JPH05201876A - Agent for reducing adverse action of fk565 - Google Patents

Abstract

PURPOSE:To provide a medicinal composition giving excellent effects for preventing and treating adverse actions such as thrombocytopenia and hepatopathy without damaging the medicinal activity of FK565, and useful as an anticancer agent, an anti AIDS agent, etc., by adding dexamethasone to the FK565 subs tance, etc. CONSTITUTION:The objective medicinal composition is characterized by adding dexamethasone as an adverse action-reducing agent to FK565 substance of the formula or its salt acceptable as a medicine. The dexamethasone is preferably administered in a dose of 0.01-10mg/kg a day for an adult.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a FK565 substance represented by the following chemical formula or a pharmaceutically acceptable salt thereof as an active ingredient.
The present invention relates to a pharmaceutical composition in which dexamethasone is added (included) to the composition as a side effect reducing agent for substance 565 or a pharmaceutically acceptable salt thereof.

[0002]

FK565 has an immunopotentiating action and is known to be useful as an anticancer agent, anti-AIDS agent, antiviral agent, etc. (JP-A-56-45449 and JP-A-60). -104019 and Japanese Patent Application Laid-Open No. 64-38030), improvement is desired in terms of side effects. The present inventors have obtained new knowledge that dexamethasone, which is known as an anti-inflammatory drug, is effective in reducing side effects of the FK565 substance, and as a result of further research, completed the present invention.

[0003]

The present invention has the chemical formula

[Chemical 2] And a pharmaceutically acceptable salt thereof and dexamethasone as an active ingredient. The FK565 substance or a pharmaceutically acceptable salt thereof is expected as an anticancer agent, an anti-AIDS agent, an antiviral agent, or a therapeutic agent for viral myocarditis. On the other hand, dexamethasone
For the side effects (for example, thrombocytopenia and liver damage that occur several hours after administration of the FK565 substance) without impairing the drug efficacy of the FK565 substance expected as an anticancer agent, anti-AIDS agent, antiviral agent, etc. To compete. Therefore F
It is useful as a therapeutic and prophylactic agent for side effects such as thrombocytopenia and liver damage occurring several hours after administration of the substance K565.

The pharmaceutically acceptable salt of the FK565 substance is, for example, an organic or inorganic salt such as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylamine salt, dicyclohexylamine salt, or acetate salt. Acids with organic or inorganic acids such as, trifluoroacetate, lactate, maleate, fumarate, tartrate, citrate, methanesulfonate, hydrochloride, sulfate, nitrate, phosphate etc. An addition salt is mentioned.

The FK565 substance and dexamethasone used in this invention are in the form of solid, semi-solid or liquid preparations containing admixture with organic or inorganic carriers or excipients suitable for oral or parenteral administration. Can be used. The FK565 substance and dexamethasone used in the present invention are, for example, tablets, pellets, capsules,
Suppositories, solutions, emulsions, suspensions and usually non-toxic, pharmaceutically acceptable carriers are mixed and used in suitable dosage forms. As the carrier, water, glucose, lactose, acacia, gelatin, mannitol, starch paste, magnesium trisilicate, talc, methylcellulose, polyethylene glycol, corn starch, keratin, colloidal silica, potato starch, urea and solid, semi-solid. Other carriers adapted for use in the preparation of liquid or liquid formulations, and also adjuvants,
Stabilizers, thickeners and colorants and fragrances may be used. The FK565 substance and dexamethasone used as a drug for the cytomegalovirus infection and the like can also contain a fosone or a bacteriostatic agent in order to stably maintain the activity of the active ingredient in the desired preparation.
The amount of the active ingredient contained in the FK565 substance and dexamethasone used as a drug for this infectious disease and the like is an amount sufficient to exert a desired therapeutic effect on the course and condition of prevention or disease.

When the FK565 substance and dexamethasone are applied to humans or animals, it is desirable to administer them by a method such as intravenous injection, subcutaneous injection, intramuscular injection or oral administration. Moreover, by administering dexamethasone before administering the FK565 substance, the side effect of the FK565 substance can be prevented. The dose of the active ingredient of this invention is
Although it varies depending on the condition such as age and degree of illness of each individual patient to be treated, in general, a daily dose of the active ingredient of about 0.01 to 10 mg / kg for humans or animals is used for prevention or treatment. Is administered.

[0007]

[Effects of the Invention] The antagonistic activity against the side effects of dexamethasone administered with FK565 will be described below. The prophylactic or therapeutic effect on the acute toxicity in rats caused by the test FK565 administration was confirmed by the death of dexamethasone.
Hematological changes and gross changes of the liver were used as indicators. Test method From the tail vein of 10 SD male rats (5 weeks old) per group to FK5
65 of 1 mg / kg was administered. Dexamethasone (1 mg / kg × 2: Yuclaf) as a concomitant drug was intraperitoneally administered twice 30 minutes before and 4 hours after the administration of FK565. After confirming life or death 24 hours after administration, blood samples were collected from the abdominal aorta of survivors, blood cell count (white blood cells, platelets) and glutamic pyruvic in serum.
transaminase (GPT), glutamic oxaloacetic transam
The inase (GOT) activity and the amount of iron (Fe) were measured. Furthermore, at the time of slaughter, the liver was visually inspected for abnormalities. The test results are shown in Table 1.

[0008]

[Table 1] As is clear from the above test results, dexamethasone is useful for the treatment and prevention of side effects such as thrombocytopenia and liver damage that occur several hours after administration of the FK565 substance.

[0009]

EXAMPLES The present invention will be described in detail below with reference to examples. Example 1 FK565 200 mg Dexamethasone 200 mg Mannitol 400 mg Magnesium stearate 10 mg Starch 50 mg The above ingredients are formulated into tablets by a conventional method.

Claims (4)

[Claims] 1. A chemical formula: In the pharmaceutical composition containing the FK565 substance represented by or a pharmaceutically acceptable salt thereof as an active ingredient,
A pharmaceutical composition in which dexamethasone is added to the composition as a side effect reducing agent for the FK565 substance or a pharmaceutically acceptable salt thereof. 2. Prevention of cancer, AIDS, viral infection or viral myocarditis, which comprises administering dexamethasone before administering a pharmaceutical composition containing the FK565 substance or a pharmaceutically acceptable salt thereof as an active ingredient. Treatment. 3. An anti-cancer agent, anti-AIDS agent or anti-viral infection agent containing FK565 substance or a pharmaceutically acceptable salt thereof and dexamethasone as active ingredients with reduced side effects. 4. An anti-cytomegalovirus infectious agent or a preventive or therapeutic agent for viral myocarditis with reduced side effects, which contains FK565 substance or a pharmaceutically acceptable salt thereof and dexamethasone as active ingredients.