liquid enteral nutritional composition that has a high content of intact pea protein and use of liqu

专利摘要:
NET ENTERAL NUTRITIVE COMPOSITION AND USE OF A NET NUTRITIVE COMPOSITION The invention relates to a liquid enteral nutritional composition comprising a specifically designed pea-based protein fraction, a fat fraction, and optionally a dietary fraction, (a) meets all nutritional needs according to general recommendations for a healthy and balanced diet, (b) which is well tolerated and minimizes the clinical complications that are normally associated with the administration of enteral nutrition to patients using tube feeding, especially with regarding reduced gastric emptying, and (c) which is appropriate for tube feeding. The liquid enteral nutritional composition comprises an innovative and new pea-based protein fraction comprising more than 25% by weight and up to 80% by weight of a vegetable protein comprising at least one source of pea protein, and fraction of fat new innovator comprising (a) 8 to 15% by weight of linoleic acid (LA); (b) from 3.0 to 6.0% by weight of a combination consisting of polyunsaturated fatty acids (omega) -3: alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) , where the amount of ALA> 2.5% by weight and (...).
公开号:BR112012018842B1
申请号:R112012018842-9
申请日:2011-01-31
公开日:2020-11-10
发明作者:Zandrie Hofman；Rogier Daniel Van Anholt；Wynette Hermina Agnes Kiers；Marianne Klebach；Marloes Heleen Van Beusekom
申请人:N.V. Nutricia；
IPC主号:

专利说明:

FIELD OF THE INVENTION
[001] The invention relates to a liquid enteral nutritional composition comprising a fraction of specifically designed pea-based protein, a fraction of fat, and optionally a dietary fraction, (a) which satisfies all nutritional needs according to the general recommendations for a healthy and balanced diet, (b) which is well tolerated and minimizes the clinical complications that are normally associated with the administration of enteral nutrition in patients using tube feeding, especially with respect to reduced gastric emptying, and ( c) that is suitable for tube feeding. CLINICAL PROBLEM
[002] Due to a variety of reasons, such as diseases, medical conditions, malnutrition, medical disabilities, post-surgery, etc., patients may not be able to obtain the necessary nutrition by eating food through the mouth, for example example, orally, when eating or drinking. Specific indications include severe malnutrition of protein energy, coma, inability to ingest oral food due to head or neck trauma, Crohn's disease, neurological disorders that result in dysphagia, strokes, surgery, and critical illnesses (for example , burns) causing metabolic stress. Therefore, the provision of medical enteral nutrition through oral nutritional supplements or tube feeding is known. Tube feeding is applied to provide nutrition to patients who cannot obtain nutrition when swallowing, using a device such as a nasogastric feeding tube or nasojejunal feeding tube, or using a percutaneous endoscopic gastronomy (PEG) feeding system or PEG-j ejuno-feeding.
[003] In the context of the present patent application, the state of being fed by nutritional supplements or by a feeding tube is called enteral feeding, which comprises all the modes of feeding via the tube mentioned above, and the nutrition used in such feeding is called enteral nutrition. The use of such enteral nutrition may be temporary for the treatment of acute conditions, or may last a lifetime in the case of chronic disabilities. Generally, said enteral nutrition is administered to patients in hospitals, nursing homes and individuals in the context of home care, where the administration of enteral nutrition, particularly by tube feeding, is of a chronic nature (such as feeding long-term enteral).
[004] Therefore, especially for individuals who require tube nutrition for longer periods of time in combination with modern medical advances resulting in increased life expectancy and better treatment of the disease, it is important to provide an ideal product composition , (a) to meet all nutritional needs, especially with regard to protein, fat and carbohydrate components for a longer period of time, and (b) minimize the clinical complications that are normally associated with the administration of enteral nutrition in patients using tube feeding.
[005] Such clinical complications include, for example, vomiting, nausea, reflux, diarrhea, constipation and retention. A distinction can be made between digestive complications of the upper and lower tracts. Complications of the lower digestive tract are typically diarrhea and constipation; complications of the upper digestive tract are typically reduced gastric emptying, retention, reflux, vomiting, aspiration, and pneumonia. In addition, reduced gastric emptying is a risk factor for increased reflux, vomiting and aspiration and therefore for the development of pneumonia. TECHNICAL PROBLEM
[006] In addition, the liquid enteral nutritional composition according to the invention must be (c) suitable as a tube feed and easy to be administered by tubes, that is, it must have a low viscosity and a low density, it must have a neutral pH, have a long life under storage, have good stability under storage, do not segregate, agglomerate or sediment. It must be suitable for heat treatments (such as sterilization and pasteurization) without a substantial change in structure, palatability (especially for oral nutritional compositions), viscosity, etc. The protein and fat fractions must be easily mixed with other components, such as a carbohydrate fraction, a digestible fiber fraction, and other components, for example, to obtain a complete liquid enteral nutritional composition. PREVIOUS TECHNICAL STATUS
[007] Until now, little attention has been focused on the development of liquid enteral nutritional compositions suitable for tube feeding that satisfy all conditions (a), (b) and (c) above.
[008] EP 1 972 345 Al (Katry Inversiones) presents a pea-based food product for enteral or oral nutrition that contains a protein fraction with a specific amino acid profile, a lipid mixture, carbohydrates, soluble and insoluble fibers , vitamins and minerals, particularly a fraction of pea-based protein consisting of 50% by weight of caseinate, 25% by weight of whey proteins and 25% by weight of pea protein, and a mixture of fat which contains specific proportions of fatty acids. Although the nutritional qualities of the claimed food product are assessed, there is no data on clinical complications when ingested by humans, particularly when used as a tube feed.
[009] EP2073781 A2 (Nestec SA) presents nutritional compositions via long-term tube specific for specific patient populations, such as elderly people. Although the nutritional qualities of the claimed food product are assessed, there is no data on clinical complications when ingested by humans, particularly when used as a tube feed.
[0010] In addition, it is known in the literature that different proteins and fats can influence gastric emptying in a different way. For example, casein is clotting in the stomach while whey proteins are not clotting in the stomach. Thus, casein is considered to be a coagulation protein with slow gastric emptying properties, and whey proteins are considered to be non-coagulant proteins with much faster gastric emptying. It is unknown whether or not other proteins are clotting in the stomach or whether or not they can influence gastric emptying. BRIEF DESCRIPTION OF THE INVENTION
[0011] The aim of the present invention is to provide a liquid enteral nutritional composition, (a) that satisfies all nutritional needs, especially with regard to the components of protein and fat, according to the general recommendations for a healthy diet and balanced, (b) which is well tolerated and minimizes the clinical complications that are normally associated with the administration of enteral nutrition to patients using tube feeding, especially with respect to reduced gastric emptying, and (c) which is appropriate for tube feeding with respect to typical parameters such as stability, life under storage, viscosity, etc.
[0012] Surprisingly, the authors of the present invention found that said objective could be achieved by a liquid enteral nutritional composition as indicated in any of the attached claims, which comprises an innovative and new pea-based protein fraction comprising more than 25% by weight and up to 80% by weight of a vegetable protein comprising at least one source of pea protein, and an innovative and new fat fraction comprising (a) 8 to 15% by weight of linoleic acid (OVER THERE); (b) from 3.0 to 6.0% by weight of a combination consisting of polyunsaturated ω-3 fatty acids: alpha-linolenic acid (ALA), docosahexaenoic acid (DMA) and eicosapentaenoic acid (EPA), in whereas the amount of ALA> 2.5% by weight and the combined amount of DHA and EPA = 2.5% by weight; (c) 10 to 20% by weight of at least one medium chain fatty acid (MCFA); and (d) 35 to 79% by weight of at least one monounsaturated fatty acid (MUFA).
[0013] Each of the innovative and new protein and fat fractions is claimed separately in two copendent patent applications, and is believed to satisfy the ideal nutritional requirement (condition (a)), while combined in the enteral nutritional composition liquid according to the invention, they minimize clinical complications, especially of the upper digestive tract (condition (b)).
[0014] In a further embodiment, to minimize complications of the lower digestive tract, the liquid enteral nutritional composition according to the invention can additionally comprise any dietary fibers, or any mixture of dietary fibers, particularly as indicated in EP 0756828 BI. More particularly, the liquid enteral nutritional composition comprises from 5 to 120 g / 1 of dietary fiber, wherein the fraction of dietary fiber consists of 15 to 50% by weight of non-soluble polysaccharides, from 15 to 45% by weight of non-insoluble starch polysaccharides, from 8 to 70% by weight of non-digestible oligosaccharides comprising at least 8% by weight, based on fiber, of hydrolyzed inulin, and comprising resistant starch.
[0015] In a further embodiment, the liquid enteral nutritional composition according to the invention additionally comprises one or more of a fraction of carbohydrate and micronutrients.
[0016] A lower incidence of clinical indications was observed for the composition according to the invention, compared to a composition according to the state of the art, particularly for clinical complications of the upper digestive tract (nausea, vomiting, use of antacids) , but also for clinical complications of the lower digestive tract (diarrhea, constipation), adverse events related to the gastrointestinal tract, adverse events related to pneumonia, and serious adverse events. DETAILED DESCRIPTION OF THE INVENTION
[0017] Protein fraction
[0018] According to one embodiment, the pea-based protein fraction comprises more than 25% by weight and up to 80% by weight of vegetable protein comprising at least one source of pea protein.
[0019] According to one embodiment, the pea-based protein fraction comprises at least 8%, preferably at least 10%, and more preferably at least 15%, of the total energy of the composition.
[0020] According to one embodiment, the liquid nutritional composition according to the invention preferably contains between 1 and 20 grams of protein per 100 ml, more preferably between 2 and 15 grams per 100 ml, and most preferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 grams of protein per 100 ml of a liquid product or any integer or non-integer fraction interspersed.
[0021] In the context of the present patent application, when reference is made to a "protein mixture", a "protein fraction", or a "protein composition" according to the invention, it must mean a collection of proteins, proteinaceous matter, peptides and amino acids, free or in any linked form. Thus, the protein fraction of a nutritional composition is the sum of all proteins, proteinaceous matter, peptides and amino acids, free or in any linked form present in the nutritional composition. In addition, the term "protein mix" refers to a collection of proteins, proteinaceous matter, peptides and amino acids as such, in any form, as well as a collection of proteins, proteinaceous matter, peptides and amino acids simultaneously present in a matrix, such as an aqueous matrix, such as a liquid enteral nutritional composition. In the latter case, the protein mixture can be indicated as a fraction of proteins in that matrix.
