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WO2006038319A1 - Préparation solide intra-orale fixée - Google Patents

Préparation solide intra-orale fixée Download PDF

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Publication number
WO2006038319A1
WO2006038319A1 PCT/JP2005/003869 JP2005003869W WO2006038319A1 WO 2006038319 A1 WO2006038319 A1 WO 2006038319A1 JP 2005003869 W JP2005003869 W JP 2005003869W WO 2006038319 A1 WO2006038319 A1 WO 2006038319A1
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WO
WIPO (PCT)
Prior art keywords
solid preparation
shape
mucosa
contact surface
preparation according
Prior art date
Application number
PCT/JP2005/003869
Other languages
English (en)
Japanese (ja)
Inventor
Masao Kakehi
Original Assignee
Kobayashi Pharmaceutical Co., Ltd.
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.)
Filing date
Publication date
Application filed by Kobayashi Pharmaceutical Co., Ltd. filed Critical Kobayashi Pharmaceutical Co., Ltd.
Publication of WO2006038319A1 publication Critical patent/WO2006038319A1/fr

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Classifications

    • 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

Definitions

  • the present invention relates to a solid preparation that stably settles in the oral cavity, particularly on the mucous membrane of the palate.
  • oral mucosa preparations for oral mucosa in which active ingredients such as drugs are administered to the oral mucosa and saliva by adhering (adhering) to the oral mucosa have been proposed and are actually distributed.
  • these oral mucosal preparations can be used not only for systemic action of the active ingredient via mucosal absorption, but also as a dosage form for oral dissolution or sustained release. It is intended to gradually deliver the active ingredient to the gastrointestinal system while suppressing the occurrence of side effects of the drug, or to allow the active ingredient to act on a local area such as the throat for a long time.
  • the oral mucosa preparation is of a type that adheres to the mucous membrane, and therefore has the advantage of avoiding the above-mentioned disadvantages observed in preparations such as troches and drop preparations.
  • tablet-type oral mucosal preparations In contrast to ointment-type and film-type oral mucosal preparations, tablet-type oral mucosal preparations generally have good shape retention and can contain sufficient amounts of active ingredients. , Oral mucosa It can be said that it is ideal as a dosage form for pharmaceutical preparations.
  • bioadhesive tablets in which linear and Z or curved concave portions are formed on one surface thereof, and edible
  • a candy or tablet see Patent Document 2 and the like, which is formed into a plate-like body having a thickening agent and having a concave fitting at the center of at least one surface.
  • Patent Document 1 JP-A-11-152221
  • Patent Document 2 Japanese Patent Application Laid-Open No. 64-86835
  • the present invention provides a solid preparation that does not cause disintegration due to the foreign body sensation exhibited by the preparation for oral mucosa recognized in the prior art, while maintaining good adhesion to the oral mucosa. With the goal.
  • the gist of the present invention resides in a solid preparation having a mucosal contact surface whose central longitudinal cross-sectional shape is formed in a convex shape and containing an adhesive.
  • central longitudinal cross-sectional shape refers to the flat surface from the top (the thickest portion) of the solid preparation located at the center of the solid product placed on the flat surface. This refers to the cross-sectional shape that appears by cutting the solid preparation in the direction perpendicular to the thickness direction of the solid preparation.
  • central cross-sectional shape refers to a midpoint located half the height of the top of a solid formulation located in the middle of a solid formulation placed on a flat surface. Thus, it refers to a cross-sectional shape that appears by cutting a solid preparation in a direction parallel to the flat surface.
  • minor axis refers to one of the shorter diameters of a pair of plane axes that define the central longitudinal sectional shape or the central transverse sectional shape of a solid preparation.
  • major axis refers to the other diameter longer than the minor axis.
  • the unit expressing the amount of the component of the solid preparation of the present invention including the pressure-sensitive adhesive is expressed in% by weight.
  • a solid preparation comprising a mucosa contact surface having a central longitudinal cross-sectional shape formed into a convex shape and containing an adhesive.
