NZ220516A - Promoting growth rate in ovine livestock using glycolipid antibiotics - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £20516 "><-• 6 • " 'j- ? .'-.1 c- f- r> c> A ■ p ■< t *0 DRAWINGS Patents Form No. 5 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION OVINE GROWTH PROMOTION AGENT *7We, THE STATE OF WESTERN AUSTRALIA, of Baron-Hay Court, South Perth, in the State of Western Australia, Commonwealth of Australia, hereby declare the invention, for which tf/we pray that a patent may be granted to -me/us, and the method by which it is to be performed, to be particularly described in and ff the following statement: { *- i^i _,o 12* ^ - (followed by Page la) juu^88 / ,o/ -/ft.- ^?05 16 ABSTRACT An ovine growth promotion agent comprising a glycolipid antibiotic.

C (bliowcd kg. . 2 205 t 6 THIS INVENTION relates to compositions for use with sheep, goats and like livestock for the promotion of growth.

A particular application of the invention relates to compositions for the promotion of fleece growth of sheep, goats and like livestock (hereinafter referred to as ovine livestock).

It is known to use antibiotics selected from the group comprising ionophores and glycopeptides for use with ovine ruminants for the promotion of body weight growth rates and feed conversion efficiencies. In addition it has been found that selected ionophores can increase the growth rate of sheep including the fleece of sheep as a result of the ionophores increasing the availability of protein in situations here dietary protein is extensively degraded in the rumen.

The action of the glycolipids in promoting body weight growth rates is unknown in sheep although it is known that they seem to have little effect upon the degradation of carbohydrate in the rumen.

As a result of studies it has been found that some glycolipid antibiotics promote growth rates in sheep including both body weight and fleece.

In one form this invention resides in an ovine growth promotion agent comprising a glycolipid antibiotic.

According to a preferred feature of the invention the glycolipid antibiotic comprises flavomycin.

According to a preferred feature of the invention the agent promotes body weight increase. 2 205f 6 According to a preferred feature of the invention the agent promotes fleece growth.

According to a preferred feature of the invention the agent is intended for animals being fed a high or low-protein diet at a maintenance level or ad libitum.

According to a preferred feature of the invention the agent is contained in slow release bodies.

According to a further feature of the invention resides in a method of promoting growth rate in ovine livestock comprising supplementing the diet of the animals with a glycolipid antibiotic.

According to a preferred feature of the method the glycolipid antibiotic comprises flavomycin.

According to a preferred feature of the embodiment the diet of the animals is of a substantially high or low-protein nature.

According to a further preferred feature of the invention the diet is at maintenance level or ad libitum.

According to a preferred feature of the invention the agent is added to feed at a rate 5 to 30mg/kg of feed.

According to a further preferred feature of the invention the agent is administered at a rate of 0.1 to 3.0mg per kilogram of liveweight per day. '1205 f6 According to a further preferred feature of the invention the agent administered at a rate of 0.1 to l.Omg per kilogram of liveweight per day.

According to a further preferred feature of the invention the agent is administered directly to the rumen.

The invention will be more fully understood in the light of the following discussion of two experimental trials according to several particular examples of the invention.

The use of feed additives in ruminant diets has been shown to be effective in improving liveweight gains and feed conversion efficiencies in cattle and sheep. These improvements occur mainly as a result of an improvement in the efficiency of rumen fermentation patterns, and also as a result of an increased supply of dietary protein to the animal.

The following discussion results from two experiments carried out by the Western Australian Department of Agriculture which were designed to investigate the effect of the feed additive flavomycin on wool production. The objectives were to measure liveweight changes and wool production in wether sheep fed either a low-protein (chaff) or a high-protein (lucerne and lupin) diet, containing different levels of flavomycin. 22051b Experiment 1 Treatments and Experimental Design Diets and Feeding The composition of the two basal diets is shown in Table 1.

Table 1. Composition of experimental diets % Total N, g/kg DM Diet 1 Oaten chaff 100 10.0 Diet 2 Lucerne 60) (Pelleted) Lupins 25) __ _ Barley 15) Both diets also contain a mineral premix (Western Australian Department of Agriculture specifications) at 10 kg/tonne.

