JP2013018758A - Solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid preparation capable of staying inside the stomach after being taken, and discharging a drug surely to the inside of the stomach.SOLUTION: This solid preparation 1 has a pair of edible films 10, a space part 20 formed by bonding each peripheral part of the pair of edible films 10, and a drug containing part 30 stored in the space part 20. The volume ratio of the drug containing part 30 to the volume of the space part 20 interior is 0.5-0.95. Inert gas is filled in the space part 20. The shape of the space part is approximately spherical. Further, the edible film 10 has an adhesion preventing layer 11, a gel forming layer 12 and a bonding layer 13.

Description

  The present invention relates to a solid preparation.

  As oral administration agents containing drugs and taken from the mouth, for example, solid preparations such as tablets and capsules are known.

  Such an orally administered drug may have a reduced compliance due to various causes such as discomfort due to the bitterness or astringency of the drug, nausea or vomiting due to the drug, or rejection of the drug.

  In order to make swallowing relatively easy, various attempts have been made, for example, a structure in which the surface is dissolved by saliva in the oral cavity, or a structure in which it absorbs water and forms a gel. (For example, refer to Patent Document 1).

  However, since the conventional solid preparation easily sinks in the gastric juice due to its high specific gravity, it has been difficult to sufficiently retain it in the stomach. For this reason, it has been difficult to stably release the drug inside the stomach.

JP 11-116469 A

  An object of the present invention is to provide a solid preparation that stays in the stomach after administration and can reliably release the drug into the stomach.

Such an object is achieved by the present inventions (1) to (6) below.
(1) a pair of edible films;
A space formed by joining the pair of edible films at their outer edges, and
A drug-containing part encapsulated in the space part,
A solid preparation, wherein the volume ratio of the drug-containing part to the space part is 0.5 to 0.95.

  (2) The solid preparation according to (1), wherein the space is filled with an inert gas.

  (3) The solid preparation according to (1) or (2), wherein the space portion has a substantially spherical shape.

  (4) The solid preparation according to any one of (1) to (3), wherein the drug-containing part is composed of a tablet that has been compressed.

  (5) The edible film is provided with an adhesion preventing layer that prevents the solid preparation from adhering to the inner wall of the oral cavity by dissolving in water on the surface opposite to the space portion (1). The solid preparation according to any one of (4) to (4).

(6) The edible film has an adhesive layer on the space portion side,
The pair of edible films is the solid preparation according to any one of the above (1) to (5), in which the adhesive layers on the outer edge of each edible film are joined.

  According to the present invention, it is possible to provide a solid preparation capable of floating in gastric juice and staying in the stomach after being taken and capable of releasing the drug in the stomach.

It is a front view which shows suitable embodiment of the solid formulation of this embodiment. It is a top view which shows suitable embodiment of the solid formulation of this embodiment. It is sectional drawing of the solid formulation in AA of FIG. It is sectional drawing which shows suitable embodiment of an edible film.

Hereinafter, the present invention will be described in detail based on preferred embodiments.
FIG. 1 is a front view showing a preferred embodiment of the solid preparation of the present embodiment, FIG. 2 is a plan view showing a preferred embodiment of the solid preparation of the present embodiment, and FIG. 3 is AA of FIG. FIG. 4 is a cross-sectional view showing a preferred embodiment of an edible film.

  As shown in FIGS. 1 to 3, the solid preparation 1 includes a pair of edible films 10, a space portion 20 formed by joining the peripheral portions of the pair of edible films 10, and the space portion 20. And a contained drug-containing portion 30.

  The edible film 10 is a film made of an edible material. The space part 20 mentioned later is formed by joining a pair of such edible films 10 in the outer edge part.

  In the present embodiment, the edible film 10 includes an adhesion preventing layer 11, a gel forming layer 12, and an adhesive layer 13, as shown in FIG.

  The adhesion preventing layer 11 is laminated on the main surface opposite to the space 20 and is provided as a surface layer located on the surface of the edible film 10.

  Moreover, the adhesion prevention layer 11 has a function which melt | dissolves rapidly with water | moisture contents, such as saliva, in the oral cavity, and prevents that the solid formulation 1 (edible film 10) adheres to the inner wall in an oral cavity.