  • the pressure-sensitive adhesive contained in the solid preparation of the present invention is a water-soluble polymer substance that develops adhesiveness when it comes into contact with the mucous membrane in the oral cavity, and is a polysaccharide, a cellulosic polymer substance, a synthetic polymer substance, a natural substance Water-soluble polymer materials that are derived from polymer materials, amino acid-based polymer materials, rubber-based polymer materials, and the like and commonly used in oral products can be used.
  • pullulan, pullulan derivatives and polysaccharides such as starch; hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropinoremethinoresenorerose, hydroxyethinoremethenoresenorelose, canoleboxymethylcellulose salts (carboxymethylcellulose, carboxymethylcellulose sodium) And carboxymethylcellulose potassium), methylcellulose, ethyl cellulose, polyacrylic acid, polyacrylates (such as sodium polyacrylate and acrylic acid-octyl ester copolymer), and copolymers of methacrylic acids (meta Cellulosic polymers such as polymers of crylic acid and n-butyl acrylate, polymers of methacrylic acid and methyl methacrylate, and polymers of methacrylic acid and ethyl acrylate); carboxyvinyl polymer, polyethylene Synthetic polymer substances such as glycol, polybulylpyrrolidone, polybulualcohol; lectin
  • the amount of these pressure-sensitive adhesives varies depending on the type of pressure-sensitive adhesive and the intended use of the solid preparation, but is usually about 5.0 to about 80% by weight, preferably about 5.0 to about It is prepared in the range of 70% by weight, and most preferably from about 5.0 to about 60% by weight. This means that if it is less than about 5.0% by weight, it is difficult to stably fix the solid preparation on the palate surface, and if the amount exceeds about 60% by weight and eventually about 80% by weight, the adhesive This is due to the difficulty in blending ingredients other than the agent and the appearance of an unpleasant stickiness when taken.
  • the active ingredient having a pharmacological effect that can be blended in the solid preparation of the present invention can be used as long as it is technically capable of being incorporated into tablets, for example, crude drugs, Antitussive expectorant, halitosis remover, bactericidal disinfectant, antibiotics, stomatitis agent, topical anesthetic, periodontal disease agent, caries preventive agent, antirheumatic agent, hypersensitivity agent, neurostimulant, analgesic , Antiparkinsonian,
  • crude drugs Antitussive expectorant, hal
  • Herbal medicines include licorice, kiyonin, chixenin ginseng, peanut, batachinoki, genjin, koboushi, senega, chimpi, trash shazenso, baimo, bukkyou, kikiyou, maou, hange, shazenso, tokon, carrot, oohi, kehi, Pepper, stasha, chili, capsicum, nutmeg, rose, ryu nou, giraffe, eucalyptus, wikiweed, genus pepper, scallops, ketchei, and the like can be used in the present invention. Any one of these powers is not limited to these. Can be used alone, or two or more can be used in combination.
  • Antitussive expectorant agents include dihydrocodine phosphate, hydrocodine sexoxanol phosphate, codine phosphate, dextromethorphan phenolphthalein, dextromethorphan hydrobromide, chipepidine citrate , Tipepidine hibenzate, Nos force pin, Nos force pin hydrochloride, potassium guaiacol sulfonate, guaifenesin, dextromethorphan, phenolphthalate phosphate, ambroquinol hydrochloride, glycerin monoguaiacol ether, etc. can be used in the present invention. Any one of these forces can be used alone, or two or more can be used in combination.
  • menthol As a bad breath remover, menthol, eucalyptus, key skin aldehyde, vanillin, lemongrass, chlorophyllins, polyphenols, flavonoids, camphor, bonito oil, wikiweed, tea ingredients, etc. can be used in the present invention.
  • the present invention is not limited to these. Only one of these can be used, or two or more can be used in combination.
  • Disinfectants include cetyl pyridinium salt, chlorhexidine hydrochloride, decalium chloride, chlorhexidine dalconate, isopropylmethylphenol, iodine, povidone, benzethonium chloride, benzalkco chloride -Um, triclosan, thymol, yowi calum, phenol, hinokitiol, etc. are the forces that can be used in the present invention. The above can also be used together.
  • Antibiotics include minocycline hydrochloride, cephalexin, tetracycline hydrochloride, fradiomycin, and the like, which are not limited to these, and only one of these may be used, or Two or more types can be used together it can.
  • the force that can be used in the present invention is not limited to these, and any one of these forces may be used, or both Can also be used together.
  • Examples of local anesthetics include dibu force hydrochloride, lidocaine, benzocaine, pro force in, tetra force in and the like that can be used in the present invention. You can use only one type, or you can use two or more types together.
  • cephalexin As an agent for periodontal disease, cephalexin, tetracycline hydrochloride, minocycline hydrochloride, fradiomycin and the like can be used in the present invention. Any one of these is not limited thereto. It is possible to use only one or use two or more types together.
