JP2012041366A - Oral administration preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a preparation for oral administration completely masking taste, odor and the like of a medicine contained in a medicine-containing layer.SOLUTION: The oral administration preparation 1a comprises a first water-swellable gel-forming layer 12a and a second water-swellable gel-forming layer 12' made in the outermost layer, wherein the peripheral part of the first water-swellable gel-forming layer 12a is connected with the peripheral part of the second water-swellable gel-forming layer 12' by hot melting the adhesive layers 13, 13' containing hot melt adhesive so that the medicine-containing layer 11 is sealed inside the preparation 1a for oral administration.

Description

  The present invention relates to an oral administration agent.

Orally administered drugs may have reduced medication compliance due to various causes such as drug discomfort due to bitterness or astringency, nausea or vomiting due to medication, or medication rejection.
For example, in the case of solid preparations (for example, tablets, capsules, etc.), which are common dosage forms for oral administration, it is difficult to swallow them as they are, so usually they must be taken with a large amount of water, resulting in reduced compliance. There is a case. In particular, elderly and infants may not be able to swallow solid preparations, and medication compliance is often reduced. In the case of a solid preparation, there is a risk of accidentally clogging the trachea and a risk of sticking to the esophagus to form an esophageal tumor.

  Therefore, as shown in FIG. 5, the water-swellable gel-forming layers 12 and 12 ′ are laminated on the upper surface and the lower surface of the drug-containing layer 11, respectively, so that the water-swellable gel-forming layers 12 and 12 ′ are the outermost layers. 1 g of an orally administered agent has been developed (see Patent Document 1).

  When 1 g of orally administered agent is administered into the oral cavity of a patient, the water-swellable gel-forming layers 12 and 12 ′ swell with water such as saliva to form a gel. As a result, 1 g of the orally-administered drug changes to a dosage form having a size, shape, elasticity, viscosity, etc. that are easy to swallow, so that it can be taken easily and the risk of clogging the patient's trachea is reduced. And even infants can take it safely. In addition, in the case of a patient with little saliva and the water-swellable gel-forming layers 12 and 12 'are not sufficiently swollen and gel-formed, the same can be achieved by taking them with a small amount of water or pre-dipping in water before administration. The effect can be demonstrated. The amount of water required at this time is very small compared to the amount of water required when taking solid preparations such as tablets and capsules.

  Further, when 1 g of the orally administered agent is administered into the oral cavity of a patient, the water-swellable gel-forming layers 12 and 12 ′ swell and gel with water such as saliva, and the drug-containing layer 11 is covered with the gel. . Thereby, since the taste (for example, bitter taste, astringency), smell, etc. of the drug contained in the drug-containing layer 11 is masked, it is possible to prevent a decrease in compliance.

  Furthermore, by processing 1 g of an orally administered preparation into a film-form preparation (sheet-form preparation), the water content in the preparation can be kept lower than in a jelly-form preparation containing a large amount of water. (The drug that is easily hydrolyzed) can be improved, the handling is facilitated, and the packaging cost can be reduced.

  Furthermore, since the drug-containing layer 11 and the water-swellable gel-forming layers 12 and 12 ′ are formed as separate layers, 1 g of the orally-administered drug increases the drug amount of the drug-containing layer 11 and increases the drug-containing layer 11. Even if the film strength of the film is lowered, the strength of the film-form preparation as a whole can be maintained by imparting film-forming properties to the water-swellable gel-forming layers 12 and 12 ′. Therefore, the drug-containing layer 11 of 1 g of the orally-administered agent can contain a wide variety of drugs ranging from a very small amount of drug to a large amount of drug, and an insoluble and bulky drug that tends to cause a decrease in film strength.

International Publication WO02 / 087622

However, as shown in FIG. 5, there is a portion where the drug-containing layer 11 is exposed at the end of the orally administered agent 1g. In this portion, even if the water-swellable gel forming layers 12 and 12 ′ are swollen by water such as saliva and gelled, they are not covered with the gel, so that the drug-containing layer 11 remains exposed. For this reason, 1 g of the orally administered agent cannot completely mask the taste and smell of the drug contained in the drug-containing layer 11.
Then, an object of this invention is to provide the oral administration agent which can completely mask the taste, smell, etc. of the drug contained in the drug-containing layer.

  In order to solve the above-mentioned problems, the present invention provides an orally-administered agent in which a first water-swellable gel-forming layer and a second water-swellable gel-forming layer are provided on the outermost layer, and the drug is administered orally. Provided is the oral administration agent in which a peripheral edge of the first water-swellable gel-forming layer and a peripheral edge of the second water-swellable gel-forming layer are bonded so as to be enclosed in the agent. .

  In the oral administration agent of the present invention, the entire drug contained in the oral administration agent is covered with the first and second water-swellable gel-forming layers. Therefore, when the oral administration agent of the present invention is administered into the oral cavity of a patient, the first and second water-swellable gel-forming layers swell and gel with moisture such as saliva and are contained inside the oral administration agent. Since the entire drug is covered with a gel, the taste and smell of the drug are completely masked.

  In the oral administration agent of the present invention, the drug may be encapsulated in the oral administration agent in any state. For example, the drug can be encapsulated in the oral administration agent in a state in which it is contained in the drug-containing layer, or in a state where it is formulated into an appropriate dosage form such as a tablet, powder or liquid. In one aspect of the oral administration agent of the present invention, the drug-containing layer has a drug-containing layer provided between the first water-swellable gel-forming layer and the second water-swellable gel-forming layer. Is bound to the inside of the orally administered agent, the peripheral edge of the first water-swellable gel-forming layer is bonded to the peripheral edge of the second water-swellable gel-forming layer.

  In the oral administration agent of the present invention, the peripheral part of the first water-swellable gel-forming layer and the peripheral part of the second water-swellable gel-forming layer are adhesive layers containing an adhesive that can be thermally fused. It is bonded by being heat-sealed.

  In the oral administration agent of the present invention, the “outermost layer” means a layer constituting the outer surface of the oral administration agent when the oral administration agent is in the oral cavity of a patient or the like. Therefore, the “outermost layer” includes not only the layer constituting the outer surface of the orally-administered agent before administration but also the outer surface of the orally-administered agent before administration, but the oral-administered agent when in the oral cavity of the patient. A layer constituting the outer surface is also included. For example, even when another layer is provided as an outer layer of the water-swellable gel-forming layer, if this outer layer is decomposed or dissolved by moisture such as saliva in the patient's mouth, In the oral cavity, the water-swellable gel-forming layer constitutes the outer surface of the orally-administered agent, so that the water-swellable gel-forming layer is provided in the outermost layer of the orally-administered agent.

  ADVANTAGE OF THE INVENTION According to this invention, the oral administration agent which can completely mask the taste, smell, etc. of the drug contained in a drug content layer is provided.

(A) is a top view which shows 1st embodiment of the oral administration agent of this invention, (b) is sectional drawing (XX sectional drawing of Fig.1 (a)) which shows the embodiment. (A) is a top view which shows 2nd embodiment of the oral administration agent of this invention, (b) is sectional drawing (XX sectional drawing of Fig.2 (a)) which shows the embodiment. It is sectional drawing which shows another embodiment of the oral administration agent of this invention. It is sectional drawing which shows another embodiment of the oral administration agent of this invention. It is sectional drawing which shows the conventional oral administration agent.

