GB2137087A

GB2137087A - Improving Milk Production

Info

Publication number: GB2137087A
Application number: GB08307603A
Authority: GB
Inventors: Henry Smith; Ian Peter Reynolds
Original assignee: American Cyanamid Co
Current assignee: Wyeth Holdings LLC
Priority date: 1983-03-18
Filing date: 1983-03-18
Publication date: 1984-10-03
Also published as: SE458009B; SE8401489D0; GB2137087B; NZ207475A; DK121084A; DK162689C; AT383255B; IT1177595B; ATA89684A; AU2567984A; FR2542615A1; IT8447864A1; FR2542615B1; GB8307603D0; NL8400848A; AU2270688A; IT8447864A0; DK162689B; CA1225031A; BE899189A

Abstract

Lactating ruminants e.g. dairy cattle, goats, and sheep are orally administered 0.025 mg to 0.25 mg of avoparcin per kg of body weight per day to improve milk production.

Description

SPECIFICATION Method for Improving Milk Production in Lactating Ruminants This invention relates to a method for increasing milk production in lactating ruminant animals such as dairy cattle, goats, and sheep.

More particularly, this invention relates to a method for increasing milk production in lactating ruminant animals by orally administering thereto, during the lactating period, from about 0.025 mg to 0.25 mg and preferably 0.04 mg to 0.1 7 mg of avoparcin or a salt or complex thereof, per kg of animal body weight per day. The antibiotic avoparcin is also sometimes referred to as antibiotic AV290 and is generally prepared by a fermentation process.

Avoparcin (AV290) consists essentially of two water-soluble glycopeptides, hereinafter referred to as the a and p components of avoparcin. These components are discussed in the following publications: W. J. McGahren, et al., "Structure of Avoparcin Components," Journal of the American Chemical Society, 102, 1671(1980) and "Avoparcin," Journal of the American Chemical Society, lol, 2237 (1979).

The structure of avoparcin (AV290) is illustrated in Figure I below. The a component has the configuration shown in Figure I, wherein R' and R are each hydrogen, and the jB component is similar excepting that R' is hydrogen, and R is chlorine.

FIGURE I

a-avoparcin R'= R = Hydrogen B-avoparcin R'= Hydrogen, R = Chlorine In accordance with the present invention, avoparcin is orally administered to lactating ruminants in or with their feed as an animal feed premix or concentrate. It may also be offered in the form of a top dressing for the animal's feed or administered thereto incorporated in a slow release bolus designed to continuously provide the animal with the desired quantity of antibiotic during part of or throughout the complete lactating period.

The antibiotic may be used in its essentially pure crystalline form or may be employed as a pharmaceutically acceptable salt such as the hydrochloride salt of the antibiotic or as an antibiotic complex such as the alkylated sulfate, syn-tan or tru-tan complex of avoparcin. In the conduct of the present invention, it has likewise been found that the antibiotic avoparcin is effective for increasing milk production in lactating ruminants when the antibiotic is orally administered in any of the abovesaid forms but associated with the dried solids of the whole harvest fermentation mash in which it was produced.

Administration of from about 0.025 mg to 0.25 mg of avoparcin per kg of animal body weight per day (i.e., 0.025-0.25 mg/kg body weight per day) amounts to approximately 15 to 150 mg per head per day for lactating dairy cattle and from about 1.5 mg to 1 5 mg per head per day for lactating goats or sheep.

When the antibiotic is administered in the form of a salt or complex, the amount of salt or complex used should, of course, be adjusted to provide the dosage level of avoparcin previously indicated.

Although avoparcin has been an important, commercially available antibiotic used in the feed of meat-producing animals to accelerate the growth rate thereof, we have found that when said antibiotic is administered to lactating dairy cattle at the dosage levels recommended for growth promotion in beef cattle (greater than 150 mg per head per day), milk production and/or milk quality remains essentially unchanged or is measurably reduced. This finding is in direct contradiction to the disclosure of UK Patent Application No. 2096895A which states that improved lactation is realized if avoparcin and other glycopeptide antibiotics are administered to lactating ruminants following a dosage schedule approximating that followed for improved feed utilization in steers.UK Application No. 2096895A demonstrates that such a dosage schedule does indeed achieve improved milk production when the glycopeptide antibiotic is actapianin, but no data is presented for avoparcin and the authors of the UK application appear to have assumed that other glycopeptide antibiotics such as avoparcin would behave similarly.

