WO2004108164A1

WO2004108164A1 - Composition for coating and coated preparation

Info

Publication number: WO2004108164A1
Application number: PCT/JP2004/008166
Authority: WO
Inventors: Tuneaki Tottori; Hiroko Kusano; Yasuki Kato
Original assignee: Kyowa Hakko Kogyo Co., Ltd.
Priority date: 2003-06-04
Filing date: 2004-06-04
Publication date: 2004-12-16
Also published as: JPWO2004108164A1

Abstract

A composition characterized by comprising finely fibrous cellulose and a coating base for preparations and containing substantially no chitosan. The composition is used in producing a coated preparation comprising a core substance comprising an effective ingredient, e.g., a medicine, food, agricultural chemical, or chemical for animals, and a coating film with which the core substance is coated. It is useful for forming the coating film, which has high strength during the production and/or storage of the coated preparation or even when the coated preparation comes into contact with moisture or water. Also provided is a coated preparation which includes a coating film comprising the composition.

Description

Specification

Coating composition and coating preparation

Technical field

The present invention relates to a composition which can be used for a coating film in a coating preparation, a coating preparation comprising a core substance and a coating film covering the core substance, and the like.

Background art

As preparations containing active ingredients such as pharmaceuticals, foods, agricultural chemicals, veterinary medicines, etc., coating preparations comprising a core substance and a coating film covering the core substance are widely used. Coating is a technique widely used in the pharmaceutical field for the purpose of masking the taste or odor of an active ingredient and improving light stability. For example, in a tablet or granule-shaped preparation, it is possible to produce a preparation by coating a core substance using a coating composition containing a conventionally known coating base for a preparation. Widely used.

In such a coating preparation, if the coating film is peeled or cracked during the production and / or storage of the preparation, the quality of the product may be deteriorated, and particularly, the product may come into contact with moisture. In some cases, the strength of the coating film is reduced, and peeling, cracking, and the like may easily occur. In addition, the strength of the coating film decreases due to contact with water after taking the drug, and due to the peeling or cracking of the coating film, the release of the drug or the masking of taste or smell cannot be controlled, and sufficient functions are not achieved. Sometimes I can't do it. Therefore, it is required to increase the strength of the coating film, particularly when the film comes into contact with moisture or moisture.

Heretofore, as a method for improving the strength of a coating film of a pharmaceutical, there is known a method of preparing a coating film from a composition containing a crystal cell orifice (Japanese Patent Application Laid-Open (JP-A) No. 2002-110630).

2002-284674).

On the other hand, microfibrous cellulose (see JP-A-56-100801) produced by passing a suspension of fibrous cell mouth through a small-diameter orifice at high pressure is known. To date, microfibrous cellulose has been used for the purpose of maintaining the viscosity of foods, cosmetics, paints, etc., strengthening food raw materials, retaining moisture, improving food stability, etc., as well as adding low calorie additives or emulsifying stability. It is known to use as a cellulose coating or the like characterized by being produced by spraying a chemical aid on a substrate (see JP-A-10-95803). Furthermore, with microfibrous cellulose A coating composition containing chitosan is also known (see JP-A-7-2701). In addition, a composition containing bacterial cellulose (see JP-A-10-95803), a capsulated microfibril cellulose and a composition containing the same (see Japanese Patent Application Laid-Open No. 9-509694), and a microcrystalline cellulose. An aqueous suspension of microcrystalline cellulose produced by passing a suspension through a small diameter orifice at a high pressure (see Japanese Patent Publication No. 57-234642), a non-woody microfibrous cellulose and a coating containing the same for coating. Compositions (see JP-T-2002-521577) and the like are also known.

Disclosure of the invention

An object of the present invention is to provide a coating preparation comprising a core substance containing an active ingredient such as a drug, food, agrochemical, and veterinary drug, and a coating film covering the core substance. A composition useful for preparing a coating film having high strength even during storage and / or during storage or even when the coating formulation comes into contact with moisture or moisture, a coating composition containing the composition in a coating film. To provide pharmaceutical preparations.

The present invention relates to the following (1) to (31).

(1) A composition comprising microfibrous cellulose and a pharmaceutical coating base, and substantially free of chitosan.

(2) The composition according to the above (1), wherein the ratio of the content of the coating base for pharmaceutical preparation to the content of the microfibrous cellulose is 1:99 to 19: 1.

(3) The composition according to the above (1) or (2), wherein the content of the microfibrous cellulose is 0.1 to 95% by mass relative to the total solid content in the composition.

(4) The composition according to any one of the above (1) to (3), wherein the pharmaceutical coating base is a cellulosic polymer, an acrylic acid polymer, a coating base for sugar coating, shellac or zein.

(5) Any one of the above (1) to (4), wherein the microfibrous cellulose is microfibrous cellulose produced by treating woody cellulose, powdered cellulose or cellulose containing crystal cell mouth with a high-pressure homogenizer. A composition according to any one of the above.

(6) The composition according to any one of the above (1) to (4), which is microfibrillated cell mouth opening force teria cellulose or microfibrillated cellulose. 8166

(7) A coating preparation comprising a core substance containing an active ingredient, and a coating film containing the microfibrous cellulose covering the core substance and a coating base for preparations.

(8) The coating preparation according to the above (7), wherein the coating film is a coating film containing substantially no chitosan.

(9) The coated preparation according to (7) or (8), wherein the ratio of the content of the coating base for preparation to the content of microfibrous cellulose in the coating film is 1:99 to 19: 1. .

(10) The content of microfibrous cellulose in the coating film is 0.1 to 95 mass based on the total solid content in the film. /. The coated preparation according to any one of the above (7) to (9).

(11) The coating according to any one of (7) to (10), wherein the coating base for the preparation is a cellulose-based polymer, an acrylic acid-based polymer, a coating base for sugar coating, shellac or zein. Formulation.

(12) Any one of the above (7) to (11), wherein the microfibrous cellulose is microfibrous cellulose produced by treating woody cellulose, powdered cellulose, or cellulose containing crystal cellulose with a high-pressure homogenizer. A coated preparation according to any one of the above.

(13) The coated preparation according to any one of (7) and (11), wherein the microfibrous cellulose is bacterial cellulose or microfibrillated cellulose. -

(14) The coated preparation according to any one of the above (7) to (13), wherein the coating preparation is a tablet or a granule.

(15) In a coating preparation containing a core substance containing the active ingredient and a coating or coating film containing a coating base for preparations covering the core substance, microfibrous cellulose is present in the coating film. A method for imparting strength to the coating preparation.

(16) In a coating preparation comprising a core substance containing an active ingredient and a coating film containing a coating base for pharmaceutical preparation covering the core substance, a microfibrous cellulose and coating for pharmaceutical preparation are formed on the core substance. A method for imparting strength to the coating preparation, characterized by forming a coating film by spraying a composition containing a base.

(17) The core according to the above (15) or (16), wherein the pharmaceutical coating base is a cellulosic polymer, an acrylic acid-based polymer, a sugar coating coating base, ceramic or zein. A method for imparting strength to a tinting preparation.

