JP2020002019A - Oral composition - Google Patents

Abstract

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

Description

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

  Periodontal disease (also called periodontal lesion) refers to a state in which the healthy state of periodontal tissue is impaired, including diseases such as alveolar pyorrhea and gingivitis. Periodontal tissue consists of gum (gum) and alveolar bone (bone tissue supporting the teeth), cementum covering the root (root of the tooth), periodontal ligament connecting the root and alveolar bone, etc. It has a strong structure for However, if bacteria settle between teeth and gums and plaque (dental plaque) accumulates, a healthy state is impaired, and QOL such as wobble of teeth and bad breath occurs. The risk of periodontal disease increases due to deterioration of the oral environment such as decrease in saliva due to aging and diseases such as lifestyle, aging and 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 prevalence of 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.

  For periodontal disease, advanced alveolar pyorrhea has been surgically treated to remove dental plaque, tartar, etc. from the lesion to improve it. On the other hand, chemical approaches have also been used in combination with surgical procedures or alone to improve alveolar pyorrhea. Although alveolar pyorrhea progresses to the inside of the gums, the chemical approach has the advantage over surgical procedures in that it can be effective from the tooth to gum gap to the back. Among such chemical approaches, means for suppressing or reducing bacteria causing inflammation with an antibacterial agent or a bactericide using a naturally-derived component (Patent Document 1), a substance for promoting regeneration of periodontal tissue Has been reported so far, for example, to act on a lesion to promote regeneration (Patent Document 2).

JP 2016-113460 A JP 2017-12188 A

  However, continuous administration of fungicides and antibacterials can create resistant bacteria, especially by using a single agent. In addition, these agents themselves cannot repair periodontal tissue. On the other hand, regeneration promoters such as enamel protein-derived peptides are naturally-derived, but because they use genetic recombination technology in the agents themselves and in the manufacturing process, production and quality control to ensure safety are complicated, Because of the high cost, it was not a component that could be widely applied to oral compositions.

  Therefore, the present invention is to improve the self-healing ability of a living body by using a safe ingredient which has been used for a long time in administration and ingestion to humans, thereby improving periodontal damage caused by gingivitis and alveolar pyorrhea. It is intended to provide a composition for repairing and regenerating tissue.

  The present inventors have found that in oral tissues such as periodontal tissue, hyaluronic acid, salts of hyaluronic acid, kumazasa extract, and mallow extract, promote regeneration and repair of periodontal tissue, activation and repair of gingival cells Of the present invention have been newly found to have excellent effects on promotion of anti-inflammatory activity, prevention and treatment of alveolar purulence, suppression of inflammation, improvement of the barrier function of gingival cells, and promotion of antibacterial activity.

That is, the present invention provides the following.
Item 1.
(A) A composition for promoting periodontal tissue regeneration and / or repair, comprising at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, kumazasa extract, and mallow extract object.
Item 2.
(A) A composition for promoting gingival cell activation and / or repair, comprising at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salts, kumazasa extract, and mallow extract object.
Item 3.
(A) A composition for preventing and / or treating alveolar pyorrhea, characterized by containing at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, kumazasa extract and mallow extract. .
Item 4.
(A) An anti-inflammatory composition in the oral cavity 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, characterized by containing at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, a kumazasa extract, and a mallow extract.
Item 6.
(A) A composition for promoting antibacterial activity in the oral cavity, characterized by containing at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, kumazasa extract and mallow extract.
Item 7.
Item 7. 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, the inflammation is suppressed by containing at least one or more selected from the group consisting of (A) hyaluronic acid, a salt of hyaluronic acid, kumazasa extract, and mallow extract. Can enhance the self-healing function originally possessed. In addition, periodontal tissue damaged by gingivitis, alveolar pyorrhea, and the like can be effectively repaired and regenerated.

[Composition]
A composition for promoting periodontal tissue regeneration and / or repair, a composition for promoting gingival cells and / or promoting repair, a composition for preventing and / or treating alveolar pyorrhea, and a 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,
(A) It contains at least one or more selected from the group consisting of hyaluronic acid, hyaluronic acid salts, Kumazasa extract, and mallow extract.

[(A) component]
Among the components (A), known substances can be used as hyaluronic acid, and examples thereof include hyaluronic acid, derivatives thereof, 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 constituent units. Hyaluronic acid can be extracted and collected from animal tissues such as cockscomb, shark skin, umbilical cord, eyeballs, skin, and cartilage, hyaluronic acid-producing microorganisms such as Streptococcus microorganisms, animal cells or plant cells. . Also, commercially available products can be purchased.

  The viscosity average molecular weight of hyaluronic acid is not particularly limited as long as the effects of the present invention are exhibited, but is, for example, 0.1 to 5,000,000 in terms of viscosity average molecular weight. Here, the viscosity average molecular weight can be determined, for example, by a known measurement method such as a method described in General Test Method, Viscosity Measurement Method, First Method: Capillary Viscometer Method of the 17th Revised Japanese Pharmacopoeia.

