INVENTION
Russian Federation Patent RU2229882

MEDICINE

MEDICINE

Name of the inventor: Kirillov GV (RU); Kovtun VY (RU); Ogorodnikov VV (RU); Fetisov NI
The name of the patentee: Research and Production Center "Farmzaschita"
Address for correspondence: 141400, Moscow region, Khimki, Vashutinskoe w, 11, NPC "Farmzaschita" A.N.Gvozdetskomu director..
Starting date of the patent: 2002.04.05

A new tableted drug for transient relief of disability and early primary response to irradiation, comprising a 1,2,3,9-tetrahydro-9-methyl-3 - [(2-methyl-1H-imidazol-1-yl) methyl] -4 -carbazol-4-one, or its hydrates or its salt (ondansetron Latran) and benzamide derivative selected from the group ArCONH 2, wherein aryl represents unsubstituted phenyl or phenyl substituted in 3-position amino or acylamino group which They are in a weight ratio of 1: 20-500. The product has high activity, high reliability and easy to use.

DESCRIPTION OF THE INVENTION

The invention relates to a novel combination drug, which can be used as a human means of protection against early transient disability and for the relief of the primary reaction to irradiation.

It discloses the use of 1,2,3,9-tetrahydro-9-methyl-3 - [(2-methyl-1H-imidazol-1-yl) methyl] -4H-carbazol-4-one or its hydrates or salts thereof (I) as a means of the cupping emetic response induced by cytotoxic drugs or other application means chemotherapy and / or radiation or rentgenoradioterapii tumors. The most commonly used for this purpose hydrochloride dihydrate 1,2,3,9-Tetrahydro-9-methyl-3 - [(2-methyl-1H-imidazol-1-yl) methyl] -4H-carbazol-4-one (ondansetron , latran®) (UK patents №2153821, 2290963, European patent №191562, 219,929;. Russian patent №1528319, 2041876, 2159614, etc. The order of the chief of the Russian Defense Ministry GVMU №224 from 01.06.1996 "on taking over the supply of the medical service of the Armed forces Russian Latran 0,004 tablets, coated tablets ").

The disadvantage of this drug is the lack of protection from Latran other signs of the primary reaction to irradiation and the ability to protect against early transient incapacitation.

The object of the invention is to provide a medicament for the protection of humans from early transient disability and for the relief of the primary reaction to irradiation in the form of a tablet dosage form (as the most comfortable in the conditions of war). The problem is dictated by modern methods of warfare, especially for use in a combat so-called tactical nuclear weapons. Under these conditions, the soldiers receive a very significant radiation dose. We do not know the means of population and military personnel from the early transient incapacitation while knocking over the primary reaction to irradiation. In terms of military operations and, in particular, in the use of nuclear (including neutron) weapons is particularly important is the use of such funds in the form of a tablet, because in these conditions greatly reduced the critical ability of people and possible panic that could lead to uncontrollable consequences.

This object is achieved creating a combination drug consisting of 1,2,3,9-tetrahydro-9-methyl-3 - [(2-methyl-1H-imidazol-1-yl) methyl] -4H-carbazol-4-one or its hydrates or salts thereof (1) and the benzamide derivative (II), selected from the group ArCONH 2, wherein aryl represents unsubstituted phenyl or phenyl substituted in 3-position amino or acylamino, and auxiliary substances required for obtaining a tablet dosage form.

Most preferred is the use of 1,2,3,9-tetrahydro-9-metpl-3 - [(2-methyl-1H-imidazol-1-yl) methyl] -4H-carbazol-4-one as hydrochloride dihydrate (ondansetron , latrana®).

As a benzamide derivative can be used alone benzamide, 3-aminobenzamide, or acyl derivatives of 3-aminobenzamide, for example, 3- (butyrylamino) -benzamide.

The invention provides a drug composition I: II = 1: 20-500 (weight ratio), the composition preferably I: I = 1: 50-250.

