RU2252759C1 - Preparation for interrupting and treating ischemic cardiac disease and method for its manufacturing - Google Patents

Abstract

FIELD: pharmaceutics, medicine.

SUBSTANCE: the present innovation deals with cardiotherapy for treating and preventing coronary deficiency. The preparation is designed as a plate (film) consisted of three layers, each of them is manufactured out of co-polymer of vinyl pyrrolidone, acrylamide and nitroglycerin-containing ethylacrylate; moreover, internal layer additionally contains solid fat - cacao oil, and weight ratio for the sum of external layers to internal corresponds to 1 : 1. The suggested preparation could additionally contain brilliant green dyestuff. The preparation should be manufactured out of pre-obtained mixture of nitroglycerin and copolymer in solution of alcohol and water followed by layer-by-layer forming three-layer film due to spreading the mixture onto solid bottom plate and drying at 30-50 C. The innovation provides higher adhesion to gingival mucosal surface, decreased side action, improved bioavailability and stability of therapeutic effect.

EFFECT: higher efficiency of therapy.

3 cl, 3 ex

Description

The invention relates to the pharmaceutical industry, more specifically to the development and study of prolonged dosage forms used in cardiotherapy for the treatment and prevention of coronary insufficiency.

It is known that the prolongation effect is achieved by applying polymer shells that dissolve in the gastrointestinal tract, for example, Sustak, Nitrong, etc. (Mashkovsky M.D. “Medicines”, M. 1993, v. 1 , p. 490). Such funds can be used with oral administration only for the prevention of coronary heart disease and do not provide immediate relief of an attack of angina pectoris.

Closest to the proposed is a means for stopping and treating coronary heart disease, containing a copolymer, nitroglycerin and a dispersion of solid fats, which ensures prolonged isolation of a cardiopreparation (RF Patent No. 806037, publ. 02.23.81, Bulluten of inventions No. 7).

However, the known tool has a significant drawback. Along with the positive effect of imparting the required lipophilicity, the fat dispersion introduced into the agent significantly reduces the adhesion of the agent to the gum surface, as a result of which the bioavailability and stability of the therapeutic effect are worsened, undesirable cases of migration of the agent through the oral cavity, chewing and swallowing are observed, which is accompanied by an excessively large intake of nitroglycerin in blood and a pronounced side symptom of a headache (V. Metelitsa “Handbook of clinical pharmacology of cardiovascular tny medicines ”, M. 2002, pp. 86-87).

The technical task of the invention is to increase the adhesion of the agent to the mucous surface of the gum, excluding its migration in the oral cavity, possible chewing and swallowing, reducing side effects, improving the bioavailability and stability of the therapeutic effect.

The technical result is achieved in that the means for stopping and treating coronary heart disease, containing nitroglycerin, a copolymer and a dispersion of solid fat, is made of three layers, each of which contains a copolymer of vinyl pyrrolidone, acrylamide and ethyl acrylate as a copolymer, and the dispersion of solid fat contains cocoa butter distributed only in the inner layer, while the ratio of components in the layers is (% wt.):

outer layers

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate 92.0-96.0

- nitroglycerin 4.0-8.0,

the inner layer

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate 75.0-88.0

- nitroglycerin 4.0-10.0

- cocoa butter 8.0-15.0

with a mass ratio of the sum of the outer layers to the inner layer of 1: 1.

To identify dosages of nitroglycerin, the product may additionally contain a brilliant green dye in the amount of (1-3) 10 ^-2 % of the mass.

The tool is obtained using the dissolution of the copolymer and nitroglycerin in compatible solvents or in a common solvent, and the formation is carried out sequentially in three layers from solutions with a concentration of from 12 to 30% wt. on solid substrates followed by drying at a temperature of 30-50 ° C. From the resulting tape or plate, a tool of the required size and shape is formed.

The proposed method is illustrated by examples.

Example 1

Prepare a composition of the following composition:

for forming the outer layers

- nitroglycerin - 2.0

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate - 46.0

In 210 g of distilled or demineralized water, 46 g of a copolymer of vinyl pyrrolidone, acrylamide, ethyl acrylate are dissolved. The copolymer solution is mixed with 50 g of a 4% alcohol solution of nitroglycerin. A solution of 17.8% concentration is obtained, which is subjected to deaeration;

for forming the inner layer

- nitroglycerin - 2.0

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate - 42.0

- cocoa butter - 8.0

42 g of a copolymer of vinyl pyrrolidone, acrylamide, ethyl acrylate are dissolved in 190 g of distilled or demineralized water to obtain a solution of 21% concentration, 8 g of cocoa butter are placed in 50 g of a 4% alcohol solution of nitroglycerin, heated to 35-40 ° C until complete melting cocoa butter, intensively mixed for 5-10 minutes and cooled to 18-20 ° C. A suspension is obtained which, with constant stirring, is introduced into the copolymer solution prepared previously.

The solutions are sequentially applied in any known manner layer by layer onto an inert substrate, dried at a temperature of 30 to 50 ° C, and plates of the required size and shape are formed from the resulting tape or plate, providing a predetermined dosage of the drug substance - nitroglycerin.

Example 2

Prepare a composition of the following composition:

for the formation of the outer layers -

- nitroglycerin - 4.0

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate - 44.0;

to form the inner layer -

- nitroglycerin - 4.0

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate - 36.0

- cocoa butter - 12.0

Then proceed as described in example 1.

Example 3

Prepare a composition of the following composition: for the formation of the outer layers -

- nitroglycerin - 8.0

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate - 88.0

- diamond green - 0.01 (in excess of 100);

to form the inner layer -

- nitroglycerin - 8.0

- vinylpyrrolidone copolymer

acrylamide, ethyl acrylate - 81.0

- cocoa butter - 15.0

- diamond green - 0.02 (over 100)

During the mixing of solutions of the copolymer and nitroglycerin during the preparation of the compositions for the outer layers and the inner layer, 0.01 g and 0.02 g of brilliant green are respectively introduced into the composition.

Then proceed as described in example 1.

Unlike the known drug, the proposed drug does not contain lipophilic particles in the outer layers of the hydrophilic carrier, provides good adhesion to the gingival mucosa, promotes more uniform release of the drug substance, reduces the side effect in the form of a headache and eliminates the possibility of a sharp change in blood pressure, improves bioavailability and stability of the therapeutic effect of the drug.

Claims (3)

1. A tool for stopping and treating coronary heart disease, containing a copolymer, nitroglycerin and a dispersion of solid fats, characterized in that it is made in the form of a plate (film) of three layers, each of which contains a copolymer of vinyl pyrrolidone, acrylamide and ethyl acrylate, internal the layer additionally contains cocoa butter as a dispersion of solid fats, while the ratio of the components in the layers is, wt.%: outer layers - - vinylpyrrolidone copolymer acrylamide, ethyl acrylate 92.0-96.0 nitroglycerin 4.0-8.0, the inner layer - - vinylpyrrolidone copolymer acrylamide, ethyl acrylate 75.0-88.0 nitroglycerin 4.0-10.0 cocoa butter 8.0-15.0 with a mass ratio of the sum of the outer layers to the inner layer of 1: 1. 2. The tool according to claim 1, characterized in that it further comprises a brilliant green dye in an amount of (1-3) · 10 ^-2 wt.%. 3. A method of manufacturing a means for stopping and treating coronary heart disease, comprising combining a copolymer and nitroglycerin with the subsequent formation of a plate (film), characterized in that the formation is carried out layer by layer on an inert substrate of two outer and inner layers of water-alcohol solutions with a concentration of 12- 30 wt.% Followed by drying at a temperature of 30-50 ° C.