Probiotic preparation for veterinary use

 

(57) Abstract:

The invention is intended for biotechnology and veterinary medicine. The product contains bacteria Bifidobacterium globosum VGNKI BF-4-DEPOT, a strain of Streptococcus faecium VGNKI 27/11-IN-DEPT and the combination of virulent polarizator staphylococcal bacteriophages. The formula also contains aluminum oxide, aluminum hydroxide, carbohydrate and filler. From strains of staphylococcal bacteriophages it contains strains VGNKI 89/CMAI-FS-1-DEPT and VGNKI 90/CMAI-BS-2-DEPT. Of carbohydrates, the preparation may contain lactose and/or sucrose and fillers - starch, milk powder, whey milk, whole milk powder, powdered sugar or food sugar. The drug may also optionally contain various combinations of dry backass acidophilic bacteria and/or dry culture of bacteriophages pseudomonads strains VGNKI 86/CMAI-A1-DEPT, VGNKI 87-Zmei-B2-DEPT, VGNKI 88/CMAI-C1-DEPT. The drug has simultaneously prophylactic and therapeutic efficacy in intestinal dysbacteriosis, promotes bowel disease animals from staphylococci and Pseudomonas aeruginosa, has a broad spectrum antibacterial and paralytically activity and boosts the immune status of the animals. 5 C.Biopreparat, possessing a wide spectrum of antibacterial and paralytically activity, but can also increase the immune status of the animals and birds and to restore normal flora.

Known probiotic preparations SBA, STF-1/56, designed to restore intestinal biocenosis due to the antagonistic properties of strains of bacteria of probionts (Antipov C. A., Ermakov, I. N., Kosheleva E. K., Badalyan K. M. "Application of the SBA as restimulative tools//Vsesojuzn. Proc. "Micro - stimulators and inhibitors Rast. and animals" 3 - 5 Oct.1989: abstracts. Dokl. h 1, Tashkent, 1989, page 14; Mishurov C. N., Chiriaev F. C., Antagonistic properties of the drug STF-1/56 regarding Salmonella and Escherichia coli//veterinary medicine, 1988, 10, S. 34 - 36).

The mechanism of action of probiotics is based on adhesive and antagonistic properties of bacterial probionts, displacing from the composition of the intestinal population of conditionally pathogenic microorganisms and nonspecific controlling the redundancy of their growth.

However, the known probiotic preparations have a limited range of actions and have a weak antagonistic activity against staphylococci and practically does not inhibit growth of sinign 1986, H. 1. C. 9 - 10).

However, it is known that intestinal dysbiosis accompanied by a reduction in natural resistance of the organism and is often complicated by infections caused by Staphylococcus, Pseudomonas and enteropathogenic bacteria (Blokhin, I. N., Dorofeyuk Century, The Dysbacteriosis. M., 1979; Korshunov C. M., Pinegin B. C., N. Volodin.N. and the other is the Study of the intestinal microflora in the formation and postradiation chemotherapy dysbacteriosis. // In: "Theoretical and practical problems of gnotobiology", M, 1986, S. 190).

Excessive presence in the intestinal biocenosis of these groups of microorganisms makes it difficult for the prevention and treatment of gastrointestinal diseases and reduces the effectiveness of probiotics.

Known therapeutic bacteriophage preparations used for the renovation of the gastrointestinal tract from staphylococci and Pseudomonas aeruginosa (In kN.: The practitioner's Handbook.// Ultidev Y. I., Komarov F. I., Navashin S. M. and others, Ed. by A. I. of Vorobeva. - 7th ed. -M.: Publishing house of ONYX, 1998; Topical issues of bacteriophage and applied immunology. - Tbilisi, 1984, S. 168-266; gg Bogomazova, N. N. Voroshilov, V. M. Bondarenko, etc. - Immunobiological SV is, however, known bacteriophage preparations do not possess a sufficiently broad spectrum of lytic activity. The possibility of occurrence in the population of pathogenic microorganisms favoritestest forms is on the order of 10(-7)- 10(-8)and reduces the effectiveness of phage therapy.

