GB2186796A - Veterinary preparations containing salbutamol - Google Patents

Abstract

Salbutamol, and salts thereof, are used to increase the growth rate and/or lean to fat ratio in domestic livestock without inducing polyphagia. The salbutamol is administered orally, for instance in admixture with feedstuffs at a concentration in the range of 2-12 ppm. The method is particularly useful in pig rearing, but is also suitable in cattle, sheep and poultry.

Description

SPECIFICATION Veterinary preparations This invention relates to veterinary preparations and to their use as growth promoters in domestic livestock such as pigs, sheep, cattle and poultry. The invention also relates to methods for improving the growth rate of these animals by improving their feed conversion efficiency and/or by increasing the ratio of carcass lean to carcass fat.

Because of the present requirements of the consumer, it is desirable to produce leaner domestic livestock with a high ratio of carcass lean to carcass fat. Thus, by increasing the lean content and decreasing the fat content, the carcasses of the animals grade to a higher standard at slaughter.

It is particularly desirable to increase the lean content and decrease the subcutaneous fat in pigs, particularly those pigs prone to higher fat deposition. It is important, however to maintain the quality of the tissues and the organoleptic qualities of the carcasses after slaughter.

British Patent specification No. 1392889 describes the use of certain fi-adrenergic drugs to induce polyphagia domestic animals whereby, by eating beyond the normal level of satiety they gain weight at a faster rate than untreated animals. However, no evidence is provided to suggest that the feed conversion efficiency of the animals is increased and the very large increases in feed intake rates reported suggest that in most cases feed conversion efficiency will be reduced, even though the rate of gain (not reported) may be increased. There is also no reference to the effect of the drugs on the ratio of lean to fat content of the carcasses, suggesting that such an effect is at an insignificant level.

The ss-adrenergic drugs are said to produce polyphagia over a wide daily intake range but a preference is expressed for the daily intake range 25 micrograms to 2.5 mg, which corresponds to the only results which are reported in the specification. The above daily intake ranges are given in respect of all meat producing animals without reference to species or weight and it is not possible to derive from this information the correct daily intake rate for any particular drug in relation to any particular class of animal for the induction of polyphagia. It is to be assumed that in practice, a daily intake rate which produces polyphagia should be chosen on the basis of a preliminary trial.

We have surprisingly found that in the case of salbutamol, one of the fi-adrenergic drugs for which results are reported in British Patent specification No. 1392889, administration at higher daily intake rates than those which appear to have been investigated in relation to induction of polyphagia produces increased growth rates and/or increased ratios of lean to fat content of carcasses without inducing polyphagia, and thereby improves feed conversion efficiency. In our experiments in pigs, the animals were fed ad libitum at a rate approximating to or slightly below the normal level, which is generally accepted as about 1200g feed per day for a 20kg pig and 3200g feed per day for a 90kg pig (Nutrient Requirement of Pigs: Technical Review by the Agricultural Research Council Working Party published by The Commonwealth Agricultural Bureau, 1981).It was clearly shown that a daily intake of salbutamol in the range 2 to 10 ppm in the feed produced increased growth rates and improvements in meat quality without inducing polyphagia.

According to the present invention therefore we provide a method for improving the growth rate, feed conversion efficiency and/or the ratio of carcass lean to carcass fat of domestic animals comprising the administration to said animals of salbutamol or an acid addition salt thereof at a daily intake level exceeding the maximum daily intake for significant induction of polyphagia.

Acid addition salts of salbutamol include salts with organic and inorganic acids. The preferred form of salbutamol for use in the method of the invention is salbutamol sulphate.

Polyphagia is a condition wherein the satiety threshold is raised in the subject so that, where feeding is unrestricted, significantly greater quantities of food are consumed than is normal. For practical purposes, polyphagia can be shown to have been induced in a group of animals when the daily feed intake of the group is significantly greater than that of a control group of closely similar animals. In that biological variation is inevitable, between individual animals, and even in an individual animal at different times, a significant level of polyphagia can only be determined from ad libitum feed intake studies if the daily feed intakes of the groups of animals are averaged over a period of time.