(18) The strength to the coated preparation according to any of (15) to (17), wherein the ratio of the amount of the coating base for preparation to the amount of microfibrous cellulose is 1:99 -19: 1. Assignment method.

(19) The strength of the coating preparation according to any of (15) to (18) above, wherein the amount of the microfibrous cellulose is 0.1 to 95% by mass based on the total solid content in the coating film. Giving method.

(20) The microfibrous cellulose as described in (15), wherein the microfibrous cell opening is a microfibrous cellulose produced by treating a woody cell opening, powdered cellulose or cellulose containing crystalline cell opening with a high-pressure homogenizer. The method for imparting strength to a coating preparation according to any one of claims to (19).

(21) The method for imparting strength to a coating preparation according to any one of the above (15) to (19), wherein the microfibrous cell mouth is a bacterial cell mouth or a microfibrillated cellulose.

(22) The method for imparting strength to a coating preparation according to any one of the above (15) to (21), wherein the coating preparation is a tablet or a granule.

(23) a step of mixing components other than water and / or an organic solvent of a liquid composition containing microfibrous cellulose and a coating base for pharmaceutical preparations in water and / or an organic solvent; and A method for producing a coating preparation, which comprises a step of spraying a mixture onto a core substance containing an active ingredient to form a coating film.

(24) The coating preparation according to the above (23), wherein the microfibrous cellulose is microfibrous cellulose produced by treating woody cellulose, powdered cellulose, or cellulose containing crystalline cellulose with a high-pressure homogenizer. Manufacturing method.

(25) The method for producing a coating preparation according to the above (23), wherein the microfibrous cellulose is bacterial cellulose or microfibrillated cellulose.

(26) The method for producing a coated preparation according to any one of the above (23) to (25), wherein the mixing is a mixing with a homogenizer.

(27) Any of (23) to (26) above, wherein the ratio of the content of the pharmaceutical coating base to the content of microfibrous cellulose in the obtained mixed solution is 1:99 to 19: 1. The code described in Manufacturing method of the preparation.

(28) The method according to any one of (23) to (27), wherein the content of the microfibrous cellulose in the obtained mixed solution is 0.1 to 95% by mass based on the total solid content in the mixed solution. A method for producing the coating composition according to the above.

(29) The coating preparation according to any one of the above (23) to (28), wherein the preparation coating base is a cell-based polymer, an acrylic acid-based polymer, a coating base for sugar coating, a ceramic or zein. Manufacturing method.

(30) The method for producing a coating preparation according to any one of the above (23) to (29), wherein the coating preparation is a tablet or a granule.

(31) A coated preparation produced by the method for producing a coating preparation according to any one of (23) to (30). The microfibrous cellulose used in the present invention is not particularly limited.For example, microfibrous cellulose produced by treating a suspension of woody cell mouth, powdered cellulose, crystalline cellulose, etc. with a high-pressure homogenizer. Fibrous cellulose and the like can be mentioned, and preferably, a microfibrillated cell mouth is obtained by treatment with the high-pressure homogenizer. Specifically, cellulose fibers such as wood pulp are finely ground or beaten by various conventionally known methods (JP-A-3-163135, JP-A-56-100801, etc.), and commercially available Fibrous cellulose (for example, trade name: SEritsch (Daicel Chemical Industries, Ltd.)) and the like. Also, bacterial cellulose and the like can be used. Furthermore, the specific surface area of the microfibrous cellulose used in the present invention is preferably 3 m ² / g or more, and more preferably 5 m ² / g or more.

The coating base for pharmaceutical preparation in the present invention is not particularly limited as long as it is acceptable for use in pharmaceuticals, foods, agricultural chemicals, veterinary drugs, etc., and is preferably a pharmaceutical, food, agricultural chemical, veterinary drug, etc. Polymers and sugars that are acceptable for use, more preferably water-insoluble or poorly soluble, or polymers that exhibit pH-dependent solubility and are acceptable for use in pharmaceuticals, foods, agricultural chemicals, veterinary drugs, etc. And the like. More specifically, ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropylmethyl cellulose sulfate, hydroxypropyl methylcellulose acetate succinate, Cellulose polymers such as cellulose acetate fluorocarboxylate, carboxymethylethylcellulose, cellulose acetate, etc .; ethyl acrylate / methyl methacrylate copolymer, amino alkyl methacrylate copolymer E, amino alkyl methacrylate copolymer RS, methyl acryl Acrylic acid polymers such as acid copolymer L, methacrylic acid copolymer LD, and methacrylic acid copolymer S; coating bases for sugar coating such as sucrose and maltitol; polysaccharides such as pullulan, dextrin, sodium alginate, xanthan gum; Cellulose, zein, etc. are preferable. Cellulose-based polymer, acrylic acid-based polymer, coating base for sugar coating, shellac, zein, etc. are preferable. Cellulose-based polymer, acrylic acid-based polymer, cerac, zein, etc. are preferable. Yo More preferably, specifically, ethylcellulose cellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose cellulose ester, hydroxypropylmethylcellulose acetate succinate, cellulose acetate phthalate, carboxymethylethylcellulose, cellulose acetate, Ethyl acrylate; methyl methacrylate copolymer, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, methyl acrylate copolymer L, methacrylate copolymer LD, methyl acrylate copolymer S, ceramics, zein and the like are preferred. It is also preferable to use the above-mentioned coating base for pharmaceutical preparations dispersed in water in advance. For example, an aqueous dispersion of ethyl cellulose [trade name: Aquacoat (Asahi Kasei), Sureis (Colorcon)], aminoalkylmethacrylate Evening acrylate copolymer RS aqueous dispersion [trade name: Oy Dragit RS30D, Oy Dragit RL30D (Higuchi Shokai)], Ethyl acrylate / methyl methacrylate methyl copolymer aqueous dispersion [trade name: Oy Dragit NE30D (Higuchi Shokai) )], Aqueous shellac (Freund Corporation) and the like.

The composition of the present invention is a composition containing microfibrous cellulose and a pharmaceutical coating base, and substantially free of chitosan, and preferably contains water and / or an organic solvent, more preferably water. It is a liquid composition or a composition obtained by solidifying the liquid composition by a formulation technique well known in the art.

The content of the microfibrous cellulose in the composition of the present invention is not particularly limited, but is preferably from 0.1 to 95% by mass, and more preferably from 10 to 80% by mass based on the total solid content in the composition. Is more preferable, and more preferably 20 to 50% by mass.

Pharmaceutical Coating for Content of Microfibrous Cellulose in Composition of the Invention The ratio of the content of the base material is preferably 1:99 to 19: 1, more preferably 1:19 to 9: 1, and further preferably 3: 7 to 7: 3. Preferably, the ratio is 4: 6 to 5: 5, and most preferably.