  By providing such an adhesion preventing layer 11, when the solid preparation 1 is administered into the oral cavity, the surface portion of the adhesion preventing layer 11 quickly dissolves in saliva. A liquid film is quickly formed between the inner wall and the inner wall, so that the solid preparation 1 becomes slippery with respect to the inner wall. For this reason, the solid preparation 1 is prevented from coming into contact with the inner wall and hardly adheres to the inner wall of the oral cavity. Moreover, even if it is a case where a part of solid formulation 1 adheres to an inner wall, the solid formulation 1 will become easy to peel from an inner wall. Thereby, while being able to prevent the solid formulation 1 adhering to an inner wall and causing discomfort, it becomes easy to swallow the solid formulation 1. In addition, the drug can be reliably transported to a target site in the body. Moreover, it becomes possible to apply the chemical | medical agent which exhibits unpleasant taste (for example, bitterness, astringency, a feeling of numbness), smell, etc. to the solid formulation 1.

  The material constituting the adhesion preventing layer 11 (adhesion preventing agent) is not particularly limited. For example, hydroxyalkyl cellulose, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyoxyl stearate, polyoxyethylene polyoxypropylene glycol, polyoxy Water-soluble polymer materials such as ethylene hydrogenated castor oil, gum arabic and gelatin, erythritol, sorbitol, xylitol, mannitol, inositol, maltitol, lactitol, glucose, xylose, mannose, fructose, galactose, sucrose, fructose, sucrose, etc. , Propylene glycol, glycerin, and the like. Among these, one or a combination of two or more can be used. Examples of the hydroxyalkyl cellulose include hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and the like.

  Among the above-mentioned, the adhesion preventing layer 11 preferably contains a water-soluble polymer material as an adhesion preventing agent. The water-soluble polymer material can be suitably dissolved in moisture and has a molecular chain with an appropriate length. For this reason, the water-soluble polymer material can appropriately entangle the molecular chains of a plurality of water-soluble polymers constituting the water-soluble polymer material. Can be unevenly distributed. For this reason, it is prevented that the solid formulation 1 adheres to the inner wall of an oral cavity reliably over a longer period. In addition, the water-soluble polymer material as described above can also function as a base of the adhesion preventing layer 11, can facilitate the production of the edible film 10, and the produced edible film 10. The durability at the time of storage can be made particularly excellent. In particular, among the above-mentioned water-soluble polymer materials, when at least one selected from hydroxypropylmethylcellulose, polyethylene glycol and polyvinyl alcohol is used, the above-described effects can be obtained more remarkably.

  Moreover, the adhesion preventing layer 11 may contain components other than those described above. For example, the adhesion preventing layer 11 may include a plasticizer, a masking agent, a preservative, a colorant, and the like.

  Examples of the plasticizer include glycerin, polyethylene glycol, triethyl citrate, propylene glycol, polyoxyethylene / polyoxypropylene glycol, triacetylene, polysorbate 80, and the like. Examples of masking agents include sweeteners such as saccharin, glycyrrhizic acid, sucrose, fructose, mannitol, acesulfame potassium, saccharin sodium, stevia extract, aspartame, sucralose, neotame, thaumatin; and sour tastes such as citric acid, tartaric acid, and fumaric acid. The charge; etc. are mentioned. Examples of the preservative include benzalkonium chloride and paraben. Examples of the colorant include titanium oxide, iron sesquioxide, and food red.

  The gel forming layer 12 is provided between the adhesion preventing layer 11 and an adhesive layer 13 described later, and is a layer that can swell to form a gel by absorbing moisture.

  The gel-forming layer 12 quickly absorbs moisture in saliva in the oral cavity to form a gel, so that in the oral cavity, the solid preparation 1 is quickly given flexibility and is easy to swallow. Become.

  The gel forming layer 12 includes a gel forming agent that swells by absorbing moisture to form a gel. By including such a gel-forming agent, the gel-forming layer 12 can easily and quickly absorb the surrounding water and form a gel.

  The gel forming agent is not particularly limited, and examples thereof include carboxyvinyl polymer, starch and derivatives thereof, agar, alginic acid, arabinogalactan, galactomannan, cellulose and derivatives thereof, carrageen, dextran, tragacanth, gelatin, pectin, and hyaluron. Acid, gellan gum, collagen, casein, xanthan gum and the like can be mentioned, and one or more of these can be used in combination.

