GB1561592A

GB1561592A - Antibacterial composition

Info

Publication number: GB1561592A
Application number: GB18316/76A
Authority: GB
Original assignee: Beecham Group PLC
Current assignee: Beecham Group PLC
Priority date: 1976-05-05
Filing date: 1976-05-05
Publication date: 1980-02-27
Also published as: JPS52134025A; JPS61804B2

Description

(54) ANTIBACTERIAL COMPOSITION (71) We, BEECHAM GROUP LIMITED, a British Company, of Beecham House, Great West Road, Brentford, Middlesex, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to an anti-bacterial pharmaceutical composition.

More specificaily this invention relates to an injectable pharmaceutical composition which contains a penicillin and a synergist.

British Patent Specification No. 1508977 discloses inter alia that salts of clavulanic acid, which has the formula (I):

may be included in injectable pharmaceutical compositions. The said Specification also discloses that when such compositions also contain a penicillin the resulting composition is Particularly effective against many strains of bacteria. It has now been discovered that an unusually broad spectrum of activity can be obtained with certain specific co-formulations of penicillin and synergist.

Accordingly the present invention provides a pharmaceutical composition adapted for administration by injection which comprises a pharmaceutically acceptable salt of clavulanic acid and a pharmaceutically acceptable salt of a compound of the formula (II):

wherein R' is H or OH and a pharmaceutically acceptable excipient.

Generally clavulanic acid and the compound of formula (II) are present in the form of a sodium salt. These salts should normally be water free.

The weight ratio of the salt of clavulanic acid present to the salt of the compound of formula (II) present will normally be from 1:20 to 2:1, more usually from 1:10 to 1:1, for example, 1:5, 1:3 or 1:2.

Most suitably the composition of this invention will contain a salt of the compound of the formula (II) wherein R1 is OH.

The compositions of this invention may be formulated with conventional excipients as described in the aforementloned British Patent or in other conventional excipients used in the penicillin art for preparing injectable compositions. Such compositions may be prepared by conventional methods of blending and sterilization.

Particularly suitable compositions of this invention will be in unit dose form and will contain 25-500 mg of the salt of clavulanic acid and 15W1500 mg of a salt of a compound of the formula (II).

Preferred compositions of this invention will contain 50--250 mg of the salt of clavulanic acid and 200--600 mg of a salt of a compound of the formula (II).

The weights of the antibacterial agents in the preceding compositions are expressed on the basis of the pure free acid equivalent present in the composition.

A particularly suitable form of the compositions of this invention comprises a mixture of the dry salts sealed in glass vials, the whole being sterile.

Such compositions may be prepared by filling the freeze dried salt of clavulanic acid and the freeze dried salt of the compound of the formula (II) into vials and then sterilizing in conventional manner (e.g. uv or ethylene oxide) before sealing.

The compositions of this invention have a particularly broad spectrum of activity against gram-negative organisms including strains of Escherichia coli, Kiebsiella aerogenes, Proteus mirabilis, Proteus morgan ii, Proteus vulgaris and Pseudomonas aerogenosa.

The broad spectrum of the compositons of this invention is illustrated by the antibacterial Minimum Inhibitory Concentration data given in Table 1 for a 10:1 mixture of the sodium salt of the compound of the formula (II) wherein R' is OH (Penicillin A) and sodium clavulanate.

TABLE 1 MICs Obtained Against Strains Selected for their Resistance to Ampicillin, Ticarcillin and Cephaloridine

MtC (Lrg/ml) Penicillin A + Sodium Clavulanate Sodium Organism Penicillin A 10: 1 Clavulanate Escherichia coli JT39 2000 8 + 0.8 31 Escherichia coli JT98 500 8 + 0.8 31 Klebsiella aerogenes Ba95 2000 31 t 31 125 Proteus mirabilis C889 2000 8 + 0.8 31 ProteusmorganjiDulO 2000 4 + 0.4 31 Proteus vulgaris Q3618 2000 1 + 0.1 62 The following Example illustrates the invention: Glass vials are each filled with the following anhydrous components: Sodium Clavulanate 100 mg Sodium Penicillin A 500mg Preservative l0 mg The vials are sealed and the vial and contents sterilised by exposure to ultraviolet radiation.

Claims

WHAT WE CLAIM IS:

l. A pharmaceutical composition adapted for administration by injection which comprises a pharmaceutically acceptable salt of clavulanic acid and a pharmaceutically acceptable salt of a compound of the formula (II):

wherein R, is H or OH; and a pharmaceutically acceptable excipient.
2. A composition as claimed in claim 1 wherein the salt of clavulanic acid is the water-free sodium salt and the salt of the compound of the formula (II) is the waterfree sodium salt.
3. A composition as claimed in claims 1 or 2 wherein the weight ratio of the salt of clavulanic acid present to the salt of the compound of the formula (II) present is l:lO to 1:1.
4. A composition as claimed in any of clairns 1--3 wherein R is OH.
5. A composition as claimed in any of claims 1--4 in unit dose form which comprising 50--250 mg of the salt of clavulanic acid and 200--600 mg of the salt of the compound of the formula (II) per unit dose.