DD283766A5 - AGENTS TO INCREASE GROWTH IN ANIMALS - Google Patents

Abstract

The invention relates to an agent for increasing the weight gain or improved feed utilization or both in monogastric or polygastric animals, characterized by a content of forskolin or one of its analogues. Containing forskolin; Liveweight gain increase; Improved feed conversion; livestock}

Description

An agent for increasing the weight of the live mass or improved feed utilization or both in mono- or polygastric animals

Field of application of the invention

The invention relates to an agent and its use for improving the growth and feed utilization in animals, in particular livestock.

Characteristic of the Prior Art Forskolin (I)

(D

and its naturally occurring analogs such as 1,9-dideoxy, 9-deoxy, 1, S-dideaoxy-Y-deacetyl, 1-deoxy, 7-deacetyl and 6-acetyl-7-deacetyl-forskolin , represent a group of labdan terpenoids isolated from the plant Ooleua forskohlii (BriqUo). Forskolin is one of the important diterpenes of the plant Coleus forskohlii and then as a valuable drug in the treatment of various diseases, such as glaucoma, hypertension, heart failure, inflammation,

- 1a -

Allergies and disorders generally caused by disrupting cAMP production can be used (see Tetrahedron Letters 19 1669 (1977), J. Med Chem 26, 486 (1983).) In addition to porskolin and the natural derivatives mentioned also a series of structurally related labdan derivatives have become known which show a related biological activity. See, for example, DE-A-35 02 686. It has now been found that porcrosine and its analogues are known as therapeutic agents for the treatment of diseases can be used advantageously in the agricultural sector «.

Object of the invention

By the means according to the invention, an increase in living mass gain or improvement of putter utilization in livestock is achieved

Explanation of the essence of the invention

The present invention has for its object to find suitable means for increasing the Lebensendmassezunahme or improve the Puttervei evaluation in livestock

According to the invention the object is achieved by a means for increasing the Lebensendmassezunähme or improved feed utilization or both in mono- or polygastric animals, characterized by

a content of porakolin or one of its analogues

The invention also relates to the use of forskolin and its analogues for increasing the increase in live males or improved feed utilization or both in monogastric or polyglobal animals.

Of particular interest is the use in livestock male and / or male Geachlechts and castrated animals, such as broilers, sows, piglets, hogs, calves and Maatrindern. But other animals, such as rabbits or fish are suitable.

As the analog analogous to forskolin, structurally related natural or synthetic labdane derivatives having similar biological activity can be used.

The active ingredient is preferably administered to the animals at a dosage of 0.01 to 40 mg per kg of body mass and day. The active ingredient can be administered to the animals in a variety of ways.

It is possible, for example, to add the active substance as pure substance, crude product, for example after the plant extraction, or as active substance-containing plant parts or in a suitable preparation to the complete feed or supplementary feed or also part of the daily ration. The food can be in liquid or solid form. Alternatively, you can add the Y / irkstoff or a Wirkatoffzubereitung the Trinkwasaer. Also ea is possible, the active ingredient with conventional aids in one

To bring oral or solid galenical preparation to be administered and administered as such or added to the feed. Parenteral administration of the active ingredient by means of an implant is also possible. 5

A preferred form of application of the active ingredient in many cases is the addition to the feed in the form of a concentrate (Praemix). Bas concentrate can be prepared, for example, by mixing the active ingredient, the crude product or the active ingredient-containing plant parts with a physiologically compatible, solid or liquid carrier. As a solid carrier, for example, grain by-products, such as wheat, wheat bran or de-oiled rice bran, but also maize flour, soybean meal, bolus alba or calcium carbonate into consideration. As the liquid carrier, physiological salt solutions, water and physiologically acceptable organic solvents can be used. It is possible to use suitable additives, such as emulsifiers, dispersing, suspending, wetting or gelling agents. The concentrate (Praemix) usually contains 0.1 to 10 wt .- ^, preferably 0.5 to 5 wt .- #, the active ingredient, and depending on the application, the active ingredient concentration can also be below or exceeded.

When administered with animal feed, it is expedient to proceed in such a way that a concentrate is homogeneously mixed with the feed. The feeds include commonly used feeds such as various cereals, oil recovery byproducts (e.g., soybean meal) and other energy and protein carriers such as tapioca and fishmeal, as well as feed mixtures, supplemental feeds or mineral mixtures made therefrom.

