FR2542615A1 - AGENT FOR INCREASING MILK PRODUCTION IN RUMINANTS DURING LACTATION, COMPRISING AVOPARCIN - Google Patents

Abstract

THE PRESENT INVENTION CONCERNS AN AGENT FOR INCREASING MILK PRODUCTION IN RUMINANTS DURING LACTATION SUCH AS DAIRY COWS, GOATS AND SHEEP. IT INCLUDES AVOPARCINE OR ONE OF ITS SALTS OR COMPLEXES, ADMINISTRATING ORALLY. BREEDING OF RUMINANTS.

Description

The present invention relates to an agent for increasing

  to bring about the production of milk in ruminants

  of lactation such as dairy cows, goats and ewes.

  More particularly, the present invention

  contains an agent to increase milk production in lactating ruminants consisting of avoparcin or a salt or a complex of this substance. This agent may be administered during the lactation period from 0.04 mg to 0 mg. , About 33 mg, preferably 0.08 to 0.25 mg,

  per kg body weight of the animal per day The antibiotic

  Avoparcin is sometimes referred to as "AV 290 antibiotic" and is usually

fermentation process.

  Avoparcin (AV 290) is essentially

  of two water-soluble glycopeptides, hereinafter

  under the name of constituents a and B of avoparcin These con-

  are discussed in the publications

  W McGahren et al, "Structure of the Constitu-

  of Avoparcin ", Journal of the American Chemical Society, 102, 1671 (1980) and" Avoparcin ", Journal of the

  American Chemical Society, 101, 2237 (1979).

  The structure of avoparcin (AV 290) is illustrated

  shown in Figure I in the Annex - The constituent has

  figuration shown in Figure I, in which R 'and R

  both are hydrogen and constituent 8 is

  except that R 'is hydrogen and R is chlorine.

  o C avoparcin R 'R = avoparcin hydrogen R' = hydrogen, R = chlorine According to the present invention, avoparcin is administered orally to lactating ruminants in or with their feed in the form of a premix for animal feed or a concentrate It can also be presented in the form of a seasoning to the

  food surface of the animal or administered to the animal

  poorly incorporated into a slow-release "bowl" designed for

  continuously supply the animal with the desired amount of antibiotic

  tick for the duration of the lactation period.

  The antibiotic can be used in its form

  substantially pure crystalline form or in the form of a pharmaceutically

  ceutically acceptable antibiotic hydrochloride

  tick or antibiotic complex like complex

  of alkylsulfate, Syn-tan or Tru-tan from avoparcin.

  In the practice of the present invention, it has been discovered that

  also green that the avoparcin antibiotic is effective in increasing milk production in lactating ruminants when administered orally in any of the above forms, but associated with the dried solids of the entire crop of porridge

  fermentation in which it was produced.

  Administration of approximately 0.04 mg to 0.33 mg of a-

  voparcin per kg body weight of the animal per day (ie 0.04-0.33 mg / kg body weight per day) is approximately 24-200 mg per head per day for dairy cows during lactation and 2.4 to 25 mg per head per day for goats or ewes

of lactation.

  When the antibiotic is administered in the form of

  salt or complex, -the amount of salt or complex

  should, of course, be adjusted to ensure

  the dose of avoparcin previously indicated.

  Although avoparcin is an important antibiotic

  so much, available on the market, used in the feeding of slaughter animals to accelerate their growth, we discovered that when this antibiotic is administered

  dairy cows during the lactation period at doses of

  ordered to promote the growth of cattle, the pro-

  milk production and / or quality drop in a measurable way.

  So the idea that all glycopeptides, including

  actoplanin, avoparcin A-35512, vancomycin,

  Tocein A-477, K-288 and AM-374 are substantially equivalent as milk production enhancers for lactating dairy ruminants, as suggested by the Applicant in United Kingdom Patent Application 2,096. 895 A, published on October 27, 1982, is

  erroneous and / or misleading at least as regards the inclusion

  of avoparcin in the indicated glycopeptides.

  As will be shown below, avoparcin

  lactating dairy cows at doses of approximately 50 mg to 150 mg per head per day increases milk production and / or milk quality, while

  the administration of avoparcin to dairy cows

  lactation at doses of 300 to 600 mg per head per day lowers milk production and / or milk quality

treated animals.

  The invention is illustrated in more detail by the

examples given below.

EXAMPLE 1

  Evaluation of avoparcin for increased production

  of milk and / or the improvement of milk quality in

  dairy cows during lactation.

  The experimental design used in this evaluation

  consists of three periods Period I is a pre-

  28-day experimental period in which all cows in the dairy herd are counted and the appropriate subjects are selected for the experiment Period II comprises 28 days during which avoparcin treatments are applied, and period III, 28 days following is a period "after treatment" by avoparcin.

  the experiment lasted three months.