The closest analogue is the biopreparation "Streptavidin", which includes dry backmask Bifidobacterium Bifidobacterium globosum VGNKI N CF-4/DEPT, dry backmask streptococcal strain of Streptococcus faecium VGNKI N 27/11-IN-DEPT, carbohydrate, aluminum oxide, aluminum hydroxide and the filler (RU N 2086248, A 61 K 35/74, publ. 10.08.97).

Lack of preparation "Streptavidin" is a low efficacy against Staphylococcus aureus and Pseudomonas aeruginosa bacteria.

The objective of the invention is the creation of highly efficient products with a wide range of actions for the treatment and prevention of dysbiosis and intestinal dysfunctions of animals and poultry.

The technical result of the invention is to obtain a comprehensive probiotic and bacteriophagous of the drug, to reduce the treatment time, to get more persistent and pronounced therapeutic effect, can improve the immune status of animals and poultry and steadily the x virulent staphylococcal and pseudomonads bacteriophages, with different receptors on the bacterial surface, which can reduce the frequency of emergence of resistant forms of microorganisms with a wide range of political action, and bacteria-probionts capable korrigirovat intestinal biocenosis due to antagonistic and colonization properties of the used strains.

The essence of the invention. Probiotic product contains dry backass bifidobacteria, dry backass streptococcal dry culture staphylococcal bacteriophage strains VGNKI N 89/CMAI-FS-1-DEPT and VGNKI N 90/CMAI-BS-2-DEPOT, carbohydrates, aluminum oxide, aluminum hydroxide and a filler, in the following ratio of components, g/kg of the drug:

Dry backmask bifidobacteria content 10-3000 billion microbial cells (M. K.) 1 g - 2,04 - 4,0

Dry backmask streptococcal content 10-3000 billion, M. K. 1 g - 2,0 - 4,0

Dry culture staphylococcal bacteriophage strains VGNKI N 89/CMAI-FS-1-DEPT and VGNKI N 90/CMAI-BS-2-DEPT activity 10(-9)- 10(-12)PFU/g - 0,5 - 2,0

Carbohydrate - 20-40

Alumina - 30-60

Aluminium hydroxide - 100-300

Filler - Rest

Of carbohydrates, the preparation may contain lactose and/or sucrose and fillers - starch, milk powder, dry sivaramakrishna to contain various combinations of dry backass acidophilus bacteria content 10-3000 billion M. K. 1 g and/or a dry culture of bacteriophages pseudomonads strains VGNKI No. 86/CMAI-A1-DEPT, VGNKI N 87/CMAI-B2-DEPT, VGNKI N 88/CMAI-C1-DEPT activity of each strain of 10(-9)- 10(-12)PFU/g

In the composition of the drug can be used any strains of bifidobacteria, streptococci and lactic acid bacteria, characterized by high adhesion power and antagonistic activity. In particular, there can be used known strains of Bifidobacterium globosum VGNKI N BF-4-DEPT, Streptococcus faecium VGNKI N 27/11-IN-DEPT and strain acidophilus bacteria Lactobacillus acidophilus N A-105-DEPT/VGNKI.

Included in the drug strains of bifidobacteria and streptococci have the adhesive and antagonistic activity against pathogenic microflora, participate in the processes of intestinal microbial digestion, produce enzymes, acids and other biologically active substances.

Highly virulent polarizaiton bacteriophages, are included in the product are new strains obtained from various sources on livestock farms (manure, sewage, sludge removal from the equipment, the contents of the intestines, purulent external and internal foci).

Strains of sineg the AMI: strains of Pseudomonas phages No. 86/CMAI-A1-DEPT, N 87/CMAI-B2-DEPOT, No. 88/CMAI-C1-DEPT, strains of staphylococcal bacteriophages numbers N 89/CMAI-FS-1-DEPT, N 90/CMAI-BS-2-DEPT.

Strains of bacteriophages have a wide spectrum of lytic activity against wide range of pathogens staphylococcosis and Pseudomonas animals. The main methods used in the study of the properties of the selected bacterial viruses described in the monograph by Adams (Adams M Bacteriophages, M., and World, 1961).

