DE3409147A1 - METHOD FOR INCREASING MILK PRODUCTION IN MILK-RETURNING - Google Patents

Description

The invention relates to a method for increasing milk production in dairy ruminants such as cows, goats and sheep.

More specifically, the present invention relates to a such a method in which the animals are given about 0.04 to 0.33 mg, and preferably 0.08 to 0.25 mg avoparcin or a salt or complex the same can be administered orally per kg of animal body weight per day. The antibiotic avoparcin is used sometimes called and is called AV290 antibiotic

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generally produced by a fermentation process.

Avoparcin (AV290) consists essentially of two
water-soluble glycopeptides, which are referred to below as "α- and ß-components of avoparcin". These components are described in the following publications: WJMcGahren et al., "Structure of Avoparcin Components", Journal of the American Chemical Society, 102 , 1671 (1980), and "Avoparcin", Journal of the American Chemical Society, JOI ₁ , 2237 (1979).

The structure of avoparcin (AV290) is shown in Figure I below. The α component has the configuration shown in Figure I, where R ¹ and R, respectively
stand for hydrogen. The configuration of the ß-component is similar. In this case, R ¹ stands for hydrogen and R for chlorine.

FIGURE I

T-T

a-Avoparcin R '= R = hydrogen ß-Avoparcin R '= hydrogen, R = chlorine

In accordance with the present invention, avoparcin is administered orally to lactating ruminants in or together with their feed, e.g. as an animal feed premix or concentrate. It can also be in the form of a bait preparation are offered or administered to the animals by adding it to a drug depot preparation, e.g. a drug ball with delayed release of active ingredient, which is designed in such a way, that the animal is supplied with the desired amount of the antibiotic during the lactation period.

The antibiotic can be used in its substantially pure, crystalline form. It can also be used as a pharmaceutically acceptable salt can be used, e.g. as the hydrochloride salt of the antibiotic. An antibiotic complex like the can also be used alkylated sulfate, syn-tan or tru-tan complex des Avoparcins. In the course of the present invention it was also found that the antibiotic Avoparcin is effective in terms of increasing milk production in dairy ruminants, if that Antibiotic in any of the forms mentioned above is administered orally, however, from the dried ones Solids of the entire »harvested fermentation mash in which it was formed is accompanied.

Administration of © twa Q "04 mg to O _f 33 mg Avoparcin / kg of animal body weight / day resulting in amounts of about 24 to 200 mg / kg / head / day for lactating cows and from about 2.4 mg to 25 mg / kg / Head / day for lactating goats or sheep »

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If the antibiotic is in the form of a salt or a Complex is administered, the amount of salt or complex used should of course be adjusted accordingly be that the above-mentioned dose level of avoparcin is guaranteed.

Avoparcin is an important, commercially available antibiotic that is added to the feed of meat-producing Was added to animals to accelerate their growth. However, it was found by the inventors that when this antibiotic is administered to dairy cows at dose levels such as those for the Growth promotion in beef cattle are recommended, milk production and / or milk quality can be measured is decreased.

The concept that all glycopeptides including Actoplanin, Avoparcin A-35512, Vancomycin, Ristocein A-477, K-288 and AM-374 are substantially equivalent as agents for increasing milk production in dairy farmers Ruminants as published by the applicant in British Patent Application 2,096,895A on October 27, 1982, is therefore incorrect and / or misleading, at least as to the inclusion of avoparcin in the glycopeptides mentioned above.

As will be shown below, when administered to dairy cows, avoparcin increases with dose levels from about 50 mg to 150 mg / head / day milk production and / or milk quality, whereas administration of avoparcin to dairy cows In amounts of 300 mg / body weight / day to 600 mg / body weight / day leads to a reduction in milk production and / or the quality of the milk of the treated animals.

In the following the invention is illustrated by means of examples explained in more detail.

example 1

Evaluation of avoparcin with regard to the increase in milk production and / or the quality of milk from lactating cows

The experimental set-up used in this evaluation included three periods. Period I was a pre-experimental 28 day period during which all dairy cows in the herd were registered and a selection of suitable ones Test animals was made. Period II comprised 28 days of the avoparcin treatments and Period III included a subsequent 28 days post-avorparcin treatment. The entire Experiment extended over a period of three months.