  The derivative of hyaluronic acid is not particularly limited as long as it is pharmacologically or physiologically acceptable.For example, acetylated hyaluronic acid in which hydroxyl groups are acetylated, sulfated hyaluronic acid in which hydroxyl groups are sulfated, cationization Cationized hyaluronic acid, hydrolyzed 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, acetylated hyaluronic acid, cationized hyaluronic acid, hydrolyzed hyaluronic acid, hyaluronic acid crosspolymer and / or propylene glycol hyaluronic acid are preferably 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 thereof include salts with metals. Preferably, a sodium salt or a potassium salt is used as a salt of hyaluronic acid or a derivative thereof. Specific salts of hyaluronic acid or a derivative thereof include, for example, sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, ammonium hyaluronate, monoethanolamine hyaluronate, and acetylated sodium hyaluronate. Acetylated potassium hyaluronate, acetylated calcium hyaluronate, acetylated magnesium hyaluronate, acetylated zinc hyaluronate, acetylated ammonium hyaluronate, sodium hyaluronate crosspolymer, and hydroxypropyltrimonium hyaluronate. Preferably, a sodium salt or a potassium salt is used as a salt of hyaluronic acid or a derivative thereof, and more preferably, a sodium salt is used.

  Among the components (A), Kumazasa extract is an extract obtained from Kumazasa (Sasa veitchii or Sasa veitchii (Carr.) REHD. (Gramineae)). Kumazasa is a plant belonging to the Poaceae family, and can be used as it grows naturally in the mountains of Japan. As the extraction solvent, a polar solvent can be used. 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 A polyhydric alcohol having 2 to 5 carbon atoms such as propylene glycol, dipropylene glycol, glycerin, diglycerin, and ethylene glycol; 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 can be appropriately selected depending on the purpose. Examples thereof include leaves, flowers, underground portions, bark, branches, above-ground portions, and mixtures thereof. Among them, leaves are preferable.

  A commercial product can also be used for Kumazasa extract. Examples of commercially available products of Kumazasa extract include Kumazasa extract (manufactured by Maruzen Pharmaceutical Co., Ltd.) or Falco Rex Kumazasa E (manufactured by Ichimaru Falcos).

  Among the components (A), the mallow extract is an extract obtained from the mallow family Malvaceae (Malva sylvestris Linne (Malvaceae)) as a raw material. Usbania mallow is a perennial plant native to Europe and a plant that grows in the wild, but is also cultivated for use as herbs and crude drugs. As the extraction solvent, a polar solvent can be used. Examples of the polar solvent include 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. A 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 Mixtures are mentioned, and among these, a lower alcohol, a polyhydric alcohol, purified water, or a mixture of two or more selected from these solvents is preferable, and ethanol, 1,3-butylene glycol is more preferable. , 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 can be appropriately selected depending on the intended purpose.Examples include leaves, flowers, stems, roots, aboveground parts, underground parts, and mixtures thereof, and are preferably Flowers and leaves.

  As the mallow extract, a commercially available product can be used. Examples of commercial products of the mallow extract include, for example, trade names: Usbenioi extract LA, usbenioi extract BG, mallow moisture (both manufactured by Maruzen Pharmaceutical Co., Ltd.), and trade names: Falcolex Xeniaoi B (manufactured by Ichimaru Falcos). No.

  In the present invention, when an extract is obtained from Kumazasa or Usbania oil, the extraction method is not particularly limited, but all or a part of dried matter of Usbania oil or Kumazasa, or powder obtained by crushing and pulverizing the dried material From the solvent. The extract of Kumazasa or Usuaniaoi may be used as it is, or may be used after dilution or concentration. In order to obtain an extract of Kumazasa or Usvenia oy, it is also possible to use Kumazasa or Usvenia oy which has been preserved by freeze-drying.

  In the present invention, the total content of the component (A) is not particularly limited, but is preferably 0.000001 to 5% by mass based on the total amount of the composition, from the viewpoint of remarkably exerting the effects of the present invention. Preferably, it is 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 content is a solid content conversion amount.

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

  In the present invention, of the component (A), the content of the Kumazasa extract alone is, for example, from 0.000001 to solid content, based on the total amount of the composition, from the viewpoint of remarkably exerting the effects of the present invention. The amount is preferably 1% by mass, more preferably 0.000003 to 0.5% by mass, still more preferably 0.000005 to 0.3% by mass, and 0.00001 to 0.2% by mass. Is still more preferable, the content is particularly 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 mallow extract alone as 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 remarkably exhibiting the effects of the present invention. %, More preferably 0.000003 to 0.5% by mass, even more preferably 0.000005 to 0.3% by mass, and more preferably 0.000005 to 0.2% by mass. More preferably, it is particularly 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, from the viewpoint of excellent periodontal tissue regeneration ability, the component (A) is preferably at least hyaluronic acid or its salt or Kumazasa extract, and more preferably hyaluronic acid or its salt.