  The gel forming agent may be cross-linked by ionic bond or covalent bond or may not be cross-linked.

  Further, the gel forming layer 12 may include a water absorption accelerator that promotes water absorption of the gel forming layer 12. When the gel forming layer 12 contains a water absorption accelerator, the water absorption speed of the gel forming layer 12 in the oral cavity is sufficiently high. For this reason, the swallowability of the solid preparation 1 is particularly excellent.

  As the water absorption accelerator, for example, a component having a relatively high solubility in water can be used. Since a component having a relatively high solubility in water dissolves in water, water can be transported into the gel forming layer 12, and as a result, the gel forming layer 12 can quickly absorb moisture.

  The water absorption promoter is not particularly limited. For example, glycols such as propylene glycol, polyethylene glycol, polypropylene glycol, polyoxyl stearate, polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, glycerin, erythritol, sorbitol , Sugars such as xylitol, mannitol, inositol, maltitol, lactitol, glucose, xylose, mannose, fructose, galactose, sucrose, fructose, sucrose, etc., among which one or more can be used in combination .

  Moreover, the gel forming layer 12 may contain components other than those described above. For example, it may contain a plasticizer, a masking agent, a preservative, a colorant and the like described in the description of the adhesion preventing layer 11.

  The adhesive layer 13 is a layer having a function of adhering the peripheral portions of the pair of edible films 10 and is provided on the space 20 side.

  The material constituting the adhesive layer 13 is not particularly limited, but is preferably composed of at least one material selected from the group consisting of polyvinyl pyrrolidone, vinyl acetate, and vinyl acetate / vinyl pyrrolidone copolymer. Thereby, it becomes possible to join the edible films 10 easily with heat.

  Moreover, the adhesive layer 13 may contain components other than those described above. For example, it may contain a plasticizer, a masking agent, a preservative, a colorant and the like described in the description of the adhesion preventing layer 11.

  The space portion 20 is a space formed by joining the peripheral portions of the pair of edible films 10 described above, and has a function of accommodating a drug-containing portion 30 described later.

  The shape of the space 20 is preferably substantially spherical as shown in FIGS. Thereby, when taking the solid preparation 1, the contact area with the oral cavity, the esophagus, etc. can be made comparatively small, and it becomes possible to swallow easily.

  The space 20 is preferably filled with an inert gas. Thereby, the stability of the drug in the drug containing part 30 can be improved.

Note that in this specification, an inert gas refers to a gas that hardly causes a chemical reaction, and is a concept that includes, for example, a rare gas group element such as helium, neon, or argon, nitrogen, and the like.
The oxygen concentration in the space 20 is preferably 1% or less, more preferably 0.1% or less, and particularly preferably 0.01% or less.

The drug containing part 30 is a part containing the drug to be administered.
In the present invention, the volume ratio of the drug-containing part 30 to the volume inside the space part 20 is 0.5 to 0.95. By having such characteristics, the solid preparation 1 can float in the gastric juice and stay in the stomach without sinking into the gastric juice as in the conventional solid preparation in the stomach after taking. As a result, a necessary amount of drug can be reliably released into the stomach.

  In the present invention, the volume ratio of the drug-containing part 30 to the space part 20 is 0.5 to 0.95, but more preferably 0.6 to 0.9. Thereby, the effect of this invention can be made more remarkable.

