RU2200018C1 - Method of preparing injection form of preparation chondroitin sulfate - Google Patents

Abstract

FIELD: medicine, pharmaceutical technology, pharmacy. SUBSTANCE: invention relates to method of preparing injection form of the preparation chondroitin sulfate used for treatment of arthrological and rheumatic diseases. Method involves separate preparing chondroitin sulfate solutions in sterile water, benzyl alcohol and sodium hydroxide followed by addition of sterilized solutions of sodium hydroxide (up to pH 6.2-6.8) and benzyl alcohol to chondroitin sulfate sterilized solution. Invention provides the development of a novel method of preparing the preparation preventing formation of derivatives of chondroitin sulfate and the preparation coloring. EFFECT: improved method of preparing. 1 ex

Description

 The invention relates to medicine, specifically to the preparation of an injectable form of a preparation of chondroitin sulfate (CH) for the treatment of arthrological and rheumatic diseases based on the Na salt of chondroitin sulfate, a mucopolysaccharide from animal tissues.

 The specified drug, which was named "Mukosat" by the Ministry of Health of Russia, can be used to treat degenerative age-related diseases of the joints and spine, severe injuries of the musculoskeletal tissue. The drug affects metabolic processes in the connective tissue, including cartilage, stimulating and normalizing the biosynthesis of glycosaminoglycans.

 Known agent for the treatment of arthrological diseases, which is a mixture of chondroitin sulfates A and C in a ratio of 3: 2-1: 1, a preservative - benzyl alcohol and pyrogen-free water. This product is prepared by dissolving benzyl alcohol and cholesterol in pyrogen-free water, after which the pH is adjusted to 7.5 with a sodium hydroxide solution, filtered sterile and poured into ampoules (1).

A known method of obtaining a drug for the treatment of arthrological diseases, which includes: dissolving benzyl alcohol in water, establishing a 30% solution of sodium hydroxide pH 7.2-7.4, subsequent dissolution in the resulting solution of cholesterol, heating the mixture to 50 ^o C with further sterilizing filtration, filling in ampoules and their sealing (2) (prototype).

 The disadvantages of the known methods include the fact that often in the manufacture of a preparation containing cholesterol (consisting of uronic acid and hexosamine) and benzyl alcohol, a pink color of the solution appears at a pH of 7.2-7.5, which intensifies during storage. The appearance of a pink color indicates the appearance in the solution of some derivatives of cholesterol, the presence of which excludes the use of the drug for therapeutic purposes.

 The objective of the invention is to develop such a method of preparation of the drug, which eliminates the occurrence of pink staining solution.

 This problem is solved by the fact that upon receipt of the injectable form of the drug, its components are prepared separately. Namely: the substance of chondroitin sulfate is dissolved in heated injection water, followed by sterilizing filtration of the solution. Next, solutions of benzyl alcohol and sodium hydroxide are prepared, then sterilized solutions of sodium hydroxide and benzyl alcohol and water for injection are added to the cooled sterile cholesterol solution with stirring. The resulting mixture, the pH of which is 6.2-6.8, is poured into ampoules of 1 or 2 ml, after which the ampoules are sealed.

 In the preparation obtained by the claimed method, staining does not occur.

 The claimed method is as follows.

 Solutions of the following components are preliminarily prepared (per 1 ml of injection water): 100 mg of a substance of chondroitin sulfate (solution “A”); 9-11 mg of benzyl alcohol (solution "B"); 0.04-0.05 mg sodium hydroxide (solution "B"). Then, sterile solutions “B” are added to the cooled sterile solution “A” with stirring to a pH of 6.2–6.8 and “B” (solution “G” is obtained). In solution "G" add sterile injection water up to 1 liter. Then the drug is poured into ampoules of 1 or 2 ml, after which the ampoules are sealed.

 The claimed method is illustrated by example.

Example 1. Preparation of solution "A". In 400 ml of injection water, heated to a temperature of 50 ^o C, dissolve 100.0 g of cholesterol (in terms of absolutely dry substance). After complete dissolution of the cholesterol, the solution is cooled to room temperature, the volume of the solution is adjusted with injection water to 600 ml, and it is subjected to sterilizing filtration.

 Preparation of solution "B". To 9.0-11.0 g of benzyl alcohol add 250 ml of injection water and mix until the benzyl alcohol is completely dissolved.

 Preparation of solution "B". 0.04-0.05 g of sodium hydroxide is dissolved in 50 ml of water for injection.

 Preparation of solution "G". In a sterile solution "A" with constant stirring, 50 ml of solution "B" is sterilely filtered, and then 15-20 minutes after adding solution "B", while stirring the solution, sterilely filtered with 250 ml of solution "B". Stirring after adding solution "B" is continued for 15-20 minutes.

 Getting the drug. In a sterile container with a solution of "G" through the sterilizing filter make the missing amount (up to 1 l) of injection water.

 Pouring a solution of the drug. The solution is poured into ampoules of 1.0 or 2.0 ml. Ampoules are sealed.

 In the preparation prepared by this method, the development of staining does not occur.

Sources of information
1. Patent of the Russian Federation 2021812, cl. NKI A 61 K 35/42, 37/20, С 08 В 37/08, 10/30/1994 (State Institute of Blood Substitutes and Medicines).

 2. The regulations for the production of a solution of chondroitin sulfate for injection // All-Union Scientific Research Institute of the technology of blood substitutes and hormonal preparations. - M., 1994.

Claims (1)

A method for preparing an injection form of a preparation of chondroitin sulfate (CH), comprising dissolving benzyl alcohol, cholesterol and sodium hydroxide in injection water, using heating to 50 ^° C, sterilizing filtration, filling in ampoules and seals, characterized in that solutions of the components of the drug are prepared separately, first, the cholesterol substance is dissolved in heated injection water, followed by sterilization and cooling (solution A), then a solution of benzyl alcohol (solution B) and a solution of sodium hydroxide (solution B) A solution is then added with stirring to solution B of pH 6.2-6.8 and the solution B, the mixture was diluted with water injection, dispensed into vials and sealed.