Hereinafter, the present invention will be described with reference to the drawings.
[First embodiment]
Fig.1 (a) is a top view which shows 1st embodiment of the oral administration agent of this invention, FIG.1 (b) is sectional drawing (XX sectional drawing of Fig.1 (a)) which shows the embodiment. .
As shown in FIG. 1, the oral administration agent 1a according to the first embodiment includes water-swellable gel-forming layers 12 and 12 ′ provided in the outermost layer of the oral administration agent 1a, water-swellable gel-forming layer 12 and A peripheral portion of the water-swellable gel-forming layer 12 and the water-swellable gel so that the drug-containing layer 11 is enclosed in the oral administration agent 1a. The peripheral portion of the formation layer 12 ′ is directly coupled.

  The orally administered agent 1a is preferably a film-form preparation (sheet-form preparation). When the orally-administered agent 1a is a film-form preparation, the water content in the preparation can be kept low. Therefore, compared to a jelly-form preparation containing a large amount of water, the drug contained in the drug-containing layer 11 (especially water) It is possible to improve the stability of drugs that are easily decomposed. In addition, the preparation can be handled easily and the packaging cost of the preparation can be reduced.

  The drug-containing layer 11 is a layer containing a drug to be administered. The drug contained in the drug-containing layer 11 is usually contained in the drug-containing layer 11 in a state of being formulated into an appropriate dosage form such as a film, powder, tablet or the like. The dosage form of the drug contained in the drug-containing layer 11 is not particularly limited as long as the formation of the drug-containing layer 11 is not impaired. The drug-containing layer 11 may be composed of only the drug to be administered, but is usually a pharmaceutically acceptable excipient as a base for holding the drug to be administered in a desired state in the drug-containing layer. Contains agents, binders, disintegrants, masking agents, colorants and the like.

  The thickness of the drug-containing layer 11 can be appropriately adjusted within a range that can be administered orally. When the orally administered agent 1a is a film-form preparation, the thickness of the drug-containing layer 11 is preferably 0.1 to 1000 μm, and more preferably 10 to 200 μm. When the thickness of the drug-containing layer 11 is less than 0.1 μm, it becomes difficult to form a film with high accuracy (that is, the drug content of the drug-containing layer 11 varies), whereas the thickness of the drug-containing layer 11 If the thickness exceeds 1000 μm, the film becomes stiff and difficult to take.

  The base contained in the drug-containing layer 11 together with the drug is not particularly limited, and can be appropriately selected depending on the purpose of addition. Specific examples of the base contained in the drug-containing layer 11 include crystalline cellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, ethylcellulose, cellulose acetate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate. Cellulose such as succinate, carboxymethylethyl cellulose and derivatives thereof or pharmaceutically acceptable salts thereof (for example, sodium salt); starch such as α-starch, oxidized starch, sodium carboxymethyl starch, hydroxypropyl starch, dextrin, dextran And their derivatives; sucrose, maltose, lactose, glucose, fructose, pullulan, xantha Sugars such as gum and cyclodextrin; sugar alcohols such as xylitol, mannitol, sorbitol; dimethylaminoethyl methacrylate / methacrylic acid copolymer, methacrylic acid / ethyl acrylate copolymer, methacrylic acid / methyl methacrylate copolymer, Acrylic acid derivatives such as ethyl methacrylate / methacrylated trimethylammonium copolymer, dimethylaminoethyl methacrylate / methacrylated methyl copolymer, methacrylic acid / acrylated ethyl copolymer; shellac; polyvinyl acetal diethylaminoacetate; poly Polyvinyl acetate; polyvinyl alcohol; polyvinyl pyrrolidone; vinyl acetate-vinyl pyrrolidone copolymer; natural rubbers such as gum arabic and tragacanth; Polyglucosamines such as chitin and chitosan; proteins such as gelatin, casein, and soy protein; titanium oxide; calcium monohydrogen phosphate; calcium carbonate; talc; stearate; magnesium metasilicate aluminate; Depending on the purpose of addition, one or more of these can be selected and used.

The base contained in the drug-containing layer 11 is preferably an edible polymer. The edible polymer may be either a synthetic polymer or a natural polymer, and the type thereof is not particularly limited.
The edible polymer is preferably a gastric polymer or an enteric polymer.
Among edible polymers, preferred are cellulose or cellulose derivatives, polyvinyl pyrrolidone, polyvinyl acetate, vinyl pyrrolidone-vinyl acetate copolymer, etc., and particularly preferred are hydroxypropyl cellulose, hydroxypropyl methylcellulose. Examples thereof include phthalate, polyvinyl pyrrolidone, polyvinyl acetate, and vinyl pyrrolidone-vinyl acetate copolymer. Hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, polyvinylpyrrolidone, polyvinyl acetate, and vinylpyrrolidone-vinyl acetate copolymer are excellent in film-forming properties, and are useful when the drug-containing layer 11 is formed into a film.

  The amount of the base contained in the drug-containing layer 11 is an amount that enables the drug-containing layer 11 to be formed, and the amount can be appropriately adjusted according to the type of the base, etc. The content of the containing layer 11 is usually 20% by weight or more, preferably 60% by weight or more, and more preferably 70% by weight or more. When the total content of the base is less than 20% by weight, the drug-containing layer 11 is not sufficiently formed. The upper limit of the content of the base is a value obtained by subtracting the minimum content of the drug contained in the drug-containing layer 11 from 100% by weight, and can be appropriately set according to the type of drug. For example, when the minimum content of the drug is 0.01% by weight of the drug-containing layer 11, the upper limit of the content of the base is 99.99% by weight of the drug-containing layer 11.