Flavomycin was included in the diets at intended levels of 5, 15 and 30mg/kg feed. For the pelleted diet, the additive and the mineral premix were included in the dietary mixture prior to pelleting. For the chaff diet, the additive and the mineral premix were mixed together and added to each animals feed each day. The amount of feed given to each animal was calculated on the basis of liveweight to provide sufficient energy for maintaining a constant weight. These amounts were reassessed each weeK* " o'\ following weighing. / . "S z 2 2 ' Animals ^ -i Mature, mixed-age Merino wethers were used. These animals 2205i6 had been run together in one flock throughout the year 1984/85. They were housed in individual pens throughout the course of the experiment.

Design Eighty animals were used in the experiment and were allocated to the treatments as follows: Control 16 Flavomycin LI 5mg/kg feed 8 L2 15mg/kg feed 8 L3 30mg/kg feed _8 40 x 2 diets = 80 animals Experimental Procedure Prior to the start of the experiment, the sheep were shorn and the fleece weights recorded for use as covariates in the subsequent statistical analysis. Animals were then allocated to treatments according to age and liveweight and were fed 800 g of the appropriate basal diet with no additive for a preliminary period of 3 weeks.

The experimental period was of 9 weeks duration. During this time, animals were weighed weekly, and fed a quantity of the appropriate experimental diet calculated to maintain liveweight.

At the start of the experimental period, patches of wool (40 mm width, approx. 200 mm length) were bare shorn along the midside of each animal. After 9 weeks, the staple length of the wool regrowth was measured, the patches were bare shorn again and the wool production from the measured area of skin was weighted. Dyebands were also placed along a line of wool immediately adjacent to the skin. This was done at the start of the experiment and repeated along the 2 205 1 6 same position after 4 weeks. The dyebanded area was then clipped at the end of the experiment for subsequent fibre diameter analysis.

The sheep were then shorn completely at the end of the experiment, and the fleece weights recorded.

In the 6th week of the experiment, samples of rumen fluid were taken from each sheep by stomach tube, and analysed for pH, rumen ammonia concentration and molar proportions of the volatile fatty acids (VFAs), acetate (Ac) propionate (Pr) and butyrate (Bu).

The wool obtained from the clipped patches was washed and dried to measure the clean wool growth per unit area.

Results Inclusion of flavomycin in both diets at all levels improved the liveweight changes of the animals during the 9 week period (P<0.10): these changes in liveweight are shown in Table 2. It can been seen that the overall effect of including flavomycin in the diet was a net change in liveweight of +2.70 or +0.57 kg for animals eating chaff and lucerne diets respectively, compared with only +1.67 and -0.17 kg for the control animals. ? 205 1 6 Table 2. Liveweight changes (kg/head) from week 1 to week 9.

Treatment Chaff Diet Lucerne Control +1.67 -0.17 Flavomycin: LI +2.26 +1.11 L2 +2.38 +0.14 L3 +3.46* +0.46 * Significantly different from the control P 0.05 Table 3 gives the results of the wool growth measurements in terms of total fleece weight (kg) grown during the 12 week period (= 3 weeks pre-experiment + 9 weeks experimental), clean wool growth and staple length (both for the 9 weeks experimental period). Animals on the lucerne pellets diet grew significantly more wool (P< 0.0001), measured as total fleece weight, wool growth/cm2 and staple length, than did those on the chaff diet.

Table 3. Mean total fleece weight, clean wool growth and staple length of sheep eating oat chaff or lucerne chaff/lupin based pellets containing different levels of flavomycin. 2 205 1 6 Diet Fleece weight Clean-wool growth Staple length kg/12 weeks mg/cm /9 weeks mm/9 weeks Oat chaff Control 1.05 3.22 19.1 Flavomycin: LI 1.22 3.60 19.0 L2 1.06 3.54 17.4 L3 1.13 3.31 18.6 Lucerne pellets Control 1.21 4.03 20.9 Flavomycin: LI 1.15 4.00 20.1 L2 1.30 4.66* 20.8 L3 1.14 4.23 20.9 SEM 0.05 0.28 0.8 * Significantly different from the control P < 0.10 On the chaff diet, animals receiving flavomycin grew more wool although the differences was not significant, than the control animals (1.10 kg v. 1.05 kg for additives and controls respectively). This difference was also seen with the wool growth data from the midside patches, in which 2 wool growth was on average 3.48 mg/cm for the three 2 levels of flavomycin compared with 3.22 mg/cm for the control animals. For the lucerne diet, heavier fleece weights were only seen for flavomycin at L2 (15 mg/kg) and this was also apparent in the clean wool growth data (4.66 2 v. 4.03 mg/cm for animals on L2 and control treatments respective, p<0.10).

