KR950009945B1 - "veterinary preparation containing an antibiotic mixture of gentamicin and lincomycin as an additive to drinking water or animal feed and its use in pig breeding - Google Patents

Abstract

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Description

[Name of invention]

Veterinary preparations containing antibiotic mixtures of gentamicin and lincomycin as additives in beverages or animal feed and for their use in pig breeding

Detailed description of the invention

Technical Field of the Invention

This patent application is an additional application of Slovenia Patent Application No. P-9200002, which relates to a veterinary preparation as an additive to a beverage or animal feed containing an antibiotic mixture of gentamicin and rincomycin, both antibiotics being in free base form or gentamicin. It is added in the form of acid addition salts such as sulphate and lincomycin hydrochloride, and the present application also relates to their use for the prevention and treatment of dysentery and colitis in pigs, and for the prevention of endemic pneumonia, resulting in increased pig weight gain. To reduce losses, reduce the number of lean animals and improve feed use (conversion).

[Problems with Technology]

In pig-intensive pigs, the largest loss of weaned pigs is caused by the gastrointestinal tract and pneumonia, so antibiotics or combinations that are effective as additives in drinking water or animal feed can effectively prevent and prevent such infectious diseases. There is always a need for treatment, which can increase weight gain and reduce the mortality rate of piglets.

[Old technology]

The use of different antibiotics or combinations of antibiotics is known in the literature, which are said to be added to animal feeds and beverages to prevent and treat infectious diseases in fleshing animals and to simultaneously increase weight gain.

Lincomycin is a known antibiotic described in US Pat. No. 3,086,912, which contains a number of microorganisms, in particular Gram-positive bacteria such as Staphylococcus, Streptococcus, Crosstridium, Bacillus anthracis and Corybacterium spp., Bordetella and Sea. Inhibits the growth and reproduction of some Gram-negative bacteria, such as Mophilus, some Nocardia, and Actinomyces. Lincomycin is effective against swine Treponema hyodysenteriae, Mycoplasma hyopneumoniae and Myopurasma Galliceticum bacteria. It acts bacteriostatically on susceptible microorganisms and acts bactericidally at high concentrations (2-3 times MIC).

U. S. Patent No. 3,155, 580 describes galenic preparations based on lincomycin and its acid addition salts as active ingredients for the treatment of infectious diseases in humans and animals caused by bacteria, which are prophylactic and increase in weight gain in meat animals. Used for.

U.S. Patent No. 3,150,042 discloses the use of lincomycin for the prevention and treatment of spores in animals, and antibiotics have been used as additives in conventional animal feeds or in suitable amounts of beverages. It describes the administration of tablets and sterile injection solutions.

Gentamicin is an antibiotic described in US Pat. Nos. 3,091,572 and 3,136,704 and consists of a component having three structures, gentamicin C ₁ , C ₂ and C _1a . Gentamicin A is also well known and is complex and differs from other components. In galenic agents, gentamicin is a very effective antibiotic against Gram-positive and Gram-negative microorganisms such as Staphylococcus, Klebsiella, Pneumonas and Puroteus spp. And can be used in both human and animal pharmaceuticals.

Spectinomycin is described in US Pat. No. 3,234,094 as an antibiotic isolated from a fermentation broth of Streptomyces spectabilis. Spectinomycin has antimicrobial activity against mycopurasma, some Gram-positive bacteria and most Gram-negative bacteria and is used as a veterinary medicine. U. S. Patent No. 3,245, 497 describes an animal feed containing an effective amount of spectinomycin to speed up the growth of a meat animal.

U.S. Patent No. 3,261,687 describes a method of increasing the weight gain of animal feeds and meat animals containing a combination of the antibiotic spectinomycin (sulfate form) and lincomycin (hydrochloride form), which includes animal feed or The antibiotic ratio of the food was 1 to 10 parts by weight of spectinomycin and 1 part by weight of lincomycin. The combination of antibiotics in animal feeds and beverages yielded unexpected results and addition rates. The combination of two antibiotics added to animal feed is synergistic and is suitable for preventing and treating infectious diseases in fat animals.

Furthermore, U.S. Patent No. 3,679,787 discloses a combination of lincomycin and spectinomycin in combination with a carrier as a dosage unit, which states that the combination is synergistic against infectious diseases caused by mycopurasma, which is suitable for treating animal diseases. It is.

