WO2008026310A1 - Agent protecteur pour une muqueuse orale contenant du tréhalose - Google Patents

Agent protecteur pour une muqueuse orale contenant du tréhalose Download PDF

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Publication number
WO2008026310A1
WO2008026310A1 PCT/JP2007/000911 JP2007000911W WO2008026310A1 WO 2008026310 A1 WO2008026310 A1 WO 2008026310A1 JP 2007000911 W JP2007000911 W JP 2007000911W WO 2008026310 A1 WO2008026310 A1 WO 2008026310A1
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WO
WIPO (PCT)
Prior art keywords
agent
protective agent
oral mucosa
oral
trehalose
Prior art date
Application number
PCT/JP2007/000911
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English (en)
Japanese (ja)
Inventor
Tsuyoshi Takato
Yuichi Tei
Yoshiyuki Mori
Shigeki Suzuki
Hideki Iimura
Original Assignee
Cellex K.K.
The University Of Tokyo
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Cellex K.K., The University Of Tokyo filed Critical Cellex K.K.
Priority to JP2008531954A priority Critical patent/JPWO2008026310A1/ja
Publication of WO2008026310A1 publication Critical patent/WO2008026310A1/fr

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    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms

Definitions

  • the present invention relates to an oral mucosa protective agent for protecting the mucous membrane in the oral cavity containing trehalose as an active ingredient. More specifically, the present invention relates to a protective agent for oral mucosa, which is effective as a therapeutic agent or preventive agent for dry mouth or dry mice, especially by protecting the tissue from dry irritation with trehalose.
  • Patent Document 1 relates to a pharmaceutical composition for transmucosal administration, and claim 1 contains “trehalose, ointment, cream, gel cream” , Lotion, aerosol, liquid, suppository
  • An invention consisting of “a pharmaceutical composition for transmucosal administration, characterized in that it is a dosage form” is described. That is, claim 1 of Patent No. 3, 4 1 8, 4 2 3 includes “a pharmaceutical composition for transmucosal administration containing trehalose and being a liquid”.
  • the invention disclosed in the publication is intended to alleviate the irritation caused by administration of a hormonal agent from the nasal cavity, and is not intended for oral administration.
  • Trehalose is formulated in a pharmaceutical composition for transmucosal administration (paragraph 0 0 0 6 of the same publication), and trehalose is not a physiologically active substance (paragraph 0 of the publication). Ten ) .
  • Patent Document 2 discloses the use of trehalose as a saccharide for “a pharmaceutical composition for preventing or treating skin or mucosal disease”.
  • “the mechanism of action of sugars is to regulate the state of water in the composition of extracellular fluids or intercellular fluids, and to supply monosaccharides that can be used as cytoplasmic energy, such as glucose and fructose, It is also thought that the reduction of the oxidative degradation of the intercellular fluid is delayed due to its reducibility ”(paragraph 0 0 0 7).
  • saccharides are considered to be an energy source, and there are no examples using trehalose.
  • Japanese Patent Application Laid-Open No. 6 1-1 0 0 5 1 2 (Patent Document 3) relates to “skin moisturizing composition and method”, “skin moisturizing composition containing an effective amount of trehalose” It has been found that it is possible to treat dry skin and / or suppress dryness of the skin by topical application. ”(Right line, page 2, lines 7 to 7).
  • Japanese Patent Application Laid-Open No. 6 1-1 0 0 5 1 2 discloses that trehalose is used only to prevent skin dryness. In other words, although trehalose has been suggested to prevent skin dryness, there is no mention or suggestion that it can protect the oral mucosa from dryness.
  • Patent Document 4 Japanese Patent No. 2,896,211
  • the gazette of the same publication basically uses the gum to promote saliva secretion, thereby drying the mouth. Is to prevent.
  • xylitol, a sugar alcohol, and trehalose, a disaccharide have completely different molecular structures and completely different physical properties except that they are sweeteners.
  • Patent Document 1 Japanese Patent Nos. 3, 4 1 8 and 4 2 3
  • Patent Document 2 Japanese Patent Laid-Open No. 2 0 0 2 _ 3 0 8 7 8 3
  • Patent Document 3 JP-A-6 1-1 0 0 5 1 2
  • Patent Document 4 Japanese Patent No. 2, 896, 211
  • An object of the present invention is to provide an oral mucosal protective agent for protecting the mucous membrane in the oral cavity from dry irritation during the treatment.
