JPH11189548A - Amorphous pharmaceutical composition and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition effective for improving the absorbability of a scarcely absorbable drug through digestive tracts and reducing the side actions of the drug on the digestive tracts by dissolving a scarcely absorbable drug in heated and melted polyoxyethylene polyoxypropylene glycol. SOLUTION: The objective composition is produced by heating and melting a polyoxyethylene polyoxypropylene glycol at 60-70 deg.C and dissolving a scarcely absorbable drug (aspirin, prednisolone, etc.), in the molten liquid. The powder properties are further improved by homogeneously mixing the above composition in dissolved state with a protein or a polymer compound such as albumin or casein sodium and solidifying the mixture by drying. A diluent (lactose, starch, magnesium carbonate, etc.), may be used in place of the above protein or polymer compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a drug which is poorly absorbed from the gastrointestinal tract when administered orally, that is, a poorly-absorbable drug is added to polyoxyethylene / polyoxypropylene / glycol in an amorphous form by the method described below. The present invention relates to a dispersed pharmaceutical composition, that is, an amorphous pharmaceutical composition, further comprising a protein or polymer compound such as albumin or sodium caseinate, or an excipient as a carrier. It is about things. For more information,
Improves the absorption of pharmaceuticals, increases the availability of the administered drug in vivo, and reduces adverse effects on the digestive tract, which is undesirable for the human body, while at the same time formulating the drug (eg, when making tablets) The present invention relates to a pharmaceutical composition having improved powder properties.

[0002]

2. Description of the Related Art Drugs (solid substances) which are in a solid phase at ordinary temperature usually exist in the form of crystals. Even if this is formulated into a tablet for oral administration and made into tablets, capsules, granules, powders and the like, the drug itself is in a crystalline state as a matter of course. When these drugs are orally administered, it is known that crystalline drugs (crystalline drugs) do not absorb better from the digestive tract mucosa than solutions or amorphous forms of drugs (amorphous drugs). I have. Even if it is a solid, if it is amorphous, the drug molecules are dispersed one by one, so that it is easily absorbed as in the case of a solution.

[0003] As a method for improving the absorption of poorly absorbable drugs, several attempts have been made in the past focusing on this point. Examples thereof include “pharmaceutical composition using natural albumin as a carrier” (Japanese Patent No. 2654445). In these conventional methods, a drug is dissolved in a solvent such as a fatty oil or an organic solvent, and then suspended in a solution containing albumin or PVP.
(Eg, spray drying) to obtain a pharmaceutical composition. The principle is that a non-crystalline drug is physicochemically bound to albumin or PVP (protein binding in albumin) and dispersed to keep the drug in an amorphous form (amorphous pharmaceutical composition). Object).

[0004]

However, the problem with these methods is that the volume of the prepared pharmaceutical composition is large. That is, since the dispersion of the amorphous drug depends on the physicochemical bond between the albumin or PVP and the drug, a relatively large amount of albumin or PVP is required. The prepared pharmaceutical composition is not dry and lacks fluidity. Formulation is difficult for the above two reasons. That is, it is difficult to make a tablet with a tableting machine or to fill a capsule. In other words, poor powder properties in the formulation. Since it is a necessary condition that the drug is once dissolved in a solvent, a drug for which an appropriate solvent cannot be obtained cannot use the conventional technique, and this is a limiting factor.

[0005] Accordingly, an object of the present invention is to provide a pharmaceutical composition which improves gastrointestinal absorption of a poorly absorbable drug and reduces side effects of the drug on the gastrointestinal tract. It is an object of the present invention to provide an amorphous pharmaceutical composition which has solved the above problems and a method for obtaining the same.

[0006]

Means for Solving the Problems The inventors of the present invention have argued that the invention of a method that does not use solvents such as fatty oils and organic solvents is important in order to disperse poorly absorbable drugs in a pharmaceutical composition in an amorphous state. And the importance of inventing a form that does not depend on physicochemical binding, such as protein binding, as a method for dispersing an amorphous drug. In order to make a crystalline drug amorphous, it is necessary to dissolve it in some solvent. Therefore, the present inventors have considered using a substance that is powder (solid) at room temperature and becomes liquid at high temperature as a solvent. It becomes a liquid at a temperature high enough that most of the drug does not decompose, and dissolves the poorly absorbable drug in it to make it amorphous, and at room temperature, a powder in which the amorphous drug is directly dispersed can be obtained. It was thought that this problem would be solved if a substance satisfying the following conditions could be obtained.

