NZ526114A - Compositions for animal treatment - Google Patents

Abstract

Disclosed are oral compositions for increasing milk production in lactating animals and/or treating/controlling infective diarrhea, the composition including a nutritional support product selected from milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels, blended powders, or combinations thereof, and between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides.

Description

52 6 1 1 4 Intellectual Property Office of NZ 2 3 m 2003 RECEDED Patents Form No. 5 Our Ref: BRP504373 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION DIVISIONAL OUT OF NZ 515869 ANTE-DATED TO 2 DECEMBER 2002 COMPOSITIONS FOR ANIMAL TREATMENT We, MED-CHEM INGREDIENTS LIMITED, a New Zealand company of CI- Alliott Thompson Francis Ltd, Level 2, 25 Teed Street, New Market, Auckland, New Zealand hereby declare the invention, for which We pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement: PT053657348 BRP'.MAG 300096838_1 2 COMPOSITIONS AND METHODS FOR ANIMAL TREATMENT FIELD OF THE INVENTION The invention relates to the use of indigestible oligosaccharides to improve the health and productivity of ruminant animals and to an oligosaccharide composition of use in such a method. In one aspect in particular the invention relates to the use of gluco- and/or isomalto-oligosaccharides to treat/control 10 infective diarrhea in ruminant animals and to a composition of use in that treatment/control. Further, in another aspect the invention relates to a method of increasing lactation in animals, and in particular adult bovine animals, via the use of gluco- and/or isomalto-oligosaccharides and to a composition of use in such a method.

BACKGROUND Bacterial and viral infection of the digestive tract in newborn and adult animals, resulting in the onset of infective diarrhea, is a significant cause of animal 20 fatality, animal health risk and cross infection to the human population. There is a significant economic impact on the agricultural sector from reduced natural production and disease and health control costs. Traditional methods of dealing with these infections include the use of antibiotic preparations and remedial electrolyte compounds that are administered as injectable or oral 25 drenching solutions. Such methods can be expensive and can be difficult to administer, particularly for animals grazed in remote pastures. In addition, there is a move away, in some sectors of the agricultural community, from antibiotic use to more natural, non-invasive, treatment methods.

There is also a desire to maximise milk production, in dairy herds in particular, in order to maximise economic returns to the farmer. Therefore the ability to assist in increasing milk production would also be a desirable aim. 3 The ability to provide an alternative method of improving the health and production of ruminant animals and/or compositions of use in such a method will have a clear economic benefit to the farming community.

OBJECT OF THE INVENTION It is one object of the invention to assist in the improvement of the health and production of ruminant animals.

It is an alternative object to assist in increasing milk production in lactating ruminant animals and/or to assist in the treatment/control of infective diarrhea in ruminant animals.

SUMMARY OF THE INVENTION According to an aspect of the invention there is provided an oral composition for increasing milk production in lactating animals and/or treating/controlling infective diarrhea, the composition including a nutritional support product selected from those including milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels or blended powders, and between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides.

Preferably the gluco and/or isomalto oligosaccharide is present in an amount of between about 300 and 5000 ppm or, more preferably between about 300 and 1000 ppm.

Preferably the nutritional support product is a water gel system.

Preferably the water gel system is thermostable.

Preferably the thermostable water gel system is capable of passing through the rumen gut.

Preferably the water gel system includes Trehalose. 300407193-1 intellectual Property Offine of M.Z. 19 MAY 2005 RECEIVE Preferably the water gel system includes a hydrocolloid and Trehalose.

Preferably the water gel system includes a hydrocolloid selected from any one or more of kappa carrageenan, Xanthan Gum or Gum Acacia.

Preferably the water gel system includes inorganic mineral salts, attractant and other additives.

According to another aspect of the invention there is provided an oral composition for increasing milk production in lactating animals and/or treating/ controlling infective diarrhea, the composition including between about 7-15% of gluco- and/or isomalto-oligosaccharides, 2.0 - 6.0 % Trehalose, about 1.2 -4.7% hydrocolloid, and water.

Preferably the hydrocolloid in the composition is selected from any one or more of kappa carrageenan, Gum Acacia, or Xanthan Gum.

Preferably the composition contains 1.0- 3.5% kappa carrageenan, 0.2 - 0.7% Gum Acacia, 0 - 0.5% Xanthan Gum.

Preferably the composition contains excipients including any of the following inorganic mineral salts, vitamins, attractants and other additives.

According to a further aspect of the present invention there is provided an oral composition for the treatment or control of the effects of viral infections, the composition including a nutritional support product selected from those including milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels or blended powders, and between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides.

Preferably the viral infection is caused by Rotavirus or Coronavirus.