  • sodium fluoride, potassium fluoride, ammonium fluoride, stannous fluoride, sodium monofluorophosphate and the like can be used in the present invention. Any one of these forces can be used, or two or more can be used in combination.
  • potassium nitrate ammonium lactate, strontium chloride, and the like are powers that can be used in the present invention. Or two or more types can be used in combination.
  • analgesics examples include indomethacin, ibuprofen, acetaminophen, salicylic acid, aspirin, diclofenac sodium, ketoprofen, fluefenamic acid, fenbufen, piroxicam, flurbiprofen, aspirin aluminum, ethenzamid, isopropylantipyrine, and sazapyrine.
  • the forces that salicylamide and the like can be used in the present invention are not limited to these. Any one of these forces can be used alone, or two or more can be used in combination.
  • neurostimulants include methylephedrine, methylephedrine hydrochloride, phenylpronoline hydrochloride, methoxyphenamine hydrochloride, trimethquinol hydrochloride, diprofylline, aminophylline, theophylline, caffeine, caffeine benzoate, Forces that anhydrous caffeine and the like can be used in the present invention are not limited to these. Only one type can be used, or two or more types can be used in combination.
  • sodium cromoglycate can be used in the present invention.
  • diphenhydramine hydrochloride bromide reryl urea, allylic isopropyl cetyl urea, power nokoso, buttoukou, kanso, sansonin and the like can be used in the present invention. You can use only one type, or you can use two or more types together.
  • Anti-inflammatory agents include lysozyme chloride, glycyrrhetinic acid, glycyrrhizic acid, dipotassium dallicyllittinate, ammonium glycyrrhizinate, kanzo, indomethacin, allantoin, azulene, hydrocortisone, prodnisolone, fluorocinolone acetonide , Methyl prednisolone, hydrocortisone acetate, tranexamic acid, and the like can be used in the present invention. These are not limited to these. Any one of these forces can be used, or two or more can be used in combination. .
  • antihistamine examples include chlorfelamine maleate, diphenhydramine hydrochloride, diphenhydramine, diphenhydramine salicylate, carbinoxamine maleate, talemastine fumarate, metataridine hydrochloride, dimenhydrinate, promethazine hydrochloride, promethazine hydrochloride and the like. Forces that can be used These are not limited to these, but only one type can be used, or two or more types can be used in combination.
  • lysozyme chloride dextranase, amylase, and the like can be used in the present invention. These are not limited to these. Two or more types can be used in combination.
  • vitamin Bl vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin E, vitamin A, and derivatives thereof can be used in the present invention. Only one of these can be used, or two or more can be used together.
  • Gastrointestinal drugs include funnel extract, cimetidine, famotidine, latidine hydrochloride, sodium hydrogen carbonate, precipitated calcium carbonate, magnesium aluminate metasilicate, neucillin, synthetic hydrotalcite, borei, aluminum kaylate, keihi , Obata, Shokyo, Senbu Li, copper chlorophyllin sodium, copper chlorophyllin potassium, aldioxa, methylmethionone sulfone chloride, sucralfate, cetraxate hydrochloride, teprenone, glycyrrhizic acid, glycyrrhizinate, etc. can be used in the present invention, but are not limited thereto. It is possible to use only one type of these forces, or use two or more types together.
  • viable colonic fungi examples include bifidobacteria, acidophilus, fecalis, lactobacilli, thermophilus, lactic acid bacteria (such as spore-forming lactic acid bacteria (latavon)), and butyric acid bacteria. Power Any one of these, not limited to these, can be used alone, or two or more can be used in combination.
  • succinate As laxatives, sennoside, senna, bisacodyl, picosulfate sodium, phenovaline, phenolphthalein, diau, aloe, malt extract, castor oil, heavy magnesium oxide, plantago's butter, dioctylsodium sulfo
  • the force that succinate can be used in the present invention is not limited to these. Any one of these may be used alone, or two or more may be used in combination.
  • metocarbamol As the agents for stiff shoulder muscle pain and joint pain, metocarbamol, sodium chondroitin sulfate, and the like are powers that can be used in the present invention. Or both can be used together.
  • Examples of the refreshing agent include 1 menthol, dl menthol, heart force oil, camphor, heart force water, borneol, peppermint essential oil, spearmint essential oil, and the like that can be used in the present invention. Any one of these can be used alone, or two or more can be used in combination.
  • the blending amount of these refreshing agents is adjusted within a range that does not hinder the effect of the active ingredient and reliably imparts a refreshing feeling, but is usually prepared within a range of about 10% by weight or less based on the total amount of the solid preparation. Is done.