  • An object of the present invention is to provide a therapeutic or prophylactic agent for xerostomia or dry mice.
  • An object of the present invention is to provide a therapeutic or preventive agent for a traumatic ulcer caused by a denture.
  • the present invention basically relates to an oral mucosa protective agent containing trehalose as an active ingredient in an effective amount.
  • the oral mucosal protective agent of the present invention can effectively prevent the situation where the oral cavity dries, so that the treated part and the surrounding mucous membrane are particularly dry during the treatment. This is based on the knowledge that it is possible to prevent damage caused by dry stimulation caused by the above.
  • an agent containing an effective amount of trehalose as an active ingredient can effectively prevent a situation where the oral cavity dries, it is effective to suffer from xerostomia or dry mouth. Moisturizes the mouth of patients suffering from xerostomia or dry mouth, It is based on the knowledge that it is effective for the treatment of imouth. Since the oral mucosa protective agent of the present invention uses, for example, trehalose as an active ingredient, it can provide an oral mucosa protective agent with excellent taste.
  • the present invention relates to a mucosal protective agent for protecting the oral mucosa, which basically contains trehalose or a pharmaceutically acceptable solvate thereof as an active ingredient.
  • Trehalose acts as a substitute for water in tissues and cells, and even when water is lost from tissues and cells, it is thought to protect cells from damage caused by drying.
  • a preferred embodiment of the oral mucosa protective agent of the present invention is the above-mentioned oral mucosa protective agent containing a thickener, and the thickener is preferably pullulan.
  • the thickener is preferably pullulan.
  • a preferred embodiment of the oral mucosa protective agent of the present invention is the above-described oral mucosa protective agent containing a wetting agent, and since it contains a wetting agent, rapid evaporation of moisture due to rapid drying by air or the like.
  • a preferred embodiment of the oral mucosa protective agent of the present invention is the oral mucosa protective agent according to any one of the above, which contains an antioxidant.
  • a preferred embodiment of the oral mucosa protective agent of the present invention is the oral mucosa protective agent according to any one of the above, containing an antibacterial agent.
  • the oral mucosa protective agent is a liquid agent, and the pH of the liquid agent is 5.7 to 8.5 (5.7 or more and 8.5 or less, The same shall apply hereinafter.)
  • the oral mucosa protective agent according to any one of the above.
  • the pH of trehalose aqueous solution (30% aqueous solution) is 4.5 to 6.5.
  • the enamel that protects the tooth surface generally melts and causes caries.
  • Trehalose does not produce insoluble glucan, which contributes to caries with low acid production in the oral cavity. Trehalose also inhibits the adhesion of insoluble glucan derived from sugar by about 60%.
  • Preferred embodiments of the oral mucosal protective agent of the present invention include: “menthol, vanitol, peppermint oil, spearmint oil, methyl salicylate, eugenol, eucalypt !, limonene cetylpyridinium chloride, chlorogluconate One or more selected from the group consisting of xidine, triclosan, isopropylmethylphenol, dipotassium glycyrrhizinate, sodium azulene sulfonate, decalinium chloride, lysozyme chloride, hinokitiol, sodium lauroyl sarcosine, lactoferrin, and paraben
  • the oral mucosa protective agent according to any one of the above, which comprises the above compound.
  • the oral mucosal protective agent of the present invention contains an aromatic component, a bactericidal agent, a saliva component (enzyme, glycoprotein), an anti-inflammatory agent or an antifungal agent, and the like, and the aromatic property is adjusted. preferable.
  • Preferred embodiments of the oral mucosa protective agent of the present invention include: spray liquid (agent for injecting a chemical liquid toward a target site), liquid for spraying or vaporizing administration, mouthwash, mouthwash, foam aerosol,
  • spray liquid agent for injecting a chemical liquid toward a target site
  • liquid for spraying or vaporizing administration mouthwash, mouthwash, foam aerosol
  • the oral mucosa protective agent according to any one of the above, which is a perfusate or an infusion pack-containing solution is a perfusate or an infusion pack-containing solution. That is, the oral mucosal protective agent of the present invention can be made into a dosage form suitable for the purpose of the target disease.