Results from sheep given both diets with flavomycin indicate that clean wool growth was significantly (P 2?0 5 1 6 0.05) greater than in similar animals receiving ionophore or glycopeptide growth promoters.

Table 4 gives the results of the rumen parameters measured. Totals VFAs (mmol/1) were higher on the lucerne/lupins diet than on the chaff diet. Including flavomycin in the diet had no significant effect on the total VFAs, except at LI on the chaff diet when the VFA levels were reduced by 22%, nor did it alter the molar proportions of the VFAs. This observation is similar to that reported by Rowe et aJ^. (1982) where no changes in VFA were found.

Rumen NH^ concentrations were more than 10 times higher in animals fed pellets compared with those given (291 or 23 mg/1 respectively). Flavomycin increased ammonia concentrations in sheep on the pelleted diet by up to 29%, but its effect on the chaff diet NH^ levels were inconsistent.

Table 4. Mean total VFAs, ratio Pr/(Ac + 2Bu) and NH3 levels in the rumen of sheep eating oat chaff or lucerne-lupin based pellets containing different levels of flavomycin. 2 205 i 6 Total VFAs Pr/(Ac + 2Bu) NH mmol/1 % mg7L Chaff Control 58.2 24.0 22.8 LI 45.3* .2 21.7 L2 55.9 .4 .4 L3 59.3 .9 .9 Pellets Control 72.0 26.9 291.0 LI 70.0 23.4 367.9* L2 68.5 .5 324.3 L3 70.3 28.1 376.2** SEM 4.9 3.0 27.6 Significantly different from the controls: * P < 0.05; ** P 0.01 Summary 1. The inclusion of flavomycin in both the chaff and the pelleted diets improved liveweight changes. 2. Feeding lucerne/lupin pellets resulted in higher wool growth compared with feeding chaff: total fleece weights increased by 15% and clean wool growth per unit area increased by 25%. 3. Including flavomycin in the diets resulted in increased wool growth per unit area (8 and 7% for chaff and lucerne diets respectively). 4.

Flavomycin had no consistency effects on rumen VFA levels or proportions. It did however increase NH^ concentrations in animals eating the pelleted diet. 2 205 H6 . Dose responses to flavomycin inclusion were not apparent for any of the parameters measured.

Experiment 2 Treatments and experimental design Animals Weaner Merino wethers were used, that were housed throughout the experiment in individual pens in a covered shed with mesh flooring, with free access to water.

Dietary treatments Two basal diets were used. The first was wheaten chaff, which was offered to the animals in loose form. The second was a pelleted mixture of (kg/tonne) lucerne (590), lupins (250) and barley (150)/ A mineral premix (Department OF Agriculture) was included with each diet at 10 kg/tonne.

Flavomycin was incorporated at 10 and 20 mg/kg feed into each of the two diets, and these treatments are termed F1 and F2 respectively.

Forty kg batches of the chaff diet were prepared by mixing the appropriate quantity of additive with the mineral premix, combined in 5 1 water, and adding this mix to the chaff using a revolving drum mixer. For the pelleted diet, the mineral premix and the additives were incorporated during the pelleting process.

Experimental design and procedures At the start of the experiment, all animals were shorn. ? 205 1 6 and allocated to treatments according to liveweight.

Fifteen sheep were allocated to each treatment group, and 30 to each of the control groups, which received the two basal diets with no additives.

During an introductory period of 3 weeks, animals were offered the appropriate basal diet with no additives in increasing quantities until the daily amount of feed offered to each animal was 10 - 15 per cent greater than the previous day's intake. Refusals were collected and weighed daily. Diets were then changed to those containing the additive, and animals were offered their appropriate diets in two equal feeds morning and afternoon at these ad libitum levels of feeding for 9 weeks.

Animals were weighed weekly. Wool growth was measured over two consecutive 4 week period by close-clipping an area o approximately 100 m on the right hand midside of each sheep at 4 week intervals. The first clip was made 7 days after the animals were first offered the treatment diets to allow for the emergence of the wool follicle.