Further, the composition of the present invention may contain any of various plasticizers and / or water-soluble components. Examples of the plasticizer include triethyl citrate, getyl furate, macrogol, and glycerin. And glycerin fatty acid ester, triacetin, propylene glycol and the like, and preferably, triethyl citrate, glycerin fatty acid ester and the like. The water-soluble component is not particularly limited as long as it is soluble in water and is acceptable for use in pharmaceuticals, foods, agricultural chemicals, veterinary drugs, and the like. Examples thereof include lactose, sucrose, D-mannitol, sorbitol, and erythritol. 1,1, sodium, potassium chloride, calcium chloride, sodium phosphate, potassium phosphate, calcium phosphate, citrate, sodium citrate, succinate, sodium succinate, sodium acetate, tartaric acid, urine, hydroxypropylcellulose, hydroxy Propyl methylcellulose, methylcellulose, hydroxyethylcellulose, hydroxyethylmethylcellulose, carboxymethylcellulose, carboxymethylethylcellulose, hydroxypropyl cellulose, carboxyvinyl polymer, polyvinyl alcohol Pyrrolidone, polyvinyl alcohol, macrogol, starch, gelatin, dextrin, pullulan, agar, arabia gum, etc., preferably lactose, sucrose, D-mannitol, hydroxypropyl methylcellulose, etc. It can be used in combination of more than one kind. Further, it may contain a lubricant (eg, talc, glyceryl monostearate, etc.) and / or a coloring agent (eg, titanium oxide, iron sesquioxide, yellow sesquioxide, etc.).

The composition of the present invention can be obtained as a liquid composition by mixing and dissolving and dispersing components other than water and / or an organic solvent in water and / or an organic solvent. For example, woody cellulose, powdered cellulose, crystalline cellulose, or the like, which is a raw material of microfibrous cellulose, may be suspended in water and / or an organic solvent, preferably water, together with other components, if desired, to obtain a high-pressure liquid. Microfibrous cellulose is produced by treating with a homogenizer, etc., followed by dissolution and dispersion by mixing the remaining components other than water and / or organic solvent in water and / or organic solvent, preferably in water Liquid by doing The composition can be obtained in the form of a solid. To mix the components of the composition of the present invention other than water and / or the organic solvent in the water and / or the organic solvent, a method known in the art is used, but a method of mixing with a homogenizer is preferable. . Before mixing the components of the composition of the present invention other than water and / or the organic solvent in the water and / or the organic solvent, the water and / or the organic solvent solution or suspension of the microfibrous cellulose is mixed. Is preferably stirred with a homogenizer.

The composition of the present invention can be used, for example, as a coating agent for a coating preparation.

The coating preparation of the present invention comprises a core substance containing an active ingredient such as a pharmaceutical, a food, a pesticide, or an animal drug, a coating film containing the microfibrous cellulose covering the core substance and a coating base for a preparation. Which is in the form of tablets, pills, granules, fine granules, capsules, etc., but is preferably a tablet or a granule, and more preferably a tablet. And a coated preparation obtained by coating the composition of the present invention on the core substance.

The coating formulation of the present invention can be obtained by formulation techniques well known in the art, for example, water and / or a liquid composition containing microfibrous cellulose and a formulation coating base. Or a process for preparing a composition by mixing components other than the organic solvent in water and / or an organic solvent, and a process of coating the obtained composition on a core material to form a coating film. And so on.

Coating of the above core material can be performed using existing pharmaceutical equipment such as a fluidized bed coating device, a tumbling fluidized bed coating device, a centrifugal tumbling fluidized coating device, and a pan coating device. A method known in the art is used. For example, a composition obtained by dissolving and dispersing components other than water and / or an organic solvent in a liquid composition containing microfibrillated cellulose and a coating base for pharmaceutical preparations in water and / or an organic solvent. Spray coating method for spraying the product with existing formulation equipment, sugar coating method for spraying and spreading the composition with existing formulation equipment, mixing microfibrous cellulose and formulation coating base Spraying and laminating the mixed powder with existing pharmaceutical equipment Powder laminating coating method, in which the mixed powder is compression-molded around the core material with existing pharmaceutical equipment, etc. Coating or sugar coating The spray coating method is preferred, and the spray coating method is more preferred.

The amount of the coating film in the coating preparation is not particularly limited, but is preferably 0.5 to 100% by mass, and preferably 0.5 to 50% by mass with respect to the core substance. /. And more preferably 1 to 30 mass. /. Is more preferable.

The core substance may be in any form of tablets, pills, granules, fine granules, capsules and the like, but is preferably a tablet or a granule, more preferably a tablet, and Can be manufactured by a known method. For example, a tablet can be produced by mixing and compressing the active ingredient and a pharmaceutical additive. Before the compression molding, if necessary, a conventional formulation treatment such as wet or dry granulation may be performed. Pills can be manufactured by mixing an active ingredient and a pharmaceutical additive, kneading, dividing, molding, and coating with starch or the like. Condyle granules can be produced by wet or dry granulation after mixing the active ingredient and excipients, and after granulation, the granules may be subjected to a rounding treatment. Capsules can be made by filling granules and / or tablets into capsules.

The above-mentioned formulation additives are not particularly limited, and any of them that can be used as a solid formulation can be used. Excipients such as lactose, sucrose, D-mannitol, xylidol, erythritol, sorbitol, maltitol, calcium citrate, calcium phosphate, crystalline cellulose, magnesium aluminate metasilicate, etc .; corn starch, potato Disintegrants such as starch, sodium carboxymethylsulfate, partially starch arsenide, carboxymethylcellulose calcium, carboxymethylcellulose, low-substituted hydroxypropylcellulose, crosslinked carboxymethylcellulose sodium, crosslinked polyvinylpyrrolidone; Binders such as propylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, dextrin, and arsenic starch; stearin Lubricants such as magnesium phosphate, calcium stearate, talc, light anhydrous silicic acid and hydrous silicon dioxide; gelling agents such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, methylcell mouth, carboxyvinyl polymer, etc. Surface activity of phospholipid, glycerin fatty acid ester, sorbin fatty acid ester, polyoxyethylene fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxetylene alkyl ether, sucrose fatty acid ester, etc. Agent; Flavors such as orange and strawberry; iron sesquioxide, yellow iron sesquioxide, food yellow 5, food yellow 4, coloring agents such as aluminum chelate; sweeteners such as saccharin and aspartame; citric acid, citric acid Flavoring agents such as sodium, succinic acid, tartaric acid, fumaric acid, and glutamic acid; and solubilizing agents such as cyclodextrin, arginine, lysine, and triaminomethane.

Examples of the capsule include, but are not particularly limited to, a gelatin capsule, a hydroxymethylpyrmethylcellulose capsule, a chitosan capsule, a pullulan capsule and the like.