A total of 28 Frisian cows were selected from a dairy herd of over 60 animals. Every cow had at least 6 and not more than 22 weeks before calving and was currently producing daily milk yield Range from 17 to 32 1. Four balanced treatment groups were carefully selected, and it is true that each group comprised animals which were comparable in terms of milk yield and lactation status. each such balanced group became then randomly assigned to one of four experimental treatments. The group A did not receive avoparcin and served as an untreated control group. Groups B, C and D received 50, 150 or 300 mg avoparcin / head / day, continuously over a period of 28 days. Each of the test cows received their allocation to avoparcin in one

Meal during afternoon milking. Carefully weighed amounts of avoparcin (i.e. 1 g, 3 g, and 6 g Avotan ^ 50, Avoparcin, the 5% active ingredient premix,.

for treatments B, C and D) were incorporated in 250 g portions of an edible corn-based concentrate.

At the beginning of the investigation, the cows ate grass. During the first week of Period II were they completely switched to background food, consisting of 35 kg of fresh silage, an amount of the it is believed that it is used for conservation purposes only. A balanced dairy concentrate (180 g CP / kg) was fed throughout the experiment, with one equivalent to the total milk produced Rate of 0.4 kg / l.

Milk quantities were recorded and milk samples were taken four times during the pre-experimental Period I and daily for the first three days of avoparcin feeding. Then the Milk quantities and the samples taken on alternate days until the end of the entire test period · The measurement of the milk quantities and the withdrawal of sample was taken periodically during the 28 days immediately following the end of the avoparcin feeding (Period III) continued.

When milk samples were taken, these were both in the morning (5.30 a.m.) and during the evening milking (3.30 p.m.) collected and the samples of a day combined. Analysis of the composition in terms of Butterfat, protein and lactose were performed using standardized, automated techniques.

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In the course of the trial, antibiotic therapy for mastitis was required in five cows. Two cows were seriously ill and were removed from the test. Accordingly, the final results are given for seven cows in groups A and D and for six cows in groups B and C, respectively.

Tables I and II show the mean daily milk and fat contents for the four treatment groups as recorded during the experiment became. Table III presents a summary of these values, the mean values of each Group with regard to milk yield and butterfat content are shown, which are directly in the case of the cows before treatment, during the 28 days of avoparcin feeding and similarly during the 28 days, subsequent to the end of the avoparcin treatment. During the pre-treatment phase (Pre-treatment phase) are the group aif of a stage. However, one notices after the avoparcin treatment clear differences. It is noted that the untreated control animals, namely group A, as well as the Group that had received 300 mg avoparcin / head / day, namely group D, had a significantly larger drop in milk production as well as a certain decrease. show fall in the butterfat content, in comparison with groups B and C. In particular, the drop in milk yield continues with these groups (A and D) continued for the 28 days following the end of treatment. During the avorparcin feeding period (II) In both groups B and C, the decrease in the Milk yield at a lower daily rate than in the untreated control group A. If you have the Examined Decrease in Total Yield [by looking at the

Average milk yields both during the period the avoparcin feeding (II) as well as during the 28 days after the end of this period (III) and this Compares average values with the average milk yields obtained in period (I) one can see that the decrease in the total milk yield in groups B, i.e. at 50 mg / head / Day, and C, i.e. at 150 mg / head / day, only about 1/4 to 1/2 of the decrease is that of the untreated control group A or that with avoparcin 300 mg / head / day treated group D is observed. Indeed, the biggest drop will be in both milk yield and in the case of butterfat in the group that received 300 mg / head / day.

Table III shows the mean values of milk yield and concentrated butter for the respective groups. for the period during the last two weeks of the avoparcin treatment and during the last four two weeks of the period following the end of avoparcin treatment.

The values in Tables I and III are also shown graphically below.

W ---- * - i, ** I ₀ ft _m

10

Table I Milk production during period (l) 28 days pre- treatment

The mean milk yield (l / day) of the untreated cows is given and assigned to the following groups are: group (A) untreated control animals, group (B) 50 mg / head / day avoparcin, group (C) 150 mg / Head / day avoparcin or group (D) 300 mg / head / day avoparcin.

