CS218148B1 - A preparation for increasing the resilience of farm animals - Google Patents

Abstract

This is an instant, quick-to-use preparation with controllable ingredients, allowing for rapid creation of immunoglobulin reserves when administered orally — and thus the defense of young farm animals against infectious diseases. The preparation uses cheap mixed gammaglobulin of low electrophoretic purity, obtained from slaughter blood. The enzymatic activity of young animals is inhibited by an industrial-grade trypsin inhibitor obtained in the production of therapeutic and diagnostic preparations. Similarly, industrial-grade emulsifier C is used. The preparation can alternatively be used in livestock breeding against infectious diseases of young animals. It can also be used as a preventive agent against infectious diseases of young animals of some mammals.

Description

BACKGROUND OF THE INVENTION The present invention relates to an instant preparation for increasing the resistance of livestock.

In addition to improving hygiene and other breeding conditions, vitamin and complex nutrition, the way of transition to plant nutrition, etc., a very important factor in increasing the resistance of infants to infectious diseases is to reduce losses caused by the death of livestock.

Born livestock begin to develop relatively late to defend against antigens pathogenic microbes causing serious infectious diseases. For example, calves begin to produce their own immunoglobulin only four weeks after birth and their full blood serum levels can only be ascertained eight weeks after birth.

In a short period of time after birth, the pups have the ability to receive immunoglobulins (calves, kids and lambs within 24 hours, piglets within 36 hours after birth) by the gastrointestinal tract.

Due to the quantitatively and qualitatively different content of immunologlohulins in the colostrum of individual females, an important factor for timely strengthening of insufficient or incompletely developed immunological reactions of pups - administration of immunoglobulins through the digestive tract.

Intensive research into the transmission of passive immunity from mother to infant for more than 70 years has yielded clear conclusions. For example, T. Smith and RB Little, in 1922, reduced colostrum-free calves by administering orally or intravenously blood serum of adult animals ("Cow serum as a substitute for colostrum in the new born calves" by Younnal exper. Media. 36 , 453-468).

The passage of immunoglobulins from the blood serum of adult animals into the bloodstream of calves through their gastrointestinal tract was later proven by CP Millstein and A. Feinstein (“Structural differences and similarities between two bovine immunoglobulins Ig-G1 and IG-G2”, ARC Institute of Animal Physiology, Babraham, Cambridge, Report for 1966-1967, p. 41).

The time of transmission, passive immunity of the gastrointestinal tract of the infant was also clearly identified. E.g. TW Brambell establishes this period for bovine animals 24 hours after birth, for pigs for 86 hours, for sheep, goats and horses for 24 hours, for dogs and cats for 1 to 2 days. "North Holland Publishing Company" , Amsterdam, London 1970).

Regarding the production of the baby's own antibodies, for example, RG Hansen and PH Phillips between 1947 and 1949 found that individual fractions of calf serum proteins that were not fed with colostrum reached normal levels only 8 weeks after birth and that they did not produce calves within 4 weeks after birth. own antibodies at all. ("Studies on proteins from bovine colostrum", Yournal biol. Chem. 179: 523-5217).

Also important is the finding in 1961 by JT Huber, NL Jakobson, RS Allen, PA Hartman that the activity of the digestive enzymes of born calves (pancreatic amylase, lipase and protease) is lowest in the first days after birth, increases during the week and changes later only slightly ("Digestive enzyme activitis in the young Calf", Yournal Dairy Sci, 44, 1491-1531).

Based on research findings, a number of products are produced both in the world and in the Czech Republic, which are intended to transmit immunoglobulin to the gastrointestinal tract of newborn livestock.

SUMMARY OF THE INVENTION The present invention is based on the convenient composition of the formulation, the ease of use, the controllability of the individual components of the formulation and its method of manufacture.

The composition of the preparation prevents both the possibility of denaturation of immunoglobulins during manufacture and use. Serum gamaglobulin produced from the serum of normal slaughter animals is used as the active ingredient. The instant form ensures easy solubility of the preparation in safe water or physiological saline solution and thus easy and quick use at any hour in operating agricultural conditions without expert veterinary supervision. ·

The composition of the instant mixture for various alternative uses respects the need to prevent the cleavage of the immunoglobulins in the gastrointestinal tract of the pups, thereby permitting their passage into the bloodstream.

By its nature, it is a preparation enabling the application of gnotobiological and other knowledge, since the instant mixture has individual components controllable. The essence of the preparation allows its easy and quick (in a limited time) administration of the preparation.

It is used in addition to globulin blends made cheaply from slaughter blood also in some cases specific globulins of immunized animals. Gamaglohulins of lower electrophoretic purity and lower titers of active antibodies (no concentration) may be used, but do not interfere with the addition of albumin and other fractions contained in the blood serum.

