Title of Invention	"NUTRITIONAL COMPOSITION COMPRISING INDIGESTIBLE OLIGOSACCHARIDES"
Abstract	The present invention provides a method and composition for the treatment and/or prevention of respiratory tract infection and/or respiratory tract infection disease, said method comprising orally administering a composition to a mammal, said composition comprising a galactose containing indigestible oligosaccharide and at least 5 wt.% digestible galactose saccharide.

Full Text

NUTRITIONAL COMPOSITION COMPRISING INDIGESTIBLE OLIGOSACCHARIDES FIELD OF THE INVENTION The present invention provides a method for the prevention and/or treatment of respiratory tract infections, said method comprising the administration of indigestible oligosaccharides. BACKGROUND OF THE INVENTION The respiratory tract is a common site for infection by pathogens. It becomes infected frequently because it is in direct contact with the physical environment and is exposed to microorganisms in the air, There are several microorganisms that cause illness in infants, Respiratory syncytial was (RSV) is the leading cause of serious lower respiratory tract disease in infants and children. Primary RSV infection occws most often in children from 6 weeks to 2 years of age. RSV is estimated to cause as much as 75% of all childhood brortchiolitis and up to 40% of all pediarric pneumonias. Children at increased risk from RSV infection include proterm. infants and children with bronchopulmonary dysplasia, congenital heart disease, congenital or acquired immunodeficiency and cystic fibrosis The fatality rate in infants with heart or lung disease who are hospitalized with RSV infection is 3%-4%. Treatment options for established RSV disease are limited. Severe RSV disease of the lower respiratory tract often requires considerable supportive .-are, including administration of humidified oxygen and respiratory assistance. Parainfluenza viral infection results in serious respiratory tract disease in infants and children. Infectious parainfluenza account for approximately 20% of all hospitalizations of pediatric patients suffering from respiratory tract infections worldwide. Infants breast fed with mothers milk have a reduced occurrence of respiratory tract infection. In the art, it is presently believed that this reduced occurrence is. because mothers milk contains imniunoglobulin with virus or other microorganism neutralizing activity. Treatment of respiratory infection is often difficult. Only a few effective drugs are available and often treatment requires pulmonary administration of the drug. In young infants this leads to significant stress, Therefore there is a need for further effective agents that preferably can be administered without imposing or decreasing imposing stress on infants and children. Recently is has been described that administration, of infant formula enriched with prebiotics (galactooligosaccharides), probiotics, nucleotides and LC-PUFA and with a low level of lactose is useful for infants suffering from respiratory infections (Rivero et al (2004), J Pediatr Gastroenterol Nutr 39:suppl.l, P1121). In a multicentre clinical trial, the present inventors have now surprisingly found that enteral administration of a combination of. a) a galactose containing indigestible oligosaccharide containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose; and b) a digestible galactose saccharide results in a reduced occurrence of respiratory tract infections, see example 6. The present method has the advantage that the active principle is safe and can be suitably admixed to nutrition. This leads to significantly reduced stress, particularly in infants. Hence, in one aspect, the present invention comprises the oral administration of a nutritional composition which reduces the occurrence of respiratory tract infection. The present invention is particularly surprising because until now, it was believe that a low lactose content was essential for the prevention of respiratory disorder in infants. The present inventors found that administering a nutritional composition containing a transgalactooligosaccharide and rich in lactose is particularly effective preventing or treating respiratory infection. The present inventors have found that both the galactose containing indigestible oligosaccharide and a digestible galactose saccharide are essential for optimal treatment and/or prevention of respiratory infection and/or respiratory infection disease. Moreover, particularly lactose contributes to a reduced occurrence of respiratory tract infection. Additionally, the present invention is also of significant commercial .importance. The manufacture of low lactose formula requires for example the use of a non-milk protein source (e.g. soy protein) or an additional treatment of milk wherein the lactose is removed (e.g. ultrafiltration). Both options are often undesirable as they increase costs and may provide sub-optimal nutrition. » ii-': la a further aspect the present invention provides a method for the treatment and/or prevention of respiratory tract infection and respiratory tract infection disease, said method comprising administering a nutritional composition. Administration of the present active principle as a nutritional