According to a further aspect of the present invention there is provided the use of a composition including a nutritional support product selected from those including milk, reconstituted milk, milk replacer, water, fortified water, electrolyte 300407193-1 solutions, water gels or blended powders, and between about 150 and 5000 ppm of gluco- and/or isomalto-olgosaccharides in the manufacture of a medicament for the treatment or mitigation of the effects of viral infections.

According to a further aspect of the present invention there is provided the use of a composition including between about 7% and about 15% of gluco- and/or isomalto-oligosaccharides in the manufacture of a medicament for the treatment or mitigation of the effects of viral infections.

Preferably the viral infection is caused by Rotavirus or Coronavirus.

According to a further aspect of the present invention there is provided an oral composition for increasing milk production in lactating animals and/or treating/controlling infective diarrhea, the composition including a nutritional support product selected from those including milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels or blended powders, and hydrolysed dextrin, the hydrolysed dextrin including between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides.

Further embodiments will become apparent from the following description and drawings.

Intellectual Property Office of M.Z. 300407193-1 6 preferably between about 300 and 5000 ppm and more preferably between about 300 and 1000 ppm.

According to another aspect of the invention there is provided a method of 5 treating/combating infective diarrhea in ruminant animals including the step of orally administering to the ruminant animal a composition containing an effective amount of a gluco- and/or isomalto-oligosaccharide.

Preferably the composition also includes a nutritional support product.

Preferably the nutritional support product is selected from milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels or blended powders.

Preferably the nutritional support product is a water gel system.

Preferably the water gel system is thermostable.

Preferably the thermostable water gel system is capable of passing through the 20 rumen gut.

Preferably the amount of indigestible oligosaccharide is administered to the animal at a daily rate of between about 2-60 grams.

Preferably the amount of indigestible oligosaccharide is administered to the animal at a daily rate of between about 5-30 grams.

Preferably the amount of indigestible oligosaccharide is administered to the animal at a daily rate of between about 10-30 grams in bovine animals and 30 about 2-20 grams for ovine animals.

Preferably the amount of indigestible oligosaccharide is administered to the animal at a daily rate of between about 15-25 grams in bovine animals and about 5-10 grams for ovine animals. 7 Preferably the indigestible oligosaccharide is present in the composition in an amount of between about 150 and 5000 ppm, more preferably between about 300 and 5000 ppm and more preferably between about 300 and 1000 ppm.

Preferably the method treats infective diarrhea caused by E. coli, ETEC, EPEC, EHEC, EIEC, Salmonella, Salmonella Brandenburg, Listeria monocytogenes, Clostridium perfringens. Campylobacter, Staphylococcus aureus, Streptococcus, Rotavirus, Coronavirus, Cryptosporidia.

Preferably the method treats infective diarrhea caused by E. coli and/or Salmonella Brandenburg.

According to another aspect of the invention there is provided a composition for increasing milk production in lactating animals and/or treating/controlling 15 infective diarrhea, the composition including a nutritional support product and between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides.

Preferably the gluco and/or isomalto oligosaccharide is present in an amount of between about 300 and 5000 ppm or, more preferably between about 300 and 20 1000 ppm.

Preferably the nutritional support product is a product such as milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels or blended powders.

Preferably the nutritional support product is a water gel system.

Preferably the water gel system is thermostable.

Preferably the thermostable water gel system is capable of passing through the rumen gut.

Preferably the water gel system includes Trehalose.

Preferably the water gel system includes a hydrocolloid and Trehalose. 8 Preferably the water gel system includes any one or more of kappa carrageenan, Xanthan Gum or Gum Acacia.

Preferably the water gel system includes inorganic mineral salts, attractant and other additives.

According to another aspect of the invention there is provided a composition for increasing milk production in lactating animals and/or treating/controlling infective diarrhea, the composition including between about 7-15% of gluco-and/or isomalto-oligosaccharides, 2.0 - 6.0 % Trehalose, about 1.2 - 4.7% hydrocolloid, and water.

Preferably the hydrocolloid in the composition is selected from any one or more of kappa carrageenan, Gum Acacia, or Xanthan Gum.

Preferably the composition contains 1.0 - 3.5% kappa carrageenan, 0.2 - 0.7% Gum Acacia, 0 - 0.5% Xanthan Gum.

Preferably the composition contains excipients including any of the following inorganic mineral salts, vitamins, attractants and other additives.

Further embodiments will become apparent from the following description and drawings.

BRIEF DESCRIPTION OF THE FIGURES The invention will now be described with reference to preferred embodiments of the invention depicted by way of example in the following figures.

Figure 1: A graph showing the incidence of scouring in calves that were orally administered a preferred composition as described herein, in comparison to control calves. 9 Figure 2: A graph showing the milk volume produced by bovine animals that were orally administered a preferred composition as described herein, in comparison to control bovine animals.

