A palatable nutritional composition comprising a nucleotide and / or a nucleoside and a taste-masking agent

Abstract

The present invention relates to the use of a taste-masking agent selected from the group consisting of cellulose; starch; xanthan gum; gellan gum; alginate; galactomannan, such as fenugreek, guar gum, tara gum, locust bean gum and cassia gum; gum karaya; gum tragacanth; carrageenan; and mixtures thereof for improving one or more of the mouthfeel, taste, aftertaste and odour of a liquid aqueous nutritional composition comprising a nucleotide and / or a nucleoside. The present invention also relates to a nutritional composition comprising a bitter nucleotide and / or a nucleoside component having improved organoleptic properties, such as improved mouthfeel, taste, aftertaste and odour. In particular, the present invention relates to a composition comprising said bitter nucleotide and / or a nucleoside component, in particular comprising a uridine-containing nucleotide and / or a nucleoside in combination with a bitter edible oil, such as fish oil.

Description

Technical Field

[0001] This invention relates to the use of a taste masking agent for improving one or more of the mouthfeel, flavor, aftertaste, and odor of a liquid aqueous nutritional composition containing a nucleotide and / or a nucleoside. The invention also relates to a liquid aqueous nutritional composition containing a nucleotide and / or a nucleoside component that has improved sensory characteristics, such as improved mouthfeel, flavor, aftertaste, and odor. Specifically, the invention relates to a composition containing a nucleotide and / or a nucleoside component—particularly a uridine-containing nucleotide and / or a nucleoside combined with an unpalatable edible oil (e.g., fish oil). Background Technology

[0002] Memory loss, dementia, and decreased brain function are major problems, especially for people over middle age. Significant efforts have been devoted to treating and / or preventing these conditions associated with impaired neurological function. People over 50 are particularly susceptible to these conditions.

[0003] One way to solve this problem is to administer a uridine-containing nucleotide and / or nucleoside, preferably in the form of a nutritional composition.

[0004] WO2006 / 031683 (MIT, March 23, 2006) teaches the administration of a composition containing uridine or a uridine derivative to inhibit or prevent cognitive decline in subjects, said decline being caused by cardiovascular disease, neurodegenerative disease, or mental illness. Urate, particularly uridine monophosphate (UMP), is a nutrient that enhances the synthesis and release of neurotransmitters and membrane synthesis via nerve cells and brain cells. The administration of a nutritional supplement containing uridine and high concentrations of macronutrients and micronutrients to middle-aged patients aims to prevent memory decline.

[0005] However, when targeting patients who are frequently troubled by decreased appetite or disrupted eating behaviors, such nutritional supplements need to meet several requirements. They should be easily digestible to avoid insufficient intake of active ingredients. To this end, efforts are being made to obtain a product that is palatable and has a sufficiently low viscosity to make it easy to swallow.

[0006] There is a desire to administer the active ingredient in liquid form to middle-aged patients and Alzheimer's patients. Furthermore, there is a strong preference for administering the active ingredient in relatively small doses so that the administration does not interfere with normal nutritional intake. In addition, palatability is of paramount importance in ensuring compliance with products intended for consumption over many days, weeks, months, or years.

[0007] Therefore, based on the fact that nucleotides / nucleosides—especially nucleotides containing uridine and / or cytidine—can be advantageously used by patients suffering from memory impairment, the inventors of this invention have designed a liquid composition containing uridine monophosphate suitable for administration to middle-aged patients and Alzheimer's disease patients, namely a liquid composition prepared by mixing different components including a large amount of uridine monophosphate, edible oil, protein, and preferably minerals.

[0008] However, unexpectedly, nucleotides containing uridine and / or cytidine—especially nutritional compositions containing said uridine and / or cytidine nucleotides—have an unpleasant taste, as further characterized by qualitative descriptive analysis (QDA). Uridine itself is considered “extremely bitter,” and uridine monophosphate is considered “sickly” or “salty.” This problem with products containing large amounts of nucleotides and / or nucleosides is being recognized in the art for the first time.

[0009] The problem is further exacerbated by the fact that the product preferably contains a fish oil that has its own fishy smell and odor, which, combined with the taste of nucleotides containing uridine and / or cytidine, has an off-taste, such as "greasy" and "nauseating".

[0010] Surprisingly, it was found that using a masking agent selected from the following substances significantly improved the mouthfeel, taste, aftertaste, and odor of liquid aqueous nutritional compositions containing a nucleotide and / or a nucleoside and optionally an unpleasant edible oil (especially fish oil): cellulose; starch; xanthate gum; gellan gum; alginate; galactomannan, such as fenugreek, guar gum, tara gum, locust bean gum, and cassia gum; black privet gum; tragacanth gum; carrageenan; and mixtures thereof. Summary of the Invention

[0011] On one hand, the present invention relates to the use of a masking agent selected from the group consisting of cellulose, starch, xanthate gum, gellan gum, alginate, galactomannan, such as fenugreek, guar gum, aralia gum, locust bean gum, and Chinese cinnamon bark gum; ebony gum; tragacanth gum; carrageenan; and mixtures thereof. Most preferably, the masking agent is cellulose. The masking agent itself is generally considered to have an inconspicuous taste and odor, and is therefore distinct from flavoring agents.