In fact, and as will hereinafter be demonstrated, avoparcin administered to lactating dairy cattle at dosage levels from about 1 5 mg up to 1 50 mg per head per day does increase milk production and/or milk quality, whereas, administration to avoparcin to lactating dairy cattle at levels exceeding 1 50 mg per head per day actually reduces milk production and/or the quality of the milk of the treated animals. The present invention is therefore highly surprisingly in view of the data given in UK Application No. 2096795A, which shows that with actaplanin optimum milk and butterfat yields correspond with the dosage levels for optimum weight gain.

The invention in the subject application is further demonstrated by the Examples set forth below.

EXAMPLE 1 Evaluation of Avoparcin for Increasing Milk Production and/or the Quality of Milk of Lactating Dairy Cattle The experimental design utiiized in this evaluation consisted of three periods. Period I was a preexperimental 28-day period when all the cows in the milking herd were recorded, and selection of suitable subjects for the trial occurred. Period II consisted of 28 days where the avoparcin treatments were given, and Period Ill constituted a following 28-day post-avoparcin treatment. The entire experiment took place over a three-month period.

A total of 28 Friesian dairy cows was selected from a milking herd of over 60 animals. Each cow had been calved for a minimum of six and no longer than 22 weeks and currently had a daily milk yield in the range of 1 7-32 litres. Four balanced treatment groups were carefully composed so that each contained animals which were paired with respect to milk yield and stage of lactation. Each balanced group was then assigned at random to one of four experimental treatments. Group A received no avoparcin and acted as an untreated control group. Groups B, C, and D received 50, 150, and 300 mg of avoparcin per head per day, respectively, over a consecutive 28-day period. Each of the experimental cows received its allocation of avoparcin in one meal at the afternoon milking.Carefully weighed amounts of avoparcin (i.e., 1 g, 3 g, and 6 g AVOTANe 50, avoparcin, the 5% active ingredient premix, for treatments B, C, and D respectively) were included in 250 g lots of a palatable maize-based concentrate.

At the start of the study, the cows were at grass. During the first week of Period II, they were fully changed over onto the winter basal ration consisting of 35 kg fresh silage which was estimated to supply maintenance alone. A balanced dairy concentrate (1 80 g CP/kg) was given for all the milk produced at the rate of 0.4 kg per litre throughout the experiment.

Milk yields were recorded, and milk samples were taken on four occasions in the preexperimental Period I and daily for the first three days of avoparcin feeding. Thereafter, milk yields and samples were taken on alternate days until the end of the entire experimental period. Milk yields and samples continued to be taken periodically during the 28 days immediately following the end of avoparcin feeding (Period Ill).

Milk samples, where taken, were collected at both morning (05-30 h) and evening milking (15.30 h) and combined for any one day. Compositional analyses for butterfat, protein, and lactose were performed by standard automated techniques.

During the course of the trial, five cows required antibiotic therapy for mastitis. Two cows were severely affected and were removed from the study. Consequently, final data are reported on seven cows from each groups A and D, and six cows each from groups B and C.

Tables I and II detail the mean daily yields and butterfats of the four treatment groups as recorded during the trial. Table Ill details an obvious consideration of that data in presenting mean group milk yields and butterfat contents of the cows immediately pretreatment, during the 28 days of avoparcin feeding; and, similarly, during the 28 days following the end of avoparcin treatment. The groups were closely matched during the pre-treatment phase; but, clearly after avoparcin treatment, it appeared that the untreated controls, group A, and the group which received 300 mg of avoparcin per head per day, group D, showed a substantially greater decline in milk production and some depression in butterfat content, compared to groups B and C. The milk yield decline, in particular, is continued in these groups (A and D) for the 28 days following the end of treatment.During the avoparcin feeding period (II), both groups, B and C, declined in yields at a slower daily rate than the untreated control group A. When the overall yield decline is examined (by averaging milk yields during both the period of avoparcin feeding (II), and the 28 days following the end of this period (III), and comparing said averages with the average milk yields obtained in period 1), it can be seen that the decline in overall milk yields obtained with groups B, 50 mg per head per day; and C, 1 50 mg per head per day, is only about 1/4 to 1/2 of the decline obtained with the untreated controls, group A and group D, treated with avoparcin at 300 mg per head per day. Actually, the greatest declines in both milk yield and butterfat were observed in the group receiving 300 mg per head per day.

Table Ill provides group mean values of milk yield and butterfat immediately pre-treatment, during the last two weeks of avoparcin treatment, and during the final two weeks of the period following the end of avoparcin treatment.