  The drug contained in the drug-containing layer 11 is a drug to be administered to a patient or the like, and is not particularly limited as long as it can be administered orally. As drugs that can be administered orally, for example, drugs acting on the central nervous system include hypnotics such as amobarbital, estazolam, triazolam, nitrazepam, pentobarbital; amitriptine hydrochloride, imipramine hydrochloride, oxazolam, chlordiazepoxide, chlorpromazine, diazepam, sulpiride, Psychotropic drugs such as haloperidol; antiparkinson drugs such as trihexyphenidyl and levodopa; analgesics and anti-inflammatory drugs such as aspirin, isopropylantipyrine, indomethacin, diclofenac sodium, mefenamic acid, streptokinase, streptodolase, serrapeptase, and pronase Central nervous system metabolism stimulators such as ATP and vinpocetine; drugs acting on the respiratory tract include expectorants such as carbocysteine and promhexine hydrochloride; Anti-asthmatic drugs such as rustin, oxatomide, theophylline, terbutaline sulfate, tranilast, procaterol hydrochloride, ketotifen fumarate; drugs acting on the circulatory system include cardiotonic drugs such as aminophylline, digitoxin, digoxin; adimarin, disopyramide, procainamide hydrochloride Antiarrhythmic agents such as methiletine hydrochloride; amyl nitrite, alprenolol hydrochloride, isosorbide nitrate, nicorandil, oxyfedrine, dipyridamole, dirazep hydrochloride, diltiazem hydrochloride, nitroglycerin, nifedipine, verapamil hydrochloride; Peripheral vasodilators such as caridinogenase; atenolol, captopril, clonidine hydrochloride, metoprolol tartrate, spironolactone, triamterene, trichlormethiazide, nicardipine, hydride hydrochloride Antihypertensive drugs such as azine, hydrochlorothiazide, prazosin hydrochloride, furosemide, propranolol hydrochloride, enalapril maleate, methyldopa, labetalol hydrochloride, reserpine; anti-arteriosclerotic drugs such as clofibrate, dextran sulfate, nicomol, niceritrol; blood and hematopoietic agents Hemostatic drugs such as sodium carbazochrome sulfonate and tranexamic acid; Antithrombotic drugs such as ticlopidine hydrochloride and warfarin potassium; Antianemic drugs such as iron sulfate; Azulene, aldioxa, cimetidine, hydrochloric acid as drugs acting on the digestive system Anti-ulcer drugs such as ranitidine, famotidine, teprenone, rebamipide; antiemetics such as domperidone and metoclopramide; clogging drugs such as sennoside; digestive enzyme preparations; therapeutic drugs for liver diseases such as glycyrrhizin and liver extract preparations; Anti-diabetic drugs such as glibenclamide, chlorpropamide, tolbutamide, etc. as drugs acting on axic diseases; Gout therapeutic agents such as allopurinol, colchicine; Acetazolamide as drugs in the ophthalmic area; Difenidol hydrochloride, Mesyl Anti-vertigo drugs such as betahistine acid; chemotherapeutic drugs and antibiotics such as isoniazid, ethambutol hydrochloride, ofloxacin, erythromycin stearate, cefaclor, norfloxacin, fosfomycin calcium, minocycline hydrochloride, rifampicin, rokitamycin; Famide, tegafur, etc .; as an immunosuppressant, azathioprine, etc .; as hormones and endocrine therapeutics, progesterone, salivary gland hormone, thiamazole, prednisolone, betame Zon, liothyronine, levothyroxine, etc .; in vivo active substances (autocoid), antihistamines such as clemastine fumarate, D-chlorpheniramine maleate; vitamins such as alphacalcidol, cobamide, tocopherol nicotinate, mecoparamine, etc. One type or two or more types can be selected and used depending on the purpose of treatment / prevention.

  The amount of the drug contained in the drug-containing layer 11 is not particularly limited and can be appropriately adjusted according to the type of drug, but is usually 80% by weight or less, preferably 40% by weight or less of the drug-containing layer 11, Preferably it is 30 weight% or less. When the drug content exceeds 80% by weight, the film strength decreases when the orally administered preparation 1a is a film-form preparation. The lower limit of the drug content is appropriately set according to the type of drug contained in the drug-containing layer 11, and is usually about 0.01% by weight.

  The drug-containing layer 11 can contain a wide variety of drugs ranging from a very small dose to a large amount of drug. Here, a small dose means that a single dose is 1 mg or less, and a large dose means that a single dose is 300 mg or more.

  Even when the orally-administered agent 1a is a film-form preparation, the drug-containing layer 11 has a wide variety of drugs ranging from a very small dose to a large amount of drug, and an insoluble and bulky drug that tends to cause a decrease in film strength. Can be contained. This is because the drug-containing layer 11 and the water-swellable gel-forming layers 12 and 12 ′ are formed as separate layers, so that the drug content of the drug-containing layer 11 increases and the film strength of the drug-containing layer 11 increases. This is because the strength of the film-form preparation as a whole can be maintained by imparting film-forming properties to the water-swellable gel-forming layers 12 and 12 ′ even if it is lowered.

The water-swellable gel-forming layers 12 and 12 ′ contain a water-swellable gel-forming agent and can swell with moisture to form a gel.
The thickness of the water-swellable gel-forming layers 12 and 12 ′ can be adjusted as appropriate within the range in which oral administration is possible, but when the oral administration agent 1 is a film-form preparation, it is preferably 10 to 1000 μm. More preferably, it is 20-500 micrometers. If the thickness of the water-swellable gel-forming layers 12 and 12 ′ is less than 10 μm, gel formation is insufficient, and the masking action such as the taste and smell of the drug by the water-swellable gel-forming layers 12 and 12 ′ is insufficient. On the other hand, when the thickness of the water-swellable gel-forming layers 12 and 12 ′ exceeds 1000 μm, when administered into the oral cavity of a patient or the like, the saliva alone cannot swell enough to form a gel, It becomes difficult to take.

The type of the water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12 and 12 ′ is not particularly limited as long as it can swell with moisture to form a gel, and is a crosslinked one. Even if it exists, it may not be crosslinked.
Examples of the water-swellable gel-forming agent include carboxyvinyl polymer, starch and derivatives thereof, agar, alginic acid, arabinogalactan, galactomannan, cellulose and derivatives thereof, carrageen, dextran, tragacanth, gelatin, pectin, hyaluronic acid, gellan gum , Collagen, casein, xanthan gum, etc., and one or more of these can be selected and used.

The water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12 and 12 ′ is preferably a crosslinked carboxyvinyl polymer, particularly preferably a crosslinked polyacrylic acid. Cross-linked carboxyvinyl polymers, particularly cross-linked polyacrylic acid, do not adversely affect the film-forming ability of the film-forming agent and can exhibit a moderate gel strength when swollen.
Crosslinking can be performed with a crosslinking agent depending on the type of molecule to be crosslinked. The carboxyvinyl polymer can be crosslinked by, for example, a polyvalent metal compound. Specific examples of such polyvalent metal compounds include calcium chloride, magnesium chloride, aluminum chloride, aluminum sulfate, potassium alum, iron chloride alum, ammonium alum, ferric sulfate, aluminum hydroxide, aluminum silicate, and phosphoric acid. Aluminum, iron citrate, magnesium oxide, calcium oxide, zinc oxide, zinc sulfate and the like can be mentioned, and one or more of these can be selected and used.

  The amount of the water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12 and 12 ′ can be appropriately adjusted according to the type of the water-swellable gel-forming agent, but preferably the water-swellable gel It is 15 to 70% by weight of the formed layer.

  When the orally administered agent 1a is a film-form preparation, it is necessary to form the water-swellable gel-forming layers 12 and 12 'in a film form. In this case, the film-formability of the water-swellable gel-forming layers 12 and 12' In order to improve this, it is preferable that the water-swellable gel-forming layers 12 and 12 ′ contain a film-forming agent.

  The type of the film forming agent is not particularly limited as long as it has film forming ability. Specific examples of the film forming agent include polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate, polyvinyl acetate phthalate, hydroxyalkyl cellulose (for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose), alkylcellulose (for example, Methyl cellulose, ethyl cellulose), carboxyalkyl cellulose (for example, carboxymethyl cellulose), (meth) acrylic acid and its ester, xanthan gum, carrageenan, alginic acid, and the like. One or more of these may be selected and used. it can.

  The amount of the film-forming agent contained in the water-swellable gel-forming layers 12 and 12 ′ can be appropriately adjusted according to the type of the film-forming agent, but preferably the water-swellable gel-forming layers 12 and 12 ′. 30 to 85% by weight.