Strains of Pseudomonas aeruginosa bacteriophages VGNKI No. 86/CMAI-A1-DEPT, VGNKI N 87/CMAI-B2-DEPT and VGNKI N 88/CMAI-C1-DEPT characterized by the following properties:

The morphology and sizes of phage particles. The electron microscopy data. The strain of phage VGNKI No. 86/CMAI-A1-DEPT has an isometric head with a diameter of 62 nm and a shrinking tail bone (145 x 20 nm). Apparatus for adsorption of phage - basal plate and 6 (six) tail fibrils. The length of the fibrils is 50 nm.

The strain of phage consists of an elongated head (92 x 58 nm) and nesokrushimogo tail bone (170 x 12 nm). Apparatus for adsorption of phage includes organelles two types. Side organelles adsorption of phage fixed to Pilah (fimbriae) Pseudomonas aeruginosa. In addition, at the end of the caudal process of the phage three distinct terminal PHA through pili to the cell surface.

The strain of phage VGNKI N 88/CMAI-C1-DEPT consists of isometric head shape (64 nm) and short nesokrushimogo tail bone length 10-11 nm. Any additional structural elements of the phage N 88/CMAI-C1-DEPT not found.

All three strains of bacteriophages contain DNA.

The strain of phage VGNKI No. 86/CMAI-A1-DEPT, strain of phage VGNKI N 87/CMAI-B2-DEPT and strain of phage N 88/CMAI-C1-DEPT - virulent bacterial viruses. Strains of P. aeruginosa, lysogeny these phages could not be identified.

The lytic properties of phages. To evaluate lytic spectra of bacterial viruses were used two collections of strains of Pseudomonas aeruginosa. One collection consisted of 40 isolates of Pseudomonas aeruginosa isolated from mastitis cows in different regions of the Russian Federation. The second collection consisted of 28 isolates of Pseudomonas aeruginosa isolated from soil and manure samples Chelyabinsk region.

The strain of bacteriophage VGNKI No. 86/CMAI-A1-DEPT analyzes 48 strains of Pseudomonas aeruginosa from 68.

Range owners phage VGNKI N 87/CMAI-B2-DEPT - 47 cultures of P. aeruginosa.

Phage VGNKI N 88/CMAI-C1-DEPT of active compared to 43 strains from the same sample (68 isolates).

Combined product of the three phages is as the host cell used a strain of P. aeruginosa RAO.

Physico-chemical properties of phages. All three phage retain lytic activity in solutions with pH from 4 to 10.5.

Incubation of the phage suspension VGNKI N 87/CMAI-B2-DEPT at 60oC for 30 min leads to a decrease in the titer of phage in 2 lg. Phage VGNKI No. 86/CMAI-A1-DEPT more resistant to this treatment (reduction of concentration of 1 lg). The lytic properties of phage VGNKI N 88/CMAI-C1-DEN is not changed by heating the sample to 60oC.

A single freeze-thaw almost no effect on the biological properties of phages.

When stored in the cold (4-8oC) phage preparations do not lose lytic activity during the year. Strains of staphylococcal bacteriophages VGNKI N 89/CMAI-FS-1-DEPT and VGNKI N 90/CMAI-BS-2-DEPT characterized by the following properties:

The morphology and sizes of phage particles. The electron microscopy data. A strain of Staphylococcus bacteriophage VGNKI N 89/CMAI-FS-1-DEPT consists of an icosahedral head with a diameter of 85 nm and a shrinking of the caudal process length of 200 nm and a width of 15 nm. After reduction the case of bone has a length of 100 nm and a width of 20 nm. Apparatus for adsorption of phage - basal plate with fimbriae. Basal plate has a diameter of 45-50 nm.

Other morphological details have not been investigated. The lytic properties of phages. To evaluate lytic properties of phages was used collection VGNKI of 117 coagulasepositive pathogenic strains of Staphylococcus aureus isolated from mastitis cows, purulent content of external wounds, fecal content in different livestock farms of the Moscow region, from domestic animals and poultry in the Chelyabinsk region, Republic of Udmurtia, Kirov region.

A strain of Staphylococcus bacteriophage VGNKI N 89/CMAI-FS-1-DEPT analyzes 102 strains from this collection.

The strain of phage VGNKI N 90/CMAI-B8-2-DEPT analyzes 97 strains from this collection.

The combination of these two phages analyzes all 117 strains of staphylococci.

