FR2479228A1 - CEPHAPIRINE SALTS WITH AMINO ACIDS - Google Patents

Abstract

SALTS OF CEPHAPIRINE WITH AN AMINO ACID SELECTED FROM THE GROUP CONSISTING OF L-LYSINE, L-ARGININE AND ACETYLCYSTEINE. THESE SALTS ARE OBTAINED BY REACTING AN AQUEOUS SOLUTION OF CEPHAPIRINE WITH AN AQUEOUS SOLUTION OF AN AMINO ACID OR ITS DERIVATIVE, SELECTED FROM THE GROUP CONSISTING OF L-LYSINE, L-ARGININE AND ACETYLCYSTEINE. TO ISOLATE THE SALT, THE AQUEOUS SOLUTION IS SUBJECT TO LYOPHILIZATION.

Description

The invention relates to novel cephapirin salts with amino

acids, these salts having a

  antibiotic activity. Cephapirin is an antibiotic

  as well known, described in US Patent No. 3,422,100 and published Japanese patent application

under No. 44-26107.

  Cephapirin is usually administered

  parenterally in the form of its sodium salt.

  It is well known that the sodium salts of this

  type of antibiotic and, in particular, cephapirin

  no, are painful administration by injection.

  The invention proposes to provide new cephapirin salts which are injectable without inducing

  painful reaction when administered.

  It also relates to cephapirin salts which increase the absorption of the antibiotic substance and

  which, when absorbed by the organism, are capable of

  the cephapirin-specific antibiotic activity of their own specific activity, which may be

  have some interest from a pharmacological point of view.

  These results are obtained by salification of cephapirin with an amino acid selected from

  group consisting of L-lysine, L-arginine and acetyl-

  cysteine. To obtain this salification, cephapirin is reacted in aqueous solution and at room temperature with an aqueous solution of an amino acid or its derivative, selected from the group consisting of L-lysine, L-arginine and l-arginine. acetylcistine, the salt of

  cephapirin being isolated from the aqueous solution by

philisation.

  The invention will be better understood using the

  description below of a process for preparing the three

  salts which are the subject of the invention, given as

purely illustrative example.

Example 1

Cephapirin Lysinate Formula

- S -CH -XH

oN CHP2COCH3

COQH. H2N- (CH2) 4-CH-COOH

H2

  Two-distilled water (500 ml) and cephapirin in the acid form (42.3 g, 0.1 mole) were added to a reaction flask; the pH is measured and it is found that it is at 3.5. A 50 Lysine aqueous base solution containing 14.6 g (0.1 mole) of L-lysine base is added; the mixture is stirred for 1 hour at 0 C. Complete dissolution is obtained and the pH is raised to 8. Bleaching carbon (1.5 g) is added to the resulting solution, which is filtered through filters. filter plates, and poured into a cup

  until you get a 1 cm thick layer. The solution

  The mixture is then frozen at -40 ° C. and freeze-dried. After 24 hours, the resulting material is removed and sieved. We

  obtains cephapirine lysinate (54 g).

KF: 1.5%

  TLC: single product Z-7D (c = 1, H20: + 127

  Microbiological titre = 730 mcg / mg as cephapid

in the form of acid.

- 3 -

Example 2

  Cephapirine arginine salt having the formula

N 5 "-S-CH 2 -CO-NH

CH2OCOCH3

COOH. H2N \ (C H2

C-NH- (CH 2) 3 -H-COOH

  A double-distilled water (450 ml) and cephapirin were added to a reaction flask at 0 ° C.

  the acid form (42.3 g, 0.1 mole); the pH is 3.5.

  At 0 ° C., a 10% aqueous solution of

  L-arginine (210 ml) containing 21 g of L-arginine.

  The reaction mixture is maintained at 0 C

  30 minutes; the pH is raised to 8.5. We add car-

  bleaching bone (5 g) to the resulting solution, which is filtered through filter plates and poured into

  cup until a layer of 1 cm thick is

  sor. After pre-freezing at -45 C, we begin the

  philisation. It ends after 24 hours, the material obtained being removed and sieved; we get salt

arginine of cephapirin (55 g).

KF: 1.2%

  TLC: simple product Zq7D (c = 1, H20): + 120

  Microbiological titre: 687 mcg / g, like cephapins

in the form of acid.

- 4 -

Example 3

  Cephapirin acetylcysteate having the formula

  HS -C2 -CH-COO. > -S-CHH2-CO-NH H2 3

NH-COCH3 0

  COOH Water (500 ml) and cephapirin in the form of acid (42.0 g 0.1 mol) are introduced into a reaction flask. After cooling to 0 C, add

  an aqueous solution containing 16.3 g (0.1 mol) of acetyl

  cistéine. Complete dissolution is obtained; the correct pH

  respondent is 2.1. The mixture is allowed to react for 1 hour; 3 g of carbon are then added. The solution obtained is filtered through filter plates, poured into a cup until a layer of

  1 cm thick and pre-frozen.

  At -40 ° C, the solution is completely frozen and lyophilized. Lyophilization is complete in 36 hours. The obtained material is sieved and we obtain

  cephapirin acetylcysteate (55.6 g).

KF: 1%

  TLC: single product t-D (c: 1, H20): + 118 microbiological title: 707 mcg / mg as the

cephapirin in the form of acid.

- 5 -

Claims (5)

CLAIMS -   1. Cephapirin salt with an amino acid selected from the group consisting of L-lysine, L-arginine and acetylcysteine.   2. Cephapirine salt which is a cephapirine lysinate having the formula \, \ S-CH -CONH - S 2- CH 2 C 20 COOH   COOH. H2N- (CH2) 4-CH-COOH   3. Cephapirin salt which is a salt of cephapirin arginine having the formula S N-S-CH 2 -CO-NEF (IC 2 COH N9 S CH2> e CH 2OCOCH3 COOH. H2 N NEH2 sC-NH- (CH2) 3-CH-COOH NH   4. Cephapirine salt which is an acetylcysteine cephapirin with the formula S HS-CH-CH-COOH. N-S-CHE-CO-NH S 2 1 2 N CH2OCOCH3 NH-COCH3 COO 2479Z28   - 6 - 5. Process for preparing a cephapirine salt   according to one of claims 1 to 4, characterized in that   cephapirin is reacted at room temperature with an aqueous solution of an amino acid or its derivative, selected from the group consisting of L-lysine, L-arginine and acetylcysteine, the salt of cephapirin   being isolated from the aqueous solution by lyophilization.