  The film forming agent contained in the water-swellable gel-forming layers 12 and 12 'is preferably water-soluble. When the film-forming agent is water-soluble, water easily enters the water-swellable gel-forming layers 12 and 12 ′, and the water-swellable gel-forming layers 12 and 12 ′ rapidly swell and form gels in the oral cavity. Can be made.

  Examples of the water-soluble film forming agent include polyvinyl alcohol; hydroxyalkyl cellulose such as hydroxypropylcellulose, hydroxypropylmethylcellulose, and methylcellulose; polyvinylpyrrolidone; xanthan gum; carrageenan; alginic acid, and the like. Can be selected and used.

  The water-swellable gel-forming layers 12 and 12 ′ may contain a plasticizer in order to impart appropriate flexibility to the water-swellable gel-forming layers 12 and 12 ′. Examples of the plasticizer include propylene glycol, polyethylene glycol, glycerin, sorbitol, glycerin triacetate, diethyl phthalate, triethyl citrate, lauric acid, sucrose, and the like. Can be used.

  The water-swellable gel forming layers 12 and 12 ′ may contain a masking agent for masking the taste, smell, etc. of the drug contained in the drug-containing layer 11. When the water-swellable gel-forming layers 12 and 12 ′ contain a masking agent, the masking action such as the taste and smell of the drug by the water-swellable gel-forming layers 12 and 12 ′ can be improved. As the masking agent, for example, those that give acidity such as citric acid, tartaric acid, fumaric acid, sweeteners such as saccharin, glycyrrhizic acid, sucrose, fructose, mannitol, refreshing agents such as menthol, mint oil, peppermint, spearmint, Natural or synthetic fragrance | flavor etc. are mentioned, These 1 type (s) or 2 or more types can be selected and used.

  When the water-swellable gel forming layers 12 and 12 'contain polyvinyl alcohol or the like as a film forming agent, these film forming agents can also serve as a masking agent. Thus, it is preferable to use a film forming agent having a masking action, and it is also preferable to use a water-swellable gel forming agent having a masking action.

  The water-swellable gel-forming layers 12 and 12 ′ may contain a preservative such as methyl hydroxypropyl and propyl; a colorant such as an edible lake colorant.

  Incorporation of additives into the water-swellable gel-forming layers 12 and 12 'generally reduces the strength of the water-swellable gel-forming layers 12 and 12', so that the water-swellable gel-forming layers 12 and 12 ' Water easily enters, and water that has entered the water-swellable gel-forming layers 12 and 12 ′ tends to cause swelling and gel formation of the water-swellable gel-forming agent.

  As shown in FIG. 1, in the orally administered agent 1a, the upper surface and the lower surface of the drug-containing layer 11 are respectively covered with the central portions (portions surrounded by the peripheral edge portion) of the water-swellable gel-forming layers 12 and 12 ′. The side surface of the drug-containing layer 11 is covered by the peripheral edges of the combined water-swellable gel-forming layers 12 and 12 ′. That is, the entire drug-containing layer 11 is covered with the water-swellable gel-forming layers 12 and 12 '. Therefore, when the orally-administered agent 1a is administered into the oral cavity of a patient, the water-swellable gel-forming layers 12 and 12 'are swollen and gelled by moisture such as saliva, and the entire drug-containing layer 11 is covered with the gel Therefore, the taste and smell of the drug contained in the drug-containing layer 11 are completely masked.

  As shown in FIG. 1, water-swellable gel-forming layers 12 and 12 'are provided on the outermost layer of the orally administered agent 1a. Therefore, when the water-swellable gel-forming layers 12 and 12 ′ are gelled, the orally-administered agent 1 a is changed to a dosage form having a size, shape, elasticity, viscosity and the like that are easy to swallow. Thereby, the patient can take the oral administration agent 1a easily. In addition, since the risk of clogging the patient's trachea during oral administration is reduced, the oral administration agent 1a can be safely taken even if the patient is an elderly person or an infant. For patients with low saliva and water-swellable gel-forming layers 12 and 12 'that are not sufficiently gelled, the same effect can be achieved by taking them with a small amount of water or pre-dipping in water before administration. be able to. The amount of water required at this time is very small compared to the amount of water required when taking solid preparations such as tablets and capsules.

The orally administered agent 1a can be produced, for example, according to the following method.
[First production method]
A suspension containing a water-swellable gel-forming agent and a film-forming agent (for example, purified water) is applied and sprayed on the upper surface of a holding substrate such as a plastic film or a mount, and then dried. A water-swellable gel-forming layer 12 is formed to produce a first laminate in which the water-swellable gel-forming layer 12 is laminated on the upper surface of the holding substrate.
On the other hand, in the same manner as described above, after the water-swellable gel-forming layer 12 ′ is formed on the upper surface of a holding substrate such as a plastic film or a mount, the drug and the additive are applied to the upper surface of the water-swellable gel-forming layer 12 ′. A drug-containing layer 11 is formed by applying and spraying a suspension (solvent is, for example, ethanol) containing additives such as a form, a binder, and a disintegrant, followed by drying. At this time, the size of the lower surface of the drug-containing layer 11 is smaller than the size of the upper surface of the water-swellable gel-forming layer 12 ′ (that is, the drug-containing layer 11 is an upper surface of the water-swellable gel-forming layer 12 ′. And adjust so that the peripheral edge of the upper surface of the water-swellable gel-forming layer 12 ′ is exposed). The method for forming the drug-containing layer 11 is not limited to the above method. For example, the drug-containing layer 11 is formed on the upper surface of the water-swellable gel-forming layer 12 ′ by printing using a known method such as a screen printing method. It can also be formed. Thus, a second laminate is produced in which the water-swellable gel-forming layer 12 ′ and the drug-containing layer 11 are sequentially laminated on the upper surface of the holding substrate.
Next, the peripheral edge surface of the water-swellable gel-forming layer 12 and the peripheral edge surface of the water-swellable gel-forming layer 12 ′ are gelled by wetting with water, and the gelated peripheral edges are pressure-bonded and then dried. At this time, since the contact portions are integrated and gelled and dried, the peripheral portion of the water-swellable gel-forming layer 12 and the peripheral portion of the water-swellable gel-forming layer 12 ′ are directly bonded. Thus, the oral administration agent 1a in which the drug-containing layer 11 is encapsulated is produced by directly adhering the peripheral part of the water-swellable gel-forming layer 12 and the peripheral part of the water-swellable gel-forming layer 12 ′. Can do.

[Second production method]
In the same manner as in the first production method, the first laminate in which the water-swellable gel-forming layer 12 is laminated on the upper surface of the holding substrate, and the water-swellable gel-forming layer 12 ′ on the upper surface of the holding substrate. The laminated second laminated body is manufactured.
On the other hand, after applying or spraying a suspension containing an additive such as a drug and an excipient, a binder, a disintegrant, etc. (solvent is, for example, ethanol) on the upper surface of a holding substrate such as a plastic film or a mount This is dried to form a drug-containing film. The drug-containing film thus formed is peeled off from the holding substrate, and the obtained drug-containing film is removed from the water-swellable gel-forming layer 12 ′ of the first laminate or the water-swellable gel-forming layer 12 ′ of the second laminate. Install on top.
Then, in the same manner as described above, by directly bonding the peripheral edge of the water-swellable gel-forming layer 12 of the first laminate and the peripheral edge of the water-swellable gel-forming layer 12 ′ of the second laminate, It is possible to produce an orally administered agent 1a in which a drug-containing film is enclosed.

