CA1225031A

CA1225031A - Method for improving milk production in lactating ruminants

Info

Publication number: CA1225031A
Application number: CA000449847A
Authority: CA
Inventors: Ian P. Reynolds; Harry Smith
Original assignee: American Cyanamid Co
Current assignee: F Hoffmann La Roche AG
Priority date: 1983-03-18
Filing date: 1984-03-16
Publication date: 1987-08-04
Also published as: DK121084D0; AT383255B; JPS59179039A; AU2567984A; IT8447864A1; GB8307603D0; FR2542615A1; NL8400848A; IT1177595B; DE3409147A1; SE8401489L; ATA89684A; NZ207475A; BE899189A; SE8401489D0; DK162689C; CH658164A5; IT8447864A0; DK121084A; GB2137087B

Abstract

Abstract of the Disclosure A feed composition and premix therefor, are disclosed whereby avoparcin can be administered to lactating ruminant animals, particularly dairy cattle, sheep and goats, in a range of from 0.04 to 0.33 my avoparcin per leg of animal body weight per day.
This feed additive causes an increase in milk production.

Description

29,259 I

METHOD FOR IMP OWING MILK PRODUCTION
IN LACTATING RUMINANTS
This invention relates to a method for in-creasing milk production in lactating ruminant animals such as dairy cattle, goats, and sheep ore particularly, this invention relates to a method for increasing milk production in lactating rum-Nat animals by orally administering thereto, during the lactating period, from about 0.04 my to 0.33 my and preferably 0.0~ my to .25 my 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 AVOW and is generally prepared by a ferment station process.
Avoparcin (AVOW) consists essentially of two water-soluble glycopeptides, hereinafter referred to as the and Components of avoparcin. These components are discussed in the following publications: W. J. McGahren, et at., "Structure of Avoparcin Components," Journal of the American Chemical Society, 102, 1671 (1980) and "Avoparcin," Journal of the American Chemical Society, 01, 2237 (1979).
The structure of avoparcin (AVOW is thus-treated in Figure I below. The to component has the configuration shown in Figure I, wherein R' and R are each hydrogen, and the component is similar excepting that R' is hydrogen, and R is chlorine.

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FIGURE I

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Joy_ owe; owe owe owe "; I Cut 1-0~ 0 ~-avoparcin R'- R = Hydrogen ~-avoparcin R'= Hydrogen; R = Chlorine In accordance with the present invention, avow porcine is orally administered to lactating ruminants in or with their feed as an animal feed premix or concern-irate. 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 bonus designed to contain-usual provide the animal with the desired quantity of antibiotic throughout the lactating period.
The antibiotic may be used in its essentially pure crystalline form or may be employed as a pharmacy-tidally acceptable salt such as the hydrochloride salt of the antibiotic or as an antibiotic complex such as the alkylated sulfate, suntan or Truman complex of avopar-gin. 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 above-said forms but associated with the dried solids of the whole harvest fermentation mash in which it was produced.
Administration of from about 0.04 my to 0.33 my of avoparcin per kg of animal body weight per day (i.e., 0.04--0.33 mg/kg body weight per day) amounts to approxi-mutely 24 to 200 mg/kg per head per day for lactating dairy cattle and from about 2.4 my to 25 my per kg 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.

I ~2~3~

Although avoparcin has been an important, come Marshall 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 5 to lactating dairy cattle at the dosage levels recomb mended for growth promotion in beef cattle, milk pro-diction and/or milk quality is measurably reduced.
Therefore, the concept that all glycopeptides including: actoplanin, avoparcin A-35512, vancomycin, 10 ristocein A-477, K-288, and AM-374 are essentially equip valet as milk production enhancing agents for lactating dairy ruminants as suggested by the applicant in United Kingdom Patent Application AYE, published October 27, 1982, is erroneous and/or misleading, at least with respect to the inclusion of avoparcin amongst the glyco-peptizes indicated.
As will hereinafter be demonstrated, avoparcir, administered to lactating dairy cattle at dosage levels from about 50 my and 150 my per head per day increases 20 milk production and/or milk quality; whereas, ad minis-traction of avoparcin to lactating dairy cattle at 300 my per body weight per day to 600 my per body weight per day reduces milk production and/or the quality of the milk of the treated animals.
The invention in the subject application is further demonstrated by the examples set forth below.