We have observed that the method of the invention is especiaily effective in non-ruminants, and, in particular, in pigs. The increase in the ratio of lean to fat content is particularly beneficial in the case of pigs prone to high fat deposition such as castrates and gilts and pigs which genetically lay down more fat, such as the Yorkshire, Duroc, Hampshire, Camborough blue and Saddleback breeds and crossbreeds from these.

The salbutamol compound is preferably administered in the range 5 to 400 micrograms/kg live weight per day. In general, it is preferred that the daily intake of salbutamol should be above 30 micrograms/kg live weight, more preferably above 40 micrograms/kg, especially where pigs are concerned. A preferred upper daily intake limit is 250 micrograms/kg. Optimal levels vary somewhat from species to species but can readily be determined.

The salbutamol compound is preferably given orally, conveniently in admixture with the feed.

A daily intake of the drug is preferred. In the case of pigs, the feed is advantageously administered over a period of at least 60 days and the animals may be fed ad libitum or to appetite.

Such oral administration contrasts with the parenteral mode of administration recommended in British Patent specification No. 1392889 where induction of polyphagia and consequent high and variable levels of feed intake would make controlled administration of the drug more difficult.

According to a particularly preferred feature of the invention we provide a method for increasing the growth rate, feed conversion efficiency and/or the ratio of carcass lean to carcass fat of pigs comprising the administration to said pigs of salbutamol or an acid addition salt thereof by the oral route at a daily intake greater than 40 micrograms per kilogram.

The preferred concentration of salbutamol or salt thereof in the feed, for daily ingestion of the drug, is 2 to 12 parts per million (ppm). This contrasts with the concentrations recommended in British Patent Specification No. 1392889 which are in the range 0.1 to 1.5 ppm with the optimal results reported corresponding to the lower end of the above range.

According to a further feature of the invention we provide an animal feed composition for improving the growth rate and feed conversion efficiency of domestic animals said composition containing 2 to 12 parts per million of salbutamol or an acid addition salt thereof.

The concentration of salbutamol or salt thereof in the feed compositions is more preferably less than 8 ppm, for example in the range 2-4 ppm, the most preferred range being 2-3 ppm.

At the higher concentrations of salbutamol or salt thereof, the feed may be less palatable than the unmedicated feed. In this case, it may be beneficial to mask the flavour of the drug, for example by incorporation of flavouring agents or encapsulation of the drug in readily digestable material.

The animal feeds generally used are various mixtures of grain and high protein raw materials containing for example, barley or maize mixed with soya or fish meal or similar high protein materials. Alternatively, the animals may be fed on food by-products such as skim milk, whey or bakery offal.

The animal feed compositions are commonly prepared by admixing or incorporating a premix comprising salbutamol or an acid addition salt such as salbutamol sulphate with a sufficient amount of animal feed to provide the desired concentration of salbutamol compound in the feed.

Alternatively, the premix may be first supplemented with a vitamin/mineral/amino acids mixture before incorporation into the animal feed.

For commercial purposes, the premix may contain the active ingredient mixed in a high concentration with a carrier material which is usually a desirable inclusion in the complete feed such as wheat flour, soya bean meal, corn oil, ground maize, barley, mineral mixtures such as vermiculite or diatomaceous earth, corn gluten meal, corn distillers solubles, soya flour, calcium sulphate, limestone flour or calcium carbonate. The premixes may for example, have a concentration of 0.01% to 2.0% by weight of the active ingredient with a preferred concentration of 0.4%-1.0% by weight of active ingredient. The premix or the supplemented premix may be mixed with the complete animal feed, spread over the animal feed or dissolved in water.

Preferably, the premix is supplied as a concentrate which contains 0.40% w/w of salbutamol sulphate blended with wheat flour up to 100.00% w/w. The dry blend is agglomerated with water and dried and the product is then sieved and packed,.