Biological properties of phages. A strain of Staphylococcus bacteriophage VGNKI N 89/CMAI-FS-1-DEPT has a latent period of infection 25-30 minutes Yield - 60 particles per cell.

When playing a strain of Staphylococcus bacteriophage VGNKI N 90/CMAI-BS-2-DEPT cells masters latent period lasts 40-45 minutes, the yield of 40-45 particles per cell. Physico-chemical properties of phages. Both phage retain lytic activity in rest for 30 min leads to a decrease in the titer of phage in 1 lg. The lytic properties of phage VGNKI N 90/CMAI-BS-2-DEPT not change when heated to 60oC for 30 minutes

Strain VGNKI N 89/CMAI-FS-1-DEPT has a buoyant density of 1.47 g/ml Content HZ-nucleotides in dvuhtsepochnyj linear DNA is 32%.

A strain of Staphylococcus bacteriophage VGNKI N 90/CMAI-BS-2-DEPOT has a buoyant density of 1.48 g/ml Content HZ-pairs in double-stranded linear DNA is 35%.

When stored in the cold (4-10oC) phages do not lose lytic activity for 18 months.

The invention is illustrated by the following examples.

Example 1. The drug "Pagosa" containing a culture of a strain of Streptococcus faecium VGNKI N 27/11-IN-the DEPOT (or any other culture of streptococcal strains used in probiotic preparations), culture Bifidobacterium globosum VGNKI N BF-4-DEPOT (or any other culture of bifidobacteria), combination polarizator staphylococcal bacteriophage strains VGNKI N 89/CMAI-FS-1-DEPT, VGNKI N 90/CMAI-BS-2-DEPT prepared as follows:

Used in the drug strains of microorganisms separately cultivated on liquid nutrient media adopted for the cultivation of bifidobacteria and streptococci, or among the project within (162) h biomass yield of each species of bacteria not less than 10 billion living microbial cells in 1 ml of culture suspension. The obtained culture was concentrated in 10-15 times depending on the density of the culture of sediments washed from the products of metabolism in the separators or microfiltration units. Concentrated bacterial suspension is dried by sublimation method according to the conventional technology.

In the resulting dry semi-finished products contained at least 500 billion living microbial cells per gram.

Separately receive dry biomass staphylococcal bacteriophage strains VGNKI N 89/CMAI-FS-1-DEPT and VGNKI N 90/CMAI-BS-2-DEPT. For this pre-grown culture of host cells in a liquid medium, infecting phages and cultured until complete lysis of the microorganisms. The resulting fagholizata purified. The concentration of phage in the lysates is determined by titration method agar layer (Adams, 1961).

The technology of phage, non strains of host cells, the purification method are the subject of know-how.

Purified cultures of phage freeze-dried way of achieving active values of the phage in 1 gram of the obtained dry cake mix not less than 10(-9)- 10(-12)PFU/g

The activity of each is yokokawa of bacteriophages for faguibine strains, isolated from cattle", approved by the BS of the Ministry of agriculture of the USSR 16.09.1976, isolates cultures of staphylococci isolated from purulent lesions, internal organs and intestinal contents of different species of animals and test strains.

Dry backass each strain are mixed together in a ratio of 1:1.

Dry semi-finished products of bacteriophages are mixed together in a ratio of 1: 1.

Next, a dry mixture of strains mixed with dry bacteriophage in the ratio of 1: 1, add carbohydrate, oxide and hydroxide of aluminum and the filler (starch, sugar powder, skimmed milk powder, whole milk substitute) in the following ratio of components, g/kg:

Dry backmask strain of Streptococcus content 30-1000 billion living microbial cells/g - 3

Dry backmask strain of bifidobacteria content 30-1000 billion living microbial cells/g - 3

Dry culture of staphylococcal bacteriophages VGNKI N 89/CMAI-FS-1-DEPT, VGNKI N 90/CMAI-BS-2-DEPT activity 10(-9)- 10(-12)PFU/g - 1

Carbohydrate (lactose or sucrose) - 30

Aluminum oxide - 50

Aluminium hydroxide - 200

Filler - Up to 1000

The composition allows to obtain a series of drug with a total value KOE streptococci and filatochev phage activity from 10(-6)up to 10(-9)The BATTLE in one gram.