  A total of 28 dairy cows are selected

  on a herd of more than 60 animals Each of the cows calved for at least 6 weeks and 22 weeks at most and gives, at that moment, 17-32 liters of milk a day.

  Four balanced groups are carefully

  so that each group is made up of

  Parable of milk yield and lactation stage Each of the balanced groups is then randomly assigned to one of the four experimental treatments Group A does not receive avoparcin and serves as an untreated control group Groups B, C and D receive 50, 150 and 300 mg of avoparcin respectively for 28 days in a row. Each of the experimental cows receive his dose of avoparcin in a single meal, milking

  of the afternoon Carefully weighed quantities of

  parsley (ie 1 g, 3 g and 6 g of AVOT Ai 50, avoparcin, premixed with 5% of active ingredient for the treatments B, C and D respectively) are incorporated in batches of

  2 o 250 g of a buttery concentrate with a pleasant taste.

  At the beginning of the study, the cows are green.

  During the first week of period II, they are made

  completely change the regime to make them

  winter base consisting of 35 kg of silage

  costs, which are considered as a single maintenance ration-

  They are given a balanced concentrate for animals

  in quantities corresponding to the total

  milk produced at a rate of 0,4 kg per liter produced

  during the entire duration of the experiment.

  Milk yields are recorded and milk samples are collected four times during the period

  pre-experimental and every day during the first three

  first days of feeding with avoparcin Afterwards, milk yields are recorded and samples taken from

  every other day until the end of the period of expe-

  The milk yields continue to be noted and samples are taken periodically during the 28

  days immediately following the end of the food

  with avoparcin (period III).

  Milk samples are collected at the place of morning milking (5:30) and evening milking (15:30) and mixed daily Composition analyzes: butyric fat, protein and lactose

  are made by standardized automated techniques.

  During the experiment, five cows required

  an antibiotic therapy for mastitis Two cows

  were severely affected and were withdrawn from the study.

  Therefore, the final results are given for seven cows in each of groups A and D and six cows in each of groups B and C.

  Tables I and II give the details of the returns

  average daily fat and fat contents of the four

  treatment groups recorded during the experiment.

  Table III highlights the evidence of these data by presenting milk yields and fat contents

  means per group of cows, immediately before

  28 days of avoparcin use and the same for 28 days after the end of avoparcin treatment. The groups were well matched during

  period before treatment; but after treatment with the

  In contrast, it is clear that the untreated group A controls and the group that received 300 mg of avoparcin per head per day group D showed a significantly larger drop in milk production than the B groups.

  and C, as well as a slight decrease in fat content.

  The decrease in milk yield, in particular, continues in these groups (A and D) during the 28 days following the end of treatment. During the feeding period with avoparcin (II), both groups B and C have which decline at a lower daily rate than the untreated control group A When considering the overall yield decrease (averaging milk yields during the avoparcin (II) feeding period and during the 28 days following end of this period (III), and comparing these averages with the average milk yields obtained during period I), we see that the overall milk yield reduction obtained for groups B 50 mg per head per day and C 150 mg per head per day is

  equal to only 1/4 to 1/2 of the decrease obtained for

  group A and for the group treated with avoparcin at 300 mg per head and per day group D In fact, the largest decreases in both milk yield and fat content are observed in the

  group that receives 300 mg per head per day.

  Table III gives the average values by

  group of the milk yield and the fat content im-

  mediately before treatment, during the last two weeks of treatment with avoparcin and during the last two weeks of the period following the end of treatment.

to avoparcin.

  The data in Tables I and III are also

  presented graphically in Fig II in the appendix.

TABLE I

  Milk production during period I of 28 lours before

the treatment.

  Average milk yield (liters / day) before treatment

  cows assigned to groups (A):

  untreated controls, (B): 50 mg per head per day of

  park, (C): 150 mg per capita per day of avoparcin or

  (D): 300 mg per head per day of avoparcin.

  Group A B C D Untreated 50 ma / i 150 m / i 300 ma / i Yield Yield Yield Yield Milk day 1 / i milk 1 / i milk 1 / i milk l / i

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 milk yield (l / d) 23.18 23.85 23.13 23.15 TABLE I (continued) Production of milk of period II (during 28 days

treatment).

  Average milk yield (liters / day) of untreated cows group (A) and cows given

  or 50 mg per capita per day of avoparcin group (B) -

  either 150 mg per capita per day of avoparcin group (C) -

  that is 300 mg per capita per day of avoparcin group (D) -

  during a treatment period of 28 days.