1. Powdered at normal temperature, 60 to 100 ° C
If heated to a temperature, it will melt and become liquid. 2. Excellent solubility of poorly absorbable drugs in the molten state. 3. No chemical reaction with chemically stable and poorly absorbable drugs. 4. The powder is rich in fluidity, or it must be able to ensure fluidity by an appropriate method and can be formulated. 5. When administered to the human body, should not show harmful effects on the skin, mucous membranes, or the whole body. 6. Desirably, the drug has already been used as a drug or pharmaceutical excipient, and its safety has been ensured.

The present inventors have conducted intensive studies and found that polyoxyethylene / polyoxypropylene / glycol is a substance meeting these conditions. Polyoxyethylene / polyoxypropylene / glycol melts at 60 to 70 ° C., has excellent solubility for poorly absorbable drugs, and is a chemically stable substance. Polyoxyethylene / polyoxypropylene / glycol is a white paraffin-like flake or powder at room temperature, and is a pharmaceutical additive that is currently used as a stabilizer, solubilizer, and the like. We focused on this property and dissolved the poorly absorbable drug in polyoxyethylene / polyoxypropylene / glycol heated and melted at 60 to 70 ° C.

Further, the present inventors have considered using albumin or sodium caseinate as a carrier for the purpose of further improving the powder properties. That is, the polyoxyethylene / polyoxypropylene / glycol obtained by heating and dissolving the poorly absorbable drug was uniformly dispersed as fine particles in an aqueous solution of albumin or sodium caseinate, which is a kind of protein and a high molecular compound, and dried and solidified. . This albumin or casein sodium is a polyoxyethylene polyoxypropylene
It is a carrier for a composition comprising glycol. Further, excipients (lactose, starch, magnesium carbonate, calcium phosphate, or aluminate metasilicate) used in pharmaceutical preparations can be used as the carrier. This method not only increases the drug content in the pharmaceutical composition than conventional methods and improves the powder properties, but also applies to all poorly absorbable drugs that dissolve in polyoxyethylene / polyoxypropylene / glycol. Since it can be applied and is not restricted by solvents or protein binding properties, its application range becomes extremely large.