  Examples of the drug contained in the drug-containing part 30 include drugs that act on the central nervous system such as amobarbital, estazolam, triazolam, nitrazepam, pentobarbital, and other hypnotics, amitriptine hydrochloride, imipramine hydrochloride, oxazolam, chlordiazepoxide, chlorpromazine, Psychotropic drugs such as diazepam, sulpiride, haloperidol, antiparkinson drugs such as trihexyphenidyl, levodopa, analgesics such as aspirin, isopropylantipyrine, indomethacin, diclofenac sodium, mefenamic acid, streptokinase, streptodornase, serrapeptase, pronase And central nervous system metabolism stimulators such as anti-inflammatory drugs, ATP and vinpocetine, and drugs acting on the respiratory tract, such as carbocysteine and promhexine hydrochloride Anti-asthma drugs such as glaze, azelastine hydrochloride, oxatomide, theophylline, terbutaline sulfate, tranilast, procaterol hydrochloride, ketotifen fumarate, and other drugs acting on the circulatory system include cardiotonic drugs such as aminophylline, digitoxin, digoxin, adimarin, disopyramide Antiarrhythmic drugs such as procainamide hydrochloride, mexiletine hydrochloride, amyl nitrite, alprenolol hydrochloride, isosorbide nitrate, nicorandil nitrate, oxyfedrine, dipyridamole, dilazep hydrochloride, diltiazem hydrochloride, nitroglycerin, nifedipine, verapamil hydrochloride, etc. Peripheral vasodilators such as psychiatric drugs, kallidinogenase, atenolol, captopril, clonidine hydrochloride, metoprolol tartrate, spironolactone, triamterene, trichlormethiazide, nicardi , Hydralazine hydrochloride, hydrochlorothiazide, prazosin hydrochloride, furosemide, propranolol hydrochloride, enalapril maleate, methyldopa, labetalol hydrochloride, reserpine and other antihypertensive drugs, clofibrate, dextran sulfate, anti-arteriosclerotic drugs such as nicomol, niceritrol, blood and Hematopoietic agents, hemostatic agents such as sodium carbazochrome sulfonate and tranexamic acid, antithrombotic agents such as ticlopidine hydrochloride and warfarin potassium, anti-anemic agents such as iron sulfate, drugs that act on the digestive system, azulene, aldioxa, Anti-ulcer drugs such as cimetidine, ranitidine hydrochloride, famotidine, teprenone, rebamipide, antiemetics such as domperidone and metoclopramide, suppositories such as sennoside, digestive enzyme preparations, glycyrrhizin, liver extract preparations, etc. Drugs for liver diseases, drugs acting on metabolic diseases, antidiabetic drugs such as glibenclamide, chlorpropamide, tolbutamide, gout drugs such as allopurinol and colchicine, drugs for ophthalmology, acetazolamide, drugs for otolaryngology Anti-vertigo drugs such as diphenidol hydrochloride and betahistine mesylate, chemotherapeutic drugs and antibiotics such as isoniazid, ethambutol hydrochloride, ofloxacin, erythromycin stearate, cefaclor, norfloxacin, fosfomycin calcium, minocycline hydrochloride, rifampicin, rokitamycin Drugs such as cyclophosphamide, tegafur, etc .; immunosuppressive drugs such as azathioprine, hormones and endocrine therapeutic agents such as progesterone, salivary gland hormone, thiamazole, Donisolone, betamethasone, liothyronine, levothyroxine, and other biologically active substances (ortachoids), antihistamines such as diphenhydramine hydrochloride, clemastine fumarate, chlorpheniramine maleate, alphacalcidol, cobamide, tocopherol nicotinate, mecoparamine These can be used, and one or more of these can be used in combination depending on the purpose of treatment / prevention.

  Moreover, the drug containing part 30 may contain a base. Examples of the base include cellulose such as crystalline cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, and the like. And derivatives thereof or pharmaceutically acceptable salts thereof (for example, sodium salts); starches such as α-starch, oxidized starch, sodium carboxymethyl starch, hydroxypropyl starch, dextrin, dextran, and derivatives thereof; dimethyl methacrylate Aminoethyl-methacrylic acid copolymer, methacrylic acid Ethyl laurate copolymer, methacrylic acid / methyl methacrylate copolymer, ethyl methacrylate / methacrylated trimethylammonium copolymer, dimethylaminoethyl methacrylate / methacrylated methyl copolymer, methacrylate / ethyl acrylate Acrylic acid derivatives such as copolymers; shellac; polyvinyl acetal diethylaminoacetate; polyvinyl acetate; polyvinyl alcohol; polyvinyl pyrrolidone; vinyl acetate-vinyl pyrrolidone copolymers; natural rubbers such as gum arabic and tragacanth; polyglucosamines such as chitin and chitosan Proteins such as gelatin, casein and soybean protein; calcium monohydrogen phosphate; calcium carbonate; talc; stearate; magnesium aluminate metasilicate Magnesium silicate, silicic anhydride, and the like, and depending on the purpose of addition, one or more of these can be selected and used.