Milk yield (l / day)

Group a
untreated 26.1 B.
; 50 mg / day C.
150 mg / day D.
300 mg / day Day
-28 22.9 26.3 24.8 24.5 - 9 22.0 23.0 22.7 23.0 - 1 21.7 23.1 22.6 23.0 23.18 23.0 22.4 22.1 average
Milk yield
(l / day) 23.85 23.13 23.15

M. • I. (Cont.) - fö - Tabel

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Period II Milk production during 28 days of treatment The mean milk yield (l / day) is given for the untreated cows (group A) and cows given either 50 mg / head / day of avoparcin (group B) or 150 mg Avoparcin was given / head / day (Group C) or avoparcin was given 300 mg / head / day (Group D), each over a treatment period of 28 days

Milk yield (l / day)

A.
Day untreated 21.8 group
B.
50 mg / day 150 C.
mg / day D.
300 mg / day 1 21.8 23.8 22.1 22.2 2 21.9 23.9 23.1 21.6 3 21.3 24.9 21.9 22.3 5 23.1 25.3 22.7 20.1 7th 22.7 25.7 24.8 22.7 9 22.6 26.3 24.5 21.5 11th 22.6 26.6 24.4 23.7 13th 21.2 25.8 24.3 23.1 15th 20.7 25.0 22.1 21.0 17th 19.5 25.2 20.3 21.3 19th 20.0 25.2 22.4 20.3 21 19.0 24.4 23.5 20.1 23 19.4 22.5 22.4 18.9 25th 19.5 22.4 21.2 18.7 28 21.14 22.7 21.4 18.7 through chn.
Milk delivery
(l / day) 24.85 22,, 74 21.08

^:: L. 3A 0 91

Table I (cont.)

Period III milk production during the 28 days after treatment

The mean milk yield (l / day) is given for untreated cows (group A) and cows which were treated with 50 mg / head / day of avoparcin during period II of this experiment (group B), with 150 mg / Head / day were treated with avoparcin (group C) or were treated with 300 mg / head / day avoparcin (group D)

Milk yield (l / day)

A.
Day untreated 18.9 group
B.
50 mg / taff C.
150 me / Ta « C.
300 mff / Τ + 2 18.8 22.3 20.7 19.4 + 4 19.3 22.3 20.2 19.1 + 7 18.3 22.9 21.3 19.1 + 9 18.9 21.9 20.3 18.5 +11 19.5 20.4 19.7 17.4 +14 19.4 21.0 20.4 17.6 +16 18.5 20.1 20.3 17.3 +18 18.3 20.1 18.6 17.1 +20 18.5 20.4 18.8 16.3 +22 18.0 19.9 20.4 15.5 +25 18.2 20.1 19.8 15.6 +28 18.72 20.0 19.9 15.7 average
Milk delivery
(l / day) 20.95 20.03 . 17.38

Groups B and C were reduced to six cows during Period III.

Table II

Period I Percent butterfat content of milk samples from cows during the 28 day pretreatment

The mean percentage butterfat content of milk samples from the untreated cows that had the the following groups are assigned: Group (A) untreated Control animals; Group (B) 50 mg / head / day avoparcin; Group (C) 150 mg / head / day avoparcin; and group (D) 300 mg / head / day avoparcin.

Butterfat (%)

group

ABCD day untreated. 50 mg / day 150 mg / day 300 mg / day

-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
percent
content on
Butterfat 3.86 3.79 3.78 3.90

Hf

Table II (cont.)

Period II Percent butterfat content of milk samples from cows during the 28 day treatment

It is the mean percent butterfat content of milk samples from either the untreated group of cows (A) or the group treated with 50 mg / head / day of avoparcin (B), the group treated with 150 mg / head / day with avoparcin Group (C) and group (D) treated with 300 mg / head / day with avoparcin during the 28 day treatment specified.