[0022] In the context of the present patent application, the pea-based protein fraction consists essentially of vegetable and milk proteinaceous material, particularly proteins.
[0023] In the context of this patent application, the term "vegetable" refers to protein of plant origin such as, for example, originating from vegetables such as carrots, peas, chickpeas, peas green, cowpea, field peas, purple beans, lupine, rice, soybeans, canola, hemp, zein, white corn, maize, barley, flax, seed of flaxseed, and wheat. An equivalent expression can be used, such as "vegetable", "legume" or "plant derived".
[0024] In the context of the present patent application, the expression "milk protein" refers to milk-derived protein, that is, protein derived from animal milk, such as derived from species such as camel, cow, goat, mare, human being, reindeer, sheep, water buffalo and yak.
[0025] In one embodiment, the pea-based protein fraction according to the invention comprises from 30 to 50% by weight, more particularly from 35 to 45% by weight of the intact vegetable protein in relation to the total protein in the fraction of proteins.
[0026] The pea-based protein fraction according to the invention can take any physical form, such as a powder or liquid form, and can be a solution, a suspension, a dispersion or the like. Preferably, the pea-based protein fraction according to the invention is in liquid form. Preferably, the pea-based protein fraction is an aqueous protein fraction.
[0027] Pea protein
[0028] In the past, pea protein alone was generally classified as a rather poor vegetable protein source, with a biological value (BV) of approximately 49% when compared, for example, to whole egg (100%), milk from cow (91%), casein (77%), soy (74%) and wheat (54%) (see, for example, Renner, E. (1983) Milk and dairy products in human nutrition. Volkswirtschaftlicher Verlag, Munich, Germany) and with an amino acid count (AAS) that is lower than that for whole egg (1), cow's milk (1), casein (1) and soy (0.91). The BV of a protein is the amount of nitrogen used for tissue formation divided by the absorbed amount of the food and is expressed as a percentage. AAS is the relationship between the amount of the first limiting amino acid in the protein under study (mg / g) and the amount of that amino acid in a reference protein (mg / g), optionally multiplied by true digestibility (Proetin Digestibility Corrected-AAS, PDCAA ). According to WHO recommendations (2007) on protein quality as a reference, peas have an amino acid count of less than 1.0 due to the relatively low methionine content.
[0029] In all powders, pea protein tastes pretty bad (even in the intact form) and doesn't mix too well, leaving a kind of grainy texture for the protein. However, the authors of the present invention found that the intact pea protein could be combined with one or more second proteins, preferably an intact vegetable protein, such as whey protein at a concentration of about and above 25 % by weight, in such a way that a good total mixture of amino acids could be obtained and a composition almost released by the time. Buttermilk proteins enter the bloodstream very quickly, whereas pea proteins are absorbed much more slowly.
[0030] Pea protein is relatively inexpensive (on average, pea protein can cost approximately half the price of caseinates) and is added to the mix to increase the protein content while the costs are kept quite low. Pea protein is generally well tolerated by most people, is lactose free and is not a common allergen. Pea protein has a very high cysteine content and can therefore compensate for the inadequate amount of cysteine in casein proteins. In addition, pea protein has a rather high content of arginine compared to casein, soy or whey protein which are required for muscle metabolism and facilitate the intake of body mass while reducing body fat; and it has a very high lysine content, when compared to vegetable proteins, which is necessary to build the muscle of the protein and help maintain lean body mass. The intact pea has been found to be substantially a non-clotting protein in the stomach of a human person, which means that the intact pea protein does not clot in the stomach of a human person under normal digestive conditions. In hypothesis, the coagulation of proteins in the stomach slows gastric emptying. This will result in complications in the upper gastrointestinal tract such as, for example, intestinal discomfort, aspiration pneumonia, large gastric residual volume (GRV), vomiting, nausea, swelling, and delayed gastric emptying, especially in vulnerable people, such as hospitalized patients . Thus, the discovery that intact pea protein is a non-coagulant protein can provide a source of easily digestible vegetable proteins.
[0031] Various sources of pea are readily available to a technician in the matter, for example, from Roquette (Lestrem, France) which sells a pea isolate obtained from yellow peas (Pisum sativum), and from Cosucra Groupe Warcoing (Warcoing, Belgium).
[0032] According to one embodiment, the pea protein is in substantially intact or non-hydrolyzed form. In the context of the present patent application, a "non-hydrolyzed" protein is equivalent to an "intact" protein, which means that the protein has not been subjected to a hydrolysis process. However, smaller amounts of hydrolyzed proteins may be present in the source of non-hydrolyzed proteins, or may be added to the formulation, such as additional amino acids such as, for example, leucine, isoleucine, glutamine, arginine, or dipeptides , and still others. In one embodiment of the present invention, the composition can comprise a free amino acid, or a mixture of free amino acids, up to 5 g / 100 ml, more preferably less than 2 g / 100 ml, even more preferably less than 1 g / 100 ml, and most preferably less than 0.5 g / 100 ml. According to another embodiment, the intact protein can only have a degree of hydrolysis (DH) of 10% or less, preferably 9, 8, 7, 6, 5, 4, 3, 2, 1% or less.
[0033] In this context, "small" should be understood as an amount of approximately 10% by weight or less. The term "approximately" should be interpreted as a deviation of plus or minus 10% from the value in question.
[0034] According to another embodiment, the pea-based protein fraction according to the invention comprises from 5 to 60% by weight, particularly from 10 to 30% by weight, and more particularly from 15 to 25% by weight. weight of pea protein, in relation to the total protein in the protein fraction.
[0035] Second vegetable protein
[0036] The pea-based protein fraction according to the invention can further comprise a second vegetable protein, with the exception of pea protein. Preferably, the second vegetable protein is selected from a protein group of soy, rice and wheat. Preferably, the second vegetable protein is soy protein.
[0037] In one embodiment, the second vegetable protein is substantially intact.
[0038] According to an embodiment of the invention, the second intact vegetable protein is substantially a non-coagulant protein in the stomach of a human person.
[0039] Soy protein
[0040] It has been found that intact soy is substantially a non-coagulant protein in the stomach of a human person, which means that intact soy protein does not clot in the stomach of a human person under normal digestive conditions. In hypothesis, the coagulation of proteins in the stomach slows gastric emptying. This will result in complications in the upper gastrointestinal tract such as, for example, intestinal discomfort, aspiration pneumonia, large gastric residual volume (GRV), vomiting, nausea, swelling, and delayed gastric emptying, especially in vulnerable people, such as hospitalized patients . Thus, the discovery that intact soy protein is a non-coagulant protein can provide a source of easily digestible vegetable proteins.
[0041] Soy protein has been used since 1959 as an ingredient for its functional properties in a variety of foods such as salad dressings, soups, vegetarian foods and meat imitations. Its functional properties are emulsification and texturing. Recently, the popularity of soy protein is increasing, mainly because of its health benefits. It has been proven that soy protein can help prevent cardiovascular problems, and many countries allow health claims for foods, which are rich in soy protein. In addition, health claims were made to improve heart health (lower cholesterol), improve bone health (increased bone density), relieve menopausal symptoms (reduced hot flashes), performance nutrition (recovery muscle) and weight management (hunger satisfaction). Soy protein is a vegetable protein that contains the essential amino acids in a relatively high proportion for human health. Soy protein is categorized as a high quality complete protein, although the level of methionine is slightly below the WHO 2007 recommendation for methionine content.
[0042] Soy proteins can be divided into different categories according to their production method. Soy protein isolate (SPI) is the most refined form of soy protein and is used primarily in meat products to improve the texture and quality of eating. The soy protein isolate contains approximately 90 percent protein. The soy protein concentrate (SPC) basically consists of soy without the water-soluble carbohydrates. It contains approximately 70 percent protein. Textured soy protein (TSP) is produced from the soy protein concentrate by providing some texture. TSP is available as dry flakes or loaves. It will maintain its structure when hydrated. The hydrated textured soy protein chunks have a texture similar to that of ground beef. It can be used as a meat substitute or it can be added to meat. Textured soy protein contains approximately 70 percent protein.
[0043] Various sources of soy are readily available to a technician on the subject, for example, with The Solae Company (St. Louis, MO, USA).
[0044] Milk proteins
[0045] According to one embodiment, the pea-based protein fraction according to the invention further comprises a milk protein. Preferably, the milk protein is selected from the group of casein protein and buttermilk.
[0046] Preferably, the pea-based protein fraction according to the invention comprises from 20 to 75% by weight, particularly from 50 to 70% by weight, and more particularly from 55 to 65% by weight of at least one or more milk proteins, in relation to the total protein in the protein fraction.
[0047] Preferably, the milk protein is included (non-hydrolyzed) in substantially intact form, in order to have a palatable product. Such high molecular weight proteins increase the viscosity of the heat-treated liquid product compared to hydrolyzed forms. The authors of the present invention were able to produce a product with good palatability and low viscosity, by applying the measures according to the invention. In addition, milk proteins compensate for the relatively low methionine content of plant proteins in order to have an amino acid count above 1.0 for the total protein fraction.
[0048] Buttermilk proteins
[0049] One of the most superior classes of food protein is whey protein. It is known for its excellent amino acid profile, for its ability to increase protein synthesis in a mammal (due to a higher leucine content), for its greater tolerance and increased gastric emptying, and for its interesting bioactive proteins with properties immunity enhancers (lactoglobulins, immunoglobulins, lysozyme, glutamine, cysteine and lactoferrins). Nutritionally speaking, whey protein is known as a naturally complete protein because it contains all the essential amino acids required in the daily diet. It is also one of the richest sources of branched-chain amino acids (BCAAs, particularly leucine) that play an important role in muscle protein synthesis. In addition, it has been shown that some of the individual components of whey protein prevent viral and bacterial infection and modulate immunity in animals. Buttermilk protein is the preferred choice of proteins for the treatment of people suffering from sarcopenia, but it is also suitable for healthy people, such as sports people and active elderly people. In addition, buttermilk is also a non-coagulant protein, as indicated above.