Figure 3: A graph showing the total milk fat in milk produced by bovine animals that were orally administered a preferred composition as described herein, in comparison to control bovine animals.

Figure 4: A graph showing the total milk protein in milk produced by 10 bovine animals that were orally administered a preferred composition as described herein, in comparison to control bovine animals.

DETAILED DESCRIPTION OF THE INVENTION The benefits of increasing the health and well being of farm animals, such as ruminants, is readily apparent. Many of the health problems with such animals develop from the gut which can develop parasite loading as well as bacterial and viral infections that can result in an increased occurrence of afflictions such 20 as infective diarrhea. Products are available to treat such afflictions but, these products are in general expensive (both in terms of the products themselves, and the labour required to administer them), invasive, and involve the use of antibiotics and/or electrolyte solutions.

The invention is broadly directed to methods and compositions for increasing the health and production of ruminant animals. In particular the invention seeks to reduce the incidence of problems such as infective diarrhea by using alternative non-invasive methods to antibiotic treatment and the like.

Essentially this involves feeding the animal with gluco- and/or isomalto-30 oligosaccharides at an amount effective to treat or control infective diarrhea that can ultimately lead to the death of the animal.

It has been surprisingly found that oral administration of gluco- and/or isomalto-oligosaccharides to ruminants as a food or food additive composition, 35 substantially reduces the incidence of infective diarrhea and associated health problems and substantially increases the production capability of animals.

Thus the invention in another aspect can be seen to be a method of reducing the incidence of infective diarrhea by orally administering to the animal an effective amount of gluco- and/or isomalto oligosaccharides.

In particular, it has also been surprisingly found that oral administration of gluco- and/or isomalto-oligosaccharides has the effect of increasing the milk production of adult lactating cows. Thus the invention in another aspect can be seen to be a method of increasing milk production by orally administering to the 10 animal an effective amount of gluco- and/or isomalto oligosaccharides.

Gluco-oligosaccharides and isomalto-oligosaccharides are a group of carbohydrates that resist the processes of acid and enzyme hydrolysis in the digestive tract but which are selectively fermented by mainly lactobacillus and 15 bifidobacterium. Such gluco- and/or isomalto-oligosaccharides are together referred to in this description as "functional carbohydrates" for ease of reference.

Gut populations of microbiota include toxigenic organisms such as Escherichia 20 coli, Salmonella Brandenburg (known to be associated with spontaneous abortion in sheep), pathogens like Clostridia and proteolytic bacteriocides; as well as beneficial flora including bifidobacteria and lactobacillus.

Beneficial gut flora carry out saccharolytic fermentation of carbohydrates to 25 produce short chain fatty acids which are further metabolised, or used to stimulate further growth of a limited number of colonic bacteria. Metabolic process products include vitamins and natural antibiotics. An increase in the beneficial microflora also reduces the population of harmful bacteria by a process referred to as competitive exclusion.

Proteolytic fermentation is carried out by pathogenic and toxigenic bacteria to produce mainly phenols, amines and ammonia all of which are toxic. A reduction in these bacteria by either intervention from naturally produced antibiotics or by competitive exclusion reduces the level of digestive toxins 35 absorbed back into the body with an immediate health consequence to the 11 animal. Non-limiting examples of such bacteria include E. coli, ETEC, EPEC, EHEC, EIEC, Salmonella, Salmonella Brandenburg, Listeria monocytogenes, Clostridium perfringens. Campylobacter, Staphylococcus aureus, Streptococcus. Non-limiting examples of other pathogens causing 5 complications in the animal's gut include Rotavirus, Coronavirus, Cryptosporidia.

The use of functional carbohydrates to increase the amount of beneficial bacteria and increasing saccharolytic fermentation in the gut is a non-invasive 10 method of treating and regulating intestinal gut function by increasing the competitive advantages of beneficial bacteria and by using the metabolic process products of saccharolytic fermentation.

By feeding the animal functional carbohydrates, a variety of beneficial 15 processes seem to be stimulated in the gut of the animal resulting in a treatment effect on bacterial and viral infections with a consequent reduction in fatality and an increase in animal weight gain and production to a greater extent than would be expected.

Additionally, the degradation products of saccharolytic fermentation of functional carbohydrates have a higher carbon dioxide and lower methane content in comparison to the fermentation of other kinds of carbohydrate (such as fructo-oligosaccharide). This reduction in methane emission is beneficial for the environment.

It has been reported that feeding ruminant animals the functional carbohydrates reduced the worm count thus allowing a reduction in drenching requirements (see Example 5). An effect of the method and composition of the invention appears to be a reduced parasite loading.

