|1.||A pharmaceutical or veterinary composition comprising iron and an anthelmintic.|
|2.||A composition according to claim 1, wherein the iron is in the form of an ironcarbohydrate complex.|
|3.||A composition according to claim 1, wherein the iron is in the form of an irondextran complex or an irondextrin complex.|
|4.||A composition according to claim 1, wherein the iron is in the form of a complex selected from ferric hydroxidedextran complex, ferric hydroxidedextran heptonic acid complex and ferric hydroxidedextrin heptonic acid complex.|
|5.||A composition according to claim 1, wherein the anthelmintic is a benzimidazole derivative.|
|6.||A composition according to claim 1, wherein the anthelmintic is oxfendazole.|
|7.||A composition according to any one of the preceding claims which is an aqueous dispersion suitable for administration orally or by injection.|
|8.||A composition according to any one of the preceding claims, wherein a unit dose of the composition provides from 0.5 to 50mg of anthelmintic per kg of body weight and from 0.5 to lOOOmg of iron per kg of body weight. 9. A composition according to any one of the preceding claims which is in the form of a sustained release formulation. 10. A method of treatment which comprises administering an anthelmintic in conjunction with iron to a mammal infested with, or at risk of being infested with, helminths. 11. A product containing an anthelmintic and iron as a combined preparation for simultaneous, separate or sequential use in the treatment or prevention of helminthiasis.|
Helminthiasis is a major problem in many parts of the world, affecting both animals and humans. In poorer countries, infestation of humans and livestock with Q helminths aggravates shortages of food by increasing the nutritional demand of the host.
A number of anthelmintic compounds are known. These have proved effective in the treatment of helminthiasis, but anthelmintic resistance in helminths is a growing 5 problem. This can be combatted by use of new anthelmintic compounds, but the research needed to identify or synthesise novel anthelmintic compounds is both expensive and time-consuming.
We have now surprisingly found that administration of 0 anthel intics in conjunction with iron results in significantly improved activity against helminths in the gut of infected animals in comparison with administration of anthelmintic alone, thus resulting in a more rapid cure. In the case of an anthel intic-resistant helminth, g the administration of iron in conjunction with the anthelmintic has the apparent effect of at least partially restoring the efficacy of the anthelmintic.
Thus, according to the present invention there is
provided a pharmaceutical or veterinary composition comprising iron and an anthelmintic.
The iron is preferably present in the form of an iron-carbohydrate complex. Iron-carbohydrate complexes which may be mentioned include iron-dextran complexes and iron-dextrin complexes, for example ferric hydroxide-dextran complex, ferric hydroxide-dextran heptonic acid complex and ferric hydroxide-dextrin heptonic acid complex. Of particular interest is ferric hydroxide-dextran heptonic acid complex.
Ferric hydroxide-dextran heptonic acid complex and ferric hydroxide-dextrin heptonic acid complex were disclosed in UK Patent 1183940.
Suitable anthelmintics include benzimidazole derivatives, for example oxfendazole, albendazole, thiabendazole, parbendazole, mebendazole, fenbendazole and thiophanate; imidazothiazole derivatives, for example levamisole, pyrantel and morantel; avermectins, for example ivermectin; piperazines, for example piperazine citrate; anilids and substituted phenols; and organophosphates.
Where available, pharmaceutically or veterinarily acceptable salts and derivatives of the above-mentioned compounds may be employed.
Compositions according to the invention may be administered to mammals including pigs, sheep, horses, cattle and humans.
The preferred dosages of the active ingredients will vary with the nature of the preparation used and the mammal
to which the composition is administered. For example, a 1.5ml injection comprising 20% by weight of ferric hydroxide-dextran heptonic acid complex containing 300mg of iron in an aqueous dispersion may be administered to a lamb of about 3 weeks of age, whereas a similar 10ml injection containing 2g of iron may be administered to a human.
The dosage of the anthelmintic is preferably within the normal dosage for the compound concerned, for example a 1.5ml injection may contain 7.5% by weight of leyamisole for a lamb of about 3 weeks of age.