The optimal increase in growth usually depends on the composition of the feed, in particular the protein content,

and on the content of forskolin or its analogs, which is usually traversed with increasing porcine content, a maximum of growth increase. It can also be observed that increasing the protein content of the putter maximizes the increase in growth if the content of active ingredient is kept constant. The optimal dosage can be easily determined by a factorial experimental design in relatively few preliminary tests. As a rule, the concentration of the active substance in the dye is 0.1 to 500 mg / kg, preferably 0.1 to 200 mg / kg, in particular 0.1 to 100 mg / kg.

Another form of administration of the active ingredient is in the solution or suspension in drinking water or other drinkers, e.g. the milk exchanger.

The administration of the active ingredient may also be carried out by administering directly orally to the animals, preferably during or shortly before or after feeding, the active ingredient in the form of its solid or liquid galenic preparation. The galenic preparation may be e.g. a tablet, capsule, paste, granule form, powder, bolus, juice or syrup or a Praemix concentrate as described above. In particular in grazing animals, this form of application may be of particular interest.

For administration in the form of tablets, capsules, pastes, boiled, pills, granules, juices, syrups and the like, the same excipients and additives as are known in the pharmaceutical art can be used, in particular excipients for continuous long-term administration preparations Release of the active substance · Of particular interest are preparations of the latter kind which have been specially developed for ruminants. The active ingredient can be powdered, for example. Diluents, e.g.

microcrystalline cellulose, sugar or starch are mixed to fill the capsule volume. The preparation of the tablets may also be carried out in the usual way with the addition of substances such as e.g. Cellulose, lactose, sodium chloride, starch, dextrin, cellulose derivatives, etc., take place. For the preparation of liquid preparations, the usual in pharmaceutics adjuvants such. Vegetable oils, Kollidon, cellulose derivatives and the like can be used. An aqueous solution or suspension of porskolin or its analogs may e.g. In addition to the active ingredient, secondary constituents from the crude extract of the plants, in particular ground plant parts, or contain suitable buffer substances. Per administration unit preferably 1 to 600 mg of active ingredient should be included.

In parenteral administration of the active substance, the active ingredient is preferably released by means of an implant produced and used in a conventional manner depending on the species over a few weeks or months continuously in the required dose.

Combinations with other putter additives such as antibiotics and chemotherapeutics are also possible to improve the effect.

The active ingredients used according to the invention, preferably porskolin, have a positive influence on the growth with suboptimal and optimal protein supply. Moreover, when protein supply is needed, a smaller amount of putter is usually required for the same weight gain and thus the feed conversion is increased.

In addition, a protein-saving effect is noted. In general, with porcrosin and its analogues in the area of suboptimal protein supply, a certain growth of the animals can be achieved with a putter with a lower protein content than with feeding without the addition of active ingredient.

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embodiments

1β PUtterunga test on male rats

1a) material and methods

In a feeding diet with 6θ male weight average weight of 40-170 g of live weight, the effect of 5, 10, 20 and 40 ppm forskolin in the putter at two different protein levels of the diets (15 and 20 wt% for an auboptimal or ¹ , respectively ⁾ . optimal care) on growth, the Pufeterauf would take and the putter utilization compared to the putter without content of Porskolin examined. "The diets (composition see Table 1) were 16.6 and 16.8 kJ / g dry dust isokalorischo each six animals were with Fubter same Gehaita to Porakolin and the protein Reaultate gefüttert'u.id determined for the evaluation "the respective aecha animals were kept for 28 days to two by two in Makroionkäfigen in a climatic chamber at 25 ⁰ Kostant O and 65% relative humidity,

Table 1: Composition of feed for the consumption diets

Protein content (wt.%) Content of substances 15 20

Glueooe 62.15 58.11 ovalbumin 15,79 21.08 soybean oil 8.22 7.00 Oelluloae 6.00 6.00 : c) mineral compound pre-mix 5.64 5.64 χ) trace element 0.20 0.20 x) Vitaminvormischuniz; 2.00 2.00 Energy content kJ / g TS ₀ 16.3 16.8

x) Composition of premixes according to Scheuermann Ue Lautzsch, 1982, Z ₀ Tierphys ₀ Tierernähr ₀ u. Puttermittelkdeo, 48, 224-231

1b) Test results

The test results are summarized in Tables 2 (weight development and putter intake), ^ (statistical evaluation) and 4 (feed conversion).