The use of the present invention seems to have a prophylactic effect to reduce the ability of harmful bacteria (e.g. Salmonella Brandenburg) from taking hold in the digestive tract of the animal. The incidence of Salmonella Brandenburg outbreaks is sporadic, but on the increase in New Zealand. The prophylactic 35 effect may be shown minimise the effects of Salmonella Brandenburg on birth 12 rates in sheep, thereby at least maintaining standard birth rates of flocks exposed to Salmonella Brandenburg infection. The animals could be fed the functional carbohydrate as part of an ongoing diet to increase production of the animal and its overall health, rather than simply as a treatment for animals 5 exhibiting symptoms of infective diarrhea. With the increased gut health of the animal, it may also be that a reduction in fly strike as a result of decreased scouring (infective diarrhea) could also occur.

Preferably the functional carbohydrates will be administered to the animal at 10 about 2 to 60 grams of carbohydrate per day although more could be used if available and desired. Higher amounts are likely to undesirably stimulate intestinal motility in the animals however. It is more preferred to use between about 5-30 or about 10-30 grams. For bovine animals a preferred range is between about 10-30 grams, more preferably about 15-25 grams and for the 15 ovine between about 2-20 grams, more preferably about 5-10 grams. With lambs the amount administered can be as low as 1 gram per animal per day, although 2 grams is preferred. Administration can be achieved by mixing the functional carbohydrate into stock food or other nutritional support products such as reconstituted milk, milk replacer, water, fortified water, electrolyte 20 solutions, water gels or blended powders at an amount of about 150 to 5000 ppm. It is more preferable to use between about 300 and 5000 ppm or about 300 and 1000 ppm. The total composition is then administered to the animal in an amount per day to meet the preferred administration amount. To this extent the invention could be seen to be a food or food additive. As will be readily 25 apparent, if the user desired to use natural treatments, a focus on milk and similar support products could be used. A variety of alternatives would be well known to the skilled person. Alternative forms of administration would include formulated drenches and like means as would be known to the skilled person.

The functional carbohydrates may be administered via a water gel system which acts as the nutritional support. This water gel system will preferably include a carrier system that includes kappa carrageenan, Xanthan Gum, konjac, chitosan and/or locust bean gum dispersed into a water phase containing the oligosaccharide. Other ingredients could include Trehalose, Gum 35 Acacia, inorganic mineral salts, attractants and other additives or actives. The 13 inorganic mineral salts can include Magnesium or Zinc salts to treat the staggers and facial eczema, or potassium and/or sodium salts as an electrolyte for animals grazed in hot conditions.

The combination of Xanthan gum, carrageenan and konjac provides a thermally stable, economic system that allows for a longer period of resistance in the gut of calves, sheep and deer. Longer residence time allows for staged or delayed release of the functional carbohydrates to the animal. As a result, this thermally stable system which includes the functional carbohydrates, is capable of passing through the rumen gut. It also provides a method of delivery to animals grazed in remote areas, and animals that drink from natural reservoirs. The thermostability also allows functional carbohydrates to be delivered to areas of high temperature, e.g. New Zealand high country, or milking sheds, without damage to the ingredients in the water gel system. When administered in remote areas, the amount of functional carbohydrates administered to the animal per day will vary and the amount in the composition is intended to compensate for this.

An alternative and preferred, combination would include the use of Trehalose, together with other ingredients, including hydrocolloids such as Xanthan Gum, Gum Acacia, and kappa carrageenan. This would maintain the stability benefits of the composition but, due to the use of Trehalose, water loss will be reduced as will be the formation of ice crystals in cold weather.

A preferred composition for this is set out in Table 1 below. 14 Table 1 Ingredient Amount required Kappa Carrageenan 1.0-3.5% Xanthan Gum 0 - 0.5% Gum Acacia 0.2 - 0.7% Trehalose 2.0 -6.0% Glucidex 6 7.0-15.0% Water distilled 65-89% Colour/Attractants q.s.

Inorganic Mineral salts q.s. (according to seasonal requirements) The functional carbohydrates (as defined earlier) of use in the present invention 5 are the indigestible oligosaccharides, gluco- and/or isomalto-oligosaccharides. As will be apparent to the skilled person, a number of other carbohydrates will also fall within the definition of an indigestible oligosaccharide. It is, however, known that other oligosaccharides have undesirable traits for use in ruminant animals. For example, fructo-oligosaccharide contains a natural level of 10 sweetness that may be unpalatable and can lead to an increased production of gas that is not desirable for the rumen gut. As a result, it is likely that the beneficial effects described herein may not be observed. The preferred composition of use in the method and compositions of the present invention will include gluco-oligosaccharides, or isomalto-oligosaccharides or a mixture of the 15 two. While other oligosaccharides may be present as a result of the fermentation and hydrolysis processes used to prepare the oligosaccharides, these other oligosaccharides will be present in insignificant amounts of less than about 0.2% of the total oligosaccharide.