The active ingredient that can be used in the present invention is not particularly limited as long as it is acceptable for uses such as pharmaceuticals, foods, agricultural chemicals, and veterinary drugs, and is intended for oral administration or ingestion. (1) Antipyretic analgesic and anti-inflammatory IJ (for example, indomethacin, acetylsalicylic acid, diclofenac sodium, ketoprofen, ibuprofen, mefenamic acid, azulene, phenacetin, isopropylantipyrine, acetaminophen, benzazac, phenylbuzon, flufenamic acid) , Sodium salicylate, salicylamide, sazapyrine, etodolac, etc.), (2) steroid anti-inflammatory agents (eg, dexamethasone, hydrocortisone, prednisolone, triamcinolone, etc.), (3) anti-ulcer agents (eg, e. Sodium, ene Rostil, sulpiride, cetraxate hydrochloride, gef alanate, gilsogladine maleate, cimetidine, ranitidine hydrochloride, famotidine, nizatidine, etc., (4) calcium antagonists (e.g., benidipine, benidivine hydrochloride, besylidine) Amlodipine acid, difludipine, diltiazem hydrochloride, dicardipine, dicardipine hydrochloride, verapamil hydrochloride, nilvadipine, disoldipine, nitrendipine, manidipine hydrochloride, barnidipine hydrochloride, efonidipine hydrochloride, ferodipine, cilnidipine, aranidipine, etc. ) Peripheral vasodilators (eg, ifenprodil tartrate, cinepaside maleate, cyclanderate, cinnarizine, pentoxifylline, etc.), (6) antibiotics (eg, ampicillin, α Xicillin, acetylsviramycin, cephalexin, erythromycin ethyl succinate, bacanpicillin hydrochloride, minocycline hydrochloride, chloramphenicol, tetracycline, erythromycin, cefujidimim, cefuroxime sodium, aspoxicillin, litidene mucoxyl hydrate, etc. 7) Synthetic antibacterial agents (for example, nalidixic acid, pyromidic acid, Mimic acid trihydrate, enoxacin, sinoxacin, ofloxacin, norfloxacin, ciprofloxacin hydrochloride, sulfamethoxazole'trimethoprim, etc.), (8) antiviral agents (eg, acyclovir, .gancyclovir, etc.), (9) Fungicides (eg, ditraconazole, fluconazole, etc.); (10) antiseptic agents (eg, propantheline bromide, atropine sulfate, oxapium bromide, timevidium bromide, butylscopolamine bromide, trospium chloride, Butium bromide, N-methylscopolamine methyl sulfate, Methyloctabromide pin, etc.) (11) Antitussives (for example, Tipididine hibenzate, Methyl edrine hydrochloride, Codine phosphate, Tranilast, Hydrobromic acid) Dextromethorphan, phosphoric acid. (1), hominoben hydrochloride, benproperine phosphate, ebladinone hydrochloride, clofedanol hydrochloride, efuedrine hydrochloride, noscapine, pentoxyberine citrate, oxerazine quenze, isosominyl quenate, etc.) (13) bronchodilators (e.g., theophylline, aminophylline, sodium chromoglycate, propoterol hydrochloride, trimethokinol hydrochloride, diprofyl) Phosphorus, Salbuyl sulfate, Chlorprenaline hydrochloride, Formoterol fumarate, Orciprenaline sulfate, Pilbuterol hydrochloride, Hexoprenaline sulfate, Bitolterol mesylate, Clenbuterol hydrochloride, Terbuyuline sulfate, Mabuterol hydrochloride , Phenoterol hydrobromide, methoxyphenamine hydrochloride, etc.), (14) cardiotonic agents (eg, dopamine hydrochloride, dobumin hydrochloride, docarpamine, denopamine, caffeine, digoxin, digitoxin, ubidecarenone), (15) diuresis Agents (e.g., furosemide, acetazolamide, trichlormethiazide, methyclothiazide, hydrochloride thiazide, hydroflumethiazide, ethiazide, cyclopentiazide, spironolactone, triamterene, florothiazide, pyrethynide, mefurside, ethauric acid , Azosemide, clofenamide, etc.) (16) Muscle relaxant (for example, chlorphenesin rubbamate, tolperisone hydrochloride, eperizon hydrochloride, tizanidine hydrochloride, mefenesin, chlorzoxazone, fenprobamate, metoforce Bamol, chlormezanone, pridinol mesylate, afloqualone, baclofen, dantrolene sodium, etc.), (17) a brain metabolism improving agent (for example, nicergoline, meclofenoxate hydrochloride, evening lutilerin etc.), (18) a minor tranquilizer (for example, Oxazolam, diazepam, clotiazepam, medazepam, temazepam, fludiaze Pam, meprobamate, nitrazepam, chlordiazepoxide, etc.), (19) major tranquilizer (for example, sulpiride, clocabramin hydrochloride, zotepine, chlor promazine 'hydrochloride, haloperidol, etc.), (20)? -Blocker ( For example, pisoprol fumarate, pindolol, propranolol hydrochloride, carteolol hydrochloride, metoprolol tartrate, labetrol hydrochloride, acebutolol hydrochloride, butyl alcohol hydrochloride, alprenolol hydrochloride, arotinolol hydrochloride, oxprenolol hydrochloride , Nadolol, bucmorol hydrochloride, indenolol hydrochloride, timolol maleate, befnolol hydrochloride, bupranolol hydrochloride, etc.), (21) antiarrhythmic agents (for example, proamide hydrochloride, disopyramide, adimarin, quinidine sulfate) , salt Aprindin acid, propafenone hydrochloride, mexiletine hydrochloride, azimilide hydrochloride, etc.), (22) Gout remedies (for example, aloprinol, probenecid, colchicine, sulfinvirazone, benzbromarone, bucolome, etc.), (23) Anticoagulants (for example, pikidine hydrochloride, dicoumarol, potassium perhalin, (2R, 3R) -3-acetoxy-5- [2- (dimethylamino) ethyl] -2,3-dihydro-8 -Methyl-2- (4-methylthiophenyl) -1,5-benzothiazepine-4 (5H) -one'malate, etc., (24) thrombolytic agents (eg, methyl (2E, 3Z) )-3-benzylidene-4- (3,5-dimethoxy-hy-methylbenzylidene) -N- (4-methylbiperazin-1-yl) succinamate hydrochloride, etc.), (25) Agents for liver diseases (for example, Protoporphyrin sodium, etc.), (26) anti-tenka Agents (for example, phenytoin, sodium valproate, metal biphenyl, carbamazepine, etc.), (27) antihistamine-like IJ (for example, olopatadine, olopatadine hydrochloride, oxatomide, chlorfluramine maleate, clemastine fumarate, melmastine fumarate) Evening gin, alimemazine tartrate, cyprohepdazine hydrochloride, bepotastine besylate, etc.) (28) Antiemetic (eg, domperidone, diphenidole hydrochloride, metoclopramide, histine mesylate, trimebutine maleate, etc.) , (29) antihypertensive agents (eg, dimethylaminoethyl reserpine hydrochloride, resinamine, methyldopa, prazosin hydrochloride, bunazosin hydrochloride, clonidine hydrochloride, budralazine, perapidil, 'Ν- [6- [2- [(5- Bromo-2-pyrimidinyl) oxy] ethoxy] -5- (4-methylphenyl -4-pyrimidinyl]-4- (2-hydroxy-1,1-dimethylethyl) benzenesulfonamide sodium salt, etc., (30) Hyperlipidemic agent (for example, Bravasutin sodium, Fluvasutin) (31) Sympathetic stimulants (eg, dihydroergoyumin mesylate, isoproterenol hydrochloride, etilephrine hydrochloride, etc.), (32) antidiabetic agents (for example, glibenglamide, torpedomid, glymidine sodium, etc.), (33) antitumor agents (for example, fluorouracil, doxyfluridine, tegafur'peracyl, imatinib mesylate, gefitinib, levoholinato) (34) Alkyloid-type narcotics (eg, morphine, codeine, cocaine, etc.), (35) Bimin (eg, Bimin Bl, Bismin) Min2, Bimin B6, Vitamin B12, Vitamin C, Folic acid, Piotin, Pantothenic acid, etc.), (36) Frequent urinary remedies (for example, Flavoxanit hydrochloride, Oxiptinin hydrochloride, Telolidine hydrochloride, etc.), (37) Angiotensin converting enzyme inhibitors (eg, imidabril hydrochloride, enalapril maleate, alacepril, delapril hydrochloride) (38) angiotensin II receptor antagonists (eg, andesartan cilexetil, oral sultan lipodium, valsardan, telmisartan, etc.), (39) proteins or peptides (eg, bradykinin, angiotensin) , Oxytocin, vasopressin, adrenocorticotropin (ACTH), calcitonin, insulin, glucagon, cholecystokinin, endorphin, melanosite inhibitor, melanocyte stimulating hormone, gastrin angonist, neurotensin, somatostin, brucine , Cyclosporine, enkephalin, transferrin, RGD peptide, thyroid hormone, growth hormone, gonadotropin (gonadotropin), luteinizing hormone (LHRH), asparaginase, arginase, pericase, Carboxypeptidase, gluminase minase, superoxide dismutase (S0D), tissue plasminogen actinase (t-PA), streptokinase, inulin leukin, interferon, muramyl Dipeptide, thymopoietin, granulocyte colony stimulating factor (G-CSF), condyle granulocyte macrophage colony stimulating factor (GM-CSF), erythropoietin (EP0), thrombopoietin (TP0), trypsin inhibitor, lysozyme, epidermal growth factor (EGF), insulin-like growth factor (IGF), nerve growth factor. (NGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), endothelial cell growth factor (ECGF), fibroblast ( Fibroblast) growth factor (FGF) glial cell growth factor (GGF), thymosin, specific antibody (for example, anti-EGF receptor antibody, etc.), soy protein, phospholipid binding Bean peptide, lactotripeptide, casein phosphopeptide, casein decapeptide, collagen peptide, etc.), (40) nucleic acids (eg, antisense oligonucleotides), (41) sugars (eg, chondroitin sulfate sodium, heparin) Sodium, dextranfluorescein, etc.), (42) live fungi (Bifid Bacteria, lactic acid bacteria, yeast, etc.), (43) oligosaccharides (xylose oligosaccharides, fructooligosaccharides, soybean oligosaccharides, isomaltoligosaccharides, milk fruit oligosaccharides, lactulose, galactooligosaccharides, rafinois, etc.), (44) glycerol Derivatives (diasylglycerol, etc.), (45) dietary fiber (polydextrose, indigestible dextrin, etc.), (46) carotenoids (carotene, lycopene, rutin, cryptoxanthin, zeaxanthin, etc.), (47) polypheno (48) Minerals (heme iron, calcium citrate phosphate, etc.) and (49) Amino acids (valine, leucine, isoleucine, etc.).