composition aims to reduce stress and more optimally reduces the occurrence of respiratory infections as said oligosaccharide works synergistically with long chain polyunsaturated fatty acids, the combination of choline and zinc, probiotics and/or prebiotics other than the galactose containing indigestible oligosaccharide. In a preferred embodiment, the present invention provides a method for the treatment and/or prevention of respiratory syncyticial virus infection, said method comprising administrating to an infant with the age between 0 and 2,' a nutritional composition comprising an effective amount of transgalactooligosaccharides. In still a further aspect the present invention provides a composition which is particularly suitable for the treatment and/or prevention of respiratory tract infection and disease, said composition comprising said oligosaccharide and an immunoglobulin with virus neutralizing activity, e.g. immunoglobulin with parainfluenza or RSV neutralizing activity. The immunoglobulin is preferably obtained from a cow hyperimmunised against respiratory virus. DETAILED DESCRIPTION OF PREFFEKED EMBODIMENTS The present invention provides a method for the treatment and/or prevention of respiratory tract infection and/or respiratory tract infection disease, said method comprising orally administering a composition to a mammal, said composition comprising a galactose-containing indigestible oligosacchari.de containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose, and at least 5 wt.% digestible saccharide based on total dry weight of the composition, said saccharide being selected from die group consisting of galactose and digestible galactose containing saccharide containing at least two terminal saccharide unite, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from lite group consisting of galactose and fucose. In a further aspect the present invention provides a composition suitable for the treatment and/or prevention of respiratory tract infections and/or respiratory tract infection disease comprising a. a galactose containing indigestible oligosaccharide containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose; b. an. immunoglobulin having a virus neutralizing effect; and c. a substance of non-human origin. Optionally this composition further comprises d. at least 5 wt.% digestible galactose saccharide based on total dry weight of the composition, said saccharide being selected from the group consisting of galactose and digestible galactose containing saccharide containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose. Oliqosaccharides The present invention comprises the administration of a galactose containing indigestible oligosaccharide (GAL-oligo) containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fiicise Preferably the sacchandes of the GAL-oligo are p-linked. The term "terminal sacchariride" refers to a saccharide which is bound to one other unit (e.g. galactose. glucose, fructose or fucose), The present GAL-oligo preferably contains not more than 4 terminal The term "indigestible oiigosaccbarides" as used in the present invention refers to saccharides which ate not or only partially digested in die intestine by the action of acids or digestive enzymes present in the human upper digestive tract (small intestine and stomach) but which are fermented by the human intestinal flora. In a preferred embodiment, the GAL-oligo contains at least one terminal galactose and one selected from at least terminal glucose and one terminal fucose. Even more preferably, the present galactose containing indigestible oligosaccharide comprises at least one terminal galactose and at least one terminal glucose. Preferably the oligosaccharide consists of 2 terminal saccharide units and 2 to 60 saccharide units in total. Preferably the GAL-oligo is selected from the group consisting of transgalactooligosaccharides, galactooligosaccharides, lacto-N-tetraose (LNT), lacto-Nneotetraose (neo-LNT), fucosyl-lactose, fucosylated LNT and fucosylated neo-LNT. In a particularly preferred embodiment the present method comprises the administration of transgalactooligosaccharides ([galactose]n-glucose; wherein n is an integer between 1 and 60, Le. 2, 3. 4, 5, 6, ...., 59 ,60; preferably n is selected from 2, 3, 4, 5, 6, 7, 8, 9, or 10). Transgalactooligosaccharidss (TOS) art for example sold under the trademark Vivinal™ (Borculo Domo Ingredients, Netherlands). Preferably the saccharides of the transgalactooligosaccharides are ß-linked The present composition preferably comprises 0.1 to 12 grams of the GAL-oligo per 100 gram dry weight of the composition, preferably between 0.5 and 8 grams, more preferably between 1.0 and 7.5 grams. After reconstitution of the powder in liquid and administration of the liquid formula to the infant, these amounts of GAL-oligo provide the desired effects without causing intestinal discomfort. Digestible galactose saccharide The composition used in the present method comprises digestible carbohydrate containing digestible galactose saccharide. The composition contains at least 5 wt.