[0050] As a source of whey protein to be used in the present invention, any commercially available source of whey protein can be used, that is, the whey obtained by any process for the preparation whey protein known in the art, as well as the whey protein fractions prepared from it, or the proteins that make up the volume of whey proteins that are β-lactoglobulin, the a-lactalbumin and serum albumin, such as whey, or whey in powder form, such as whey protein isolate (WPI) or whey protein concentrate curdled milk (WPC). The whey protein concentrate is rich in whey protein, but it also contains other components such as fat, lactose and glycomacroprotein (GMP), a non-globular protein related to casein. Typically, the whey protein concentrate is produced by means of membrane filtration. On the other hand, whey protein isolate consists mainly of whey proteins with minimal amounts of fat and lactose. The whey protein isolate generally requires a more rigorous separation process, such as a combination of microfiltration and ultrafiltration or ion exchange chromatography. It should be generally understood that a whey protein isolate refers to a mixture in which at least 90% by weight of the solids consists of whey proteins. A whey protein concentrate is understood to have a percentage of whey protein between the initial amount in the by-product (approximately 12% by weight) and an isolate of whey protein. In particular, sweet buttermilk, obtained as a by-product in the manufacture of cheese, acid whey, obtained as a by-product in the manufacture of acidic casein, native buttermilk, obtained by microfiltration of milk or milk. buttermilk, obtained as a by-product in the manufacture of casein rennet, can be used alone or in combination as a source of globular whey proteins.
[0051] In addition, whey proteins can originate from all types of mammalian animal species such as, for example, cows, sheep, goats, horses, buffalo and camels. Preferably, the whey protein originates from cattle.
[0052] Preferably, the source of the whey protein is available as a powder, and preferably the source of the whey protein is a WPC or a WPI.
[0053] Casein / Caseinate
[0054] Casein is one of the two types of protein found in milk, and the other is whey. Casein separates from milk when milk is curdled, a process usually performed in the manufacture of cheese, and is generally called caseinate, having lost its typical micellar structure. Casein tends to form a gel in the stomach, which slows down digestion. This makes casein an ideal source of protein to release the protein into the bloodstream for a period of time, for example, during sleep. Casein also has a high content of glutamine, a conditionally essential amino acid, necessary for the repair of muscle tissue after strenuous exercise and important for the bowel and immune function. Casein has a relatively low cysteine content, which can be compensated for by adding other proteins such as plant proteins. Cysteine is important for the endogenous synthesis of glutathione and, therefore, plays an important role in protecting against damage caused by free radicals.
[0055] Like many other nutritious compounds, casein is typically bound to a metal ion, since the molecule is more stable in this way. Specifically, casein is more generally bound to calcium (Ca2 +) and sodium (Na +), since all of these ions are found naturally in milk, or even potassium (K +) or magnesium (Mg2 +), and tends to bind to casein during the extraction process. Nutritionally, these compounds are basically interchangeable, since all forms of casein are effective sources of protein. Micellar casein refers to casein in the form of native micelles. It is a high quality milk protein and occurs naturally in milk at a concentration of approximately 2.6 g / 100 ml (Dairy Science and Technology, Walstra et al., CRC Press, 2006). It is concentrated by a process that does not denature or substantially denature casein proteins and is marketed as micellar casein isolate (MCI). The fresh skimmed milk is subjected to a microfiltration process, in exactly the same process used to concentrate the whey protein, in order to produce a substantially non-denatured pure milk protein with its native structure. The resulting material contains between 90% and 95%, preferably more than 95% by weight, of micellar casein, and the remainder consists mainly of whey protein and other non-protein nitrogen constituents and other constituents, such as lactose and inorganic salts, particularly calcium phosphate.
[0056] Within the context of the present invention, it should be understood that micellar casein can also be provided by other sources of milk protein such as, for example, sources that essentially preserve the natural 80:20 relationship between casein and buttermilk, such as milk protein concentrate (MPC), which is a powder product generally prepared through ultrafiltration with an average protein content of approximately 80% by weight, milk protein isolate (MPI) , a powder product generally prepared by precipitation with an average protein content of more than 85% by weight, and concentrated skim milk.
[0057] Within the context of the present invention, with the term "casein", both caseinate and micellar casein are indicated.
[0058] In one embodiment, casein is caseinate, preferably Na caseinate or Ca caseinate. Preferably, caseinate is Ca caseinate.
[0059] According to one embodiment, the protein mixture additionally comprises a milk protein selected from the group of Na caseinate, Ca caseinate, micellar casein and whey protein.
[0060] Preferred protein fraction
[0061] According to a preferred embodiment, the pea-based protein fraction according to the invention comprises casein, buttermilk protein, soy protein and pea protein, and preferably comprises intact soy protein and the pea protein intact. Preferably, all proteins are in substantially intact form.
[0062] According to a preferred embodiment, the pea-based protein fraction according to the invention consists of 20 to 40% by weight of casein, 20 to 40% by weight of whey protein, 13 to 25% by weight of soy protein, and 13 to 25% by weight of pea protein, in relation to the total protein in the protein fraction, where the sum of said proteins is equal to 100% by weight. The pea-based protein fraction mentioned above has an excellent amino acid profile.
[0063] Amino acid profile of the pea-based protein fraction
[0064] The pea-based protein fraction according to the invention at least satisfies, and preferably exceeds, the recommendations of the WHO amino acid profile for complete nutrition.
[0065] In one embodiment, the pea-based protein fraction according to the invention has the following amino acid profile in grams per 100 grams of total protein in the protein fraction: Cysteine: at least 1.1 g / 100 g Phenylalanine: at least 4.0 g / 100 g Tyrosine: at least 3.7 g / 100.
[0066] In another embodiment, the pea-based protein fraction according to the invention has the range of the essential amino acid profile as indicated in Table 1 in grams per 100 grams of total protein in the protein fraction. In the right column, the minimum quantity is provided according to WHO 2007 guidelines. Table 1
a: based on an average nitrogen requirement of 105 mg nitrogen / kg per day (0.66 g protein / kg body weight per day).
[0067] In an additional embodiment, the pea-based protein fraction according to the invention has the range of the amino acid profile as indicated in Table 2 in grams per 100 grams of total protein in the protein fraction, or the profile specific amino acid as indicated in the right column of Table 2. Table 2: Amino acid profile per 100 g of Total protein

Preparation of the protein fraction
[0068] The pea-based protein fraction according to the invention is prepared by mixing the pea protein and one or more individual proteins in powder form with water, for example, by dumping the individual powdered proteins out of the containers Totebin® in water, optionally comprising soluble carbohydrates, such as maltodextrins, and when mixing the resulting solution. The water temperature, which optionally comprises carbohydrates, is preferably between approximately 20 and approximately 60 degrees Celsius. For example, when a maltodextrin syrup is used, the temperature is approximately 60 degrees Celsius, which is the temperature of the syrup. Carbohydrates can also be added later. In principle, the protein mixture has now been prepared, but additional ingredients can be added, such as mineral salts, fibers, fat, etc. Pasteurization of the protein mixture can be performed without substantially raising its viscosity. For example, pasteurization can be performed for thirty seconds at 85 ° C, followed by homogenization at a pressure of 55 mega Pascals, followed by cooling the solution to 4 to 20 ° C. The pH of the resulting solution can be adjusted, for example, to a pH = 8, and the resulting solution can still be sterilized in an autoclave. The time / temperature curve depends on the type of packaging, the resulting product and the FO value, for example, for a bottled product the time / temperature curve is 121.5 to 122.5 ° C for 16 minutes. Fat fraction
[0069] To obtain the fat fraction of the present invention, the authors of the present invention first established that there is no recommendation for a fat fraction for patients in need of enteral medical nutrition. To overcome this problem, the authors of the present invention have collected a substantial number of recommendations and / or guidelines for a healthy and balanced intake of dietary fat from national and international organizations. Thereafter, the authors of the present invention defined a range that is defined by the lowest maximum and the lowest minimum of these recommendations. Subsequently, the recommendations (in%) were redefined in terms of weight% and an appropriate fat source was researched, however, not a single fat source was able to satisfy the recommendations. In this way, a composition of fat sources was designed to obtain the desired fat fraction.
[0070] After due consideration, the authors of the present invention found that said fat fraction must comprise at least specific amounts of linoleic acid (LA, 18: 2n-6), alpha-linolenic acid (ALA, 18: 3n- 3), docosahexaenoic acid (DHA, 22: 6n-3), eicosapentaenoic acid (EPA, 20: 5n-3), at least one medium chain fatty acid (MCFA, for example, 8: 0 and / or 10: 0 ), and at least one monounsaturated fatty acid (MUFA, for example, 16: 1, 18: 1, 20: 1, 22: 1 and / or 24: 1). More particularly, the fat fraction contains smaller amounts of LA than those found in the prior art, particularly in commercial products available, for example, from Abbott, Fresenius, Nestlé and Nutricia.
[0071] Surprisingly, said fat fraction could be designed based on common fat sources, could be easily manufactured and could be used for the manufacture of the liquid enteral nutritional composition according to the invention.
[0072] According to one embodiment, the liquid enteral nutritional composition according to the invention comprises a fat fraction comprising: from 8 to 15% by weight, preferably from 12.5 to 14.5% by weight, and more preferably from 13.5 to 13.9% by weight of linoleic acid (LA, 18: 2n-6); - from 3.0 to 6.0% by weight, preferably from 4.0 to 5.0% by weight, and more preferably from 4.3 to 4.7% by weight of a combination consisting of ω- fatty acids 3 polyunsaturated, alpha-linolenic acid (ALA, 18: 3n-3), docosahexaenoic acid (DHA, 22: 6n-3) and eicosapentaenoic acid (EPA, 20: 5n-3), in which the amount ALA> 2.5% by weight, more preferably> 2.7% by weight, or preferably between 2.5 and 4.0% by weight, and the combined amount of DHA and EPA = 2.5% by weight , and preferably = 1.0% by weight; - from 10 to 20% by weight, preferably from 14 to 18% by weight, and more preferably from 15.7 to 16.2% by weight of at least one medium chain fatty acid (MCFA, for example, 8: 0 and / or 10: 0); and - from 35 to 79% by weight, preferably from 40 to 70% by weight, and more preferably from 50 to 60% by weight of at least one monounsaturated fatty acid (MUFA, for example, 16: 1, 18: 1, 20: 1, 22: 1 and / or 24: 1). where all relative amounts are calculated based on the total amount of fatty acids in the fat fraction. The relative amounts need not add up to 100% by weight, since the fat fraction according to the invention can also include other types of fat.
