GB2073192A - Cefadroxil Salts - Google Patents

Abstract

Aminoacid salts of cefadroxil can be administered parenterally to release the antibiotic cefadroxil and the aminoacid. The aminoacid may be L-lysine, L-arginine or acetylcysteine.

Description

SPECIFICATION Cefadroxil Salts The antibiotic cefadroxil, i.e. p-hydroxycephalexin, is described in US Patent Specification No.

3,489,752. It is a broad-spectrum antibiotic which is usually adminsitered orally. It would be desirable to provide a form of cefadroxil which could be injected without causing painful reaction.

The novel compounds of this invention are amino-acid salts of cefadroxil. The aminoacid is preferably L-lysine, L-arginine or acetylcysteine.

A salt of the invention may be perpared by reacting an aqueous solution of cefadroxil with an aqueous solution of the aminoacid, or a derivative thereof. the reaction may be conducted at ambient temperature. The cefadroxil salt may be isolated from the aqueous solution by lyophilisation.

For administration to a subject, a salt of this invention may be provided in association with a physiologically acceptable excipient, in the form of a pharmaceutical composition. When administered, a salt of this invention may break down to the antibiotic principle cefadroxil and an aminoacid which may itself have a desirable action.

The following Examples illustrate how the compounds of this invention may be prepared.

Example 1 Cefadroxil Arginine Salt L-arginine (21 g, 0.1 mole) was added to a suspension of cefadroxil dimethylformamide solvate (43.6 g, 0.1 mole) in distilled water (300 ml); the pH rose to 8 and complete dissolution was obtained.

3 g of decolourising carbon were added to the resultant solution, which was then filtered through Decalite. The filtered solution was poured into a tray to give a 1 cm deep layer; after pre-freezing, the solution was frozen at -400C and lyophilisation was started. Lyophilisation was complete in 36 hours.

After lyophilisation, the product was screened and 50.1 g of the arginine salt of cefadroxil were obtained.

Example 2 Cephadroxyl Acetylcysteinate N-acetylcysteine (16.32 g, 0.1 mole), dissolved in distilled water (200 ml) at 1 5-200C, was added to a suspension of cefadroxil dimethylformamide solvate (43.6 g, 0.1 mole) in distilled water (350 ml). Complete dissolution was obtained. After 30 minutes, carbon (2.5 g) was added to the resultant solution at OOC. After 30 minutes stirring, the solution was filtered through Decalite. The resultant clear solution was poured into a tray to give a 1 cm deep layer which was frozen at -400C and lyophilised. Lyophilisation lasted 36 hours. The white crystalline product which was obtained was screened and 49 g of cephadroxyl acetylcysteinate were obtained.

Example 3 Cephadroxyl Lysinate Twice distilled water (600 mi) and cephadroxyl dimethylformamide solvate (43.6 g, 0.1 mole) were charged into a reaction vessel at OOC. A 50% L-lysine base aqueous solution, containing 14.6 g (0.1 mole) L-lysine, was added to the resultant suspension; the mixture was stirred for 1 hour at OOC.

Complete dissolution was obtained and the pH rose to 8.5. Decolourising carbon (1.5 g) was added to the resultant solution which was filtered through filter plates and poured into a tray to give a 1 cm deep layer was obtained. The solution was then frozen at -350C and lyophilised. The resulting material was discharged and screened; cephadroxyl lysinate (48 g) was obtained.

The results obtained in each of the above Examples could be repeated by using cefadroxil monohydrate (38.1 g) instead of the cefadroxil dimethylformamide solvate.

The properties of the products of Examples are tabulated below. Thin layer chromatography (TLC) was conducted using a 20:5:2 v/v/v mixture of acetonitrile, water and formic acid as eluent. The optical rotation values were obtained using sodium D light (c=1, H20). The microbiological (Mb) titres were obtained with respect to cefadroxil in dry base form.

Example 1 2 3 K. F. (%) 1 0.7 1.3 TLC (spots) 1 1 1 []D ( ) +118 +115 +110 Mb titre (mcg/mg) 665 668 709 The formulae of the products of the Examples may be respectively represented as follows

Claims (6)

Claims

1. An aminoacid salt of cefadroxil.

2. An aminoacid salt of cefadroxil, in which the aminoacid is L-lysine, L-arginine cr acetylcysteine

3. A compound of formula I as herein defined.

4. A compound of formula Il as herein defined.

5. A compound of formula Ill as herein defined.

6. A pharmaceutical composition comprising a compound as claimed in any preceding claim in association with a physiologically acceptable excipient.