Table 2: Weight development and putter recording

No. Content of raw protein Content of forskolin (ppm) Weight at the beginning (g) in the end Weight gain (g / 28 d) relative to control (*) 100.0 Putter up (g / d) relative to control 100 1 15 0 41.0 128.7 87.7 103.6 8.11 111.9 2 15 5 40.4 131.3 90.9 131.2 9.07 132.2 3 15 10 40.9 156.0 115.1 139.1 10.70 135.7 4 15 20 40.6 162.6 122.0 93.3 11.00 101.8 VJI 15 40 40.5 122.3 81.8 100.0 8.26 100.0 6 20 0 41.3 135.5 94.2 124.4 9.25 115.7 7 20 5 40.1 157.7 117.6 119.9 10.70 112.4 8th 20 10 40.3 153.2 112.9 127.9 10.40 115.7 9 20 20 41.4 161.9 120.5 109.4 10.70 100.6 10 20 40 39.9 143.0 103.1 9.31

Table 3s Non-linear regression calculated from data material in Table 2 (y - a + bx + ex ² ] for y = increase in body weight and χ = content of porcine in the

Content of crude protein a Constants b c 3 2 , 78, 23 -o, -o, 10 05 Correlation coefficient. R Significance P < 15 20 VO OD 00 VjJ I- 22 90 0, 0, 0.05 0.05 955, 873

Table 4: Feed conversion (g puttor / g weight gain) relative to the control group in % (the lower the number, the higher the fugue utilization)

Content of forskolin (ppm) mean

P rotein (#) 0 5 Ij) 20 40 Putterverwertung

15 100 107.7 100.8 97.3 109.3 103.7

20 100 92.4 93.8 90.5 92.0 92.2

Weight gain:

For 15 and 20 wt.% Protein up to a concentration of 20 ppm porskolin, an increase in biomass increased up to $ 39 within 28 days compared to the corresponding control group. There is a significant relationship between weight gain and porskolin concentration. In addition, a protein-saving effect becomes clear. So the animals reached 15% protein and 5, 10 or 20 ppm Porskolin with about 91 "115 or 122 g increase the growth rates of the animals at 20 i> protein in the control group and the groups with 10 or 20 ppm forskolin, corresponding to 94 , 113 or 121 g increment. Thus, with comparable growth and reduced protein content of the diet, protein utilization in the presence of porskolin is improved and excretion of nitrogen via faeces and urine is reduced.

Putter recovery:

The feed conversion is increased with needs-based (optimal) protein supply in the presence of porskolin. In the series of experiments the putter utilization at $ 20 protein content is increased up to about $ 8 (see average feed conversion in Table 4).

The above-mentioned results, which were obtained in the experiments on rats, can in their tendency also be transferred to other animals. Such is the use of

Rats have long been common in determining protein quality of feed, limiting amino acids, and protein utilization. Rat testing for the determination of protein utilization and biological value of protein in feeds is officially recognized, for example, in the USA, Canada and the Federal Republic of Germany (see, for example, C. Kies, HM Fox, pages 1-10, JM McLaughlan, MO Keith , pages 79 to 85; M. Wamack, DA Vaughan, CE Bodwell, pages 113 to 123; each of "protein Nutritional Quality of Foods and feeds, Part 1: assay Methods - Biological, Biochemical and Chemical; edited by Mendel Friedman _t 1975 »Marcel Dekker, New York).

2. Feeding ban on broilers

2a) Method

Mannlicht Lohmann broilers with a live weight of between 35 and 45 g were placed in groups of 20 animals per treatment (100 cm ² / animal) on a bed of shavings with 24-hour illumination and a temperature of 36 + 1 ⁰ C until 21 Experimental day and 26 + 1 ^e C held from the 22nd to the 35th experimental day. The food was offered ad libitum. The composition of the feed (without active ingredient) is given in Table 5. The protein content was 22% by weight (according to need).

Forskolin was introduced as root meal via a glucose premix into the ration.

Tatelle '5 i> fresh substance) Feed composition (wgt. 24.00 Soybean meal 6.00 fishmeal 2.00 fodder yeast 44.89 Corn 6.35 wheat 4.70 beef tallow 8.50 Weizennachmehl 1.00 LuzernegrUnmehl 1.40 phosphors. feed lime 0.96 carbonate. feed lime 0.04 trace element 0.09 Feed salt 0.07 DL-methionine

2b) Results

The test results are summarized in Table 6 (see page 12).

