JPH05124954A - Sheetlike solid medicinal composition - Google Patents

Abstract

(57) [Summary] [Objective] It is an object to provide a pharmaceutical composition supported on a sheet-shaped carrier having excellent handleability. [Structure] A component consisting of 92 parts by weight of crystalline cellulose, 5 parts by weight of hydroxy starch, 3 parts by weight of corn starch and a trace amount of polyvinyl alcohol is suspended in water, and the resulting product is made into a paper, and a sheet (1) having a thickness of about 1 mm is prepared. Manufactured.
On this paper, 6 parts by weight of shellac, 10 parts by weight of mestranol, 44 parts by weight of ethanol, 20 parts by weight of butanol,
A product was obtained by printing (2) with a pattern as shown in FIG. 1 using a printing ink containing a slight amount of yellow dye No. 5, punching (3) with a punch die, and inserting a slit (4) that can be separated with a cutter knife. The content of mestranol per drug was 0.02 mg.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel sheet-shaped solid pharmaceutical composition. More specifically, the present invention relates to a sheet-shaped solid pharmaceutical composition which has a very small amount of a substance having a physiological activity and is carried on a sheet-shaped carrier to prepare a pharmaceutical preparation, which is extremely easy to handle.

[0002]

BACKGROUND ART Heretofore, granules, fine granules, powders, tablets, capsules and the like have been known as a method for preparing a solid preparation of a substance having a physiologically active action in a trace amount such as prostaglandin and hormone. There is.

Among these preparations, in the case of granules, fine granules, powders, tablets and hard capsules, since the physiologically active substance is handled as a powder, it is inevitable to generate dust, which adversely affects workers. Due to the possibility of environmental pollution, it was required to install remote control equipment, to make the air conditioning line independent and to manage it closely.

[0004]

DISCLOSURE OF THE INVENTION It is an object of the present invention to provide a pharmaceutical composition in which a small amount of a substance having a physiologically active action, which does not have the above-mentioned drawbacks, is carried on a sheet-shaped carrier, and a method for producing the same. Is.

[0005]

Means for Solving the Problems The present inventors have found that the above problems can be solved by applying a technique such as printing to a physiologically active substance with a small dose per administration. The invention was completed.

That is, the present invention is characterized in that a pharmaceutically acceptable sheet-like carrier is printed, coated, sprayed or injected with a solution or suspension containing a trace amount of a substance having a physiologically active action. Is a sheet-like solid pharmaceutical composition.

The present invention will be described in detail below. As the substance having a physiologically active effect in a trace amount in the present invention, a dose of 1 mg / dose or less is preferable, and specifically, estrogen hormone flavoring agents such as mestranol, estriol, estrogen, ethinyl estradiol; , Methylestrenolone-ethinylestradiol, norgestrel-ethinylestradiol, etinodiol-mestranol and other mixed luteal / follicle hormone agents; anabolic steroid agents such as flazabol, stanozolol, ethylnandolol; thyroid hormone agents such as levothyroxine sodium;
Corticosteroids such as betamethasone, triamcinolone acetonide, betamethasone sodium phosphate, dexamethasone;

Antihistamines such as triprolidine hydrochloride;
Antiallergic agents such as clemastine fumarate, ketotifen fumarate, and azelastine hydrochloride; bronchodilators such as flumoterol fumarate, procaterol hydrochloride, hesoprenaline sulfate, mabuterol hydrochloride, clenbuterol hydrochloride, tulobuterol hydrochloride; flupenthixole hydrochloride, spiperone, timiperone, etc. For schizophrenia; minor tranquilizers such as alprazom, cloxazolam and lorazepam; tranquilizers such as etizolam and diazepam;
Anxiolytics such as mexazolam; Central nervous system stimulants such as pipadorol; Sleep-inducing and hypnotic agents such as triazolam and estazolam; Stimulants such as methamphetamine hydrochloride; Guanfacine hydrochloride, prazosin hydrochloride, terazosin hydrochloride, reserpine, arteroxilone, indapamide , Antihypertensive agents such as clonazepam; orthostatic hypotensive / migraine agents such as dihydroergotamine mesylate; cerebral and peripheral circulatory disorder improving agents such as dihydroergotoxine mesylate; maleic acid Uterine contracting hemostatic agents such as dihydroergomethrin;