I 5~31 Evaluation of avoparcin for increasing milk productionand/or the quality of milk of lactating dairy cattle.
The experimental design utilized in this oval-ration consisted of three periods. Period I was a pre-experimental 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 III constituted a following 28-day post-avoparcin treatment. The entire experiment took place over a three-month period.
A total of 28 Fruition 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 17 - 32 liters. Four balanced treatment groups were care-fully 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 avow porcine and acted as an untreated control group. Groups B, C, and D received 50, 150, and 300 my 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 AVOTAN~ 50, avoparcin, the I active ingredient premix, for treatments B, C, and D respect lively) were included in 250 g lots of a palatablemaize-based concentrate.

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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 con-sitting of 35 kg fresh silage which was estimated to supply maintenance alone. A balanced dairy concentrate (180 g CP/kg) was given for all the milk produced at the rate of 0.4 kg per lithe throughout the experiment.
Milk yields were recorded, and milk samples were taken on four occasions in the pre-experimental 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 experiment tat period. Milk yields and samples continued to be taken periodically during the I days immediately following the end of avoparcin feeding (Period III).
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 stank dart automated techniques.
During the course of the trial, five cows required antibiotic therapy for misstates. Two cows were seventy affected and were removed from the study. Con-sequently, final data are reported on seven cows from each groups A and Do and six cows each from groups B and C.

I
Tables I and II detail the mean daily yields and butterfat of the four treatment groups as recorded during the trial. Table III details an obvious consider-anion of that data in presenting mean group milk yields and butterfat contents of the cows immediately pro-treatment, 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 pretreatment phase; but, clearly after avow porcine treatment, it appeared that the untreated con-trots, group A, and the group which received 300 my of avoparcin per head per day, group D, showed a sub Stan-tidally greater decline in milk production and some de-press ion 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 I), it can be seen that the decline in overall milk yields obtained with groups B, 50 my per head per day; and C, 150 my per head per day, is only about l/4 to 1/2 of the decline obtained with the untreated con-trots, group A and group D, treated with avoparcin at 300 my per head per day. Actually, the greatest declines 3Q in both milk yield and butterfat were observed in the group receiving 300 my per head per day.

Table III provides group mean values of milk yield and butterfat immediately pretreatment, during the last two Willis of avoparcin treatment, and during the final two weeks of the period following the end of avow porcine treatment.
The data from Tables I and III are also graphically illustrated below.
TABLE I

Mean milk yield (Liters/day) of untreated cows allotted to group (A) untreated controls, group (B) 50 my per head per day avoparcin, group (C) 150 my per head per day avoparcin, or group (D) 300 my per head per day avoparcin GROUP _ B C D_ Untreated 50 mud 150 mud 300 mud Milk Yield Milk Yield Milk Yield Milk Yield Day Liters/Day Liters/Day Liters/Day Liters/Day -28 26.1 26.3 24.8 21~.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 Milk Yield (L/D) 23.18 23.85 23.13 23.15 9 ~22~î03~

TABLE I (Continued) __ Mean milk yield (Liters/day) of untreated cows group (A) and cows given either 50 my per head per day avoparcin group (B), 150 my per head per day avoparcin group (C), or 300 my per head per day avoparcin group (D) over a 28-day treatment period CROUP A B C D
Untreated 50 mud 150 mud 300 mud 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 21.3 25.3 22.7 20.1 7 23.1 25.7 24.8 22.7 9 22.7 26.3 LOWE 21.5 11 22.6 26.6 24.4 23.7 13 22.6 25.8 24.3 23.1 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 19.4 22.4 21.2 18.7 28 19.5 22.7 21.4 18.7 Average Milk Yield (L/D) 21.14 24.85 22.74 21.08 o 25~

TABLE I (Continued) PERIOD IT 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 my per head per day avoparcin group (B) 150 my per head per day avoparcin group (C), or 300 my per head per day avoparcin group (D).
GROUP _ B _ D
lo Untreated 50 mud 150 my 300 mud 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 18.3 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 Milk Yield (L/D) 18.72 20.95 20.03 17.38 Croups B and C were reduced to six cows during Period III.

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TABLE II
PERIOD I PERCENT BUTTERFAT CONTENT OF MILK SAMPLES

Mean butterfat percent of milk samples from untreated cows allotted to group (A) untreated controls, group (B) 50 my per head per day avoparcin, group (C) 150 my per head per day avoparcin, and group (D) 300 my per head per day avoparcin.