Example 2. Take the strains of the bacteria Streptococcus faecium VGNKI N 27/11-IN-DEPT, Bifidobacterium globosum VGNKI N BF/4-DEPT, Lactobacillus acidophilus N A-105-DEPT/VGNKI and strains of staphylococcal bacteriophages VGNKI N 89/CMAI-FS-1-DEPT and VGNKI N 90/CMAI-BS-2-DEPT.

Probiotic preparation is produced by a separate submerged cultivation of strains of bifidobacteria, streptococci and acidophilus bacteria in liquid nutrient media adopted for the cultivation of these species of microorganisms. Get dry backass each strain separately analogously to example 1.

Next dry backass each strain are mixed in equal proportions.

Dry semi-finished products of bacteriophages obtained in example 1, are mixed together in a ratio of 1:1.

Next, a dry mixture of strains mixed with dry bacteriophage in the ratio of 1: 1, add carbohydrate, oxide and hydroxide of aluminum and the filler (e.g., starch or sugar food, powdered sugar), in the following ratio of components, g/kg:

Dry backmask strain of Streptococcus content of 10 to 3000 billion living microbial cells in 1 g - 2

Dry backmask strain of bifidobacteria content 10-3000 billion living microbial CL is 1 g - 2

Dry culture of bacteriophages staphylococcal strains VGNKI N 89/CMAI-FS-1-DEPT, VGNKI N 90/CMAI-BS-2-DEPT activity 10(-9)- 10(-12)PFU/g - 1

Carbohydrate (lactose or sucrose) - 30

Aluminum oxide - 50

Aluminium hydroxide - 200

Filler - Up to 1000

The composition allows to obtain a series of drug with a total value of SOME streptococci, bifidobacteria and acidophilus bacteria (when equal to their proportions) from 180 million to 6 billion per gram, bacterial staphylococcal phage activity from 10(-6)up to 10(-9)The BATTLE in one gram.

Example 3. Take the strains of the bacteria Streptococcus faecium VGNKI N 27/11-IN-DEPT, Bifidobacterium globosum VGNKI N BF/4-DEPT, Lactobacillus acidophilus N A-105-DEN/VGNKI, strains of staphylococcal bacteriophages VGNKI N 89/CMAI-FS-1-DEPT, VGNKI N 90/CMAI-BS-2-DEPT and strains pseudomonads bacteriophages VGNKI No. 86/CMAI-A1-DEPT, VGNKI N 87/CMAI-B2-DEN, VGNKI N 88/CMAI-C1-DEPT. Dry semi-finished products used strains of bacteria and bacteriophages are prepared analogously to example 1 and 2.

The activity of the obtained dry semi-staphylococcal and pseudomonads of bacteriophages is not less than 10(12)The BATTLE in one gram.

A dry mixture of strains of bifidobacteria, streptokinase 1: 1 and add a carbohydrate, oxide and hydroxide of aluminum and the filler (starch, sugar powder, skimmed milk powder, whole milk substitute) in the following ratio of components, g/kg:

Dry backmask strain of Streptococcus content 30-1000 billion living microbial cells/g - 3

Dry backmask strain of bifidobacteria content 30-1000 billion living microbial cells/g - 3

Dry backmask strain acidophilus bacteria content 30-1000 billion living microbial cells/g - 3

Dry culture of bacteriophages staphylococcal strains VGNKI N 89/CMAI-FS-1-DEPT, VGNKI N 90/CMAI-BS-2-DEPT activity 10(-9)- 10(-12)PFU/g - 1

Dry culture of bacteriophages pseudomonads strains VGNKI No. 86/CMAI-A1-DEPT, VGNKI N 87/CMAI-B2-DEPT, VGNKI N 88/CMAI-C1-DEPT activity 10(-9)- 10(-12)PFU/g - 1

Carbohydrate (lactose or sucrose) - 30

Aluminum oxide - 50

Aluminium hydroxide - 200

Filler - Up to 1000

The composition allows to obtain a series of drug with a total value of SOME streptococci, bifidobacteria and acidophilus bacteria (when equal to their proportions) from 180 million to 6 billion in 1 g bacterial staphylococcal and pseudomonads phages (when equal to their activity) of 10(-6)up to 10(-9)FIGHT 1,