The preferred medicated feed for animals for example, poultry, pigs, cattle and sheep would usually contain from 2g to 8g of active ingredient per tonne of feed, the optimum amount being about 2g to 4g preferably 2g to 3g per tonne of feed.

The unmedicated feeds are generally available from animal feed suppliers. The names and address of some of the suppliers in the UK are given below: Name of Animal Feed Address Suppliers Dalgety Agriculture Ltd Dalgety House, The Promenade, Clifton, Bristol, BS8 3NJ BOCM-Silcock Ltd Basing View, Basingstoke Hants. RG21 2EO J. Bibby Agriculture Ltd Adderbury, Banbury, Oxon. OX17 3HL Example 1 Feed Composition Component Percent by weight Salbutamol Sulphate 0.0002 Wheat 59.69 Barley 20.00 Soya Bean 18.50 Mineral/Vitamin Mixture 1.81 Example 2 Pre-mix Composition Component Percent by Quantities for weight a batch size of 500 kg Salbutamol Sulphate 0.40 2.00 kg Wheat Flour to 100.00 498.00 kg The salbutamol sulphate is blended with the wheat flour. The dry blend is then agglomerated with water and dried.The product is then sieved to remove undersize and oversize agglomerates to leave 94% of particle diameters between 150 microns and 1000 microns and packed into multi walled paper sacks. The premix is then mixed throughly into the complete feed at a level of 0.5kg to 0.75 kg salbutamol sulphate premix per tonne of feed to give 2-3 ppm of salbutamol sulphate and fed to pigs continuously from approximately 6-10 kg liveweight of pigs.

Example 3 Feed Composition Basal Diet Constituents g/kg Ground Barley 739.3 Soyabean meal 44 175.3 Whitefish meal 65.0 L-lysine hydrochloride 2.0 Vitamin-trace element mix 2.5 Ground limestone 7.5 Dicalcium phosphate 6.5 Salt 1.9 Chemical Composition (as fed basis) Dry Matter (g/kg) 862.6 Digestible energy (MJ/kg) 13. 1 Crude protein (g/kg) 190.0 Total lysine (g/kg) 11.7 Threonine (g/kg) 7.4 Methionine+cystine (g/kg) 7.0 Calcium (g/kg) 10.6 Phosphorus (g/kg) 7.1 Na (g/kg) 2.0 Vitamin B12 (g/kg) 28.5 * Providing in each kg diet, 5000 i.u. Vitamin A, 1000 i.u. cholecalciferol, 2.5 mg-tocopherol acetate, 2 mg riboflavin, 5 mg DL-calcium pantothenate, 5 mg nicotinic acid, 6 g cyanocobalamin, 1 mg vitamin D (menaphthone), 125 mg Cu, 100 mg Zn, 40 mg Mn, 50 mg Fe, 0.5 mg Co, 2 mg I and 0.1 mg Se.

Medicated Feed Composition Salbutamol sulphate was mixed with the basal diet at a concentration of 2 ppm.

Similar feed compositions may also be made up containing 4, 8 and 12 ppm of salbutamol sulphate.

Example 4 Male, castrate and female pigs (pure bred Large White) in equal numbers were fed individually ad libitum on the diet set out below containing 0, 2, 6 or 10 ppm salbutamol sulphate (12 pigs per group). The pigs were fed the diets from approximately 20 kg body weight for 15 weeks.

The mean feed intake (in grams) per pig per day and the mean live weight gain (in grams) per pig per day were recorded at 5, 10 and 15 weeks.

The averages for each of these values in respect of each of the groups is set out below.

