Stable composition of the anti-inflammatory action

 

(57) Abstract:

The invention relates to medicine, and is intended for the treatment of inflammatory lung diseases, including bronchial asthma. The composition containing budesonide, water, further comprises propylene glycol, polyethylene oxide, succinic acid, Trilon B, nipagin in the following ratio, wt.%: budesonide 0,01-0,1; propylene glycol 10,0-25,0; polyethylene oxide 30,0-40,0; succinic acid of 0.05-0.5; Trilon B 0,01-0,1; nipagin 001-0,1; water up to 100.0. It can optionally contain 6-(acetylamino)hexanoic acid number from 0.0 to 5% and the polyethylene oxide - polyethylene oxide 400. It is suitable for inhalation. The invention improves the stability of the composition to reduce its toxicity. 3 C.p. f-crystals.

The invention relates to the field of medicine and is suitable for the treatment of inflammatory respiratory diseases, including bronchial asthma.

The most effective drugs currently used to treat inflammation of the respiratory tract and especially asthma, are various glucocorticoids: beclometason, fluticasone, flunisolide, triamcinolone acetonide, budesonide, etc. As a rule, these preparaing drugs on systemic action is a glucocorticosteroid budesonide - highly effective anti-inflammatory agent exclusively local action as rapidly metabolized in the liver, almost without systemic effects. These properties of budesonide resulted in its widespread use as a medicinal product for local use. The most effective action of budesonide in dissolved form. Because budesonide due to its lipophilicity practically insoluble in water, it dissolves apply various alcohols and glycols.

In the international application 96/19969 (publ. 1996) described the solutions of budesonide for the preparation of rectal dosage forms and pharmaceutical pen to use them by spraying under pressure, mg:

Budesonide - 2

(-cyclodextrin or cyclodextrin - 60

Sodium benzoate - 300

Yellow gum - 360

Ethyl alcohol - 400

Water - 60

Hydrochloric acid To pH 4.0

The composition of budesonide has certain disadvantages: the stability of the composition at 40oWith is only 6 weeks, which corresponds to 1 year of storage under natural conditions; it is not enough because for medicines required stability for 2 years the economic and physical-chemical characteristics does not meet the requirements on the drug for inhalation, namely, the high content of alcohols in solution (preferably from 93 to 98%) is not valid for inhalation drugs; alcohol can irritate and dehydrate the epithelium of the respiratory tract (the ratio of alcohol:water is from 100:0 to 80:20).

The present invention is to develop a pharmaceutical composition of lower toxicity and increased shelf life.

The technical result consists in increasing the stability of the composition and improve its biomedical properties.

The result is achieved that a stable composition of the anti-inflammatory action, containing budesonide, water, further comprises propylene glycol, polyethylene oxide, succinic acid, Trilon B, nipagin in the following ratio, wt.%:

Budesonide - 0,01-0,1

Propylene glycol - 10,0-25,0

The polyethylene oxide - 30,0-40,0

Succinic acid - 0,05-0,5

Trilon B - 0,01-0,1

Nipagin - 0,01-0,1

Water Up to 100.0

the fact that additionally contains 6-(acetylamino)hexanoic acid number from 0.0 to 5% that of the polyethylene oxide is polyethylene oxide 400, and that is suitable for inhalation.

The polyethylene oxide used in the preparation of as (Acetylamino)hexanoic acid is used as the stabilizer of budesonide in the composition and in addition to stabilizing action on budesonide in solution has a positive effect on epithelialization and regeneration of tissues of the respiratory tract, it also has anti-inflammatory properties, which is an important factor in the treatment of inflammation of the respiratory tract (encyclopedia of drugs. M, 8 ed., 2001, S. 109).

A new pharmaceutical composition is produced by a gradual mixing of the solid components from the liquid at 20-50oC.

Example 1. In a three-neck flask equipped with stirrer and reflux condenser, a load of 35 g of polyethylene oxide 400, 20 g of propylene glycol, the mass is stirred, then download 0.15 g of 6-(acetylamino)hexanoic acid, 0.05 g of nipagin, 0.05 g of budesonide, thoroughly mixed, after dissolution, add 0.15 g of succinic acid, 0.05 g of the trylon B and 100 ml of water. Heated to 40-45oC to dissolve, gradually cooled to 20o, filtered through a 0.22 μm filter. Get 100 g of the solution of budesonide containing 0.05% of budesonide, meets the requirements of the pharmaceutical agent suitable for inhalation, is stable for 2 years.

Example 2. Analogously to example 1 load of 30 g of polyethylene oxide 400, 25 g of propylene glycol, 5 g of 6-(acetylamino)hexanoic acid, 0.5 g of succinic acid. Get 100 g of the solution of budesonide containing 0.05% of budesonide, meets the requirements of the pharmaceutical crest g of polyethylene oxide 600, 25 g of propylene glycol, 5 g of 6-(acetylamino)hexanoic acid, 0.5 g of succinic acid. Get 100 g of the solution of budesonide containing 0.05% of budesonide, meets the requirements of the pharmaceutical agent suitable for inhalation, is stable for 2 years.

Example 4. Analogously to example 1 load of 40 g of polyethylene oxide 400, 10 g of propylene glycol, 0.1 g of the trylon B, 0.05 g of succinic acid. Get 100 g of the solution of budesonide containing 0.05% of budesonide, meets the requirements of the pharmaceutical agent suitable for inhalation, is stable for 2 years.

Proposed in the claims ratio of the current and auxiliary substances is best found experimentally and provides the required quality of the drug, its stability over 2 years and a high therapeutic effect.

1. Stable composition of the anti-inflammatory action, containing budesonide, characterized in that it further comprises propylene glycol, polyethylene oxide, succinic acid, Trilon B, nipagin in the following ratio, wt. %:

Budesonide - 0,01-0,1

Propylene glycol - 10,0-25,0

The polyethylene oxide - 30,0-40,0

Succinic acid - 0,05-0,5

3. Stable composition of the anti-inflammatory action on p. 1, characterized in that as polyethylene oxide contains polyethylene oxide 400.

4. Stable composition of the anti-inflammatory action on p. 1, characterized in that suitable for inhalation.

 

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