“ atopic disease ” means the clinical manifestations of allergic sensitisation and includes atopic dermatitis , atopic eczema , allergic rhinitis and asthma ; “ degree of hydrolysis ” or “ dh ” of a protein means the number of peptide bonds in the intact protein which are cleaved during the hydrolysis divided by the number of peptide bonds in the intact protein expressed as a percentage ; “ infant ” means a child under the age of 12 months ; “ follow - on formula ” means compositions intended for use by infants aged over four months and constituting the principal liquid element in the progressively diversified diet of such infants ; “ oral tolerance ” means an active state of immunological hyporesponsiveness to antigens delivered via the oral route ; “ primary prevention of allergic reaction to a dietary protein ” means prevention of establishment of such allergic reaction and includes reduction of risk of such an allergic reaction ; “ tgf - β ” or “ transforming growth factor β designates a group of at least five distinct but closely related bioactive peptides designated tgf - β1 , tgf - β2 etc and found inter alia in human milk ( tgf - β1 and tgf - β2 ) ( li et al , transforming growth factor - β regulation of immune responses , annu rev . immunol . 2006 24 : 99 - 146 ); “ weaning ” means the introduction into the diet of a young mammal of foods other than its mother &# 39 ; s milk or milk - based substitute such as infant formula ; “ weaning period ” means that period in the life of a young mammal starting with the introduction of foods other than its mothers milk or milk - based substitute therefore and ending with the cessation of breast feeding or administration of infant formula or follow - on formula . the invention provides a nutritional composition comprising a partially hydrolysed milk protein having a degree of hydrolysis between 15 and 25 % and 50 to 1000 nanograms of tgf - β per 100 ml of ready to consume composition . the milk protein may be whey protein , casein protein or a mixture thereof but preferably is whey protein . if whey protein is used , the degree of hydrolysis is preferably between 15 and 19 %. preferably , the partially hydrolysed milk protein has a residual antigenicity at least 100 times less than that of intact whey protein . the residual allergenicity of the partially hydrolysed milk protein may be measured by the technique described by fritsché et al ( int . arch . aller and appl imm ., 93 , 289 - 293 , 1990 ). such a partially hydrolysed milk protein and products containing it may be described as hypoallergenic in accordance with the provisions of eu directive 96 / 4 / ec . compositions according to the invention may be used in the weaning of young mammals including human infants and toddlers as well as the young of companion animals such as dogs and cats . preferably the nutritional composition of the invention is an infant formula , more preferably a follow - on formula for use by infants aged over four months . the milk protein may be hydrolysed in any suitable manner known in the art . in the case of whey protein , a suitable process is described in european patent no . 322 , 589 , the contents of which are incorporated herein by reference . if the whey fraction used as the starting material is substantially lactose free , it is found that the protein suffers much less lysine blockage during the hydrolysis and subsequent thermal processing . this enables the extent of lysine blockage to be reduced from about 15 % by weight of total lysine to less than about 10 % by weight of lysine ; for example about 7 % by weight of lysine blockage which greatly improves the nutritional quality of the protein source . the source of the whey protein may be acid whey , sweet whey , whey protein isolate or mixtures thereof . preferably , however , the protein source is based on whey protein isolate or modified sweet whey . sweet whey is a readily available by - product of cheese making and is frequently used in the manufacture of infant formulas based on cows &# 39 ; milk . however , sweet whey includes a component which is undesirably rich in threonine and poor in tryptophan called caseino - glyco - macropeptide ( cgmp ). removal of the cgmp from sweet whey results in a protein fraction with a threonine content closer to that of human milk . a process for removing cgmp from sweet whey is described in ep 880902 . if modified sweet whey or whey protein isolate is used as the protein source , it is preferably supplemented by free histidine in an amount of from 0 . 1 to 3 % by weight of the protein . an infant formula of the present invention may comprise from 1 . 0 to 2 . 0 grams of partially hydrolysed whey protein per 100 ml of ready to consume formula , more preferably from 1 . 5 to 1 . 