Alternatively, the present invention relates to a liquid enteral nutritional composition in which the fat fraction comprises between 30 and 50En%, preferably between 30 and 40En% of the total energy of the composition.
[0074] According to one embodiment, the liquid nutritional composition according to the invention preferably contains between 1 and 20 grams of fat per 100 ml, more preferably between 2 and 15 grams per 100 ml, and even more preferably 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 grams of fat per 100 ml of a liquid product or any fraction of whole and non-whole numbers interspersed.
[0075] In the context of the present patent application, the% of total energy is also abbreviated as En%; En% is thus briefly for the percentage of energy and represents the relative amount that a constituent contributes to the total caloric value of the composition.
[0076] In the context of this patent application, the term "at least" also includes the starting point of the open band. For example, an amount of "at least 95% by weight" means any amount equal to or greater than 95% by weight.
[0077] In the context of this patent application, the term "approximately" defines a range of plus or minus 10% of the quoted value. For example, an amount of "approximately 20% by weight" means any amount within the range of 18 to 22% by weight. Fatty acid metabolism
[0078] Strictly speaking, polyunsaturated fatty acids (PUFAs) linoleic acid (18: 2n-6, abbreviated as LA, an omega-6 fatty acid) and a-linolenic acid (18: 3n-3, abbreviated as ALA, an omega-3 fatty acid) are the only essential fatty acids for humans; all other physiologically and structurally important fatty acids can be derived from these two fatty acids. However, the conversion of LA to the longer-chain fatty acid, arachidonic acid (20: 4n-6, ARA), and the conversion of ALA to eicosapentaenoic acid (20: 5n-3, EPA) and docosahexaenoic acid (22 : n6-3, DHA) by the elongase and desaturase enzymes is not very efficient in humans. Estimates for the conversion of LA to ARA and ALA to EPA vary, but rarely exceed 10%. In addition, the conversion of ALA to DHA is estimated to be even lower, with estimates ranging from 4% to just 0.2% (Gerster 1998; Burdge et al. 2002; Goyens et al. 2006). These fatty acids (ARA, EPA, DHA) not only have important structural roles, but are also converted into eicosanoids and resolvins with a range of physiological and immunological functions (Tapiero et al. 2002; Calder 2006; Serhan 2006). ARA, EPA and DHA are called long-chain PUFAs (LCPUFA, PUFAs with a carbon chain length of more than 18) or LCPs, where ARA belongs to omega-6 LCPUFAs and EPA and DHA belong to the omega-3 LCPUFAs.
[0079] The composition of a diet mainly determines the incorporation of these fatty acids in various cells and tissues in a complex way. More predominantly, fatty acids, both derived from the diet and synthesized from precursors, compete at various levels for the same enzymes that determine incorporation into tissues and / or conversion into biologically active metabolites: for the enzymes that determine (1) incorporation in phospholipids and tissues, (2) the release of membranes and other storage, (3) the conversion to other fatty acids, and (4) the conversion to various metabolites (eicosanoids, resolvins). These eicosanoids and resolvins are involved in a wide variety of physiological and immunological processes, regulate the release of a range of hormones, and have an effect on nervous system function. Due to the competition of fatty acids for the conversion of enzymes, a relative excess in the consumption of LA will promote the formation of ARA at the expense of EPA and DHA. Similarly, a relative excess in ALA leads to greater production of EPA and DHA compared to ARA. Consequently, this will result in a shift to ARA-derived metabolites, or to EPA and DHA-derived metabolites. In this way, both the absolute amounts and the relationships between different fatty acids in the diet affect the structural and regulatory roles of fatty acids and their metabolites.
[0080] Table 3 provides a schematic representation of the fatty acid metabolism in humans that begins with the two essential fatty acids, linoleic acid and α-linolenic acid, from dietary sources (from plants). From these fatty acids, all other important important fatty acids can (theoretically) be derived by enzymatic conversion: desaturation enzymes (Δ5, Δ6) insert new double bonds between carbon atoms and the elongase enzyme adds carbon atoms to the chain carbon. Table 3. Overview of the metabolism of the various fatty acids
Overview of the most recent recommendations
[0081] Several organizations have published guidelines for the composition of enteral nutrition, focusing on the specific dietary needs of groups of particular patients. For example, ESPEN guidelines have been published for a number of patient populations (i.e., Cardiology and Pulmonology; Gastroenterology; Geriatrics; Hepatology; Loss in HIV; Intensive care; Non-surgical oncology; Kidney failure; Surgery and transplantation). However, none of these guidelines are specifically focused on the ideal dietary composition for general enteral nutrition, nor are detailed recommendations for fat composition included. On the other hand, recommendations for a healthy and balanced diet aimed at the general public are becoming more and more detailed as the glimpse into the role of nutrition in health and particularly disease prevention is progressing.
[0082] The availability and accessibility combined with public awareness of healthy nutrition means the adequacy of these dietary recommendations as a starting point when considering the fat composition of advanced medical nutrition products. Thus, it seems imperative that patients receiving general medical nutrition should benefit from the same dietary compositions that are considered to be advantageous for the general population. In order to determine the ideal levels of specific (groups of) fatty acids, a detailed comparison was made of the recommendations for a healthy and balanced dietary fat intake from national and international organizations, which include, among others, the organizations listed below. The list shown does not lend itself to being complete, but reflects the range of recommendations that apply to the "Western type" diet: • Health Council of the Netherlands (Netherlands) • British Nutrition Foundation (United Kingdom) • Scientific Advisory Committee on Nutrition (United Kingdom) • Deutsche Gesellschaft für Ernãhrung (Germany) • Superior Health Council of Belgium (Belgium) • Agence Française de Sécurité Sanitaire des Aliments (AFSSA) and Center National d'Études et de Recommandations sur La Nutrition et 1'Alimentation (CNERNA ) - Center National de la Recherche Scientifique (CNRS) (France) • Società Italiana di Nutrizione Umana (Italy) • American Heart Association Nutrition Committee (USA) • Food and Agriculture Organization & World Health Organization (FAO / WHO) • International Society for the Study of Fatty Acids and Lipids (ISSFAL).
[0083] The view on healthy fat intake has changed in the past few decades, from a reduction in total fat intake to more emphasis on distinguishing different types of fat and the recognition of so-called "healthy fats". Scientific insights into what should be considered ideal levels may differ between countries, resulting in a variety of recommendations. However, several universal recommendations can be identified: 1. Reduce your total energy intake (in part) by reducing your fat intake; 2. Reduce the intake of trans fats (mainly derived from processed foods); 3. Reduce the intake of saturated fats; 4. Reduce the consumption of omega-6 fatty acids, particularly linoleic acid (LA, 18: 3n-6); 5. Increase consumption of long-chain omega-3 fatty acids, EPA (20: 5n-3) and DHA (22: 6n-3), for example, by increasing the consumption of fish (fatty) up to at least 1- 2 times per week.
[0084] In Table 4 the authors of the present invention combined recommendations in the range of what is considered a healthy and balanced intake for fatty acids: although none of the organizations provide recommendations / guidelines for all aspects of an ideal fat intake, the combination of all recommendations / guidelines resulted in the most balanced composition that satisfies all the mentioned recommendations / guidelines.
[0085] These recommendations are aimed at the (healthy) population in general with the main objective of preventing disease and reducing mortality related to dietary practice, for example, cardiovascular diseases. Although the fat compositions of the current prior art and the feeds through straw and tube correspond mainly to the recommendations for a healthy and balanced fat intake, several differences can be identified, generally attributed to the incorporation of DHA and EPA, which is generally lacking in prior art products for enteral nutrition, and the LA content, which is systematically too high in prior art products for enteral nutrition.
[0086] Table 4. The combined national and international recommendations of thirteen national and international organizations for the intake of different types of fat. The recommendation values are expressed as percentages of daily caloric food intake; the daily intake calculated for two calorie diets, when these products are consumed as a complete dietary replacement (complete nutrition).

Implementation of recommendations
[0093] The authors of the present invention have now discovered that a fraction of fat could be designated, taking into account the recommendations for a healthy and balanced fat intake, as appropriate for enteral nutrition. After due consideration, the following fat composition is proposed, which will be discussed in more detail in the following sections, and which takes into account: 1. The inclusion of a source of EPA and / or DHA: almost all organizations recommend an intake minimum (fat) fish 1-2 times / week, which corresponds to a minimum daily intake of approximately 500 mg of EPA + DHA. 2. Selection of appropriate fat sources with a low LA content: several organizations recommend reducing the intake of LA to a minimum intake of 1 to 4% for adults. 3. The inclusion of medium chain fatty acids (MCFA): the addition of a source of MCFAs provides an easy and relatively inexpensive way to reduce the LA content (see point 2 above). In order to reduce the LA content to 4En%, an equivalent amount of 4En% MCFAs may be required (10-20% of the fat composition). 4. The inclusion of a source rich in monounsaturated fatty acid (MUFA), for example, oleic acid (18: ln-9): several organizations recommend minimum or adequate MUFA intakes between 10 and 30En%. The inclusion of sufficient amounts of MUFAs is an excellent way to limit the total amount of saturated fatty acids, as well as to replace the aforementioned omega-6 PUFAs.
[0094] In the structure of the present patent application, the terms "balanced", "best balanced" and the like are used to indicate that the fat composition according to the invention is a better solution to the recommendations for fat intake healthy and balanced than the existing commercially available fat compositions. 1. Inclusion of a source of EPA and / or DHA
[0095] The increased consumption of fish oil, with a high content of omega-3 fatty acids EPA and DHA, has an effect on a range of physiological and immunological processes, including fluidity pathways and membrane functioning and signal transduction. Most predominantly, increased intake of EPA and DHA reduces the production of pro-inflammatory mediators such as cytokines, interleukins and tumor necrosis factor (TNF). This is achieved (1) by competition with arachidonic omega-6 acid (20: 4n-6, ARA) for incorporation into membrane phospholipids, which lowers the ARA content of cell membranes and thus their availability for the synthesis of eicosanoids, and (2) competition for the same enzymes that convert ARA into pro-inflammatory eicosanoids (Calder 2006; Sijben et al. 2007).