[0012] According to the present invention, the improved taste, flavor, aftertaste and odor can be qualitatively determined using a QDA panel test to define and evaluate the taste, flavor, aftertaste and odor of the agent.

[0013] It can also be measured by consumer panel score, and as defined and explained in the experimental section, a high score can be expressed as the one that everyone likes.

[0014] On the other hand, the present invention relates to the above-mentioned uses, wherein the nucleoside is selected from adenosine, guanosine, uridine, cytidine, thymidine, inosine, derivatives thereof, and mixtures thereof, and / or the nucleotide is selected from adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), guanosine monophosphate (GMP), guanosine diphosphate (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.

[0015] In another aspect, the present invention relates to the above-mentioned uses, wherein the liquid composition further comprises an unpalatable edible oil, particularly fish oil. Preferably, the fish oil contains at least one ω-3 fatty acid selected from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Detailed Implementation

[0016] masking agent

[0017] The composition of the present invention contains a flavor masking agent. Preferably, the composition of the present invention contains a flavor masking agent selected from the following substances: cellulose; starch; xanthate gum; gellan gum; alginate; galactomannan, such as fenugreek, guar gum, aralia gum, locust bean gum and Chinese cinnamon bark gum; ebony gum; tragacanth gum; carrageenan; and mixtures thereof.

[0018] More preferably, the composition of the present invention contains a masking agent selected from xanthan gum, gellan gum, and cellulose, and mixtures thereof. The masking agent preferably has shear-thinning and / or thixotropic properties, which are considered beneficial to formulations or products using the masking agent. Even more preferably, the masking agent is selected from xanthan gum and cellulose. Most preferably, the composition of the present invention contains cellulose.

[0019] According to a preferred embodiment, the composition of the present invention contains a flavor masking agent selected from the following substances: cellulose; starch; xanthan gum; gellan gum; alginate; galactomannan, such as fenugreek, guar gum, aralia gum, locust bean gum and Chinese cinnamon bark gum; ebony gum; tragacanth gum; and carrageenan.

[0020] According to another preferred embodiment, the masking agent comprises a starch combined with at least one compound selected from: cellulose, cellulose derivatives, xanthan gum, gellan gum, alginate, guar gum, locust bean gum, black privet gum, tragacanth gum, carrageenan, alginic acid, etc. This combination has been disclosed in WO 2001 / 32034 (Smithkline Beecham, May 10, 2001) for masking the taste of unpleasant edible marine oils—i.e., water-insoluble substances. The use of this combination to improve the taste, mouthfeel, aftertaste, and odor of liquid aqueous nutritional compositions containing a nucleotide and / or a nucleoside is not implied or disclosed herein.

[0021] According to a preferred embodiment, the composition of the present invention contains at least 70% by weight of cellulose based on the total weight of the masking agents.

[0022] Preferably, the composition of the present invention contains 0.05-3% by weight, more preferably 0.1-2% by weight, and more preferably 0.3-1% by weight of one or more of the above-mentioned masking agents of the present invention, based on the total weight of the composition.

[0023] One preferred flavor masking agent is starch. Starch can be obtained from many sources, such as corn, high-amylase corn, waxy corn, potatoes, rice, and wheat, and can be in pre-coagulated or non-coagulated form.

[0024] Flavor masking agents with pseudoplasticity are usually preferred, such as xanthan gum, gellan gum, and cellulose.

[0025] One preferred flavor masking agent is xanthate gum, a polysaccharide. Its main chain consists of two β-D-glucose units linked at positions 1 and 4. Its side chains consist of two mannose units and one glucuronic acid unit; thus, the chain of xanthate gum is composed of repeating modules of five sugar units. The side chains are linked at position 3 to each additional glucose unit in the main chain. Approximately half of the terminal mannose units have a pyruvate group linked at positions 4 and 6 in a ketal form. The other mannose units have an acetyl group at position 6. Xanthate gum exhibiting pseudoplasticity and stability over a wide temperature and pH range is preferred.

[0026] Gellan gum is a linear tetrasaccharide (4)-L-rhamnopyranosyl-(α-1→3)-D-glucopyranosyl-(β-1→4)-D-glucopyranosyl-(β-1→4)-D-glucopyranosyl-(β-1→4)-(β-1→4)-glucopyranosyl ...

[0027] In a preferred embodiment, the composition contains cellulose. Preferably, the composition of the present invention contains 0.05-3% by weight of cellulose based on the total weight of the composition, more preferably 0.1-2% by weight, and more preferably 0.3-1% by weight. Cellulose is a linear homopolymer of dehydrated glucose units linked together by β-D-1,4 glycosidic bonds. Cellulose is preferably selected from high-viscosity cellulose and cellulose derivatives, such as hydroxyethyl cellulose, hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), microcrystalline cellulose (MCC), and methylcellulose.

[0028] Excellent results were found when using a large amount of nonionic cellulose ether microcrystalline cellulose, with excellent stability as well.

[0029] It was also found that the taste, flavor, aftertaste and aroma of the liquid aqueous nutrient composition of the present invention improve over time, resulting in excellent shelf life in terms of the aforementioned taste properties.

[0030] The flavor masking agent of the present invention can also act as a thickener for the liquid aqueous nutrient composition of the present invention. This function has been disclosed in our co-pending application PCT / NL2008 / 050124, the entire contents of which are incorporated herein by reference.