The data from Tables I and Ill are also graphically illustrated below.

TABLE I Milk Production During Period 1 28 Days Pre-Treatment Mean milk yield (Liters/day) of untreated cows allotted to group (A) untreated controls, group (B) 50 mg per head per day avoparcin, group (C) 1 50 mg per head per day avoparcin, or group (D) 300 mg per head per day avoparcin.

Group A B C D Untreated 50 mg/d 150 mg/d 300 mg/d Milk Yield Milk Yield Milk Yield Milk Yield Day Liters/Day Liters/Day Liters/Day Liters/Day -28 26.1 26.3 24.8 24.5 - 9 22.9 23.0 22.7 23.0 - 1 22.0 23.1 22.6 23.0 21.7 23.0 22.4 22.1 Average 23.18 23.85 23.13 23.15 Milk Yield (L/D) TABLE I (Continued) Period II Milk Production During 28 Days of Treatment Mean milk yield (Liters/day) of untreated cows group (A) and cows given either 50 mg per head per day avoparcin group (B), 1 50 mg per head per day avoparcin group (C), or 300 mg per head per day avoparcin group (D) over a 28-day treatment period.

Group A B C D Untreated 50 mg/d 1 50 mg/d 300 mg/d Milk Yield Milk Yield Milk Yield Milk Yield Day Liters/Day Liters/Day Liters/Day Liters/Day 1 21.8 23.8 22.1 22.2 2 21.8 23.9 23.1 21.6 3 21.9 24.9 21.9 22.3 5 21.3 25.3 22.7 20.1 7 23.1 25.7 24.8 22.7 9 22.7 26.3 24.5 21.5 11 22.6 26.6 24.4 23.7 13 22.6 25.8 24.3 23.1 15 21.2 25.0 22.1 21.0 17 20.7 25.2 20.3 21.3 19 19.5 25.2 22.4 20.3 21 20.0 24.4 23.5 20.1 23 19.0 22.5 22.4 18.9 25 19.4 22.4 21.2 18.7 28 19.5 22.7 21.4 18.7 Average 21.14 24.85 22.74 21.08 Milk Yield (L/D) TABLE I (Continued) Period Ill Milk Production During 28 Days Post-Treatment Mean milk yield (Liters/day) of untreated cows group (A) and cows treated during Period II of this evaluation with 50 mg per head per day avoparcin group (B) 1 50 mg per head per day avoparcin group (C), or 300 mg per head per day avoparcin group (D).

Group A B C D Untreated 50 mg/d 1 50 mg/d 300 mg/d Milk Yield Milk Yield Milk Yield Milk Yield Day Liters/Day Liters/Day Liters/Day Liters/Day + 2 18.9 22.3 20.7 19.4 + 4 18.8 22.3 20.2 19.1 + 7 19.3 22.9 21.3 19.1 + 9 18.3 21.9 20.3 18.5 +11 18.9 20.4 19.7 17.4 +14 19.5 21.0 20.4 17.6 +16 19.4 20.1 20.3 17.3 +18 18.5 20.1 18.6 17.1 +20 18.9 20.4 18.8 16.3 +22 18.5 19.9 20.4 15.5 +25 18.0 20.1 19.8 15.6 +28 18.2 20.0 19.9 15.7 Average 18.72 20.95 20.03 17.38 Milk Yield (L!D) Groups B and C were reduced to six cows during Period Ill.

TABLE II Period I Percent Butterfat Content of Milk Samples from Cows During 28 Days Pre-Treatment Mean butterfat percent of milk samples from untreated cows allotted to group (A) untreated controls, group (B) 50 mg per head per day avoparcin, group (C) 1 50 mg per head per day avoparcin, and group (D) 300 mg per head per day avoparcin.

Group A B C D Untreated 50 mg/d 1 50 mg/d 300 mg/d Day % Butterfat % Butterfat % Butterfat % Butterfat -28 4.01 3.84 3.82 4.11 - 9 3.89 3.78 3.71 3.97 - 1 3.71 3.72 3.80 3.82 0 3.82 3.80 3.80 3.71 Average 3.86 3.79 3.78 3.90 Percent Butterfat TABLE II (Continued) Period Il Percent Butterfat of Milk Samples from Cows During 28 Days of Treatment Mean butterfat percent of milk samples from cows given either no treatment group (A), or 50 mg per head per day avoparcin group (B), 1 50 mg per head per day avoparcin group (C), and 300 mg per head per day avoparcin over 28 days of treatment group (D).