Since the action of radiation or of high concentrations of cytostatic agents is accompanied by massive DNA damage structures and, consequently, a considerable increase in the level of poly (ADP-ribose), use of ADP-ribosylation inhibitors, in particular, the benzamide derivatives of the general formula II, is extremely useful from the viewpoint of protection from these damaging factors. These qualities may be particularly useful in clinical practice in the treatment of hematologic and oncologic diseases. Given that benzamide derivatives have pronounced antiviral activity (EP №0531370, Cl. A 61 K 31/00), the proposed drug is particularly useful when rentgenoradioterapii chemotherapy and cancer patients when humoral immunity significantly lowered.

The most convenient for the task in order to use the self-help and mutual aid tableted dosage form, in which the necessary pharmaceutical additives and components must be entered in addition to the active ingredients. The required dosage form is obtained by studying the compatibility of various excipients with the active principles and with each other.

The tablets may be manufactured by conventional methods can using one or more accessory ingredients. Tablets can be manufactured by a suitable molding equipment in which the active ingredients are used in an easily movable form, for example as a powder or granules, optionally mixed with a binder, a sliding additive, inert diluent, surface active or dispersing agent. Compressed tablets can be coated, sugar or consisting of a special film.

The most useful tableted dosage form coated with gastro-soluble coating. The required dosage form is obtained by studying the compatibility of different adjuvants with actives principles and with each other.

As excipients used calcium carbonate, kaolin, gelatin, starch, magnesium carbonate, microcrystalline cellulose, lactose, Aerosil, etc. Use as excipients microcrystalline cellulose, starch and aerosil.; Aerosil blend, starch and magnesium stearate as a sliding and aqueous starch solution as binder made it possible to obtain tablets with the desired core properties for the coating strength. On the basis of hydroxypropyl cellulose coated tablets designed and matched the conditions of its application.

Example

The composition of the tablet core, g:

Ondansetron hydrochloride dihydrate 0.010

benzamide 0,500

0.060 Microcrystalline cellulose

aerosil 0.010

Starch 0,018

Magnesium stearate 0.002

Was used for coating a colorless film-forming composition, wt.%:

Hydroxypropyl cellulose "Klyutsel" 1.0

Castor oil 0.4

Tween-80 0.1

Ethanol 96º: acetone (1: 1) Up to 100.0

After the coated tablets obtained have a disintegration tablets (10 ± 2) minutes and to release the active ingredients (96 ± 2)%. Shelf life of the tablets at least 2 years.

CLAIM

1. A drug for edema early disability and passing the primary reaction to irradiation, comprising a 1,2,3,9-tetrahydro-9-methyl-3 - / (2-methyl-1H-imidazol-1-yl) methyl / -4 -carbazol-4-one or its salts or hydrates (I) and the benzamide derivative (II) 2 ArCONH general formula wherein Ar represents unsubstituted phenyl or phenyl substituted in the 3-position amino or acylamino, with a weight ratio of I: II, being 1: 20-500.

2. A medicament according to claim 1, characterized in that it is a multiple unit tableted dosage form.

3. A medicament according to claim 1 or 2, characterized in that it is a multiple unit tableted dosage form layered shell.

4. A medicament according to claims 1-3, characterized in that 1,2,3,9-tetrahydro-9-methyl-3 - [(2-methyl-1H-imidazol-1-yl) methyl] -4H- carbazol-4-one is used as the hydrochloride dihydrate.

5. A medicament according to claims 1-4, characterized in that as benzamide derivative (II) used benzamide, 3-aminobenzamide, or 3- (butyrylamino) -benzamide.

6. A medicament according to claims 1-5, characterized in that the compounds I and II are used in a weight ratio of 1: 50-250.

7. A medicament according to claims 1-6, which is a multiple unit tableted dosage form, wherein the 1,2,3,9-tetrahydro-9-methyl-3 - / (2-methyl-1H-imidazol-1-yl) methyl / -4H-carbazol-4-one hydrochloride dihydrate and benzamide are in a weight ratio of 1: 50-250 and the tablet is covered gastrointestinal soluble shell.

print version
Publication date 06.01.2007gg