GB730929A - Stabilised aqueous hyaluronidase solutions and method of preparing them - Google Patents

Abstract

Aqueous hyaluronidase solutions for parenteral use are stabilized by addition of ethylene-diaminetetra-acetic acid together with sodium or calcium chloride. The hyaluronidase may be present in amounts to furnish 25 - 1000 TRU per millitre (as defined in the Specification). The ethylenediaminetetra-acetic acid may be present in amounts between 0.1 and 1 mg per millitre, and the concentration of the sodium or calcium chloride may be between 0.1 M and 0.2 M. The pH of the solution may be kept between 6.0 and 8.0 by the addition of a non-toxic buffer such as 0.01 ionic strength phosphate buffer. A preservative such as sodium ethylmercurithiosalicylate may also be present: it is preferred to make up the solution using a 1 : 10000 solution of this substance in pyrogenfree water. Small amounts of amino acids such as glycine or arginine may also be added. In an example a stock solution is prepared containing sodium ethylmercurithiosalicylate, sodium chloride and the di-sodium salt of ethylene diaminetetra-acetic acid. The solution is buffered with disodium hydrogen phosphate and sodium dihydrogen phosphate, powdered hyaluronidase dissolved therein, and diluted with further stock solution to give a solution of the desired activity. The stability of the solution may be increased by filling the sterile solution into ampules of such a size as to provide a minimum ratio of air-liquid interface to volume, and sealing.