Group A B C D Untreated 50 mg/d 1 50 mg/d 300 mg/d Day % Butterfat % Butterfat % Butterfat % Butterfat 1 3.79 3.78 3.78 3.87 2 3.75 3.65 3.21 3.70 3 3.71 3.83 3.54 3.21 5 3.54 3.80 3.37 3.57 7 3.30 3.84 3.40 3.40 9 3.27 3.97 3.58 3.42 11 3.37 3.84 3.63 3.85 13 3.25 3.79 3.44 3.25 15 3.47 3.72 3.80 3.53 17 3.40 3.54 3.59 3.50 19 3.45 3.60 3.30 3.38 21 3.57 3.71 3.41 3.35 23 3.58 3.47 3.58 3.38 25 4.05 3.70 3.78 3.66 28 4.06 3.76 3.67 3.66 Average 3.57 3.73 3.54 3.51 Percent Butterfat TABLE II (Continued) Period Ill Percent Butterfat of Milk Samples from Cows During 28 Days Post-Treatment Mean butterfat percent of milk samples from untreated cows group (A) and cows treated during Period II of this evaluation with 50 mg per head per day avoparcin group (B), 1 50 mg per head per day avoparcin group (C), and 300 mg per head per day avoparcin group (D).

Group A B C D Untreated 50 mg/d 150 mg/d 300 mg/d Day % Butterfat % Butterfat % Butterfat % Butterfat + 2 3.94 3.50 3.86 3.91 + 4 3.52 3.80 3.64 3.75 + 7 3.57 3.72 3.55 3.61 + 9 3.71 3.74 3.66 3.76 +11 3.71 3.80 3.86 3.72 +14 3.84 3.81 3.86 3.73 +16 3.91 3.77 3.79 3.71 +18 3.93 3.87 3.74 3.70 +20 3.84 3.43 3.52 3.65 +22 3.75 4.00 3.63 4.03 +25 3.99 3.96 3.78 3.82 +28 3.82 3.98 3.84 3.77 Average 3.79 3.78 3.72 3.76 Percent Butterfat TABLE Ill Average milk yield and percent butterfat content of milk samples, for periods I, II, and III, taken from untreated cows group (A), and cows treated with 50 mg per head per day avoparcin group (B), 1 50 mg per head per day avoparcin group (C), and 300 mg per head per day avoparcin group (D).

Average Average Milk Yield Percent Period Group (Liters/Day) Butterfat

Pre-treatment I # A 23.18 3.86 B 23.85 3.79 C 23.13 3.78 D D 23.15 3.90 Treatment II # A 21.14 3.57 B 24.85 3.73 C 22.74 3.54 D 21.08 3.51 Post-treatment III n A 18.72 3.79 B B 20.95 3.78 C 20.03 3.72 D 17.38 3.76 TABLE Ill (Continued) Comparison of Average Milk Yield Data and Percent Butterfat Content of Milk Samples from All Treatment Groups Taken During Period I (Pre-Treatment) VS. Treatment Period II Plus Post-Treatment Period III Treatment Average Milk Average Milk Yield Decline in Avoparcin Yield Period I Periods II s III Average Milk Yield Group mg/Head/Day (Liters/Day) (Liters/Day) (Liters/Day) A 0 23.18 19.92 3.26 B 50 23.85 22.90 0.95 C 150 23.13 21.38 1.75 D 300 23.15 19.23 3.92 Average Percent Average Percent Average Percent Butterfat Butterfat Decline in Period I Periods II # III Butterfat A 0 3.86 3.68 0.18 B 50 3.79 3.76 0.03 C 150 3.78 3.63 0.15 D 300 3.90 3.63 0.27 EXAMPLE 2 Evaluation of the Effects of 600 mg Per Head Per Day of Avoparcin on Milk Production in Lactating Friesian Dairy Cows Ten Friesian dairy cows were selected from a herd of over 60 such that each cow had been calved for 18 to 23 weeks and currently had a daily milk yield in the range of 1 3 to 1 8 litres. The basal diet consisted of 35 kg fresh silage which was calculated to supply maintenance alone. A balanced dairy concentrate feed was given for all the milk produced at the rate of 0.4 kg per litre of milk.

Each of the experimental cows received 600 mg of avoparcin in one meal per day on each of three consecutive days (one, two, and three). Weighed amounts of 600 mg avoparcin (i.e., 1 2 g AVOTANs avoparcin 50, the 5% active ingredient premix) were included in 50C g lots of a palatable maize-based concentrate. The 0.5 kg avoparcin-containing concentrate replaced 0.5 kg of the normal concentrate on each feeding occasion.

