DK156539B - GROWTH PROMOTING IMPLANT PREPARATION CONTAINING A COMBINATION OF AN ANabolic STEROID AND ESTROGENT STEROID - Google Patents

Description

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DK 156539 B

The invention relates to a novel growth-promoting implant composition containing a combination of an anabolic steroid and an estrogenic steroid which is peculiar to the characterizing part of the claim.

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The novel growth-promoting implant preparation containing a combination of an anabolic steroid and an estrogenic steroid according to the invention is intended to promote weight gain in farmed animals such as cattle and pigs, these products being particularly administered by storage in animal skin. .

Products are already known for breeding pigs and are described in Canadian Patent Specification 889,253. These products based on methyl testosterone and diethylstilbestrol are prone to leave hormonal substances in the animal's organism, especially diethylstilbestrol, whose digestive metabolism is complicated and whose elimination is slow. Therefore, at the slaughter of the animals, it is feared to find another 20 non-resorbed active ingredients with hormonal action.

The great interest of the product according to the invention lies in the fact that the association of the two active ingredients, i.e. anabolic steroid and estrogenic steroid, does not cause any hormonal disturbance in the farmed animals while allowing a faster weight gain and an improvement in the quality of the code.

Furthermore, the product of the invention will not leave 30 hormonal products in the animal organisms, the effect of which could be detrimental to the consumer. In particular, the use of an estrogen whose structure is analogous or identical to the structure of natural hormones ensures a more regular metabolism and a more complete elimination. Thus, during the slaughter, the complete disappearance of the active ingredients at the depot site can be ascertained.

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DK 156539 B

Finally, the simultaneous presence of the two active ingredients enhances the beneficial effect on growth, resulting in a significantly better weight gain.

The strength of the active ingredients may vary widely according to the animal species. For breeding cattle and especially calves, the products may contain between 1 mg and 300 mg of anabolic steroid and between 0.05 mg and 50 mg of estrogenic steroid.

For the purpose of their administration into the cattle, the products may be deposited in the skin, preferably in the ear lobe or in the skin folds at the ear. The products can also be deposited on the animals' shark or the sperm. They can either be implanted or injected in the form of solution or suspension.

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Implant preparations have the advantage of providing a slower but complete resorption.

Thus, the resorption of implant preparations is at least 20 30% after 61 days. The resorption of the active constituents they contain is substantially greater and of the order of 50%.

After 3 months, the resorption of the implant preparations is usually complete and each of the active ingredients has disappeared almost completely both at the implant site and in the rest of the organism.

The following example illustrates the composition of the invention.

The compounds used to prepare the novel composition are described in the literature, see, e.g., Apple-Zweig: Steroid Drugs, vol. I and II as well as French Patents Nos. 1,380,414, 1,492,985, 1,540,942, 1,514,122, 1,476,509 and 1,514,082.

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DK 156539 B

Example a) Implant preparation containing an anabolic steroid and an estrogenic steroid

Formula A

5 3 ~ oxo-17 beta-acetoxy ester-4,9,11-triene 140 mg estradiol 20 mg lactose-based additive on 1 tablet

Formula B

3-oxo-17 beta-acetoxyester-4,9,11-triene 140 mg 1 f) estradiol 20mg starch sodium glycolate polyvinylpyrrolidone magnesium stearate to form a final 165 mg tablet.

B) Implant preparation containing an anabolic steroid, estrogenic steroid and progestate 3-0X0-17 beta-acetoxy ester-4,9,11-triene 140 mg estradiol 20 mg 2q progesterone 200 mg lactose based adjuvant 1 tablet c) Implant preparation containing an anabolic steroid, an estrogenic steroid, a progestate, and an anti-inflammatory substance 3-0X0-17 beta-acetoxy ester-4,9,11-triene 140 mg estradiol 20 mg progesterone 200 mg dexamethasone (beta-ethoxy-beta-ethoxy) - -ethoxyacetate 0.35 mg 30 lactose additive on 1 tablet, test the effect of implantation preparations on cattle 1) Influence on the feeding characteristics 35 The experiment is carried out on black-bred bull calves weighing 56-60 kg.