Feed Average feed Average live Feed Concentration in take (g per weight gain Conversion pig per day) (g per pig Efficiency per day) (g feed/ g live weight gain) 2 ppm salbutamol sulphate 2839 1023 2.78 6 ppm salbutamol sulphate 2771 1023 2.71 10 ppm salbutamol sulphate 2771 1038 2.67 0 ppm salbutamol sulphate (controls) 2911 1000 2.91 The basal diet in the above procedure was as follows: : Basal Diet Composition (% w/v) Pig grower Pig finisher diet (t50 kg diet ( > 50 kg bodyweight) bodyweight) Barley 40.51 40.51 Wheat 10.00 10.00 Maize 15.00 15.00 Extracted soya bean meal 14.50 11.50 Provimi 55 fish meal 3.50 2.50 Weatings 10.00 15.00 Dicalcium phosphate 0.44 0.44 Limestone flour 1.05 1.05 Salt 0.25 0.25 Molasses 2.50 2.50 Fat premix (50%) 2.00 1.00 Mineral/vitamin supplement^ 0.25 0.25 Theoretical analysis (%) Oil 3.25 2.85 Crude protein 16.95 15.66 Fibre 4.48 4.61 Total digestible nutrients 71.81 70.93 Digestible energy (MJ/kg (approx.) 13.00 12.75 Lysine 0.89 0.77 Methionine and cystine 0.56 0.51 Calcium 0.87 0.81 Phosphorus 0.60 0.59 Salt 0.47 0.46 * to include a copper supplement to provide 175 ppm in grower diet, 100 ppm in finisher diet.

Claims (19)

1. A method for improving the growth rate, feed conversion efficiency and/or the ratio of carcass lean to carcass fat of domestic animals comprising the administration to said animals of salbutamol or an acid addition salt thereof at a daily intake level exceeding the maximum daily intake for significant induction of polyphagia.

2. A method as claimed in claim 1 in which salbutamol sulphate is used.

3. A method as claimed in claim 1 in which the domestic animals are other than ruminants.

4. A method as claimed in claim 3 in which the domestic animals are pigs.

5. A method as claimed in claim 4 in which the pigs are of breeds which are prone to high fat deposition.

6. A method as claimed in claim 4 or claim 5 in which the pigs are gilts or castrates.

7. A method as claimed in any of the preceding claims in which the salbutamol or an acid addition salt thereof is administered in the daily intake range 5-400 micrograms per kilogram live weight.

8. A method as claimed in claim 7 in which the salbutamol or an acid addition salt thereof is administered in the daily intake range 30-250 micrograms per kilogram live weight.

9. A method as claimed in any of the preceding claims in which the salbutamol or acid addition salt thereof is administered to the animal orally.

10. A method as claimed in claim 9 in which the salbutamol or acid addition salt thereof is administered to the animal in admixture with the feedstuff of the animal.

11. A method as claimed in claim 10 in which the concentration of salbutamol or acid addition salt thereof in the feedstuff is in the range 2-12 parts per million.

12. A method as claimed in claim 11 in which the concentration of salbutamol or acid addition salt thereof in the feedstuff is in the range 2-4 parts per million.

13. A method for increasing the growth rate, feed conversion efficiency and/or the ratio of carcass lean to carcass fat of pigs comprising the administration to said pigs of salbutamol or an acid addition salt thereof by the oral route at a daily intake greater than 40 micrograms per kilogram.

14. An animal feed composition for improving the growth rate and feed conversion efficiency of domestic animals said composition containing 2-12 parts per million of saibutamol or an acid addition salt thereof.

15. A composition as claimed in claim 14 in which salbutamol or an acid addition salt thereof is present at a concentration up to 8 parts per million.

16. A composition as claimed in claim 14 in which salbutamol or an acid addition salt thereof is present in the concentration range 2-4 parts per million.

17. A composition as claimed in any of claims 14-16 comprising grain, high protein materials, food by-products, vitamins, minerals and/or amino acids.

18. A premix composition for the preparation of a composition as claimed in any of claims 14-17 containing salbutamol or an acid addition salt thereof at a concentration in the range 0.01% to 2.0% by weight.

19. A method of preparing an animal feed composition for improving the growth rate and feed conversion efficiency of domestic animals wherein salbutamol or an acid addition salt is admixed with animal feed to a concentration in the range 2-12 parts per million.