human oral keratinocytes were seeded on a 24-well plate (CellBind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, each component shown in Tables 7-a and b was replaced with a medium in which each component was dissolved at the respective concentration, and the cells were cultured for 6 hours. After culturing, the cells were washed twice with PBS (-), RNA was extracted using RNeasay Mini Kit (manufactured by Qiagen), and then TOYOBO RiverTra Ace qPCR RT Master Mix with gDNA Remember (manufactured by TOYOBO) was used. Made. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq (manufactured by Takara Bio Inc.). As Taqman Probe, GAPDH (Hs02758991_g1), HAS1 (Hs00758053_m1), and HAS3 (Hs00193435_m1) purchased from Applied Biosystems were used.

From the measurement results, the expression promotion rate when each component was added was calculated based on the expression levels of HAS1 and HAS3 in the control of only the medium (Comparative Example 7-1 or 8-1) (Table 7-a, b). Here, the expression promotion rate is calculated as follows.
<Expression promotion rate (%)>
= ((Gene expression level in each example / Gene expression level in Comparative Example 7-1 or 8-1) -1) × 100

HAS1 is a gene known to contribute to the promotion of high molecular weight hyaluronic acid production, and HAS3 is a gene known to contribute to the promotion of low molecular weight hyaluronic acid production. From the results shown in Tables 7-a and 7-b, it was confirmed that the addition of sodium hyaluronate, Kumazasa extract, and mallow extract enhances the expression of hyaluronic acid production promoting factors HAS1 and HAS3. (Examples 7-1 to 7-6, Examples 8-1 to 8-5). In addition, it was revealed that sodium hyaluronate, in particular, exhibits a remarkable expression-enhancing effect on these genes.

Hyaluronic acid is known to be contained in the epidermis as well as in the substrate that fills the space between collagen and elastin in the dermis. It can hold a large amount of water and supports the structure of collagen and elastin, which plays an important role in the firmness, elasticity and moisturization of the gingiva. It is also known that when tissue is damaged or destroyed, hyaluronic acid production is promoted as a response to the healing process and inflammation, resulting in anti-inflammatory and tissue remodeling effects (Makoto Goto, Inflammation, Vol.15, No.2, 1995).

From the above results, sodium hyaluronate, Kumazasa extract, and Zeniaoi extract increase the amount of hyaluronic acid in the periodontal tissue by increasing the expression of HAS1 and HAS3, and bring about the repair promotion of the periodontal tissue and the anti-inflammatory effect. Furthermore, it has the effect of making the gingiva firm and elastic, and making the gingiva plump and healthy.

The epithelium in the mouth is a mucosal tissue, and there are differences in the degree of keratinization and appendages from normal skin. Furthermore, recently, gene expression levels have been compared between oral epithelial cells and cutaneous epithelial cells, and it has been reported that there was a difference in the expression of more than 10,000 kinds of genes (Anna Turabelidze et al. PLOS ONE, September 2014 issue, Vol. 9, Issue 9, e101480). Although the mechanism is not clear, in such gene expression profiles of cells in oral tissues different from skin, sodium hyaluronate, kumazasa extract, and mallow extract were used for cells in oral tissues from Test Example 1 to. It is presumed that the peculiar effect confirmed in 7 was achieved.

Periodontal tissue regeneration and / or restoration promoting composition of the present invention, gingival cell activation and / or restoration promoting composition, alveolar pyorrhea prevention and / or therapeutic composition, oral anti-inflammatory composition, oral cavity Examples of the formulation of the composition for improving the barrier function in the oral cavity and the composition for promoting the antibacterial activity in the oral cavity are shown below.

(Pharmaceutical Example 1: Foam-shaped mouthwash)
Allantoin 0.1% by mass
Cetylpyridinium chloride hydrate 0.02% by mass
Sodium hydrogen phosphate hydrate 0.04% by mass
Dipotassium glycyrrhizinate 0.1% by mass
2-Alkyl-N-Carboxymethyl-
N-Hydroxyethyl imidazolinium betaine 0.5% by mass
Polyoxyethylene cured castor oil 1% by mass
Sodium hyaluronate 0.001% by mass
Propylene glycol 10% by mass
Citric acid Appropriate amount Phenoxyethanol 0.2% by mass
Disodium edetate 0.01% by mass
Fragrance 0.1% by mass
Water balance
100% by mass in total

(Pharmaceutical Example 2: Mouthwash)
Benzethonium chloride 0.01% by mass
Polyoxyethylene cured castor oil 2% by mass
Concentrated glycerin 5% by mass
Ethanol 10% by mass
Xylitol 0.5% by mass
Kumazasa extract (in terms of solid content) 0.001% by mass
Appropriate amount of citric acid Paraben 0.1% by mass
Disodium edetate 0.01% by mass
Menthol 0.01% by mass
Fragrance 0.02% by mass
Water balance
100% by mass in total

(Pharmaceutical Example 3: Toothpaste composition)
Tocopherol acetate 0.08% by mass
Allantoin 0.05% by mass
Cetylpyridinium chloride hydrate 0.04% by mass
Dipotassium glycyrrhizinate 0.2% by mass
Liquid paraffin 12% by mass
Sorbitan monostearate 1% by mass
Polysorbate 60 2% by mass
Sodium hyaluronate 0.001% by mass
Kumazasa extract (in terms of solid content) 0.00001% by mass
Dextrin palmitate 0.3% by mass
Carboxyvinyl polymer 1.1% by mass
Cetanol 5% by mass
Sodium lauryl sulfate 2% by mass
1,3-butylene glycol 5% by mass
Arginine Appropriate amount 2 sodium edetate 0.02% by mass
Paraben 0.05% by mass
Fragrance 0.2% by mass
Water balance
100% by mass in total

(Pharmaceutical Example 4: Toothpaste composition)
Macrogol 400 1% by mass
Benzalkonium chloride 0.01% by mass
Sodium lauryl sulfate 2% by mass
Calcium pyrophosphate 40% by mass
Concentrated glycerin 15% by mass
Mallow extract (in terms of solid content) 0.001% by mass
Sodium alginate 0.2% by mass
Carrageenan 1% by mass
Citric acid Appropriate amount Phenoxyethanol 0.3% by mass
Fragrance 0.02% by mass
Water balance
100% by mass in total

Claims (6)

(A) A composition for promoting periodontal tissue regeneration and / or promoting restoration, which comprises at least one selected from the group consisting of mallow extract and Kumazasa extract. (A) A composition for promoting gingival cell activation and / or repair, which comprises at least one selected from the group consisting of mallow extract and Kumazasa extract. (A) A composition for preventing and / or treating alveolar pyorrhea, which comprises at least one selected from the group consisting of mallow extract and Kumazasa extract. (A) An anti-inflammatory composition in the oral cavity containing at least one selected from the group consisting of mallow extract and Kumazasa extract. (A) A composition for improving a barrier function in the oral cavity, which comprises at least one selected from the group consisting of a mallow extract and a bamboo strip extract. (A) A composition for promoting antibacterial activity in the oral cavity, which comprises at least one selected from the group consisting of mallow extract and Kumazasa extract.