Analgesic / analgesic agents such as N-methylscopolamine methylsulfate; Parasympathetic nerve blockers such as atropine sulfate;
Gout remedies such as colchicine; cardiac glycosides such as digitoxin, digoxin, lanatoside, proscillaridin; coronary artery dilators such as nitroglycerin; hypoglycemic agents such as glibenclaside; acne remedies such as pregnanediol;
Vitamin preparations such as hydroxocobalamin acetate, mecobalamin, cyanocobalamin, cobamamide, alfacasidol, calcitriol, vitamin B ₁ and biotin; antineoplastic agents such as carbocon; hypocalcemia improving agents such as dihydrotaxosterol; glycobromide Peptic ulcer agents such as pyronium and clevoprid malate; organic iodine preparations such as calcium diiodostearate; hair loss leukopenia inhibitors such as cepharanthin; prostaglandins such as dinoplastone.

Further, as the pharmaceutically acceptable carrier in the present invention, specifically, cellulose such as crystalline cellulose, carboxymethyl cellulose, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose, hydroxypropyl cellulose, low substituted hydroxypropyl cellulose and the like, and Derivatives thereof; various starches, α-starch, oxidized starch, sodium carboxymethyl starch, hydroxypropyl starch, dextrin, dextran and other starches and derivatives thereof;
(Poly) sugars such as sucrose, maltose, lactose, glucose, fructose, pullulan, xanthan gum, cyclodextrin; sugar alcohols such as mannitol and sorbitol; polyglucosamines such as chitin and chitosan; gelatin, casein,
Proteins such as soybean protein; inorganic carriers such as titanium oxide, calcium monohydrogen phosphate, calcium carbonate, talc, stearate, magnesium aluminometasilicate, magnesium silicate, and silicic acid anhydride, and polyethylene that imparts plasticity to the carrier. Examples thereof include glycol, glycerin fatty acid ester, castor oil, phthalic acid ester, triacetin, polypropylene glycol and the like, and these may be used by appropriately mixing a plurality of components according to the purpose.

The pharmaceutical composition of the present invention can be produced, for example, as follows. According to the production method of Japanese paper, the pharmaceutically acceptable carrier described above is scraped off with a bleached cloth with a wooden frame attached to a suspension of crystalline cellulose and an appropriate binder.
A method of drying to obtain a carrier, or a suspension containing hydroxypropylmethylcellulose and crystalline cellulose is poured onto a Teflon plate with a frame and dried to obtain a carrier. An ink containing a medicinal agent, a binder, a solvent, a plasticizer, and a pigment is prepared. The composition is printed, applied, sprayed, injected or impregnated so that a predetermined amount of the drug component is present on a certain area or volume of the carrier. For printing, use an offset printing machine, etc. 1
A predetermined amount of drug is contained in the carrier by printing once or several times. At this time, if necessary, the surface of the drug-containing carrier may be overcoated with a drug-free ink composition. Finally, the pharmaceutical composition of the present invention can be obtained by punching into any shape such as a circle, an ellipse, a polygon, or by forming a slit. In the case of film-like to plate-like preparations, it is not always necessary to punch completely because of the fact that card-like preparations can be made and packaging can be made compact.

In the present invention, when a carrier shaped into a film or plate is used, a step of carrying a chemical by printing, coating, spraying, pouring or impregnating, overcoating, covering with an edible film and punching. It is preferable that techniques such as packaging can be integrated, and that the patient's compliance can be improved by printing information such as the timing of taking on the carrier at the same time.