  The oral administration agent in which the water-swellable gel-forming layer 12 ′, the drug-containing layer 11 and the water-swellable gel-forming layer 12 are sequentially laminated by the first or second production method, and the drug-containing layer 11 is enclosed inside 1a is manufactured. The oral administration agent 1a may be punched into an arbitrary shape such as a circular shape, an elliptical shape, or a polygonal shape as necessary. When punching out the orally administered agent 1a, a portion where the peripheral portion of the water-swellable gel-forming layer 12 of the first laminate and the peripheral portion of the water-swellable gel-forming layer 12 'of the second laminate are adhered The drug-containing layer 11 is not exposed.

[Second Embodiment]
FIG. 2 (a) is a plan view showing a second embodiment of the oral administration agent of the present invention, and FIG. 2 (b) is a sectional view showing the same embodiment (XX sectional view of FIG. 2 (a)). .
As shown in FIG. 2, the orally-administered agent 1b according to the second embodiment includes water-swellable gel-forming layers 12 and 12 'provided on the outermost layer of the orally-administered agent 1b, and the water-swellable gel-forming layer 12 An adhesive layer 13 laminated on the lower surface, an adhesive layer 13 ′ laminated on the upper surface of the water-swellable gel-forming layer 12 ′, and the adhesive layer 13 and the water-swellable gel-forming layers 12 and 12 ′ A peripheral portion of the water-swellable gel-forming layer 12 and the water-swellable gel so that the drug-containing layer 11 is enclosed in the oral administration agent 1. The peripheral portion of the forming layer 12 ′ is bonded via the adhesive layers 13 and 13 ′. In FIG. 2, the same members as those in FIG. 1 are denoted by the same reference numerals, and description thereof will be omitted unless particularly required.

  The oral administration agent 1b is different from the oral administration agent 1a in the adhesion mode between the peripheral part of the water-swellable gel-forming layer 12 and the peripheral part of the water-swellable gel-forming layer 12 ′. The entire content layer 11 is covered with water-swellable gel-forming layers 12 and 12 '. Moreover, water-swellable gel-forming layers 12 and 12 'are provided on the outermost layer as in the case of the orally administered agent 1a. Therefore, the orally-administered agent 1b can exert the same effects as the orally-administered agent 1a.

  The adhesive contained in the adhesive layers 13 and 13 'is not particularly limited as long as it is a pharmaceutically acceptable adhesive. Examples of the adhesive exhibiting adhesiveness when used in a solvent-containing state include, for example, carboxyvinyl polymer, polyacrylic acid such as sodium polyacrylate, or a pharmaceutically acceptable non-toxic salt thereof, and an acrylic acid copolymer. Or a pharmaceutically acceptable salt thereof, a hydrophilic cellulose derivative such as carboxymethylcellulose and sodium salt, pullulan, povidone, karaya gum, pectin, xanthan gum, tragacanth, alginic acid, gum arabic, acidic polysaccharide or derivative thereof or pharmaceutically Examples include acceptable salts, and one or more of these can be selected and used. Examples of the adhesive exhibiting adhesiveness by heating (that is, capable of being thermally fused) include homopolymers such as vinyl acetate and polyvinyl pyrrolidone, and copolymers of vinyl acetate and vinyl pyrrolidone. Alternatively, two or more types can be selected and used.

  The thicknesses of the adhesive layers 13 and 13 ′ can be adjusted as appropriate within the range in which oral administration is possible, but when the oral administration agent 1b is a film-form preparation, it is preferably 1 to 50 μm, More preferably, it is 30 μm. When the thickness of the adhesive layers 13 and 13 ′ is less than 1 μm, poor adhesion may be caused. On the other hand, when the thickness of the adhesive layers 13 and 13 ′ exceeds 50 μm, saliva or the like is taken when the oral administration agent 1b is taken. In addition, there is a possibility that the swelling due to water may be hindered, and in the case where the adhesive contained in the adhesive layer 13 or 13 ′ is insoluble in water, there is a possibility that the feeling of dosing will be deteriorated.

The orally administered agent 1b can be produced, for example, according to the following method.
[First production method]
A suspension containing a water-swellable gel-forming agent and a film-forming agent (for example, purified water) is applied and sprayed on the upper surface of a holding substrate such as a plastic film or a mount, and then dried. A water-swellable gel forming layer 12 is formed. Next, an adhesive-containing suspension (solvent is, for example, ethanol) is applied to the upper surface of the water-swellable gel-forming layer 12 and sprayed, and then dried to form the adhesive layer 13. In this way, a first laminate in which the water-swellable gel forming layer 12 and the adhesive layer 13 are sequentially laminated on the upper surface of the holding substrate is manufactured.
On the other hand, a water-swellable gel-forming layer 12 ′ and an adhesive layer 13 ′ are sequentially formed in the same manner as described above. Next, a suspension (solvent is, for example, ethanol) containing an additive such as a drug and an excipient, a binder, and a disintegrant is applied to the upper surface of the adhesive layer 13 ′, sprayed, etc., and then dried. To form the drug-containing layer 11. At this time, the size of the lower surface of the drug-containing layer 11 is smaller than the size of the upper surface of the adhesive layer 13 ′ (that is, the drug-containing layer 11 is formed at the center of the upper surface of the adhesive layer 13 ′. , So that the peripheral edge of the upper surface of the adhesive layer 13 'remains exposed). The method for forming the drug-containing layer 11 is not limited to the above method. For example, the drug-containing layer 11 is formed on the upper surface of the adhesive layer 13 ′ by printing using a known method such as a screen printing method. You can also. In this way, a second laminate in which the water-swellable gel-forming layer 12 ′, the adhesive layer 13 ′, and the drug-containing layer 11 are sequentially laminated on the upper surface of the holding substrate is manufactured.
Next, the peripheral portion of the water-swellable gel-forming layer 12 of the first laminate and the peripheral portion of the water-swellable gel-forming layer 12 ′ of the second laminate are bonded via the adhesive layers 13 and 13 ′. Thus, the orally administered drug 1b in which the drug-containing layer 11 is enclosed can be produced. Under the present circumstances, a desired adhesion | attachment aspect can be selected by selecting the kind of adhesive agent contained in adhesive bond layer 13 and 13 '. When the adhesive layers 13 and 13 ′ contain an adhesive that can be heat-sealed, they can be bonded by heat-sealing. Heat sealing is usually 60 to 150 ° C., preferably 90 to 120 ° C., usually 0.1 kgf / cm ² or more, preferably 0.5 kgf / cm ² or more, 0.1 to 5 seconds usually preferably 0.5 It can be performed under a condition of up to 3 seconds.