[Use]
As used herein, periodontal disease or periodontal lesion refers to a state in which the healthy state of the periodontal tissue consisting of gums (so-called gums), cementum, periodontal ligament and alveolar bone has been impaired, and bacterial infection has occurred. Can be caused by:

  Among oral bacteria, three species of Porphyromonas gingivalis, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (Tannellaella forsythia) are also known as red complex, which is also known as a causative agent of periodontal disease, and is known as a periodontal disease. I have. In addition, Aggregatibacter actinomycetemcomitans and Prevotella intermedia are also known as causative bacteria of periodontal disease. In recent studies, it is known that various bacteria are also involved in complex and are involved in the progression of periodontal disease. In periodontal disease, the growth of these causative bacteria may give rise to symptoms such as giving off a characteristic bad breath, and the mouth becoming numb when waking up.

  Dental plaque releases toxins such as lipopolysaccharide (LPS) derived from oral bacteria, proteolytic enzymes (proteases), and collagenases (collagenase). Proteases and collagenases damage the gums, and LPS acts on gum cells to secrete inflammatory cytokines. These inflammatory cytokines cause inflammation of the gums and damage the gums and periodontal ligament. This leads to bleeding, swelling of the gums, and the phenomenon of the gums going down and the teeth appearing longer. In addition, inflammatory cytokines excessively activate immune cells in the body, resulting in release of RANKL, which stimulates osteoclasts, from the immune cells. As a result, the alveolar bone that supports the teeth melts, and the teeth are shaken (wobble), and the teeth eventually come off. When inflammation and excessive activation of immune cells occur, they cause tissue damage and destruction and further inflammation, resulting in a synergistic deterioration that can be said to be a negative chain of periodontal tissue destruction.

  Periodontal disease is roughly classified into two types, gingivitis (gingivitis) and alveolar pyorrhea (periodontitis), depending on the progress of the condition.

  Gingivitis (gingivitis) refers to a condition in which the cementum, periodontal ligament and alveolar bone are not destroyed but the gums are damaged. Symptoms of gingivitis (gingivitis) include, for example, redness of the gums (the gums appear red, red-black, dark, or blackened), swelling (feeling the gums are rounded and swollen), and edema (the gums are not tight) , Bleeding, bleeding (bleeding from the gums due to brushing, etc.), pain, feeling that the gums are loose, pressing on the gingiva, white pus appears, hypersensitivity (temperature change or physical Feeling of teeth tingling or tooth ache due to natural stimulation).

  Alveolar pyorrhea refers to a condition in which inflammation that has initially started on the gums is damaged and destroyed by spreading to deep periodontal tissues such as cementum, periodontal ligament, and alveolar bone. As the symptoms of alveolar pyorrhea, in addition to the symptoms caused by the above-mentioned periodontal disease bacteria and the symptoms of gingivitis (gingivitis), for example, the gums fall, the gums become thinner, gaps are formed between the teeth, Teeth appear to be elongated, teeth are likely to be caught in the gaps between teeth, the feeling of floating teeth, tooth sway, tooth wobble, and the like.

  In healthy gums 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 teeth with the alveolar bone, which supports the teeth. The gums are originally pale pink in color, firm, powerful, and have a plump appearance, and hardly bleed even after cleaning with a tooth brush or an interdental brush.

  The composition for promoting periodontal tissue regeneration or repair of the present invention can regenerate or repair periodontal tissue that has been destroyed due to periodontal disease or the like. In the present specification, “promotion” of regeneration or restoration directly enhances the intrinsic regeneration or restoration ability of periodontal tissue, and also enhances deep teeth by improving damage and inflammation of shallow periodontal tissue. Includes enhancing the ability of peripheral tissue to regenerate or repair. The promotion of periodontal tissue regeneration or restoration may include, for example, regenerating, repairing, repairing, reviving, reviving, restoring, regenerating, renewing, and promoting periodontal tissue (eg, gums and roots of teeth). It can also be described as recovering or healing towards the condition. In addition, an expression representing an improvement in the state of the periodontal tissue, such as “gum care”, can also be used. By promoting regeneration or repair of periodontal tissue, the above-mentioned symptoms of gingivitis and alveolar pyorrhea can be prevented, treated, or ameliorated.

  The periodontal tissue which is a target of the composition for promoting periodontal tissue regeneration or repair of the present invention is, for example, periodontal ligament, gum, gingival epithelium (surface of gum or mucous membrane), or alveolar bone, preferably periodontal ligament , Gums, or gingival epithelium (the surface of the gums or mucous membrane), and more preferably the periodontal ligament.

  The cells of the periodontal tissue to be targeted by the composition for promoting periodontal tissue regeneration or repair of the present invention are, for example, cells forming the gingiva or periodontal ligament, preferably gingival epithelial cells, gingival fibroblasts, or Periodontal ligament fibroblasts, more preferably periodontal ligament fibroblasts.

  Periodontal ligament fibroblasts are morphologically similar to gingival fibroblasts, and are considered to be cells responsible for maintaining periodontal ligament tissue.From the cell population of pluripotent cells and cells with different functions, It is configured. Therefore, it is regarded as an important cell for maintenance and regeneration of periodontal tissue.

