WO2022092041A1 - Oral composition - Google Patents

Oral composition Download PDF

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Publication number
WO2022092041A1
WO2022092041A1 PCT/JP2021/039363 JP2021039363W WO2022092041A1 WO 2022092041 A1 WO2022092041 A1 WO 2022092041A1 JP 2021039363 W JP2021039363 W JP 2021039363W WO 2022092041 A1 WO2022092041 A1 WO 2022092041A1
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Prior art keywords
oral
oral composition
component
salt
weight
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PCT/JP2021/039363
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French (fr)
Japanese (ja)
Inventor
一宏 鳥井
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小林製薬株式会社
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Publication of WO2022092041A1 publication Critical patent/WO2022092041A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4425—Pyridinium derivatives, e.g. pralidoxime, pyridostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

  • the present invention relates to an oral composition capable of sterilizing the oral cavity and continuously exerting a moisturizing effect on the oral mucosa.
  • Dry mouth is also called xerostomia, which is a symptom that the amount of saliva secreted decreases and the oral cavity becomes dry.
  • Dry mouth can have various causes such as aging, stress, muscle weakness, diabetes, renal failure, menopausal disorder, side effects of medication, etc., and these causes cannot be completely eliminated, so it is often used for the treatment of dry mouth.
  • Oral sprays, mouthwashes, mouthwashes, artificial saliva, troches and other oral compositions are used to moisturize the oral cavity.
  • Patent Document 1 discloses that an oral composition containing a hydrophobically modified polyether urethane and a wetting agent is effective for the prevention or treatment of dry mouth.
  • Patent Document 2 describes polyglutamate as 0.05 to 5% by mass, an organic acid such as citric acid and a salt thereof, 2 to 6% by mass, l-menthol, glycerin as 10 to 50% by mass, and a surfactant.
  • a composition for oral spray containing 0.01-0.3% by mass of monomentyl succinate is disclosed to be effective in the prevention or treatment of dry mice.
  • the oral composition effective for the prevention or treatment of dry mouth not only imparts a moisturizing effect to the oral cavity but also has a bactericidal effect.
  • an object of the present invention is to provide an oral composition capable of sterilizing the oral cavity and continuously exerting a moisturizing effect on the oral mucosa.
  • the present inventor has found that by using a quaternary ammonium salt and hypromellose in combination in an oral composition, a bactericidal effect is exhibited and synergistic of these components. It was found that the action dramatically improves the sustainability of the moisturizing effect on the oral mucosa.
  • the present invention has been completed by further studies based on such findings.
  • Item 1 An oral composition containing (A) a quaternary ammonium salt and (B) hypromellose.
  • Item 2. The oral composition according to Item 1, further comprising (C) azulene sulfonic acid and / or a salt thereof.
  • Item 3. Item 2. The oral composition according to Item 1 or 2, wherein the component (A) is at least one selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride.
  • Item 4. Item 6. The oral composition according to any one of Items 1 to 3, which is used for the prevention or treatment of dry mouth.
  • the oral composition of the present invention is effective for oral care because it can continuously exert a moisturizing effect on the oral mucosa while exhibiting a bactericidal effect, and can be suitably used for, for example, prevention or treatment of dry mouth.
  • the oral composition of the present invention is characterized by containing (A) a quaternary ammonium salt and (B) hypromellose.
  • A a quaternary ammonium salt
  • B hypromellose
  • the oral composition of the present invention contains a quaternary ammonium salt (sometimes referred to as component (A)).
  • a quaternary ammonium salt sometimes referred to as component (A)
  • component (A) By containing the quaternary ammonium salt in the external composition of the present invention, it becomes possible to exert a bactericidal effect in the oral cavity.
  • the type of the quaternary ammonium salt is not particularly limited as long as it is pharmaceutically acceptable, but for example, a quaternary ammonium salt having a bactericidal action can be preferably used.
  • a quaternary ammonium salt having a bactericidal action include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, decalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, and lauroylcolaminoformyl chloride. Examples thereof include methylpyridinium.
  • the quaternary ammonium salt may be in the form of a solvate such as a hydrate.
  • quaternary ammonium salts may be used alone or in combination of two or more.
  • cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, and more preferably cetylpyridinium chloride are mentioned.
  • cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, and more preferably cetylpyridinium chloride are preferable from the viewpoint of further improving the sustainability of the moisturizing effect on the oral mucosa.
  • one component from the quaternary ammonium salt may be used alone, or two or more components may be used in combination.
  • the content of the component (A) in the oral composition of the present invention may be appropriately set according to the type of the component (A) to be used, the formulation form of the oral composition, etc., and may be appropriately set, for example, 0.001. It is about 5% by weight, preferably 0.01 to 2% by weight, and more preferably 0.05 to 1.25% by weight.
  • the oral composition of the present invention contains hypromellose (sometimes referred to as component (B)) in addition to the component (A).
  • hypromellose sometimes referred to as component (B)
  • component (A) in combination with hypromellose, it becomes possible to dramatically improve the sustainability of the moisturizing effect on the oral mucosa by these synergistic actions.
  • Hypromellose is a known cellulose derivative also called hydroxypropylmethyl cellulose.
  • the content of the component (B) in the oral composition of the present invention may be appropriately set according to the formulation form of the oral composition and the like, and is, for example, 0.01 to 1.5% by weight, preferably 0.01 to 1.5% by weight. 0.1 to 1.5% by weight, more preferably 0.2 to 1.5% by weight, still more preferably 0.6 to 1.5% by weight.
  • the sustainability of the moisturizing effect on the oral mucosa can be dramatically improved without causing a decrease in usability due to an increase in viscosity.
  • the ratio of the component (A) to the component (B) is determined according to the content of each of these components.
  • the component is 0.1 to 20 parts by weight, preferably 0.5 to 6 parts by weight, more preferably 1 to 6 parts by weight, still more preferably 2 to 6 parts by weight.
  • the oral composition of the present invention may contain azulene sulfonic acid and / or a salt thereof (sometimes referred to as component (C)) in addition to the components (A) and (B).
  • azulene sulfonic acid and / or a salt thereof sometimes referred to as component (C)
  • the sustainability of the moisturizing effect on the oral mucosa is further improved while exhibiting both the anti-inflammatory effect and the bactericidal effect in the oral cavity. Will be possible.
  • Azulene sulfonic acid is a known anti-inflammatory component also called 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid.
  • the type of salt of azulene sulfonic acid is not particularly limited as long as it is pharmaceutically acceptable, but for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt.