The pharmaceutically acceptable edible ink composition in the above Production Examples is hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylcellulose, cellulose acetate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate. Nate, carboxymethyl ethyl cellulose,
Cellulose and derivatives thereof such as sodium carboxymethyl cellulose; soluble starch, α-starch, dextrin, dextran, starch such as sodium carboxymethyl starch, and derivatives thereof; dimethylaminoethyl methacrylate, methacrylic acid copolymer,
Acrylic acid derivatives such as ethyl methacrylic acid acrylate copolymer, methacrylic acid methyl methacrylic acid copolymer, etc .; shellac; polyvinyl acetal diethylaminoacetate; vinyl acetate; polyvinyl alcohol;
Polyvinylpyrrolidone; natural gums such as gum arabic and tragacanth; sugars and sugar alcohols such as sucrose, lactose, glucose, fructose, sorbitol, mannitol; binder components such as gelatin, casein, soybean protein and collagen Water; acidic aqueous solution; organic solvents such as alcohols, ketones, esters, ethers, glycols, (halogenated) hydrocarbons; vegetable oils;
Solvents such as animal oil, polyethylene glycol, polypropylene glycol, glycerin, castor oil, glycerin fatty acid ester, triethyl citrate, acetylated monoglyceride, diethyl phthalate, butylphthalylbutyl glycolate, tributyrin, plasticizers such as silicone,
Pigments such as titanium oxide, carbon black, iron oxide, edible tar pigments, natural pigments; metal salts of fatty acids such as stearic acid; inorganic acids and salts thereof; organic acids and salts thereof; cyclodextrin, methylhesperidin, tocopherol, etc. Various additives such as stabilizers, fragrances, surfactants, waxes, higher alcohols, defoamers and the like can be appropriately blended to form an ink component.

Furthermore, by coating with such a drug-free ink composition, the effect of masking the taste of the drug and relieving the adhesiveness of the drug to the mucous membranes such as the oral cavity and vagina can be provided. Is also possible.

The pharmaceutical composition of the present invention thus obtained is
From the viewpoint of manufacturing, (1) The process of using a minute amount of a highly bioactive drug as a powder that is difficult to handle is not required, which is a great improvement in terms of safety and hygiene of work, and at the same time, remote control equipment, air conditioning equipment, etc. Costs can be reduced because there is no need to increase the number of facilities. (2) If a roll-shaped sheet is prepared in advance by forming the carrier into a sheet shape, a compact automatic production line can be assembled without separating the printing, punching and packaging processes. (3) The size of the package can be made compact, and the packaging material, inventory space, etc. can be reduced. (4) It is possible to provide a non-conventional solid preparation method called powdering. And so on.

From the side of use, (1) by using a sheet-shaped carrier, the drug is integrated with the sheet, and it becomes possible to print information such as instructions on when to take the drug at the same time. Easier to do. (2) By using a sheet-shaped carrier, it becomes convenient to carry when it is processed into a card type preparation. The effect such as is expected.

[0017]

EFFECTS OF THE INVENTION According to the pharmaceutical composition of the present invention, a substance having a physiologically active action in a trace amount is not handled as a powder, and therefore, a preparation excellent in handleability from both the manufacturing side and the using side. Can be provided. Therefore, the composition can be applied as a medicine, a quasi drug, and a medicine for agriculture and horticulture.

[0018]

EXAMPLES The present invention will be described in detail below with reference to examples. In the examples, “part” means “part by weight”.