[0096] Multiple (mechanistic) studies have confirmed that sufficient fish consumption has the following beneficial effects: • reduction of serum inflammatory markers (eg, Zampelas et al. 2005) • decreased total heart rate (eg Mozaffarian et al. 2005) • reduced blood pressure (eg Theobald et al. 2007) • reduced fasting triglycerides and postprandial plasma (eg Schwellenbach et al. 2006) • protection against heart arrhythmias, more probably by modulating the sodium and calcium ion channels in the myocardium (for example, Chrysohoou et al. 2007).
[0097] A large number of interventions with high n-3 PUFA intakes have been published with the aim of reducing symptoms (and sometimes treating) of diseases related to chronic inflammation, including rheumatoid arthritis, asthma, cancer-associated cachexia , and inflammatory bowel disease. Other diseases that have been confirmed to be influenced by the consumption of fatty acids from fish oil are, among others, cardiovascular diseases (CVD), macular degeneration, osteoporosis, depression, schizophrenia, attention deficit / hyperactivity disorder (ADHD), disorders eating, cancer, burns, and skin problems (Calder 2006).
[0098] The composition and purity of available fish oils vary considerably. Not only are these oils different in the total amount of EPA and DHA, but the relationship between EPA and DHA is also subject to variation (see Table 5). EPA and DHA have different functions in the human body; the beneficial effects of EPA contribute mainly to the competitive inhibition of eicosanoid synthesis from ARA, and the attributes of DHA are often linked to the functioning of the membrane. Despite these differences in functionality, many intervention studies provide very little information on the exact intake of these fatty acids, not at a minimum, because these levels can be difficult to determine in the diet. Table 5. Approximate fatty acid compositions (in grams per 100 grams) g) of various fish oils commonly used. Source: "The Lipid Handbook, third edition. 2007. FD Gunstone, JL Hardwood, AJ Dijkstra (Eds.). CRC Press, USA.

[0099] The most commonly used species of fish, that is, anchovies and sardines, are characterized by a relative excess of EPA over DHA, while on the other hand tuna oil is relatively rich in DHA (Table 5). Thus, the ratio of EPA versus DHA depends on the species that is used and the production process mainly determines the amount of these fatty acids. In addition to fish oil, which contains most EPA and DHA in the form of triglycerides, EPA and DHA can also be provided as purified ethyl esters. For example, a study showed that moderate DHA supplementation (0.7 g DHA / day, from a source of purified seaweed) lowered diastolic blood pressure within three months and that effect was more pronounced than those obtained higher doses of EPA and DHA combined in other studies (Theobald et al. 2007). Similarly, supplementation with 1 g / day of DHA was as effective as 1.25 g of EPA + DHA in reducing plasma triglycerides in elderly men after eight weeks (Davidson et al. 1997). The omega-3 LCPUFAs of ethyl esters and triglycerides are equally well incorporated in plasma lipids, despite any possible differences in the initial absorption timing (Luley et al. 1990; Hansen et al. 1993).
[00100] Dietary LCPUFAs can also be administered in the form of phospholipids, for example, derived from eggs. Although some studies have reported an upper intestinal absorption of phospholipid omega-3 LCPUFAs compared to triglycerides (Carnielli et al. 1998), others have reported similar appearances of LCPUFAs in the plasma lipid fraction and virtually equal rates of incorporation of ARA and DHA into cells red blood from phospholipids or triglycerides in young children (Sala-Vila et al. 2004; Sala-Vila et al. 2006).
[00101] As explained above, dietary alpha linolenic acid (ALA) can be converted to the long-chain omega-3 fatty acids EPA and DHA through enzymatic conversion. The possibility arises that, with the increase in ALA consumption, the levels of EPA and DHA tissue may be high. The rich sources of ALA are plant oils such as flaxseed oil (approximately 60% ALA), perilla oil (approximately 50% ALA), and canola oil (approximately 10%). However, the conversion of ALA to EPA (less than 10% dietary ALA) and DHA (less than 4% dietary ALA) in adults is not very efficient and is further reduced by 40-50% with an increase in diet based on omega-6 PUFAs (Gerster 1998; Williams et al. 2006). This suggests that high intakes of ALA will be required to obtain the equivalent of the recommended intakes of EPA + DHA. Thus, the addition of preformed EPA + DHA seems imperative.
[00102] In conclusion, increasing the dietary intake of LCPUFA Omega-3 reduces the risk of various diseases, including cardiovascular disease. In addition, an improvement in overall health can be expected from a reduction in pro-inflammatory markers, reduced serum triglycerides, and / or a reduction in blood pressure. Recommended intakes of EPA + DHA range from 0.15 to 0.5En%. To satisfy the minimum recommended intake of most organizations, the daily intake of EPA + DHA should be at least 500 mg / day (based on a minimum daily food intake of 1,500 kcal / day).
[00103] The fat fraction according to the invention comprises between 3.0 and 6% by weight of a combination consisting of polyunsaturated ω-3 fatty acids, alpha-linolenic acid (ALA), docosahexaenoic acid ( DHA) and eicosapentaenoic acid (EPA), wherein the amount of ALA> 2.5% by weight, and more preferably> 2.7% by weight, or preferably ranges between 2.5 and 4.0% by weight, and the combined amount of DHA and EPA = 2.5% by weight, and preferably = 1.0% by weight.
[00104] Polyunsaturated ω-3 fatty acids may be present as triglycerides, ethyl esters, phospholipids, sphingolipids, glycolipids or other forms of food grades. 2. Selection of appropriate fat sources with a low LA content
[00105] Almost all current commercial products contain essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) to satisfy the minimum requirements for fatty acids. However, these two fatty acids are the precursors to the long-chain polyunsaturated fatty acids (LC PUFA) that are required for the normal physiological function of all tissues. The intake of omega-6 by the general population has increased during the last decades of industrialization and the general consensus is that the Western diet now contains too much omega-6 fatty acids and insufficient omega-3 fatty acids (Ailhaud et al. (2006) ). This has an effect on a range of physiological and immunological functions.
[00106] Recommendations for a minimum intake of LA vary from 1 to 4% of total caloric intake per day: the French organizations AFSSA and CNERNA-CNRS provided the highest recommendation of 4En% for adults. None of the national health committees and councils included a safe upper limit for LA consumption. However, the level of LA in the fat composition that is currently used in a number of commercial products is several times higher than the intake that is considered adequate to prevent a deficiency. The reasons for limiting the LA content to an amount close to the most highly recommended (adequate) intake of 4En% are discussed in the following section.
[00107] The conversion of LA and ALA fatty acids into their respective LCPUFAs is controlled by a complex of metabolic factors and dietary composition (fatty acid). Among others, the increased dietary intake of LCPUFAs reduces the conversion of LA and ALA, presumably due to the down regulation of the product of the enzymatic desaturation and elongation pathways that are responsible for the conversion of LA and ALA (Brenna 2002). In addition, Emken et al. (1994) pleasantly demonstrated that the conversion of LA as well as ALA into their respective LCPUFAs (ARA, EPA, DHA) was reduced by 40-54%, when LA intake was increased from 15 to 30 g / day in volunteers (Emken et al. 1994). These LA intakes corresponded to 4.7 and 9.3En%, respectively (2800 kcal diets / day), which are in the range of normal dietary intakes and of feeds through straw and tube currently on the market. To compensate for the reduced endogenous production of long-chain omega-3 fatty acids, EPA and DHA must be provided through the diet, which is another argument for including fish oil in the composition according to the invention.
[00108] High intakes not only reduce the conversion of LA and ALA into long-chain fatty acids, but LA also competes with ALA, EPA, as well as DHA for incorporation into tissue phospholipids: the relationship between acids Omega-6 and dietary omega-3 fatty acids have an intense effect on eventual tissue composition. Consequently, high levels of LA have a marked effect on the efficiency of fish oil supplementation. Although intakes of ARA (a product downstream from LA) also play a role, LA is the predominant PUFA in a normal (western) diet. Hibbeln et al. (2006) compared the worldwide diversity of dietary intakes of omega-6 and omega-3 fatty acids with the risks of cardiovascular and mental illness and estimated a tissue target for omega-3 LCPUFAs: 60% of omega-3 fatty acids in LCPUFAs (and 40% omega-6 fatty acids in LCPUFAs) should be sufficient to protect 98% of the population against cardiovascular mortality. Since this level is only reached in populations with extreme fish consumption (Japan, Greenland), they proposed a more moderate and realistic goal of 50% omega-3 tissue LCPUFAs (Hibbeln et al. 2006). The 50% omega-3 target for tissue LCPUFAs, for example, corresponds to a reduction of approximately 60% in the relative risk for sudden death reported by Albert et al. (2002). Using a formula that takes into account the competition between fatty acids for incorporation (Lands et al. 1992), the required intake of EPA + DHA was calculated to achieve the goal of 50% omega-3 in relation to the base intake of LA (Figure 1, Lands et al. 1992). This graph illustrates that the effectiveness of fish oil supplementation is enhanced when the intake of LA is reduced, or, in other words, the effectiveness of fish oil supplementation is greatly reduced when the intake of LA is increased. For example, a dose of more than three times EPA + DHA is required to achieve the same tissue level at an LA intake of 8.9En% than with a diet containing 3.2En% LA. Knowing that LA competes with EPA and DHA for incorporation into tissues, it is now possible to determine how the LA content of the present invention is related to recommendations for eating fish, which are in the 0.2-0 range, 5En% of EPA + DHA.
[00109] In conclusion: to make sure that the level of LA can be considered as adequate according to all the recommendations, a minimum of 4En% of LA is required (French recommendation for adults). Due to the fact that higher levels of LA will reduce the efficiency of fish oil supplementation and adversely affect the tissue's omega-6 / omega-3 ratio, this level of 4En% should preferably be considered as the maximum level for products nutritionally complete. With the modification of the oils currently used in production (see also the following section) it is feasible to lower the LA content to 4En%, although care must be taken to keep the ALA content above 1En% ALA (the minimum recommended intake more high ALA). In this way, the formula's omega-6 / omega-3 ratio can be reduced to approximately 3: 1. Preferably, the ratio of ω-6: ω-3 in the fat composition according to the invention is approximately 2.5: 1 - 3.5: 1, and preferably 3: 1, where the term approximately means one relative deviation of 10%.