Butterfat (%)

group

untreated 50 mg / day

C D mg / day 300 mg / day

1 3.79 2 3.75 3 3.71 VJl 3.54 7th 3.30 9 3.27 11th 3.37 13th 3.25 15th 3.47 17th 3.40 19th 3.45 21 3.57 23 3.58 25th 4.05 28 4.06 average
percent
salary
Butter-
fat 3.57

3.78

3.65

3.83

3.80

3.84

3.97

3.84

3.79

3.72

3.54

3.60

3.71

3.47

3.70

3.76

3.78 3.87 3.21 3.70 3.54 3.21 3.37 3.57 3.40 3.40 3.58 3.42 3.63 3.85 3.44 3.25 3.80 3.53 3.59 3.50 3.30 3.38 3.41 3.35 3.58 3.38 3.78 3.66 3.67 3.66

3.73

3.54

3.51

Table II (cont.)

Period III Percentage of butterfat in milk samples from cows during the 28-day follow-up treatment

It is the mean, percentage butterfat content of milk samples from untreated cows (group A) and the during period II of this evaluation with 50 mg / head / day with avoparcin (group B), with 150 mg / head / day with Avoparcin (group C) and 300 mg / head / day with avoparcin (Group D) treated cows.

Butterfat (%)

Day

group
B CD

mg / day 300mg / day

A.
untreated.

50 mg / day

+16
+18
+20
+22
+25
+28

average

Percentage

Butterfat

3.94
3.52
3.57
3.71
3.71
3.84
3.91
3.93
3.84

3.75
3.99
3.82

3.79

3.50 3.80 3.72 3.74 3.80 3.81 3.77 3.87 3.43 4.00 3.96 3.98

3.78

3.86
3.64
3.55
3.66
3.86
3.86
3.79
3.74
3.52
3.63
3.78
3.84

3.72

3.91 3.75 3.61 3.76 3.72 3.73 3.71 3.70 3.65 4.03 3.82

3.77 3.7.6

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Table III

Average milk yield and percentage butterfat content of milk samples during periods I, II and III taken from untreated cows (Group A) and from with 50 mg / head / day avoparcin (group B), 150 mg / head / day avoparcin (group C) and 300 mg / Head / day of avoparcin b (group D) treated cows.

period group Average
Milk yield
(l / day) Average
Percent go.
Butterfat Pre-treatment
I. A.
B.
C.
D. 23.18
23.85
23.13
23.15 3.86
3.79
3.78
3.90 treatment
II A.
B.
C.
D. 21.14
24.85
22.74
21.08 3.57
3.73
3.54
3.51 After treatment
III A.
B.
C.
D. 18.72
20.95
20.03
17.38 3.79
3.78
3.72
3.76

Table III (cont.)

Comparison of the values of the average milk yield and percentage butterfat of Milk samples from all treatment groups taken during period I (pre-treatment) versus Treatment period II plus post-treatment period III

Avoparcin group treatment average milk average milk decrease in average milk (mg / head / day) yield period I yield periods milk yield (l / day)

(l / day) II & III (l / day)

A. 0 B. 50 C. 150 D. 300

A. 0 B. 50 C. 150 D. 300

23.18 19.91 3.26 23.85 22.90 0.95 23.13 21.38 1.75 23.15 19.23 3.92

Average Percentage Average Percentage Decrease in Average Percentage

content butterfat content butterfat percentage Butter- ι;

Period I Periods II & III bold ^ '> [

3.86 3.68 0.18, ^ * '

3.79 3.76 0.03. "

3.78 3.63 0.15 V.

3.90 3.63 0.27 ^: ··

Middle Milchert and ^ QO

Avotan

; Rough (l / day) of cooling (R7 avoparcin / day / a: CPj

FIGURE II

Cows without treatment (A) or with 50 mg (B), 150 mg (C) treated cows _________ «-_ --— _—-----——.

Yield - l / day

PRE-EXPERIMENTAL

AVOPARCIN TREATMENT

J L

J L

AFTER-TREATMENT '' Ϊ \ \

-15

-10 8 11 14 17. 20 23 26 28

+7 +10 13 16 19 22 25

Belsplel

Evaluation of the effects of avoparcinol based on 600 mg / head / day milk production in lactating Frisian dairy cows __

10 Frisian dairy cows were selected from a herd of over 60, in such a way that each cow was 18 to Had calved for 23 weeks and currently had a daily milk yield ranging from 13 to 18 liters. the Basic food consisted of 35 kg of fresh silage. This amount is only used as maintenance feed. A balanced one Dairy concentrate feed was administered for all milk produced at one rate of 0.4 kg / 1 milk.