  • a preferred embodiment of the oral mucosa protective agent of the present invention relates to the oral mucosa protective agent according to any one of the above, which is a therapeutic agent or preventive agent for xerostomia, or a therapeutic agent or prophylactic agent for dry mice. That is, according to the oral mucosal protective agent of the present invention, it is possible to effectively prevent a situation in which the oral cavity dries, so that it is possible to effectively prevent dry mouth or dry mouth from being affected. Moisturizes the oral cavity of patients affected by live mice and is effective in treating dry mouth or dry mice.
  • the present invention also provides use of trehalose for producing an oral mucosa protective agent.
  • the present invention also provides an oral mucosal membrane containing an effective amount of trehalose. It also provides a method for protecting the oral mucosa during the treatment, a method for treating xerostomia or dry mice, and a method for preventing xerostomia or dry mice, including the step of administering a protective agent to the subject.
  • an oral mucosa protective agent for protecting the mucous membrane in the oral cavity from dry stimulation can be provided. Since the oral mucosal protective agent of the present invention uses, for example, trehalose as an active ingredient, it can provide an oral mucosal protective agent with excellent taste.
  • an oral mucosal protective agent for protecting the mucous membrane in the oral cavity from dry irritation during the treatment.
  • a therapeutic or prophylactic agent for dry mouth or dry mice can be provided.
  • the present invention basically relates to an oral mucosal protective agent containing trehalose or a pharmaceutically acceptable solvate thereof as an active ingredient in an effective amount.
  • Oral mucosa protective agent means, in particular, an agent that protects the mucous membrane in the oral cavity from dryness irritation. Since the oral mucosa protective agent of the present invention uses, for example, trehalose as an active ingredient, it can provide an oral mucosa protective agent with excellent taste.
  • Tre /, loin means a non-reducing disaccharide in which two molecules of glucose are linked by 1,1.
  • Tre / Rose water-containing crystal trehalose, anhydrous crystal trehalose, trehalose-containing sugar, hi, hiichi trehalose
  • Any trehalose such as a, S-tre / sucrose (neotrehalose) ⁇ , S-tre / sucrose (isotrehalose) can be used.
  • water-containing crystal trehalose or water-free crystal trehalose of Hiichi Hiichi Trehalose is preferred.
  • Trehalose is known, for example, Patent Nos.
  • Described in the gazette includes the steps of preparing anhydrous water containing trehalose by adding anhydrous crystalline trehalose and / or amorphous anhydrous trehalose to prepare the aqueous solution containing trehalose, and drying the prepared aqueous solution containing trehalose. It can be produced by a method for producing a trehalose-containing powder composition.
  • the pharmaceutically acceptable solvate means a solvate of trehalose.
  • a solvate of trehalose is trehalose dihydrate.
  • the tissue is protected from dry irritation and the like.
  • an agent using trehalose dihydrate is preferable because it has a preferable tissue protecting ability.
  • Solvates include hydrates.
  • the compound of the present invention may absorb moisture, adhere to adsorbed water, or become a hydrate when left in the atmosphere or recrystallized. Such solvates are also included in “the solvate”.
  • Active ingredient means an ingredient having a function of protecting the mucous membrane in the oral cavity from dry irritation.
  • trehalose is an active ingredient.
  • active ingredients other than trehalose may be included as appropriate.
  • Effective amount means the amount of trehalose that is effective in protecting mucosal tissues from drying irritation.
  • Trehalose is generally contained in foods as a sweet additive, stabilizer, and texture-improving agent. Trehalose may also be added as a stabilizer in medicine.
  • trehalose is used as a liquid agent for preventing the tissue from drying out. Therefore, a larger amount of trehalose can be added than when it is added as a stabilizer in medicine. preferable.
  • the weight of trehalose contained in the oral mucosa protective agent may be adjusted as appropriate according to the intended use.
  • the content of trehalose in the oral mucosa protective agents 0.
  • the oral mucosa protective agent may feel extremely sweet, but it is included in the oral mucosa protective agent to effectively prevent dry irritation.
  • the content of trehalose may be 20 weight 0 / & to 80 weight 0 / o, or 25 weight% to 50 weight%.
