The invention relates to a preparation for rehydra- ting monogastric animals, including human beings, suffering from diarrhoea, especially non-infectious diarrhoea and diarrhoea caused by rota and corona viruses.

Even in well-organized agricultural countries with good veterinary coverage, the mortality among new -born animals such as calves and pigs is still very great. For example, in Denmark in 1980 there were destroyed about 180,000 calves, which corresponds to nearly 20 of the calves born every year. The cause of a number of the deaths among calves, and also of a number of corresponding deaths among sucking pigs, is that they become stressed when they are weaned and placed, for example, in common sties or folds. When the animals are removed and thus no longer receive mother's milk, right up to half of the animals devel¬ op diarrhoea because they become stressed due to change of fodder, transportation etc. It is assumed that half of the deaths are due to diarrhoea which arises within the first month after their birth. A number of the calves also suffer from rota and corona virus infection, which is a contagious intestinal infection where cows are virus carriers and infect the calves. The disease is caused by ia. strongly reduced production of lactase, so that the animals cannot decompose the lastose in the milk with which they are fed, and hereafter diarrhoea is quickly developed by osmotic effect in the intestinal canal.

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New-born calves and pigs with diarrhoea will lose considerably in weight because of dehydration and many die.

The object of the invention is to present a prepara¬ tion for the treatment of diarrhoea, so that a very large number of the sick animals can be cured in very few days, whereby deaths due to loss of fluid is avoided and for the calves a higher growth is obtain- ed.

This is achieved by composing the preparation as dis¬ closed in the characterising part of claim 1. Sur¬ prisingly, it has been shown that a mixture of an absorbent intumescent agent, lactose-decomposing enzymes and one or more electrolytes is a quick and effective agent against diarrhoea without any appa¬ rent side effects and with a better effect than with the individual components alone. The agent can be used for the treatment of diarrhoea among all offspring of ruminants as long as these are one-stomached, ie. before they have begun cud-chewing, and for the treat¬ ment of non-infectious diarrhoea and diarrhoea caused by rota and corona viruses among all other one-stom- ached animals, including human beings. The lactose- decomposing enzyme decomposes that lactose which, for example, a calf suffering from diarrhoea is itself unable to decompose and digest. Non-decomposed lactose in the intestinal canal contributes to worsening an attack of diarrhoea. With certain other methods of treatment, it has been suggested that the lactose be decomposed in the milk before the calf receives the milk, but with the preparation according to the invention, the lactose is not decomposed until inside

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the calf's stomach and intestine which results in fewer side effects, for example in the form of sitiophobia.

The agent is produced quite simply by weighing out and mixing the individual parts so that the finished agent is supplied as a dry powder ready for use.

Another great advantage of the preparation according to the invention is that it is possible to cure animals of diarrhoea without the use of normal anti¬ biotics, and thus avoiding the disadvantages here¬ with in the form of medicinal residues in the animal, and the possibilities of developing bacteria strains resistant to antibiotics.

According to the invention it is very advantageous that the electrolytes in the preparation comprise such salts that replace salt lost by diarrhoea since by rehydration it is merely necessary to administer a preparation which will bring about both rehydration or stop dehydration and provide the lost salts and fluid.

When as disclosed in claim 3 the preparation comprises a buffer, it is not necessary to protect the enzymes by adopting special measures since the preparation itself for a period of up to 6 hours stabilises the pH-value of the stomach so that the enzymes are not inactivated, and it is not necessary to wait for the dissolution of a coating or the like in the intestine, the enzyme being immediately ready to perform its function. Thus protective measures for the enzyme are also spared.

The component parts must be such which are pharmaceu¬ tically tolerable and a combination of the parts men¬ tioned in claim 4 makes it possible to fulfill the purpose of the present invention.

By composing the preparation as disclosed in claim 5 there is obtained a simple preparation which has the required properties, ie. stopping diarrhoea, provid¬ ing the necessary salts, providing lactase and bring- ing it uninfluenced through the stomach in a simple manner.

It is especially advantageous to compose the agent as disclosed in claim 6, the reason being that it has been shown that the absorbent vegetable fibres swell up in the intestine in a very suitable and natural manner, which gives the contents of the inte-stine a gelatinous consistency so that the faeces will have a normal consistency already a few hours after the first feeding with the agent. The more quickly that a diarrhoea from which a calf or sucking pig is suffer¬ ing is brought under control, the greater are the chances of the animal surviving. The glucose content and the necessary salts in the correct amounts will promote the absorption of nutrients and give the weakened animal an easily transformable energy.