% digestible galactose saccharide based on total dry weight of the composition, said saccharide being selected from die group consisting of galactose and digestible galactose containing saccharide containing at least two terminal saccharide units, wherein at least one terminal saccharide unit is selected from the group consisting of glucose and galactose; and at least one terminal saccharide is selected from the group consisting of galactose and fucose. The composition used in the present method contains at least 5 wt% digestible galactose saccharide based on total dry weight of the present composition, preferably at least 10 wt.%, even more preferably at least 25 wt.%. The term "digestible galactose saccharide" as used in the present invention refers to mono-, di-, tri- or polysaccharides which arc digested in the intestine of normal healthy human by the action of acids or digestive enzymes present in the human upper digestive tract (small intestine and stomach). Preferably lactose is used in the present method. '" Preferably the digestible galactose saccharide. is lactose. Preferably at least 50 wt% of the carbohydrate of the composition used in the present method is lactose, preferably at least 75 wt.%, even more preferably at least 90 wt.%. The term carbohydrate as used herein refers to digestible carbohydrate, as is common practice. The composition used in the present method preferably contains at least 10 wt% lactose saccharide based on total dry weight of the present composition, preferably at least 25 wt.%, even more preferably at least 40 wt.%, most preferably at least 50 wt,%, In order to provide optimal nutrition to an infant, Le. a composition which is highly similar to human milk, the present method preferably comprises the administration of a composition, comprising between 40 and 60 wt.% lactose based on total dry weight of the composition. In a further preferred embodiment the present invention, relates to the administration of about 2 to SO grams lactose per serving, preferably about 10 to 25 grams lactose per serving. A serving is preferably between 5 and 500 ml, more preferably between 100 and 300 ml. The weight ratio digestible galactose aaccharide : galactose containing indigestible oligosaccharide is preferably above 1, more preferably above 5, even more preferably above 10. The ratio is preferably below 1000. more preferably below 100. Combinations of oligosaccharides In a particularly preferred embodiment the present method comprises the administration of the present GALoligo and an second indigestible "oligosaccharides selected from the group consisting of indigestible dextrins, xylooligosaccharides, arabinooligosaccharides, glucooligosaccharides, mannooligosaccharides, fucooligosaccharides fructans - Levan-type (ß-D-(2->6)-fructofuranosyl)n α-Dglucopyranoside) and fructans - Inulin-type (ß-D-((2->l)-fructofurauosyl)n α-Dglucopyranoside). Preferably the second oligosaccharide. is selected from the group consisting of inulin, hydrolysed inulin and fructooligosaccharides. The present composition preferably comprises between 0,5 and 12 grams of the second indigestible oligosaccharide, more preferably between 1 and 3 grams of the second indigestible oligoeaccharide per 100 gram dry weight of the present composition. The DP of the second oligosaccharide is preferably below 40, even more preferably between 10 and 30. Optimally, me present composition comprises between 1 and 12 grams water-soluble indigestible oligosaccharides in total (i.e. with or without a second, third, etc water soluble indigestible oligosaccharide) per 100 gram dry weight of the present composition, more preferably between 2 and 9 grams m total. Preferably the weight ratios; a. (oligosaccharides with DP 2 to 5): (oligosaccharides with DP 6 to 9); and b. (oligosaccharides with DP 10 to 60): (oligosaccharides with DP 6 to 9) ; are both above 1. Preferably both weight ratios are above 2, even more preferably above 5. The present method preferably comprises the administration of 0.5 to 10 gram transgalactooligosaccharides with DP between 1 and 10 per 100 gram dry weight of the composition, more preferably between 2 and 5 gram. The present invention preferably comprises O.S to 10 gram fructopolysacchaDde with DP between 15 and 40 per 100 gram dry weifbt of the composition, more preferably between 1 and 5 gram. The term "fructopolysaccharide" refers to ac indigestible polysaccharide carbohydrate comprising a chain of at least 10 ß-linked fructose units. In a farther preferred embodiment me second indigestible oligosaccharide is and acid oligosaccharide. The term acid oEgosaccharide refers to oligosaccharides comprising at least one acidic group selected from the group consisting of N-acetylneuraminic acid, N-glycoloylneuramiaic acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid group. The acid oligosaccharide preferably is a polyhexose. Preferably, at least one of the aforementioned acid groups is situated ac the terminal hexose unit of the acid oligosaccharide. Preferably the acid oligosaccharide contains a carboxylic acid at the terminal hexose unit, wherein said carboxylic acid group may be free or esterified. Methods for the manufacture of esterified pectin hydrolysates that can be suitably used in the present method and composition are provided in WO 01/60378 and/or W002/42484, which are hereby incorporated by reference. Preferably, the