Tiamulin, which has a wide range of bactericidal actions, is described in US Pat. No. 3,919,290, and particularly acts on many Gram-positive and Gram-negative bacteria, as well as mycopurasma. In terms of veterinary preparations, it has been used for the prevention and treatment of hemorrhagic dysentery and endemic pneumonia, as well as for the prevention and treatment of other diseases caused by microorganisms susceptible to thiamurine (hydrogen humarate form). It has also been used for the prevention and treatment of animal respiratory diseases due to mycopurasma and secondary infection.

[Description and Example of Resolving Technical Problem]

The present invention is based on the task of finding a combination of antibiotics effective in the composition of veterinary preparations as additives in drinking water and animal feed for use in the prevention and treatment of dysentery and colitis in pigs and in the prevention of endemic pneumonia. The result is not only to increase pig weight gain and reduce losses, but also to reduce the number of lean animals and to reduce mortality. The results obtained by such combinations of antibiotics in the composition of veterinary preparations as additives in drinking water or animal feed are superior to the action of known combinations or individual antibiotics for the same purpose and show valuable improvements in pig breeding.

Slovenia Patent Application No. P-9200002 describes animal feeds and additives or beverage additives used in poultry raising, containing 1 part by weight of gentamicin sulfate and lincomycin hydrochloride to prevent and treat infectious diseases and increase weight gain. It contains between 5 and 60 parts by weight of antibiotic mixtures, which increases efficiency factors to low conversion and decreases total mortality.

In intensive breeding of pigs, the largest loss of breasted pigs, ie pigs after about three weeks of cessation of feeding, is due to gastrointestinal tract and pneumonia diseases. Gastrointestinal disease is first caused by Escherichia coli and is caused by the disability of the young piglet as well as the newborn piglets.

Escherichia coli, along with other bacteria, is a naturally occurring group in the digestive tract, and some strains of E. coli cause disease due to changes in organ conditions.

The pathological condition of the animal is stimulated only by E. coli mutants that can produce enterotoxins. E. coli infection in pigs can be understood as a complex of gastrointestinal diseases with characteristic diarrhea. The three types of disease associated with young pigs can be distinguished as follows:

From seventh day, it is distinguished by colidiarrhoea from birth pigs, colibacilliosis from lactating pigs older than 10 days, and coligastroenteritis and colonierotoxemy from weaning pigs.

Another disease that causes significant direct and indirect losses (death and lean remaining mortality and mortality) in intensive swine breeding is endogenous mycopuramic pneumonia. The disease is first caused by Mycoplasma hyopneumoniase.

Collaboration with other bacteria in worsening microclimate conditions results in chronic disease with high morbidity and low mortality (death). In pigs 3 to 8 weeks old, the disease becomes acute and in bad microclimate conditions, mortality can be as high as 10% or more. Death was mainly caused by secondary bacterial infections, and pigs with endemic pneumonia lost much more weight and had much less conversion.

In our study on the possibility of preventing pig hepatitis and endemic pneumonia in pigs, we could achieve the desired purpose of the invention by adding the new formulation according to the present invention to drinking water or normal pig feed, It has been surprisingly found that the effect is also superior to that of commercial formulations so far known for the same purpose.

The formulation of the present invention contains lincomycin and getamicin and may be in free base form, but more preferably pharmaceutically acceptable acid addition salts such as lincomycin hydrochloride and gentamicin sulfate, 1 It is added to a normal water-soluble base material as a weight part of 1: 1: 1: 10. The best results are to include lincomycin hydrochloride: gentamicin sulfate in a ratio of 1: 1 to 1: 3. The method for preparing a veterinary preparation, which is a beverage or feed additive for pigs according to the present invention, is obtained by mixing 1 part by weight of lincomycin, 1 to 10 parts by weight of gentamicin or a pharmaceutically acceptable acid addition salt and a water-soluble carrier thereof. Preferably, it is prepared by mixing 1 part by weight of lincomycin hydrochloride, 1 to 3 parts by weight of gentamicin sulfate and a water-soluble carrier. The formulations of the present invention can be added to beverages or conventional animal feed.

The formulation is administered from the first day of weaning.

Linco-spectin, a commercial formulation containing lincomycin hydrochloride and spectinomycin sulfate in equal parts 44 Purimics (Linco-Spectin Tibet, a commercial formulation containing 44 Premix) and thiiamulin hydrogen fumarate P 2% (Tiavet Clinical trials were conducted to compare P 2% powder, and these nutrients were added to drinking water or normal pig feed according to the method recommended by the producer.