[0010] The poorly absorbable drugs to which the present invention is applied are as follows. A very hardly soluble B very hardly soluble C hardly soluble D hardly soluble Antipyretic analgesic anti-inflammatory agent Aspirin salicylate C diflunisal salcylic acid A A Ethenzamide salcylic acid A Acetaminophen Aniline D D Isopropylantipyrine pyrazolone C Ibuprofen Phenylpropionate System A Loxoprofen sodium Phenylpropionic acid system D Alclofenac phenylacetic acid system A Indomethacin indoleacetic acid system A Mefenamic acid Anthranilic acid system A Flufenamic acid Anthranilic acid system A Sulindac Indoleacetic acid system A Piroxicam Oxycamic acid system A Diclofenac sodium phenyl Acetate D Steroidal anti-inflammatory drug Prednisolone Adrenocortical hormone B Triamcinolone acetonide Adrenal cortex Lumon A Dexamethasone Adrenocortical hormone A Beclomethasone propionate Adrenocortical hormone B Hydrocortisone Adrenocortical hormone B Psychiatry agent Sulpiride A Carbamazepine Tricyclic B Clonazepam Antiepileptic drug A Phenytoin Hydantoxin A-Haloperidone A-Haloperidone A-Haloperidone A-Halperodizone Benzodiazepines A Flunitrazepam Benzodiazepines A Triazolam Benzodiazepines A Hypotensive diuretics Furosemide Rup diuretics A Ethacrynic acid Rupure diuretics B Bumetanide Rup diuretics A Hydrochlorothiazide Thiazide A Non trichloromethazide A B Chlorthalidone Non-thiazide A A Antihypertensive agent Zosin α1 blocker A Reserpine alkaloid A Labetalol αβ-blocker A Guanabenz acetate Sympathetic inhibitor A Bunazosin hydrochloride α1 blocker B Cardiorespiratory agent Theophylline xanthine C Caffeine Xanthine D D Dobutamine hydrochloride Sympathetic agonist D Sulfate Quinidine Quinidine D Lidocaine Xylidine A Digitoxin Cardiac glycoside D Digoxin Cardiac glycoside A Deslanoside Cardiac glycoside A Vinbocetin A Coronary vasodilator Nifedipine Ca antagonist A Nicardipine hydrochloride Ca antagonist C Isosorbide nitrate Nitroline Nitroline Nitroline Nitro agent B Peripheral skeletal muscle relaxant Dantrolene sodium Peripheral C Baclofen GABA derivative C Drug for treatment of ischemic heart disease Dipyridamole Adenosine degradation inhibition A Nicorandil nicotinic acid amide゛ Nitro derivative D β-blocker Athenol β-blocker A Arotinolol hydrochloride β-blocker C Nadrole β-blocker C Pindrole β-blocker A Antispasmodic Tikidium bromide C Thimepidium bromide D Antibiotic Cefaclor Cephem D Cephalexin Cephem D Cefixime A Ceftazidime C Cefpodoxime Proxetil B Cefloxazine A Cefmenoxime Hydrochloride Cephem B Antifungal agent Griseofulvin Antifungal agent A Nystatin B Amphotericin B A Miconazole Azole A Chemotherapeutic agent Nalidixic acid Pyridonecarboxylic Acid A Ofloxacin Pyridonecarboxylic acid C Pipemidic acid Pyridonecarboxylic acid B Enoxacin Pyridonecarboxylic acid A Antiviral agent Vidarabine B Antineoplastic agent Methotrexate Antifolate metabolite B Enocitabine B Carmofur B Peptic ulcer agent Cetraxate ulcer Tissue repair / protective agent D Cimetidine H2 blocker-C Famotidine H2 blocker-B Sulpiride Other therapeutic agent for ulcer A Antiallergic agent Ketotifen fumarate Suppressing transmitter release D Tranilast Suppressing transmitter release C Cazelastine hydrochloride Suppressing transmitter release C Fumaric acid Clemastine Antihistamine A Metachidine Antihistamine A A expectorant Amploxal hydrochloride expectorant D Antitussive Noscapine A Dextrometlfan hydrobromide Central antitussive D Dipepi hibenzate Gin Central B Vitamins Calcitriol Vitamin D A Tocopherol acetate Vitamin E A Tocopherol nicotinate Hyperlipidemia A Riboflavin butyrate Hyperlipidemia A Folic acid A Phytonadione Vitamin K A Agent for liver disease Malotilato A Glycyrrhizin C Antidiabetic Acetohexamide Sulfonylurea A Chlorpropamide Sulfonylurea A Tolbutamide Sulfonylurea A Hormonal agent Danazol Endometriosis A Levothyroxine sodium Thyroid hormone A Riothyronine sodium Thyroid hormone A propylthiouracil Drug B Uric acid excretion probenecid A Immunosuppressant Azathioprine A Cyclosporin A Antiemetic domperidone A

The polyoxyethylene used in the present invention
Several kinds of polyoxypropylene glycols are currently available as pharmaceutical additives. That is,
Polyoxyethylene (105), polyoxypropylene (5), glycol (alias: PEP-101), polyoxyethylene (120), polyoxypropylene (40)
Glycol (alias: Pluronic F-87), polyoxyethylene (160), polyoxypropylene (30), glycol (alias: Pluronic F68, poloxamer 1)
88), polyoxyethylene (42), polyoxypropylene (67), glycol (also known as Pluronic P12)
3, poloxamer 403), polyoxyethylene (54)
-Polyoxypropylene (39)-Glycol (alias: Pluronic P85, Poloxamer 235), Polyoxyethylene (196)-Polyoxypropylene (67)-Glycol (alias: Pluronic F127, Poloxamer 4)
07), polyoxyethylene (20), polyoxypropylene (20), glycol (also known as Pluronic L-4)
4). The point is that polyoxyethylene / polyoxypropylene / glycol that can dissolve the poorly absorbable drug can be selected, but those that are used for oral administration are more preferable.

[0012]

EXAMPLES Examples of preparation of a pharmaceutical composition according to the present invention will be shown below. Preparation of pharmaceutical composition according to the present invention (1)-indomethacin
-Pluronic F68 composition Pluronic F68 (manufactured by Asahi Denka Kogyo) 600 mg is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of indomethacin. The Pluronic F68 in which indomethacin was dissolved was cooled and solidified to obtain an indomethacin-Pluronic F68 composition.