Each of the test cows received 600 mg of avoparcin in one meal / day on each of three consecutive ones Days (1, 2 and 3). Weighed out quantities of 600 mg of avoparcin (i.e. 12 g of Avotan ^ 'Avoparcin 50, the 596 active ingredient premix) were in 500 g portions of one Edible corn-based concentrate incorporated. That

Avoparcin-containing concentrate replaced 0.5 kg of the normal concentrate with the respective feeding.

During the avoparcin feeding period (on days 1, 2 and 3) as well as on days 4, 5, 7 and 10 (i.e. 1, 2, 4 and 7 days after stopping avoparcin feeding was) the milk yields were recorded and milk samples were taken. The mean milk yields of the 52 other cows of the herd were also during the Test period determined as a control.

The milk samples were analyzed for butterfat, protein, lactose and total solids by standard methods analyzed.

Only one cow spurned something while feeding of the avoparcin-containing concentrate offered. In all other feedings, the material that was in which contained 0.5 kg concentrate, was well absorbed. At no point was the Attempt Any abnormal effect observed.

The mean milk yield of the ten cows that had received the avoparcin fell from 15.1 kg / day on day -1 (i.e. 2 days before the start of avoparcin feeding) decreased significantly to 12.7 kg / day on day 10 of the experiment. This The result can be compared with the mean milk yield of the 52 control cows, which is fairly constant remained at 16.5 kg / day (see Table IV).

Table IV

Mean milk yield (kg / day) of the ten cows which received 600 mg of avoparcin on each of three consecutive Days, and the mean milk yield of 52 cows of the same

small flocks that did not receive avoparcin

Day of experiment -1 O 1 2 3 4 5 7 10 Yield (kg / day)

10 avoparcin cows 15.1 15.0 14.9 13.4 14.4 12.9 12.9 12.8 12.7

Yield (kg / day)

52 control cows 16.7 16.7 16.6 14.8 16.3 16.6 16.4 16.2 16.6

Table V

Mean values of butterfat (%) , protein (%) , lactose (%), total solids (96), cell counts (millions), total bacteria counts (thousands), and antibiotic assay test results from milk samples from ten cows receiving 600 mg of avoparcin on each of three consecutive days

Day of the attempt -1 0 1 2 3 4th 5 7th 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 k.W. 0.74 4.61 4.63 4.67 4.71 4.65 4.70 4.69 Total festivities toffe ⁺ 12.13 12.16 11.75 12.12 12.04 12.08 11.60 11.71 11.70

Total solids were calculated by adding butterfat, protein, lactose + a constant 0.71%
kW = no value

An examination of the values given in Table V for the composition shows that with protein and lactose contents there are no changes in the milk during the trial period. However, when it comes to the butterfat content a significant decrease, as can be seen from the values for days 5, 7 and 10. The waste observed in total solids (12.13% on day -1, decreasing to 11.79 ^ on day 10) is thus a result of the reduced milk fat formation and is not based on any Changes in protein or lactose production.

From the above data it is clear that the oral administration of 600 mg / head / day of avoparcin to lactating Cows have a clearly noticeable effect on milk yield has (1556 reduction) as well as on the butterfat content (about 1096 reduction), which in turn is a Effect on the total solids content of the milk.

Claims (6)

Claims Process for increasing milk production in lactating ruminants, characterized in that that about 0.04 to 0.33 mg avoparcin / kg animal body weight / day is administered orally to the animals. 2. The method according to claim 1, characterized in that the avoparcin the ruminants at a rate of about 0.08 to 0.25 mg avoparcin / kg animal body weight / day is administered orally. 3. The method according to claim 1, characterized in that that the ruminants are selected from dairy cows, sheep and goats. 4. A method for increasing milk production in lactating cows, characterized in that one Orally administered about 25 to 200 mg avoparcin / head / day to the cows, 5. A method for increasing milk production in lactating cows, characterized in that one Orally administered avoparcin to the cows at the rate of 50 to 150 mg avoparcin / head / day. 6. A method for increasing milk production in lactating sheep and goats, characterized in that that the animals are administered orally about 2.5 to 25 mg avoparcin / head / day.