  Group A B C D Untreated 50 ma / d 150 ma / d 300 ma / i Yield Yield Yield Yield Milk day 1 / i milk 1 / i milk 1 / i milk 1 /

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 24.5 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 i (l / d)

21, 14 24, 85

22, 74 21, 08 -

  TABLE I (cont.) Production of Milk of Period III (During the 28 Days

following the treatment).

  Mean milk yield (liters / day) of untreated cows group (A) and cows treated during period II of this study with 50 mg per head per day

  of avoparcin group (B) 150 mg per head per day of

  park group (C) or 300 mg per capita per day of avopar-

group (D).

  Group A B C D Untreated 50 mg / i 150 mq / i 300 ma / i Yield Yield Yield Yield Milk day 1 / i milk 1 / i milk 1 / i milk 1 /

+ 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 (1 / d) 18.72 20.95 20.03 17.38 Groups B and C were reduced to 6 cows

during period III.

j.

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TABLE II

  Fat content during period I of samples of

  cow's milk (during the 28 days preceding the

  is lying). Fat content average percent of sample

  lons of milk, before treatment, cows which have been

  group (A): untreated controls, (B): 50 mg per capita per day of avoparcin, (C): 150 mg per capita per day

  of avoparcin, (D): 300 mg per capita per day of avoparcin.

  Group A B C D Untreated 50 my Q / i 150 mg / d 300 mq / i Day% fat% fat% fat x fat

28 4.01 3.84 3.82 4.11

9 3.89 3.78 3.71 3.97

1.71 3.72 3.80 3.82

O 3.82 3.80 3.80 3.71

  Average fat content per cent 3.86 3.79 3.78 3.90 TABLE II (continued) Fat content during period II of samples of

  cow's milk (during the 28 days of treatment).

  Fat content average percent of sample

  milk of either untreated cow group (A) or

  50 mg per head per day of counseling.

  group (B) or 150 mg per capita per day of avopar-

  group (C) or 300 mg per head per day of avoparcin

group (D).

Group A B C D Day

3

13

23

  Average fat content percent Not treated% fat 3.79 3.75 3.71 3.54 3.30 3.27 3.37 3.25 3.47 3.40 3.45 3.57 3.58 4 , 05 4.06 mq / i% fats 3.78 3.65 3.83 3.80 3.84 3.97 3.87 3.79 3.79 3.72 3.54 3.60 3.71 3.47 3 , 70 3.76 mq / i% fats 3.78 3.21 3.34 3.37 3.40 3.58 3.63 3.44 3.80 3, 59 3.30 3.41 3.58 3 , 78 3.67 300 mq / i% fats 3.87 3.70 3.21 3.47 3.40 3.42 3.85 3.25 3.53 3.50 3.38 3.35 3.38 3.66 3.66

3., 54 3.51

3, 57 3, 73

  TABLE II (continued) Fat content, during Period III, of samples

  cow's milk (during the 28 days following the

  is lying). Fat content average percent milk samples of untreated cow group (A) and cows-treated during period II of this study with mg per capita per day of avoparcin group (B) 150 mg per head per day of avoparcin group (C) or 300 mg per

  head by day of avoparcin group (D).

  Group A B C D Untreated 50 mq / i 150 m / i 300 m / i Day X is% fat% fat X increased

+ 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 fat content

3.79 3.78

3, 72 3, 76

TABLE III

  Average milk yield and average fat content of

  milk samples during periods I, II and III of untreated cows in group (A) and cows treated with 50 mg per capita per day of avoparcin group (B), mg per capita per day of avoparcin group (C) ), or

  300 mg per day per day of avoparcin group (D).

  Yield Milk content fat 0 medium average Period Before treatment I Group A B C D A B C D Treatment II After treatment III A B C D (1 / i)

23, 18

23.85

23, 13

  23.15 21.14 24.85 22.74 21.08 18.72, 95, 03 17.38 per cent 3.86 3.79 3.78 3.90 3.57 3.73 3.54 3 51 3.79 3.78 3.72 3.76 TABLE III (cont.) Comparison of Average Milk Yields and Average Fats Content Percent of All Treatment Groups in Period I (Before Treatment) with the values during the entire treatment period II plus period

after treatment III.

  Avoparcin treatment mg / head day o Average milk yield Period I (1 / d) 23,18 23,85 23,13 23,15 Average milk yield Periods II and III (11 / ji) 19,92 22 , 90 21.38 19.23 Decrease in average milk yield (1 / d) 3.26 0, 95 1.75 3.92 Average fat content per year Period I 3.86 3.79 3.78 3, 90 Fat Content Decrease Average Percent Grade Periods II and III in Average Fat Per Cent

3.68 0.18

3.76 0.03

3.63 0.15

3.63 0.27

  Group A B C D t-. A B C D o N or ru 1 Ob

EXAMPLE 2

  Evaluation of the effects of 600 mg per head and -ar iour'd'avo-

  uarcine on milk production in dairy cows

Frisians during lactation.