  • Other metal salts such as aluminum salts; Ammonium salts; Acetate, trifluoroacetate, butyrate, palmitate, stearate, fumarate, maleate, succinate, malonate, lactate , Tartrate, citrate and other carboxylates; methanesulfonate, toluenesulfonate, tosylate and other organic sulfonates; methylamine salt, triethylamine salt, triethanolamine salt, morpholine salt, piperazine salt , Pyrrolidine salt, tripyridine salt, picolin salt and other organic amine salts; examples thereof include hydrochlorides, sulfates, nitrates, hydrobromide salts, and inorganic acid salts such
  • a salt of azulene sulfonic acid is preferable, and sodium azulene sulfonic acid is more preferable, from the viewpoint of further improving the sustainability of the moisturizing effect on the oral mucosa.
  • component (C) one component from azulene sulfonic acid and a salt thereof may be used alone, or two or more components may be used in combination.
  • the content thereof may be appropriately set according to the type of the component (C) to be used, the formulation form of the oral composition, and the like. For example, 0.0001 to 5% by weight, preferably 0.001 to 1% by weight, and more preferably 0.01 to 0.5% by weight can be mentioned.
  • the ratio of the component (A) to the component (C) is determined according to the content of both components, for example, (A).
  • the component (B) are 0.01 to 10 parts by weight, preferably 0.01 to 1 part by weight, and more preferably 0.02 to 0.2 parts by weight per 1 part by weight of the component.
  • the oral composition of the present invention may contain a monohydric lower alcohol (sometimes referred to as a component (D)) in addition to the above-mentioned components (A) and (B).
  • a monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.
  • the type of monohydric lower alcohol is not particularly limited as long as it is pharmaceutically acceptable, but for example, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, n-amyl alcohol. , Se-amyl alcohol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol and the like. These monohydric lower alcohols may be used alone or in combination of two or more.
  • ethanol is preferable.
  • the content thereof is not particularly limited, but is, for example, 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably. Is 0.5 to 3% by weight.
  • the oral composition of the present invention may contain a polyhydric alcohol (sometimes referred to as a component (E)) in addition to the components (A) and (B) described above.
  • a polyhydric alcohol sometimes referred to as a component (E)
  • polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, but for example, 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol and the like.
  • a dihydric alcohol is preferable, and propylene glycol is more preferable.
  • the content thereof is not particularly limited, but is, for example, 1 to 80% by weight, preferably 10 to 75% by weight, and more preferably 30 to 70% by weight. Weight% is mentioned.
  • the oral composition of the present invention may contain water as part of the base.
  • the content thereof may be appropriately set according to the form of the formulation and the like, but is, for example, 1 to 90% by weight, preferably 10 to 70% by weight. It is preferably 25 to 60% by weight.
  • the oral composition of the present invention may contain other medicinal ingredients in addition to the above-mentioned ingredients, if necessary.
  • Such medicinal ingredients are not particularly limited as long as they can be blended in pharmaceutical products, oral care products, etc., but for example, iodine-based bactericidal ingredients (for example, iodine, povidone iodine, nonoxinol iodine and phenoxy iodine).
  • bronchial dilators include bronchial dilators, antitussives, expectorants, anti-inflammatory agents (other than azulene sulfonic acid and its salts), glucosyltransferase inhibitors, plaque inhibitors, hypersensitivity inhibitors, tooth stone preventives, antipyretic analgesics, antihistamines
  • bronchial dilators include medicines, bactericides (other than quaternary ammonium salts), gastromucosal protective medicines, caffeines, vitamin medicines, Chinese herbs, and raw medicine ingredients.
  • the oral composition of the present invention may contain a base or an additive in order to obtain a desired pharmaceutical form.
  • bases and additives are not particularly limited as long as they can be blended in pharmaceuticals, oral care products, etc., but for example, oily components, surfactants, preservatives, thickeners (other than hypromellose). ), Fragrances, flavoring agents, cooling agents, pigments, deodorants, pigments, buffers, pH adjusters and the like.
  • the shape of the oral composition of the present invention is not particularly limited and may be liquid, solid, semi-solid (gel, ointment, paste) or the like, but liquid is preferable. Be done.
  • the formulation form of the oral composition of the present invention is not limited as long as it is applied to the oral cavity and can stay in the oral cavity for a certain period of time, but for example, an oral spray (including a throat spray agent), a mouse.
  • Oral care products such as wash, mouthwash, liquid dentifrice, kneaded dentin, mouth refresher, oral pasta, gingival massage cream and the like can be mentioned.
  • an oral spray, a mouthwash, a mouthwash, and more preferably an oral spray are preferable.
  • the oral composition of the present invention When applied to the oral cavity, the oral composition of the present invention can extinguish and / or sterilize the oral cavity and can continuously exert a moisturizing effect on the oral mucosa. Therefore, for example, prevention of dry mouth or Suitable for therapeutic use.
  • the usage and volume of the oral composition of the present invention are appropriately set according to the content of each compounding component, the pharmaceutical form of the oral composition, the expected effect, etc., and are, for example, 1 to 1 per day. An appropriate amount may be applied intraorally at a frequency of 6 times.
  • Test Example 1 Oral compositions (oral sprays) having the compositions shown in Tables 1 and 2 were prepared.
  • the obtained oral composition was evaluated for its long-lasting moisturizing effect on the oral mucosa by the following method. First, the edible pig tongue (unsliced) excised as a pseudo-mucosa is lightly moistened with running water and then lightly wiped off. It was allowed to stand until the measured value at Yoshida Co., Ltd.) reached the drying index value (25 or less). Next, the obtained oral composition was placed in a spray container, and about 0.3 ml of the oral composition was spray-applied to a portion slightly from the center of the pig tongue to a portion slightly from the tip, and the temperature was 30 ° C. and the relative humidity was 30%.
  • the moisture value of the pig tongue part to which the oral composition was applied was measured using an oral moisture meter (Oral Moisture Meter Mucus, Yoshida Co., Ltd.) and calculated as follows. According to the formula, the water retention rate (%) 6 hours after application was calculated, and the value rounded off to the first digit was taken as the water retention rate (%) 6 hours after application.
  • Formulation Example 1 An oral composition (oral spray) having the composition shown in Table 3 was prepared.
  • a comparative oral composition in which the hypromellose of Formulation Examples 5 and 6 was changed to purified water was also prepared.
  • the sustainability of the moisturizing effect of these oral compositions was evaluated by the same method as in Test Example 1.
  • the water retention rate after 6 hours of application was significantly higher than that of Comparative Examples 1 to 18.
  • the water retention rate after 6 hours of application was the comparative oral composition of Formulation Examples 5 and 6, and Comparative Examples 1 to 18. Compared with, the sustainability of the moisturizing effect was significantly increased.