Practical applications and experiments have shown that the agent according to the invention is par- ticularly effective when the fibres are seed coats as disclosed in claim 7.

The relation between the individual components in the preparation according to the invention can vary

greatly, but it has been shown that the optimum effect and protection of the enzymes is achieved if the individual components are used in the ratios as disclosed in more detail in claim 8. If this agent is used immediately when an animal shows the symptoms of diarrhoea, and it is a question of so-called problem stock, then the agent according to the inven¬ tion should be used in the event of the animal mere¬ ly refusing to drink up, and a case of diarrhoea can normally be stopped merely by treating the animal a few times. It is thus possible to put an immediate stop to the life-threatening loss of water and salts (electrolytes) so that by far the majority of the animals attacked will survive and be restored to health quicker than if they are only treated with electrolytes alone or the water palliative fibres alone. This quicker restoration of the animals will therefore bring about a better growth which has been proved by clinical experiments.

By composing the preparation as disclosed in claim 9, there is obtained a preparation which will stop diarrhoea among animals and provide rehydration since the preparation will only have to be mixed in water or milk or a water/milk mixture whereupon an animal will willingly drink it.

For human application the preparation is composed without roughage and dyestuffs but with a corrigent having the composition mentioned in claim 10, a composition as disclosed in claim 11 being particular¬ ly preferred since such a preparation is effective and at the same time has a pleasant taste.

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Since vegetable fibres as disclosed in claims 3 and 4 are expensive to use, it is possible to replace the organic absorbent intumescent with a synthetic intumescent in the carboxymethyl cellulose in dif¬ ferent configurations with various radicals and various metals can be used. Innumerable different carboxymethyl celluloses are known and all of these can be used, but with different effect, the reason being that they are available with both different viscosity and different rates of intumescence. The use of a synthetic intumescent results in a cheaper product, and generally with sufficient applicability.

The preparation according to the invention as dis- closed in claim 12 is used by pouring 40-55 g of the mixture into lukewarm water, milk or a water/milk mixture at around 38 C. The result is a mixture which the animals are very willing to drink and which quickly cures them of diarrhoea because the gel form- ed by the agent in the intestinal canal has the fol¬ lowing characteristics:

a) a protective effect on the actual intest¬ inal mucosa,

b) binds some of the bacteria and their toxins to itself,

c) ensures a normal intestinal passage (peristalsis) ,

d) quickly stops the loss of fluid and electrolytes,

e) buffers the capacity due to the added electrolytes in the gel formed, protects the added lactase from inactivation for up to ^β hours, and

f) the lactase decomposes the lactose in the intestine and thus recreates a normal osmotic balance.

For human application the same results as mentioned above will be obtained. If desired, cold liquid can be used for the preparation.

Practical experiment with the preparation according to the invention.

480 sucking calves, all of them two to three weeks old, were taken in for rearing experiments under uniform optimum conditions with regard to hygiene, climate and feeding, the object being to test the effect of the preparation on dietetic-conditioned diarrhoea among sucking calves.

By the first feeding after the calves taken in had been placed in the cow-house at the research station, all of the calves each received three litres of a conventional electrolyte/water mixture, after which this was gradually changed during the course of five days to up to 7 litres of milk substitute. The calves also had free access to hay and ordinary fodder supplements.

During the course of fourteen days from the time they were taken in, 86 of the calves, ie. 17. $, contract- r ¹ .

ed stomach/intestinal disturbances. These animals were immediately treated with the preparation accord¬ ing to the invention and as disclosed in claim 12.

73 of the sick calves, ie. 84.9$, were completely cured within a few days. The 13 calves which were not cured immediately by the treatment were then given supplementary treatment with antibiotics.

From this it will be seen that the diarrhoea which is contracted early by many calves fattened on full milk and by sucking pigs is often due to virus infections and to transport stress, stress as a result of feeding change and stress from changed environment etc. , and can therefore be cured with the preparation according to the invention without the use of antibiotics. Only 13 animals out of 86, ie. approx. 15 % , required supplementary antibiotic treat¬ ment.

Course of treatment when using the preparation.

The agent is mixed in water and is dosed in accord¬ ance with the weight of the animal, the amounts used being as stated in the following table:

Weight of Dose per No. of feeds animal feeding per 24 hours approx. 20 kg \ 1 water + approx. 25g 4 - 30 kg 1 1 - + approx. 50g 4

40 kg 11 1 - + approx. 75g 3-4

50 kg 2 1 - + approx. lOOg 3

60 kg 2 \ 1 - + approx. 125g 3

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After the first twenty-four hours, it can be an ad¬ vantage to add 25-50 g curdled milk product, for example soured milk, yoghurt, junket or the like, per litre. From the third day, one can gradually change over to the normal mixed fodder.