The animals are divided into 4 groups:

. DK 156539 B

- 4 - 1) Control team, 2) a team of animals implanting a 20 mg tablet of estradiol and 200 mg of progesterone, termed implant preparation I, 53) a team of animals implanting a 20 mg tablet estradiol, 200 mg of progesterone and 140 mg of 3-oxo-17beta-acetoxyester-4,9,11-triene, termed implant preparation II, and 4) a holding animal using an implant preparation 10 containing the same ingredients as in implant preparation II and in addition 350 gamma 21-dexamethasone (beta-ethoxy-beta-ethoxy) -ethoxyacetate, which is referred to as implant preparation III.

15 The implant preparations are inserted into the skin behind the fold of the ear.

The animals are weighed at the beginning of the experiment and then 34 <'days and 61 days after implantation.

The following tables show the better results obtained for Preparation II and III than for Preparation I.

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DK 156539 B

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Forsoq A

Feed and slaughterhouse technical results:

Implant- Implant- Implant- Implantation Exercise- 5 Control para I para II para III

Number of days after implantation 61 61 61 61

Average weight at the start of the trial in kg 60.18 56.86 58.96 58.51 10 Average weight at the end of the trial in kg 123.67 124.1 129.60 131.0 Weight gain on the 34th day not 35.87 38.12 41.58 41.36

Average 15 daily weight gain over this period in kg 1,055 1,121 1,223 1,216 Weight gain on the 61st day in kg 63.49 67.24 70.64 72.49 2Q Average daily weight gain in kg 1,041 1,102 1,158 1,188

Forsoq B

In another experiment, calves are implanted in 25 tablets of the following composition: estradiol 20 mg 4 9 11 3-oxo-17beta-acetoxy-delta-estratrien 140 mg additive consisting of: starch sodium glycolate 30 polyvinylpyrrolidone magnesium stearate to form a tablet of 165 mg.

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DK 156539 B

The animals are slaughtered 42 days after implantation. Weigh the live weight at the beginning and end of the trial and slaughter weight of the carcasses.

5 The carcasses are classified according to the following criteria: general condition from 1 to 3 points, color from 1 to 3 points and fat state from 1 to 3 points.

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The following results are obtained: a) Treated animals 15 General condition Weight at + beginning of fat - Weight at end of state Weight of + color attempted by supply carcasses (maximum

Animal No. in kg_ get in kg i kg_ 9 points) 7n 54 43 149.2 95 9 58 43 152.8 97 9 73 45 163.2 106 9 74 45 153.6 95 8 76 40 153 100 9 83 40 158 , 4 104 9 87 43.6 151 96 7 90 42.2 131 85 7 25 93 42 151.8 96 6

Average 42.64 151.55 97.11 8.11 30

DK 156539 B

- 7 - (b) Control animals

General condition Weight at + grease beginning- Weight at end of state Weight of + color 5 attempted by animal carcasses (maximum

Animal No. in kg_ qet in kg in kg_ 9 points) 61 43.2 138 91 6 64 40 147.2 92 7 65 40 140.8 90 7 69 41 146.8 94 8 75 49 148.4 93 7 lü 78 42.4 150 97 5 82 44.2 150 95 7 88 40 131.4 83 5 94 42 140.4 90 9 56 43 162 96 6

Average 42.48 145.5 92.1 6.7 15

From these results, it is seen that the weight gain in the treated animals is clearly greater than in the control animals. The last column of the tables corresponds to a commercial assessment, which represents important criteria for cattle buyers. This assessment is much higher for the treated animals than for the control animals.