  Further, the drug-containing unit 30 may contain components other than those described above. For example, it may contain a plasticizer, a masking agent, a preservative, a colorant and the like described in the description of the adhesion preventing layer 11.

In addition, it is preferable that the medicine containing part 30 is comprised with the tablet formed into a tablet. Thereby, unintentional release of the drug in the oral cavity can be prevented, and the drug can be reliably released in the stomach. Moreover, even when the specific gravity of the tablet that has been compressed exceeds 1 g / cm ³ , the volume ratio of the drug-containing portion 30 to the volume inside the space portion 20 is adjusted so that the specific gravity of the solid preparation is 1 g / cm ^3. By setting it to less than that (preferably less than 0.95 g / cm ³ ), it can float in the gastric juice and stay in the stomach.

  As mentioned above, although this invention was demonstrated about embodiment of illustration, this invention is not limited to this.

  For example, the edible film constituting the solid preparation of the present invention may have an arbitrary layer other than the adhesion preventing layer, the gel forming layer, and the adhesive layer.

  Specific examples of the optional layer include a disintegration control layer made of a material containing a gastric material that dissolves when in contact with gastric juice.

  The gastric soluble material is not particularly limited, and for example, a material that dissolves under acidic conditions and hardly dissolves under neutral and alkaline conditions can be used. Specifically, as the gastric material, various inorganic compounds such as calcium carbonate and sodium hydrogen carbonate, various gastric polymers and the like can be used. These compounds can be used alone or in combination of two or more.

  Gastric soluble polymers include gastric soluble polyvinyl derivatives such as polyvinyl amino acetal and polyvinyl acetal diethyl amino acetate, methyl (meth) acrylate-butyl (meth) acrylate-dimethyl (meth) acrylate, aminoalkyl Examples include gastric soluble acrylic acid copolymers such as (meth) acrylate copolymers.

  Moreover, for example, the edible film constituting the solid preparation of the present invention may be a single layer film such as an adhesion preventing layer, a gel-forming layer, a disintegration control layer, or a laminated film thereof.

  Examples of the laminated film include an adhesion prevention layer / gel formation layer, an adhesion prevention layer / disintegration control layer, an adhesion prevention layer / adhesion layer, a gel formation layer / adhesion layer, a collapse control layer / adhesion layer, and a gel formation layer / disintegration. Control layer, disintegration control layer / gel formation layer, gel formation layer / disintegration control layer / adhesion layer, adhesion prevention layer / gel formation layer / disintegration control layer, adhesion prevention layer / disintegration control layer / gel formation layer, adhesion prevention layer / Examples thereof include a gel-forming layer / disintegration control layer / adhesion layer, an adhesion prevention layer / disintegration control layer / gel-formation layer / adhesion layer and the like, and a film having an arbitrary layer between these layers.

  In the above-described embodiment, the space portion has a substantially spherical shape. However, the present invention is not limited to this.

DESCRIPTION OF SYMBOLS 1 ... Solid preparation 10 ... Edible film 11 ... Adhesion prevention layer 12 ... Gel formation layer 13 ... Adhesive layer 20 ... Space part 30 ... Drug containing part

Claims (6)

A pair of edible films;
A space formed by joining the pair of edible films at their outer edges, and
A drug-containing part encapsulated in the space part,
A solid preparation, wherein the volume ratio of the drug-containing part to the space part is 0.5 to 0.95.   The solid preparation according to claim 1, wherein the space is filled with an inert gas.   The solid preparation according to claim 1 or 2, wherein the shape of the space is substantially spherical.   The solid preparation according to any one of claims 1 to 3, wherein the drug-containing part is composed of a tablet that has been compressed.   The edible film is provided with an adhesion preventing layer that prevents the solid preparation from adhering to the inner wall of the oral cavity by dissolving in water on the surface opposite to the space portion. The solid preparation according to any one of the above. The edible film has an adhesive layer on the space portion side,
The solid preparation according to any one of claims 1 to 5, wherein the pair of edible films are formed by bonding the adhesive layers of outer edges of the edible films.

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