Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
  • A61K31/52—Purines, e.g. adenine
  • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/111—Aromatic compounds
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K20/00—Accessory food factors for animal feeding-stuffs
  • A23K20/10—Organic substances
  • A23K20/116—Heterocyclic compounds
  • A23K20/137—Heterocyclic compounds containing two hetero atoms, of which at least one is nitrogen
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23K—FODDER
  • A23K50/00—Feeding-stuffs specially adapted for particular animals
  • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/13—Amines
  • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
  • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone

Definitions

• the present invention relates generally to animal feed supplements and particularly to methods to improve feed efficiency in pigs.
• Rhotopamine hydrochloride (RAC, PayleanTM, Elanco Animal Health, Greenfield, IN)) is a beta adrenergic agonist ( ⁇ -agonist) that Is approved for use as an in feed ingredient for pigs.
• RAC is a widely used pig feed ingredient, approved for use in most major pork- producing countries, that directs nutrients to increase the amount of lean pork while maintaining meat quality.
• RAC has been widely demonstrated to improve feed efficiency and growth rates both in Australia (Dunshea et al. 1993 Journal of Animal Science 71 : 2931-2941 ; Smits and Cadogan, 2003 Recent Advances in Animal Nutrition in Australia, Volume 14, Ed J.L. Corbett, Page 143-150) and overseas (Watkins et al. 1990 Journal of Animal Science, 68:3588-3595).
• RAC is a growth promoter but also keeps pigs leaner.
• the present inventors have developed an improved animal feed supplement and methods to improve feed efficiency of animals.
• an animal feed supplement comprising a synergistic combination of ractopamine and caffeine.
• the ractopamine is ractopamine hydrochloride.
• the supplement is for Use as a pig feed finishing diet
• the animal feed supplement can have a ratio of ractopamine to caffeine of from about 1:100 to 1:10.
• the animal feed supplement can have a ratio of ractopamine to caffeine of about 1:100, 1:95, 1:90, 1:185, 1 :80, 1:75, :70, 1:65, 1 :60, 1:55, 1:50, 1:45, :40, 1:35, 1:30, 1:25, 1£0, 1:15, 1:10.
• the ratio of ractopamine to caffeine is about 1 :50 to 1:100.
• a ratio of about 1:70 was found to be particularly useful but it will be appreciated that other ratios would be suitable.
• Commercially ractopamine is registered for use in pigs up to 20 ppm and would be commonly used at rates between about 5 ppm and 15 ppm. In other countries, such as the United Sttaes of America, typically use ractopamine at about 5 ppm in animal feeding.
• the animal feed supplement can be formulated as a free-flowing granular material that can be added to bulk feed to provide the desired amounts of ractopamine and caffeine in the feed for consumption by animals.
• the supplement contains 20 grams of ractopamine hydrochloride (active ingredient) and 1400 grams of caffeine (active ingredient) per kilogram of product
• the animal feed supplement is preferably packaged in 10 kg laminated bags with moisture barrier within the plies.
• the animal feed supplement can contain from about 1 to 100 g/kg ractopamine or about 1 to 50 g/kg ractopamine hydrochloride and from about 10 to 3000 g kg caffeine, or about 50 to 2000 g/kg caffeine or about 50 to 950 g/kg caffeine for mixing with bulk complete animal feed to provide a desired final concentration of ractopamine and caffeine to the animal feed.
• the animal fee supplement contains at least about 0 g/kg ractopamine hydrochloride and at least about 500 g/kg caffeine, Preferably, the supplement contains at least about 1% (w/w) ractopamine and at least about 50% (w/w) caffeine, preferably about 70% (w w) caffeine.
• the supplement is preferably added to bulk animal feed to obtain a final concentration of at least about 5 mg/kg ractopamine and at least about 0.5 g/kg caffeine.
• the animal feed supplement is particularly useful in finishing pigs prior to slaughter and meat processing.
• the pigs are typically fed for at (east 14 days and usually over a period of about 35+ days. Pigs typically are about 16 weeks of age and weigh in the order of 60 kg at the start time of feeding the supplement. It will be appreciated that pigs of other starting weights, lighter or heavier, can be used.
• the present inventors have found that the feed supplement containing caffeine allows the maximum response of feeding ractopamine to be extended for an additional period of at least about 14 days.