The preparation consists of microbiologically safe skimmed, gently dried milk, simple potins, monosaccharide and conditionally also some other additives, allowing very fast wettability and solubility of the dried preparation in lukewarm safe water.

The basic medium is supplemented with various kinds of simple proteins (mixed or specific immunoglobulins, namely gammaglobulins (bovine, sheep, goat or pig).

Like globulins, monosaccharide (D glucose) permeates the digestive tract without the necessary cleavage, as is the case with lactose, sucrose or maltose.

The monosaccharide is added to maintain an elevated plasma globulin ratio. The aim is to ensure that in the case of prolonged digestion (starvation) the content of globulins in blood plasma (when increasing the albumin content) does not decrease.

Denaturing of immunoglobulins is avoided in the manufacture, storage and use of the product. High temperature, acids, bases or salts of heavy metals by irreversible process · Denaturation causes loss of biological properties of proteins, preparations containing enzymes or its residues break down proteins.

Therefore, inhibition of trypsin is provided in various formulation alternatives.

Depending on the application, different product types are produced, depending on the types of globulins (bovine, ovine, caprine, porcine) and the titer of active antibodies (immunoglobulins), mixed or specific preparations.

By its nature, it is a preparation that allows rapid replenishment of immunoglobulin stocks as a suitable supplementary feed used at several-hour intervals shortly after the birth of the baby. Therefore, it is not a therapeutic or preventive treatment with precisely marked liters of active antibodies.

Preparations for increasing the resistance of young livestock in the dried state (according to alternatives to use) contain skimmed milk in an amount of 703.8 to 860.2 parts by weight

D-glucose in an amount of 32.5 to 48.75 parts by weight of starch syrup in an amount of up to 2.5 parts by weight of emulsifier C in an amount of 0.675 to 0.825 parts by weight of gatomaglbulin mixed in an amount of 4.5 to 9 parts by weight of sodium hydrophosphate in an amount of 0.133 to 1.47 parts by weight or other ingredients (vitamins, amino acids, etc.), characterized in that it contains (bovine) gamma-globlobulin mixed from low-electrophoretic purity (90 to 95%) carcass blood in an amount of 4.5 to 9 parts by weight, trypsin a soybean or bovine lung inhibitor or other industrial grade 140 UI BAEE 1 mg inhibitor in an amount of 0.060 to 0.24 parts by weight, or lyophilized porcine colostrum and emulsifier C in an amount of 0.675 to 0.825 parts by weight.

The composition according to item 1, characterized in that it additionally contains lycfilis (bovine). colloid in a volume of 20 to 30 parts by weight. It is further characterized in that it is an end-use form alternatively for the various uses of the manufactured preparation with all non-harmful controllable ingredients, the instant ability of which at the same time allows immediate and repeatable rapid administration of the preparation to born livestock under normal operating agricultural conditions.

The method of producing the composition, for example, for born calves, is carried out in a conventional operating manner by concentrating the milk after the bacteriological testing with the addition of D-glucose, emulsifier C and sodium hydrogen phosphate to 50% (+ 5% dry matter). The starch scab is added by mixing and dried gently in a spray drier.After cooling, instantization and safety tests carried out in the usual manner, the further process is characterized in that the second stage of preparation of the product is carried out so as to maintain the expiration period of the final product. is thoroughly mixed with lyophilized gamma globulin, a trypsin inhibitor, lyophilized colostrum and optionally other ingredients with maximum heating of the mixture to 30 ° C.

The preparation useful for supplementation of the immunoglobulins to the young gastrointestinal tract has several alternatives depending on the method of use, in particular it serves to supplement the immunoglobulins contained in the colostrum or whether there is a harmless lyophilized colostrum or whether the preparation is to replace the colostrum completely in healing farms. product intended for quick delivery of a baby at night.

The basic variants and their variations can be used in laboratory or industrial production of the product for individual animal species: calves (with bovine serial or mixed gammaglobulin serial), lambs (with sheep serum gammaglobulin), kids (with goat serum gammaglobulin), piglets (with gammaglobulin pigs), foals (with gammaglobulin · horse), dogs (with dog blood serum gammaglobulin), etc.

An example of a conventional, inexpensive calf preparation made by laboratory and industrial methods.

Composition:

a) laboratory, production of 10 batches

7820 g skimmed milk (treated and obtained in the prescribed manner)

325 g D glucose 25 g starch syrup

7.5 g emulsifier C g bovine gammaglobuhn mixed lyophilized

0.7 g trypsin inhibitor (140 UI - - BAEE / 1 mg)

b) industrial, production of 1 000 batches

7.82.10 ⁶ g skimmed milk (treated and obtained as prescribed)

32.5 .104 g glucose. ΙΟ ³ g emulsifier C. 1Ό ⁴ g bovine mixed gammaglobulin. ² g trypsin inhibitor (140 µl)

BAEE]

1. Milk (treated and prepared as prescribed) after bacteriological testing with addition of D glucose and emulsifier is concentrated to 50% (+ 5% dry matter) in evaporators.