  • the concentration may be adjusted appropriately according to the degree of thinning.
  • a preferred embodiment of the oral mucosa protective agent of the present invention relates to the oral mucosa protective agent according to any one of the above, which is a therapeutic agent or preventive agent for xerostomia or a dry mouse therapeutic agent or prophylactic agent. That is, according to the oral mucosa protective agent of the present invention, it is possible to effectively prevent a situation in which the oral cavity dries. Therefore, it is possible to effectively prevent dry mouth or dry mouth from being affected, and dry mouth or dry mouth. Moisturizes the mouth of patients affected by mice and is effective in treating dry mouth or dry mice.
  • the trehalose of the present invention When used as the above-mentioned therapeutic agent or prophylactic agent, it may be administered per se or may be administered in admixture with a pharmacologically acceptable carrier or the like. .
  • a pharmacologically acceptable carrier or the like Such an agent can be produced by a known method.
  • the agent using the compound of the present invention include a spray, a liquid for spray administration, a liquid for vaporization administration, a mouthwash, a mouthwash, a foam aerosol, a perfusate, or an infusion pack.
  • the spray is an agent that is contained in a spray container and sprayed.
  • a solution for spray administration is an agent that is stored in a container that is physically separated from the spray administration device, and is sprayed after being made suitable for spraying in the spray section as necessary.
  • the liquid agent for vaporization administration is an agent that is contained in a container that is physically separated from the vaporization administration part, vaporized as necessary, and administered from the vaporization administration part.
  • the mouthwash means a mouthwash or the like. However, the mouthwash of the present invention may be discharged after washing the oral cavity, or it prevents the oral cavity from drying or wets the oral cavity. It can be swallowed after being let down. In general, cleaning agents are discharged after cleaning the oral cavity, and are therefore unfavorable psychologically if accidentally swallowed.
  • the cleaning agent of the present invention basically contains only a compound having high biocompatibility, so there is no problem even if it is swallowed. Therefore, it is possible to provide psychologically superior cleaning agents. Impregnation
  • the drug is a liquid that is discharged from the mouth after rinsing.
  • liquids containing an effective amount of trehalose, particularly liquids and sprays are preferred.
  • the agent of the present invention may appropriately contain a thickener, a wetting agent, a pH adjusting agent and the like. That is, a preferred embodiment of the oral mucosa protective agent of the present invention is the oral mucosa protective agent described above containing a thickening agent.
  • a known pharmaceutically acceptable thickener can be appropriately used.
  • Thickeners include: "Pullulan, Gua gum, Lambda carrageenan, Tragacanth gum, Pectin, Mannan and other thickening polysaccharides, Methyl cellulose, Methyl hydroxypropyl cellulose, Ethyl cellulose (EC), Hydroxypropyl cellulose (HPC), Hydroxyl Methyl pyrmethylcellulose (HPMC), carboxymethylcellulose, carboxymethylethylcellulose or their salts, crystalline cellulose, cellulose acetate, cellulose acetate phthalate, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxy Cell mouth type derivatives such as propylmethyl cell mouth scallop, powdered cellulose, gum arabic, galactan, agar, quince seed, wheat starch, rice starch, Corn starch, potato starch, ginseng dolan, xanthan gum, succinoglucan, dextran, hyaluronic acid, albumin, casein, collagen
  • pullulan is preferable As demonstrated in the examples described later, pullulan has the above-mentioned effects, has good compatibility with trehalose, and also has the effect of dramatically increasing the protection effect of trehalose on drying stimuli. Pullulan is, for example, a pullulan powder with an average molecular weight of 10 million (trade name “ Ruran
  • pullulan powder with an average molecular weight of 200,000 (trade names“ Pull Run P F — 2 0 ”and“ Pull Run P I _ 2 0 ”) are commercially available. Any of these may be used.
  • the number average molecular weight of pullulan is 50,000 to 40,000 (50,000 to 40,000, the same shall apply hereinafter), preferably 150,000 to 250,000.
  • the content of the thickening agent is 5 to 100 parts by weight when trehalose is 100 parts by weight, and 10 to 80 parts by weight is acceptable. Part by weight to 50 parts by weight is more preferable.