  The gingival cell activating composition of the present invention activates cells forming periodontal tissue. Here, “activation” of a cell refers to improving the state of the cell by, for example, increasing the expression level of the gene or the cell growth ability. To represent `` activating '' a cell, for example, `` revive a weakened cell '', `` activate a cell '', `` energize a cell '', `` energize a cell '', or `` Expressions such as "revitalize", "revive", "revive", "revive", "reborn", and "make healthy" can be used. By activating gingival cells, the above-mentioned symptoms of gingivitis and alveolar pyorrhea can be prevented or ameliorated.

  The periodontal tissue targeted by the composition for gingival cell activation of the present invention is, for example, periodontal ligament, gum, gingival epithelium (surface of gum or mucous membrane), or alveolar bone, preferably periodontal ligament, gum, Or gingival epithelium (the surface of the gum or mucous membrane), and more preferably the periodontal ligament.

  The cells of the periodontal tissue to be targeted by the composition for gingival cell activation of the present invention are, for example, cells forming the gingiva or periodontal ligament, preferably oral keratinocytes, gingival fibroblasts, or periodontal ligament fibroblasts Cells, more preferably periodontal ligament fibroblasts.

  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 gingivitis and alveolar pyorrhea. Further, it can more preferably be used for preventing or improving the symptoms of alveolar pyorrhea. For example, the composition for preventing alveolar pyorrhea of the present invention can be applied to healthy gums. In order to express the prevention of gingivitis and alveolar pyorrhea, an expression added with a phrase indicating prevention of the above-mentioned gingivitis, alveolar pyorrhea and various symptoms caused by periodontal disease-causing bacteria (for example, , Prevent gum bleeding, prevent bad breath and stuffiness in the mouth, prevent gum swelling and bleeding, etc.); healthy gums, firm gums, keep gums pink, keep gums firm Expressions that describe changes to healthy gums, such as strong gums, plump gums, etc .; can be used to prevent teeth from squeezing (e.g., with cold ones), clean / fresh 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 symptoms, an expression of improving a specific part of periodontal tissue, such as “gum care”, may be used.

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

  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 cells forming periodontal tissue are stimulated by LPS or the like. . In addition, the 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 gingivitis and alveolar pyorrhea, particularly the symptoms of gingivitis, can be prevented or improved.

  Periodontal tissue targeted by the anti-inflammatory composition in the oral cavity of the present invention is, for example, periodontal ligament, gum, gingival epithelium, or alveolar bone, preferably periodontal ligament, gum, or gingival epithelium, and more preferably. Is the gingival epithelium.

  The cells of the periodontal tissue which is the target of the anti-inflammatory composition in the oral cavity of the present invention are, for example, cells forming the gingiva or periodontal ligament, preferably oral keratinocytes, gingival fibroblasts, or periodontal ligament fibroblasts Cells, and more preferably oral keratinocytes.

  The composition for improving the barrier function in the oral cavity of the present invention improves, enhances, or promotes the “barrier function” of cells forming periodontal tissue. Here, the “barrier function” refers to a function of the vicinity of the surface of a living tissue, which prevents a foreign substance from entering the inside of the tissue. For example, the barrier function of cells forming periodontal tissue can be improved by promoting expression of a gene relating to tight junction construction such as Claudin-1 and increasing the amount of the protein. 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 gum, improving or protecting the gum surface, and strengthening the gum or gum surface, etc. Can be used. By improving the barrier function, toxins such as LPS and proteolytic enzymes can enter the periodontal tissue, and from the periodontal tissue, the important nutrients and bioactive substances that are important for maintaining the healthy state of the tissue. Outflow is prevented and further damage to the periodontal tissue can be prevented. Further, the natural healing power of periodontal tissue can be improved. As a result, the above-mentioned symptoms of gingivitis and alveolar pyorrhea, particularly the symptoms of gingivitis, can be prevented or improved.

  The periodontal tissue which is the target of the composition for improving the barrier function in the oral cavity of the present invention is, for example, an epithelial tissue in the mouth, and preferably a gingival epithelium.

The cells of the periodontal tissue which 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 the antibacterial activity against foreign bacteria, fungi (molds), and the like inherent in cells forming periodontal tissue. For example, it promotes the expression of the gene for β-defensin-1, which is an antibacterial substance and a kind of protein secreted from cells, and promotes the production of β-defensin-1. In order to express the promotion of such antibacterial activity, for example, it enhances the defense function of the gums, enhances the defense power inherent in the living body, enhances the immunity, and causes periodontal disease including the bacteria exemplified above. Expressions such as suppressing, reducing, or suppressing proliferation can be used. By promoting the antibacterial activity, it is possible to prevent or ameliorate the above-mentioned symptoms caused by bacteria causing periodontal disease, symptoms of gingivitis, and symptoms of alveolar pyorrhea, particularly symptoms caused by bacteria causing periodontal disease.