, 2. Starch syrup is added to the thickened mixture by mixing and spray dried gently.

3. After cooling and instantization, a quality and bacteriological safety test (according to the standards of the human dried product) is performed.

4. Preferably, at a shorter time before removal, the preform is intimately mixed with lyophilized bovine gatomaglobullin. Product requirements (dried medium):

the product must have a clean intact packaging sealed and marked with a clear date of manufacture, bj yellow to light brown, • cj flowing consistency, mixed particle size, free of foreign matter, dj maximum contents per 1000 g dry matter:

copper 2 mg, tin 2 mg, lead 1,5 mg, (e) microbiological requirements:

total number of microorganisms in 1 g dry matter not more than 100 000 number of peripheral microbes in 1 g dry matter not more than 20 The product must not contain pathogenic and toxinogenic organisms, f j Mohr wettability at 40 ° C ... 60 s

(g) per 100 g of dry matter there are approximately 22 g of protein, 35 g of milk sugar, 32 g of glucose, 1 g of fat, 4 g of water and 6 g of minerals and other substances,

h] physico-chemical analyzes are performed according to ČSN 570 105, microbiological analyzes according to methodology ČSN 57 0101, also sampling, number and type according to examination of dried products industrially manufactured according to ČSN 570 101.

Mixing of the final product

When mixing, care must be taken not to heat the product to more than 30 ° C. When mixed well in a mixer, the mixture is filled into hygienic containers. The base medium (semi-finished product) is intimately mixed with lyophilized gammaglobulin or other ingredients such as trypsin inhibitor, lyophilized colostrum, vitamins, amino acids, etc. Substances containing or forming bases, acids or resulting from enzymatic cleavage cannot be used.

Properties of individual raw materials:

Milk

a) for the laboratory preparation of the product (in smaller quantities) it is appropriate to use milk from healthy, well-fed cows (preferably cows milked immediately after weaning) the milking is carried out in such a way as to ensure milk hygiene before preparation (for uniformly used by mixing in the prescribed ratio with gammaglobulin and D-glucose, it is necessary to store at 0 ° to-3 ° in closed sterile containers the milky acid must not exceed 8.0 ° SH no preservatives should be used (nor H2O2 hydrogen peroxide), lyophilization may be used if necessary.

a bacteriological safety test is performed

b) For industrial processing it is necessary to use milk from healthy well-fed cows (for production of 10 000 pieces of product it is necessary to milk milk for 1 day and about 800 cows), animals must be treated hygienically, milking must be done in well washed containers the milk must be delivered quickly for processing in the washed containers and cooled so that its temperature does not exceed 3 ° C the acidity of the milk must not exceed 8.0 ° SH, only H2O2 hydrogen peroxide can be used as a preservative milk is skimmed for fat content 0.5% pasteurization is performed just prior to drying or lyophilization

Glucose (hexose)

Crystalline or recrystallized D-glucose (only enzymatically produced glucose cannot be used) is used for the preparation, as follows:

dry matter at least ash in dry matter at most titration acidity ml N / 10 lye per 5 g dry matter most clarity maximum copper (Cu) content at most mg / kg coliform microorganisms per g maximum at cultivation in masopepton agar (30 ° C) sporadic or other non-pathogenic microbes in 1 g not more than%

0,0í8%

0.30 80% of the production must be technologically safe water (without above-average contents of sodium (Na), potassium (K) and magnesium (Mg)

Starch syrup

It is a constituent of the preparation by which dry matter at least ash in dry matter at most titration acidity ml 0.1 N NaOH per 100 g dry matter at most pH (dilution with water 1: 3) copper in mg 1000 g maximum (Cu) mercury (Hg), Zinc (Zn), Lead (Pb), in 20 g sulfur dioxide (SO2) in mg / 1000 g at most, in the case of poor syrup quality, omit without substitution another raw material produced by hydrolyzing potato (maize or wheat) starch in the presence of oxalic or sulfuric acids. Hydrolysate perfectly neutralized by float chalk is refined, thickened and dried,%

0.4%

4.7 to 5.4

Sodium dibasic phosphate (Na2PO4.1H2O)

Other harmless stabilizers may be used, however, taking into account that acids and bases are not suitable.