The coating preparation of the present invention can be orally administered or ingested, and the administration or ingestion amount varies depending on various conditions such as the type of the active ingredient, the condition of the patient or consumer, and body weight. For example, about 0.01 to 100 mg / lig of the active ingredient per day can be administered or taken. The administration or the number of times of administration is preferably 1 to 3 times a day.

In the method for imparting strength to a coating formulation of the present invention, imparting strength to the coating formulation refers to increasing the strength of the coating formulation and / or coating film during production and / or storage of the coating formulation. Or to increase the strength of the coating formulation and / or coating when exposed to moisture or moisture.

The strength imparting to the coated preparation of the present invention can be achieved by a coating preparation comprising a core substance containing an active ingredient and a coating film containing a coating base for preparation which covers the core substance. It can be carried out in the presence of fibrous cellulose, for example, by producing a coating preparation by the method for producing a coating preparation of the present invention.

Next, the strength of the coating film obtained from the composition of the present invention and the strength of the coating film in the coating formulation of the present invention will be described with reference to experimental examples.

Experimental example 1

Each of the compositions obtained in Examples 1 to 4 and Comparative Example 1 to be described later was weighed into a petri dish (diameter: 5.8 cm) 3800 mg (300 mg as a solid content) and weighed into a small hot air circulating thermostat (Mini Jet Oven, Toyama Sangyo) After drying at 40 ° C for 2 hours, the film was further dried at 70 ° C for 1 hour to prepare a cast film. Each of the obtained cast membranes was cut into a size of 10 × 20 to obtain a test piece. Each specimen was immersed in water at 37 ° C for 4 hours in advance. Insert the test piece with a clamp and measure the tensile strength until the test piece breaks at a pulling speed of 10 mm / min using a photograph (AG-20kNG, manufactured by Shimadzu Corporation) in water at 37 ° C. did. The results are shown in Table 1. table 1

s 1 ss * 1 in water

Member M 1 Compounding ratio * ² Tensile strength (N)

Example 1 8.5% 1: 9 12.2

Example 2 17.2% 2: 8 12.1

Example 3 26.3% 3: 7 10.2

Example 4 35.7% 4: 6 11.1

Comparative Example 1 0.0% 0: 1 7.0

* 1: Content of microfibrous cellulose relative to total solid content in coating composition (% by mass) * 2: Ratio of coating agent to microfibrous cellulose Cast membrane containing ethyl cellulose as a main component ( Compared to Comparative Example 1), the cast membrane of ethyl cellulose containing microfibrous cellulosic cellulose (Example 14) had improved tensile strength in water. In other words, it was shown that the presence of microfibrous cellulose in the coating film could improve the strength of the coating film when exposed to moisture.

Experimental example 2

With respect to the compositions obtained in Example 5 12 and Comparative Example 2 described below, each of the compositions containing 150 mg as a solid content was placed on a petri dish (diameter 5.8 cm) under hot air of a dryer using a two-fluid nozzle (nozzle). It was sprayed with a diameter of 0.8 o'clock / 2.5 mm). Using a small hot air circulating thermostat (Mini Jet Oven, manufactured by Toyama Sangyo), the film was dried at 70 ° C for 1 hour to prepare a cast film. Each of the obtained cast membranes was cut into a size of X20 thighs in five countries to obtain test pieces. Each specimen was immersed in water at 37 ° C for 4 hours. The test piece was clamped, and the tensile strength until the test piece was broken was measured at 37 ° C in water at a tensile speed of 10 mm / min using an autograph (AG-20kNG, manufactured by Shimadzu Corporation). Further, cast films prepared from the compositions obtained in Example 5 6 10 and Comparative Example 2 were cut into a size of 5 mm X 20 mm to obtain test pieces. Each test piece was inserted with a clamp, and the tensile strength until the test piece was broken at a tensile speed of 10 mm / min was measured using an autograph (AG-20kNG, manufactured by Shimadzu Corporation) in the air. Table 2 shows the results. Table i¾ w¾g ..2