  10 Frisian cows are selected from a herd of more than 60 so that each cow has calved for 18 to 23 weeks and now gives 13 to 18 liters of milk per day. The basic diet consists of 35 kg of fodder.

  fresh silage calculated for maintenance only.

* Cows are given a balanced, balanced feed for dairy animals in an amount corresponding to the total

  milk produced at the rate of 0.4 kg per liter of milk.

  Each of the cows of experience receives 600 mg

  of avoparcin in one meal a day-for 3 days

  2, and 3) Measured quantities of 600 mg of

  parsley (ie 12 g of AVOTANO-avoparcin 50, premixed with 5% of active ingredient) are incorporated in batches of

  500 g of a buttery concentrate with a pleasant taste.

  that taken, we replace 0.5 kg of normal concentrate by 0.5 kg

  of concentrate containing avoparcin.

  Milk yields are recorded and milk samples are taken during the period of administration of avoparcin (days 1, 2 and 3) and days 4, 5, 7 and 10

  (that is, 1, 2, 4 and 7 days after the judgment of the

  Avoparcin), there are also milk yields

  average of 52 other cows in the herd as witnesses,

  during the experimentation period.

  Standardized methods are used to determine

  in fats, proteins, lactose and total solids

milk samples.

  Only one cow, on one occasion, refused a certain amount of concentrate to avoparcin

  On all other occasions, the substance

  held in the 0.5 kg of concentrate was well consumed.

  At no time were there any untoward effects in any of the

cows in experimentation.

  The average milk yield of cows that received avoparcin significantly decreased by 15.1 kg /

  day 1 (that is, 2 days before the administration

  Avoparcin begins) at 12.7 kg / day on day 10 of

  This value can be compared to the efficiency

  average milk of the 52 control cows which remained relatively

  constant: about 16.5 kg / day (see Table IV).

TABLE IV

  Average milk yield (kg / day) of 10 cows who received 600 mg / day of avoparcin for 3 consecutive days and mean milk yield of 52 dairy cows of the same

  flock that have not received avoparcin.

  Day of experimentation Yield (kg / day) -1 o

1 2 3

  cows treated with avoparcin Yield (kg / day), 1 15.0 14.9 13.4 14.4 12.9 12.9 12.8 12.7 t--J 52 control cows

16.7 16.7 16.6

14.8 163 16.6 16.4 16.2 16.6

of the r> Ln o L n R 7 1 n

TABLE V

  Average percentages of fats, proteins, lactose, total solids of samples

  of 10 cows who received 600 mg of avoparcin daily for 3 consecutive days.

Day of experimentation -1

O 1 2

  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

  n. 4,74 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 are determined by addition of fats, proteins, lactose

  and a constant equal to 0.71%.

not said.

  Ln ré) Ln Fats Lactose g-. The examination of the compositional results given in Table V shows that there is no change in the protein and lactose contents of the milk during the test period. The fat content, however, shows a decrease. marked, -lightly obvious on days, 7 and 10 The decrease in the total solids content observed (from 12.13% on day 1 to 11.7% on day 10) is thus the result of the decrease in the production of fats and not any alteration of protein production

or lactose.

  From the results above, it is clear that

  oral administration of 600 mg per head per day of avopar-

  cine at lactating cows has a noticeable effect on milk yield (15% decrease) and fat

  (down about 10X), with a resulting effect on the

  total solids content in milk (The 12.3% decrease in total solids content to 11.7 X would, in fact, be sufficient to incur a penalty of 0.3 penny / l according to the "Payment Scheme". of the quality of the Committee

  Scots for marketing milk, 1981).

25426 t 5

Claims (5)

  1 Agent to increase milk production at   lactating ruminants consisting of avopar-   cine, or one of its salts or complexes.   2 Agent for increasing milk production in dairy cows during lactation, characterized in   it includes about 25 to 200 mg of avoparcin.   Agent according to claim 2, characterized in   what it includes from 50 to 150 mg of avoparcin.   4 Agent to increase milk production at   ewes and goats during the lactation period, characterized   in that it comprises about 2.5 to 25 mg of avoparcin.   A method for increasing milk production in lactating ruminants, characterized in that approximately 0.04 to 0.33 mg / kg of body weight per day of the agent is administered orally thereto according to any one of Claims 1 to 4.   6 Process according to claim 4, characterized in that the agent is administered orally to ruminants in   about 0.08 to 0.25 mg / kg per day.