  • Binders include sugars (such as glucose), sugar alcohols (sorbitol, xylitol) , Erythritol, mannitol, etc.), polybulurpyrrolidone, starches, macrogol, dextrin, tragacanth, gelatin, polybulal alcohol, shellac, gum arabic, sodium alginate, hydroxypropylcellulose, etc. Although it can be used, but not limited to these, only one of these may be used, or two or more may be used in combination.
  • sugars such as glucose
  • sugar alcohols sorbitol, xylitol
  • Erythritol Erythritol, mannitol, etc.
  • polybulurpyrrolidone starches
  • macrogol dextrin
  • tragacanth gelatin
  • polybulal alcohol shellac
  • gum arabic sodium alginate
  • hydroxypropylcellulose etc.
  • the blending amount of these binders is adjusted within a range that does not hinder the effect of the active ingredient and reliably maintains the shape retention of the solid preparation, but is usually about 90% by weight or less based on the total amount of the solid preparation. Prepared with a range.
  • sweetener examples include sodium saccharin, stepioside, stevia extract, aspartame, xylitol, starch syrup, honey, sorbitol, maltitol, mannitol, saccharides (lactose, sucrose, fructose, glucose, etc.). However, it is not limited to these, it is possible to use only one of these, or to use two or more together.
  • the amount of these sweeteners is adjusted within a range that does not hinder the effect of the active ingredient and reliably maintains the shape retention of the solid preparation, but is usually about 90% by weight or less based on the total amount of the solid preparation. Prepared with a range.
  • Natural flavors (spearmint oil, varnish oil, eucalyptus oil, wintergreen oil, cassia oil, clove oil, thyme oil, sage oil, lemon oil, orange oil, heart power oil, power rudamon oil, Coriander oil, mandarin oil, lime oil, lavender oil, rosemary oil, laurel oil, camomil oil, caraway oil, marjoram oil, bay oil, lemongrass oil, orina gum oil, pine-dollar oil, etc.), synthetic Perfume (Carbon, Anethole, Cineol, Methyl salicylate, Cynamic aldehyde, Eugenol, Thymol, Linalol, Linalyl acetate, Limonene, Menthone, Menthyl acetate, Pinene, Octylaldehyde, Citral, Pregon, Calbele acetate, Anisaldehyde Natural fragrances listed above and , Or a blended fragrance obtained by mixing a fragrance arbitrarily
  • the blending amount of these flavors is adjusted within a range that does not hinder the effect of the active ingredient and reliably maintains the shape retention of the solid preparation, but is usually about 5.0% by weight or less based on the total amount of the solid preparation.
  • disintegrants starches, methylcellulose, crystalline cellulose, cellulose derivatives (such as sodium carboxymethylcellulose), alginic acid, alginates, carbonates, organic acids, polyvinylpyrrolidone, cross-linked polybutylpyrrolidone and the like are used in the present invention. Although it is possible, it is possible to use only one of these forces, or to use two or more of them together.
  • the amount of these disintegrants is adjusted within the range that does not impede the effect of the active ingredient and reliably maintain the shape retention of the solid preparation, but is usually about 80% by weight or less based on the total amount of the solid preparation. It is prepared in the range of
  • Lubricants include talc, metal sarcophagus, fatty acids (such as stearic acid), stearates (such as magnesium stearate), talc, sucrose fatty acid esters, hydrous silicon dioxide, light anhydrous key acid, dry water Acid-aluminum gel, macrogol, etc. can be used in the present invention, but are not limited to these. Any one of these forces can be used, or two or more can be used in combination. . Of these, talc, metal stalagmite, fatty acids (such as stearic acid), stearate (such as magnesium stearate), and the like can be suitably used for tableting the solid preparation of the present invention.
  • the blending amount of these lubricants is adjusted within a range that does not hinder the effect of the active ingredient and reliably maintains the shape retention of the solid preparation, but is usually from about 0.01 to about 10 to the total amount of the solid preparation. It is prepared in the range of% by weight.
  • colorant blue 1 and yellow 4, titanium dioxide, copper chlorophyllin sodium and the like can be used in the present invention. These are not limited to these, and any one of these forces is used. Or two or more types can be used together.
  • the blending amount of these colorants is adjusted within a range that does not hinder the effect of the active ingredient and reliably maintains the shape retention of the solid preparation, but is usually about 1.0% by weight or more based on the total amount of the solid preparation. Prepared in the following range.
  • Preservatives include benzoic acids, salicylic acids, sorbic acids, norabens, cetylpyridinium chloride, decalinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine chloride, chlorhexidine darconate, isopropylmethylphenol, Powers that can be used in the present invention, such as trichomes, hinokitiol, phenol, etc., are not limited to these. More than one kind can be used in combination.