• 1 _m ^ * 2 Underwater In the air

^Kat Tensile strength (N) Tensile strength (N)

5 8.5% 1: 9 2.22 7.15

6 17.2% 2: 8 2.40 8.35

7 26.3% 3: 7 2.80

8 35.7% 4: 6 2.39

9 45.5% 5: 5 2.29

Example 10 55.6% 6: 4 2.18 15.91

Example 1 1 66.0% 7: 3 1.49

Example 12 76.9% 8: 2 1.46

Comparative Example 2 0.0% '0: 1 1AS 3.65

* 1: Content of microfibrous cellulose relative to total solid content in coating composition (% by mass) * 2: Ratio of coating agent to microfibrous cellulose

I: Not measured Compared to the cast membrane containing ethyl cellulose as a main component (Comparative Example 2), the cast membrane of ethyl cellulose containing microfibrous cellose (Examples 5 to 12) The tensile strength was improved, and the tensile strength in the air was improved for the cast film of ethyl cellulose also containing microfibrous cellulose (Examples 5, 6, and 10). In other words, it was shown that the presence of microfibrous cellulose in the coating film can improve the strength of the coating film and the strength of the coating film when exposed to moisture. In addition, the cast film of Comparative Example 2 of Experimental Example 2 was compared with the ratio of the strength increase of each cast film of Examples 1 to 4 to the cast film of Comparative Example 1 in which the composition was dried. The percentage of increase in the strength of each cast film in Examples 5 to 8 was larger than that of Example 5. By spraying the film under hot air to form the film, the coating strength in the case of contact with moisture was reduced. It was shown that it can be further improved.

Experiment 3

With respect to the compositions obtained in Example 13 and Comparative Example 3 described below, an amount of each composition containing 150 mg as a solid content was placed on a petri dish (5.8 cm in diameter) under hot air of a drier using a two-fluid nozzle (nozzle diameter). 0.8ΙΜ / 2.5ΙΜΙ). It was dried at 70 ° C for 1 hour using a small hot air circulating thermostat (MiniJittoven, manufactured by Toyama Sangyo) to prepare a cast membrane.

Each of the obtained cast films was cut into a size of 5 strokes × 20 thighs to obtain test pieces. Each specimen was immersed in water at 37 ° C for 4 hours. Insert the test piece with a clamp, and test it in water at 37 ° C using an autograph (AG-20kNG, manufactured by Shimadzu Corporation) at a pulling speed of 10 mm / min. The tensile strength until the specimen was broken was measured.

In the cast membrane containing microfibrous cellulose (Example 13), the tensile strength before the test piece was broken was 2.36N. The cast membrane containing untreated powdered cellulose (Comparative Example 3) was broken when inserted with a clamp, and could not be measured. In other words, it was shown that the presence of microfibrous cellulose in the coating film can improve the strength of the coating film when exposed to moisture.

Experimental example 4.

The coating preparations obtained in Examples 15 and 16 and Comparative Examples 5 and 6 were subjected to a temperature of 40 ° C and a relative humidity of 75 ° /. For 2 weeks. Each coated preparation before and after storage was compressed with a hardness meter (PTB31K manufactured by Japan Machinery) at a rate of 10 Omni / min in the diameter direction, and the hardness when the preparation was broken was measured. Table 3 shows the results.

Table 3

S ri 1 kai ri Mixing ratio * ² coat ink, rate) Before storage After storage

Formulation strength (N) Formulation strength (N) Example 1 5 30.0% 1: 2 3% 78.0 60.6 Example 16 30.0¾ 1: 2 5% 104.7 88.9 Comparative example 5 0.0% 0: 1 '3% 75.9 51.4 Comparative Example 6 0.0% 0: 1 '5% 113.8 72.4 Uncoated tablet 40.9 30.9

* 1: Content of microfibrous cellulose relative to the total solid content in the coating composition (% by mass) * 2: Ratio of coating agent to microfibrous cellulose

Compared to a coating preparation made from a composition containing hydroxypropyl methylcellulose as a main component (Comparative Examples 5 and 6), a coating preparation made from a composition containing microfibrous cellulose (Examples 15 and 16) was used. ) Improves the hardness after storage under humidification. That is, the presence of microfibrous cellulose in the coating film can improve the strength of the coating film in contact with moisture. It has been shown.

Next, the composition and the coating preparation of the present invention will be described in Examples and Comparative Examples. ,

Note that the present invention is not limited to these examples.

BEST MODE FOR CARRYING OUT THE INVENTION

Example 1 Ethylcellulose (Ethosel, manufactured by Dada Chemical Co., Ltd.) 365.8 mg is sufficiently dissolved in 3222 mg of ethyl cellulose (Kanto Chemical Co., Ltd.), and then glycerin fatty acid ester (Maibaset 9-40, manufactured by Westman Kodak Co., Ltd.) 73. 2 mg and microfibrous cellulose (Selish FD-100G, manufactured by Daicel Chemical Industries, Ltd.) 407. Orag (40, 7 mg as microfibrous cell mouth) were added, and the mixture was stirred and dissolved and dispersed. Ethanol (manufactured by Kanto Chemical Co., Ltd.) and purified water were added in an amount of 1194 mg and 738 mg, respectively, so that the mixing ratio of ethanol: purified water was 8: 2, and the mixture was further stirred to obtain a coating composition.

Example 2

Ethyl cellulose (Ethocel, Dow Chemical Co., Ltd.) 330.8 mg was sufficiently dissolved in ethanol (Kanto Chemical Co., Ltd.) 2913 mg, and then glycerin fatty acid ester (Mybasset 9-40, Eastman Kodak Co., Ltd.) 66.2 mg and Microfibrous cellulose (Serish FD-100G, manufactured by Daicel Chemical Industries, Ltd.) 828. Omg (82.8 mg as microfibrous cellulose) was added, and the mixture was stirred and dissolved and dispersed. Ethanol (manufactured by Kanto Chemical Co., Ltd.) and purified water (1503 mg 'and 359 mg, respectively) were added so that the mixing ratio of ethanol: purified water was 8: 2, and the mixture was further stirred to obtain a coating composition.

Example 3

Ethylcellulose (Ethosel, manufactured by Dow Chemical Company) 295. Omg was sufficiently dissolved in ethanol (manufactured by Kanto Chemical Co., Ltd.) 2594mg, and then glycerin fatty acid ester (Myvaset 9-40, manufactured by Eastman Kodak Company) 59. Omg and 1263 mg of fine fibrous cellulose (Selish FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (126.3 mg as fine fibrous cellulose) was added, and the mixture was stirred and dissolved and dispersed. Ethanol (manufactured by Kanto Kagaku) and purified water (3422 mg and 367 mg) were added so that the mixing ratio of ethanol: purified water was 8: 2, and the mixture was further stirred to obtain a coating composition.