[00110] The fat fraction according to the invention comprises between 10 and 15% by weight of linoleic acid (LA).
[00111] Linoleic acid may be present as triglycerides, phospholipids, sphingolipids, glycolipids or other forms of food grades. 3. Inclusion of medium chain fatty acids (MCFAs)
[00112] Most plant oils currently available contain LA, making it difficult to reduce the LA content in a fat composition to the recommended 4En%. Without compromising the total fat content, a possible solution is to increase other fatty acids, for example, MUFAs (ie oleic acid). Unfortunately, the available oils that are rich in MUFAs (olive oil, sunflower oil with high oleic acid content) also contain LA, which means that an increase in the MUFA content also results in an increase in the LA content. On the other hand, the saturated fatty acid content can be increased: the current saturated fatty acid contents of most saturated commercial products are well below the recommended upper intakes. However, the increase in the saturated fatty acid content cannot be considered immediately as a health benefit, since, for example, it increases serum cholesterol levels. One group of saturated fatty acids that can be considered as a healthier alternative is that of medium chain fatty acids (MCFAs) that are found naturally in the form of medium chain triglycerides (MCTs). MCTs are glycerol esters of medium chain fatty acids that consist of three medium chain saturated fatty acids (MCFAs) each of which comprises six to twelve carbon atoms.
[00113] The natural sources of MCFAs are coconut oils and palm seed oils. When hydrolyzed, these oils provide concentrated sources of MCFAs with chain lengths mainly of eight (caprylic or octanoic acid) and ten (capric or decanoic acid) carbon atoms. Thus, in practice, when MCTs or MCFAs are administered, this is often limited to fatty acids with eight and ten carbon chains, although (theoretically) MCFAs also include carbon chains of six and twelve carbon atoms.
[00114] Thus, the MCFAs according to the invention are preferably selected from MCTs that originate from coconut oils and / or palm seed oils. The chain length of the MCFAs according to the invention is 6, 7, 8, 9, 10, 11 or 12, preferably 8, 9 or 10, and more preferably 8 or 10 carbon atoms in length, or any mixture of these .
[00115] MCFAs are not considered essential and are therefore not considered as a necessary part of the normal diet. Although MCFAs are categorized as saturated fats, they have completely different biochemical and physiological properties compared to long-chain saturated fatty acids, which will be explained below. (1) Digestion and absorption of MCFAs is easier and faster compared to long-chain fatty acids (LCFAs). MCFAs absorbed from the small intestine (intact or after hydrolysis) are transported mainly through the portal vein to the liver. On the other hand, long-chain dietary triglycerides are primarily hydrolyzed in the small intestine as LCFAs and re-esterified in the mucous cells of the small intestine as long-chain triglycerides. They are then incorporated into chylomicrons and reach the circulation through the lymphatic system (Bach et al. 1996; Snook et al. 1996). In addition, MCFAs digestion and absorption are not dependent on pancreatic enzymes or bile salts. In particular, patients with malabsorption syndrome and / or pancreatic insufficiency will benefit from a diet rich in MCTs / MCFAs, and MCFAs are therefore often used as the preferred fat source for these patients (Marten et al. 2006 ). (2) MCFAs immediately cross the mitochondrial membrane and are quickly oxidized (beta-oxidation). This is (in part) due to the fact that fatty acids containing six to twelve carbons do not need carnitine to cross the mitochondrial membrane in the liver tissue of healthy, well-fed adults, which is opposed to carnitine-dependent beta-oxidation of fatty acids with fourteen carbon atoms or more (Calabrese et al. 1999). Beta-oxidation of fatty acids results in the production of acetyl-CoA, which penetrates the Kreb cycle to produce energy, but acetyl-CoA can also be converted into acetoacetate, beta-hydroxybutyrate and acetone, collectively called ketone bodies. Rapid absorption of MCFAs in mitochondria can lead to additional production of acetyl-CoA and increased production of ketone bodies (ketogenic effect), which can also be metabolized in the liver, but can also be transported through the systemic circulation to other tissues for serve as a directly available energy source (Marten et al. 2006). (3) The preferred p-oxidation of MCFA by mitochondria can protect PUFA against oxidation, which should increase the availability of EPA and DHA for incorporation into tissue phospholipids. A small number of studies have indeed suggested the existence of such an effect. For example, in one study, premature children were fed enterally and given a formula with 40% MCFA (MCT) or a formula without MCFA for seven days (Rodriguez et al. 2003). After that period, oxidation of a standard dose of labeled LA was significantly reduced in the MCFA-treated group. Similarly, parenteral administration of an MCFA emulsion combined with long chain triglycerides (1: 1 ratio) for eight days resulted in slightly elevated levels of LCPUFA in plasma phospholipids and triacylglycerides compared to an emulsion with only PUFAs in another study with premature children (Lehner et al. 2006). However, the evidence for the protection of PUFAs through the provision of MCTs / MCFAs in adults is limited. (4) The preference for β-oxidation of MCFAs by mitochondria for energy production is greater compared to LCFAs, which (theoretically) means that less fatty acids are stored in adipose tissue when provided as MCFAs and more of them are used for generate energy (Metges et al. 1991).
[00116] The amount of MCFA or MCT required to reduce the LA content is relatively small: for example, for a commercial product such as Nutrison Standard (NV Nutricia), approximately 4En% of MCFAs (C8 + C10) are sufficient - together with a modification of other sources of vegetable oil - to reduce the LA content from 8.3 to 4En%. This should correspond to approximately 10 to 15% of the fat composition as MCFA, or to 6-8 g of MCFA (C8 + C10) per day (1,500 kcal / day). At these levels, gastrointestinal discomfort is unlikely to occur, since higher levels have been reported to be well tolerated. For example, a 40En% fat diet, of which 50% consisted of MCT, was generally well tolerated, although minor gastrointestinal discomfort and occasional nausea have been reported during the first few days of consumption (Bourque et al. 2003). Similarly, a diet with as much as 67% fat as MCT (40% fat) has been reported to be tolerated by volunteers (St-Onge et al. 2003).
[00117] In conclusion, to help lower the LA content of the fat composition, the total PUFA can be reduced by increasing the amount of saturated fat: the total saturated fatty acid content of most current commercial products is low ( <5En%) and can be increased within the recommended upper levels (10-12En%). Although MCFAs are categorized as saturated fat, these fatty acids are easily digestible and are quickly oxidized to produce energy, unlike long-chain fatty acids that are stored in adipose tissue. The inclusion of MCTs / MCFAs can be used as a healthy way to reduce the LA content of products (within limits). Only small amounts of MCT / MCFA (10-15% of the fat composition) are required to lower the LA content to the desired level of 4En%, as long as other vegetable oils are also modified.
[00118] The fat fraction according to the invention comprises between 10 and 20% by weight, preferably from 14 to 18% by weight, and more preferably from 15.7 to 16.2% by weight of medium chain fatty acids (MCFAs).
[00119] Medium chain fatty acids may be present as triglycerides, phospholipids, sphingolipids, glycolipids or other forms of food grades. (5) Inclusion of a source rich in monounsaturated fatty acids (MUFAs)
[00120] Unsaturated fatty acids are sensitive to oxidation, which leads to the production of harmful oxygen radicals and oxidative damage to the surrounding molecules and cells. Since the sensitivity to fatty acid oxidation depends on the number of double bonds in the fatty acid carbon chain, monounsaturated fatty acids (MUFAs) are less susceptible to oxidation than polyunsaturated fatty acids.
[00121] The development of atherosclerosis, a chronic inflammatory response in the artery walls, is caused by the deposition of lipoproteins (plasma proteins that contain cholesterol and triglycerides) in the arterial wall. Oxidized low-density lipoprotein (LDL) is believed to be more harmful to the arterial wall than native LDL and oxidation of LDL contributes to the development of atherosclerosis. High concentrations of circulating oxidized LDL show a positive relationship with the severity of acute coronary events and are predictors for CHD in CHD patients and in the general population (Covas, 2007).
[00122] The substitution of fatty acids saturated with oleic acid reduces the risk of developing CHD, among others, by incorporating oleic acid at the expense of linoleic acid (C18: 2n-6), which reduces the sensitivity of LDL to oxidation ( Reaven et al., 1993; Covas, 2007). In addition, total blood LDL concentration, as well as factor VII clotting activity, decrease when foods high in saturated fat are replaced with foods high in sunflower oil high in oleic acid in middle-aged men and women. age within a matter of weeks (Allman-Farinelli et al., 2005).
[00123] Monounsaturated fatty acid is preferably selected from the group of palmitoleic acid (16: 1), oleic acid (18: 1), eicosenoic acid (20: 1), erucic acid (22: 1), nerve acid (24: 1) 1) or mixtures of these. More preferably, the monounsaturated fatty acid comprises oleic acid. More preferably, at least 80% by weight of the monounsaturated fatty acid consists of oleic acid.
[00124] The fat fraction according to the invention comprises between 35 and 79% by weight, preferably from 50 to 70% by weight, and more preferably from 50 to 60% by weight of at least one monounsaturated fatty acid.
[00125] Suitable sources for increasing the MUFA content include, for example, sunflower oil with high oleic acid content, safflower oil with high oleic acid content, and olive oil.
[00126] Monounsaturated fatty acids can be present as triglycerides, phospholipids, sphingolipids, glycolipids or other forms of food grades. Preparation of the fat fraction
[00127] When indicated as the fat fraction according to the invention, the fat composition can be available as a combination or mixture as such, it can be available as a set of components at a defined concentration in a nutritional composition, it can be prepared as such, or can be prepared by adding the different components LA, an ALA, DHA, EPA, MCFA and MUFA, or sources that comprise said components together with other ingredients to produce a nutritional composition comprising the fat composition according to with the invention. It can also be available as a set of parts, comprising the separate components LA, ALA, DHA, EPA, MCFA and MUFA, or sources that comprise said components to be combined together in the defined quantities, optionally accompanied by instructions on way on how to do that.
[00128] The fat composition according to the invention may further comprise another fatty acid, preferably a fatty acid selected from the group of saturated fatty acids with the exception of MCFA and polyunsaturated fatty acids with the exception of ALA, DHA and EPA.
