VETERINARY COMPOSITION

Abstract: A topical formulation comprising ampicillin or a veterinarily acceptable salt thereof, a veterinarily acceptable salt of cloxacillin, and a veterinarily acceptable oil as carrier, is described which is useful in the treatment or prophylaxis of eye infections in animals.

Description: GB-A-2 119 649 describes a method for the treatment of infectious keratoconjunctivitis in animals, which comprises administering to the animal by topical instillation, a formulation comprising a salt of cloxacillin and a veterinarily acceptable oil as carrier. The method is especially applicable in the treatment of Infectious Bovine Keratoconjunctivitis. The invention provides the use of a formulation comprising ampicillin or a veterinarily acceptable salt thereof, a veterinarily acceptable salt of cloxacillin, and a veterinarily acceptable oil as carrier, for the manufacture of a medicament for topical use in the treatment or prophylaxis of eye infections in animals. The formulations of the invention provide prolonged inhibitory levels of antibiotic and are useful in the treatment of eye infections in animals caused by a wide range of organisms. As used herein the term "eye infection" includes but is not limited to conjunctivitis, such as infectious keratoconjunctivitis. The ampicillin is typically present as the trihydrate and comprises 3 to 10% w/w, preferably 5% w/w, of the formulation (calculated as the free acid). The formulations suitably contain sodium or benzathine cloxacillin. Typically, the concentration of cloxacillin salt is from 5 to 20% w/w, preferably 10% of the formulation (calculated as the free acid). Suitably, the oil base is a mineral oil base, preferably liquid paraffin gelled with from 0 to 5% by weight of the base of aluminium stearate, or a mixture of soft paraffin and liquid paraffin, or a vegetable oil such as arachis oil. The formulation may additionally contain pain relieving agents, antiinflammatory agents such as corticosteroids, and the like. Preferably, the formulation comprises up to 0.5%, more particularly 0.25%, prednisolone. Preferably the penicillins are present in the form of finely divided particles, as described in EP-A-0271 306 (USSN 129,989). Advantageously, the penicillins are administered in the form of particles, at least 65% by weight of which have a size in the range 0-5 µ, suspended in a hydrophobic oily vehicle which comprises an oil and a gelling agent. Advantageously at least 94% of the particles have a size in the range 0-13 µ. Preferably less than 55% of the particles are larger than 3 µ. The particles may be prepared by techniques including bead-milling, and micronization. The use of bead milling is particularly preferred, as it obviates the need for handling the finely divided penicillins in dry powder form. Suitable vehicles are as set out above. A number of known containers suitable for instillation of the formulation into an infected eye may be used. Preferably, the container is a sealable aluminium tube, or a polyethylene syringe. The dosage regimes will vary according to the size of the sufferer. A suitable dosage unit is generally between 20 to 250 mg of penicillin per eye. For the treatment of cattle, sheep, goats and horses a dose of about 100 mg of penicillin per eye is appropriate. A smaller dose, such as about 50 mg per eye, is suitable in the treatment of domestic animals, such as dogs or cats. The treatment may require a single application of the formulation, or severe infections may require more than one application. Veterinary formulations for use in the present invention may be prepared by mixing the penicillins with the vehicle and with any other components of the formulation. The process may suitably be carried out as follows:- (a) the oil is mixed with the gelling or thickening agent, and the mixture is heat sterilized and allowed to cool, (b) the powdered active ingredient is mixed into the base with stirring, (c) high shear mixing equipment is used to produce a fine homogenous dispersion, and (d) the mixture is subjected to bead-milling. The formulation is then packed in an appropriate form for administration, eg. syringe or tube. The following Examples illustrate the invention. Example 1 Base composition The base was prepared by heating together and sterilising the aluminium stearate and liquid paraffin. When cool the sterile antibiotics were added and incorporated by high shear mixing. The mixture was then passed through a rotary bead mill under the following conditions: Equipment: ′Dyno-Mill′ Model KDL Pilot Zirconium beads: 1.0-1.25 mm Gap setting: 0.3 mm Feed rate: 4.2 litres/hour Rotor speed: 2400 RPM Part of the finished suspension was filled as 3 g doses into lacquered aluminium tubes. Example 2 Base composition The process was carried out as in Example 1, except that 0.25% prednisolone was added to the base immediately prior to the antibiotic agents, by admixture with a small portion of base which was then added to the bulk of the base.

Claims: 1. The use of a formulation comprising ampicillin or a veterinarily acceptable salt thereof, a veterinarily acceptable salt of cloxacillin, and a veterinarily acceptable oil as carrier, for the manufacture of a medicament for topical use in the treatment or prophylaxis of eye infections in animals. 2. Use according to claim 1, wherein the ampicillin is present as the trihydrate and comprises 3 to 10% w/w of the formulation. 3. Use according to claim 1 or 2, wherein the cloxacillin is present as the sodium or benzathine salt and comprises from 5 to 20% w/w of the formulation. 4. Use according to any one of claims 1 to 3, wherein the veterinarily acceptable oil is a mineral oil. 5. Use according to any preceding claim, wherein the formulation additionally comprises one or more pain relieving agents and/or antiinflammatory agents. 6. Use according to claim 5, wherein the formulation comprises up to 0.5% prednisolone. 7. Use according to any preceding claim, wherein the penicillins are present in the form of finely divided particles, at least 65% by weight of which have a size in the range 0-5 µ, suspended in a hydrophobic oily vehicle which comprises an oil and a gelling agent. 8. Use according to claim 7, wherein at least 94% of the particles have a size in the range 0-13 µ. 9. Use according to claim 7 or 8, wherein the particles are prepared by bead-milling. 10. Use according to any one of the preceding claims, wherein the formulation is in unit dosage form containing not more than 250 mg of penicillin per unit dose.

Inventors: DOWRICK, JOHN SIDNEY BEECHAM PARMACEUTICALS
Applicants: BEECHAM GROUP PLC
Application year: 1989
Main classification: A61K31
IPC codes: A61P43, A61K31, A61K9, A61P31