Example 4

257.5 mg of ethyl cellulose (Ethocel, manufactured by Dow Chemical Company) is sufficiently dissolved in 2263 mg of ethanol (manufactured by Kanto Kagaku Co., Ltd.), and then glycerin fatty acid ester (Myvaset 9-40, manufactured by Eastman Kodak Company) 1714 mg of microfibrillated cellulose (Serish FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (171.4 mg as microfibrous cellulose) was added, and the mixture was stirred and dissolved and dispersed. Ethanol (Kanto) so that the mixing ratio of ethanol: purified water is 8: 2 (Manufactured by Kagaku) and purified water were added in amounts of 5353 mg and 361 mg, respectively, and further stirred to obtain a coating composition.

Comparative Example 1

A mixed solvent of ethanol (manufactured by Kanto Chemical Co., Ltd.) 2816 mg and purified water 704 nig (mixing mass ratio of ethanol: purified water = 8: 2) was mixed with 400 mg of ethyl cellulose (Ethocel, manufactured by Dow Chemical Co.) and glycerin fatty acid ester (mybaset 9 -40, manufactured by Eastman Kodak Co., Ltd.), and dissolved sufficiently to obtain a coating composition. Example 5

Dissolve 10 g of ethyl cellulose (Ethosel, manufactured by Dow Chemical) and 2 g of glycerin fatty acid ester (Myvasset 9-40, manufactured by Eastman Kodak) in 88 g of ethanol (Kanto Kagaku). did.

To 11.4 g of solution A, add 12.7 g of ethanol, 4.6 g of purified water, and 1.3 g of microfibrous cellulose (Cellius FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (0.13 g as microfibrous cellulose), and homogenize at 11000 rpm. After stirring for 10 minutes, a composition for coating was obtained. Example 6

To 10.3 g of solution A in Example 5, 13.7 g of ethanol, 3.4 g of purified water, and 2.6 g of fine fibrous cellulose (Selitsch FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (0.26 g of fine fibrous cellulose) were added. The mixture was stirred with a homogenizer to obtain a coating composition. Example 7

To 9.2 g of solution A in Example 5, 22.3 g of ethanol, 4.Og of purified water and 3.9 g of fine fibrous cellulose (Selitsch FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (0.39 g as fine fibrous cellulose) were added. The mixture was stirred with a homogenizer to obtain a coating composition. Example 8

Solution A in Example 5 8. Og was mixed with 34.6 g of ethanol, 5.6 g of purified water, and 5.4 g of microfibrous cellulose (Selish FD-100Gs manufactured by Daicel Chemical Industries, Ltd.) (0.54 g as microfibrous cellulose). In addition, the mixture was stirred with a homogenizer to obtain a composition for coating. Example 9

Solution A in Example 5 was mixed with 6,8 g of solution A in an amount of 47.3 g of ethanol, 7.2 g of purified water, and a fine fibrous cell. 6.8 g (0.68 g as microfibrous cellulose) of Lurose (Selitsch FD-100G, manufactured by Daicel Chemical Industries, Ltd.) was added, and the mixture was stirred with a homogenizer to obtain a coating composition. Example 10

To 5 and 0 g of solution A in Example 5, 54.5 g of ethanol, 8.50 g of purified water and fine fibrous cellulose (Seritsch FD-100G, manufactured by Daicel Chemical Industries, Ltd.) 7.5 g (0.75 g as fine fibrous cellulose) Was added and stirred with a homogenizer to obtain a coating composition. Example 11

To 6 g of solution A in Example 5, 66.9 g of ethanol, 9.5 g of purified water, and 8.9 g of fine fibrous cellulose (Selitsch FD-100G, manufactured by Daicel Chemical Industries, Ltd.) were added 8.9 g (0.89 g as fine fibrous cellulose). In addition, the mixture was stirred with a homogenizer to obtain a coating composition. Example 12

2.6 g of solution A in Example 5 was mixed with 79.7 g of ethanol, 11.2 g of purified water, and 10.4 g of fine fibrous cellulose (Selish FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (1.04 g of fine fibrous cell opening). g) was added, and the mixture was stirred with a homogenizer to obtain a coating composition. Comparative Example 2

0.88 g of purified water was added to 4, Og of solution A in Example 5, and mixed to obtain a composition for coating. Example 13

20 g of powdered cellulose (ARBOCEL M80, manufactured by J. RETTE AIER) was dispersed in 980 g of purified water. The obtained dispersion was continuously passed through a high-pressure homogenizer (Microfluidizer 1, manufactured by Mizuho Industry Co., Ltd.) 20 times under a pressure of 100 MPa to obtain a suspension of microfibrous cellulose. This suspension was diluted with purified water, and 10 g of the suspension (O.lg as microfibrous cellulose) was stirred with a homogenizer (Ultra Yulux T25, manufactured by Japan Co., Ltd.) for 10 minutes at 110 rpm, and then amino Alkyl methacrylate acrylate copolymer RS (Eid Ladgit RS30D, manufactured by Higuchi Shokai) 0.33 g (0.1 g as a solid content), 9.67 g of purified water and 0.02 g of triethyl citrate (Citroflex, Cal Yuichi Food Science) It was added, dissolved and dispersed to obtain a coating composition. Comparative Example 3

0.1 lg of powdered cellulose (ARBOCEL M80, manufactured by J. RETTE Kako AIER) was dispersed in 9.9 g of purified water. Aminoalkyl methyl acrylate copolymer 0.33 (0.1 g as solid content), purified water 9.67 g and triethyl citrate 0.02 g were added to the resulting dispersion, dissolved and dispersed, and coated. The composition for use was obtained. Example 14

Hydroxypropyl methylcellulose (TC-5, manufactured by Shin-Etsu Chemical Co., Ltd.) 12.6 g and polyethylene glycol (Macrogol 6000, manufactured by NOF Corporation) 1. were dissolved in a mixture of 133 g of ethanol (manufactured by Kanto Kagaku) and 133 g of purified water. . Separately, 60. Og of fine fibrous cellulose (Ceritz FD-100G, manufactured by Daicel Chemical Industries, Ltd.) (6.0 g of fine fibrous cellulose) was dispersed in a mixture of 157 g of ethanol and 103 g of purified water. The mixture was homogenized with a homogenizer (Ultra Tarax T25, manufactured by Japan Ltd.) at 11,000 rpm for 10 minutes. The two solutions were mixed to obtain a coating composition.

Comparative Example 4

16.2 g of hydroxypropylpyrmethylcellulose (TC-5, Shin-Etsu Chemical Co., Ltd.) and 1.8 g of polyethylene glycol (Macrogol 6000, Nippon Oil & Fats Co., Ltd.) were added to 171 g of ethanol (Kanto Chemical Co., Ltd.) and 171 g of purified water. The composition was dissolved in the mixed solution to obtain a coating composition. Example 15

TBM type mixer (TBM-8, manufactured by Tokuju Kogyo Co., Ltd.) containing 4450 g of lactose (Even Bretez 80, manufactured by Megure Japan), 500 g of microcrystalline cellulose (Avicel 1-1101, manufactured by Asahi Kasei Corporation) and 50 g of magnesium stearate ), And the resulting mixed powder is mixed with a punch-type tableting machine (Correct 12HUK, manufactured by Kikusui Seisakusho) using a pestle with a diameter of 7 and a radius of curvature of 10 strokes. Tablets were made to have a thickness of 3.7 thighs to obtain uncoated tablets.