[0031] In the context of this invention, it is important to distinguish between slowing the sedimentation of already formed particles and / or increasing viscosity, and reducing and / or preventing particle formation. In the case of this invention, stabilizing the already suspended particles is less important. After all, in such cases, sediment formation will still occur because, over time, particles with larger masses will reach the bottom of the packaging. To address the problems of this invention, a key aspect is that thickeners prevent and / or reduce particle formation, thereby reducing the formation of deposits at the bottom of the packaging.

[0032] While the inventors do not wish to be confined to theory, it is speculated that the reduction in particle formation may contribute in part to the improvement of the mouthfeel, taste, aftertaste, and aroma of the liquid aqueous nutrient composition of the present invention.

[0033] Due to the limited water solubility and / or dispersibility of nonionic cellulose ethers, the liquid aqueous nutritional compositions of the present invention preferably also contain a significant amount of anionic polymeric polysaccharides. In a preferred embodiment, the anionic polysaccharides are selected from guar gum, carboxymethyl cellulose, hemicellulose, pectin, alginate, konjac flour, psyllium, tragacanth gum, xanthate gum, ebony gum, chia, wellan, ghatti, or okra, or hydrolysates of these oligosaccharides or polycarbohydrates. These anionic polysaccharides are beneficial for the production of stable aqueous foods, particularly heat-treated or sterilized liquid products containing at least one nucleotide, optionally an unpalatable edible oil (e.g., seafood oil), and one or more proteins, as well as another edible oil or fat. The anionic polymeric polysaccharides, such as guar gum or anionic cellulose, enhance the stability of the aqueous system and prevent cellulose aggregation / clothing. In one embodiment, anionic cellulose is preferred, preferably carboxymethyl cellulose (CMC).

[0034] In a preferred embodiment, the liquid aqueous nutrient composition of the present invention contains a mixture of MCC and anionic polymeric polysaccharide—preferably CMC. The liquid aqueous nutrient composition of the present invention preferably contains 0.05-3.0 wt%, preferably 0.05-1 wt%, more preferably 0.3-1.0 wt% of a mixture of microcrystalline cellulose (MCC) and anionic polymeric polysaccharide based on the total weight of the composition. The relative weight ratio of nonionic cellulose to anionic polymeric polysaccharide is preferably at least 3:1, more preferably 4:1 to 9:1. In one embodiment, preferably at least 70 wt%, more preferably 75-90 wt% of the cellulose present in the liquid aqueous nutrient composition of the present invention is provided by MCC. Typically, commercially available MCC is coated with CMC or carboxymethyl cellulose. In the most preferred embodiment, the remainder consists of CMC. Suitable candidates are Avicel-plus BV2312 and Vivapur MCG591F, which are commercially available from FMC biopolymers and Rettenmaier, respectively. The report described particularly good results for the Vivapur MCG591F.

[0035] It was also found that the optimal characteristics were obtained by a masking agent with a certain particle size. Preferably, the masking agent of the present invention is a mixture of particles in which at least 50% by weight of the particles have a particle size of 20-200 micrometers. The larger the particle size, the longer the deposition can be avoided.

[0036] The inventors have discovered that the amount of cellulose in the liquid aqueous nutrient composition of the present invention is preferably more than 0.05% by weight, more preferably at least 0.1% by weight, more preferably at least 0.3% by weight, and most preferably about 0.4% by weight, based on the total weight of the composition. It is believed that at these concentrations, a relatively weak three-dimensional network structure is established, which effectively keeps the components within the liquid matrix, resulting in no sediment formation and a good taste. To control the viscosity and taste of the composition, it is preferable that the composition contains less than 1.0% by weight, more preferably less than 0.8% by weight of cellulose.

[0037] In addition to cellulose, gellan gum, and / or xanthan gum thickeners, the content of other thickeners in the liquid aqueous nutritional composition of the present invention is preferably low. Other thickeners are substances known to increase the viscosity of the composition without substantially altering other properties (e.g., taste) of the composition. Preferably, the composition contains less than 0.1 wt%, more preferably less than 0.05 wt% of the other food thickeners, and most preferably, it contains none of the other food thickeners. In one embodiment, the weight ratio of the compounds with thickening effects other than cellulose and xanthan gum to the total weight of the cellulose and xanthan gum thickeners of the present invention is less than 0.1, preferably less than 0.01, and more preferably 0. More preferably, the weight ratio of the compounds with thickening effects other than cellulose to the total weight of the cellulose thickeners present in the composition is less than 0.1, more preferably less than 0.01, and most preferably 0.

[0038] Physical characteristics

[0039] The composition can be characterized by its rheological properties. For this purpose, viscosity measurements are performed using either a cup and bob geometry or a plate and cone geometry. The samples can be appropriately analyzed using an MCR 300 rheometer (Anton Paar Physica, Graz, Austria).

[0040] The cup-and-hammer viscometer operates by determining the precise volume of the specimen to be sheared in the test chamber, measuring and plotting the torque required to reach a certain rotational speed. The cup-and-hammer viscometer has two classic geometries, known as the "Couette" or "Searle" systems—distinguished by whether the cup or hammer rotates. Either can be used to determine the storage modulus G', loss modulus G" and loss factor at 0.1 Hz and 20 °C with strains from 1 to 100%. The tangent of the loss factor is δ = G" / G'. Structural strength is assessed by measuring G' and G" respectively. The storage modulus and loss modulus can be appropriately determined using a DG 26.7 cup and a large cylinder (Anton Paar Physica, Graz, Austria). These amplitude scan measurements can be performed at strains from 0.01 to 1000% and 10 s. -1 The shear rate is determined. It is preferable to add the sample to the cup at least 10 minutes before starting the measurement.