Untreated 50 mud 150 mud 300 my Day % Butterfat % Butterfat Butterfat % Butterfat -28 I~.01 3.84 3.82 4.11 _ 9 3.89 3.78 3-71 3.97 3.71 3.72 3.80 3.82 0 3.82 3.80 3.80 3.71 Average Percent Butterfat 3.86 3.79 3.78 3.90 -12_ ~Z5~3~

TABLE II (Continued) PERIOD If PERCENT BUTTERFAT OF MILK SAMPLES

Mean butterfat percent of milk samples from cows given either no treatment group (A), or 50 my per head per day avoparcin group (B), 150 my per head per day avoparcin group (C), and 300 my per head per day avoparcin over 28 days of treatment group I
10 CROUP A B _ D
Untreated 50 mud 150 mud 300 mud Butterfat % Butterfat % Butterfat % Butterfat 1 3.79 3.78 3.78 3.87 2 3.75 3.65 3.~1 3.70 15 3 3.71 3.83 3.54 3.21 3.54 3.80 3.37 3.57 7 3.30 3.84 Lowe 3.40 9 3.27 3.97 3.58 3.42 2011 3.37 3.84 3.63 3.85 13 3.25 3.79 3.4~ 3.25 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

4.05 3.70 3.78 3.66 28 owe 3.76 3.67 3.66 Average Percent Butterfat 3.57 3.73 3.54 3.51 - 1 3 - ~503~

TABLE II (Continued) PERIOD III PERCENT BUTTERFAT OF MILK SAMPLES

Mean butterfat percent of milk samples from untreated cows group (A) and cows treated during Period II
of this evaluation with 50 my per head per day avoparcin group (B), 150 my per head per day avoparcin group (C), and 300 my per head per day avoparcin group (D).

Untreated 50 mud 150 mud 300 mud Day % Butterfat g Butterfat g 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 Percent Butterfat 3.79 3.78 3.72 3.76 "

TABLE III
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 my per S head per day avoparcin group (B), 150 my per head per day avoparcin group (C), and 300 my per head per day avoparcin group (Do.
Average Average Milk Yield Percent Period Group (Liters/Day)Butterfat Pretreatment ) A 23.18 3.86 I ) B 23.85 3.79 ) C 23.13 3.78 ) D 23.15 3.90 Treatment ) A 21.14 3.57 II ) B 24.85 3.73 ) C 22.74 3.54 ) D 21.08 3.51 Post-treatment j A 18.72 3.79 III ) B 20.95 3.78 ) C 20.03 3.72 ) D 17.38 3.76 I

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Evaluation of the effects of 600 my per head per day of avoparcin on milk production in lactating Fruition dairy cows Ten Fruition dairy cows were selected from a herd of over 60 such that each cow had been calved for I to 23 weeks and currently had a daily milk yield in the range of 13 to 18 liters. 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 lithe of milk.
Each of the experimental cows received 600 my of avoparcin in one meal per day on each of three consecutive days (one, two, and three). Weighed amounts of 600 my avoparcin (i.e., 12 g AVOTAN~ avoparcin 50, the I active ingredient premix) were included in 500 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.

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Milk samples were analyzed for butterfat, protein, lactose, and total solids content by standard methods.
Only one cow on one occasion refused some of

5 the avoparcin-containing concentrate offered. On all other occasions, the material 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 export-mint.
The mean milk yield of the ten cows which received avoparcin fell significantly from 15.1 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 export-mint. This can be compared with the mean milk yield of 15 52 control cows which remained fairly constant at about 16.5 kg per day. (See Table IV).

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An examination of the compositional data given in Table V shows no changes in protein and lactose content of the mink 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 lo 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 rung per head per day of avoparcin to lactating cows caused a marked and noticeable effect on milk yield (15% 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

WHAT IS CLAIMED IS:

1. A feed premix composition for lactating rumi-nant animals containing avoparcin in an amount to administer about 0.04 to 0.33 mg of avoparcin per kg of animal body weight per day.

2. A composition according to Claim 1 containing avoparcin in an amount to administer about 0.08 mg to 0.25 mg of avoparcin per kg of animal body weight per day.

3. A composition according to Claim 1 for dairy cattle, sheep or goats.

4. A feed premix composition for lactating dairy cattle containing avoparcin in an amount to administer from about 25 mg to 200 mg of avoparcin per head per day.

5. A composition according to Claim 4 containing avoparcin in an amount to administer about 50 mg to 150 mg avoparcin per head per day.

6. A feed composition for lactating sheep and goats containing avoparcin in an amount to administer from 2.5 mg to 25 mg of avoparcin per head per day.