The results obtained in comparative clinical trials on pigs-specifically described by way of example-are compared to other commercial formulations, resulting in a reduction in total loss and death from dysentery and pneumonia syndrome during breeding. Among them, there were no deaths and the percentage of pigs (fragments) of fragile constitution decreased, and additionally, conversion (use of feed) was shown to be the lowest when applying the formulation of the present invention. It can be seen that the gain in body weight is improved.

Based on the obtained results, it can be seen that the preparation of the present invention can be administered for the prevention and treatment of dysentery and coliform disease in pigs and for the prevention of endemic pneumonia, thus increasing the weight gain.

The combination of the two antibiotics is preferably added at a concentration of 1 mg / ml to 200 mg / ml for the beverage, with best results obtained by adding two antibiotic concentrations of about 50 mg / ml for the beverage.

The combination of two antibiotics is added at a total concentration of 0.5 kg / t to 5 kg / t for pig feed, preferably at a concentration of about 1.5 kg / t for solid feed.

Hereinafter, the present invention will be described in detail and the present invention is not limited thereto.

EXAMPLE

Example 1

Comparative clinical trials of the combination of antibiotics of the present invention with the lincomycin-spectinomycin combination and thiamurine in pigs.

Comparative experiments of the aforementioned antibiotics or antibiotic combinations were performed clinically to test the efficacy of the antibiotic combinations of the present invention for the prevention of E. coliosis and endemic pneumonia in pigs and to achieve weight gain.

The combination of antibiotics of the present invention was prepared in powder form with the following ingredients.

Lincomycin Hydrochloride

(lincomycin hydrochloride) 1.5 g

Gentamicin Sulfate

(gentamicin sulfate) 4.0 g

Polyethylene Glycol 4000 Powder

(polyethyleneglycol 4000 powder) 2.0g

Lactose

(lactose) 42.5 g

50.0 g

This formulation was prepared by mixing the finely ground solid components in the mixer and added to the following beverage or animal feed.

Lincomycin-Spectinomycin antibiotic combination contains Linco-Spectin with 1: 1 ratio of lincomycin hydrochloride and spectinomycin sulfate 44 was applied in the form of a commercial formulation of Premix (Upon Co., USA), while thiamurin was a Tiavet containing thiamurin hydrogen fumarate. It was applied in the form of a commercial formulation of P 2% power (pliva, creatia).

Weaning pigs were divided into three groups for clinical trials of the formulations of the present invention:

1 group of 1620 weaning pigs fed the formulation of the invention,

-Linco-Spectin 1 group of 1687 weaning pigs fed 44 Premix formulations,

-Tiavet 1 group of 1602 weaning pigs fed the P 2% power formulation,

Three groups of young pigs had the same gene origin.

The preparation of this beverage was added to the beverage at a dose of 50 g in 100 ml of water from the first day after weaning to the 21st day. There were no side effects observed in the animals fed the formulation of the present invention in drinking water.

Before placing the test animals, the building was washed with hot water under pressure, VirKon (krka, Slovenia) It was disinfected with the preparation, which is a mixture which is isotonic and stabilized with peroxide compounds, surfactants, organic acids and organic buffers. The main component is potassium peroxalate (50%).

Immediately after placement, administer 200 g of BCK forte + E powder (Alkaloid, Skopje, Macedonia), a vitamin preparation containing vitamins A, B ₃ , E, C, B ₁ , B ₂ , B ₆ and B ₁₂ of young pigs, to 100 ml of water. The amount was supplied in the drinking water for 2 days.

From the first day after weaning to the 21st day, young pigs were fed the drink of the preparation of the present invention at a dose of 50 g in 100 ml of water.

The appearance of dysentery, pneumonia, and death in the animals tested was examined daily.

Pigs were weighed during weaning and weighed when transferred to breeding sites (Tables 2 and 3).

The results of experiments using the formulations of the invention are shown in Tables 2, 3, 4 and 5.

During the clinical trial of the formulation of the present invention, 26 young pigs (1.6%), which lag behind the weight gain, were separated in two separate chambers. None of these pigs died until they were transferred to a feeding place.

During the breeding period, 3.45% of young pigs died of diarrhea syndrome and 1.3% of young pigs died of pneumonia syndrome (Table 3).