[0041] It was found that better results were obtained when G' was greater than G” but close to G (i.e., 0.1 < tangent δ < 100). In this case, deposition is greatly slowed down or even avoided. At larger values, consumers will experience an undesirable "gel-like" taste, which can be described as somewhat sticky, slippery, or gooey. The best results were obtained when the tangent δ < 10, and more preferably when the tangent δ is greater than 0.2. As measured at 0.1 Hz and 20°C, the tangent δ at any strain from 1 to 100% should be within the above range. A substantially linear relationship can be observed within the strain range of 1 to 100%. For comparison, G” > G’ is used when the masking agent of the present invention is absent, indicating that the low-viscosity product has lower structural strength. It has a purely liquid characteristic and a tangent δ > 1000.

[0042] Even more preferably, when similar measurements are performed but the strain is 100-1000%, the tangent value δ is also kept in the range of 0.1-100, preferably greater than 0.2.

[0043] The liquid aqueous nutrient composition of the present invention preferably has a low viscosity, preferably within 100 seconds. -1 The shear rate and viscosity measured at 20°C are 1-100 mPa·s. High viscosity should be avoided because it is often accompanied by unacceptable taste characteristics and is difficult for the target group (e.g., middle-aged patients and Alzheimer's patients) to consume. More preferably, the composition of the present invention is preferably provided in the form of a beverage that can be consumed through a straw, which makes the product easier to consume and improves compliance. In a preferred embodiment, the viscosity of the composition of the present invention is 100 mPa·s. -1The shear rate is less than 80 mPa·s at 20°C, more preferably less than 100 sec. -1 The shear rates at 20°C are 1-40 mPa·s. These viscosities can be measured using a plate-cone geometry. A plate-cone viscometer uses a cone with a very shallow angle that is in direct contact with a plate. In this system, the shear rate below the plate is constant to the precision of the rheological curve and the appropriate degree of deconvolution; the viscosity can be obtained directly from a graph of shear stress (torque) versus shear rate (angular velocity).

[0044] Preferably, the liquid aqueous nutrient composition of the present invention meets the FSMP index and therefore contains a high amount of minerals and vitamins. Thus, the product typically has a molar osmotic concentration of 300-800 mOsm / kg.

[0045] To prevent viscosity from increasing due to protein gelation, the pH of the liquid is preferably maintained at approximately neutral in the presence of proteins; however, for good palatability, the pH is preferably slightly acidic. The liquid aqueous nutrient composition of the present invention preferably has a pH range of 5-7.5, more preferably 6-7.

[0046] The liquid aqueous nutrient composition of the present invention preferably has a dry matter content in the range of 10-40% by weight, more preferably 10-30% by weight.

[0047] nucleosides and nucleotides

[0048] The liquid aqueous nutrient composition of the present invention contains a nucleotide and / or nucleoside, preferably a nucleotide. Nucleotides are generally more effectively absorbed by the human body.

[0049] In the context of this invention, a nucleoside is a meglumine composed of a nucleobase bonded to a ribose or deoxyribose sugar. Examples include cytidine, uridine, adenosine, guanosine, thymidine, and inosine, their deoxy derivatives, their acylated derivatives, and their phosphate derivatives. When a nucleoside is phosphorylated (monophosphorylation, diphosphorylation, or triphosphorylation), it forms a nucleotide, which is a molecular structural unit of DNA and RNA.

[0050] The liquid aqueous nutrient composition of the present invention contains at least 50 mg of nucleotides and / or nucleosides per 100 ml of composition, preferably 80-3000 mg of nucleotides and / or nucleosides, more preferably 100-2000 mg of nucleotides and / or nucleosides, and most preferably 200-1000 mg of nucleotides and / or nucleosides.

[0051] Preferably, the liquid aqueous nutrient composition of the present invention is characterized by containing nucleotides primarily relative to nucleosides. Therefore, the weight ratio of nucleotides to nucleosides is preferably greater than 2.0, more preferably greater than 4.0, most preferably greater than 10.0, and particularly greater than 20. These ratios are particularly preferred for the liquid aqueous nutrient composition of the present invention with a pH of 2.0-8.0, more preferably 5-7.5, more preferably 5.5-7.5, and most preferably 6-7.

[0052] The inventors have discovered that the present invention works particularly well when the liquid aqueous nutrient composition of the present invention contains uridine or uridine nucleotides—preferably uridine nucleotides, preferably at least one uridine nucleotide selected from uridine monophosphate (UMP), uridine diphosphate (UDP) and uridine triphosphate (UTP)—or a mixture thereof.

[0053] Furthermore, the liquid aqueous nutrient composition of the present invention may contain cytidine or cytidine nucleoside—preferably cytidine nucleotide, preferably containing at least one cytidine phosphate selected from cytidine monophosphate (CMP), cytidine diphosphate (CDP) and cytidine triphosphate (CTP)—or a mixture thereof.