Most preferably gluco-oligosaccharides are used by themselves or will comprise the major part of a gluco/isomalto oligosaccharide mixture. Isomalto-oligosaccharides are usually sourced in a powder form, which tends to be hydrophilic in nature, and is therefore difficult to store. Alternatively the isomalto-oligosaccharides can be sourced as a 50% syrup, which increases the purchase and storage costs. The gluco-oligosaccharides can be sourced as a powder which is easier to use and store, and therefore tends to be more cost effective. A source of gluco-oligosaccharide, as listed in Table 1 above, is Glucidex 6.

The effect of the administration of functional carbohydrates on milk production is marked but the reason for it is unclear. It may simply be a function of improved health in the animals, but it does not seem that this alone would account for the production increases shown (see Example 3 - Table 4). The 10 results are not clearly derived from simply the observed effects on infective diarrhea and the gut microflora of the animal.

It is possible that gluco-oligosaccharides will be the only oligosaccharide that produces the effect on lactation as this forms the major part of the 15 oligosaccharides administered to the animal. It is also possible that isomalto-oligosaccharide alone will work but further work will be required to confirm this.

Examples Example 1 Bovine calf initial trials.

Random groups of new born bovines were selected to provide a cross population of animals likely to be exposed to a range of infection risk. Gluco-oligosaccharide ("GOS") at an amount of 20 g per day was included in food 25 regimes and the animals monitored for signs of infective diarrhea. A control group study without the added gluco-oligosaccharide in the food regime was also similarly monitored.

The study of newborn calves was to determine if enteral dosing would reduce 30 the occurrence of diarrhea. An increase in the rate of survival of the study population would be an outcome and improved weight gain of the animals a term result. The results are reported in Table 2. 16 Table 2 Group 1 Control 1 Group 2 Control 2 Number of calves 75 115 180 180 Age of calves + 4 days + 4 days + 4 days + 4 days Dosage rate 20g/day Nil 30g/day Nil Number of calves with diarrhea 7/ 9.3% 55/ 47.8% 2/1.1% 22/12.2% Fatalities 2/2.6% 13/11.3% 1/0.6% /2.8% The calves in the Group 1 study were housed in covered calf pens with strawed floor and fed from mechanical feeding stations with a calf milk replacer to which 5 the gluco oligosaccharide was separately added in a dispersed solution.

At the onset of diarrhea the affected calf was dosed with an electrolyte solution to prevent unnecessary fatality and recorded as a diarrhea event. The feeding regime was not altered.

The results of the study indicate that dosing calves with gluco-oligosaccharide is effective in reducing the incidence of infective diarrhea. The reduction in incidence of diarrhea from 47.8% to the 9.3% is considered significant and indicates the beneficial effect of the treatment regime. In addition, the reduction 15 in fatality from 11.5% to 2.6% is also significant.

The results of the Group 2 study confirm that significant reductions in both diarrhea and fatality rates were observed and support the conclusions drawn from the first study group. 17 Example 2 Bovine calf field trials.

A group of 15 farms comprising a mix of calf rearers, dairy farmers and dairy beef farmers were supplied with an oligosaccharide composition consisting of enzymatically hydrolysed dextrin including approximately between 1.5 and 3% of the total mixture as isomalto-oligosaccharide and the remainder largely gluco-oligosaccharide, as described by the properties set out in Table 3.

Table 3 Property Characteristic Dextrose Equivalent Degree of Polymerisation DP1 0.2% DP2 0.8% DP 3 1.5% DP 4 1.7% DP 5 1.8% DP 6 2.3% DP 7 2.7% DP 8 2.3% DP 9 1.9% DP 10-20 27.9% DP >20 57% Molecular Weight >5000-6000 Alcohol Insoluble Fibres % DS <20 % Glucosidic Linkages (1-4) 50-64 (1-6) 20-25 (1-2) 7-10 (1-3) 9-11 Glucose % 0.5% Maltose 1.0% Oligo/Poly 98.5% 18 The farms were in diverse locations to provide a random cross section of conditions. A total number of 2963 calves were monitored. The feeding of newborn calves remains a universally similar method in the first few weeks of life.

A group of 5 farms was established as non user sites, totaling 1030 calves and also in diverse locations to provide a random profile.

The trial period commenced on 1 July 2002 and concluded on 29 September 10 2002. The oligosaccharide composition was added to calf milk or calf milk replacer at the user sites at the rate of 20 grams per calf daily. This was continued until the calf was weaned from milk feeding.

The number of calves either born or received onto each farm was recorded in 15 each week and multiplied by seven to give Calfdays, a representation of the number of days of monitoring per calf. The number of calves that were observed and treated for scouring was also recorded and the days that each calf scoured for also recorded (Scourdays). Calf fatalities were also recorded but the cause of death not specifically isolated in all cases. This proved to be 20 impractical in the field as it requires veterinary autopsy.