Abstract

[Problem] The objective of the present invention is to provide an oral composition that can eliminate bacteria inside the oral cavity and that is capable of maintaining continuous moisturizing effect on the oral mucosa. [Solution] An oral composition containing (A) a quaternary ammonium salt and (B) hypromellose.

Description

口腔用組成物Oral composition
　本発明は、口腔内を殺菌でき、しかも口腔粘膜に対して保湿作用を持続的に発揮できる口腔用組成物に関する。 The present invention relates to an oral composition capable of sterilizing the oral cavity and continuously exerting a moisturizing effect on the oral mucosa.
　近年、ドライマウスの罹患者が増加傾向にある。ドライマウスは、口腔乾燥症とも称され、唾液の分泌量が低下し、口腔内が乾く症状である。ドライマウスは、加齢、ストレス、筋力低下、糖尿病、腎不全、更年期障害、服薬の副作用等の様々な原因が考えられ、これらの原因を完全に払拭できないことも多く、ドライマウスの治療には、口腔用スプレー、含嗽剤、マウスウォッシュ、人工唾液、トローチ等の口腔用組成物を使用して口腔内に潤いを付与する対処療法に頼らざるを得ない状況である。 In recent years, the number of people affected by dry mouth has been increasing. Dry mouth is also called xerostomia, which is a symptom that the amount of saliva secreted decreases and the oral cavity becomes dry. Dry mouth can have various causes such as aging, stress, muscle weakness, diabetes, renal failure, menopausal disorder, side effects of medication, etc., and these causes cannot be completely eliminated, so it is often used for the treatment of dry mouth. , Oral sprays, mouthwashes, mouthwashes, artificial saliva, troches and other oral compositions are used to moisturize the oral cavity.
　従来、ドライマウスの予防又は改善に有効な口腔用組成物について種々報告されている。例えば、特許文献１には、疎水変性ポリエーテルウレタン及び湿潤剤を含む口腔用組成物が、ドライマウスの予防又は治療に有効であることが開示されている。また、特許文献２には、ポリグルタミン酸塩０．０５～５質量％、クエン酸等の有機酸及びその塩、２～６質量％、ｌ－メントール、グリセリン１０～５０質量％、界面活性剤、及びモノメンチルサクシネート０．０１～０．３質量％を含有する口腔スプレー用組成物が、ドライマウスの予防又は治療に有効であることが開示されている。 Conventionally, various oral compositions effective for prevention or improvement of dry mouth have been reported. For example, Patent Document 1 discloses that an oral composition containing a hydrophobically modified polyether urethane and a wetting agent is effective for the prevention or treatment of dry mouth. Further, Patent Document 2 describes polyglutamate as 0.05 to 5% by mass, an organic acid such as citric acid and a salt thereof, 2 to 6% by mass, l-menthol, glycerin as 10 to 50% by mass, and a surfactant. And a composition for oral spray containing 0.01-0.3% by mass of monomentyl succinate is disclosed to be effective in the prevention or treatment of dry mice.
特開２０１２－１５３６７７号公報Japanese Unexamined Patent Publication No. 2012-153677 特開２０１１－１０５６５１号公報Japanese Unexamined Patent Publication No. 2011-105651
　ドライマウスの予防又は治療には、口腔粘膜に対して一時的に保湿効果を付与するだけでなく、その効果を持続させることが重要になる。また、ドライマウスは、口腔粘膜の乾燥によって細菌に対するバリア機能が低下しているため、口腔内で細菌感染や炎症が起き易くなっている。そのため、ドライマウスの予防又は治療に有効な口腔用組成物には、口腔内に保湿効果を付与するだけでなく、殺菌効果があることが望ましいといえる。 For the prevention or treatment of dry mouth, it is important not only to temporarily give a moisturizing effect to the oral mucosa, but also to maintain the effect. In addition, since the barrier function against bacteria of dry mouth is lowered due to the drying of the oral mucosa, bacterial infection and inflammation are likely to occur in the oral cavity. Therefore, it is desirable that the oral composition effective for the prevention or treatment of dry mouth not only imparts a moisturizing effect to the oral cavity but also has a bactericidal effect.
　そこで、本発明は、口腔内を殺菌でき、しかも口腔粘膜に対する保湿効果が持続的に奏し得る口腔用組成物を提供することを目的とする。 Therefore, an object of the present invention is to provide an oral composition capable of sterilizing the oral cavity and continuously exerting a moisturizing effect on the oral mucosa.
　本発明者は、前記課題を解決すべく鋭意検討を行ったところ、口腔用組成物において、第四級アンモニウム塩とヒプロメロースとを併用することにより、殺菌効果を奏しつつ、これらの成分の相乗的作用によって口腔粘膜に対する保湿効果の持続性が飛躍的に向上することを見出した。本発明は、かかる知見に基づいて更に検討を重ねることにより完成したものである。 As a result of diligent studies to solve the above problems, the present inventor has found that by using a quaternary ammonium salt and hypromellose in combination in an oral composition, a bactericidal effect is exhibited and synergistic of these components. It was found that the action dramatically improves the sustainability of the moisturizing effect on the oral mucosa. The present invention has been completed by further studies based on such findings.
　即ち、本発明は、下記に掲げる態様の発明を提供する。
項１．　(A)第四級アンモニウム塩、及び(B)ヒプロメロースを含有する、口腔用組成物。項２．　更に、(C)アズレンスルホン酸及び／又はその塩を含む、項１に記載の口腔用組成物。
項３．　前記(A)成分が、塩化セチルピリジニウム、塩化ベンゼトニウム、及び塩化ベンザルコニウムよりなる群から選択される少なくとも１種である、項１又は２に記載の口腔用組成物。
項４．　ドライマウスの予防又は治療に使用される、項１～３のいずれかに記載の口腔用組成物。 That is, the present invention provides the inventions of the following aspects.
Item 1. An oral composition containing (A) a quaternary ammonium salt and (B) hypromellose. Item 2. Item 2. The oral composition according to Item 1, further comprising (C) azulene sulfonic acid and / or a salt thereof.
Item 3. Item 2. The oral composition according to Item 1 or 2, wherein the component (A) is at least one selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride.
Item 4. Item 6. The oral composition according to any one of Items 1 to 3, which is used for the prevention or treatment of dry mouth.
　本発明の口腔用組成物は、殺菌効果を奏しつつ、口腔粘膜に対する保湿効果を持続的に奏し得るので口腔ケアに有効であり、例えばドライマウスの予防又は治療等の用途で好適に使用できる。 The oral composition of the present invention is effective for oral care because it can continuously exert a moisturizing effect on the oral mucosa while exhibiting a bactericidal effect, and can be suitably used for, for example, prevention or treatment of dry mouth.
　本発明の口腔用組成物は、(A)第四級アンモニウム塩、及び(B)ヒプロメロースを含有することを特徴とする。以下、本発明の口腔用組成物について説明する。 The oral composition of the present invention is characterized by containing (A) a quaternary ammonium salt and (B) hypromellose. Hereinafter, the oral composition of the present invention will be described.
［(A)第四級アンモニウム塩］
　本発明の口腔用組成物は、第四級アンモニウム塩（(A)成分と表記することもある）を含有する。本発明の外用組成物において、第四級アンモニウム塩を含むことにより、口腔内で殺菌効果を奏することが可能になる。 [(A) Quaternary ammonium salt]
The oral composition of the present invention contains a quaternary ammonium salt (sometimes referred to as component (A)). By containing the quaternary ammonium salt in the external composition of the present invention, it becomes possible to exert a bactericidal effect in the oral cavity.