  • oral mucosal protective agents as liquids or sprays, ensure appropriate viscosity and prevent deterioration of jetability due to gel formation and jelly formation to ensure good adhesion to mucosal tissues. From the viewpoint, the content in the liquid composition may be determined.
  • a wetting agent is a compound added to moisten and moisturize tissue.
  • wetting agents include mucin, glycerin, propylene glycol, sorbitol, and polyethylene glycol.
  • a wetting agent with excellent biocompatibility is desired.
  • Mucin is physiologically desirable because it is a moisturizer and moisturizer contained in saliva.
  • Glycerin is preferable in terms of taste and safety.
  • the content of the wetting agent is 5 to 100 parts by weight when trehalose is 100 parts by weight. 80 parts by weight 20 parts by weight to 60 parts by weight is more preferable.
  • An antioxidant is a compound for preventing tissue mucous membranes from being oxidized by oxygen in the air.
  • the oral mucosa protective agent of the present invention is preferably one that can reduce oxidative stimulation. Therefore, by including an antioxidant in the oral mucosa protective agent, it is possible to reduce oxidative stimulation and effectively prevent the liquid agent itself from being oxidized and deteriorated.
  • an antioxidant in the oral mucosa protective agent of the present invention an ascorbic acid derivative can be mentioned. As such an antioxidant, one with excellent stability and low irritation is desirable. From such a viewpoint, ascorbic acid glycoside is particularly preferable.
  • Antioxidants only need to be included in the oral mucosa protective agent in amounts that are generally contained in liquid preparations.
  • the antibacterial agent means a compound having an antibacterial action.
  • the oral cavity there are about 1 X 10 1 1 bacteria in 1 gram of tissue. And there are countless pathogens in those bacteria, and when these pathogens enter the living body, the living body will be damaged.
  • Saliva contains antibacterial substances such as lactoferrin lysozyme, which inhibits bacterial growth. Therefore, lactoferrin or lysozyme that is contained in saliva and has excellent biological friendliness is preferable as an antibacterial agent. Lactoferrin has a function to bind ferric ions in the oral cavity.
  • an oral mucosal protective agent containing lysozyme is preferable because it can degrade the cell wall of cells and kill bacteria.
  • known disinfectants may be used. Specifically, isopropyl methylphenol, shoji oil, thymol
  • Chlorhexidine hydrochloride or cetylpyridinium chloride It is preferable that these antibacterial agents contain an effective amount to exert antibacterial action. Yes.
  • a preferred embodiment of the oral mucosa protective agent of the present invention is the oral mucosa protective agent according to any one of the above, wherein the oral mucosa protective agent is a liquid agent, and the pH of the liquid agent is 5.7 to 8.5. It is.
  • the pH of trehalose aqueous solution (30% aqueous solution) is 4.5 to 6.5. When the pH is less than 5.5, the enamel that protects the tooth surface generally melts and causes caries. Trehalose has low acid production in the oral cavity, and no insoluble glucan, which contributes to caries, has been observed. Trehalose also suppresses adhesion of insoluble glucan derived from sugar by about 60%.
  • the agent of the present invention is also intended to be used without irritating the oral cavity with water, etc. after administration. In order to prevent such a situation, it is preferable to set the acidity as described above.
  • an alkaline pH adjusting agent or an acidic pH adjusting agent may be added as appropriate.
  • an alkaline agent “sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, calcium carbonate, calcium lactate, disodium succinate, sodium malate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, phosphorus
  • trisodium acid sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, calcium carbonate, calcium lactate, disodium succinate, sodium malate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, phosphorus
  • the acid agent one or more selected from the group consisting of “acetic acid, citrate, tartaric acid, propionic acid, hydrochloric acid, fumaric acid, adipic acid, benzoic acid, malic acid, phosphoric acid, lactic acid, gluconic acid” Compounds.
  • Examples of the pharmacologically acceptable carrier include sterilized water, purified water, distilled water, sterilized organic solvent, aqueous starch, artificial saliva, physiological saline, alcohol, oil, and starch.
  • the oral mucosa protective agent may contain one appropriately selected from preservatives and flavoring agents.