  • sustained-release regulator polyvinyl acetate, ethyl cellulose, aminoalkyl metaacrylate copolymer, and the like can be used in the present invention. They can be used or both can be used together.
  • sucrose fatty acid ester polyoxyethylene hydrogenated castor oil, sorbitan monostearate, polysorbate, glyceryl monostearate, sodium lauryl sulfate, lauromacrogol and the like can be used in the present invention.
  • a certain force It is not limited to these. Any one of these forces can be used, or two or more can be used in combination.
  • the blending amount of these colorants is adjusted within a range that does not hinder the effect of the active ingredient and reliably maintains the shape retention of the solid preparation, but is usually about 5.0% by weight or less based on the total amount of the solid preparation. Prepared with a range.
  • solubilizer glycerin, concentrated glycerin, propylene glycol, ethanol, fluidized rubber ⁇ raffin, purified water, macrogol, polysorbate and the like can be used in the present invention, but are not limited thereto. Any one of these can be used alone, or two or more can be used in combination.
  • wetting agent glycerin, propylene glycol, sorbitol solution, water, ethanol, dilute ethanol and the like can be used in the present invention. Or you can use two or more types together.
  • the solid preparation of the present invention can be produced by a conventional tableting preparation method.
  • a certain amount of the powder raw material obtained through the process of micronizing the raw material of the solid preparation and mixing the powder is directly pressed into a desired shape using a punch, die or press and compressed into tablets. Is done.
  • a granulated product obtained by adding a liquid component such as a fragrance to a finely powdered raw material can be used as a powder raw material or a part thereof.
  • a granulated product obtained by granulating a finely pulverized raw material without adding a liquid component can be used as a powder raw material or a part thereof.
  • the inventor of the present application has conducted extensive research to alleviate the fragility (disintegration) of a solid preparation of the type that is fixed in the oral cavity.
  • the idea was to form a convex shape. It has been clarified that the cracking phenomenon of the solid preparation is caused by a gap formed between the palate surface (curved surface) and the solid preparation. In other words, when the gap between the palate surface and the solid preparation becomes large, the contact area between the palate surface and the solid preparation decreases, that is, the support area of the solid preparation is reduced. As a result, the solid preparation is liable to be destroyed upon contact with the tongue.
  • the solid preparation of the type that settles in the oral cavity is markedly reduced in adhesion to the oral mucosa when cracked in the mouth.
  • the present inventor who should solve these problems blends a solid preparation with an adhesive, and forms the central longitudinal cross-sectional shape of the mucosa-contacting surface into a convex shape so that the The contact area with the solid preparation was increased, and the solid preparation was made difficult to break.
  • This configuration improves the shape retention while maintaining the adherence of the solid preparation to the oral mucosa and eliminates even the foreign body sensation that was observed with conventional solid preparations. is there.
  • the central longitudinal cross-sectional shape of the mucosa contact surface described above is preferably a semi-elliptical shape or a semi-spindle shape in order to bring out the effects of the present invention.
  • the central cross-sectional shape of the mucosa contact surface is preferably a circular shape, an elliptical shape or an oval shape for the same reason.
  • the solid preparation of the present invention is processed into a three-dimensional shape including these cross-sectional shapes, preferably a semi-elliptical sphere shape, an elliptic sphere shape, or a disk shape.
  • the semi-elliptical or semi-spindle shape forming the central longitudinal cross-sectional shape is about 0.1 to about 3.0 mm, preferably about 0.5 to about 2.5 mm, and about 3.0 to about 20 mm, preferably about Those having a major axis of about 5.0 to about 16.0 mm are preferred. This means that if the long diameter of the solid preparation in the central longitudinal cross-sectional shape is too large, the gap between the palate surface and the solid preparation becomes excessive, and the solid preparation tends to crack, and if it is too small, the solid preparation is attached. According to the fact that the wearing power tends to decrease.