2) Examination of Metaplasic Modifications of Prostate in Calves 25 Administration of estrogens induces metaplasic modifications of prostate in calves. Immature bull calves are used which are separated into four groups: 1) a control group that receives no implantation preparation, 2) a group of animals in which a 20 mg estradiol tablet is implanted, 35

DK 156539 B

- 8 - 3) a group of animals implanting a tablet of 20 mg of estradiol and 40 mg of 3-oxo-17beta-acetoxyestra-4.9, 11 triene, and 4) a group of animals receiving an implant preparation on 5 mg of estradiol and 140 mg of 3-oxo-17beta-acetoxyester-4,9,11-triene.

The implant preparations are administered by subcutaneous route and the animals are slaughtered 90 days later.

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The results obtained are shown in the following table, where the plus signs represent a conventional scale for the intensity of the metaplasia. The absence of metaplasia is indicated by 0.

Hold Animals No. Prostate Metaplasia 15

Control 042 0

Hold I 040 0 045 0 029 0 675 0 671 0 9n 673 0 099 0 678 0 684 0 685 0 674 0

Animals that have received 649 +++ 2c- 20 mg of estradiol 669 +++

Team II 654 +++ 059 +++ 050 +++ 034 +++ 048 +++ 060 +++ 042 +++ 30 - 9 -

DK 156539 B

Hold_ The Animals No. Prostate Metaplasia

Animals, soin received 016 + 20 mg estradiol + 40 mg 037 + 3-oxo-17beta-acetoxy-030 + estra-4,9,11-triene 018 + 5 Hold III 019 + 667 0 662 + 650 +++ 670 + 661 0 666 + 10 639 ° iU 660 + 659 +

Animals receiving 037 0 20 mg estradiol + 140 mg 047 0 3-oxo-17beta-acetoxy-627 0 estra-4,9,11-triene 098 0

Hold IV 640 0 15 630 0 637 0 634 0

From these results, it is seen that the animals treated with estradiol have pronounced prostate metaplasia. The animals in

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group III shows less pronounced prostate metaplasia and the animals in group IV have no prostate metaplasia. The hormonal effect of estradiol is thus completely eliminated.

Furthermore, the following comparison has been made with the known technique based on estradiol and testosterone according to German patent 1,047,596.

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DK 156539B

- ίο - (a) The nitrogen balance obtained with the products according to the invention is that which is obtained with the products according to the said German patent, extremely superior, see Annexes I and I '.

5 b) The weight gain obtained with the products according to the invention is that which is obtained with the products according to the German patent, extremely superior, see Annex II.

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DK 156539 B

Bilaq II

Zootechnical and slaughter results Male calf of Norman breed.

Implantation 72 days for slaughter.

C

estradiol 20 mg estradiol 20 mg ++ s

Treatments_ Testosterone 200 mg R 1697 140 mqX

Number of animals 9 13

Duration of the fat (days) 107 107

Average weight at the start of the experiment (kg) 48.55 ± 1.313 49.00 ± 0.751

Average weight at end of test (kg) 156.89 +4.070 173.85 ± 2.172 15 Weight gain (kg) 108.34 +3.848 124.85 +2.133 ***

Average Weight Gain G.M.Q. (kg) 1.012 + 0.0359 1.167 ± 0.0199 *** n Weight of cold carcasses 100.88 +2.647 110.21 + 1.685 **

The averages are indicated by the typical uncertainty of the average Student's "t" test: ** P <0.01 25 *** P <0.001 x) R 1697-3-oxo-17beta-acetoxyestra-4,9,11-triene .

The product of the invention induces an unexpected weight gain and improves the nitrogen balance surprisingly, but does not cause metaplasia phenomena.

Claims (1)

- 14 - EN 156539 B Growth-promoting implant preparation containing a combination of an anabolic steroid and an estrogenic steroid, characterized in that the anabolic steroid is 3-oxo-17beta-acetoxyestra-4,9,11-triene and the estrogenic 5 steroid is estradiol.