[00129] The fat composition according to the invention can be manufactured by a person skilled in the art by combining the appropriate fat sources in appropriate amounts. According to one embodiment, the following sources can be combined: canola oil, sunflower oil with high oleic acid content, fish oil and MCT oil. They are combined more particularly: approximately 37% by weight of canola oil, approximately 42% by weight of high oleic acid sunflower oil, approximately 2% by weight of fish oil and approximately 17% by weight of MCT oil . It should be obvious to a person skilled in the art that the amounts provided above may vary to some extent depending on the specific composition of the fat source. Carbohydrate fraction
[00130] Advantageously, the nutritional composition according to the invention comprises one or more digestible carbohydrates. Digestible carbohydrates positively influence a patient's operational capabilities, and increase the beneficial effect of the nutritional composition according to the invention.
[00131] According to one embodiment, the liquid nutritional composition according to the invention preferably contains between 1 and 50 grams of digestible carbohydrates per 100 ml, more preferably between 5 and 30 grams per 100 ml, and most preferably still 5, 6 , 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 grams of digestible carbohydrates per 100 ml of a liquid product or any fraction of integer and whole numbers interspersed.
[00132] According to one embodiment, the liquid nutritional composition according to the invention preferably contains a carbohydrate fraction comprising between 30 and 62En% of the total energy of the composition.
[00133] Examples of digestible carbohydrates include digestible pentoses, digestible hexoses, and digestible oligosaccharides, for example, digestible disaccharides and digestible traccharides. More specifically, one or more digestible carbohydrates can be chosen by being selected from the group of galactose, mannose, ribose, sucrose, trehalose, palatinose, lactose, maltodextrose, maltose and glucose. Dietary fiber fraction
[00134] It is generally known that dietary fiber plays an important role in the nutrition of healthy people. It maintains the function of the intestine and eliminates toxic compounds by providing a volume of defecation and substrate to the intestinal flora, and keeps the intestine wall in good condition. Hospital patients who normally receive enteral clinical nutrition need fiber for these purposes, and consuming the right fiber mix is especially important for patients suffering from intestinal problems, such as ulcerative colitis, Crohn's disease, and others , and who received antibiotics. In addition, people with constipation or diarrhea have a special interest in this type of nutrition, and the same applies to people who cannot consume the recommended daily amount of fiber for any reason (for example, diet). An ideal fiber composition: - will be similar to the normal fiber composition as consumed by healthy people in Western countries; - will produce beneficial short-chain fatty acids (SCFA) in a balanced relationship and at a sufficient and uniform rate during transit through the ileum and the large intestine; - it will not produce gas at too high or too low levels; - it will give the stools enough mass to facilitate defecation; - will not dramatically increase the viscosity of the stool.
[00135] A large number of enteral nutritional compositions are known which comprise ideal and less than ideal dietary fiber compositions, such as those presented in WO 93/100020 A2, EP 0483070 A2, EP 0486425 A2, EP 0504055 A2, EP 0570791 A2, and particularly in EP 0756828 BI.
[00136] The enteral nutritional composition according to the invention is suitable to comprise any dietary fiber, or any mixture of dietary fibers. In particular, the enteral nutritional composition according to the invention is suitable to comprise one or more of fructooligosaccharides, inulin, acacia fiber, gum arabic, soy polysaccharide, alpha cellulose and resistant starch.
[00137] In a preferred embodiment, the enteral nutritional composition according to the invention comprises a mixture of dietary fibers as indicated in patent document EP 075 828 BI. More particularly, the liquid enteral nutritional composition comprises from 5 to 120 g / 1 of dietary fiber, wherein the fraction of dietary fiber consists of 15 to 50% by weight of polysaccharides other than soluble starch, 15 to 45% by weight of non-insoluble starch polysaccharides, 8 to 70% by weight of non-digestible oligosaccharides comprising at least 8% by weight, based on fiber, of hydrolyzed inulin, and comprising resistant starch.
[00138] In a preferred embodiment, the enteral nutritional composition according to the invention comprises the dietary fiber mixture as indicated in Table 6. Table 6 - Preferred dietary fiber mixture according to the invention
Micronutrients
[00139] The liquid nutritional composition according to the invention may contain mineral salts, trace elements, vitamins and other micronutrients, and the amounts of these are generally within the ranges as specified for Food for Special Medical Purposes Specials] (FSMP).
[00140] More specifically, one or more of the following micronutrients may be particularly present: sodium, potassium, chlorine, calcium, phosphorus, manganese, molybdenum, zinc, selenium, magnesium, chromium, iron, copper, fluorine, iodine, vitamin A ( retinol), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B8 (biotin), vitamin Bll (folic acid), vitamin B12 ( cyanocobalamin), vitamin C (ascorbic acid), vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), vitamin E (alpha-tocopherol), vitamin K, carotenoids, taurine, cysteine, choline, carnitine, and coenzyme Q10. Viscosity
[00141] In one embodiment of the present invention, the viscosity of the liquid enteral nutritional composition is less than 500 mPa.s, measured at 20 ° C (i.e., room temperature) at a shear rate of 100 s-1, preferably between 10 and 200 mPa.s, more preferably between 10 and 100 mPa.s, and even more preferably below 50 mPa.s. Viscosity can be appropriately determined using a rotational viscosity meter using cone / plate geometry. This viscosity is ideal for the oral administration of the liquid enteral nutritional composition according to the invention because a person can easily consume a portion that has a low viscosity as indicated by the present invention. This viscosity is also ideal for unit dosages that are fed via a tube.
[00142] In an embodiment of the present invention, the density of the composition varies between 1.00 g / ml and 1.20 g / ml, and especially between 1.05 g / ml and 1.15 g / ml. Nutritional composition
[00143] Surprisingly, the pea-based protein mixture and the fat mixture according to the invention make it possible to produce a nutritional composition, particularly a liquid enteral nutritional composition with a long shelf life and a low viscosity, more particularly as a tube feed. Accordingly, the invention also relates to a pea-based protein mixture according to the invention for use in the manufacture of a nutritional composition, particularly a liquid nutritional composition, particularly for use as a tube feed, and more particularly for long-tube feeding.
[00144] According to a further embodiment, the liquid enteral nutritional composition according to the invention optionally comprises one or more of a carbohydrate fraction, a dietary fiber fraction, and micronutrients.
[00145] More preferably, such liquid nutritional composition is sterilized or pasteurized. Dosing unit
[00146] The liquid enteral nutritional composition according to the invention is preferably in the form of a complete food, that is, it can satisfy all the nutritional needs of the user. In this way, the liquid enteral nutritional composition according to the invention preferably contains 1,000 to 2,500 kcal per daily dosage. Depending on the condition of the patient, a daily dose is approximately 25 to 35 kcal / kg of body weight / day. Therefore, a typical daily dose for a 70 kg person contains approximately 2,000 kcal. The complete food can be in the form of multiple dosage units, for example, from 8 (250 ml / unit) to 2 units (1 1 / unit) per day for an energy source of 2,000 kcal / day using an enteral nutritional composition liquid according to the invention of 1.0 kcal / ml. Preferably, the nutritional composition is adapted for tube feeding.
[00147] The liquid enteral nutritional composition can also be an oral food supplement, for example, to be used in addition to a non-medical food or normal diet. Preferably, as an oral supplement, the liquid enteral nutritional composition contains less than 1,500 kcal per daily dosage, and particularly as a supplement the liquid enteral nutritional composition contains from 500 to 1,000 kcal per daily dose. The food supplement can be in the form of multiple dosage units, for example, from two (250 ml / unit) to ten units (50 ml / unit) per day for a 500 kcal / day energy source using a nutritional composition liquid enteral according to the invention of 1.0 kcal / ml.
[00148] Preferably, the nutritional composition is packaged, stored and supplied in a container such as a plastic bag or a purse or the like. A variety of such containers are known, for example, 500 ml, 1000 ml and 1500 ml containers are known in the art. It should be noted that any suitable container can be used to package, store and supply the nutritional composition according to the invention.
[00149] In one embodiment of the present invention, the liquid enteral nutritional composition is provided in a ready-to-use liquid form and does not require reconstitution or mixing before use. The liquid enteral nutritional composition according to the invention can be fed via tube or administered orally. For example, the composition according to the invention can be supplied in a can, ear, and hand bag. However, a composition can be provided to a person in need of it in powder form, suitable for reconstitution using an aqueous solution or water in such a way that the enteral nutritional composition according to the invention is produced. Thus, in an embodiment of the present invention, the present composition can be in the form of a powder, accompanied with instructions to be dissolved or reconstituted in an aqueous composition or water to obtain the liquid nutritive enteral composition according to the present invention. In an embodiment of the present invention, the present liquid nutritional enteral composition can thus be obtained by dissolving or reconstituting a powder, preferably in an aqueous composition, particularly water, and more particularly sterile water. Such a reconstituted liquid composition does not need to be sterilized or pasteurized if used or administered immediately thereafter, but it can also be sterilized or pasteurized on site prior to administration.
[00150] In one embodiment of the present invention, the composition according to the invention is packaged. The package may have any suitable shape, for example, a block-shaped box, for example, to be emptied with a straw; a cardboard or plastic bowl with a removable lid; a small bottle, for example, for the 80 ml to 200 ml range, and small glasses, for example, for the 10 ml to 30 ml range. Another suitable form of packaging is the inclusion of small volumes of liquid (for example, 10 ml to 20 ml) in solid or semi-solid edible casings or capsules, for example, gelatin type covers, and others. Another suitable form of packaging is a powder in a container, for example, a sachet, preferably with instructions for dissolving or reconstituting it in an aqueous composition or water. Preparation
[00151] The liquid nutritional composition according to the invention can be prepared using standard methods known to a person skilled in the art. For example, the liquid nutritional composition, the protein fraction and the fat fraction according to the invention can be prepared as indicated above ("Preparation of the protein mixture", and "Preparation of the fat mixture"). According to one embodiment, the method for preparing the liquid nutritional composition according to the invention comprises at least the following steps: (a) mixing the sources of protein, carbohydrate and fiber with water to obtain a mixture A (for example, see: "Preparation of protein fraction"); (b) mixing said mixture A with a mineral solution comprising mineral salts and trace elements to obtain a mixture B; (c) adjusting the pH of said mixture B by at least approximately 8; (d) heating said mixture B to a temperature ranging from approximately 70 to 90 ° C for a maximum of approximately 30 seconds; (e) adding a fat mixture to said mixture B to obtain a mixture C and homogenizing said mixture C (for example, see: "Preparation of the fat fraction"); (f) mixing said mixture C with a vitamin solution to obtain a mixture D; (g) adjusting the pH of said mixture to a value that varies between approximately 7.8 and 8; (h) placing said mixture D in a container; and (i) sterilizing said container, for example, in an autoclave. Efficiency
[00152] The present invention also relates to a method of providing nutrition to a person in need thereof, which comprises the steps of administering to said person the nutritional composition according to the present invention. Said person can be an elderly person, a person who is in a sick state, a person who is recovering from a sick state, or a person who is malnourished.