Preparation of pharmaceutical composition according to the present invention (2) -A
600 mg of a pharmonic composition of domesatin / pluronic F68 / albumin (Pluronic F68, manufactured by Asahi Denka Kogyo Co., Ltd.) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of indomethacin. In a 100 ml beaker, 1.6 g of albumin is dissolved in 15 ml of water, and Pluronic F68 in which indomethacin is dissolved is added. The mixture is emulsified at 25,000 rpm for 15 minutes using a biomixer (EM-1 manufactured by Nippon Seiki). After being transferred to a metal container and freeze-dried overnight after freezing, an indomethacin-pluronic F68-albumin composition was obtained.

Preparation of pharmaceutical composition according to the present invention (3) -A
Domesatin / Pluronic F68 / Sodium caseinate
600 mg of the composition Pluronic F68 (manufactured by Asahi Denka Kogyo) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of indomethacin. Dissolve 1.6 g of sodium caseinate in 15 ml of water in a 100 ml beaker, add Pluronic F68 in which indomethacin is dissolved, and use a biomixer (EM-1 manufactured by Nippon Seiki) at 25,000 rpm 15 mi.
Emulsify with n. After being transferred to a metal container and freeze-dried overnight after freezing, an indomethacin-pluronic F68 / sodium caseinate composition was obtained.

Preparation of pharmaceutical composition according to the present invention (4)
600 mg of Bamipid / Pluronic F68 / Albumin composition Pluronic F68 (manufactured by Asahi Denka Kogyo) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of rebamipide. In a 100 ml beaker, 1.6 g of albumin is dissolved in 15 ml of water, and Pluronic F68 in which rebamipide is dissolved is added. The mixture is emulsified at 25,000 rpm for 15 min using a biomixer (EM-1 manufactured by Nippon Seiki). After being transferred to a metal container and freeze-dried overnight after freezing, a rebamipide pluronic F68 / albumin composition was obtained.

Preparation of the pharmaceutical composition according to the present invention (5)
Anocobalamin / Pluronic F68 / albumin composition 600 mg of Pluronic F68 (manufactured by Asahi Denka Kogyo) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of cyanocobalamin. In a 100 ml beaker, 1.6 g of albumin is dissolved in 15 ml of water, and Pluronic F68 in which cyanocobalamin is dissolved is added. The mixture is emulsified using a biomixer (EM-1 manufactured by Nippon Seiki) at 25,000 rpm for 15 min. After being transferred to a metal container and freeze-dried overnight after freezing, a cyanocobalamin / pluronic F68 / albumin composition was obtained.

Preparation of pharmaceutical composition according to the present invention (6)
600 mg of Bidecarenone Pluronic F68 / Albumin composition Pluronic F68 (manufactured by Asahi Denka Kogyo) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of ubidecarenone. In a 100 ml beaker, 1.6 g of albumin is dissolved in 15 ml of water, and Pluronic F68 in which ubidecarenone is dissolved is added. The mixture is emulsified at 25,000 rpm for 15 minutes using a biomixer (EM-1 manufactured by Nippon Seiki). After being transferred to a metal container and freeze-dried overnight after freezing, a ubidecarenone-pluronic F68 / albumin composition was obtained.

Preparation of pharmaceutical composition according to the present invention (7)
Bidecarenone Pluronic F68 / Sodium caseinate
600 mg of the composition Pluronic F68 (manufactured by Asahi Denka Kogyo) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of ubidecarenone. Dissolve 1.6 g of sodium caseinate in 15 ml of water in a 100 ml beaker, add Pluronic F68 in which ubidecarenone is dissolved, and use a biomixer (EM-1 manufactured by Nippon Seiki) at 25,000 rpm 15 mi.
Emulsify with n. After being transferred to a metal container and freeze-dried overnight after freezing, a ubidecarenone-pluronic F68 / sodium caseinate composition was obtained.

Preparation of pharmaceutical composition according to the present invention (8) -A
Buprofen / Pluronic F68 / Sodium caseinate
600 mg of the composition Pluronic F68 (manufactured by Asahi Denka Kogyo) is placed in a 10 ml Erlenmeyer flask and melted in a water bath at about 70 ° C. After melting,
Dissolve 100 mg of ibuprofen. In a 100 ml beaker, 1.6 g of albumin is dissolved in 15 ml of water, and Pluronic F68 in which ibuprofen is dissolved is added. The mixture is emulsified at 25,000 rpm for 15 minutes using a biomixer (EM-1 manufactured by Nippon Seiki). After being transferred to a metal container and freeze-dried overnight after freezing, an ibuprofen / pluronic F68 / sodium caseinate composition was obtained.