[0054] Most preferably, the liquid aqueous nutrient composition of the present invention contains UMP, because UMP is most effectively absorbed by the human body. Furthermore, surprisingly, the inventors have discovered that UMP contributes to product stability because it binds to calcium and even further reduces calcium-induced protein aggregation.

[0055] Therefore, the inclusion of UMP in the liquid aqueous nutritional composition of the present invention enables high efficacy to be achieved with the lowest possible dose and / or a smaller administration volume to the subject. Preferably, at least 50% by weight, more preferably at least 75% by weight, and most preferably at least 95% by weight of uridine is provided by UMP in the liquid aqueous nutritional composition of the present invention. The liquid aqueous nutritional composition of the present invention preferably contains 0.08-3g of uridine per 100ml of composition, more preferably 0.1-2g of uridine per 100ml of composition, and more preferably 0.2-1g of uridine per 100ml of composition.

[0056] The liquid aqueous nutrient composition of the present invention preferably contains 0.08-3g UMP per 100ml of composition, more preferably 0.1-2g UMP per 100ml of composition, and more preferably 0.2-1g UMP per 100ml of composition.

[0057] Preferably, the weight ratio of uridine to cytidine is greater than 1.0, more preferably at least 2.0, and most preferably greater than 5.0. Although cytidine is a precursor of uridine that crosses the blood-brain barrier, the composition of the present invention containing uridine is more potent and effective.

[0058] In another preferred embodiment, the liquid aqueous nutrient composition of the present invention preferably does not contain large amounts of other nucleotides. Therefore, preferably, the weight ratio of adenosine to uridine in the composition of the present invention is less than 0.1, more preferably less than 0.01, and most preferably 0. Preferably, the weight ratio of guanosine to uridine in the composition of the present invention is less than 0.1, more preferably less than 0.01, and most preferably 0. Preferably, the weight ratio of inosine to uridine in the composition of the present invention is less than 0.1, more preferably less than 0.01, and most preferably 0.

[0059] Unpalatable cooking oil

[0060] The liquid aqueous nutrient composition of the present invention preferably contains an unpalatable edible oil, suitably derived from an animal, plant, or mineral. Animal oils are typically derived from animal organs and tissues; plant oils are typically derived from plant seeds. Exemplary, non-limiting examples of oils include animal oils, such as marine animal oils like seal oil, whale oil, krill oil, fish oils like capelin oil and cod liver oils like cod liver oil, and fish oils produced from other body parts (also called fish oil); and plant oils, such as algae oil, castor oil, soybean oil, corn oil, and flaxseed oil.

[0061] Preferably, the unpalatable edible oil is fish oil containing docosahexaenoic acid (22:6 ω-3; DHA) and / or eicosapentaenoic acid (20:5 ω-3; EPA). Therefore, the liquid aqueous nutritional composition of the present invention contains at least one ω-3 fatty acid selected from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The liquid aqueous nutritional composition of the present invention preferably contains 100-5000 mg of one or more of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) per 100 ml, more preferably 500-3000 mg per 100 ml of the composition. This means that it is preferable that at least one of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is present in the composition of the present invention, thereby the concentration of DHA only, EPA only, or the sum of EPA and DHA is preferably 100-5000 mg per 100 ml of the composition, more preferably 500-3000 mg per 100 ml of the composition.

[0062] The compositions of the present invention preferably contain very low amounts of arachidonic acid (AA; 20:4ω-6). Preferably, the weight ratio of DHA / AA in the compositions of the present invention is at least 5, more preferably at least 10, and more preferably at least 15. The ratio of ω-6 to ω-3 fatty acids in the products of the present invention is preferably less than 0.5, and more preferably less than 0.2.

[0063] protein

[0064] The liquid aqueous nutritional composition of the present invention contains protein, preferably whole protein. Protein enables the production of palatable products. In particular, middle-aged patients and Alzheimer's disease (AD) patients can benefit from protein because it can enhance their motor skills. Preferably, the liquid aqueous nutritional composition of the present invention contains milk protein. Preferably, the liquid aqueous nutritional composition of the present invention contains a protein selected from whey protein, casein, or caseinate. Preferably, the liquid aqueous nutritional composition of the present invention contains caseinate; more preferably, the liquid aqueous nutritional composition of the present invention contains at least 70% by weight, more preferably at least 90% by weight, of casein and / or caseinate based on total protein.

[0065] Preferably, the protein is contained in its whole (unhydrolyzed) form to obtain a palatable product. Compared to its hydrolyzed form, this type of high molecular weight protein can increase the viscosity of the heat-treated liquid product. The inventors of this invention are able to prepare an acceptable product with good palatability and limited viscosity by applying the method of this invention, while also avoiding precipitation.

[0066] Preferably, the liquid aqueous nutrient composition of the present invention contains 0.2-10g of protein per 100ml, more preferably 1-6g of protein per 100ml, and most preferably 2-5g of protein per 100ml.

[0067] Other components

[0068] Preferably, the liquid aqueous nutrient composition of the present invention further contains one or more other components, preferably one or more minerals, a phospholipid, a digestible carbohydrate, an organic acid, an edible fat other than unpalatable edible oils, an indigestible carbohydrate, a preservative, a colorant, and a flavoring agent.