acid oligosaccharide has one, preferably two, terminal uronic acid units, which may be free or esterified. Preferably the terminal uronic acid unit is selected from the group consisting of galacturonic acid, glucuronic acid, guluronic acid, iduronic acid, mannuronic acid, riburonic acid and alturonic acid. These units may be free or esterified. In an even more preferred embodiment, the terminal hexose unit has a double bond, which is preferably situated between the Q. and Cs position of the terminal hexose unit. Preferably one of the terminal hexose units comprises the double bond. The terminal hexose (e.g. uronic acid) preferably has a structure according to Fig 1. Fig. 1: Preferred terminal hexose acid group wherein; R is preferably selected from the group consisting of hydrogen, hydroxy or acid group, preferably hydroxy (see'above); and at least one selected from the group consisting of R2, R3, R4 and R5 represents Nacetylneuramintc acid, N-glycoloylneuraminic acid, free or estarifled carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining of R2, R3 R4 and Rs representing hydroxy and/or hydrogen. Preferably one selected from the group consisting of R2, R3, R4 and R5 represents N-acetyhieuraminic acid, Nglycoloylneuraminic acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining of R2, RS, R/t and RS represent hydroxy and/or hydrogen. Even more preferably one selected from the group consisting of R2, R3, R4 and RS represents free or esterified carboxylic acid and the remaining of R2, R3, R4 and Rs represent hydroxy and/or hydrogen; and n is an integer and .eefers to a number of hexose units (see also Degree of Polymerisation, below), which may be any hexose unit. Suitably n is an integer between 1-5000 representing the number of hexose units said hexose units preferaby being uronic acid, even more preferably being galactaronic acid units. The carboxylic acid groups on these units may be free or (partly) esterified, and are preferably at least partly methylated. Most preferably, R2 and R3 represent hydroxy, R1 represent hydrogen and R5 represents free or esterified carboxylic acid. The acid oligosaccharide as used in the present method, has a degree of polymerisation (DP) between 1 and 5000, preferably between 1 and 1000, more preferably between 2 and 250, even more preferably between 2 and 50, most preferably between 2 and 10. If & mixture of acid oiigosacchatides with different degrees of polymerisation is used, the average DP of the acid oligosaccharide mixture is preferably between 2 and 1000, more preferably between 3 and 250, even more preferably between 3 and 50. The acid oligosacchandes are preferably characterised by a degree of methoxylation above 20%, preferably above 50 % even more preferably above 70%. Preferably the acid oligosaccharides have a degree of methylation above 20%, preferably above 50 '% even more preferably above 70%. The acid oligosaccharide is preferably administered in an amount of between 10 mg and 100 gram per day, preferably between 100 mg and 50 grams per day, even more between 0.5 and 20 gram per day T Respiratory tract infection The present invention provides a method for the treatment and/or prevention of respiratory tract infection, which is typically caused by bacterial, viral or fungal, infection. In a preferred embodiment the present method provides a method for the treatment and/or prevention of respiratory tract infection caused by Pneumococcus, Legionella, Streptococcus, Pseudomonas, Staphylococcus, Heconofilis, Mycoplasma, Mycobqcteria, Chlamitia, Moraxella, C^iella, Nocardia, Ktebsiella, Enterobacter, Proteus, Serratia, Acinetobacter, OrthomyxavMela, Myxovims, Orthomyxokvirus, Khinovirvs, Echoviruses, CoxsacJdeviruses, Adenovirus, ParainfluQnzavirus, Respiratory Symcytial virus (RSV), Cororurtirus, Measles virus, Cytomegalovirus, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Cryptocaccus Aspergullus, Mucorales. The present method is particularly suitable for the treatment and /or prevention of respiratory syncyu'al virus infection. In a preferred embodiment, the present method relates to the treatment and/or prevention of respiratory tract infection disease, preferably selected from the group consisting of tuberculosis, bronchitis, bronciolitis, tracheitis, pneumonia, sinusinitis, rhinitis, severe acute respiratory syndrome (SARS), croup epiglottitis, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, aspergillosis, mucorroycosis and lung abcess. In a particularly preferred embodiment the invention provides a method for the treatment and/or prevention of viral pneumonia and/or bronchitis. The present method is also suitable for the treatment and/or prevention of symptoms of respiratory tract infection selected from the group consisting of irritation in the lungs, congestion hi the lungs, excessive mucus production, breathlessness (i.e. difficulty witli breaming), particularly breathlessness. Treatment group The present method is particularly suitable for treatment and/or prevention of respiratory infections in children with the age between 0 and 10 years, preferably infante with the age between 0 and 4 years. The present method can advantageously be used for the treatment and/or prevention of the above mentioned