  In addition, 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 kills the action of bacteria or the like, from the viewpoint of suppressing the amount of an antibacterial agent or a bactericide and suppressing the emergence of resistant bacteria. Agent can be used in combination.

  The periodontal tissue which is a target of the composition for promoting antibacterial activity in the oral cavity of the present invention is, for example, an epithelial tissue in the mouth, and preferably gingival epithelium.

  The cells of the periodontal tissue to which the composition for promoting antibacterial activity in the oral cavity of the present invention is, for example, oral keratinocytes.

  The composition of the present invention increases the expression of HAS1 and HAS3, which are hyaluronic acid synthesis genes, and increases the production of hyaluronic acid in oral tissues. 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 moisture retention of oral tissues, and a composition for enhancing the moisture retention of oral tissues. Such promotion of hyaluronic acid production in the oral cavity, enhancement of the water retention of the oral tissue, and enhancement of the moisturizing power of the oral tissue are accompanied by an increase in the water content of the oral tissue, such as making the gums fresh and plump. Can also be expressed as a change. The periodontal tissue targeted by these compositions is, for example, epithelial tissue in the mouth, preferably gingival epithelium. The cells of the periodontal tissue to be subjected to these compositions are, for example, periodontal ligament fibroblasts, gingival fibroblasts, or oral keratinocytes, and preferably oral keratinocytes.

  The composition for periodontal tissue regeneration and / or repair promotion of the present invention, the composition for gingival cell activation and / or repair promotion, and the composition for prevention and / or treatment of alveolar pyorrhea, and for anti-inflammatory in the oral cavity The composition, the composition for improving the barrier function, and the composition for promoting the antibacterial activity have an effect of improving directly or indirectly in any classification (stage) of gingivitis (gingivitis) and alveolar pyorrhea.

  As used herein, “prevention” refers to preventing or delaying the onset of a disease or condition, or reducing the risk of developing a disease or condition.

  As used herein, the term “improvement” refers to improvement or alleviation of a disease, symptom or health condition, prevention or delay of a disease, symptom, or deterioration of health condition, or reversal, prevention, or delay of progression of a disease or condition.

As used herein, "treatment" refers to improving or alleviating a disease, symptom or health condition, or preventing or delaying a disease, symptom or health condition, or reversing or preventing the progress of a disease or condition. Or to act to delay.
[Application site]
It is known that periodontal disease can occur on some or all of the teeth in the oral cavity, but the compositions of the present invention can be used either locally or entirely 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 from the viewpoint that those who have or may have alveolar pyorrhea increase with aging, preferably adults, more preferably 30 years or older, more preferably middle-aged (45 or older) to older (55 or older).

  Since the composition of the present invention has a high safety of the components, diabetes, cardiovascular disease, cerebral infarction, or a state prior to these diseases in which the use of the drug is restricted by administration or ingestion of another drug, Alternatively, it is suitably used for a person having osteoporosis. Above all, it is clear that diabetes is associated with alveolar pyorrhea, and osteoporosis is associated with alveolar pyorrhea because some of the pharmaceutical ingredients for alveolar pyorrhea are contraindicated. Those having are preferred subjects of the compositions 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 the other components, the formulation, the method of use, and the like, and may be within a physiologically or pharmaceutically acceptable range. The pH is not particularly limited, but is preferably pH 3 to 9, more preferably 4 to 8.5, and still more preferably 4.5 to 7.5 from the viewpoint of improving the feeling of use. From the viewpoint of reducing the risk of acid corrosion), the pH is preferably adjusted to 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 a form known as pharmaceuticals, quasi-drugs, and cosmetics. For example, a liquid preparation, a foam (foam) preparation, a cream preparation, a paste preparation, a spray preparation, a pasta preparation , Gels, films, tablets (troches and the like), and the like. From the viewpoint of allowing a small amount of the composition to stay for a long time and acting on periodontal tissues and bacteria causing periodontal disease, liquid preparations and foams are preferred. , 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 pharmaceuticals, quasi-drugs, cosmetics, or foods. For example, mouthwashes, mouthwashes such as mouthwashes, dentifrices ( Toothpaste, liquid toothpaste, foamed toothpaste, toothpaste, etc.), serum applied to the gums, troches, lozenges, candies, chewing gums, etc., but the germs that cause gaps in periodontal tissues in the mouth and periodontal disease From the viewpoint of acting on lipsticks, preferred are mouthwashes, mouthwashes, or dentifrices, and more preferred are mouthwashes, mouthwashes, liquid dentifrices, and foamed dentifrices.

  The composition of the present invention can be used in combination with an antibacterial or bactericidal component 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, sanguinarine, delmopinol, lauroyl sarcosine sodium (LSS), alkyldiaminoethylglycine, triclosan, isopropylmethylphenol, hinokitiol, thymol , Catechin, lactoferrin, lactoperoxidase, dextranase, lysozyme, protease, Manuka honey extract, nisin, chitosan 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 anti-inflammatory agents, as long as the effects of the present invention are not impaired.