　第四級アンモニウム塩の種類については、薬学的に許容されることを限度として特に制限されないが、例えば、殺菌作用を有する第四級アンモニウム塩を好適に使用できる。このような第四級アンモニウム塩としては、具体的には、塩化セチルピリジニウム、塩化ベンゼトニウム、塩化ベンザルコニウム、塩化デカリニウム、塩化アルキルジメチルアンモニウム、塩化アルキルトリメチルアンモニウム、塩化メチルベンゼトニウム、塩化ラウロイルコラミノホルミルメチルピリジニウム等が挙げられる。第四級アンモニウム塩は、水和物等の溶媒和物の形態であってもよい。これらの第四級アンモニウム塩は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。これらの第四級アンモニウム塩の中でも、好ましくは塩化セチルピリジニウム、塩化ベンゼトニウム、塩化ベンザルコニウム、より好ましくは塩化セチルピリジニウムが挙げられる。 The type of the quaternary ammonium salt is not particularly limited as long as it is pharmaceutically acceptable, but for example, a quaternary ammonium salt having a bactericidal action can be preferably used. Specific examples of such a quaternary ammonium salt include cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, decalinium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, and lauroylcolaminoformyl chloride. Examples thereof include methylpyridinium. The quaternary ammonium salt may be in the form of a solvate such as a hydrate. These quaternary ammonium salts may be used alone or in combination of two or more. Among these quaternary ammonium salts, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, and more preferably cetylpyridinium chloride are mentioned.
　(A)成分の中でも、口腔粘膜に対する保湿効果の持続性をより一層向上させるという観点から、好ましくは塩化セチルピリジニウム、塩化ベンゼトニウム、塩化ベンザルコニウム、より好ましく塩化セチルピリジニウムが挙げられる。 Among the components (A), cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, and more preferably cetylpyridinium chloride are preferable from the viewpoint of further improving the sustainability of the moisturizing effect on the oral mucosa.
　(A)成分として、第四級アンモニウム塩の中から１種の成分を単独で使用してもよく、また２種以上の成分を組み合わせて使用してもよい。 As the component (A), one component from the quaternary ammonium salt may be used alone, or two or more components may be used in combination.
　本発明の口腔用組成物における(A)成分の含有量については、使用する(A)成分の種類、口腔用組成物の製剤形態等に応じて適宜設定すればよいが、例えば、０．００１～５重量％、好ましくは０．０１～２重量％、より好ましくは０．０５～１．２５重量％が挙げられる。 The content of the component (A) in the oral composition of the present invention may be appropriately set according to the type of the component (A) to be used, the formulation form of the oral composition, etc., and may be appropriately set, for example, 0.001. It is about 5% by weight, preferably 0.01 to 2% by weight, and more preferably 0.05 to 1.25% by weight.
［(B)ヒプロメロース］
　本発明の口腔用組成物は、前記(A)成分に加えて、ヒプロメロース（(B)成分と表記することもある）を含有する。前記(A)成分とヒプロメロースを併用することによって、これらの相乗的作用により、口腔粘膜に対する保湿効果の持続性を飛躍的に向上させることが可能になる。 [(B) Hypromellose]
The oral composition of the present invention contains hypromellose (sometimes referred to as component (B)) in addition to the component (A). By using the component (A) in combination with hypromellose, it becomes possible to dramatically improve the sustainability of the moisturizing effect on the oral mucosa by these synergistic actions.
　ヒプロメロースとは、ヒドロキシプロピルメチルセルロースとも称される公知のセルロース誘導体である。 Hypromellose is a known cellulose derivative also called hydroxypropylmethyl cellulose.
　本発明の口腔用組成物における(B)成分の含有量については、口腔用組成物の製剤形態等に応じて適宜設定すればよいが、例えば、０．０１～１．５重量％、好ましくは０．１～１．５重量％、より好ましくは０．２～１．５重量％、更に好ましくは０．６～１．５重量％が挙げられる。(B)成分の含有量が前記範囲を充足することにより、粘度の増加による使用感の低下を招くことなく、口腔粘膜に対する保湿効果の持続性を飛躍的に向上させることができる。 The content of the component (B) in the oral composition of the present invention may be appropriately set according to the formulation form of the oral composition and the like, and is, for example, 0.01 to 1.5% by weight, preferably 0.01 to 1.5% by weight. 0.1 to 1.5% by weight, more preferably 0.2 to 1.5% by weight, still more preferably 0.6 to 1.5% by weight. When the content of the component (B) satisfies the above range, the sustainability of the moisturizing effect on the oral mucosa can be dramatically improved without causing a decrease in usability due to an increase in viscosity.
　本発明の口腔用組成物において、(A)成分と(B)成分の比率については、これらの両成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(B)成分が０．１～２０重量部、好ましくは０．５～６重量部、より好ましくは１～６重量部、更に好ましくは２～６重量部が挙げられる。 In the oral composition of the present invention, the ratio of the component (A) to the component (B) is determined according to the content of each of these components. For example, (B) per part by weight of the component (A). ) The component is 0.1 to 20 parts by weight, preferably 0.5 to 6 parts by weight, more preferably 1 to 6 parts by weight, still more preferably 2 to 6 parts by weight.
［(C)アズレンスルホン酸及び／又はその塩］
　本発明の口腔用組成物は、前記(A)及び(B)成分に加えて、アズレンスルホン酸及び／又はその塩（(C)成分と表記することもある）を含んでいてもよい。本発明の口腔用組成物において、アズレンスルホン酸及び／又はその塩を含むことにより、口腔内で消炎効果と殺菌効果の双方を奏させつつ、口腔粘膜に対する保湿効果の持続性をより一層向上させることが可能になる。 [(C) Azulene sulfonic acid and / or a salt thereof]
The oral composition of the present invention may contain azulene sulfonic acid and / or a salt thereof (sometimes referred to as component (C)) in addition to the components (A) and (B). By containing azulene sulfonic acid and / or a salt thereof in the oral composition of the present invention, the sustainability of the moisturizing effect on the oral mucosa is further improved while exhibiting both the anti-inflammatory effect and the bactericidal effect in the oral cavity. Will be possible.
　アズレンスルホン酸は、１，４－ジメチル－７－イソプロピルアズレン－３－スルホン酸とも称される公知の抗炎症成分である。 Azulene sulfonic acid is a known anti-inflammatory component also called 1,4-dimethyl-7-isopropylazulene-3-sulfonic acid.
　アズレンスルホン酸の塩の種類については、薬学的に許容されることを限度として特に制限されないが、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩等のアルカリ土類金属塩；アルミニウム塩等のその他の金属塩；アンモニウム塩；酢酸塩、トリフルオロ酢酸塩、酪酸塩、パルミチン酸塩、ステアリン酸塩、フマル酸塩、マレイン酸塩、コハク酸塩、マロン酸塩、乳酸塩、酒石酸塩、クエン酸塩等のカルボン酸塩；メタンスルホン酸塩、トルエンスルホン酸塩、トシル酸塩等の有機スルホン酸塩；メチルアミン塩、トリエチルアミン塩、トリエタノールアミン塩、モルホリン塩、ピペラジン塩、ピロリジン塩、トリピリジン塩、ピコリン塩等の有機アミン塩；塩酸塩、硫酸塩、硝酸塩、臭化水素酸塩、リン酸塩等の無機酸塩等が挙げられる。これらの塩の中でも、好ましくはアルカリ金属塩、より好ましくはナトリウム塩が挙げられる。 The type of salt of azulene sulfonic acid is not particularly limited as long as it is pharmaceutically acceptable, but for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt. Other metal salts such as aluminum salts; Ammonium salts; Acetate, trifluoroacetate, butyrate, palmitate, stearate, fumarate, maleate, succinate, malonate, lactate , Tartrate, citrate and other carboxylates; methanesulfonate, toluenesulfonate, tosylate and other organic sulfonates; methylamine salt, triethylamine salt, triethanolamine salt, morpholine salt, piperazine salt , Pyrrolidine salt, tripyridine salt, picolin salt and other organic amine salts; examples thereof include hydrochlorides, sulfates, nitrates, hydrobromide salts, and inorganic acid salts such as phosphates. Among these salts, an alkali metal salt is preferable, and a sodium salt is more preferable.