Food grade quality labeled 'clean' in industrial manufacturing (blending protects skin with clothing and gloves, eyes with chemical goggles and lungs with a dust fan. It is not possible to eat, drink and smoke in the workplace and observe personal hygiene rules) In the preparation of the preparation, due to its slight solubility, the stabilizer is first dissolved in the skimmed milk in the prescribed ratio. After dissolution, it is added to the other media components ready for concentration and drying. Emulsifier C is used in normal market quality supplied for food purposes. It shall comply with the following requirements:

monoglyceride content 30% water content maximum 1% acid value maximum 10 melting point minimum 40 ° soap content 0

Bovine gammaglobulin (mixed) may be used in a commercial product of low electrophoretic purity mixed with other fractions of bovine serum.

preferably alcohol fractionation 90 to 95 ´% bovine serum aminoacetic acid mg 140 UI BAEE A = 253 η M purification electrophoretic purity source stabilizer tripsin inhibitor (in soybeans or bovine

Lung)

Product packaging The final product is filled into NTN bottles or, in cases where there is no further storage, in sterile paper folding boxes with an inner weld bag, in closed thermoplastic coated plastic film bags or in other functionally satisfactory packaging. The packaging must indicate the weight, method of dilution and preparation, method of storage and method of use.

Storage of freeze-dried parts (gammaglobulin, co sharp) is well assured at -18 ° C for 3 years, dried medium in the dark and dry at 2 ° C to 5 ° C for 1 hour. storage temperatures of up to 5 ° C are six months and it is recommended that the product be used within 14 days under refrigerated conditions.

When giving birth to a baby! calves must be observed all hygiene rules and when heating the mixture to ensure that the temperature is not exceeded and thus the denaturation of small proteins and their biological properties are lost.

Depending on the conditions of use, the preparation may be administered in various ways:

Method 1 (administration of the product with fresh or lyophilized colostrum) The dose of the preparation is mixed into 1 liter of colostrum (colostrum) while stirring, the colostrum container is immersed in a water bath of approximately 40 ° C so that the colostrum temperature is maintained between 35 ° to -37 ° C and did not fall below 30 ° C when administered to calves. Care must be taken not to exceed the specified temperature.

The calves are supplied with a rubber teat bottle with an aperture approximately 7 mm in diameter. Bottles and teats must be cleanly washed with hot water with the addition of cleaning agents and again thoroughly rinsed with clean water.

2. the method with safe water of the specified temperature is administered to the weaned calves or at the time of interruption of the feeding by their own mother.

The dried preparation is mixed with a safe warm line to a maximum temperature of 40 ° in a ratio of 1 dose of the preparation and 400 g of safe water or physiological solution.

(Administration of the product to calves as in bottle 1.

3. in cases where heated colostrum or wholesome water to a prescribed temperature cannot be ensured in other cases, the product may be administered in portions in a gelatin or wafer-free (sucrose-free) wafer by pressing against the root of the animal's tongue.

Duration of administration of single doses to calves born:

(usually served 3 times in a row)

1. 2 doses (exceptionally 1 dose at night) within 2 hours after delivery

2. 2 doses within 7 hours after delivery

3. 1 dose up to 12 hours postpartum, ie up to 5 doses up to 12 hours postpartum.

Delay of this dosing cycle is possible by a maximum of 3 hours. Except for the first batch where no delay is possible at all.

Product for other livestock species

The base medium of the formulation is the same as bovine medium. Preparations for different types of pups vary

(a) a type of mixed or specific gammaglobulin. E.g. gammaglobulin sheep, goat, pig, horse, dog, cat

(b) by weight of the product to be administered, per kg of 1 ml of calf 2 (+ 5 ° / o) g of dried product

c) the time period of administration of the preparation (e.g., in piglets is 2 hours after birth, after 8, 14, 16 16, 32 hours at a maximum delay of 4 hours).

product mixed in the prescribed ratio

Claims (2)

SUBJECT A preparation for improving the resistance of young livestock in the dried state, comprising milk in an amount of 703.8 to 860.02 parts by weight, D-glucose in an amount of 32.5 to 48.75 parts by weight, emulsifier C in an amount of 0.675 to 0.825 parts by weight, stabilizer preferably sodium hydrogen phosphate in an amount of 0.133 to 1.47 parts by weight, or starch syrup in an amount of up to 2.5% by weight parts and, optionally, other invention sets, in particular vitamins and amino acids, characterized in that it contains bovine gammaglobulin mixed or specific with an electrophoretic purity of 90 to 95% in an amount of 4.5 to 9 parts by weight, a trypsin inhibitor from soybeans or bovine lungs, optionally another industrial grade inhibitor in an amount of 0.060 to 0.24 parts by weight. 2. The composition of claim 1 further comprising lyophilized colostrum in an amount of 20 to 30 parts by weight.