Next, a confirmation test was performed as follows to confirm that the drug in the pharmaceutical composition prepared by the above method was amorphous. Test method: 7 kinds of test drugs, namely, indomethacin only, pluronic F68 only, indomethacin / pluronic F68 composition, indomethacin / pluronic F68 / albumin composition, indomethacin / pluronic F68 / albumin physical mixture, indomethacin / pluronic F68 / Sodium caseinate composition,
In order to examine the crystallinity of the physical mixture of indomethatine / pluronic F68 / sodium caseinate, each was mounted on a standard sample holder, and an X-ray analysis image was obtained using an X-ray analyzer. Test results: The powder X-ray analysis images of the seven types of samples are shown in FIGS.

Hereinafter, experimental results which proved the easy absorbability of the present pharmaceutical composition will be described. (1) Gastrointestinal absorption test of indomethacin / pluronic F68 / albumin composition and indomethacin / pluronic F68 / sodium casein composition Test method: Preparation of SD rats in 3 groups (5 rats / group), the above preparation (2) and preparation Indomethacin prepared in (3)
Pluronic F68 / albumin composition and indomethatin / Pluronic F68 / sodium caseinate composition,
And, using indomethacin crystals, it was orally administered at a dose of 3 mg / kg as indomethacin, blood was collected at a predetermined time, and the indomethatin concentration in the blood was measured by HPLC. Test results: The blood concentration of each group showed the highest value 30 minutes after administration, and the values of the indomethacin / pluronic F68 / albumin composition group and the indomethatine / pluronic F68 / sodium caseinate composition group were higher than those of the indomethacin crystal group. It was significantly higher. AUC of indomethacin / pluronic F68 / albumin composition group and indomethatine / pluronic F68 / sodium caseinate composition group
Was 2.5 times that of the indomethacin crystal group. (FIG. 8)

(2) Ibuprofen Pluronic F68
-Gastrointestinal absorption test of albumin composition Test method: Ibuprofen Pluronic F68 prepared in the above-mentioned preparation (8) was divided into 2 groups (3 rats / group) of SD rats.
-Using an albumin composition and ibuprofen crystals, ibuprofen was orally administered at a dose of 3 mg / kg, blood was collected at a predetermined time, and the ibuprofen concentration in the blood was measured by HPLC. Test result: The blood concentration of the ibuprofen / pluronic F68 / albumin composition group showed the highest value 60 minutes after administration (Cmax: 5.99). On the other hand, the ibuprofen crystal group showed the highest value after 120 minutes (Cmax: 3.7).
3). The ibuprofen / pluronic F68 / albumin composition had a clear absorption and a high maximum blood concentration.
(FIG. 9)

(3) Indomethacin Pluronic F68
Gastrointestinal absorption test of the composition Test method: Two groups (5 rats / group) of SD rats were mixed with indomethacin-pluronic F68 prepared in the above preparation (1).
Using the composition and indomethacin crystals, orally administered at a dose of 3 mg / kg as indomethacin, blood was collected at a predetermined time, and the indomethatin concentration in the blood was measured by HPLC. Test result: The blood concentration of each group showed the highest value 30 minutes after administration, and the value of the indomethacin-pluronic F68 composition group was significantly higher than that of the indomethacin crystal group. The AUC of the indomethacin-Pluronic F68 composition group was 2.4 times that of the indomethacin crystal group. (FIG. 10)

The following test was conducted to confirm that the improvement of indomethacin absorption by the present pharmaceutical composition reflects its pharmacological action. Indomethacin / Pluronic F68 / Albumin composition
And pharmacological action of indomethacin crystals Test method: To compare the pharmacological action on carrageenan edema, 0.1 ml of 1% carrageenan saline was intradermally administered to the right footpad skin of rats, and 10 ml of water was orally administered. The footpad volume was measured at predetermined intervals, and the edema rate was calculated. The test drug was suspended in a 1% aqueous solution of gum arabic and orally administered 1 hour before administration of caranigen. Test result: Edema rate of control group (group not receiving drug) was 6
6%, 50% in the indomethacin crystal group,
The indomethacin / pluronic F68 / albumin composition group exhibited an edema rate of 40%, indicating suppression of edema, that is, enhancement of the anti-inflammatory effect. (FIG. 11)