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

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

  In the composition of the present invention, a fluorine compound such as sodium fluoride, sodium monofluorophosphate (MFP), tin fluoride, or the like as a remineralizing agent or a remineralization promoting substance is provided 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.

  In the composition of the present invention, chlorophyll, sodium polyphosphate, oak extract, tocopherol acetate (vitamin E), sodium pyrophosphate, polyethylene glycol, zinc chloride, as other medicinal ingredients, 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 may be a humectant such as glycerin, polyethylene glycol, 1,3-butylene glycol, or dipropylene glycol; a sweetener such as saccharin sodium or sucralose; or a cooling agent such as menthol, as long as the effects of the present invention are not impaired. Fragrances such as anethole; nonionic surfactants such as glycerin fatty acid ester and polyoxyethylene hydrogenated castor oil; anionic surfactants such as sodium lauryl sulfate; pH adjusting agents other than the above components; And components conventionally used in oral compositions, such as anti-inflammatory agents, preservatives, coloring agents, abrasives, vitamins, and solvents (such as ethanol).

  The composition of the present invention is divided into once to several times a day, usually taken or administered at 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day or at any time and interval. 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.

  In the test examples herein, sodium hyaluronate, Kumazasa extract, and mallow extract, the concentrations of each component are all expressed by a value obtained by dividing the mass of the component in terms of solid content by the solution volume. The operation and measurement method using a commercially available kit followed the manual attached to the kit unless otherwise specified.

[Cells / medium]
Human oral keratinocytes (epithelial cells) used were Human Oral Keratinocyte: HOK (Kurabo Co., Ltd., Lot No. 12885). Unless otherwise specified, human oral keratinocytes were cultured using Oral keratinocyte medium (Sciencecell, No. 2611) at 37 ° C. in an environment of 5% carbon dioxide and 95% air.

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

[Test Example 1. Anti-inflammatory effects on inflammation of oral keratinocytes (gene expression analysis)]
Human oral keratinocytes (epithelial cells) were seeded on a 24 well plate (Cell Bind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, the medium was replaced with a medium in which each component shown in Table 1 was dissolved at each concentration, and cultured.
On the next day, Escherichia coli-derived lipopolysaccharide (Lipopolysaccharides from Escherichia coli: LPS, manufactured by Sigma) and the components shown in Table 1 were exchanged with a medium in which each component was dissolved at each concentration, and the cells were further cultured for 6 hours. In addition, a group treated with a medium to which LPS and each component were not added was also provided in order to calculate the amount of background gene expression. After culturing, the plate is washed twice with PBS (-), RNA is extracted using RNeasy (registered trademark) Mini Kit (manufactured by Qiagen), and then TOYOBO Reverse TraAce qPCR RT Master Mix with gDNA Remover (manufactured by TOYOBO) Was used to produce cDNA. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq. The Taqman Probe used was GAPDH (Hs0275891_g1), IL-8 (Hs00174103_m1), and IL-1A (Hs00174092_m1) purchased from Applied Biosystems.

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 Based on the difference between the gene expression levels of IL-1α and IL-8 in the group treated with (Comparative Example 1-1), the gene expression levels of IL-1α and IL-8 in each Example and LPS From the difference between the gene expression level of each of IL-1α and IL-8 in the group treated with the medium to which each component was not added (Comparative Example 1-1), IL-1α and IL-8 when each component was added. Each expression reduction rate was calculated. Table 1 shows the results. Here, the expression reduction rate is calculated as follows.
<Expression reduction rate (%)>
= (1-((gene expression amount in each example-gene expression amount in comparative example 1-1) / (gene expression amount in comparative example 1-2-gene expression amount in comparative example 1-1))) * 100

  From these results, it was found that stimulating oral keratinocytes with LPS, which is a bacterial toxin, promotes the expression of inflammatory cytokines IL-1α and IL-8 (Comparative Example 1-2). It was confirmed that the expression was reduced by adding the extract of Kumazasa and the mallow extract (Example 1-1 to Example 1-6).

[Test Example 2. Anti-inflammatory effect on inflammation of oral keratinocytes (expression analysis at protein level)]
Human oral keratinocytes were seeded on a 96-well plate (manufactured by Cell Bind, Corning) at a cell number of 5600 cells / well. After culturing for 24 hours, the medium was replaced with a medium in which each component shown in Table 2 was dissolved at each concentration, and cultured.
On the next day, 100 μg of LPS and a medium in which each component shown in Table 2 was dissolved at each concentration were exchanged, and the cells were further cultured for one day. After the culture, the 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). The culture plate from which the supernatant was removed was washed twice with PBS, and Hoechst 33342 was diluted 1000-fold in the medium and replaced with the medium in the well. After culturing for 10 minutes, images were taken with Image Xpress ((Molecular Devices)) (16 visual fields / well), analyzed using a dedicated cell counting program (MetaXpress) of the instrument, and the number of cells was measured.Each group obtained by ELISA Of IL-1α was divided by the value of the number of cells obtained by Hoechst staining to determine the amount of IL-1α protein expressed per cell number, and treated only with medium without LPS or components. In this case (Comparative Example 2-1), the expression level of IL-1α protein per cell was set to 1, and the relative protein expression level when LPS and each component were added was calculated.