Feel prophylactic efficacy of a series of drug Pagosa":

obtained in example 3, total concentration of bacteria in one gram of 180 million M. K., activity of phages 2x10(-6)The BATTLE in one gram;

obtained in example 3, total concentration of bacteria in one gram 600 million M. K., concentration of active phages 10(-9)The BATTLE in one gram;

is obtained according to the example 2, the total concentration of bacteria in one gram of 180 million M. K. and activity of phages 110(-6)PFU/g;

- obtained in example 1 with the total concentration of bacteria in one gram of 180 million M. K. and activity of phage 110(-6)PFU/g

As a biological model for testing drug "Pagosa" use puppies 3-3,5 months of age from nursery prone to staph infections. The laboratory examination of feces according to the standard technique puppies were inoculated Staphylococcus and bacteria of the group of Escherichia coli at concentrations above the accepted physiological norm, and Pseudomonas aeruginosa.

Visual inspection puppies lag behind in growth and development, the appetite is perverted or missing, palpation of the abdominal wall hard, painful, swollen, defecation cal form 5 groups puppies 3-3,5 months of age.

The first group of puppies ask orally with food once a day for 5 days 1 g of the product prepared according to example 1, with the concentration of CFU bacteria 180 million, with a total activity of bacteriophages 210(-6)PFU/g

The second group of puppies ask similarly, within 5 days of one gram of a preparation prepared according to example 1, with the total concentration of CFU bacteria 600 million, the total activity of bacteriophages 210(9)PFU/g

The third group of puppies ask similarly, within 5 days of one gram of a preparation prepared according to example 2, with the total concentration of CFU bacteria 180 million, with a total activity of staphylococcal bacteriophages 110(-6)PFU/g

The fourth group of puppies ask similarly for 5 days on 1 g of the product prepared according to example 1, with the total concentration of CFU bacteria 180 million, the activity of staphylococcal bacteriophages 110(-6)PFU/g

The fifth group of puppies is used as a control and feeding them twice a day with 20 ml of a commercial preparation of staphylococcal bacteriophage together with symptomatic and antibacterial therapy.

Take into account the efficiency of the test preparation h is SS="ptx2">

Puppies first group beginning of the recovery activity of the gastrointestinal tract is observed in the second or third day after the beginning of the drug. The defecation is normalized, faeces without admixture of mucus and without ihorozny smell. Behavioral responses of puppies intensified. After giving the drug to 5 days of its application behavioral responses puppies recovered fully, appetite normal. According to bacteriological research is SOME of lactobacilli in puppies this group is lg 6,5+0,8. Nacina CFU Staphylococcus reduced to the limits of physiological norm and is lg 3,2+0,2. Three of 6 puppies in the intestinal biocenosis staphylococci in a dilution of 10(-3)no. Coagulasepositive staphylococci and Pseudomonas aeruginosa absent in all of the puppies in this group.

Puppies of the second group, the activity of the gastrointestinal tract is fully restored to a 3-5 day giving the drug. According to bacteriological research is SOME of staphylococci puppies this group is lg 2,4+0,3. Coagulasepositive staphylococci and Pseudomonas aeruginosa are missing. The value of CFU of lactobacilli in the intestinal content is lg 7,9+0,6, bacteria group kiseop intestinal biocenosis restored to a 4-7 day after the beginning of the giving of drugs.

Puppies both experimental groups at the end of the summer residences of the test drug in the contents of the gastrointestinal tract in a dilution of 10(-2)no staphylococci and Pseudomonas aeruginosa.

Puppies in the control group treated with a commercial preparation of bacteriophages, antibiotics and symptomatic therapy, the recovery of activity of the gastrointestinal tract occurs 12-14 days after the start of treatment. The act of defecation is not completely restored. Bacteriological examination of the contents of the gastrointestinal tract is SOME lactobacilli puppies in this group on day 14 of treatment is lg 5,8+0.2, which is significantly below the physiological norm. The value of SOME of staphylococal is lg 4,5+0,7. In 2 of the 5 puppies this group inoculated coagulasepositive staphylococci and Pseudomonas aeruginosa. The number of bacteria of Escherichia coli group is lg 9,4+0,7.