  • Preferred embodiments of the oral mucosal protective agent of the present invention include "menthol, gantoyl, peppermint oil, spearmint oil, methyl salicylate, eugenol, eucalyptol, limonene cetylpyridinium chloride, chlorhexidine gluconate, Triclosan, isopropylmethylphenol, glycy Any one of the above-mentioned compounds containing one or more compounds selected from the group consisting of dipotassium ruritinate, sodium azulenesulfonate, decalinium chloride, lysozyme chloride, hinokitiol, sodium lauroyl sarcosine, lactoferrin, and paraben That is, the oral mucosa protective agent of the present invention contains an aromatic component, a bactericidal agent, a saliva component (enzyme
  • preservatives for example, paraoxybenzoates such as methylparaben and propylparaben, chlorobutanol, benzyl alcohol, alcohols such as phenylethyl alcohol, benzalkonium chloride, phenol, cresol Such phenols, thimerosal, dehydroacetic acid, and sorbic acid.
  • flavoring agents include sweeteners, acidulants, and fragrances.
  • Diluents include sterilized water, sterilized organic solvents, aqueous starch, artificial saliva, and physiological saline.
  • the agent of the present invention can be produced according to a known method using the compound of the present invention or the pharmaceutical composition of the present invention.
  • the liquid can be obtained by using the compound of the present invention or the pharmaceutical composition of the present invention and mixing it with sterilized water, sterilized organic solvent, aqueous starch, artificial saliva, physiological saline or the like.
  • the gum-like oral mucosa protective agent can be produced according to a known method for producing a gum.
  • the amount of the compound of the present invention to be used may be appropriately adjusted according to symptoms, age, sex, administration method and the like.
  • surgery may be performed after rinsing the mouth with the oral mucosal protective agent of 5 m I to 1 O O m I of the present invention.
  • a liquid or spray oral mucosa protective agent may be appropriately administered to the affected area and surrounding mucosa.
  • the mouth should be rinsed with a liquid oral mucosal protective agent of 1 m I to 1 O O m I as a prophylactic or therapeutic agent for xerostomia or dry mouth.
  • the frequency of administration may be, for example, 1 to several times per day depending on the symptoms.
  • trehalose or a pharmaceutically acceptable product thereof is used as a treatment target.
  • a method for treating xerostomia or dry mice which comprises administering an oral mucosal protective agent for protecting the mucous membrane in the oral cavity containing the solvate as an active ingredient.
  • the oral mucosal protective agent can be appropriately selected from the various patterns described above.
  • the present invention relates to the use of trehalose or a pharmaceutically acceptable solvate thereof for producing a prophylactic or therapeutic agent for dry mouth or dry mouth (especially use as a main component). Also provide.
  • Trehalose (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) 10 g and pullulan (manufactured by Hayashibara Biochemical Laboratories Co., Ltd.) 4 g were dissolved in sterile purified water (manufactured by Hikari Pharmaceutical Co., Ltd.). The solution was adjusted to pH 7.4 using 0.2 m o I / I sodium bicarbonate aqueous solution, and sterilized purified water (manufactured by Hikari Pharmaceutical Co., Ltd.) was added to make 1 O O g. Filtration was performed using a 0.22 micrometer filter to obtain an oral mucosa protective agent. Sodium bicarbonate was a Japanese pharmacopoeia product.
  • Example 1 Example 1
  • Trehalose manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • pullulan manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • concentrated glycerin 5 g dissolved in sterile purified water did. Adjust the acidity of the solution to pH 7.4 using an aqueous solution of 0.1 mol / I sodium bicarbonate, add sterile purified water (manufactured by Hikari Pharmaceutical Co., Ltd.), and add 100 g did.
  • Using a filter with a pore size of 0.22 micrometer it was filtered to obtain an oral mucosa protective agent.
  • Concentrated glycerin and sodium bicarbonate were Japanese Pharmacopoeia.
  • Trehalose manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • pullulan manufactured by Hayashibara Biochemical Laboratories Co., Ltd.
  • concentrated glycerin 2 g Dissolved in company manufacture Adjust the acidity of the solution to pH 7.4 using 0.03 g aqueous solution of 0.1 mol / I sodium bicarbonate, add sterile purified water (manufactured by Hikari Pharmaceutical Co., Ltd.), and add 1 OO g It was.
  • An oral mucosa protective agent was obtained by filtration using a 0.22 micrometer filter. Concentrated glycerin and sodium hydrogen carbonate were Japanese Pharmacopoeia.