Based on the difference between the expression levels of IL-1α (Comparative Example 2-2) in the control to which LPS (100 μg / mL) was added and only the medium without LPS or each component (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 amount in each example-protein expression amount in comparative example 2-1) / (protein expression amount in comparative example 2-2-protein expression amount in comparative example 2-1))) x 100

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

[Test Example 3. Improvement of antibacterial function of oral keratinocytes (gene expression analysis)]
Human oral keratinocytes were seeded on a 24 well plate (Cell Bind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, the medium was replaced with a medium in which each component shown in Table 3 was dissolved at each concentration, and culturing was performed for 6 hours. After culturing, the cells were washed twice with PBS (−), and RNA was extracted using RNeasy Mini Kit (manufactured by Qiagen), and then TOYOBO Reverse TraAce qPCR RT Master Mix with gDNA Remover (manufactured by TOYOBO using TOYOBO) Produced. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq (manufactured by Takara Bio Inc.). In addition, GAPDH (Hs0275891_g1) and Defensin-1 (Hs00608345_m1) purchased from Applied Biosystems were used for Taqman Probe.

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

  From these results, by adding sodium hyaluronate, Kumazasa extract, or mallow extract, the expression of β-Defensin-1 known as a cell-derived antibacterial factor is enhanced, and sodium hyaluronate is particularly remarkable. (Examples 3-1 to 3-6).

[Test Example 4. Improvement effect of barrier function of oral keratinocytes (gene expression analysis)]
Human oral keratinocytes were seeded on a 24 well plate (Cell Bind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, each medium shown in Table 4 was replaced with a medium in which each component was dissolved at each concentration, and culturing was performed for 6 hours. After culturing, the cells were washed twice with PBS (−), and RNA was extracted using RNeasy Mini Kit (manufactured by Qiagen), and then TOYOBO Reverse TraAce qPCR RT Master Mix with gDNA Remover (manufactured by TOYOBO using TOYOBO) Produced. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq (manufactured by Takara Bio Inc.). In addition, GAPDH (Hs0275891_g1) and Claudin-1 (Hs00221623_m1) purchased from Applied Biosystem were used for Taqman Probe.

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

  From these results, it can be seen that the addition of sodium hyaluronate, Kumazasa extract or mallow extract enhances the expression of Claudin-1, which is known as a core protein of tight junction construction that contributes to the barrier function. (Example 4-1 to Example 4-5).

[Test Example 5 Effect of improving barrier function of oral keratinocytes (electrical resistance value)]
Human oral keratinocytes were seeded at 96,000 cells / well on an insert of a 12-well plate (12 mm Transwell (registered trademark) with 0.4 μm Pore Polyester Membrane Insert, Sterile, Corning). After culturing for 3 days, the medium was replaced with a differentiation-inducing medium (Oral Keratinocyte medium supplemented with 2 mM Ca ²⁺ ) in which TNFα and sodium hyaluronate were dissolved at the concentrations shown in Table 5, and cultured for 5 days. Thereafter, the electric resistance value (TER value) of the insert was measured using a Millicell (registered trademark) ERS-2 Voltohmmeter (manufactured by Millipore).

From the measurement results, based on the difference between the TER value in the differentiation-inducing medium alone (control) and the TER value in the case where only TNF-α was added (Comparative Example 5-1), the TER value in the example and the TER value in Comparative Example 5- The barrier function improvement rate when sodium hyaluronate was added was calculated from the difference in TER value in Table 1 (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)) x 100

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

[Test Example 6: Cell Proliferation Effect of Periodontal Ligament Fibroblasts (Intracellular Enzyme Measurement)]
Human periodontal ligament fibroblasts were seeded on a 96-well plate (Cell Bind, Corning) at a cell count of 3000 cells / well. After culturing for 6 hours, the concentration was changed overnight from 10% to 0.2% of fetal bovine serum (FBS) (MP Biomedicals, Lot No. A15035). Twenty-four hours after cell seeding, the medium was replaced with a 0.2% FBS-containing medium in which sodium hyaluronate, Kumazasa extract, and mallow extract were dissolved at the concentrations shown in Table 6, and cultured for 48 to 72 hours. After the culture, the cells were washed once with a serum-free medium, and the number of cells was measured using Cell Counting Kit-8 (CCK-8, Dojindo).

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

  In regeneration or repair of periodontal tissue, proliferation and migration of periodontal ligament fibroblasts are important. From the results shown in Table 6, it was confirmed that when sodium hyaluronate or Kumazasa extract was added to periodontal ligament fibroblasts, the cell proliferation and the enzymatic activity indicating the degree of cell activation increased (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 (Cell Bind, manufactured by Corning) at a cell number of 32000 cells / well. After culturing for 24 hours, the medium was replaced with a medium in which the components shown in Tables 7-a and 7b were dissolved at the respective concentrations, and culturing was performed 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 Reverse TraAce qPCR RT Master Mix with gDNA Remover (manufactured by TOYOBO using TOYOBO) was used. Produced. The prepared cDNA was analyzed by qRT-PCR using Premix Ex Taq (manufactured by Takara Bio Inc.). In addition, GAPDH (Hs0275891_g1), HAS1 (Hs00758053_m1), and HAS3 (Hs00193435_m1) purchased from Applied Biosystem were used for Taqman Probe.