There are also cattle stock among which stomach/ intestine disturbances are a recurrent problem. In such cases it can be an advantage to give for example the calves the preparation according to the invention as soon as they just refuse to drink up the normal feed, for example consisting of full-cream milk or other milk mixtures or the like.

Comparative experiment

The curative properties against diarrhoea of the preparation according to the invention were compared by a controlled experiment with the properties of Calmix neo at a Dutch calf fattening station.

For the experiments there were used in all 230 calves which were divided in 5 groups of 46 animals each. They were placed in wooden pens with floor grating and being ventilated. One week old calves were used. The animals were weighed before the experiment, after 29 days and after 58 days. At the beginning there is given 1.5 i water and 75 g electrolytes as first feeding. The fodder consisted of a bag of Heftica per calf followed by Hemeka start and fattening accord¬ ing to the usual schedule.

In case of diarrhoea either the preparation accord¬ ing to the invention or Calmix neo is given.

The experiment results are given in the table below.

Average results Conservative Preparation Curative treatment treatment according to (Calmix neo) the invention

No. of calves 15 15 Average weight at start 41.6 kg 38.3 kg after 29 days 47.5 kg 45.3 kg 58 days 74.4 kg 73.7 kg

Average weight after 29 days 5.9 kg • 7.0 kg 58 days 32.8 kg 35.4 kg

Average weight after 29 days 5.9 kg 7.0 kg

29-58 days 26.9 kg 28.4 kg

Average Weight/day after 29 days 203 g 241 g

59 days 565 g 610 g

The curative properties of the preparation prove to be good. After 58 days the calves showed an average of 2.6 kg larger growth than the control group which was treated with Calmix neo. Moreover, the average weight per day among the animals which were treated with the preparation according to the invention, increased in the second period more than the animals treated with Calmix neo. This shows that not only are the absorption and the digestive capacity of the intestine less influenced but they are at the same

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time more quickly recreated. This result supports the fact that the pharmacokinetics of the preparation according to the invention builds on a protection of the intestinal wall against pathogenic attacks coupled with a compensation for lack of lactase by means of acid resistant lactase whereby the secre¬ tion as well as the osmotic component are combatted.

Example 1

The preparation according to the invention can be composed, for example, as follows:

1000 g contains: Magnesium oxide 5.75 g

Citric acid 13.50 g

Potassium chloride 24.00 g

Sodium citrate 26.50 g electrolytes

Sodium chloride 41.50 g Sodium bicarbonate 68.00 g

Glucose 350.00 g

Terra rubrum 2.50 dyestuff

Wheat bran 68.00 g roughage

Isphagola husk

(dried seed coats of plantago ovata) 400.00 g absorbent fibre

Lactase 0.25 g enzyme

Total 1000.00 g

The invididual ingredients, all of which are avail¬ able as dry powders, are mixed mechanically and are thereafter immediately ready for use.

The agent according to the invention must not be administered in dry form, butmust be suspended in water and administered as a solution or suspension. The intumescence occurs hereafter in the intestinal canal during a suitable period, whereb.y by absorption of fluid said intumescence swells up and gives the contents of the intestine a suitable consistency, and binds and receives some of the bacteria and their toxins so that a diarrhoea is at one stopped.

Example 2

The preparation according to the invention can also have the following composition which is particularly preferred for human application:

1000 g contains

Magnesium oxide 6.17 g

Citric acid 14.50 g

Potassium chloride 25.75 g

Sodium citrate 28.45 g

Sodium chloride 44.56 g

Sodium bicarbonate 73.00 g

Glucose 375.80 g

Isphagula husk, crushed . 429.50 g

Lactase 0.27 g

Oil of peppermint 2.00 R

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^_^ATlθ ^J

Example 3

A suspension or solution of the preparation prepared in example 1 is produced by mixing 50 g preparation to 1 liter of water. The pH-value in the fresh prep¬ aration is 8.56. By filtration to a pH-value of 5.73 there is used 40.5 meq hydrochloric acid which shows that there is a not inconsiderable Buffer effect in the preparation which will "neutralise" the hydro- chloric acid in the stomach and consequently protect the lactase. -

The chemicals used in the examples are ordinary commercial chemicals and the lactase is preferably CHBS lactase 25.000 from Chr. Hansens Laboratorium, Copenhagen.