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WO 2009/082227 Al (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 2 July 2009 (02.07.2009) WO 2009/082227 Al (51) International Patent Classification: 1, NL-6708 SE Wageningen (NL). GROENENDIJK, A23L 1/0522 (2006.01) A61K 31/7072 (2006.01) Martine [NL/NL]; Mazurkastraat 50, NL-2992 GP A23L 1/0526 (2006.01) A61K 35/60 (2006.01) Barendrecht (NL). KAMPHUIS, Patrick Joseph Gerar- A23L 1/0528 (2006.01) A61K 47/36 (2006.01) dus Hendrikus [NL/NL]; Adriaen van Ostadelaan 118, A23L 1/053 (2006.01) A61K 47/38 (2006.01) NL-3583 AM Utrecht (NL). A23L 1/0532 (2006.01) A23L 1/22 (2006.01) A23L 1/0534 (2006.01) A61P 25/28 (2006.01) (74) Agent: KETELAARS, Maarten; Nederlandsch Oc- A23L 1/30 (2006.01) A61K 9/00 (2006.01) trooibureau, J.W. Frisolaan 13, NL-2517 JS The Hague A61K 31/7052 (2006.01) (NL). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/NL2008/050843 kind of national protection available): AE, AG, AL, AM, AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, (22) International Filing Date: EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, 22 December 2008 (22.12.2008) IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, (25) Filing Language: English MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (30) Priority Data: 0712381 1.7 20 December 2007 (20.12.2007) EP (84) Designated States (unless otherwise indicated, for every PCT/NL2008/050124 kind of regional protection available): ARIPO (BW, GH, 4 March 2008 (04.03.2008) NL GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), (71) Applicant (for all designated States except US): N.V. European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, NUTRICIA [NLML]; Eerste Stationsstraat 186, NL-2712 FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, HM Zoetermeer (NL). NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (72) Inventors; and (75) Inventors/Applicants (for US only): DE KORT, Es¬ Published: ther Jacqueline [NL/NL]; Nienke van Hichtumstraat — with international search report (54) Title: A PALATABLE NUTRITIONAL COMPOSITION COMPRISING A NUCLEOTIDE AND/OR A NUCLEOSIDE AND A TASTE MASKING AGENT (57) Abstract: The present invention relates to the use of a taste masking agent selected from the group of cellulose; starch; xanthan gum; gellan gum; alginate; galactomannans such as fenugreek, guar gum, tara gum, locust bean gum, and cassia gum; gum karaya; gum tragacanth; carrageenan; and mixture thereof, for improving one or more of mouth feel, taste, aftertaste and smell of a liquid aqueous nutritional composition comprising a nucleotide and/or a nucleoside. It also relates to a nutritional composition comprising an unsavoury nucleotide and/or a nucleoside component, having improved sensory characteristics such as improved mouth feel, taste, aftertaste and smell.In particular, it relates to a composition comprising said un- savoury nucleotide and/or a nucleoside component, in particular comprising an uridine- containing nucleotide and/or a nucleoside in combination with an unsavoury edible oil, such as a fish oil. A PALATABLE NUTRITIONAL COMPOSITION COMPRISING A NUCLEOTIDE AND/OR A NUCLEOSIDE AND A TASTE MASKING AGENT FIELD OF THE INVENTION The present invention relates to the use of a taste masking agent for improving one or more of mouth feel, taste, aftertaste and smell of a liquid aqueous nutritional composition com prising a nucleotide and/or a nucleoside. It also relates to a liquid aqueous nutritional com position comprising a nucleotide and/or a nucleoside component, having improved sensory characteristics such as improved mouth feel, taste, aftertaste and smell. In particular, it re lates to a composition comprising a nucleotide and/or a nucleoside component, in particu lar comprising an uridine-containing nucleotide and/or a nucleoside in combination with an unsavoury edible oil, such as a fish oil. BACKGROUND OF THE INVENTION Memory loss, dementia and reduced brain function are major problems, particularly in eld erly. Significant effort is put in the treatment and/or prevention of these disorders related with impaired nerve functioning. Persons older than 50 years of age are particularly prone to developing such disorders. One way to tackle the problem is the administration of an uridine-containing nucleotide and/or a nucleoside, preferably in the form of a nutritional composition. WO2006/031683 (MIT, 23 March 2006) teaches to administer a composition comprising uridine or a source of uridine, thereby inhibiting or preventing a decline in a cognitive func tion in a subject, wherein said decline is a result of a cardiovascular disease, neurodegen erative disease, or psychiatric disease. Uridine, in particular in the form of uridine m ono phosphate (UMP), is