disease, infection and remature innfants (an infant born before 37 weeks gestation). The present method is particularly suitable for the treatment and/or prevention of respiratory infections in immunocompromised mammalian subjects, preferably elderly (human above the age of about 60), subjects infected with human immunodeficiency virus (HIV), subjects suffering from one or more of the following diseases: nephrotic syndrome, multiple myeloma, lymphoma, Hodgkin's disease, subjects which have undergone organ transplantation, subjects with chronic illnesses of the hart, kidney or lungs (especially chronic obstructive pulmonary disease (COPD), lung emphysema, sarcoidosis, cystic fybrosis, bronchiectasis, lung cancer, atelectasis, respiratory failure, occupational lung diseases, asthma), diabetes and alcoholism. The present method is advantageously used for the treatment and/or prevention of patients with COPD, HTV infection and/or diabetes, as these patients are often weakened by the disease. In a further preferred embodiment, the present method comprises the administration of the present composition to bumans, mostly hospitalized patients, that are on a ventilator or artificial breathing machine, or in the intensive care unit, as these patients are particularly vulnerable for viral infections. Drug treatment of respiratory tract infection in. infants with the age between 0 and 4 ia often cumbersome because many of the medicaments have to be administered via the pulmonary route. The present invention provides a method for treatment and/or prevention of respiratory infections comprising orally administering a nutritional composition, Ilence, the present method also overcomes the problem of pulmonary administration. The nutritional composition suitable for use in the present method preferably contains between 10 and 60 en% lipid, between 5 and 50 en% protein, between 15 and 90 en% carbohydrate. More preferably the nutritional composition contains between 7.5 to 12-5 energy % protein; 40 to 55 energy % carbohydrates; and 35 to 50 energy % fat (en% is short for energy percentage and represents the relative amount each constituent contributes to the total caloric value of the preparation). The nutritional composition preferably also contains at least one long chain polyunsaturated fatty acid (LC-PUFA) preferably selected from the group consisting of eicosapentaenoic acid (EPA, n~3), docosahexaenoic acid (DHA, n-3) and arachidonic acid (AA, n-6), as these further reduce the respiratory tract infections and/or symptoms thereof. Preferably the present composition contains AA and DHA, even, more preferably AA, DHA and EPA. The present combination of indigestible oligosaccharid r/s) and LC-PUFA acts synergistically. Preferably the present composition contuses at laast Q.I wt.%, preferably at least 0.25 Wt%, more preferably at least 0.5 wt%, even more preferably at least 0.75 wt.% LCPUFA with 20 and 22 carbon atoms of the total rat content. The content of LC-PUFA with 20 and 22 carbon atoms in the present composition, preferably does not exceed 15 wt.% of the total fat content, preferably does not exceed 10 wt.%, even more preferably does not exceed 5 wt,% of the total fat content The EPA content preferably does not exceed 15 wt% of the total fat, more preferably does not exceed 5 wt.%, most preferably does not exceed 1 wt.%, but is preferably at least 0.05 wt%, more preferably at least 6.1 wt% of ,the total fat The DHA content preferably does not exceed 10 wt.%, more preferably does not exceed 5 wt.%, most preferably does not exceed 1 wt.%, but is at least 0.1 wt% of the total fat. The present composition preferably comprises at least 0.1 wt% AA, even more preferably at least 0.25 wt.% AA, most preferably at least 0.5 wt.% AA based on total fat. The AA content preferably does not exceed 5 wt.%, more preferably does not exceed 1 wt% of the total fat. ' Composition suitable for administration to adults may comprise increased amounts of LC-PUFA. The EPA content in this case preferably does not exceed 15 wt.% of the total fat, more preferably does not exceed 10 wt.%, but is preferably at least 0.05 wt%V more preferably at least 0.1 wt.% of the total fat The DHA content preferably does not exceed 15 wt.%, more preferably does not exceed 10 wt.%, but is at least 0.1 wt% of die total fat. The present composition preferably comprises at least 0.1 wt% AA, even more preferably at least 0.25 wt.% AA, most preferably at least 0,5 wt% AA based on total fit. The AA content preferably does not exceed 15 wt.%, more preferably does not exceed 10 wt.