• a method of increasing feed efficiency of a pig comprising feeding to a pig over a period of time an animal feed containing animal feed supplement according to the first aspect of the present Invention.
• a method of increasing feed efficiency of a pig comprising feeding to a pig over a period of time an animal feed supplemented with a synergistic combination of ractopamine and caffeine.
• the ractopamine and caffeine may be provided to the animal feed in combination as a feed supplement or provided individually to bulk feed to obtain the desired amounts of ractopamine and caffeine in the feed.
• the animal feed is formulated as a finisher diet for pigs.
• the animal feed after supplementation can have from about 1 mg kg to 50 mg/kg (w/w) ractopamine and from about 0.02 g kg to 5 g/kg (w w) caffeine.
• the animal feed after supplementation can have from about 5 mg/kg to 20 mg kg (w/w) ractopamine and from about 0.1 g kg to 1 g/kg (w/w) caffeine.
• a final concentration of about 7.5 ppm ractopamine and about 0.5 kg t caffeine is used in the bulk feed.
• a final concentration of about 5 ppm ractopamine arid about 0.5 kg/t caffeine can also be used in the bulk feed.
• the animal feed contains at least about 7.5 mg/kg ractopamine and at least about 0.5 g/kg caffeine. It will be appreciated that other concentrations can be used,
• the ractopamine may be present in the animal feed at an amount of about 0.0375% (w/w) and the caffeine may be present in the animal feed at an amount of about 0.05% (w/w).
• the pig can be fed over a period of at least 14 days and up to about 60 days, Preferably, the pig is fed over a period of at least 26 days to improve feed efficiency of the pig above that generally observed with RAC alone over the same period of time.
• the animal feed to which the supplement is added is a typical pig finishing feed containing the essential cHetary requirements for the pig.
• a typical finisher feed for growing pigs is formulated to meet these nutritional specifications using a range of energy and protein sources including but not limited to wheat, barley, sorghum, corn, soybean meal, lupins, canola meal, meat meal and bone meal.
• An example of a typical Australian finisher diet is displayed in Table 1.
• a particularly useful animal feed to which the supplement is added is a pig finishing feed containing approximately 13.8 J digestible energy (DE) kg, 14-15% crude protein, approximately 3% crude fat, approximately 3*4% crude fibre and a minimum available lysine: DE ratio of 0.48 g/ J DE. It will be appreciated that that diet specifications may differ depending on age, weight, sex, and genotype of the animal as well as the dietary ingredients available locally to the producer.
• the feed efficiency of pigs may be improved by about 1 to 5% using the feed supplement containing the synergistic combination of ractopamine and caffeine according to the present invention.
• the increase In feed efficiency Is up to about 5% Improvement above feeding ractopamine alone.
• Feeding with the supplement is preferably for at least about 2 weeks.
• pigs are fed for 21 to 35 days.
• the response may be observed for even longer periods of time and may be used in combination with feeding RAC alone for an initial 2-3 week period followed by the addition of the feed supplement containing both RAC and caffeine for a further period of at least 1 days.
• Feed efficiency js defined as the mass of food eaten / body mass gain over a specified period.
• an improved pig feed containing essential dietary requirements and a synergistic combination of ractopamine and caffeine.
• the improved pig feed is formulated to meet required nutritional specifications using a range of energy and protein sources including but not limited to wheat, barley, sorghum, corn, soybean meal, lupins, canola meal, meat meal and bone meal.
• the pig feed is formulated as a finisher diet for pigs.
• the improved pig feed can have from about 1 mg kg to 50 mg/kg (w/w) ractopamine and from about 0.02 g kg to 5 g/kg (w/w) caffeine.
• the improved pig feed can have from about 5 mg/kg to 20 mg/kg (w w) ractopamine, and from about 0.1 g/kg to 1 g/kg (w w) caffeine.
• a final concentration of about 7.5 ppm ractopamine and about 0.5 kg/t caffeine has been found to be particulary useful as a finishing diet for pigs.
• a final concentration of about 5 ppm ractopamine and about 0.5 kg t caffeine can also be used in the improved pig feed.
• Rhotopamine is a beta adrenergic agonist ( ⁇ -agonist) that is approved for use as an in feed ingredient for pigs.
