GB2072675A - Cephapirin salts - Google Patents

Abstract

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

Description

SPECIFICATION Cephapirin salts The antibiotic cephapirin is described in US Patent Specification No.3,422,100. Cephapirin is usually administered parenterally as its sodium salt, but it is well known that the injection of this salt, and of antiobiotics in sodium salt form in general, is painful. It would therefore be desirable to provide a cephapirin salt which allows ready absorption of the antiobiotic on administration and whose injection does not cause pain.

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

Basalt of the invention may be prepared by reacting an aqueous solution of cephapirin with an aqueous solution of the aminoacid, or a derivative thereof. The reaction may be conducted at ambient temperature.

The cephapirin 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 cephapirin 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 Cephapirin lysina te Twice-distilled water (500 ml) and cephapirin (in acid form) (42.3 g, 0.1 moleS were charged at 0 C into a reaction vessel; the pH was 3.5. A 50% aqueous solution of L-lysine base, containing 14.6 g (0.1 mole) of L-lysine base, was added; the mixture was stirred for 1 hour at 0 C. Complete dissolution ensued and the pH rose to 8. 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. The solution was then frozen at -40 C and lyophilised. After 24 hours the resulting material was discharged and screened. 54 g cephapirin lysinate were obtained.

EXAMPLE 2 Cephapirin arginine salt Twice-distilled water (450 ml) and cephapirin (in acid form) (42.3 g, 0.1 mole) were charged at 0 C into a reaction vessel; the pH was 3.5. A 10% aqueous solution of L-arginine (210 ml), containing 21 g of L-arginine, was added at 0 C. The reaction mixture was kept at OOC for 30 minutes; the pH rose to 8.5. Decolourising carbon (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. Lyophilisation was conducted by freezing the solution at -45 C for 24 hours.

The resulting material was discharged and screened. 55 g cephapirin arginine salt were obtained.

EXAMPLE 3 Cephapirin acetylcysteinate Water (500 ml) and cephapirin (in acid form) (42.3 g, 0.1 mole) were charged into a reaction vessel. After cooling at 0 C, an aqueous solution containing 16.3 g (0.1 mole) of acetylcysteine was added. Complete dissolution was obtained; the resultant pH was 2.1. The mixture was allowed to react for 1 hour and then carbon (3 g) was added. The resultant solution was filtered through filter plates, poured into a tray to give a 1 cm deep layer. The solution was subjected to pre-freezing. At -40"c, the solution was completely frozen and was lyophilised for 36 hours. The resultant material was screened and 55.6 g cephapirin acetylcysteinate were obtained.

The properties of the products of the Examples are tabulated below. The optical rotation values were obtained using sodium D light (c= 1, H2O). The microbiological (Mb)titres were obtained with respect to cephapirin in the acid form.

Example 1 2 3 K.F.(%) 1.2 1.2 1 TLC (spots) 1 1 1 [a]D( ) +127 +120 +118 Mb titre (mcg/mg) 730 687 707 The formulae of the products of the Examples may be respectively represented as follows

Claims (6)

1. An aminoacid salt of cephapirin.

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

3. A compound of formula las 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.