% of the total fat The present method does not include a method comprising the administration of a composition consisting of human milk. Hence, preferably the present method includes, the administration of a composition comprising a substance of non-human origin which is preferably a nutritional substance suitable for oral administration to a human, more preferably a fiber carbohydrate, far and/or protein of non-human origin, preferably from plant, animal, bacterial or synthetic origin, Immunoglobulin The present invention also provides for a composition which is particularly suitable for use in a method for the treatment and/or prevention of respiratory tract infection, said composition comprising the above described indigestible oligosaccharide(s) and an immunoglobulin having a virus neutralizing effect, preferably an immunoglobulin capable of neutralizing a virus selected from the group consisting of Myxovirus, Orthomyxokvirus, Rhinovirtts, Echoviruses, Coxsadcievirufes, Adenovirus, Respiratory Syrcytial virus (RSV), Coronavirus, Measles vints and Cytomegalovirus. The immunoglobulin preferably la IgA and/or IgG, and preferably is obtained from a hyperimmunised mammal, preferably a cow. Methods for obtaining these inununoglobulins from a hyperunmunised mammal are well known to the skilled man and are for example described in GB1573995. The hyperimmunised mammal is preferably immunised with an antigen capable of Stimulating the production of immunoglobulins with virus neutralising activity, said virus being selected from the group of Myxovirus, Orthomyxokvtrus, Rhinovirus. Echovirvses, CoxsacMeviruses, Adenovints, Respiratory Syncytial virus (RSV), Coronavirus, Measles virus and Cytomegalovirus. In a particularly preferred embodiment the present composition comprises an immunogiobulin with RSV neutralizing activity. The present composition does not include a composition consisting of human milk. Hence, preferably the present composition comprises a substance of non-human origin, preferably a nntntional substance, more preferably from, plant, animal, bacterial or synthetic origin. The substance is preferably a fiber, carbohydrate, fat or protein. The present composition is also advantageously combined with at least one selected from the group consisting of LC-PUFA (as described above), digestible galactose saccharide (see above), probiotics (as described below), choline (see below) and zinc (see below), Probiotics In a further preferred embodiment, the present method comprises the administration of the above-described indigestible oligosaccharide(s) and a probiotic. Preferably the probiotic is selected from the group Lactobacillus, Lactococcus, Bifidobacterium, Enterococcus, Propionibacterium, Pediococcwi, Bacillus and Streptococcus and more preferably from the group consisting of Lactobacillus and Bifidobacterium. The probiotic is preferably a non-pathogenic lactic acid-producing bacterium. The combination of the present indigestible oligosaccharide(s) and the probiotic bacteria acts aynergistically. Chpljne and zjnc In a further preferred embodiment, the present composition includes zinc and/or choline. Both zinc and choline stimulate the formation of healthy lung tissue membranes, and thereby result in an improved resistance to infection. Compositions including zinc and/or choline can advantageously be used in the present method. The present composition preferably contains between 5 and 500 mg choline per 100 gram dry weight of the composition, more preferably between 20 and 100 mg choline, even more preferably between 40 and 6G mg choline. The present composition preferably contains between 1 and 100 mg zinc per 100 gram dry weight of the composition, more preferably between 2 and 50 mg zinc, even more preferably between 10 and 25 mg zinc, > i f ! ' ' - EXAMPLES Packaged infant milk: formula provided with a label indicating that the formula can be suitably used to prevent respiratory tract infection by respiratory syncytial virus i - '• formula containing per 100 ml final product (and per 13.1 g powder): 8 energy % protein 1-4 g (casein whey mixture) 45 energy % digestible carbohydrates 7.5 g 47 energy % fat 3.5 g transgalactooh'gosacchaiides (TOS) 0.3 g Example 2: Packaged infant milk formula according to example 1, wherein the packaging is provided with a label indicating that the formula can be suitably used to reduce difficulty with breathing, Example 3: Packaged infant milk formula according to example 1, further containing per 100 ml final product (and pei 13.1 g powder); Raftilin HP, Orafti BE) 0.1 g 1,3xl08 cm tuna fish oil 0.3 gram 40% arachidonic acid oil 0.3 gram (DSM Food Specialties, Delft, Netherlands) Example 4; Packaged infant milk formula according to example 3, further containing per 100 ml final product (and per 13.1 g powder); choljne 6,5 mg zinc 2 mg Example 5: Packaged infant milk formula according to example 1, further containing immnnoglobuin with respiratory syncytial virus neutralizing activity as described in EP0808173. Example 6: Effectiveness of transgalactooiigsaccnarides in standard infant formula's for prevention of respiratory tract infections in infants of the age until 1 year. Method; A muldcentre clinical trial was performed in Italy, including 7 centers and 56 paediatricians. At the moment breast-feeding was stopped, infants were divided into two groups. The infants in Group A (n=69) were administered Nutrilon™ 1 or 2 supplemented with oligosacchaiides to a final concentration of 0.36 g transgalactooligosaccharides/100 ml (Vivinal-GOS™; Borculo Domo Ingredients, Netherlands) and 0.04 g fructopolysaccharide/100 ml (Raftiline HP™, Orafti, Tienen, Belgium). The infants in control group B (n=82) received standard NutrilonTM I or 2. Nutrilon 1™ contains 45 en% carbohydrate, 8 en% protein and 47 en% fat; about 97 wt% lactose based on total carbohydrate; 7.3 gram lactose pej 100 ml; about 54 gram lactose pet 