This provided a comparative data base in each group of users and non users of total calf days for the period and the total number of scour days.

The results which are plotted in Figure 1 show a clear reduction in the rate of scouring in the calf population that was treated with the oligosaccharide composition. In cases where infective scouring occurred in the treated population the effects were much less severe and recovery rates were quicker. Calf fatality rates in the non treated group were significantly higher for the 30 infected animals.

The results show a consistently lower rate of scouring in the treated group which for the first three weeks record a zero result whilst infection in the control group is present from the outset. 19 During the week of 19 August 2002 there was a rapid increase in the scour rate of the control group as a result of an outbreak of rotavirus on two farms. These farms were located geographically far apart. The treated group recorded an increase in scour rates in the prior 2 weeks of 5 and 12 August 2002 but at 5 much lower rates. Rotavirus is reported as a common affliction in calves in the August month. There is the likelihood of a favourable environment for infection due to seasonal change in this month. The data reflects this.

The rate of infection of the treated group for the whole period is 2.29 scourdays 10 per 100 calfdays whilst in the control group the rate is 16.82 scourdays per 100 calfdays. This is an effective rate of 7.34 times the rate of infection in the control group over the treated group.

The user group is a wider base in number and site than the control but the 15 probability of an adverse result appearing is much greater in a wider group.

There is little or no predictability in result in either groups as the calves are newborn, site selection having taken place prior to the calving season.

Calves suffer from infective diarrhea from three basic causes, bacteriological, 20 viral and nutritional. Calves that suffer from high stress immediately post birth are also likely to scour. The reasons are traceable often to transport to and from saleyards shortly after birth, exposure to virus and bacteria in saleyard environments, inadequate supply of colostrum immediately after birth or protein overload from protein rich feed.

The data indicates strongly that the administration of the oligosaccharide composition of the present invention in the diet of the animal alleviates or mitigates the adverse effect of infective diarrhea in newborn calves.

Example 3 Bovine lactating adult initial trials.

Random groups of adult bovines were selected to provide a cross population of animals likely to be exposed to a range of infection risk. Gluco-oligosaccharide ("GOS") at an amount of 20 g per day was included in food regimes and the 35 animals monitored for signs of infective diarrhea. A control group study without the added gluco-oligosaccharide in the food regime was also similarly monitored.

The study of adult lactating cows was to determine if enteral dosing with functional carbohydrate would improve milk yield per animal as a consequence of increased digestive function and reduced infective diarrhea. Functional carbohydrate as used in Example 1 was given to the cows in group 1 by direct drenching. Functional carbohydrate as used in Example 1 was given to the cows in group 2 by addition to the cows' water supply using a Dosetron system. Daily milk production per animal measured for each group. The results are reported in Table 4.

Table 4 Group 1 Control 1 Group 2 Control 2 Number of cows 101 246 262 262 Dosage/cow GOS 10g/day Nil 10g/day nil Milk yield per cow. Average litres/day Pre 1561 3640 4188 4213 During 1646 3735 4506 4339 +5.4% +2.6% +7.6% +3.0% Milk Fat % Pre 4.84 4.63 4.22 4.20 During .02 4.68 4.65 4.33 +3.7% +1.1% +10.2% +3.1% Total Protein Pre 3.43 3.52 3.42 3.42 During 3.98 3.68 3.77 3.51 +16.0% +4.5% +10.2% +2.6% Faecal Appearance Pre Loose Loose Loose Loose During Firm at day 6 Loose/firm Firm at day 10 Loose at day 14 21 The trials were conducted at a time when pasture feed remained of a consistent nature. Defecation was monitored as an indicator of digestive differences or change between the control and study group.

The results of the study indicate that feeding functional carbohydrate to cows increases milk production, improves digestive function and reduces infective diarrhea. In particular the percentage increase of milk production per cow and the percentage increase of milk fat in the milk produced is significant and offer economic benefits to farmers using the functional carbohydrates as a food 10 supplement.

Example 4 Bovine lactating adult field trials.

A trial herd of 440 milking cows (noted as TRD) was orally administered 15 15 grams of the oligosaccharide composition as described in Example 2, in a solution of water by metered drench gun daily over the period of the study. The daily yield of the herd for milk volume, milk fat and protein was recorded and plotted. Intervention points were included in the trial to assess if natural production would alter if the treatment was discontinued and restarted.

An averaged profile of 8 other herds totaling 1772 cows was also established comprising the following Table 5 Herd A 160 Herd B 200 Herd C 192 Herd D 334 Herd E 230 Herd F 186 Herd G 280 Herd H 190 Total: 1772 22 The daily yields of these herds was also recorded and averaged to 440. The results were plotted to provide a control performance profile (see Figures 2, 3 and 4).