[0069] mineral

[0070] To meet important nutritional needs, the liquid aqueous nutrient composition of the present invention contains divalent cations, particularly calcium. Preferably, the liquid aqueous nutrient composition of the present invention contains 10-150 mg of calcium per 100 kcal, more preferably 40-100 mg of calcium per 100 kcal. Alternatively or additionally, the liquid aqueous nutrient composition of the present invention preferably contains 10-150 mg of calcium per 100 ml, more preferably 40-100 mg of calcium per 100 ml. Calcium can cause specific problems related to protein aggregation. Therefore, the liquid aqueous nutrient composition of the present invention preferably contains an insoluble calcium source. In a preferred embodiment, the calcium salt (one or more) used in the liquid aqueous nutrient composition of the present invention has a solubility of less than 0.15 g per 100 ml (softened) water at 20°C and pH 7, more preferably less than 0.1 g per 100 ml (softened) water, and even more preferably less than 0.06 g per 100 ml (softened) water.

[0071] The calcium salt is preferably selected from calcium carbonate, calcium sulfate, calcium citrate (e.g., monocalcium citrate or tricalcium citrate), calcium salts coated with a substance having limited solubility in water at pH 7 and soluble at pH below about 5 (hereinafter referred to as coated calcium salts), and mixtures thereof. Examples of coatings and methods for preparing coated calcium salts are given in WO00 / 038829, the entire contents of which are incorporated herein by reference. Preferably, the liquid aqueous nutrient composition of the present invention contains calcium citrate.

[0072] In some embodiments, particularly for compositions containing small amounts of nucleotides or nucleosides, phosphates need to be added. These phosphates can be added to provide the patient with the necessary minerals. Preferably, the liquid aqueous nutritional composition of the present invention contains phosphates of sodium, potassium, calcium, and / or magnesium. The liquid aqueous nutritional composition of the present invention preferably contains 30-80 mg of phosphorus per 100 kcal.

[0073] Phospholipids

[0074] Preferably, the liquid aqueous nutrient composition of the present invention contains a phospholipid, preferably 0.1-50% by weight of phospholipid based on the total weight of lipids, more preferably 0.5-20% by weight, and even more preferably 1-5% by weight of phospholipid based on the total weight of lipids. Preferably, the liquid aqueous nutrient composition of the present invention contains at least one selected from phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. The total amount of lipids is preferably 10-30% by weight on a dry matter basis, and / or 2-6 g of lipids per 100 ml of liquid composition. The inclusion of phospholipids improves the stability of the liquid aqueous nutrient composition of the present invention.

[0075] Digestible carbohydrates

[0076] Advantageously, the liquid aqueous nutritional composition of the present invention contains digestible carbohydrates. These digestible carbohydrates can positively influence the performance skills of subjects and enhance the beneficial effects of the liquid aqueous nutritional composition of the present invention. The liquid aqueous nutritional composition of the present invention preferably contains 1-50g of digestible carbohydrates per 100ml of liquid product, more preferably 5-30g per 100ml, and even more preferably 10-30g of carbohydrates per 100ml. The total amount of digestible carbohydrates, based on dry matter, is preferably 25-80% by weight, more preferably 40-80% by weight.

[0077] organic acids

[0078] Preferably, the liquid aqueous nutrient composition of the present invention contains an organic acid, preferably 0.5-10% by weight of organic acid (one or more), more preferably 1.5-6% by weight, based on the total weight of digestible carbohydrates. Preferably, the liquid aqueous nutrient composition of the present invention contains citric acid, preferably 0.5-10% by weight of citric acid, more preferably 1.5-6% by weight, based on the total weight of digestible carbohydrates.

[0079] Other edible fats

[0080] For the type of fat, a wide range of choices are possible besides the aforementioned unpalatable edible fats, as long as the fat possesses food-grade qualities. The fat may include medium-chain triglycerides (MCTs, primarily 8-10 carbon atoms long), long-chain triglycerides (LCTs), or any combination of both. MCTs are beneficial because they are easily absorbed and metabolized. Furthermore, the use of MCTs reduces the risk of malabsorption. LCT sources, such as rapeseed oil (especially low-erucic acid rapeseed oil), sunflower oil, corn oil, palm kernel fat, coconut fat, palm oil, or mixtures thereof, are preferred because they provide more energy per unit of fat. In one embodiment, the fat is a liquid fat, i.e., an oil.

[0081] Undigested carbohydrates

[0082] The enteric liquid nutrition composition of the present invention may optionally be enhanced with indigestible carbohydrates (dietary fiber), such as oligosaccharides. These oligosaccharides may include fructooligosaccharides (FOS), galacto-oligosaccharides (GOS), trans-galacto-oligosaccharides (TOS), xylooligosaccharides (XOS), soybean oligosaccharides, etc. Optionally, high molecular weight compounds—such as inulin, resistant starch, etc.—may also be included in the composition of the present invention. In another embodiment of the invention, the composition may contain a mixture of neutral and acidic oligosaccharides, as disclosed in WO2005 / 039597 (NVNutricia), the entire contents of which are incorporated herein by reference.