[Second production method]
In the same manner as in the first manufacturing method, the first laminate in which the water-swellable gel-forming layer 12 and the adhesive layer 13 are sequentially laminated on the upper surface of the holding substrate, and the water-swelling property on the upper surface of the holding substrate. A second laminate in which the gel forming layer 12 ′ and the adhesive layer 13 ′ are sequentially laminated is manufactured.
On the other hand, after applying or spraying a suspension containing an additive such as a drug and an excipient, a binder, a disintegrant, etc. (solvent is, for example, ethanol) on the upper surface of a holding substrate such as a plastic film or a mount This is dried to form the drug-containing layer 11. The drug-containing layer 11 thus formed is peeled from the holding substrate to obtain a drug-containing film, which is placed on the upper surface of the adhesive layer 13 of the first laminate or the adhesive layer 13 ′ of the second laminate. .
Next, in the same manner as described above, the peripheral portion of the adhesive layer 13 of the first laminate and the peripheral portion of the adhesive layer 13 ′ of the second laminate are adhered to each other so that the drug-containing film is enclosed inside. The oral administration agent 1b thus prepared can be produced.

  By the first or second production method, the water-swellable gel-forming layer 12 ′, the adhesive layer 13 ′, the drug-containing layer 11, the adhesive layer 13 and the water-swellable gel-forming layer 12 are sequentially laminated, and the drug-containing The oral administration agent 1b in which the layer 11 is encapsulated is manufactured. The oral administration agent 1b may be punched into an arbitrary shape such as a circular shape, an oval shape, or a polygonal shape as necessary. When punching out the orally-administered agent 1b, a portion where the peripheral portion of the water-swellable gel-forming layer 12 of the first laminate and the peripheral portion of the water-swellable gel-forming layer 12 'of the second laminate are bonded The drug-containing layer 11 is not exposed.

The following changes are possible in the orally administered agents 1a and 1b.
Orally administered agents 1a and 1b may have a functional layer other than the drug-containing layer, the water-swellable gel-forming layer, and the adhesive layer. Examples of the functional layer include a layer for adjusting the film thickness. When the orally-administered agents 1a and 1b are film-form preparations, the ease of handling of the orally-administered agents 1a and 1b can be improved by providing such a layer to increase the film thickness. Such a functional layer is provided between the water-swellable gel-forming layers 12 and 12 ′.

  Although the orally administered agents 1a and 1b have one drug-containing layer, the number of drug-containing layers is not particularly limited, and the orally administered agents 1a and 1b may have a plurality of drug-containing layers. When the orally administered agents 1a and 1b have a plurality of drug-containing layers, the drug-containing layers can be laminated directly or via an intermediate layer. One drug-containing layer may be formed by a plurality of drug-containing layers formed side by side.

  The orally administered agents 1a and 1b have two water-swellable gel-forming layers, but may have another water-swellable gel-forming layer. Such a water-swellable gel-forming layer may be provided between the water-swellable gel-forming layer 12 and the water-swellable gel-forming layer 12 ′ or outside the water-swellable gel-forming layers 12 and 12 ′. It may be provided.

  Although the drug-containing layer is encapsulated in the orally administered agents 1a and 1b, a drug that does not form the drug-containing layer may be encapsulated. For example, a drug formulated in an appropriate dosage form such as a tablet or powder may be encapsulated without forming a drug-containing layer. By using the formulated drug, the drug can be easily encapsulated inside the orally administered agents 1a and 1b (see the second production method above). In addition, by encapsulating the formulated drug inside the orally-administered agents 1a and 1b, the amount of useless drug consumed in the production of the orally-administered agents 1a and 1b can be suppressed, and cost reduction can be achieved. Can do.

  In the oral administration agent 1b, the adhesive layers 13 and 13 ′ are laminated on the entire lower surface of the water-swellable gel-forming layer 12 and the entire upper surface of the water-swellable gel-forming layer 12 ′, respectively. As long as the peripheral part of the forming layer 12 and the peripheral part of the water-swellable gel-forming layer 12 ′ can be combined, the size of the adhesive layers 13 and 13 ′, the position where the adhesive layers 13 and 13 ′ are provided, etc. Is not particularly limited. For example, like the orally-administered drug 1c shown in FIG. 3, the adhesive layers 13 and 13 ′ are respectively a part of the lower surface (peripheral portion) of the water-swellable gel-forming layer 12 and the water-swellable gel-forming layer 12 ′. You may laminate | stack on a part (periphery part) of an upper surface.

  The orally administered agent 1b has two adhesive layers 13 and 13 'between the peripheral edge of the water-swellable gel-forming layer 12 and the peripheral edge of the water-swellable gel-forming layer 12', but the water-swellable gel is formed. As long as the periphery of the layer 12 and the periphery of the water-swellable gel-forming layer 12 ′ can be combined, the periphery of the water-swellable gel-forming layer 12 and the periphery of the water-swellable gel-forming layer 12 ′ The number of adhesive layers provided therebetween is not particularly limited. For example, it is provided between the peripheral edge of the water-swellable gel-forming layer 12 and the peripheral edge of the water-swellable gel-forming layer 12 ′ as in the orally administered agents 1d to 1f shown in FIGS. One adhesive layer may be provided.

Hereinafter, the present invention will be described in more detail with reference to production examples and test examples.
(1) Preparation of water-swellable gel-forming layer forming liquid (coating liquid A) In order to form a water-swellable gel-forming layer, a coating liquid A having the following composition was prepared. That is, 140 g of purified water was taken, 1 g of potassium alum was added thereto, and the mixture was stirred for about 10 minutes for complete dissolution. Next, 6 g of polyacrylic acid (Carbopol 974P (BF Goodrich)) was slowly added with stirring and stirred for about 1 hour to completely dissolve. Next, 17 g of polyvinyl alcohol (Gosenol EG-05T (Nippon Synthetic Chemical)) was slowly added with stirring, and the mixture was completely dissolved by stirring for about 1 hour while heating to 70 ° C.
In addition, polyacrylic acid is bridge | crosslinked by the aluminum ion which ionizes potassium alum, and the crosslinked polyacrylic acid plays a role as a water-swellable gel-forming agent, and polyvinyl alcohol plays a role as a film-forming agent.

(2) Preparation of Adhesive Layer Formation Liquid (Coating Liquid B) In order to form an adhesive layer, a coating liquid B having the following composition was prepared. That is, 25 g of ethanol is taken, and 6 g of polyvinylpyrrolidone (PVP K-90 (ISP Japan)) is slowly added with stirring, and 1 g of glycerin is further added, followed by stirring for about 20 minutes for complete dissolution. It was. Polyvinyl pyrrolidone is a thermoplastic polymer and can be heat-sealed.

(3) Preparation of drug-containing layer forming liquid (coating liquid C) In order to form a drug-containing layer, a coating liquid C having the following composition was prepared. That is, after adding 7 g of famotidine which is a gastric ulcer drug and 0.2 g of titanium oxide in ethanol or purified water and sufficiently dispersing using a homogenizer, the following (a) to (k):
(A) Polyvinylpyrrolidone (PVP K-30 (ISP Japan))
(B) Polyvinylpyrrolidone-vinyl acetate copolymer (S-630 (ISP Japan))
(C) Carboxymethylcellulose sodium (Kanto Chemical)
(D) Hydroxypropyl cellulose (HPC SL grade (Nihon Soda))
(E) gum arabic (f) guar gum (g) xanthan gum (h) tragacanth gum (i) locust bean gum (j) carrageenan (k) sodium alginate base (binder) 20 g is slowly added with stirring The mixture was stirred for about 20 minutes to completely dissolve. The amount of the solvent at this time was appropriately adjusted so that the viscosity was 2000 to 6000 mPa · s.