Example 1 [Printing] 1) Production of sheet Crystalline cellulose 92 parts Hydroxypropyl starch 5 parts Corn starch 3 parts Polyvinyl alcohol A trace amount is suspended in 500 parts of water, and a bleaching cloth is applied to a wooden frame. Then, it was dried to obtain a sheet having a thickness of about 1 mm. 2) Preparation of Printing Ink An ink consisting of 6 parts of shellac, 10 parts of mestranol, 44 parts of ethanol, 20 parts of butanol, and a yellow dye No. 5 was prepared. 3) Printing with tablet printing machine A design roll is manufactured with the design shown in Fig. 1, and the carrier sheet is fixed to the gravure roll with cellophane tape. In a manual operation, ink was placed on the engraved portion of the design roll and transferred to a rubber roll, and then transferred to a sheet as usual. Mestranol 0.
The ink concentration was adjusted with ethanol to contain 02 mg. A prototype was obtained by making a slit 4 with a punching cutter using a punching punch as shown in FIG. In FIG. 1, 1 is a carrier sheet,
2 indicates a layer printed with an ink containing mestranol.

Example 2 [Coating] 1) The same sheet as in Example 1 was used. 2) Preparation of printing ink Hydroxypropyl cellulose 7 parts Polyethylene glycol 6000 0.7 part Cyanocobalamin 1 part Titanium oxide 1.3 parts Ethanol 85 parts Red No. 3 dye An ink consisting of a trace amount was prepared. 3) Using the tray and roller of the copy plate, while rolling the roller directly on the sheet, 0.1 mg of cyanocobalamin was applied per cm ^{2 of the} sheet so that the entire surface was coated.
After drying, a slit 4 having a width of 5 mm as shown in FIG. A sheet having a width of 20 mm was used. Further, in FIG. 2, reference numeral 1 indicates a sheet, and a shaded portion indicates a cyanocobalamin application portion.

Example 3 [Spraying] 1) The same sheet as in Example 1 was used. 2) Preparation of spray liquid A spray liquid consisting of hydroxypropylmethylcellulose 6 parts, polyethylene glycol 6000 0.7 parts, thiamine hydrochloride 2 parts, titanium oxide 1.3 parts, yellow No. 5 dye, and a small amount of purified water 90 parts was prepared. 3) Using a hand spray gun, the coating solution was sprayed and dried repeatedly on a sheet having a width of 20 mm so that 1 mg of thiamine hydrochloride was placed on 1 cm ^{2 of} the sheet. After drying, a slit having a width of 5 mm as shown in FIG.

Example 4 [Injection] 1) The same sheet as in Example 1 was used. 2) Preparation of injectable solution (1) An injectable solution (1) comprising 7 parts of shellac, 0.5 part of castor oil, 5 parts of norgestrel, 5 dyes of Blue No. 2 and 87.5 parts of ethanol was prepared. In addition, (2) an injection solution (2) was prepared, which consisted of 7 parts of shellac, 0.5 part of castor oil, 0.5 part of ethinyl estradiol, 0.5 part of Red No. 3 dye, and 92 parts of ethanol. 3) Using a micropipette on the sheet as shown in FIG. 3, 1 injection liquid (1) and 1 injection liquid (2) per drug, respectively.
0 μl (norgestrel 0.5 mg, ethinyl estradiol 0.05 mg) was injected and dried. After drying, as shown in FIG. 3, a slit having a width of 5 mm and being separable was inserted by a cutter to obtain a prototype. As described above, when one drug unit obtained in Examples 1 to 4 was tested by the Japanese Pharmacopoeia Disintegration Test Method (water), all disintegrated within 5 minutes.

[Brief description of drawings]

FIG. 1 is a diagram showing a state in which a drug is printed on a sheet by offset printing and contained.

FIG. 2 is a diagram showing a state in which a medicine is carried on a sheet by coating or spraying.

FIG. 3 is a diagram showing a state in which a drug is injected into a sheet and carried.

[Explanation of symbols]

1 ... Sheet, 2 ... Ink-printed layer containing sumetranol,
3 ... A line punched so as not to separate from the sheet, 4 ... A slit that can be separated, 5 ... A spot containing nogestrel, 6 ... A spot containing ethinyl estradiol

Claims (1)

[Claims] 1. A sheet-like product obtained by printing, coating, spraying or injecting a solution or suspension containing a trace amount of a substance having a physiologically active action on a pharmaceutically acceptable sheet-like carrier. Solid pharmaceutical composition.