  • Example 1 The oral mucosa protective solutions obtained in Example 1, Example 2 and Comparative Example were evaluated using 4 subjects.
  • the evaluation procedure is as follows.
  • Procedure 1 Place a roll kette on the bilateral maxillary second molar flank and mandibular mouth yard, which is the salivary gland opening, and apply the solution of Example 1 and Example 2 or the reference sample as a control to the palate. , Sprayed on the left and right mucous membranes and the back of the tongue (total 1.2 g) to moisten the oral cavity.
  • Procedure 2 A byte block was placed on the right molar part, an intravaginal vacuum was placed on the left jaw corner of the lower jaw, aspirated, air flow was generated in the oral cavity, and the air was dried. After 5 minutes, the intraoral vacuum was removed.
  • Step 3 Afterwards, the salivary duct was attached, the tip of the tongue was attached to the lower gum, and the mouth was left open for 5 minutes.
  • Table l. 3 ⁇ 4 Reduce moisture on the back surface.
  • Example 1 It can be seen from Table 1 that the transition of the moisture on the back surface of the tongue significantly decreases in the dry environment of the comparative example. Comparing Example 1 or Example 2 with the comparative example, it can be seen that the example can more effectively prevent the mucous membrane from drying than the comparative example. There was no significant difference between Example 1 and Example 2 in the persistence of moistness in the mouth, and Example 2 was slightly better. In Example 1, sweet taste was weaker than in Example 2. Subject B gained an unclear taste. In addition, Example 3 had a strong sweet taste and many people preferred Example 2.
  • Dry protection performance was evaluated by examining changes in oral mucosa protective solutions obtained in Example 2 and the comparative example by visual observation of the filiform nipple with a digital camera using five subjects.
  • the evaluation procedure was as follows.
  • Procedure 1 Roll to the bilateral maxillary second molar side of the salivary gland opening and lower yard Place a jar, and use the solution of the example or the reference solution as a control.
  • the spray was sprayed on four places on the back of the tongue (1.2 g in total) to moisten the oral cavity.
  • Step 2 Place a byte block on the right molar part, place an intra-oral vacuum on the left mandibular corner of the mandible, and suck it to create an air flow in the oral cavity.
  • Step 3 After that, the salivary duct was attached, the tongue tip was attached to the lower gum, and the mouth was kept open for 5 minutes.
  • step 2 Before the start, after step 2 and after step 3, the state of the papilla was observed with a digital force lens (Micro Skin Scope, Inc.) under visible light.
  • a digital force lens Micro Skin Scope, Inc.
  • step 2 Before starting, after step 2 and after step 3, the size of the nipple papilla was photographed with a digital camera (Micro Skin Scope, Inc.) under visible light, together with the reference (Machinichi), The major axis and minor axis were measured from the image and the area corresponding to the ellipse was calculated. The results are shown in Table 2.
  • Table 2 shows the change in the area ratio after 5 minutes and 10 minutes when the area of the nipple nipple before spraying is 1.000. Due to air drying, the fungiform nipples are slightly atrophic and reduced in area in the liquid of the example, but there is no significant difference between before and after spraying, before and after spraying, after 10 and after 5 and 10 minutes. Inhibition of unacceptable contraction was observed. In the reference example, obvious atrophy was observed after 5 and 10 minutes, and there was a significant difference between before and after spraying, before and after spraying, after 10 and after 5 and 10 minutes. Shrinkage due to drying. After 10 minutes, it shrank to 0.505 before spraying.
  • the oral mucosa protective agent is effective during dental surgery and as a therapeutic or prophylactic agent for xerostomia or dry mouth, it can be suitably used in the pharmaceutical industry.

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  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention a pour but de proposer un agent protecteur pour une muqueuse orale, destiné à protéger la muqueuse dans la cavité buccale vis-à-vis d'une irritation sèche. Le but peut être atteint, en principe, par un agent protecteur pour une muqueuse orale contenant une quantité efficace de tréhalose en tant qu'ingrédient actif. Comme il est démontré par les exemples, conformément à l'agent protecteur pour une muqueuse orale de l'invention, une condition sèche dans la cavité buccale peut être efficacement empêchée ; par conséquent, en particulier pendant une opération chirurgicale, le risque de recevoir une lésion provenant d'une irritation sèche provoquée par le séchage de la zone subissant l'opération chirurgicale et de sa muqueuse périphérique est empêché.