　(C)成分の中でも、口腔粘膜に対する保湿効果の持続性をより一層向上させるという観点から、好ましくはアズレンスルホン酸の塩、より好ましくはアズレンスルホン酸ナトリウムが挙げられる。 Among the components (C), a salt of azulene sulfonic acid is preferable, and sodium azulene sulfonic acid is more preferable, from the viewpoint of further improving the sustainability of the moisturizing effect on the oral mucosa.
　(C)成分として、アズレンスルホン酸、及びその塩の中から１種の成分を単独で使用してもよく、また２種以上の成分を組み合わせて使用してもよい。 As the component (C), one component from azulene sulfonic acid and a salt thereof may be used alone, or two or more components may be used in combination.
　本発明の口腔用組成物に(C)成分を含有させる場合、その含有量については、使用する(C)成分の種類、口腔用組成物の製剤形態等に応じて適宜設定すればよいが、例えば、０．０００１～５重量％、好ましくは０．００１～１重量％、より好ましくは０．０１～０．５重量％が挙げられる。 When the oral composition of the present invention contains the component (C), the content thereof may be appropriately set according to the type of the component (C) to be used, the formulation form of the oral composition, and the like. For example, 0.0001 to 5% by weight, preferably 0.001 to 1% by weight, and more preferably 0.01 to 0.5% by weight can be mentioned.
　本発明の口腔用組成物に(C)成分を含有させる場合、(A)成分と(C)成分の比率については、これらの両成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(B)成分が０．０１～１０重量部、好ましくは０．０１～１重量部、より好ましくは０．０２～０．２重量部が挙げられる。 When the component (C) is contained in the oral composition of the present invention, the ratio of the component (A) to the component (C) is determined according to the content of both components, for example, (A). Examples of the component (B) are 0.01 to 10 parts by weight, preferably 0.01 to 1 part by weight, and more preferably 0.02 to 0.2 parts by weight per 1 part by weight of the component.
［(D)１価低級アルコール］
　本発明の口腔用組成物は、前述する(A)及び(B)成分に加えて、１価低級アルコール（(D)成分と表記することもある）を含んでいてもよい。本発明において、１価低級アルコールとは炭素数１～５の１価アルコールを指す。 [(D) Monohydric lower alcohol]
The oral composition of the present invention may contain a monohydric lower alcohol (sometimes referred to as a component (D)) in addition to the above-mentioned components (A) and (B). In the present invention, the monohydric lower alcohol refers to a monohydric alcohol having 1 to 5 carbon atoms.
　１価低級アルコールの種類については、薬学的に許容されることを限度として特に制限されないが、例えば、エタノール、ｎ－プロパノール、イソプロパノール、ｎ－ブタノール、ｓｅｃ－ブタノール、ｔｅｒｔ－ブタノール、ｎ－アミルアルコール、ｓｅｃ－アミルアルコール、イソアミルアルコール、ｔｅｒｔ－アミルアルコール、ネオペンチルアルコール等が挙げられる。これらの１価低級アルコールは、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The type of monohydric lower alcohol is not particularly limited as long as it is pharmaceutically acceptable, but for example, ethanol, n-propanol, isopropanol, n-butanol, sec-butanol, tert-butanol, n-amyl alcohol. , Se-amyl alcohol, isoamyl alcohol, tert-amyl alcohol, neopentyl alcohol and the like. These monohydric lower alcohols may be used alone or in combination of two or more.
　これらの１価低級アルコールの中でも、好ましくはエタノールが挙げられる。 Among these monohydric lower alcohols, ethanol is preferable.
　本発明の口腔用組成物に(D)成分を含有させる場合、その含有量については、特に制限されないが、例えば、０．０１～１０重量％、好ましくは０．１～５重量％、より好ましくは０．５～３重量％が挙げられる。 When the component (D) is contained in the oral composition of the present invention, the content thereof is not particularly limited, but is, for example, 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably. Is 0.5 to 3% by weight.
［(E)多価アルコール］
　本発明の口腔用組成物は、前述する(A)及び(B)成分に加えて、多価アルコール（(E)成分と表記することもある）を含んでいてもよい。 [(E) Multivalent alcohol]
The oral composition of the present invention may contain a polyhydric alcohol (sometimes referred to as a component (E)) in addition to the components (A) and (B) described above.
　多価アルコールの種類については、薬学的に許容されることを限度として特に制限されないが、例えば、１，３－ブチレングリコール、エチレングリコール、プロピレングリコール、イソプレングリコール、ジエチレングリコール、ジプロピレングリコール、ポリエチレングリコール等の２価アルコール；グリセリン等が挙げられる。これらの多価アルコールは、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The type of polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, but for example, 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol and the like. Dihydric alcohol; glycerin and the like. These polyhydric alcohols may be used alone or in combination of two or more.
　これらの多価アルコールの中でも、好ましくは２価アルコール、より好ましくはプロピレングリコールが挙げられる。 Among these polyhydric alcohols, a dihydric alcohol is preferable, and propylene glycol is more preferable.
　本発明の口腔用組成物に(E)成分を含有させる場合、その含有量については、特に制限されないが、例えば、１～８０重量％、好ましくは１０～７５重量％、より好ましくは３０～７０重量％が挙げられる。 When the component (E) is contained in the oral composition of the present invention, the content thereof is not particularly limited, but is, for example, 1 to 80% by weight, preferably 10 to 75% by weight, and more preferably 30 to 70% by weight. Weight% is mentioned.
［水］
　本発明の口腔用組成物には、基剤の一部として水が含まれていてもよい。本発明の口腔用組成物が水を含む場合、その含有量については、その製剤形態等に応じて適宜設定すればよいが、例えば、１～９０重量％、好ましくは１０～７０重量％、より好ましくは２５～６０重量％が挙げられる。 [water]
The oral composition of the present invention may contain water as part of the base. When the oral composition of the present invention contains water, the content thereof may be appropriately set according to the form of the formulation and the like, but is, for example, 1 to 90% by weight, preferably 10 to 70% by weight. It is preferably 25 to 60% by weight.
［その他の成分］
　本発明の口腔用組成物は、前述する成分以外に、必要に応じて他の薬効成分が含まれていてもよい。このような薬効成分としては、医薬品、口腔ケア製品等に配合可能なものであることを限度として特に制限されないが、例えば、ヨウ素系殺菌成分（例えば、ヨウ素、ポビドンヨード、ノノキシノールヨード及びフェノキシヨード等）、気管支拡張薬、鎮咳薬、去痰薬、抗炎症剤（アズレンスルホン酸及びその塩以外）、グルコシルトランスフェラーゼ阻害剤、プラーク抑制剤、知覚過敏抑制剤、歯石予防剤、解熱鎮痛薬、抗ヒスタミン薬、殺菌剤（第四級アンモニウム塩以外）、胃粘膜保護薬、カフェイン類、ビタミン薬、漢方薬、生薬成分等が挙げられる。 [Other ingredients]