[Comparative Testing]

Two groups of pigs were tested at the same time and used the same generation and same pig house. Two pig house buildings were washed with hot water before migrating young pigs. (Virkon , Krka, Slovenia).

Linco-Spectin in feed to 1687 weaning pigs as first comparison 44 Purimics (Linco-Spectin 44 premix) The product was given at 1 kg per tonne of feed for 21 days as recommended by the producer. Concerning the farm's technological process, the drug was administered to young pigs beginning on the eighth day after weaning.

Tibet in feed to 1602 weaning pigs as second comparison (Tiavet ) P2% powder product was given as 1.25Kg per ton of feed for 21 days according to the producer's recommendation (Table 1). This group was also administered at the beginning of day 8 after weaning.

In addition, in addition to the above-mentioned antibiotics in the feed, the vitamin preparation of BCK-forte + E in drinking water was given in an amount of 200 g in 100 l of water for 2 days for parallel testing of young pigs. Parallel animals were also examined daily for the appearance of diarrhea, pneumonia and death. Pigs were weighed when we moved to weaning and kennels (Tables 2 and 3).

During clinical trials, Linco-Spectin 89 lean pigs (5.28%) were isolated from 44 premix groups, 27 of them died (30.3%). In the P2% powder group, 112 animals (6.9%) with less weight gain were isolated, 38 of them died (33.9%).

TABLE 1

Number of animals, products and dosages by group

TABLE 2

Average weight and average daily increase of young pigs during weaning and kennel migration

In Table 2, the group of young pigs administered the formulation of the present invention to the beverages showed the highest average weight and showed the largest daily increase at the time of migration.

TABLE 3

Total loss rate, number of deaths of diarrhea or pneumonia and conversion of feed during breeding period

Table 3 shows that the total loss rate and mortality due to diarrhea and pneumonia syndrome during the breeding time in the group administered the formulation of the present invention was the lowest compared to the parallel test group.

Feed conversion was lowest in the formulation administration group of the present invention.

TABLE 4

The number of lean young pigs and their mortality rate

Table 4 shows that the formulation administration group of the present invention had the lowest percentage of lean young pigs and no deaths in this group, whereas more than 30% of them died in the comparison group.

Table 5 shows the formulation of the present invention, Linco-Spectins 44 Premix and Tiavet The total results of all groups treated with P 2% are shown.

Summary of clinical trial results of the formulations of the present invention:

Weaning pigs showed no side effects in clinical trials of the formulations of the present invention.

The group of weaning pigs administered the formulation of the present invention is Linco-Spectins 44 Premix and Tiavet Comparison with the comparison group receiving P 2% of the commercial formulation showed superiority in the following points:

Average daily gain,

Average feed conversion,

Percentage of total losses,

Percentage of dead piglets with pneumonia symptoms,

Percentage of dead piglets with diarrhoea symptoms,

Percent of poorly developed piglets,

Percent of poorly developed piglets that died,

TABLE 5

Example 2

The combination of the present invention is made of the following components of the pig feed to be added.

For Prestarter:

For prestarter: 8th to 26th day

For starters: 26 to 47 days

For growth: period 47-80

Claims (5)

A veterinary preparation which is a beverage or feed additive for pigs, characterized by containing 1 part by weight of lincomycin and 1 to 10 parts by weight of gentamicin or a pharmaceutically acceptable acid addition salt thereof and a water soluble carrier. The veterinary preparation according to claim 1, which contains 1 part by weight of lincomycin hydrochloride and 1 to 3 parts by weight of an antibiotic mixture of gentamicin sulfate. A method for preparing a veterinary preparation which is a beverage or feed additive for pigs, characterized by mixing 1 part by weight of lincomycin, 1 to 10 parts by weight of gentamicin or their pharmaceutically acceptable acid addition salts with a water soluble carrier. 4. The method of claim 3, wherein 1 part by weight of lincomycin hydrochloride, 1 to 3 parts by weight of gentamycin sulfate and a water-soluble carrier are mixed with each other. Contains an antibiotic mixture of 1 part by weight of lincomycin hydrochloride and 1 to 3 parts by weight of gentamicin sulfate for the prevention and treatment of swine dysentery and coliformosis and for the prevention of endemic pneumonia and thereby to increase the weight gain of the pig. Use of a veterinary preparation which is a drink or feed additive for pigs.