The composition obtained in Example 14 was applied to 230 g of the uncoated tablet using a pan coating machine (Doriaco Ichiichi DRC200, manufactured by Powrex) until the coating rate became about 3% for 130 mg of uncoated tablet. Spray coated and dried at about 50 ° C. to give a coating formulation of hydroxypropylmethylcellulose and microfibrillated cellulose. Example 16

The composition obtained in Example 14 was coated on the core substance in Example 15 by 5% by mass with respect to the core substance in the same manner as in Example 15 to obtain a coated preparation.

Comparative Example 5

The composition obtained in Comparative Example 4 was added to the core substance in Example 15 in the same manner as in Example 15, and 3 parts by weight based on the core substance. /. Coating yielded a coated formulation.

Comparative Example 6

The composition obtained in Comparative Example 4 was coated on the core substance in Example 15 by 5% by mass with respect to the core substance in the same manner as in Example 15 to obtain a coating preparation.

Industrial applicability

According to the present invention, it is used for a coating preparation comprising a core substance containing an active ingredient such as a drug, food, agrochemical, veterinary drug, etc. and a coating film covering the core substance, during the production and / or storage of the coating preparation. Or a composition useful for preparing a coating film having high strength even when the coating formulation comes into contact with moisture or water-a coating formulation containing the composition in a coating film Etc. are provided.

Claims

The scope of the claims

1. A composition comprising microfibrous cellulose and a coating base for pharmaceutical preparations, and substantially free of chitosan.

2. The composition according to claim 1, wherein the ratio of the content of the pharmaceutical coating base to the content of microfibrous cellulose is 1:99 to 19: 1.

3. The composition according to claim 1, wherein the content of the microfibrous cellulose is 0.1 to 95% by mass relative to the total amount of solids in the composition.

4. The composition according to any one of claims 1 to 3, wherein the pharmaceutical coating base is a cellulosic polymer, an acrylic acid-based polymer, a coating base for sugar coating, shellac or zein.

5. The microfibrous cellulose is microfibrous cellulose produced by treating a cellulose containing woody cellulose, powdered cellulose or crystalline cellulose with a high-pressure homogenizer. 5. The composition according to any of 4.

6. The composition according to any one of claims 1 to 4, wherein the microfibrillated cellulose is bacterial cellulose or microfibrillated cellulose.

7. A coating preparation comprising a core substance containing an active ingredient, and a coating film containing microfibrous cellulose covering the core substance and a coating base for preparations.

8. The coating preparation according to claim 7, wherein the coating film is a coating film containing substantially no chitosan.

9. The coating preparation according to claim 7, wherein the ratio of the content of the coating base for preparation to the content of microfibrous cellulose in the coating film is 1:99 to 19: 1.

10. The coated preparation according to any one of claims 7 to 9, wherein the content of the microfibrous cellulose in the coating film is 0.1 to 95% by mass based on the total solid content in the coating film.

11. Claims wherein the pharmaceutical coating base is a cellulosic polymer, acrylic acid-based polymer, sugar coating coating base, ceramic or zein? 11. The coated preparation according to any one of claims 10 to 10.

12. Microfibrous cellulose is woody cellulose, powdered cellulose or crystalline cell The coating preparation according to any one of claims 7 to 7, wherein the coating preparation is microfibrillated cellulose produced by treating cellulose containing loin with a high-pressure homogenizer.

13. Claims wherein the microfibrous cellulose is bacterial cellulose or microfibrillated cellulose? 12. The coating preparation according to any one of items 11 to 11.

14. The coated preparation according to any one of claims 7 to 13, wherein the coating preparation is a tablet or a granule.

15. In a coating preparation comprising a core substance containing an active ingredient and a coating film containing a coating base for pharmaceutical preparation covering the core substance, the presence of microfibrous cellulose in the coating film is determined. A method for imparting strength to the coating preparation, which is characterized by the following.

16. In the process of producing a coating preparation comprising a core substance containing an active ingredient and a coating film containing a coating base for a preparation covering the core substance, microfibrous cellulose and a coating composition for a preparation are coated on the core substance. A method for imparting strength to said coating preparation, characterized by forming a coating film by spraying a composition containing a coating base.

17. The method for imparting strength to a coating preparation according to claim 15 or 16, wherein the coating base for the preparation is a cellulose polymer, an acrylic acid polymer, a coating base for sugar coating, shellac or zein.

18. The method for imparting strength to a coated preparation according to any one of claims 15 to 17, wherein the ratio of the amount of the coating base for preparation to the amount of microfibrous cellulose is 1:99 to 19: 1.

19. The amount of microfibrous cellulose is 0.1 to 95 mass based on the total solid content in the coating film. /. The method for imparting strength to a coated preparation according to any one of claims 15 to 18, wherein

20. The microfibrous cellulose according to any one of claims 15 to 19, wherein the microfibrous cellulose is microfibrous cellulose produced by treating woody cellulose, powdered cellulose or cellulose containing crystalline cellulose with a high-pressure homogenizer. A method for imparting strength to coating preparations.

21. Strengthening of the coated preparation according to any one of claims 15 to 19, wherein the microfibrous cellose is bacterial cellulose or microfibrillated cellulose. Giving method.

22. The method for imparting strength to a coating preparation according to any one of claims 15 to 21, wherein the coating preparation is a tablet or a granule.

23. a step of mixing components other than water and / or an organic solvent of a liquid composition containing a microfibrous cell opening and a coating base for pharmaceutical preparations in water and / or an organic solvent; A method for producing a coating preparation, comprising a step of spraying the obtained mixture onto a core substance containing an active ingredient to form a coating film.

24. The production of a coating formulation according to claim 23, wherein the microfibrous cellulose is microfibrous cellulose produced by treating woody cellulose, powdered cellulose or cellulose containing crystalline cellulose with a high-pressure homogenizer. Method.

25. The method for producing a coating preparation according to claim 23, wherein the microfibrous cellulose is bacterial cellulose or microfibrillated cellulose.

26. The method for producing a coated preparation according to any one of claims 23 to 25, wherein the mixing is mixing with a homogenizer.

27. The method according to any one of claims 23 to 26, wherein the ratio of the content of the pharmaceutical coating base to the content of the microfibrous cellulose in the obtained mixture is 1:99 to 19: 1. Manufacturing method of coating preparation.

28. The method according to any one of claims 23 to 27, wherein the content of the microfibrous cellulose in the obtained mixture is 0.1 to 95% by mass relative to the total amount of solids in the mixture. Manufacturing method of coating preparation.

29. The method for producing a coating preparation according to any one of claims 23 to 28, wherein the coating base for the preparation is a cellulosic polymer, an acrylic acid-based polymer, a coating base for sugar coating, shellac or zein.

30. The method for producing a coated preparation according to any one of claims 23 to 29, wherein the coated preparation is a tablet or a granule.

31. A coated preparation produced by the method for producing a coated preparation according to any one of claims 23 to 30.