The oral composition of the present invention may contain other medicinal ingredients in addition to the above-mentioned ingredients, if necessary. Such medicinal ingredients are not particularly limited as long as they can be blended in pharmaceutical products, oral care products, etc., but for example, iodine-based bactericidal ingredients (for example, iodine, povidone iodine, nonoxinol iodine and phenoxy iodine). Etc.), bronchial dilators, antitussives, expectorants, anti-inflammatory agents (other than azulene sulfonic acid and its salts), glucosyltransferase inhibitors, plaque inhibitors, hypersensitivity inhibitors, tooth stone preventives, antipyretic analgesics, antihistamines Examples include medicines, bactericides (other than quaternary ammonium salts), gastromucosal protective medicines, caffeines, vitamin medicines, Chinese herbs, and raw medicine ingredients.
　また、本発明の口腔用組成物には、所望の製剤形態にするために、基剤や添加剤が含まれていてもよい。このような基剤や添加剤としては、医薬品、口腔ケア製品等に配合可能でものであることを限度として特に制限されないが、例えば、油性成分、界面活性剤、防腐剤、増粘剤（ヒプロメロース以外）、香料、矯味剤、清涼化剤、色素、消臭剤、顔料、緩衝剤、ｐＨ調整剤等が挙げられる。 Further, the oral composition of the present invention may contain a base or an additive in order to obtain a desired pharmaceutical form. Such bases and additives are not particularly limited as long as they can be blended in pharmaceuticals, oral care products, etc., but for example, oily components, surfactants, preservatives, thickeners (other than hypromellose). ), Fragrances, flavoring agents, cooling agents, pigments, deodorants, pigments, buffers, pH adjusters and the like.
［形状・製剤形態］
　本発明の口腔用組成物の形状については、特に制限されず、液状、固形状、半固形状（ゲル状、軟膏状、ペースト状）等のいずれであってもよいが、好ましくは液状が挙げられる。 [Shape / formulation form]
The shape of the oral composition of the present invention is not particularly limited and may be liquid, solid, semi-solid (gel, ointment, paste) or the like, but liquid is preferable. Be done.
　本発明の口腔用組成物の製剤形態は、口腔内に適用されて口腔内で一定時間滞留し得るものである限り制限されないが、例えば、口腔用スプレー（喉用のスプレー剤を含む）、マウスウォッシュ、含嗽剤、液状歯磨剤、練歯磨剤、口中清涼剤、口腔用パスタ剤、歯肉マッサージクリーム等の口腔ケア製品が挙げられる。これらの中でも、好ましくは口腔用スプレー、マウスウォッシュ、含嗽剤、より好ましくは口腔用スプレーが挙げられる。 The formulation form of the oral composition of the present invention is not limited as long as it is applied to the oral cavity and can stay in the oral cavity for a certain period of time, but for example, an oral spray (including a throat spray agent), a mouse. Oral care products such as wash, mouthwash, liquid dentifrice, kneaded dentin, mouth refresher, oral pasta, gingival massage cream and the like can be mentioned. Among these, an oral spray, a mouthwash, a mouthwash, and more preferably an oral spray are preferable.
［使用方法］
　本発明の口腔用組成物は、口腔内に適用することにより、口腔内を消炎及び／又は殺菌でき、更に口腔粘膜に対して保湿作用を持続的に発揮できるので、例えば、ドライマウスの予防又は治療用途に好適に使用される。 [how to use]
When applied to the oral cavity, the oral composition of the present invention can extinguish and / or sterilize the oral cavity and can continuously exert a moisturizing effect on the oral mucosa. Therefore, for example, prevention of dry mouth or Suitable for therapeutic use.
　本発明の口腔用組成物の用法及び容量については、各配合成分の含有量、口腔用組成物の製剤形態、期待される効果等に応じて適宜設定されるが、例えば、１日に１～６回の頻度で適量を口腔内に適用すればよい。 The usage and volume of the oral composition of the present invention are appropriately set according to the content of each compounding component, the pharmaceutical form of the oral composition, the expected effect, etc., and are, for example, 1 to 1 per day. An appropriate amount may be applied intraorally at a frequency of 6 times.
　以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be described in more detail with reference to examples below, but the present invention is not limited thereto.
試験例１
　表１及び２に示す組成の口腔用組成物（口腔用スプレー）を調製した。得られた口腔用組成物について、以下の方法で口腔粘膜に対する保湿効果の持続性を評価した。先ず、疑似粘膜として切除した食用の豚舌（スライスしていない状態）を流水で軽く濡らした後に軽く拭き取り、３０℃、相対湿度３０％ＲＨの環境下で、口腔水分計（口腔水分計ムーカス、株式会社ヨシダ）での測定値が乾燥指標値（２５以下）になるまで静置した。次いで、得られた口腔用組成物をスプレー容器に収容して、約０．３ｍｌの口腔用組成物を前記豚舌の中心からやや先端よりの部位に噴霧塗布し、３０℃、相対湿度３０％ＲＨの雰囲気で６時間静置した。口腔用組成物の塗布直後と塗布６時間後に、口腔水分計（口腔水分計ムーカス、株式会社ヨシダ））を用いて、口腔用組成物を塗布した豚舌部位の水分値を測定し、下記算出式に従って、塗布６時間後の水分保持率（％）を算出し、小数点第一位の値を四捨五入した値を塗布６時間後の水分保持率（％）とした。
Figure JPOXMLDOC01-appb-M000001
 Test Example 1
Oral compositions (oral sprays) having the compositions shown in Tables 1 and 2 were prepared. The obtained oral composition was evaluated for its long-lasting moisturizing effect on the oral mucosa by the following method. First, the edible pig tongue (unsliced) excised as a pseudo-mucosa is lightly moistened with running water and then lightly wiped off. It was allowed to stand until the measured value at Yoshida Co., Ltd.) reached the drying index value (25 or less). Next, the obtained oral composition was placed in a spray container, and about 0.3 ml of the oral composition was spray-applied to a portion slightly from the center of the pig tongue to a portion slightly from the tip, and the temperature was 30 ° C. and the relative humidity was 30%. It was allowed to stand for 6 hours in the atmosphere of RH. Immediately after application of the oral composition and 6 hours after application, the moisture value of the pig tongue part to which the oral composition was applied was measured using an oral moisture meter (Oral Moisture Meter Mucus, Yoshida Co., Ltd.) and calculated as follows. According to the formula, the water retention rate (%) 6 hours after application was calculated, and the value rounded off to the first digit was taken as the water retention rate (%) 6 hours after application.
Figure JPOXMLDOC01-appb-M000001
　結果を表１及び２に示す。塩化セチルピリジニウム単独では、塗布６時間後の水分保持率が低く、保湿効果を持続できなかった（比較例１）。また、ヒプロメロース、ヒドロキシエチルセルロース、及びカルボキシビニルポリマーでも、それぞれ単独では、塗布６時間後の水分保持率は幾分高くなっていたが、依然として不十分であった（比較例６～８）。更に、塩化セチルピリジニウムと共に、ヒドロキシエチルセルロース又はカルボキシビニルポリマーを併用しても、塗布６時間後の水分保持率は相加的な向上程度しか認められなかった（比較例２～５、９～１３及び１５～１８）。これに対して、塩化セチルピリジニウムとヒプロメロースを併用した場合には、塗布６時間後の水分保持率が相乗的に向上しており、保湿効果の持続性が格段に高まっていた（実施例１～６）。特に、塩化セチルピリジニウムとヒプロメロースとアズレンスルホン酸ナトリウムを併用した場合には、塗布６時間後の水分保持率がより一層向上しており、保湿効果の持続性が格段顕著に高まっていた（実施例４～６）。なお、実施例１～３の口腔用組成物は、塩化セチルピリジニウムを含んでいるので、殺菌効果を奏することが可能な組成になっており、実施例４～６の口腔用組成物は、塩化セチルピリジニウム及びアズレンスルホン酸ナトリウムを含んでいるので、殺菌効果及び消炎効果を奏することが可能な組成になっている。