PCT/JP2007/000911 2006-08-29 2007-08-27 Agent protecteur pour une muqueuse orale contenant du tréhalose WO2008026310A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2008531954A JPWO2008026310A1 (ja) 2006-08-29 2007-08-27 トレハロース含有口腔粘膜保護剤

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JP2006232878 2006-08-29
JP2006-232878 2006-08-29

Publications (1)

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WO2008026310A1 true WO2008026310A1 (fr) 2008-03-06

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* Cited by examiner, † Cited by third party
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JP2011026269A (ja) * 2009-07-28 2011-02-10 Wakodo Co Ltd 口腔用清拭材
JP2014518555A (ja) * 2011-04-19 2014-07-31 アームズ ファーマシューティカル エルエルシー 有害な微生物を阻害する方法及びそのためのバリア形成組成物
US20150080331A1 (en) * 2013-09-16 2015-03-19 Healios Oncology Nutrition, LLC Glutamine & trehalose compositions
JP2016063832A (ja) * 2016-01-26 2016-04-28 公益財団法人ヒューマンサイエンス振興財団 容器詰飲料
US10426761B2 (en) 2011-04-19 2019-10-01 Arms Pharmaceutical, Llc Method for treatment of disease caused or aggravated by microorganisms or relieving symptoms thereof
JP2020070279A (ja) * 2018-11-02 2020-05-07 アース製薬株式会社 口腔用薬液噴霧製品
CN112451416A (zh) * 2020-12-04 2021-03-09 吉林省七维生物科技有限公司 一种医用口腔含漱液及其制备方法
CN114504646A (zh) * 2022-02-18 2022-05-17 深圳南粤药业有限公司 一种含粘蛋白的人工唾液组合物及其制备方法与应用
EP4125927A4 (fr) * 2020-04-17 2023-12-13 Next21 Kabushiki Kaisha Médicament contenant du tréhalose ou un dérivé de tréhalose et vaporisateur nasal

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011026269A (ja) * 2009-07-28 2011-02-10 Wakodo Co Ltd 口腔用清拭材
US10426761B2 (en) 2011-04-19 2019-10-01 Arms Pharmaceutical, Llc Method for treatment of disease caused or aggravated by microorganisms or relieving symptoms thereof
JP2014518555A (ja) * 2011-04-19 2014-07-31 アームズ ファーマシューティカル エルエルシー 有害な微生物を阻害する方法及びそのためのバリア形成組成物
JP2017081951A (ja) * 2011-04-19 2017-05-18 アームズ ファーマシューティカル エルエルシーＡｒｍｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｌｌｃ． 有害な微生物を阻害する方法及びそのためのバリア形成組成物
US10398645B2 (en) 2011-04-19 2019-09-03 Arms Pharmaceutical, Llc Method of inhibiting harmful microorganisms and barrier-forming composition therefor
US20150080331A1 (en) * 2013-09-16 2015-03-19 Healios Oncology Nutrition, LLC Glutamine & trehalose compositions
US9849144B2 (en) * 2013-09-16 2017-12-26 Healios Oncology Nutrition, LLC Glutamine and trehalose compositions
JP2016063832A (ja) * 2016-01-26 2016-04-28 公益財団法人ヒューマンサイエンス振興財団 容器詰飲料
JP2020070279A (ja) * 2018-11-02 2020-05-07 アース製薬株式会社 口腔用薬液噴霧製品
JP7140636B2 (ja) 2018-11-02 2022-09-21 アース製薬株式会社 口腔用薬液噴霧製品
EP4125927A4 (fr) * 2020-04-17 2023-12-13 Next21 Kabushiki Kaisha Médicament contenant du tréhalose ou un dérivé de tréhalose et vaporisateur nasal
CN112451416A (zh) * 2020-12-04 2021-03-09 吉林省七维生物科技有限公司 一种医用口腔含漱液及其制备方法
CN114504646A (zh) * 2022-02-18 2022-05-17 深圳南粤药业有限公司 一种含粘蛋白的人工唾液组合物及其制备方法与应用

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