[Production Example 1] Production of orally administered drug A (1) Formation of water-swellable gel-forming layer An applicator having a gap adjusted so that the coating liquid A is sufficiently defoamed and the thickness after drying is 30 μm. Using, spread-coating on the opposite surface of the polyethylene resin terephthalate film (product of Lintec Co., Ltd., product name: SP-PET3801) on the silicone resin release treatment surface, drying at 80 ° C. for about 10 minutes to form a water-swellable gel-forming layer Formed. Thus, the laminated body A by which the water swellable gel formation layer was laminated | stacked on the said polyethylene terephthalate film was manufactured. Similarly, another laminate A was produced.

(2) Formation of drug-containing layer After sufficiently defoaming the coating liquid C, 100 μL of the solution was dropped on the upper surface of the water-swellable gel-forming layer of the laminate A and dried at 80 ° C. for about 15 minutes. Thus, a drug-containing layer was formed. At this time, the drug-containing layer was formed not on the entire top surface of the water-swellable gel-forming layer but on a part of the top surface. That is, the drug-containing layer, the upper surface of water-swellable gel-forming layer (area: approximately 4.9 cm ²⁾ central portion of: is laminated on (area about 1.8 cm ^2), the peripheral portion of the water-swellable gel-forming layer Was formed so as not to be laminated. Thus, a laminate B was produced in which a water-swellable gel-forming layer and a drug-containing layer were sequentially laminated on the polyethylene terephthalate film.

(3) Manufacture of an orally administered drug by direct adhesion between water-swellable gel-forming layers Purified on the peripheral surface of the water-swellable gel-forming layer of laminate A and the peripheral surface of the water-swellable gel-forming layer of laminate B After water is applied and gelled, the gelled peripheral edges are pressure-bonded, then one polyethylene terephthalate film is peeled off, and dried at 80 ° C. for about 5 minutes, whereby the water-swellable gel-forming layer of laminate A The peripheral edge of the laminate and the peripheral edge of the water-swellable gel-forming layer of the laminate B were directly bonded. Thus, a water-swellable gel-forming layer, a drug-containing layer, and a water-swellable gel-forming layer are sequentially laminated on the polyethylene terephthalate film, and a laminate in which the drug-containing layer is enclosed is manufactured. The body was punched out to produce an orally administered drug A. When punching out the laminate, the portion where the water-swellable gel-forming layers were bonded to each other was punched out so that the drug-containing layer was not exposed.

[Production Example 2] Production of orally-administered drug B (1) Formation of water-swellable gel-forming layer Applicator with a gap adjusted so that coating liquid A is sufficiently defoamed and the thickness after drying is 30 μm Using, spread-coating on the opposite surface of the polyethylene resin terephthalate film (product of Lintec Co., Ltd., product name: SP-PET3801) on the silicone resin release treatment surface, drying at 80 ° C. for about 10 minutes to form a water-swellable gel-forming layer Formed.

(2) Formation of the adhesive layer The coating liquid B is sufficiently defoamed, and using an applicator in which the gap is adjusted so that the thickness after drying is 20 μm, the entire upper surface of the water-swellable gel-forming layer is formed. The coating was spread and dried at 80 ° C. for about 3 minutes to form an adhesive layer. Thus, a laminate C was produced in which a water-swellable gel-forming layer and an adhesive layer were sequentially laminated on the polyethylene terephthalate film. Similarly, another laminate C was produced.

(3) Formation of drug-containing layer After sufficiently defoaming the coating liquid C, 100 μL of the solution was dropped on the upper surface of the adhesive layer of the laminate C and dried at 80 ° C. for about 15 minutes to contain the drug. A layer was formed. At this time, the drug-containing layer was formed not on the entire top surface of the adhesive layer but on a part of the top surface. That is, the drug-containing layer, the upper surface of the adhesive layer: the central part of (area of approximately 4.9 cm ^2): is laminated on (area about 1.8 cm ^2), formed so as not to be laminated on the peripheral portion of the adhesive layer I let you. Thus, a laminate D was produced in which a water-swellable gel-forming layer, an adhesive layer, and a drug-containing layer were sequentially laminated on the polyethylene terephthalate film.

(4) Manufacture of an orally administered agent by heat-sealing adhesive layers to each other The peripheral edge portion of the adhesive layer of the laminate C and the peripheral edge portion of the adhesive layer of the laminate D are 100 ° C., 1 kgf / cm ² , 2 It was heat-sealed under the conditions for 2 seconds. In this way, a water-swellable gel-forming layer, an adhesive layer, a drug-containing layer, an adhesive layer and a water-swellable gel-forming layer were sequentially laminated on the polyethylene terephthalate film, and the drug-containing layer was sealed inside. A laminate was produced, and the laminate was punched out to produce an oral administration agent B. When the laminate was punched out, the portion where the adhesive layers were heat-sealed was punched out so that the drug-containing layer was not exposed.

[Production Example 3] Production of orally administered drugs C to F (1) Production of orally administered drug C 7 g of famotidine which is a gastric ulcer drug and 0.2 g of titanium oxide were added to ethanol and sufficiently dispersed using a homogenizer. Thereafter, 20 g of polyvinylpyrrolidone (PVP K-90 (ISP Japan)) was slowly added thereto while stirring, and the mixture was completely dissolved by stirring for about 20 minutes. The amount of the solvent at this time was appropriately adjusted so that the viscosity was 2000 to 6000 mPa · s.
The coating liquid prepared in this manner was sufficiently defoamed, and using an applicator with a gap adjusted so that the thickness after drying was 70 μm, a polyethylene terephthalate film (product name: SP-PET3801 manufactured by Lintec Corporation) was used. It spread-applied on the surface opposite to the silicone resin release treatment surface and dried at 80 ° C. for about 15 minutes to form a drug-containing layer. Next, the drug-containing layer was peeled from the polyethylene terephthalate film to obtain a drug-containing film.
After the drug-containing film is placed on the adhesive layer of the laminate C, the periphery of the adhesive layer of the laminate C and the periphery of the adhesive layer of another laminate C are set at 100 ° C., 1 kgf / cm. ² Heat-sealed under conditions of 2 seconds. The drug-containing film was placed at the center (area: about 1.8 cm ² ) of the upper surface (area: about 4.9 cm ² ) of the adhesive layer. In this way, a water-swellable gel-forming layer, an adhesive layer, a drug-containing film, an adhesive layer, and a water-swellable gel-forming layer were sequentially laminated on the polyethylene terephthalate film, and the drug-containing film was sealed inside. A laminate was produced, and the laminate was punched out to produce an oral administration agent C. When the laminate was punched out, the part where the adhesive layers were heat-sealed was punched out so that the drug-containing film was not exposed.