100 gram dry weight of the complete composition. Nutrilon 213* contains 47 en% carbohydrate, 10 en% protein and 43 en% fat; about 96 wt% lactose based on total carbohydrate; 7.9 gram lactose per 100 ml; about 54 gram lactose per 100 gram dry weight of the complete composition. Results: The age of the infants varied between 2 and 9 months and the infants were followed for 6 months. Both groups did not show any difference in nutritional intake. In group A a total number of 32 upper respiratory tract infection episodes was observed. In control group B a total number of 60 upper respiratory tract infection episodes was observed. Thus the incidence of upper respiratory infection episodes was significant (p Example 7: Sachet Sachet containing 1 gram lactose and 0.5 gram transgalactooligosacchavides, for addition to a liquid nutrition containing fat, protein and carbohydrate designed for ingestion by patients suffering from COPD or diabetes, said sachet being provided with a label indicating that addition of the contents of the sachet to the nutrition reduces trie incidence of respiratory tract infection development We Claim 1. A nutritional composition comprising a) a galactose containing indigestible oligosaccharide containing at minimum two terminal saccharide units, wherein one terminal saccharide unit is selected from the group consisting of glucose and galactose; and the other terminal saccharide is selected from the group consisting of galactose and fucose;and b) at minimum 5 wt.% digestible galactose saccharide based on total dry weight of the composition, said saccharide is selected from the group consisting of galactose and digestible galactose containing saccharide containing at minimum two terminal saccharide units, wherein one terminal saccharide unit is selected from the group consisting of glucose and galactose; and the other terminal saccharide is selected from the group consisting of galactose and fucose. 2. The composition as claimed in claim 1, said composition comprising (a) 10 to 60 en% lipid; 5 to 50 en% protein; and 15 to 90 en% carbohydrate; (b) 40 to 60 wt.% lactose based on total dry weight of the composition; (c) 0.1 to 12 grams transgalactooligosaccharides with a degree of polymerisation (DP), 2 to 10 per 100 gram dry weight of the composition;and (d) long chain polyunsaturated fatty acid (LC-PUFA) selected from the group consisting of eicosapentaenoic acid (EPA, n-3), docosahexaenoic acid (DHA, n-3) and arachidonic acid (AA, n-6). 3. The composition as claimed in claim 1, wherein the galactose containing indigestible oligosaccharide is selected from the group comprising a terminal galactose and a terminal glucose. 4. The composition as claimed in claim 3, wherein the galactose containing indigestible oligosaccharide is transgalactooligosaccharides with a degree of polymerisation (DP) of 2 to 10. 5. The composition as claimed in any one of the preceding claims, wherein the said composition optionally comprises fat, carbohydrate and/or protein of plant, animal, bacterial or synthetic origin. 6. The composition as claimed in any claim 1, wherein the said composition comprises 0.1 to 12 grams galactose containing indigestible oligosaccharide per 100 gram dry weight of the composition. 7. The composition as claimed in any one of the preceding claims, wherein the composition optionally comprises a second indigestible oligosaccharide selected from the group consisting of fructootigosaccharides, hydrolysed inulin and inulin. 8. The composition as claimed in claim 1, wherein the said composition contains long chain polyunsaturated fatty acid (LC-PUFA) selected from the group consisting of eicosapentaenoic acid (EPA, n-3), docosahexaenoic acid (DHA, n-3) and arachidonic acid (AA, n-6). 9. The composition as claimed in any one of the preceding claims, wherein the said composition optionally comprises probiotic bacteria selected from the group Lactobacillus, Bifidobacterium, Lactococcus, Pediococcus, Enterococcus, Propionibacterium, Bacillus and Streptococcus. 10. The composition as claimed in claim 1, wherein the said composition comprises 10 to 60 en% lipid, 5 to 50 en% protein and 15 to 90 en% carbohydrate. 11. The composition as claimed in any one of the preceding claims, wherein the said composition optionally comprises acid oligosaccharides. 12. The composition as claimed in any one of the preceding claims, wherein the said composition optionally comprises an immunoglobulin with respiratory syncytial virus neutralizing activity. 13. The composition as claimed in claim 1, said composition optionally comprising a) an immunoglobulin having a virus neutralizing effect; and b) fat, carbohydrate/protein of plant, animal, bacterial or synthetic origin. 14. The composition as claimed in claim 13, wherein the immunoglobulin having a virus neutralizing effect is an immunoglobulin capable of neutralizing a virus selected from the group consisting of Myxovirus, Orthomyxokvirus, Rhinovirus, Echoviruses, Coxsackieviruses, Adenovirus, Respiratory Syncytial virus (RSV), Coronavirus, Measles virus and Cytomegalovirus. 15. A composition as claimed in claim 1, wherein the said composition is beneficial in case of respiratory tract infection and respiratory tract infection disease.