All the herds are located in the same geographic region. Environmental and pasture differences were as far as possible minimized. No changes were made to the normal farming management of the herds.

The trial commenced on 01 January 2002. The trial herd performance against 10 the average profile was recorded for 43 days without dosing with the composition described in Example 2. On 13 February 2002 dosing of the trial herd commenced. Daily production data was recorded from 01 January 2002 to 15 May 2002 for both trial herd and the control herds.

Dosage of the trial animals commenced on 13 February, 2002 and continued on a daily basis until 08 March 2002 when dosing was stopped for a short period. Dosing was recommenced on 22 March 2002 and continued until the herds were dried off.

With reference to Figures 2, 3 and 4, in the pretrial period 01 January 2002 - 05 February 2002 there is no significant difference to be seen in milk volume, milk fat or protein content between the control herd profile and that of the trial herd (TRD). This indicates that despite differences in location, possibly feed composition and farm practice, there is little difference in the outcomes of 25 natural production between the herds. The averaged control herd profile can be seen as a reliable guide to performance.

Shortly after the commencement of dosing on 13 February 2002, with the composition described in Example 2, a significant trend begins to appear in the 30 production data for the three component items - volume, fat and protein. This also is observed on recommencement of dosing at 22 March 2002.

The differences in total milk volume, fat and protein contents recorded at various time intervals are entered in the Tables 6, 7 and 8, and indicate similar 35 differences in superior production of the dosed herd. 23 Table 6 Comparison of Total Milk Volume (Litres) between dosed and non-dosed herds.

Date No dosing (Control) Dosed Difference (%) 05 Mar 02 4082 4760 +678 (16.6%) From 15 Feb 2002 to: 05 Mar 02 98056 109670 +11615 (11.8%) From 15 Feb 2002 to: 07 May 02 228970 310820 +81850 (35.7%) Table 7 Comparison of Total Milk Fat (kg) between dosed and non-dosed herds.

Date No dosing (Control) Dosed Difference (%) 05 Mar 02 242 275 +33.3 (13.7%) From 15 Feb 2002 to: 05 Mar 02 5579 6169 +590 (10.6%) From 15 Feb 2002 to: 07 May 02 13628 18497 +4869 (35.7%) Table 8 Comparison of Total Milk Protein (kg)between dosed and non- dosed herds.

Date No dosing (Control) Dosed Difference (%) 05 Mar 02 164 193 +29.2 (17.8%) From 15 Feb 2002 to: 05 Mar 02 3871 4361 +490 (12.7%) From 15 Feb 2002 to: 07 May 02 9398 13044 +3646 (38.7%) 24 During the period of the trial there would have been a natural decline in the feed value of pasture. This is a natural phenomenon and it appears that increased efficacy in digestive function by dosing with the composition of the present invention modulates gut flora in the animals enabling better absorption 5 of the available nutrients from pasture than would otherwise occur. The trial data supports this contention. The difference between the herds toward the end of the season is marked.

The trial data indicates that when dosing was discontinued at 8 March 2002 10 that the production indicators trend back to the control profile and, at recommencement, on 22 March 2002, there is an upward trend in performance.

Example 5 Parasite loading in ovine animals.

Following weaning, a flock of lambs were orally administered 2g per day per animal of the composition described in Example 2 via a water trough. The lambs were then monitored for parasitic infection and growth and these observations are recorded in Table 9.

Table 9 Date Worm Count Comments January 2002 Weaned and drenched 04 February 2002 Drenched - oligosaccharide composition started in feeding regime 18 February 2002 Zero February 2002 03 March 2002 Zero 19 March 2002 125 March 2002 150 Average weight = 38.6 kg 26 March 2002 Drenched 08 May 2002 Drenched Average weight = 41 kg (5kg heavier than usual at this age) Lambs go onto swedes 12 June 2002 300 Drenched 05 August 2002 60 28 August 2002 90 Shorn 21 September 2002 Zero Traditional farming practices mean that the lambs would usually be drenched every three weeks from weaning through until May/June 2002. The decreased 5 parasite loading shown in these lambs meant that the number of drenches required in this time was cut down from the usual number of 7 to 5. A worm count of 300 - 400 is usually the trigger for drenching. In this flock, a more conservative worm count of 200 - 300 is used as the trigger. Using the more traditional trigger levels of 300 - 400. The number of drenches could have 10 been further reduced to 4. 26 There are trends apparent from the observation of this flock, that the use of the oligosaccharide composition appears to be beneficial for reducing parasite loading (and the associated costs and labour of drenching) and for improving the general health and weight of the lambs. More evidence is required to 5 determine the mechanism behind this apparent benefit of using the oligosaccharide composition however it is suspected that the general improvement of gut health in the animals that are being administered the oligosaccharides will be a key factor.