(2) Manufacture of Orally Administered Drug D The coating solution prepared in (1) above was prepared by subjecting the laminate C to a screen printing method using a 60 mesh (wire diameter 140 μm) screen formed with a 15 mmφ plate. the upper surface of the adhesive layer (area: approximately 4.9 cm ²⁾ central portion of: printing on (area about 1.8 cm ^2), and dried at 80 ° C. for about 15 minutes. This was repeated until the thickness after drying was 70 μm to form a drug-containing layer. Thus, a laminate E was produced in which a water-swellable gel-forming layer, an adhesive layer and a drug-containing layer were sequentially laminated on the polyethylene terephthalate film. The peripheral edge of the adhesive layer of the laminate C and the peripheral edge of the adhesive layer of the laminate E were heat-sealed under the conditions of 100 ° C., 1 kgf / cm ² and 2 seconds. In this way, a water-swellable gel-forming layer, an adhesive layer, a drug-containing layer, an adhesive layer and a water-swellable gel-forming layer were sequentially laminated on the polyethylene terephthalate film, and the drug-containing layer was sealed inside. A laminate was produced, and the laminate was punched out to produce an oral administration agent D. When the laminate was punched out, the portion where the adhesive layers were heat-sealed was punched out so that the drug-containing layer was not exposed.

(3) Manufacture of Orally Administered Drug E Adhesive layer of laminate C was obtained by adding 500 mg of powder obtained by adding famotidine and lactose (excipient) to a mortar at 1:49 (weight ratio) and mixing thoroughly. Then, the peripheral edge of the adhesive layer of the laminate C and the peripheral edge of the adhesive layer of another laminate C are thermally melted at 100 ° C., 1 kgf / cm ² , for 2 seconds. I wore it. Thus, a laminate in which a water-swellable gel-forming layer, an adhesive layer, a drug powder, an adhesive layer, and a water-swellable gel-forming layer are sequentially laminated on the polyethylene terephthalate film, and the drug powder is enclosed inside. And the laminate was punched out to produce an orally-administered drug E. When the laminate was punched out, the portion where the adhesive layers were heat-sealed was punched out so that the drug powder was not exposed.

(4) Production of Orally Administered Drug F A powder obtained by mixing famotidine and polyvinylpyrrolidone (PVP K-90 (ISP Japan)) at 1:49 (weight ratio) was punched with a tableting machine used in the KBr tablet method. Locked. After the obtained tablet is placed on the upper surface of the adhesive layer of the laminate C, the peripheral portion of the adhesive layer of the laminate C and the peripheral portion of the adhesive layer of another laminate C are set at 100 ° C., 1 kgf. / Cm ² , and heat-sealed under conditions of 2 seconds. In this way, a water-swellable gel-forming layer, an adhesive layer, a tablet, an adhesive layer and a water-swellable gel-forming layer are sequentially laminated on the polyethylene terephthalate film, and a laminate in which the tablet is enclosed is manufactured. Then, the laminate was punched out to produce an orally administered agent F. When the laminate was punched out, the part where the adhesive layers were heat-sealed was punched out so that the tablets were not exposed.

[Test Example 1] Evaluation test on masking of taste of drug The oral administration agent A produced in Production Example 1 and the oral administration agent B produced in Production Example 2 were taken at random to subject 10 without water. The taste masking ability of the drug was evaluated according to the following three-stage evaluation criteria. The results regarding the oral administration agent A are shown in Table 1, and the results concerning the oral administration agent B are shown in Table 2.
[Evaluation criteria for masking ability]
1 ... I feel the taste of drugs.
2 ... Slightly feel the taste of the drug.
3 ... I do not feel the taste of the drug.

  As shown in Table 1 and Table 2, when the peripheral portions of the water-swellable gel-forming layers are directly bonded to each other (oral administration agent A), the peripheral portions of the water-swellable gel-forming layers are connected to each other via the adhesive layer. In any case of adhering (orally administered agent B), the taste of the drug contained in the drug-containing layer was completely masked regardless of the type of base contained in the drug-containing layer.

[Test Example 2]
With respect to the orally administered drugs C to F produced in Production Example 3, drug taste masking ability was evaluated in the same manner as in Test Example 1. The results are shown in Table 3.

  As shown in Table 3, the taste of the drug contained in the drug-containing layer was completely masked regardless of the dosage form of the drug encapsulated inside the orally administered drug.

1a, 1b, 1c, 1d, 1e, 1f, 1g ... Orally administered agent 11 ... Drug-containing layer 12, 12 '... Water-swellable gel-forming layer 13, 13' ... Adhesive layer

Claims (11)

An oral administration agent in which a first water-swellable gel-forming layer and a second water-swellable gel-forming layer are provided in the outermost layer,
The peripheral portion of the first water-swellable gel-forming layer and the peripheral portion of the second water-swellable gel-forming layer can be heat-sealed so that the drug is enclosed in the oral administration agent. The said oral administration agent couple | bonded by heat-seal | fusing through the adhesive bond layer containing an adhesive agent. A drug-containing layer provided between the first water-swellable gel-forming layer and the second water-swellable gel-forming layer;
The peripheral part of the first water-swellable gel-forming layer and the peripheral part of the second water-swellable gel-forming layer are thermally fused so that the drug-containing layer is enclosed in the oral administration agent. The oral administration agent according to claim 1, wherein the oral administration agent is bonded by being heat-sealed through an adhesive layer containing an attachable adhesive.   The oral administration agent according to claim 1 or 2, wherein the heat-fusible adhesive is a polyvinylpyrrolidone homopolymer.   The first water-swellable gel-forming layer and the second water-swellable gel-forming layer are formed from a water-swellable gel-forming layer forming liquid containing a water-swellable gel-forming agent and a crosslinking agent. The oral administration agent as described in any one of Claims 1-3.   The oral administration agent according to claim 4, wherein the water-swellable gel-forming agent is a carboxyvinyl polymer.   The oral administration agent according to claim 4 or 5, wherein the crosslinking agent is a polyvalent metal compound. A method for producing an orally administered agent, comprising:
A step of producing a first laminate in which an adhesive layer containing a first water-swellable gel-forming layer and an adhesive capable of being thermally fused is sequentially laminated on the upper surface of the first holding substrate;
The second water-swellable gel-forming layer, the adhesive layer containing a heat-fusible adhesive, and the drug-containing layer contain the drug more than the size of the upper surface of the second water-swellable gel-forming layer. Producing a second laminate sequentially laminated on the upper surface of the second holding substrate so that the size of the lower surface of the layer is reduced;
The peripheral part of the first water-swellable gel-forming layer and the peripheral part of the second water-swellable gel-forming layer, so that the drug-containing layer is enclosed in the oral administration agent, Adhering by heat fusion via the adhesive layer laminated on the first water-swellable gel-forming layer and the adhesive layer laminated on the second water-swellable gel-forming layer. A method for producing an orally administered drug.   The method for producing an oral administration agent according to claim 7, wherein the heat-fusible adhesive is a polyvinylpyrrolidone homopolymer.   The first water-swellable gel-forming layer and the second water-swellable gel-forming layer are formed from a water-swellable gel-forming layer forming liquid containing a water-swellable gel-forming agent and a crosslinking agent. The manufacturing method of the oral administration agent of Claim 7 or 8.   The method for producing an oral administration agent according to claim 9, wherein the water-swellable gel-forming agent is a carboxyvinyl polymer.   The method for producing an oral administration agent according to claim 9 or 10, wherein the crosslinking agent is a polyvalent metal compound.

Images