Milk yields were recorded and milk samples taken during the avoparcin feeding period (days one, two, and three) and on days four, five, seven, and ten (i.e., one, two, four, and seven days after avoparcin feeding had ceased). Mean milk yields of 52 other cows in the herd were also taken during the experimental period as a control.

Milk samples were analyzed for butterfat, protein, lactose, and total solids content by standard methods.

Only one cow on one occasion refused some of the avoparcin-containing concentrate offered. On all other occasions, the materiai contained in the 0.5 kg concentrate was well consumed. At no time were any untoward effects noted in any of the cows on the experiment.

The mean milk yield of the ten cows which received avoparcin fell significantly from 1 5.1 kg per day on day -one (i.e two days before avoparcin feeding commenced) to 12.7 kg per day on day ten of the experiment. This can be compared with the mean milk yield of 52 control cows which remained fairly constant at about 1 6.5 kg per day. (See Table IV).

TABLE IV Mean Milk Yield (kg Per Day) of Ten Cows which Received 600 mg Avoparcin on Each of Three Consecutive Days and the Mean Milk Yield of 52 Dairy Cows in the Same Herd which had Not Received Avoparcin Day of Experiment -1 0 1 2 3 4 5 7 10 Yield (kg per day) 15.1 15.0 14.9 13.4 14.4 12.9 12.9 12.8 12.7a 10 avoparcin cows Yield (kg per day) 16.7 1 6.7 1 6.6 14.8 1 6.3 1 6.6 1 6.4 1 6.2 1 6.6 52 control cows TABLE V Mean Butterfat Percent, Protein Percent, Lactose Percent, Total Solids Percent, Cell Count (Millions), Total Bacterial Count (Thousands), and Antibiotic Assay Test Results of Milk Samples from Ten Cows which Received 600 mg Avoparcin on Each of Three Consecutive Days Day of Experiment -1 0 1 2 3 4 5 7 10 Butterfat 3.55 3.33 3.34 3.39 3.41 3.33 2.97 3.00 2.96 Protein 3.28 3.38 3.39 3.39 3.25 3.33 3.29 3.30 3.35 Lactose n.d -.74 4.61 4.63 4.67 4.71 4.65 4.70 4.69 *Total Solids 12.13 12.16 11.75 12.12 12.04 12.08 11.60 11.71 11.70 *Total solids calculated by summation of butterfat, protein, lactose+constant 0.71% n.d.=no data.

An examination of the compositional data given in Table V shows no changes in protein and lactose content of the milk over the experimental period. Butterfat content, however, does show a marked depression clearly evident on days five, seven, and ten. The fall in total solids content observed (12.13% on day -1 falling to 11.7% by day 10) is thus a result of the lowered milk fat production and not any alteration in protein or lactose production.

From the above data, it is clear that the oral administration of 600 mg per head per day of avoparcin to lactating cows caused a marked and noticeable effect on milk yield (1 5% reduction) and butterfat (about 10% reduction with a consequent effect on the total solid content of the milk. (The reduction to 11.7% total solids from 12.1% would, in fact, be enough to incur a penalty of 0.3 p/l based on the Scottish Milk Marketing Board Compositional Quality Payments Scheme, 1981).

Claims

1. A method for increasing milk production in lactating ruminant animals comprising orally administering thereto from about 0.025 mg to 0.25 mg of avoparcin per kg of animal body weight per day.

2. A method according to Claim 1 wherein said avoparcin is orally administered to said ruminant animals at the rate of from about 0.04 mg to 0.17 mg of avoparcin per kg of animal body weight per day.

3. A method according to Claim 1 wherein said ruminant animals are selected from the group consisting of dairy cattle, sheep, and goats.

4. A method for increasing milk production in lactating dairy cattle comprising orally administering to said cattle from about 15 mg to 1 50 mg of avoparcin per head per day.

5. A method for increasing milk production in lactating dairy cattle comprising orally administering avoparcin to said dairy cattle at the rate of 25 mg to 100 mg of avoparcin per head per day.

6. A method for increasing milk production in lactating dairy cattle comprising orally administering avoparcin to said animals at the rate of about 50 mg of avoparcin per head per day.

7. A method for increasing milk production in lactating sheep and goats comprising orally administering thereto from about 1.5 mg to 1 5 mg of avoparcin per head per day.