9 g / 100 ml . a follow - on formula of the present invention contains from 50 to 1000 nanograms of tgf - β per 100 ml of ready to consume formula , more preferably from 50 to 500 nanograms per 100 ml and most preferably 200 to 300 nanograms per 100 ml . preferably , a follow - on formula of the present invention contains both tgf - β1 and tgf - β2 , more preferably in a ratio between 1 : 5 and 1 : 50 . tgf - β may be added to the formula in the form of a whey protein fraction enriched in these bioactive peptides such as tm0301 or xp - 828l from armor proteins , france or in the form of a polypeptide growth factor isolated from milk as described for example in ep 313515 or wo 92 / 00994 . alternatively , a recombinant tgf - β may be used if preferred . a follow - on formula according to the present invention may contain a carbohydrate source . any carbohydrate source conventionally found in infant formulae such as lactose , saccharose , maltodextrin , starch and mixtures thereof may be used although the preferred source of carbohydrates is lactose . preferably the carbohydrate source contributes between 35 and 65 % of the total energy of the formula . a follow - on formula according to the present invention may contain a source of lipids . the lipid source may be any lipid or fat which is suitable for use in infant formulas . preferred fat sources include palm olein , high oleic sunflower oil and high oleic safflower oil . the essential fatty acids linoleic and α - linolenic acid may also be added as may small amounts of oils containing high quantities of preformed arachidonic acid and docosahexaenoic acid such as fish oils or microbial oils . in total , the fat content is preferably such as to contribute between 30 to 55 % of the total energy of the formula . the fat source preferably has a ratio of n - 6 to n - 3 fatty acids of about 5 : 1 to about 15 : 1 ; for example about 8 : 1 to about 10 : 1 . the follow - on formula may also contain all vitamins and minerals understood to be essential in the daily diet and in nutritionally significant amounts . minimum requirements have been established for certain vitamins and minerals . examples of minerals , vitamins and other nutrients optionally present in the infant formula include vitamin a , vitamin b1 , vitamin b2 , vitamin b6 , vitamin b12 , vitamin e , vitamin k , vitamin c , vitamin d , folic acid , inositol , niacin , biotin , pantothenic acid , choline , calcium , phosphorous , iodine , iron , magnesium , copper , zinc , manganese , chloride , potassium , sodium , selenium , chromium , molybdenum , taurine , and l - carnitine . minerals are usually added in salt form . the presence and amounts of specific minerals and other vitamins will vary depending on the intended infant population . if necessary , the formula may contain emulsifiers and stabilisers such as soy lecithin , citric acid esters of mono - and di - glycerides , and the like . the formula may optionally contain other substances which may have a beneficial effect such as lactoferrin , nucleotides , nucleosides , and the like . finally , the formula may contain indigestible oligosaccharides such as galacto - oligosaccharides for example in an amount of from 0 . 3 to 7 %. the formula may be prepared in any suitable manner . for example , it may be prepared by blending together the partially hydrolysed milk protein , the carbohydrate source , and the fat source in appropriate proportions . if used , the emulsifiers may be included at this point . the tgf - β may also be added at this point . the vitamins and minerals may be added at this point but are usually added later to avoid thermal degradation . any lipophilic vitamins , emulsifiers and the like may be dissolved into the fat source prior to blending . water , preferably water which has been subjected to reverse osmosis , may then be mixed in to form a liquid mixture . the temperature of the water is conveniently about 50 ° c . to about 80 ° c . to aid dispersal of the ingredients . commercially available liquefiers may be used to form the liquid mixture . the liquid mixture is then homogenised ; for example in two stages . the liquid mixture may then be thermally treated to reduce bacterial loads , by rapidly heating the liquid mixture to a temperature in the range of about 80 ° c . to about 150 ° c . for about 5 seconds to about 5 minutes , for example . this may be carried out by steam injection , autoclave or by heat exchanger ; for example a plate heat exchanger . then , the liquid mixture may be cooled to about 60 ° c . to about 85 ° c . ; for example by flash cooling . the liquid mixture may then be again homogenised ; for example in two stages at about 10 mpa to about 30 mpa in the first stage and about 2 mpa to about 10 mpa in the second stage . the homogenised mixture may then be further cooled to add any heat sensitive components ; such as vitamins and minerals . the ph and solids content of the homogenised mixture are conveniently adjusted at this point . the homogenised mixture is transferred to a suitable drying apparatus such as a spray drier or freeze drier and converted to powder . the powder should have a moisture content of less than about 5 % by weight . the tgf - β may be added at this point by dry mixing if not added previously . if a liquid product is preferred , the homogenised mixture may be sterilised then aseptically filled into suitable containers . an example of the composition of a follow - on formula according to the present invention is given below . this composition is given by way of illustration only .
a nutritional composition comprising a partially hydrolysed milk protein having a degree of hydrolysis between 15 and 25 % and 50 to 1000 nanograms of tgf - β per 100 ml of ready to consume composition and methods for the primary prevention of allergic reactions to newly introduced dietary protein at weaning and the prevention of development of atopic diseases in a young mammal at weaning comprising feeding to the young mammal a therapeutic amount of the composition are disclosed .