  • the oval or oval shape that forms the central cross-sectional shape is about Those having a minor axis of 2.0 to about 20 mm, preferably about 3.0 to about 16 mm, and a major axis of about 3.0 to about 20 mm, preferably about 5.0 to about 16.0 mm are preferred.
  • the circular shape forming the central cross-sectional shape preferably has a diameter of about 3.0 to about 20 mm, preferably about 5.0 to about 16.0 mm.
  • the ratio of the minor axis Z to the major axis in the central longitudinal section is adjusted to a ratio of about 0.001 to about 0.20, preferably about 0.01 to about 0.15. This is because, if the ratio of the minor axis to the major axis in the central longitudinal cross-sectional shape becomes too small, the shape of the solid preparation becomes infinitely thin and flat, and the solid preparation easily breaks. . On the other hand, if this ratio becomes too large, the central longitudinal cross-sectional shape of the contact surface of the mucosa of the solid preparation becomes sharp, which reduces the contact area between the palate surface and the solid preparation, This results in a decrease in adhesion to the surface of the palate.
  • a counter mucosa abutting surface having a central longitudinal cross-sectional shape formed in a convex shape and pointing in a direction different from the mucosa abutting surface is further provided on the back side of the mucosa abutting surface. It is also possible.
  • the active ingredient is preferentially formulated in the non-mucosal surface, so that the supply of the active ingredient to the throat and gastrointestinal tract is facilitated by contact with the tongue.
  • the thickness (periphery height) of the non-mucosal surface is at most about 5.0 mm or less, preferably about 3.0 mm or less. Preferably, it is adjusted to about 0.4 mm to about 5.0 mm.
  • a columnar support layer having an end face shape of any one of a circular shape, an oval shape, and an oval shape and supporting the mucosa contact surface is further provided on the back side of the mucosa contact surface.
  • an effective ingredient can be efficiently supplied to the throat and gastrointestinal tract by intensively blending the active ingredient into the support layer.
  • the thickness (height) of the support layer is at most about 5.0 mm or less, preferably about 3.0 mm or less, more preferably Adjust to about 0.4 mm-about 5.0 mm.
  • one end face of the above support layer that is, the mucosal contact surface is not provided. It is also possible to further provide a mucosa contact surface having a central longitudinal cross-sectional shape formed into a convex shape on the free end surface of the support layer.
  • the mucosal contact surface of the solid preparation of the present invention is used to bring out the effect of the present invention to improve the shape retaining property and eliminate the feeling of foreign matter without impairing the adhesive force of the solid preparation.
  • any dosage form capable of realizing a mucosal contact surface is acceptable.
  • pills, sheets, patches, tablets can be used, but the tablet form is preferred in view of mass productivity.
  • tablets in addition to tablets that dissolve completely in the mouth, water-insoluble elements, for example, incompletely soluble tablets with a water-insoluble film layer can be used.
  • the adhesive is placed on the mucosa contacting surface.
  • a multi-layer tablet it is possible to provide a difference in dissolution rate for each layer.
  • the weight of the tablet is preferably adjusted in the range of about 0.1 to about l.Og / tablet from the viewpoint of preventing the solid preparation from collapsing and suppressing the appearance of foreign matter.
  • the dissolution rate of the tablet is generally about 3 to about 180 minutes, preferably about 5 minutes to about 60 minutes, more preferably about 10 minutes to about 40 minutes in the case of a sustained release preparation for oral use. To completely dissolve. This is because if the dissolution rate is too fast and the action time is too short, sufficient transmucosal absorption of the active ingredient and appropriate action of the active ingredient on the throat cannot be expected. Conversely, if the dissolution rate is slow and the action time is too long, the concentration of the active ingredient, particularly the concentration of the active ingredient taken into saliva or blood, becomes too dilute, and sufficient pharmacological effects are obtained. By not being able to hope.
  • the mixture is pressure-molded into a predetermined shape.
  • Comparative Example 4-16 is a tablet produced according to the method described in Example 3 of Patent Document 2.
  • Comparative Example 7 is a tablet produced according to the method described in Paragraph No. 0062 of Patent Document 1.
  • the solid preparation of the present invention is stably settled on the mucous membrane of the palate and is useful as a means for continuously supplying an active ingredient such as a drug to the whole body and Z or a disease site.