• RAC has been widely demonstrated to improve feed efficiency and growth rates both in Australia (Dunshea et al 1993, Smits and Cadogan, 2003) and overseas (Schinckel et a/. 2001).
• PayleanTM is commonly included in finisher diets from Autumn through to Spring to improve growth rates and the efficiency of feed utilisation, however the use of PayleanTM during autumn has been questioned with overweight pigs a significant issue at this time of the year.
• Rhotopamine is sold by Banco Animal Health (Greenfield, IN USA) under the brand PayleanTM as a free-flowing granular material, manufactured to provide 20 grams of ractopamine hydrochloride (active Ingredient) per kilogram of product PayleanTM is packaged in 10 kg laminated bags with moisture barrier within the plies. PayleanTM is manufactured to meet three-year expiry dating.
• PayleanTM is marketed for increased carcass leanness, increased dressing percent, improved rate of weight gain and improved feed efficiency by feeding pigs at 10 mg/kg (0.001%) of the complete feed, Thoroughly mix 500 grams of PayleanTM Premix in 1000 kg of complete swine feed (90% dry matter basis) to provide 10 g ractopamine HCI per tonne ⁇ of feed. To ensure adequate mixing, an intermediate blending step should be performed prior to manufacturing a complete feed.
• PayleanTM is also marketed for improved rate of weight gain and feed efficiency by feeding 5 mg/kg - 10 mg/kg (0.0005% - 0.001%) of the complete feed. Thoroughly mix 250 grams of PayleanTM Premix in 1000 kg of complete swine feed (90% dry matter basis) to provide 5 g ractopamine HCI per tonne of feed. To ensure adequate mixing, an
• intermediate blending step should be performed prior to manufacturing a complete feed.
• Caffeine was obtained from CSPC Innovation Pharmaceutical Co Ltd - a Chinese off-patent manufacturer. Caffeine is readily available in bulk from fine chemical suppliers. Caffeine can be added to the complete animal feed at a concentration of from about 0.02 g/kg to 5 g/kg (w w) caffeine. Preferably, the animal feed after supplementation can have from about 0.1 g/kg to 1 g/kg (w/w) caffeine. Preferably, a final concentration of about 0.5 kg/t caffeine is used in the bulk feed. Animal feed supplement
• An animal feed supplement containing ractopamine and caffeine can be prepared by adding caffeine to a bulk pack of PayleanTM to provide the desired concentrated amounts of ractopamine and caffeine. The feed supplement can then be added to bulk animal feed to provide the desired amounts of ractopamine and caffeine to be consumed by the animal.
• the animal feed supplement can contain from about 1 to 50 g/kg ractopamine hydrochloride and from about 50 to 950 g kg caffeine for mixing with bulk complete animal feed to provide a desired final concentration of ractopamine and caffeine to the animal feed.
• Ractopamine and caffeine can be mixed in any suiiable carrier materiel, such as milled grain or other edible material and pelleted by standard techniques to give a concentrated supplement for adding to animal feed to give a final desired feeding quantity of ractopamine and caffeine.
• the animal feed is a typical pig finishing feed containing the essential dietary requirements for the pig.
• a typical finisher feed for growing pigs is formulated to meet these nutritional specifications using a range of energy and protein sources including but not limited to wheat, barley, sorghum, corn, soybean meal, lupins, canola meal, meat meal and bone meal.
• An example of a typical Australian finisher diet is displayed in Table 1.
• a particularly useful animal feed to which the supplement is added is a pig finishing feed containing approximately 13.8 MJ digestible energy (DE)/kg, 1 -15% crude protein, approximately 3% crude fat, approximately 3-4% crude fibre and a minimum available lysine: DE ratio of 0.48 g/MJ . It will be appreciated that that diet specifications may differ depending on age, weight, sex, and genotype of the animal as well as the dietary ingredients available locally to the producer.
• DE digestible energy
• the desired amounts of ractopamine and caffeine can be added separately to the bulk feed or can be provided by adding an animal feed supplement containing ractopamine and caffeine.
• the supplemented animal feed can have from about 1 mg/kg to 50 mg kg (w/w) ractopamine and from about 0.02 g/kg to 5 g/kg (w/w) caffeine.
• the animal feed after supplementation can have from about 5 mg/kg to 20 mg kg (w/w) ractopamine and from about 0.1 g/kg to 1 g/kg (w/w) caffeine.