Gastric mucosal damage is known as a side effect of indomethacin, and the following test was conducted to confirm whether or not the present pharmaceutical composition can suppress this side effect. Indomethacin treatment for indomethacin ulcer
Test method for effect of Luronic F68 / albumin composition : SD rats (male) weighing about 200 g were pre-fed for at least one week, fasted for 24 hours, and each test drug was suspended in an aqueous solution of gum arabic to give a dose of 30 mg / kg. Oral administration. After leaving for 8 hours under fasting and water-free condition, ether was sacrificed and the stomach was removed. Fix with 1% formalin solution, dissect and dissect along the greater curvature, measure the length (mm) of each mucosal ulcer generated in the glandular stomach with a microscope, and calculate the total length per animal. The ulcer index was used. Test result: The ulcer index of the indomethacin / pluronic F68 / albumin composition was significantly lower than that of the indomethacin crystal. It was shown that ulcer formation due to indomethacin was suppressed by using the indomethacin / pluronic F68 / albumin composition. (Figure 1
2)

[Brief description of the drawings]

FIG. 1 is a graph showing the results of an amorphousness confirmation test-X-ray diffraction image of each sample.

FIG. 2 is a view showing the results of an amorphousness confirmation test—X-ray diffraction images of each sample.

FIG. 3 is a graph showing results of an amorphousness confirmation test-X-ray diffraction image of each sample.

FIG. 4 is a view showing the results of an amorphousness confirmation test-X-ray diffraction image of each sample.

FIG. 5 is a view showing the results of an amorphousness confirmation test—X-ray diffraction images of each sample.

FIG. 6 is a graph showing results of an amorphousness confirmation test-X-ray diffraction image of each sample.

FIG. 7 is a diagram showing a confirmation test result of amorphousness-X-ray diffraction image of each sample.

FIG. 8 is a graph showing blood indomethatin concentrations after oral administration (3 mg / kg) of indomethacin / pluronic F68 / albumin composition, indomethatin / pluronic F68 / sodium casein composition and indomethacin crystals in rats.

FIG. 9 is a graph showing blood ibuprofen concentrations after oral administration (3 mg / kg) of ibuprofen / pluronic F68 / albumin composition and ibuprofen crystals in rats.

FIG. 10 is a graph showing blood indomethatin concentrations after oral administration (3 mg / kg) of an indomethacin-pluronic F68 composition and indomethacin crystals in rats.

FIG. 11 shows the edema rate of indomethacin / pluronic F68 / albumin composition and indomethacin crystals.

FIG. 12 is a graph showing the ulcer index of indomethacin / pluronic F68 / albumin composition and indomethacin crystals.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Hiroshi Mizushima 1-1-11 Umeoka, Setagaya-ku, Tokyo (72) Inventor Shinichi Kawai 3-3-3 Denon Chofu, Ota-ku, Tokyo (72) Inventor Rie Igarashi (72) Inventor Akira Suzuki Kada 747, Tondabayashi-shi, Osaka (72) Inventor Yasuo Kosaka 1484-23, Sendabori, Matsudo-shi, Chiba (72) Inventor Tetsuji Ehata Tokyo 2-17-16 Kunitachi-shi Kita

Claims (8)

[Claims] 1. An amorphous pharmaceutical composition produced by dissolving a poorly absorbable drug in polyoxyethylene / polyoxypropylene / glycol melted by heating. 2. An amorphous pharmaceutical composition comprising polyoxyethylene / polyoxypropylene / glycol and a poorly absorbable drug. 3. An amorphous pharmaceutical composition produced by dissolving a poorly-absorbable drug in heat-melted polyoxyethylene / polyoxypropylene / glycol, in a dissolved state, a protein or other polymer compound. Amorphous pharmaceutical composition characterized by being produced by uniformly mixing with the above. 4. An amorphous pharmaceutical composition comprising polyoxyethylene / polyoxypropylene / glycol, a protein or other polymer compound, and a poorly-absorbable drug. 5. The amorphous pharmaceutical composition according to claim 3, wherein the protein or other high molecular compound is albumin or sodium caseinate. 6. An amorphous pharmaceutical composition characterized by being produced by dissolving a poorly absorbable drug in polyoxyethylene / polyoxypropylene / glycol melted by heating and further mixing an excipient. 7. An amorphous pharmaceutical composition comprising polyoxyethylene / polyoxypropylene / glycol, an excipient and a poorly absorbable drug. 8. The amorphous pharmaceutical composition according to claim 6, wherein the excipient is lactose, starch, magnesium carbonate, calcium phosphate or aluminate metasilicate.