[0083] Flavorings

[0084] The nutritional compositions of the present invention may also contain a flavoring agent, which may be natural, artificial, or a mixture thereof. The addition of a flavoring agent can increase the palatability of the nutritional compositions of the present invention, thereby facilitating their intake and giving them a pleasant taste. While the nutritional compositions of the present invention without the flavoring agents described herein are already pleasant to taste, the addition of a flavoring agent that imparts a specific flavor can further improve palatability, thereby increasing patient compliance. Commonly used flavoring agents include chocolate, vanilla, coffee, caramel, cinnamon, strawberry, lemon, peach, orange, forest fruit, creamy flavor, nutty, coconut, etc. The nutritional compositions of the present invention may also contain artificial sweeteners, such as saccharin, aspartame, etc. Other embodiments will be apparent to those skilled in the art. A particularly preferred flavoring agent is selected from vanilla, creamy flavor, nutty, coconut, and caramel. Suitable flavoring agents may be used alone or in mixtures in amounts of about 0.005% to about 2.0% by weight, preferably less than 1% by weight, of the composition. The dosage can be easily determined by technicians based on application, taste requirements, and other factors.

[0085] Other features

[0086] People suffering from neuropathy or neurological problems often experience eating difficulties. Their sensory abilities and / or muscle control begin to impair, and in some cases, their strong desire to adopt appropriate eating habits also begins to decline. Some of these patients may experience an overall decrease in appetite, and a relatively large proportion of such patients become malnourished. Preferably, the product has an energy density of 0.8-4.5 kcal per g of composition, more preferably 0.9-2.5 kcal per ml.

[0087] Liquid nutrition products preferably have a long shelf life. However, increasing shelf life through heat treatment often leads to instability in product and / or palatability, resulting in unacceptable products. The liquid aqueous nutrition composition of the present invention can be heat-treated without significantly adversely affecting palatability. Therefore, the liquid aqueous nutrition composition of the present invention is preferably heat-treated, and more preferably, sterilized. In a preferred embodiment, the liquid aqueous nutrition composition of the present invention is subjected to ultra-high temperature (UHT) treatment. The UHT treatment is preferably carried out in a production line, i.e., before the final liquid product is packaged into the sales unit.

[0088] application

[0089] While in one particular embodiment, the invention specifically relates to the use of the liquid compositions of the invention for the prevention and / or treatment of neurodegenerative diseases (preferably selected from memory loss and / or cognitive impairment, Alzheimer's disease, Parkinson's disease, and / or dementia), and particularly to the use of the compositions of the invention for promoting and / or supporting healthy brain function, the invention also generally relates to any composition containing an unpalatable nucleotide and / or a nucleoside component—particularly a uridine-containing nucleotide and / or a nucleoside combined with an unpalatable edible oil (e.g., fish oil)—and for any particular purpose.

[0090] The composition can be specifically used for dietary management of subjects with neurodegenerative diseases, preferably selected from memory loss and / or cognitive impairment, Alzheimer's disease, Parkinson's disease and / or dementia.

[0091] The compositions of the present invention are preferably administered in doses of 25-500 ml, more preferably 50-250 ml, and more preferably 75-150 ml. Preferably, the compositions are administered once daily. The relatively limited volume facilitates uptake by the target patient group, such as middle-aged patients and Alzheimer's disease (AD) patients, preferably those over 50 years of age. Attached Figure Description

[0092] Figure 1 Bigraphies of various formulations after rotation with maximum variance (axes F1 and F2: 87.61%). m = taste; s = odor; t = flavor; at = aftertaste.

[0093] Figure 2: a) Spider web diagram R1 (solid line) relative to P2 (dashed line), and b) R1 (solid line) relative to V2 (dashed line); * Attributes that indicate significant differences. m = taste; s = odor; t = flavor; at = aftertaste.

[0094] Figure 3 Results of a consumer panel survey of four flavors (vanilla, strawberry, hot milk coffee, and peach / orange).

[0095] test

[0096] Research Design

[0097] Qualitative descriptive analysis (QDA) was performed on a series of formulations with varying amounts of protein, fat, masking agents, and maltodextrin / sucrose ratios (see Table 1 for reference formulations and...). Figure 1 All batches of the formulation were prepared with an orange / peach flavor. The study involved a single-blind slurping assessment of 19 attributes of the formulation, using a QDA panel of 11 trained evaluators who scored on a 100mm linear scale. The QDA panel received descriptions of the product's attributes (e.g., fishy taste, strength, fruity flavor, nausea, etc.) without indicating whether the product was most or least appreciated (level of pleasure).

[0098] Statistical analysis was performed using XLSTAT 7.5.2. Principal component analysis (PCA) was conducted using uniformly weighted summation and varimax rotation of axes (Addinsoft SARL). Significance was found at the 0.05 significance level (two-tailed test).

[0099] The objective of this study was to analyze whether the amounts of protein, fat, masking agents, or the maltodextrin / sucrose ratio affected the amount of off-note (mouth, taste, aftertaste, and odor) in the formulation.

[0100] The following reference formulations were used (Table 1).

[0101] Table 1

[0102]

[0103]

[0104] Experiment 1

[0105] The following formulations were tested (Table 2):

[0106] Table 2

[0107]

[0108] QDA results showed that, compared to the reference group S-R1, the more proteins (S-P2, S-P3) or masking agents (S-V2, S-V3) added, the less specific taste, aftertaste, and odor the product produced, and significantly reduced the so-called "nauseating taste." However, adding extra low-erucic acid rapeseed oil (S-P3) or more sucrose than maltodextrin (S-C3) did not help reduce negative properties.