In general, we prefer a unit dose of the composition to provide from 0.5 to 50mg, more preferably 1 to 25mg, of anthelmintic per kg of body weight; and from 0.5 to lOOOmg, more preferably 10 to lOOmg, of iron per kg of body weight. The composition of the invention may be administered orally (for example as a drench to animals) or by injection (intravenous or intramuscular) . In either case we prefer the composition to be in the form of an aqueous dispersion. By "dispersion" we mean a colloidal dispersion, a suspension or a solution, depending ^ upon the solubility of the materials to be dispersed in the aqueous phase.
In order to produce suitable compositions the active ingredients may be worked up with inorganic or organic pharmaceutically or veterinarily acceptable adjuvants, carriers or excipients. Examples of such adjuvants, carriers or excipients are: for tablets and dragees: diluents, for example
lactose; binders, for example cellulosic materials such as microcrystalline cellulose and methyl cellulose; disintegrating agents, for example starches such as maize starch; stabilisers, for example to prevent hydrolysis of the active ingredients; flavouring agents, for example sugars; fillers; stearates; and inorganic diluents, for example talc; for syrups, suspensions, dispersions, solutions and drenches: a liquid vehicle in which the active ingredients may be dissolved or suspended, for example water; and suspending agents, for example cellulose derivatives and gums. Drenches may be administered with a drenching gun or bottle or a similar device adapted to administer a metered dose to an animal. The drench may be supplied in the form of a wettable powder which can be dissolved or dispersed in water by a user. Such a powder may comprise the active ingredient, a colloid to make a drench of suitable viscosity for the gun, and a surface active agent to assist in dispersion or dissolution of the powder in water. The drench may also be supplied in li-quid form in which case it is desirable to incorporate a preservative such as glycerin or sodium benzoate; for hard or soft capsules: diluents, eg lactose; glidants, for example stearates; inorganic materials, for example silica or talc; stabilisers; and dispersing agents.
The composition may also contain further adjuvants, for example a composition for use in a tablet may contain lubricants and glidants to assist in tabletting, for
example magnesium stearate, or wetting agents to assist in granulation, eg dioctyl sodium sulphosuccinate. The composition may also, if desired, contain pharmaceutically or veterinarily acceptable dyes or colourants, and may, if desired, be coated using conventional film or sugar coating techniques.
The composition may also be in the form of a slow release formulation, for example a sustained release bolus, injection or capsule. According to a further aspect of the invention, there is provided a method of treatment which comprises administering an anthelmintic in conjunction with iron to a mammal infested with, or at risk of being infested with, helminths. This method of treatment could be executed by sequential administration of anthelmintic and then iron. Thus, according to a third aspect of the invention, there are provided products containing an anthelmintic and iron as a combined preparation for simultaneous, separate or sequential use in the treatment or prevention of helminthiasis. However, we prefer to execute the method of treatment by administration of a composition according to the invention, as this has the advantage of single administration resulting in a saving of time for the person carrying out the treatment, and less distress for the mammals being treated.
The invention is illustrated, but in no way limited, by the following example.
The efficacy of a commercial preparation of oxfendazole was evaluated against artificially induced infections of adult (21 day) benzimidazole anthelmintic resistant strains of Haemonchus contortus and Ostertaσia circumcincta. when given by mouth on a single occasion each at a dose rate of 5mg per kg of body weight. Efficacy was also assessed following the administration of iron supplement either by injection or by mouth on a single occasion at a dose rate of 600mg per animal. At the start of the experiment (day 0) , fifty 12-16 week old Dorset lambs, reared parasite free from birth, were each infected with 5000 benzimidazole anthelmintic resistant I . contortus and C_i. circumcincta infective third stage larvae. Nineteen days later (day 19) , the lambs were divided into ten groups. Four groups of lambs were treated with Gleptoferron (a commercially available aqueous colloidal dispersion of ferric hydroxide-dextran heptonic acid complex) either by intramuscular injection or by oral drench. Two days later (day 21) , five groups were treated with the anthelmintic orally and four groups with Gleptoferron either orally or by intramuscular injection. Fourteen days later (day 35) , the lambs were killed and the numbers of H__ contortus and C_j_ circumcincta present in 1/100 aliquots of the abomasum and abomasal digest were counted.
The overall efficacy of oxfendazole alone was 48.1%. The overall efficacy of iron injection alone (day 21) was
4.7%. The overall efficacy of simultaneous administration of oxfendazole and iron injection was 67.9%.