Documents:

1243-DELNP-2007-Abstract-(28-09-2011).pdf

1243-delnp-2007-abstract.pdf

1243-DELNP-2007-Claims-(28-09-2011).pdf

1243-delnp-2007-claims.pdf

1243-DELNP-2007-Correspondence Others-(28-09-2011).pdf

1243-delnp-2007-correspondence-others-1.pdf

1243-DELNP-2007-Correspondence-Others.pdf

1243-delnp-2007-description (complete).pdf

1243-DELNP-2007-Form-1-(28-09-2011).pdf

1243-DELNP-2007-Form-1.pdf

1243-DELNP-2007-Form-13-(28-09-2011).pdf

1243-delnp-2007-form-18.pdf

1243-DELNP-2007-Form-2-(28-09-2011).pdf

1243-delnp-2007-form-2.pdf

1243-delnp-2007-form-26.pdf

1243-DELNP-2007-Form-3-(28-09-2011).pdf

1243-DELNP-2007-Form-3.pdf

1243-DELNP-2007-Form-5-(28-09-2011).pdf

1243-delnp-2007-form-5.pdf

1243-DELNP-2007-GPA-(28-09-2011).pdf

1243-delnp-2007-pct-210.pdf

1243-delnp-2007-pct-304.pdf

1243-delnp-2007-pct-306.pdf

1243-DELNP-2007-Petition 137-(28-09-2011).pdf