RU2496496C1 - Pharmaceutical composition possessing gaba activity - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine and concerns a pharmaceutical composition possessing GABA activity containing 4[(4'-nicotinoylamino)butyroylamino]butanoic acid, nicotinoyl gamma-amino-butyric acid, homopantothenic acid calcium salt and additives in the following proportions, wt %: 4[(4'-nicotinoylamino)butyroylamino]butanoic acid 3-50, nicotinoyl gamma-amino-butyric acid 10-95, homopantothenic acid calcium salt 0-80, additives the rest possessing higher activity with a low dose of the active ingredients.

EFFECT: preparing the new pharmaceutical composition.

2 tbl, 2 ex

Description

The invention relates to the field of pharmaceuticals and medicine and relates to a pharmaceutical composition having GABAergic activity, which may find application in psychiatry and neurology.

Known GABAergic agent - pantogam (calcium salt of D - (+) - α, γ-dioxi-β, β-dimethylbutyryl-γ-aminobutyric acid, also called calcium salt of homopantothenic acid [1]. The tool is used in children with mental failure (mental retardation) and oligophrenia, as well as with delayed speech development.The drug is indicated as part of complex therapy and, in some cases, independently for the treatment of children suffering from epilepsy. with a slowdown in mental processes.The drug is also used for urinary disorders in children and adults (enuresis and daytime urinary incontinence) [2]. A single dose for adults is usually 0.5-1 g, for children 0.25-0.5 g The daily dose for adults is 1.5-3 g, for children 0.75-3 g. The drug has side effects - rhinitis, conjunctivitis, skin rashes, sleep disturbances or drowsiness, tinnitus and is contraindicated in pregnancy. and during lactation.

Also known is a GABAergic agent, Picamilon (nicotinoyl gamma-aminobutyric acid) [3]. The drug dilates the vessels of the brain, has a tranquilizing, psychostimulating, antiplatelet and antioxidant effect. It improves the functional state of the brain due to the normalization of tissue metabolism and the effect on cerebral circulation (increases the volumetric and linear velocity of cerebral blood flow, reduces the resistance of cerebral vessels, inhibits platelet aggregation, improves microcirculation).

With a course admission, it increases physical and mental performance, reduces headache, improves memory, normalizes sleep; contributes to the reduction or disappearance of feelings of anxiety, tension, fear; improves the condition of patients with motor and speech disorders. Tablets of 0.02 and 0.05 g. The daily dose is daily - 0.06-0.15 g.

Contraindications - chronic renal failure, pregnancy, lactation, hypersensitivity to nicotinoylgamma-aminobutyric acid (picamilon).

Possible side effects are irritability, agitation, anxiety, dizziness, headache, allergic reactions, and nausea.

Known 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid, exhibiting nootropic activity [4].

All of these drugs have side effects caused by their effect on the central nervous system. The smallest side effects are nicotinoyl gamma-aminobutyric acid, the calcium salt of homopantothenic acid and 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid. Such drugs as nicotinoyl gamma-aminobutyric acid and the calcium salt of homopantothenic acid, widely used in medicine, have significant drawbacks, in particular, due to the relatively large therapeutic doses (difficulties in passing the blood-brain barrier). The difficulty of passing the above drugs through the blood-brain barrier leads to significant difficulties in choosing an effective dose, the need to use high dosages.

The objective of the present invention is to provide a pharmaceutical composition of gamma-ergic preparations, which can significantly reduce the dosage.

In accordance with the invention, a pharmaceutical composition is described having GABAergic activity, containing 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid, nicotinoyl gamma-aminobutyric acid, calcium salt of homopantothenic acid and auxiliary substances in the following ratio, wt.%:

4 [(4'-nicotinoylamino) butyroylamino] butanoic acid 3-50; nicotinoyl gamma-aminobutyric acid 10-95; homopantothenic acid calcium salt 0-80; excipients (talc, calcium stearate, magnesium stearate) rest.

To obtain the described composition, a granulate is prepared from 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid - Granulate 1, nicotinoyl gamma-aminobutyric acid Granulate 2 and calcium salt of homopantothenic acid Granulate 3. A neutral granulate is prepared (free of active ingredients) (starch sugar) - Granulate 0.

Depending on the composition, the calculated quantities of granules are weighed and transferred to a mixer, excipients are added. Stir until a homogeneous mixture is formed. The mixture is transferred to a tablet press or capsule-filling press feeder. Then carry out the manufacture of tablets or capsules.

The invention is illustrated by the following examples.

Example 1

From 1 kg of 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid, granules are prepared by granulation in a fluidized bed under irrigation of 200 ml of a 2% solution of low molecular weight pyrrolidone. Get Granulate 1. The content of the main substance of 99.6%.

From 1 kg of nicotinoyl gamma-aminobutyric acid, granules are prepared by granulation in a fluidized bed under irrigation of 200 ml of a 2% solution of low molecular weight pyrrolidone. Get Granulate 2. The content of the main substance of 99.6%.

From 1 kg of the calcium salt of homopantothenic acid, granules are prepared by granulation in a fluidized bed with irrigation of 200 ml of a 2% solution of low molecular weight pyrrolidone. Get Granulate 3. The content of the basic substance is 99.6%.