  The results are shown in Tables 1 and 2. With cetylpyridinium chloride alone, the water retention rate 6 hours after application was low, and the moisturizing effect could not be maintained (Comparative Example 1). In addition, hypromellose, hydroxyethyl cellulose, and carboxyvinyl polymer alone had a slightly higher water retention rate after 6 hours of application, but were still insufficient (Comparative Examples 6 to 8). Furthermore, even when hydroxyethyl cellulose or carboxyvinyl polymer was used in combination with cetylpyridinium chloride, the water retention rate after 6 hours of application was only additively improved (Comparative Examples 2 to 5, 9 to 13 and). 15-18). On the other hand, when cetylpyridinium chloride and hypromellose were used in combination, the water retention rate after 6 hours of application was synergistically improved, and the sustainability of the moisturizing effect was significantly enhanced (Examples 1 to 1). 6). In particular, when cetylpyridinium chloride, hypromellose and sodium azulene sulfonate were used in combination, the water retention rate 6 hours after application was further improved, and the sustainability of the moisturizing effect was remarkably enhanced (Example). 4-6). Since the oral compositions of Examples 1 to 3 contain cetylpyridinium chloride, the composition is capable of exhibiting a bactericidal effect, and the oral compositions of Examples 4 to 6 are chloride. Since it contains cetylpyridinium and sodium azulene sulfonate, it has a composition capable of exerting a bactericidal effect and an anti-inflammatory effect.
Figure JPOXMLDOC01-appb-T000002
 　