Samples of rumen fluid (20 ml) were taken once from each sheep 2h after the morning feed using a stomach tube.

The pH of the rumen fluid was measured, and the samples then acidified with two drops of concentrated H_S0. and 2 4 stored at -20°C for analysis of volatile fatty acid (VFA) and ammonia concentration.

The wool obtained from the clipped patches was washed and dried to measure the clean wool growth per unit area. Fibre diameter was measured using a Fibre Fineness Distribution Analyser. 2?A5 I Results Mean daily intakes and liveweight changes for the two consecutive 4 week periods, termed run 1 and run 2, are shown in Table 5.

Table 5. Mean daily intakes (g/d) and liveweight gains (g/ d) of sheep eating lucerne-based pellets or oaten chaff containing two levels of inclusion of flavomycin (Fl, F2).

Additive Run 1 (week:s 1~4) Run 2 (weeks 5-8) (mg/kg/feed) Feed intake Liveweight Feed Liveweight gain intake gain Lucerne-based pellets Controls Fl 10 F2 20 1503 1573 1500 352 359 344 1727 1875 1835 231 289 303 SED 23.4 18.7 79.0 22.2 Wheaten chaff Controls Fl 10 F2 20 865 895 853 149 165 175 926 920 962 38 25 30 SED 22.9 14.1 48.5 .2 SED, standard error of difference for comparing means of control groups with means of treatment groups. 2 70S ? e Significant differences in both feed intake and liveweight gain were observed between the first 4 weeks and the second 4 weeks of the experiment: intake was higher during run 2, but liveweight gains were lower (P< 0.001).

Animals ate significantly more of the lucerne pellets than of the chaff (P< 0.001). Feed intake of both pellets and chaff did not differ between the control animals and animals receiving diets containing flavomycin, for either run 1 or run 2.

During the first 4 week period (run 1) flavomycin had no significant effect on liveweight gain compared with the controls for either of the diets. In the second 4 weeks however, flavomycin increased liveweight gains of sheep eating the pellets compared with the controls by 28 per cent (P 0.001). There was no evidence of significant dose response effects with increasing levels of additive inclusion. These effects were not seen with the animals eating the chaff diet, where liveweight gains were only 38.1 and 27.1 g/hd/d for controls and flavomycin respectively, and these values did not differ significantly from each other (P<0.05).

The amount of clean wool grown by sheep eating the pellets was greater than that grown by animals eating the chaff (P <" .001) . In both clippings, flavomycin increased wool growth compared with the amount of wool grown by the control animals on the pelleted diet.

Responses to flavomycin inclusion compared with the controls were 16 and 9 per cent for run 1 (week 1-4) and run 2 (weeks 5-8) respectively.

In both run 1 and run 2, increasing levels of flavomycin resulted in increasing responses to wool growth compared 2 205 f 6 with the control for the pelleted diet, of 10 and 22 per cent for run 1 and of 3 and 15 per cent for run 2, for Fl and F2 respectively. However, flavomycin had no significant effect on wool growth of animals eating the chaff diet.

Table 6 also gives mean fibre diameter (FD) values for the different treatments. o Table 6. Clean wool growth (g/m /d) and fibre diameter {-ex.) of sheep eating lucerne-based pellets or oaten chaff containing two levels of flavomycin (Fl, F2).

Additive Clean wool growth Fibre diameter (mg/kg/feed) Run 1 (weeks 1- -4) Run 2 (weeks -8) Lucerne- -based pellets Controls Fl 10 F2 20 11.53 12.74 14.09 11.55 11.83 13.25 24.9 25.1 24.9 SED 0.62 0.60 0.58 Wheaten chaff Controls Fl 10 F2 20 .47 5.86 6.76 6.15 5.77 5.75 18.7 18.6 17.6 SED 0.45 0. 39 0.49 SED, standard error of difference for comparing means of control groups with means of treatment groups.

Fibre diameters of animals on the lucerne pellet diet were greater than that of animals on the chaff diet (25.1 -I~7- 205 1 & compared with 18.5 micron respectively, P < 0.001). There were no significant differences on either diet between control animals and those receiving flavomycin.

Total VFA concentrations (mmOL/L) were higher on the pelleted diet than on the chaff diet as give at Table 7.