Example 6 Preferred water-gel composition The water gel tablet is made in the following way: 0.1 grams of Xanthan Gum, 0.2 grams of Acacia Gum, 2.0 grams of Trehalose (Hayashibara Treha) and 10 grams of Glucidex 6 (Roquette Freres) is dissolved in water. 1.2 grams of kappa carrageenan (FMC Gelcarin GP911) is dissolved into the solution and then the solution is heated to 65°C while maintaining a slow agitation. The temperature is then reduced to 25°C. At this point, a mineral premix and other optional additives may be added to the mixture if required.

The mixture, now viscous, is passed through a sized aperture and dropped into a chilled water bath containing 15% potassium chloride. The formed gel tablets are removed from the potassium chloride solution and passed over a cold air column and then coated in a dry polyol such as sorbitol powder.

The tablet formed is thermostable and has good resistance to water loss and ice crystal formation.

The foregoing describes the invention including preferred forms thereof. Alterations and modifications that would be obvious to the skilled person are intended to fall within the scope of the invention as disclosed and claimed.

Claims (15)

27 WHAT IS CLAIMED IS:

1. An oral composition for increasing milk production in lactating animals and/or treating/controlling infective diarrhea, the composition including a nutritional support product selected from milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels, blended powders, or combinations thereof, and between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides.

2. The composition according to claim 1 wherein the composition includes between about 300 and 5000 ppm gluco- and/or isomalto-oligosaccharides.

3. The composition according to claim 1 wherein the composition includes between about 300 and 1000 ppm gluco- and/or isomalto-oligosaccharides.

4. The composition according to claim 1, 2, or 3 wherein the nutritional support product is a water gel system.

5. The composition according to claim 4 wherein the water gel system is thermostable.

6. The composition according to claims 4 or 5 wherein the water gel system includes Trehalose and a hydrocolloid.

7. The composition according to claim 6 including a hydrocolloid selected from any one or more of Xanthan Gum, Gum Acacia, and kappa carrageenan.

8. An oral composition for increasing milk production in lactating animals and/or treating and controlling infective diarrhea, the composition including between about 7-15% of gluco- and/or isomalto- oligosaccharides, about 2.0 -6.0% Trehalose, about 1.2 -4.7% 300421641 I r~ ——. TJ503726 I intellectual Propertv I Office of N.Z. J 1 5 JUN 2005 I r— i i 28 hydrocolloid, and water.

9. The composition according to claim 8 wherein the hydrocolloid in the composition contains about 1.0 - 3.5% kappa carrageenan, about 0.2 -0.7% Gum Acacia and about 0 - .05% Xanthan Gum.

10. The composition according to claims 8 or 9 wherein the composition further contains excipients selected from any of the following: inorganic mineral salts, vitamins, attractants and other additives.

11. An oral composition for increasing milk production in ruminant lactating animals and/or treating and controlling infective diarrhea substantially as herein described with particular reference to any one of the accompanying Examples or Figures excluding comparatives.

12. An oral composition for the treatment or control of the effects of viral infections, the composition including a nutritional support product selected from milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels, blended powders, or combinations thereof, and between about 150 and 5000 ppm of gluco-and/or isomalto-oligosaccharides.

13. The composition according to claim 12, wherein the viral infection is caused by Rotavirus or Coronavirus.

14. The use of a composition including a nutritional support product selected from milk, reconstituted milk, milk replacer, water, fortified water, electrolyte solutions, water gels, blended powders, or combinations thereof, and between about 150 and 5000 ppm of gluco-and/or isomalto-oligosaccharides in the manufacture of a medicament for the treatment or mitigation of the effects of viral infections.

15. The use of a composition including between about 7% and about 15% of gluco- and/or isomalto-oligosaccharides in the manufacture of a medicament for the treatment or mitigation of the effects of viral 300421641 TJ503726 Intellectual Property Office of N.Z. 1 5 JUN 2005 /N P"* a % a 29 17. % 18. infections. The use according to claim 14 or 15, wherein the viral infection is caused by Rotavirus or Coronavirus. An oral composition for increasing milk production in lactating animals and/or treating/controlling infective diarrhea, the composition including a nutritional support product selected from milk, reconstituted milk, milk replacer, a milk product, water, fortified water, electrolyte solutions, water gels, blended powders, or combinations thereof, and hydrolysed dextrin, the hydrolysed dextrin including between about 150 and 5000 ppm of gluco- and/or isomalto-oligosaccharides. The composition according to any one of claims 1,12, 14 and 17 wherein the nutritional support product is selected from milk or a milk based nutritional support product. The composition according to any one of claims 1, 12, 14, 17 and 18 wherein the composition is administered as a drench. VITAL AN LIMITED By their Attorneys BALDWINS Intellectual Property Office of N.Z. 300421641 TJ503726 1 5 JUN 2005 R E C EI V E D