[0109] With the addition of protein or a masking agent, the product thickens and achieves a creamier texture. This makes the fat globules less likely to reach the tongue and reduces the perception of nucleotides and fishy flavors. A comparison of the 6g / 100ml protein batch (S-P2) and the 0.4% masking agent batch (S-V2) with the reference batch (S-R1) is also shown. Figure 2a and Figure 2b In the case of fishy odor, no significant improvement was observed even with the addition of a higher concentration of the masking agent (S-V3). Furthermore, a portion of the fishy odor characteristic is a (volatile) aldehyde, which can bind to, for example, lysine or glutamine. This binding increases over shelf life, and the amount of the odor characteristic decreases, resulting in an increase in palatability with increasing shelf life.

[0110] With the addition of more low-erucic acid rapeseed oil (S-P3), it was expected that the fish oil would be diluted, thus reducing the fishy flavor. However, with the increased oil content, it appeared that more oil was in contact with the surface of the tongue, resulting in a more intense fishy taste.

[0111] The effect of increasing sweetness on masking aberrations is smaller than the effect of adding more protein or masking agents.

[0112] Experiment 2

[0113] Four flavors (vanilla, strawberry, hot milk coffee, and peach / orange) of the reference formulation (S-R1) and the formulation with 0.4% cellulose masking agent (S-V2) were analyzed in an internal consumer panel. The panel rated the products from “strongly disliked” to “strongly liked”. Results were summarized in… Figure 3 In all flavor developments, all flavor variations contained the same flavoring agent (and concentration), indicating that the addition of 0.4% cellulose improved the scores, with vanilla receiving the highest score.

[0114] in conclusion

[0115] Adding additional protein or masking agents can reduce the fish-specific taste, odor, and aftertaste, as well as the "nauseating" taste, of the formulations of this invention. Flavor development shows that adding 0.4% cellulose significantly improves the scores of different flavors.

Claims

1. The use of a masking agent selected from the group consisting of cellulose, cellulose derivatives, xanthate gum, and gellan gum, wherein the composition further comprises fish oil.

2. The use of claim 1, wherein the liquid aqueous nutrient composition contains at least 50 mg of the uridine nucleotide and / or the uridine nucleoside per 100 ml of the composition.

3. The use according to claim 1 or 2, wherein the liquid aqueous nutrient composition contains uridine monophosphate (UMP) in an amount of 0.08-3 g per 100 ml of composition.

4. The use of claim 1 or 2, wherein the fish oil contains at least one ω-3 fatty acid selected from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

5. The use of claim 1, wherein the fish oil contains at least one ω-3 fatty acid selected from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and the liquid aqueous nutrient composition contains uridine monophosphate (UMP) in an amount of 0.08-3 g per 100 ml of the composition.

6. The use of claim 1 or 2, wherein the liquid aqueous nutrient composition contains one or more of docosahexaenoic acid and eicosapentaenoic acid in a total of 100-5000 mg per 100 ml of the composition.

7. The use of claim 1, wherein the liquid aqueous nutrient composition contains one or more of docosahexaenoic acid and eicosapentaenoic acid in a total of 100-5000 mg per 100 ml of the composition, and the liquid aqueous nutrient composition contains uridine monophosphate (UMP) in an amount of 0.08-3 g per 100 ml of the composition.

8. The use of claim 1, 2, 5 or 7, wherein the liquid aqueous nutrient composition contains 0.05-3% by weight of a masking agent based on the total weight of the composition.

9. The use of claim 1, 2, 5 or 7, wherein the masking agent is high-viscosity cellulose.

10. The use of claim 1, 2, 5 or 7, wherein the masking agent is selected from hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), microcrystalline cellulose (MCC) and methylcellulose.

11. The use of claim 1, 2, 5 or 7, wherein the liquid aqueous nutrient composition contains 0.5-1% by weight of a mixture of microcrystalline cellulose and anionic polymeric polysaccharides based on the total weight of the composition.

12. The use of claim 1, 2, 5 or 7, wherein the liquid aqueous nutrient composition contains 0.5-1% by weight of a mixture of microcrystalline cellulose and carboxymethyl cellulose based on the total weight of the composition.

13. The use of claim 1, 2, 5 or 7, wherein the liquid aqueous nutrient composition further comprises one or more proteins and a flavoring agent.

14. The use of claim 1, 2, 5 or 7, wherein the liquid aqueous nutrient composition contains 0.2-10 g of protein per 100 ml of the composition.

15. The use of claim 1, wherein the liquid aqueous nutrient composition comprises: (i) at least 50 mg of uridine nucleotides and / or uridine nucleotides selected from uridine monophosphate (UMP), uridine diphosphate (UDP) and uridine triphosphate (UTP) or mixtures thereof per 100 ml composition; (ii) 0.05-3% by weight of a flavor masking agent based on the total weight of the composition, wherein the flavor masking agent is selected from: cellulose; cellulose derivatives; xanthate gum; and gellan gum; and (iii) Fish oil containing one or more of docosahexaenoic acid and eicosapentaenoic acid per 100 ml in total of 100-5000 mg.

16. The use of claim 15, wherein the liquid aqueous nutrient composition further comprises 0.2-10 g of protein per 100 ml of the composition.