The use of drugs contributes to restore intestinal biocenosis bowel disease from staphylococci and Pseudomonas aeruginosa, from excessive colonization by bacteria of Escherichia coli group and stimulates the growth and development of puppies.

Example 5. Conduct performance testing pamatkami syndrome mastitis-metritis-agalactia (MMA).

For testing form 6 groups of lactating sows with a diagnosis of MMA with roughly the same number of piglets under the lactating sow.

In the first group, ask the product prepared according to example 3, total concentration of bacteria 180 million M. K., the total concentration of phages 210(-6)PFU/g, sows oral individually once daily for 5 days 2 g of the drug, previously diluted with boiled warm water.

The second group of sows ask oral individually once a day for 5 days on 2 g of the product prepared according to example 3, total concentration of CFU bacteria-probionts 600 million, the total activity of bacteriophages 210(-9)PFU/g, previously diluted with warm boiled water.

The third group of sows used as the control and prevention of gastrointestinal disease in suckling piglets spend their one-time treatment with antibiotics.

In the fourth group product manufactured according to example 3, total concentration of bacteria 180 million M. K., a total activity of phages 210(-6)PFU/g, set the pre-weaned piglets from 3 days of age, individually, oral reci

In the fifth group of the drug, manufactured according to example 3, total concentration of bacteria 600 million M. K., a total activity of phages 2 10(-9)PFU/g, set the pre-weaned piglets from 3 days of age, within 5 days individually, oral 0.5 g per head, pre-plant preparation with warm boiled water.

Piglets in the 6th group used as control and prevention of gastrointestinal diseases conduct a one-time treatment with antibiotics.

Accounting indicators carried out 12 days after the giving of drugs on the General preservation and increase in live weight of piglets.

The results obtained are presented in table 2.

The obtained data show that use of the drug "Pagosa" pregnant sows syndrome mastitis-metritis-agalactia contributes to enhancing the security of suckling piglets. The drug pre-weaned piglets under lactating sows syndrome mastif-metritis-agalactia enhances the natural resistance of piglets and increase their safety.

Thus, the drug has a prophylactic and therapeutic efficacy in intestinal dysbacteriosis, leading the group of Escherichia coli and increases the natural resistance of animals.

1. Probiotic preparation for veterinary use containing dry backass bifidobacteria, streptococci, aluminum oxide, aluminum hydroxide, carbohydrate lactose and/or sucrose and a filler, characterized in that it further comprises a dry culture of staphylococcal bacteriophage strains VGNKI 89/CMAI-FS-1-DEPT and VGNKI 90/CMAI-BS-2-DEPT in the following ratio of components, g/kg of the drug:

Dry backmask bifidobacteria content of 10 to 3000 billion, M. K. 1 g - 2,0 - 4,0

Dry backmask streptococci with a content of 10 to 3000 billion, M. K. 1 g - 2,0 - 4,0

Dry culture staphylococcal bacteriophage strains VGNKI 89/CMAI-FS-1-DEPT and VGNKI 90/CMAI-BS-2-DEPT activity 10(-9)- 10(-12)The FIGHT-g - 0,5 - 2,0

Carbohydrate - 20 - 40

Alumina - 30 - 60

Aluminium hydroxide - 100 - 300

Filler - Rest

2. The drug under item 1, characterized in that it contains bifidobacteria strain Bifidobacterium globosum VGNKI BF-4/DEPT of streptococcal strains of Streptococcus faecium VGNKI 27/11-IN-DEPT.

3. The drug under item 1, characterized in that the fillers it contains starch, milk powder, whey milk, whole milk powder, powdered sugar or food sugar.

4. The drug under item 1, wherein temte 2 - 4 g per 1 kg of the drug.

5. The drug under item 4, characterized in that acidophilus bacteria it contains Lactobacillus acidophilus AND-105-DEPT/VGNKI.

6. The drug under item 4, characterized in that it further comprises a dry culture of bacteriophages pseudomonads strains VGNKI 86/CMAI-A1-DEPT, VGNKI 87/CMAI-B2-DEPT, VGNKI 88/CMAI-C1-DEPT activity of each strain of 10(-9)- 10(-12)The FIGHT,

 

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