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  • Pharmacology & Pharmacy (AREA)
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Abstract

La présente invention a pour objet une préparation solide qui présente des caractéristiques améliorées en termes de rétention de forme et ne procure pas de sensation liée à la présence d'un corps étranger, ceci sans incidence sur sa capacité à adhérer de la façon voulue à la membrane muqueuse du palais. La présente invention décrit plus particulièrement une préparation solide comprenant un agent adhésif, dont l’une des faces est mise en contact avec la membrane muqueuse. La section verticale médiane de ladite préparation présente un profil de forme convexe.
PCT/JP2005/003869 2004-09-30 2005-03-07 Préparation solide intra-orale fixée WO2006038319A1 (fr)

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JP2004287872A JP2006096728A (ja) 2004-09-30 2004-09-30 口腔内定着型固形製剤
JP2004-287872 2004-09-30

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WO2006038319A1 true WO2006038319A1 (fr) 2006-04-13

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011201817A (ja) * 2010-03-26 2011-10-13 Nrl Pharma Inc 口腔貼付用錠剤

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5765934B2 (ja) * 2009-12-28 2015-08-19 サンスター株式会社 口腔用組成物
JP5775970B2 (ja) 2013-05-31 2015-09-09 久光製薬株式会社 口腔貼付剤

Citations (8)

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Publication number Priority date Publication date Assignee Title
JPS58174307A (ja) * 1982-04-06 1983-10-13 Teikoku Seiyaku Kk 可食性口腔内貼付薬
JPS62116688U (fr) * 1986-01-14 1987-07-24
JPH02250826A (ja) * 1989-03-22 1990-10-08 Sekisui Chem Co Ltd 口腔内貼付用バンデージ
JPH03164139A (ja) * 1989-08-30 1991-07-16 Eitarou Souhonpo:Kk 口腔囲壁に密着する飴
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JP2001288074A (ja) * 2000-04-10 2001-10-16 Taiho Yakuhin Kogyo Kk フィルム状トローチ
WO2002011694A2 (fr) * 2000-08-03 2002-02-14 Knoll Gmbh Compositions et formes posologiques en vue d'une application dans la cavite orale dans le cadre du traitement de mycoses
WO2003039465A2 (fr) * 2001-11-05 2003-05-15 Orahealth Corporation Traitement d'aphtes au moyen de patchs permettant de guerir et de soulager la douleur rapidement

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JPS58174307A (ja) * 1982-04-06 1983-10-13 Teikoku Seiyaku Kk 可食性口腔内貼付薬
JPS62116688U (fr) * 1986-01-14 1987-07-24
JPH02250826A (ja) * 1989-03-22 1990-10-08 Sekisui Chem Co Ltd 口腔内貼付用バンデージ
JPH03164139A (ja) * 1989-08-30 1991-07-16 Eitarou Souhonpo:Kk 口腔囲壁に密着する飴
JP2001508037A (ja) * 1996-10-18 2001-06-19 ビロテックス コーポレイション 粘膜表面への、薬学的化合物の送達に適する薬学的キャリアデバイス
JP2001288074A (ja) * 2000-04-10 2001-10-16 Taiho Yakuhin Kogyo Kk フィルム状トローチ
WO2002011694A2 (fr) * 2000-08-03 2002-02-14 Knoll Gmbh Compositions et formes posologiques en vue d'une application dans la cavite orale dans le cadre du traitement de mycoses
WO2003039465A2 (fr) * 2001-11-05 2003-05-15 Orahealth Corporation Traitement d'aphtes au moyen de patchs permettant de guerir et de soulager la douleur rapidement

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JP2011201817A (ja) * 2010-03-26 2011-10-13 Nrl Pharma Inc 口腔貼付用錠剤

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