20 grams of Granulate 1, 250 grams of Granulate 2, 700 grams of Granulate 3, 10 grams of calcium stearate, 20 grams of talc are placed in the mixer. The mixture is thoroughly mixed until smooth. From the prepared mixture tablets are made weighing 0.05 grams.

Capsules No. 3 of 0.05 grams are filled with the prepared mixture.

The estimated daily dose is 1 to 3 tablets or capsules per day, or

4 [(4'-nicotinoylamino) butyroylamino]

butanoic acid from 0.0010 to 0.003 g; nicotinoyl gamma-aminobutyric acid from 0.0125 to 0.0375 g; homopantothenic acid calcium salt from 0.035 to 0.05 g.

Example 2

From 1 kg of 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid, granules are prepared by granulation in a fluidized bed under irrigation of 200 ml of a 2% solution of low molecular weight pyrrolidone. Get Granulate 1. The content of the main substance of 99.6%.

From 1 kg of nicotinoyl gamma-aminobutyric acid, granules are prepared by granulation in a fluidized bed under irrigation of 200 ml of a 2% solution of low molecular weight pyrrolidone. Get Granulate 2. The content of the main substance of 99.6%.

From 1 kg of starch-sugar (0.5 kg of starch and 0.5 kg of powdered sugar) the mixture is prepared Granulate 0 by granulation in a fluidized bed with irrigation 200 ml of a 2% solution of low molecular weight pyrrolidone. Get Granulate 0. The content of the basic substance is 99.6%.

20 grams of Granulate 1, 250 grams of Granulate 2, 700 grams of Granulate 0 10 grams of calcium stearate, 20 grams of talc are placed in the mixer. The mixture is thoroughly mixed until smooth. From the prepared mixture, tablets weighing 0.1 grams are made. The prepared mixture is filled into capsules No. 3 of 0.1 grams. The estimated daily dose is 1 to 3 tablets or capsules per day, or

4 [(4'-nicotinoylamino) butyroylamino] butanoic acid from 0.0020 to 0.006 g; nicotinoyl gamma-aminobutyric acid from 0.025 to 0.075 g.

Table 1 shows examples of compositions made from mixtures prepared from the quantities of granules indicated in the corresponding columns, excipients were used similarly to examples 1-2.

Table 1 Composition number Granulate 1 gram Granulate 2 grams Granulate 3 grams Granulate 0 gram BUT AT FROM B / A one twenty 240 710 0 3 24 70 8 2 twenty 240 0 710 3 24 0 8 3 60 240 0 680 6 24 0 6 four one hundred one hundred 0 800 10 10 0 one 5 twenty 960 0 0 2 96 0 48 6 490 490 0 0 49 49 0 one 7 60 920 0 0 6 90 0 fifteen 8 one hundred one hundred 780 0 10 10 78 one 9 one hundred one hundred 500 280 10 10 fifty one 10 twenty 500 460 0 2 fifty 46 25

Where,

A — Content (%) of 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid in a tablet.

B — Content (%) of nicotinoyl gamma-aminobutyric acid in a tablet.

C - Content (%) of the calcium salt of homopantothenic acid in the tablet.

B / A — Ratio of nicotinoyl gamma-aminobutyric acid to 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid.

Table 2 shows the daily doses of the active substances according to examples 1-10 in comparison with the individual daily doses according to the literary bottom.

table 2 Example No. D r K g L r D1 g K1 g L1 g one 0.0045 0.075 0.105 0.03 0.15 3.0 2 0.0045 0.075 0.03 0.15 3 0.009 0.075 0.03 0.15 four 0.015 0.015 0.03 0.15 5 0.003 0.14 0.03 0.15 6 0.072 0.072 0.03 0.15 7 0.009 0.13 0.03 0.15 8 0.015 0.015 0.118 0.03 3.0 9 0.015 0.015 0.073 0.03 3.0 10 0.003 0.073 0.062 0.03 3.0

Where,

D - The maximum daily dose of 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid;

K - The maximum daily dose of nicotinoyl gamma-aminobutyric acid;

L - The maximum daily dose of the calcium salt of homopantothenic acid;

D1, K1, L1 - daily dosages calculated according to [4].

Bibliography

1. Mashkovsky M. D., "Medicines", M., NGO "New Wave", 2001, part 1, p. 116.

2. SU 850083, A1, 07.30.1981.

3. "Encyclopedia of drugs", Ch. Ed., Yu.F. Krylov, M., radar, 200 g., P. 720.

4. RU 2436772, C2, 08/10/2011.

Claims (1)

A pharmaceutical composition having GABAergic activity, containing 4 [(4'-nicotinoylamino) butyroylamino] butanoic acid, nicotinoyl gamma-aminobutyric acid, calcium salt of homopantothenic acid and excipients in the following ratio, wt.%:
4 [(4'-nicotinoylamino) butyroylamino] butanoic acid 3-50 nicotinoyl gamma-aminobutyric acid 10-95 homopantothenic acid calcium salt 0-80 excipients (talc, calcium stearate, magnesium stearate) rest