 
Figure JPOXMLDOC01-appb-T000002
 　

 
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
処方例
　表３に示す組成の口腔用組成物（口腔用スプレー）を調製した。また比較のために、処方例５及び６のヒプロメロースを精製水に変更した比較用口腔用組成物も調製した。これらの口腔用組成物を試験例１と同じ方法で保湿効果の持続性を評価した。処方例１～４は、いずれも、塗布６時間後の水分保持率は比較例１～１８と比較して保湿効果の持続性が格段に高まっていた。また、塩化セチルピリジニウムを塩化ベンザルコニウム又は塩化ベンゼトニウムに置換した処方例５及び６でも、塗布６時間後の水分保持率は処方例５及び６の比較用口腔組成物、並びに比較例１～１８と比較して保湿効果の持続性が格段に高まっていた。 Formulation Example An oral composition (oral spray) having the composition shown in Table 3 was prepared. For comparison, a comparative oral composition in which the hypromellose of Formulation Examples 5 and 6 was changed to purified water was also prepared. The sustainability of the moisturizing effect of these oral compositions was evaluated by the same method as in Test Example 1. In each of Formulation Examples 1 to 4, the water retention rate after 6 hours of application was significantly higher than that of Comparative Examples 1 to 18. Further, even in Formulation Examples 5 and 6 in which cetylpyridinium chloride was replaced with benzalkonium chloride or benzethonium chloride, the water retention rate after 6 hours of application was the comparative oral composition of Formulation Examples 5 and 6, and Comparative Examples 1 to 18. Compared with, the sustainability of the moisturizing effect was significantly increased.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004

Claims (4)

  1. 　(A)第四級アンモニウム塩、及び(B)ヒプロメロースを含有する、口腔用組成物。 An oral composition containing (A) a quaternary ammonium salt and (B) hypromellose.
  2. 　更に、(C)アズレンスルホン酸及び／又はその塩を含む、請求項１に記載の口腔用組成物。 The oral composition according to claim 1, further comprising (C) azulene sulfonic acid and / or a salt thereof.
  3. 　前記(A)成分が、塩化セチルピリジニウム、塩化ベンゼトニウム、及び塩化ベンザルコニウムよりなる群から選択される少なくとも１種である、請求項１又は２に記載の口腔用組成物。 The oral composition according to claim 1 or 2, wherein the component (A) is at least one selected from the group consisting of cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride.
  4. 　ドライマウスの予防又は治療に使用される、請求項１～３のいずれかに記載の口腔用組成物。 The oral composition according to any one of claims 1 to 3, which is used for the prevention or treatment of dry mouth.
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Citations (3)

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JP2009242349A (en) * 2008-03-31 2009-10-22 Kobayashi Pharmaceut Co Ltd Dry mouth ameliorating agent
JP2013043869A (en) * 2011-08-25 2013-03-04 Lion Corp Ointment composition for oral cavity and oral cavity biofilm bactericide
JP2019006736A (en) * 2017-06-28 2019-01-17 小林製薬株式会社 Pharmaceutical composition

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JP2009242349A (en) * 2008-03-31 2009-10-22 Kobayashi Pharmaceut Co Ltd Dry mouth ameliorating agent
JP2013043869A (en) * 2011-08-25 2013-03-04 Lion Corp Ointment composition for oral cavity and oral cavity biofilm bactericide
JP2019006736A (en) * 2017-06-28 2019-01-17 小林製薬株式会社 Pharmaceutical composition

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