a nutrient that increases synthesis and release of neurotransmitters and membrane synthesis by neural cells and brain cells. Nutritional products containing uridine and high concentrations of macro- and micronutrients are administered to elderly patients, with the aim to prevent memory decline. However, when targeting this group of patients often troubled by reduced appetite or dis turbed eating behaviour, such a nutritional product needs to satisfy a number of require ments. It should be readily consumable, thus avoiding an insufficient intake of the active ingredients. For that purpose, it is strived for a product that is desirably palatable and which has a sufficiently low viscosity so it can be easily swallowed. It is desirable to administer active ingredients to elderly and Alzheimer patients in liquid form. Furthermore, it is highly desirable to administer the active ingredients in a relatively small dosage form such that the administration does not interfere with normal nutritional intake. Additionally palatability is of utmost importance to ensure compliance products need to be consumed for many days, weeks, months or years. Hence, based on the knowledge that nucleotides/nucleosides, particularly uridine-and/or cytidine-containing nucleotides, are advantageously used by patients suffering from mem ory impairment, the present inventors designed a liquid composition containing uridine monophosphate suitable for administration to elderly and Alzheimer patients, i.e. a liquid composition prepared by admixing different ingredients including a large amount of uridine monophosphate, edible oils, proteins and preferably also minerals. However, unexpectedly, the uridine- and/or cytidine-containing nucleotides, in particular the nutritional composition comprising said uridine- and/or cytidine-containing nucleo tides had a unpleasant taste, as further characterised by Qualitative Descriptive Analysis (QDA). Uridine as such is rated as "very bitter", uridine monophosphate is rated as "sickly" or "salty". It is the first time that this problem is recognized in the art for this type of prod uct, high in nucleotides and/or nucleosides. The problem is further aggravated by the fact that the product in question preferably con tains a fish oil, having a fishy taste and smell of its own, which is - in combination with the taste of the uridine- and/or cytidine-containing nucleotides experienced as off-tastes like "oily" and "sickly". Unexpectedly, it was found that mouth feel, taste, aftertaste and smell of a liquid aqueous nutritional composition comprising a nucleotide and/or a nucleoside, and optionally an un- savoury edible oil, in particular a fish oil, could be improved considerably with the use of a taste masking agent selected from the group of cellulose ; starch ; xanthan gum ; gellan gum ; alginate ; galactomannans such as fenugreek, guar gum, tara gum, locust bean gum, and cassia gum ; gum karaya ; gum tragacanth ; carrageenan ; and mixture thereof. SUMMARY DESCRIPTION OF THE INVENTION In one aspect, the present invention is concerned with the use of a taste masking agent se lected from the group of cellulose ; starch ; xanthan gum ; gellan gum ; alginate ; galacto mannans such as fenugreek, guar gum, tara gum, locust bean gum, and cassia gum ; gum karaya ; gum tragacanth ; carrageenan ; and mixture thereof, for improving one or more of mouth feel, taste, aftertaste and smell of a liquid aqueous nutritional composition compris ing a nucleotide and/or a nucleoside. Most preferably, the taste masking agent is cellulose. The taste masking agent itself is normally considered neutral in taste and smell, and thus distinguishes from flavouring agents. According to the invention, an improved mouth feel, taste, aftertaste and smell can be quali tatively determined using a QDA panel test which defines and rates mouth feel, taste, after taste and smell in a formulation. It can also be determined in a consumer panel score, and can be expressed as a higher score for overall liking as defined and explained in the experimental section. In a further aspect, the present invention is concerned with the aforementioned use, wherein the nucleoside is selected from the group of adenosine, guanosine, uridine, cytidine, thymidine, inosine, derivatives thereof, and mixtures thereof and/or the nucleo tide is selected from the group of adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), guanosine monophosphate (GMP), guanosine d i phosphate (GDP), guanosine triphosphate (GTP), uridine monophosphate (UMP), uridine diphosphate (UDP), uridine triphosphate (UTP), cytidine monophosphate (CMP), cytidine diphosphate (CDP), and cytidine triphosphate (CTP), and mixtures thereof.
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