The method of purification of clinical dextran fractions

 

(57) Abstract:

Usage: in the pharmaceutical industry to improve the quality of products based on dextran - poliglyukina and reopoligliukina. The inventive aqueous solutions of clinical dextran fractions sequentially passed through sulfonation on the basis of a copolymer of styrene with divinylbenzene macroporous structure at pH of 4.0 - 5.5 and through the anion exchange resin is a macroporous copolymer of styrene with divinylbenzene, containing benzyltrimethylammonium group, at a pH of 8.0 to 9.5.

The invention can be used in pharmaceutical industry to improve the quality of products based on dextran - poliglyukina and reopoligliukina.

Known in the literature cleaning methods clinical dextran fractions are based on the use of activated carbon to remove opalescence and obtain a pyrogen-free solutions, but this treatment does not provide demineralization solutions.

Well-known and widely used in industry cleaning method dextranomer drugs, which is in the handling of slurries of coal, followed by demineralization (1).

w = 35 000 5 000 for reopoligliukina) was added activated charcoal and stirred at 120aboutC for 30 min, filtered, cooled and implement demineralization, sequentially passing the solution through the ion RL-2 (N+form), EDE-10P (HE-form). The desalted solution is sterilized with repeated addition of activated carbon at 120aboutC for 30 min, cooled, filtered, dispensed into vials and re-sterilize the finished product.

The disadvantages of this method are the inability to use activated charcoal and apply the gel resin is completely clear clinical fractions of dextran from organic impurities and residues producer of native dextran, which is the cause of reactogenicity blood substitutes based on dextran. It should be noted that the use of coal leads to an inevitable loss of the desired product due to the irreversible sorption of dextrans on coal.

In addition, there is the issue of education gray films and drop flocculent precipitate during storage of drugs due to the presence of particulate coal in ready lekforma.

It should be noted that there is a method of cleaning preparations multistage requires complex equipment dextranomer products, simplifying and reducing the time of the process and increase the yield of the target product.

This objective is achieved in that in the method of purification of clinical dextran fractions, including the serial transmission of their aqueous solutions through a cation-exchange and anion-exchange resin, as a cation-exchange resin used sulfonation on the basis of a copolymer of styrene with divinylbenzene macroporous structure, and as the anion exchange resin is a macroporous copolymer of styrene with divinylbenzene, containing benzyltrimethylammonium group, and passing through sulfonation carried out at pH 4.0-5.5, and through the anion exchange resin at pH of 8.5 to 9.5.

The method in accordance with the invention is as follows: cation-exchange and anion-exchange resin pretreated 1-3% hydrogen peroxide solution for 10-30 min and then washed with pyrogen-free water to a pH of 4-5,5 and pH 8-9,5, respectively. An aqueous solution of clinical faction dextran sequentially passed through the prepared cation exchange resin and anion exchange resin, filtered, dispensed into vials and sterilized finished product 20 min at 120aboutC. the Process of purification of aqueous solutions clinical fry cleanup clinical factions within the selected conditions allows to obtain sterile, pyrogen-free, clear, colorless dosage forms antishock products, stable during storage.

The advantage of this method compared to known is the simplification and reduction in the duration of the cleaning process of clinical dextran fractions by eliminating processing stages activated carbon at elevated temperature 120aboutWith and sterilization with activated carbon at 120aboutWith and all associated operations that simultaneously leads to increased yield of the target product by 5.5% to 8%.

The use of ion exchange resins, macroporous structures (Rthen400-1200 ) with highly developed specific surface (up to 350 m g) allows you to combine the processes of chemical cleaning solutions, demineralization and destruction of pyrogenic substances.

P R I m e R 1. Macroporous cation exchange resin type KU-23 treated with 1% hydrogen peroxide solution for 25 min and washed with pyrogen-free water to a pH of 4.0. Anion exchange resin is a macroporous structure type AM-p treated with 2% peroxide solution in Dorada for 10 min and washed with pyrogen-free water to a pH of 9.5.5 l of an aqueous solution of clinical fractions of dextran with Mw= 350005000 (Neopolis solution with C = 9.9%, and which is poured into bottles and sterilized. Get a sterile, pyrogen-free, clear, colorless finished product - reopoliglyukin with the release of 97.3%.

Finished dosage form reopoligliukina obtained by the present method, kept at 80 2,5aboutWith over 14 days. Control: reopoliglyukin obtained by a known method - transparent, light-yellow solution. Received - transparent, light-yellow solution. Control - yellow solution with flocculent sludge.

P R I m m e R 2. Macroporous cation exchange resin type KU-23 treated with 2.5% hydrogen peroxide solution for 10 min and washed with pyrogen-free water to a pH of 5.5. Anyhoooooo macroporous resin type AM-P treated with 1.5% hydrogen peroxide solution for 15 min and washed with pyrogen-free water up to pH 8.0. 5 l of an aqueous solution of clinical fractions of dextran with Mw= 60000 10000 and = 6,7% sequentially passed through the prepared cation exchange resin and anion exchange resin and filtered. Get 5,47 l of a solution with C = 6,03%, which is poured into bottles and sterilized. Get a sterile, pyrogen-free, clear, colorless finished product - poliglyukin with the yield of 98.5%.

Output poliglyukina at the stage of purification by known JV shall Bo kept at 80 2,5aboutWith over 14 days. Control: poliglyukin obtained by a known method is transparent, colourless solution. Received: clear, colorless solution. The control - light-yellow solution, there is a "snake".

The METHOD of PURIFICATION of CLINICAL DEXTRAN FRACTIONS, including the serial transmission of their aqueous solutions through a cation-exchange and anion-exchange resin, characterized in that as the cation exchange resin used sulfonation on the basis of a copolymer of styrene with divinylbenzene macroporous structure, and as the anion exchange resin is a macroporous copolymer of styrene with divinylbenzene, containing benzyltrimethylammonium group, and passing through sulfonation carried out at a pH of 4.0 - 5.5, and through the anion exchange resin at pH 8.0 to 9.5.

 

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