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

  HAS1 is a gene that is known to contribute to the promotion of the production of high molecular weight hyaluronic acid, and HAS3 is a gene that is known to contribute to the promotion of the production of low molecular weight hyaluronic acid. 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 HAS1 and HAS3, which are hyaluronic acid production promoting factors. (Example 7-1 to Example 7-6, Example 8-1 to Example 8-5). In addition, it has been clarified that sodium hyaluronate has a remarkable effect of enhancing the expression of these genes.

  Hyaluronic acid is known to be contained in the matrix that fills the space between collagen and elastin in the dermis, as well as in the epidermis. It can hold a large amount of water and supports the structure of collagen and elastin, which plays an important role in gingival firmness, elasticity and moisturizing. 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 an anti-inflammatory effect and a tissue repair effect (Shin Goto, Inflammation, Vol.15, No.2, 1995).

  From the above results, sodium hyaluronate, Kumazasa extract, and mallow extract increase the expression of HAS1 and HAS3, thereby increasing the amount of hyaluronic acid in periodontal tissue, promoting the restoration of periodontal tissue, and providing an anti-inflammatory effect. In addition, it has the effect of giving the gums firmness and elasticity, and making the gums full and healthy.

  The epithelium in the mouth is a mucosal tissue, and has a different degree of keratinization and accessory organs from normal skin. Furthermore, recently, gene expression levels have been compared between oral epithelial cells and skin epithelial cells, and it has been reported that there was a difference in the expression of 10,000 or more genes (Anna Turabelidze et al., PLOS ONE, September 2014, Vol. 9, Issue 9, e101480). Although the mechanism is not clear, in such a gene expression profile of cells of the oral tissue different from the skin, sodium hyaluronate, Kumazasa extract, and mallow extract were tested on cells of the oral tissue. It is presumed that the specific effect confirmed in 7 was achieved.

  Composition for promoting periodontal tissue regeneration and / or repair, composition for promoting gingival cells and / or promoting repair, composition for preventing and / or treating alveolar pyorrhea, anti-inflammatory composition in the oral cavity, oral cavity of the present invention Examples of the formulation of the composition for improving the barrier function in Example 1 and the composition for promoting the antibacterial activity in the oral cavity are shown below.

(Formulation 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 hydrogenated castor oil 1% by mass
Sodium hyaluronate 0.001% by mass
Propylene glycol 10% by mass
Citric acid qs phenoxyethanol 0.2% by mass
Disodium edetate 0.01% by mass
Spice 0.1% by mass
Water balance 100% by mass

(Formulation Example 2: Mouthwash)
Benzethonium chloride 0.01% by mass
Polyoxyethylene hydrogenated castor oil 2% by mass
5% by mass of concentrated glycerin
Ethanol 10% by mass
Xylitol 0.5% by mass
Kumazasa extract (as solid content) 0.001% by mass
Citric acid appropriate amount 0.1% by mass of paraben
Disodium edetate 0.01% by mass
Menthol 0.01% by mass
Perfume 0.02% by mass
Water balance 100% by mass

(Formulation Example 3: Dentifrice composition)
0.08% by mass of tocopherol acetate
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 qs disodium edetate 0.02 mass%
Paraben 0.05% by mass
Perfume 0.2% by mass
Water balance 100% by mass

(Formulation Example 4: Dentifrice 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 (as solid content) 0.001% by mass
Sodium alginate 0.2% by mass
Carrageenan 1% by mass
Citric acid suitable amount phenoxyethanol 0.3% by mass
Perfume 0.02% by mass
Water balance 100% by mass

Claims (7)

  (A) for promoting periodontal tissue regeneration and / or repair, characterized by containing at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salts, kumazasa extract, and mallow extract Composition.   (A) A composition for promoting gingival cell activation and / or repair, comprising at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salts, kumazasa extract, and mallow extract object.   (A) A composition for preventing and / or treating alveolar pyorrhea, which comprises at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, kumazasa extract, and mallow extract. .   (A) An anti-inflammatory composition in the oral cavity, comprising at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salts, kumazasa extract, and mallow extract.   (A) A composition for improving a barrier function in the oral cavity, comprising: at least one selected from the group consisting of hyaluronic acid, a salt of hyaluronic acid, a kumazasa extract, and a mallow extract.   (A) A composition for promoting antibacterial activity in the oral cavity, comprising at least one selected from the group consisting of hyaluronic acid, hyaluronic acid salts, kumazasa extract, and mallow extract.   The composition according to any one of claims 1 to 6, wherein the component (A) is hyaluronic acid and / or a salt thereof.