CS247688B1 - Method of lysine salt with acetylsalicylid acid production - Google Patents

Abstract

A method for producing a lysine salt with an acid acetylsalicylic is that alcoholic solution of acetylsalieylic acid in ethanol, for example, introduced into aqueous lysine acid solution. Listed salt appears in the form of an injection solution clinically analgesic.

Description

BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of a salt of lysine with acetic acid.

This salt is in the form of a solution for injection a potent, clinically used analgesic (Fyaiatr. Vest. 59 »1 (1981),

Z. Rheumatol. 42, 86 (1983), Prakt. Medicine. 64, 842 (1984)). According to the prior art, this salt is prepared by mixing both components and the product obtained by freeze-drying (French patent (Fr. Demande) 2,115,060 (Chem. Abstr. 78, P 79 877 k), or the two components are mixed in a less polar solvent, for example in acetone or alcohol by pouring an aqueous solution of lysine (base) into an alcoholic solution of acetylsalicylic acid (French Patent No. 1 299 904, Spanish Patent No. 456 529) - after seeding, the precipitated salt is recovered by filtration and dried under vacuum.

However, it has been found that conventional commercial preparations produced in this way always show an increased amount of salicylic acid, which is produced by the process of hydrolysis of acetylsalicylic acid. The requirement for a suitable preparation is subject to a minimum content of salicylic acid which is undesirable and produces toxic side effects.

Surprisingly, it has been found that the salt of lysine and acetylsalicylic acid can be prepared advantageously in high yield and purity by the process according to the invention, characterized in that lysine is present in the form of an aqueous solution having a concentration of 25 to 50% by weight, optionally with 0.1 up to 0.5 mole of glycine, based on 1 mole of lysine, is reacted with an equivalent amount of acetylsalicylic acid in the form of a saturated solution of 1 to 3 carbon atoms, e.g. 5 to 30 ° C, preferably at 25 ° C. The precipitated salt is separated, washed with the alkanol used to dissolve the acetylsalicylic acid and freed of volatiles.

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The process according to the invention is further characterized in that all operations are carried out under sterile conditions. When all operations of the process according to the invention are carried out under sterile conditions, the product is available in the form of an injectable solution. according to the invention 2%.

The following examples illustrate the process according to the invention but do not limit it in any way.

Example 1

To an aqueous 32.11% DL-lysine solution (47 mL) was added a solution of acetylsalicylic acid (18 g) in 96% ethanol (150 mL) with stirring at 24 ° C for 5-6 minutes. 96% ethanol (500 ml) was added and after seeding a crystalline product precipitated, which after 45 minutes of storage at +3 ° C was filtered off, washed successively with ethanol (200 ml) and finally vigorously aspirated and dried in a vacuum oven at 30 ° C 29.4 g (90%) of the product with m.p. Mp 140-142 ° C.

Example 2

To an aqueous 32.11% DL-lysine solution (47 mL) was added glycine (750 mg), and after stirring for 10 minutes, a solution of acetylsalicylic acid (18 g) in 96% ethanol (150 mL) was added to the reaction solution (20 ° C). ml) and the reaction solution was worked up as described in Example 1. * 28.1 g (86.3%) of the product having a melting point of 139-141 ° C were obtained.

Example 3

To an aqueous 32.11% solution of DL-lysine (4.7 mL) cooled to + 4 ° C was added, with stirring, a pre-cooled solution (+ 10 ° C) of acetylsalicylic acid (1.8 g) in 96% ethanol (20 mL). ) so that the temperature of the reaction solution does not exceed +10 ° C. Thereafter, 96% ethanol (10 ml) was added to the reaction solution and after standing for 1 hour at +3 ° C, the precipitated crystalline product was treated in a similar manner to that described in Example 1. 3.1 g (95%) of the product with m.p. M.p. 142-143 ° C.

Example _{4,247 M8}

K vodném. A solution of acetylsalicylic acid (1.8 g) in 96% ethanol (10 ml) was added under stirring at 21 ° C with a 38% DL-lysine solution (3.9 ml) and further worked up as described in Example 3. 2 7 g (83%) of the product of m.p.

M.p. 141-143 ° C.

Claims (2)

Process for the preparation of a salt of lysine with acetylsalicylic acid, optionally with the addition of a stabilizer, for example glycine, characterized in that lysine in the form of an aqueous solution having a concentration of 25 to 50% by weight, optionally with the addition of 0.1 to 0.5 moles of glycine, per mole of lysine, reacted with an equivalent amount of acetylsalicylic acid in the form of a saturated solution in C 1 -C 3 alkanol, wherein the alcoholic acetylsalicylic acid solution is introduced into the aqueous lysine solution at a temperature of +5 to 30 ° C, and the precipitated salt separated, washed with the alkanol used to dissolve the acetylsalicylic acid and freed from the volatiles. 2. The method according to claim 1, wherein all operations are carried out under sterile conditions.