• a final concentration of about 7.5 ppm ractopamine and about 0.5 kg/t caffeine has been found to be particularly useful for pigs in a finishing diet.
• a total of 1212 pigs (female and ImprovacTM vaccinated males, Large White x Landrace, PrimeGroTM Genetics) were identified at 16 weeks of age in commercial grower/finisher accommodation (pens of 10-1 pigs of the same sex). Pigs were selected to start on trial over three days during week 20 of the test year. Prior to the start of the trial, all pigs were offered a commercial grower diet (no PayleanTM) and had been in their allocated pens from 13 weeks of age.
• ImprovacTM vaccine (Pfizer Animal Health) is comprised of a synthetic, incomplete analogue of natural gonadotrophln-releasing factor (GnRF) which is conjugated to a earner protein. ImprovacTM is routinely used on male pigs to reduce the presence of the two major sources of boar taint (androstenone and skatole) without resorting to physical castration.
• GnRF gonadotrophln-releasing factor
• AH male pigs received a priming vaccination of ImprovacTM at 13 weeks of age and the second vaccination at 16 weeks of age (during the first week of the experimental period). Pen weights were recorded at the beginning of the experimental period (day 0, 17 weeks of age) and again at day 14 and day 35 (prior to slaughter). Pen feed intakes were also recorded over these time periods as measured by feed
• Table 1 Ingredient composition and analysed nutrient profile of each of the experimental finisher diets, % of diet (as fed basis).
• Vitamin & minerals 0.09 0.09 0.09 0.09 0.09
• a total of 168 pigs (female and immunocastrated males, Large White x Landrace, PrimeGroTM Genetics) were identified at 21 weeks of age and transferred into the research facility. Pigs were selected over a two week period. Pigs were weighed upon entry to the facility and allocated within sex to pens of 2 pigs per pen of similar body weight. At 22 weeks of age pigs were individually weighed and allocated on a pen basis to one of three treatments: A: Control; B: RAC 7.5 ppm, C: RAC 7.5 ppm + caffeine 0.5 kg/t.
• the dietary compositions of the three experimental diets are displayed in the Table 4
• the diets were formulated to mimic commercial production with the two RAC diets formulated to a higher lysine specification to enable the lean tissue deposition response to be observed.
• the interpretation of results is then a direct measure of the impact of commercial diets without RAC and commercial diets that do contain RAC. Diets were pelleted and fed ad libitum from 22 weeks of age through to slaughter at 26 weeks of age. All animals had ad libitum access to water via nipple drinkers for the entire experimental period.
• Table 4 Ingredient composition and analysed nutrient profile of each of the experimental finisher diets, % of diet (as fed basis).
• the priming ImprovacTM vaccinations were administered to the male pigs at 13 weeks of age, the secondary vaccination at 17 weeks of age, and a third vaccination at 21 weeks of age upon entry to the facility.
• Individual weights were recorded at entry, at the beginning of the experimental period (day 0, 22 weeks of age), day 1 and day 28 of the test period.
• Pen feed intakes were also recorded over these time periods as measured by feed disappearance and feed conversion efficiency subsequently calculated. All deaths and removals were recorded and taken into account when calculating feed intake and feed efficiency by the adjustment of the number of days that pigs were on trial.
• a total of 701 pigs (female and immunocastrated males, Large White x Landrace, PrimeGroTM Genetics) were identified at 17 weeks of age in pens of 11-14 pigs of the same sex. All animals were selected to start the trial on the one day. Prior to the start of the trial, all pigs were offered a commercial grower diet (no Paylean) and had been in their allocated pens from 10 weeks of age. No remixing of pigs occurred before the start of the test period.
• the priming ImprovacTM vaccination was administered to the male pigs at 13 weeks of age and the second vaccination at 17 weeks of age (day 0 of the experimental period). Pen weights were recorded at the beginning of the experimental period (day 0, 17 weeks of age) and again at day and day 35 (prior to slaughter). Pen feed intakes were also recorded over these time periods as measured by feed disappearance and feed conversion efficiency subsequently calculated. All deaths and removals were recorded and taken into account when calculating feed intake and feed efficiency by the adjustment of the number of days that pigs were on trial.
• Table 7 Ingredient composition and analysed nutrient profile of each of the experimental finisher diets, % of diet (as fed basis).

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