Growth:

Broiler liver mass gain was improved up to $ 9 compared to the control group (see Table 6).

Feed intake and feed conversion: Feed intake was increased by the content of forskolin roots. However, the increase in feed intake was significantly lower than the increase in live weight as can be seen from the better feed conversion (i.e., lower number). The increase in feed intake also indicates a beneficial effect on the digestion of nutrients, so that more food can be consumed with faster passage of the chyme.

Putter recovery:

Increased growth compared to putter intake improved feed conversion by up to 7 # (Table 6). The positive effects on feed conversion and feed intake indicate improved intermediate use of feed ingredients. This is also to be expected in broilers (see experiment with rats) with a reduction of N excretions.

12

Table 6 *)

Content Weight (Mass) Mass- Putter- Feed

Forskolin (g) increase absorption recovery

(ppm) at am (g / d) g / d g feed /

Beginning of end of g increase

0 121.7 1,580.2 41.7 84.8 2.08 ± 17.4 ± 230.1 ± 6 "2 ± 0.34 100.0 100.0 100.0 100.0 2 122.6 1,715.2 45.4 88.4 1.97 ± 16.9 ± 196.2 ± 5.4 ± 0.24 108.5 109.0 104.0 94.6 4 126.9 1,682.5 44.4 86.2 1.99 ± 17.2 ± 253.7 ± 6.9 ± 0.38 106.4 106.0 101.6 95.7 8th 120.8 1,643.0 43.5 83.8 1.95 ± 17.1 ± 192.3 ± 5.3 ± 0.24 103.9 104.3 98.7 93.8 16 121, 6 1,629.5 43.1 86.7 2.04 ± 16.1 ± 242.4 ± 6.6 ± 0.33 103.1 103.4 102.0 97.9 32 122.6 1,642.7 43.3 86.4 2.02 ± 18.6 ± 182.9 ± 5.0 ± 0.28 103.9 103.9 101, 8 97.2

*) The first row in each category with the same forskolin content gives the averaged value, the second row the spreading range and the third row the percentage value relative to the control group without forskolin content in the feed.

Claims (13)

Pat entansprüohe 1. means for increasing the Lebensmassezunahme or improved feed utilization or both in monogastric or polygastric animals, characterized by a content of forskolin or one of its analogues in addition to solid or liquid feed or galenic auxiliaries and additives or drinking water. . 2. Composition according to claim 1, characterized gekennszeichnet that it is a solid or liquid sole or supplementary feed or drinking water. 2 8 3 7 6 -15- 3 "agent according to claim 1, characterized in that it is a solid or liquid concentrate (Praemix). 4. Composition according to claim 1, characterized in that it comprises an oral, solid or liquid galenische preparation to be applied, preferably a tablet, capsule, paste, a granule, a powder, a juice, a syrup, a bolus or slow-release Bolus, represents. 5. Composition according to claim 1, characterized in that it represents an implant for the parenteral administration of forskolin with a continuous release over a few weeks or months. 6. A composition according to any one of claims 1 to 5, characterized in that it contains F _o rskolin as a pure substance, crude extracts, dried plants or parts of plants or mixtures thereof. 7. Composition according to claim 3 _5, characterized in that it contains the active ingredient in a concentration of 0.1 to 500 mg / kg Putter, preferably 0.1 to 200 mg / kg of feed, in particular 0.1 to 100 mg / kg of feed contains 8. Composition according to claim 4 », characterized in that it contains forskolin or its analogues in a concentration of 0.1 to 10 wt .- #. 9. Composition according to claim 5, characterized in that it contains the active ingredient in a concentration of 1 to 600 mg per administration unit. 10. A process for the preparation of the composition according to claim 2, characterized in that mixing forskolin or its analogues in a suitable form with solid or liquid feed or galenic auxiliaries and additives or with the drinking water. 11. The use of forskolin and its analogs, characterized in that they are used to increase the weight gain or improved feed utilization or both in mono- or polygastric animals. 12. Use according to claim 1, characterized in that one or more of the means defined in claims 2 to 10 is used. 13 »Use according to claim 1 or 12, characterized in that the dosage is 0.01 to 40 mg forskolin per kg body mass of the animals and per day.