Table 7. Mean rumen pH, total volatile fatty acid (VFA) concentration, VFA molar proportions and ammonia (NH^) concentration in sheep eating lucerne-based pellets or oaten chaff containing two levels of inclusion of flavomycin (Fl, F2).

Additive (mg/kg/feed) PH Total VFA (mmol/L) Pr : Ac (%) NH (mg7L) Lucerne-based pellets Controls 6.50 112.7 32 .8 216.0 Fl 10 6.80 85.5 32 .3 160.0 F2 20 6.76 110.6 38 .8 175.7 SED 14.8 Wheaten chaff Controls 6.41 77.7 43 .4 68.6 Fl 10 6.64 63.8 38 .4 64.2 F2 20 6.65 70.5 41 .2 82.3 SED 0.063 4.2 1 .7 6.1 SED, standard error of difference for comparing means of control groups with means of treatment groups.

Inclusions of flavomycin reduced the total concentrations of VFA (P< 0.001), and increased the molar proportion of ■2 205 1 6 propionate relative to acetate (Pr:Ac) compared with the control when treatment F2 was included in the pelleted diet. Rumen NH^ concentrations were significantly higher for animals receiving the pelleted diet than those eating the chaff (186.7 and 65.0 mg/1 respectively, p < 0.001). Flavomycin reduced ammonia concentrations only on the pelleted diet.

Summary 1. The inclusion of flavomycin in the lucerne pelleted diet improved liveweight changes by 28% during the second four weeks of the experiment compared with animals receiving the same diet without flavomycin. 2. Flavomycin had no significant effect on voluntary feed intake of either the lucerne pellets of the chaff. 3. Including flavomycin in the pelleted diet increased clean wool growth by 16 and 9 per cent for weeks 1-4 and 5-8 of the experiment respectively, but had no significant effect on wool growth of animals eating the chaff diet. 4. Inclusion of flavomycin had no effect on fibre diameter compared with control animals.

. Flavomycin reduced the total concentrations of rumen VFA levels for both the pellet and the chaff diet, also reduced rumen ammonia concentrations in animals eating the pelleted diet.

It should be appreciated that the scope of the invention need not be restricted by the particular scope of the 2 205 1 $ experiments described above. It is likely that higher levels of flavomycin will also be effective in increasing wool growth and liveweight gain. The scope for administering flavomycin directly into the rumen as a slow-release bolus is clearly recognised. 220516

Claims (16)

WHAT WE CLAIM IS:

1. A method of promoting the growth rate in ovine livestock comprising supplementing the diet of the livestock with an ovine growth promotion agent comprising a glycolipid antibiotic.

2. A method as claimed in claim 1 wherein the glycolipid antibiotic comprises flavomycin.

3. A method as claimed in claim 1 or claim 2 wherein the agent promotes body weight increase.

4. A method as claimed in any one of claims 1-3 wherein the agent promotes fleece growth.

5. A method as claimed in any one of claims 1-4 wherein the agent is an additive to a low protein feed.

6. S. A method as claimed in any one of claims 1-4 wherein the agent is an additive to a high protein feed.

7. . A method as claimed in any one of claims 1-6 wherein the agent is contained in a slow release bolus.

8. A method as claimed in any one of claims 1-7 wherein the livestock are fed the supplemented feed at maintenance level.

9. A method as claimed in any one of claims 1-7 wherein the livestock are fed the supplemented feed ad libitum.

10. A method as claimed at any one of claims 1-9 wherein the agent is added at a rate between . lmg to 3. Omg per kilogram of liveweight per day.

11. A method as claimed at any one of claims 1-10 wherein the 220516 21 agent is added to feed at a rate of 5 to 30mg per kilogram of feed.

12. A method as claimed in claim 10 wherein the rate is between . lmg to l.Omg per kilogram of liveweight per day.

13. A method as claimed in any one of claims 1-4, wherein the agent is introduced directly into the rumen of the livestock.

14. A method of promoting growth in ovine livestock as claimed in claim 1, substantially as set out in this specification, with reference to any one of the examples.

15. The product when produced by any one of claims 1-14.

16. Ovine livestock treated according to the method of any one of claims 1-14. THE STATE OF WESTERN AUSTRALIA Baldwin Son & Carey