[00153] The present invention also relates to the use of a liquid nutritional composition according to the invention, such as tube feeding, particularly for long tube feeding. As used herein, the term "long-term" means more than one month (thirty days). It is obvious that nutrition, when appropriate for long-term nutrition, is also suitable for any other shorter nutrition period, such as medium-term nutrition (ten to thirty days) and short-term nutrition (between one and ten days).
[00154] When administered to patients in need of enteral nutrition, a lower incidence of clinical indications was observed for the composition according to the invention, compared to a composition according to the state of the art, particularly for clinical complications of the digestive tract upper (nausea, vomiting, use of antacids), but also for clinical complications of the lower digestive tract (diarrhea, constipation), adverse events related to the gastrointestinal tract, adverse events related to pneumonia, and serious adverse events.
[00155] According to one embodiment, the liquid enteral nutritional composition according to the invention can be administered to a patient in need of it, to prevent said clinical complications of the upper and lower digestive tracts.
[00156] According to another embodiment, the liquid enteral nutritional composition according to the invention can be administered to a patient in need thereof, who has been fed an enteral nutritional composition of the prior art and / or has developed said complications clinics of the upper and lower digestive tracts, to treat and reduce said clinical complications of the upper and lower digestive tracts.
[00157] Thus, the present invention also relates to the use of a liquid enteral nutritional composition according to the invention, for the manufacture of a medicament for the prevention and / or treatment of conditions of the upper and / or lower digestive tracts in a tube fed patient. Preferably, the conditions are selected from the group of nausea and vomiting.
[00158] The invention will now be further elucidated by several examples, without being limited by them. Experimental Part Example 1
[00159] Methods: In a cross-sectional randomized, double-blind, crossover controlled study from two countries, 28 residents of nursing homes with long-term tube feeding received in a different order a tube feed comprising the nutritional composition according to the invention (NN) and a control product (Nutrison MF, Nutricia, Netherlands (N), see Table 7) for four weeks (two weeks each product). Safe use for recording (serious) adverse events ((S) AE), use of medication, incidence of diarrhea and constipation based on stool frequency and consistency (using the Bristol Stool Shape Scale), and subjective gastrointestinal complaints . Statistical analyzes were performed for the ITT and PP population when comparing NN with N. The statistical tests are performed on two sides with a significant level of 5%. All confidence intervals are presented on two sides with a 95% confidence coefficient. Table 7: Composition of the tested product and the control product per 100 ml




[00160] Results: The average age and BMI of the ITT population (n = 28) were 63 years old and 25.5 kg / m2. The average period (minimum - maximum) of tube feeding before the study was 26 (1 - 208) months. The average daily intake during the study was 1,339 (786 - 2,100) ml with NN and 1,178 (786 - 2,000) ml with N (p = 0.043). A definite trend towards a lower incidence of constipation was observed in NN (31% versus 50%, p = 0.070). The incidences of all other parameters tested were generally lower in NN compared to N (NN versus N: nausea 8% versus 20%, vomiting 4% versus 12%, flatulence 19% versus 16%, diarrhea 31% versus 36% , constipation 23 versus 36%, laxative use 73% versus 79%, antidiarrheals 0% versus 0%, antacids 54% versus 57%, antibiotics 4% versus 18%, opioids 15% versus 18, gastrointestinal AE 12% versus 18% , AE pneumonia 8% versus 14%, other AE 8% versus 14%, SAE 4% versus 14%), although the differences were not significant at a significance level of 0.05. PP analyzes (n = 21) revealed similar trends. Example 2
[00161] Table 8 shows a number of compositions according to the invention, suitable as adult tube feeding, pediatric tube feeding or adult oral nutritional supplement. Table 8: Enteral compositions according to the Invention

* in these examples 3.9 g of fat is equal to 3.7 g of fatty acids; 5.8 g of fat is equal to 5.5 g of fatty acids; 9.3 g of fat is equal to 8.7 g of fatty acids.
[00162] It should be understood that several changes and modifications in the currently preferred realizations described here will be apparent to the elements versed in the technique. Such changes and modifications can be made without deviating from the objective and scope of the invention and without diminishing its advantages. It is therefore intended that such changes and modifications are covered by the attached claims. References Ailhaud, G., F. Massiera, P. Weill, P. Legrand, J. M. Alessandri and P. Guesnet (2006). "Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in ex-cessive adipose tissue development and relationship to obesity." Prog Lipid Res 45 (3): 203-36. Albert, C. M., H. Campos, M. J. Stampfer, P. M. Ridker, J. E. Manson, W. C. Willett and J. Ma (2002). "Blood levels of long-chain n-3 fatty acids and the risk of sudden death." N Engl J Med 346 (15): 1113-8. Allman-Farinelli, M. A., K. Gomes, et al. (2005). "A diet rich in high-oleic-acid sun-flower oil favorably alters low-density lipoprotein cholesterol, triglycerides, and factor VII coagulant activity." J Am Diet Assoc 105 (7): 1071-9. Bach, A. C., Y. Ingenbleek and A. Frey (1996). "The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy " J Lipid Res 37 (4): 708-26. Bemelmans, W. J., J. Broer, E. J. Feskens, A. J. Smit, F. A. Muskiet, J. D. Lefrandt, V. J. Bom, J. F. May and B. Meyboom-de Jong (2002). "Effect of an increased in-take of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study." Am J Clin Nutr 75 (2): 221-7. Bourque, C., M. P. St-Onge, A. A. Papamandjaris, J. S. Cohn and P. J. Jones (2003). "Consumption of an oil composed of medium chain triacyglycerols, phytosterols, and N-3 fatty acids improves cardiovascular risk profile in overweight women." Metabolism 52 (6): 771-7. Brenna, J. T. (2002). "Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man." Curr Opin Clin Nutr Metab Care 5 (2): 127-32. Burdge, G. C. and S. A. Wootton (2002). "Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women." Br J Nutr 88 (4): 411-20. Calabrese, C., S. Myer, S. Munson, P. Turet and T. C. Birdsall (1999). "A cross-over study of the effect of a single oral feeding of medium chain triglyceride oil vs. canola oil on post-ingestion plasma triglyceride levels in healthy men." Altern Med Rev 4 (1): 23-8. Calder, P. C. (2006). "n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases." Am J Clin Nutr 83 (6 Suppl): 1505S-1519S. Carnielli, V.P., G. Verlato, F. Pederzini, I. Luijendijk, A. Boerlage, D. Pedrotti and P. J. Sauer (1998). "Intestinal absorption of long-chain polyunsaturated fatty acids in preterm infants fed breast milk or formula." Am J Clin Nutr 67 (1): 97-103. Covas, M. I. (2007). "Olive oil and the cardiovascular system." Pharmacol Res 55 (3): 175-86. Chrysohoou, C., D. B. Panagiotakos, C. Pitsavos, J. Skoumas, X. Krinos, Y. Chloptsios, V. Nikolaou and C. Stefanadis (2007). "Long-term fish consumption is associated with protection against arrhythmia in healthy persons in a Mediter-ranean region - the ATTICA study." Am J Clin Nutr 85 (5): 1385-91. Davidson, M. H., K. C. Maki, J. Kalkowski, E. J. Schaefer, S. A. Torri and K. B. Dren-nan (1997). "Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial." J Am Coll Nutr 16 (3): 236-43. Deutsche Gesellschaft für Ernâhrung e. V. (2006). Evidenzbasierte Leitlinie: Fettkon-sum und Prevention ausgewâhlter ernahrungsmitbedingter Krankheiten. Bonn. Emken, E. A., R. 0. Adlof and R. M. Gulley (1994). "Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males." Biochim Biophys Acta 1213 (3): 277-88. Gerster, H. (1998). "Can adults adequately convert alpha-linolenic acid (18: 3n-3) to eicosapentaenoic acid (20: 5n-3) and docosahexaenoic acid (22: 6n-3) " Int J Vi-tam Nutr Res 68 (3): 159-73. Goyens, P. L., M. E. Spilker, P. L. Zock, M. B. Katan and R. P. Mensink (2006). "Con-version of alpha-linolenic acid in humans is influenced by the absolute amounts of alphalinolenic acid and linoleic acid in the diet and not by their ratio." Am J Clin Nutr 84 (1): 44-53. Hansen, J. B., J. 0. Olsen, L. Wilsgard, V. Lyngmo and B. Svensson (1993). "Com-parative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on lipids, haemostasis and platelet function in normolipaemic men." Eur J Clin Nutr 47 (7): 497-507. Health Council of the Netherlands (2006). Guidelines for a healthy diet 2006. publica-tion nr. 2006/21. The Hague. Hibbeln, J. R., L. R. Nieminen, T. L. Blasbalg, J. A. Riggs and W. E. Lands (2006). "Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity." Am J Clin Nutr 83 (6 Suppl): 1483S-1493S. ISSFAL (2004). Recommendations for intake of polyunsaturated fatty acids in healthy humans. Brighton, International Society for the Study of Fatty Acids and Lipids. Lands, W. E., B. Libelt, A. Morris, N. C. Kramer, T. E. Prewitt, P. Bowen, D. Schmeis-ser, M. H. Davidson and J. H. Burns (1992). "Maintenance of lower proportions of (n - 6) eicosanoid precursors in phospholipids of human plasma in response to added dietary (n - 3) fatty acids." Biochim Biophys Acta 1180 (2): 147-62. Lehner, F., H. Demmelmair, W. Roschinger, T. Decsi, M. Szasz, K. Adamovich, R. Arnecke and B. Koletzko (2006). "Metabolic effects of intravenous LCT or MCT / LCT lipid emulsions in preterm infants." J Lipid Res 47 (2): 404-11. Luley, C., H. Wieland and J. Grünwald (1990). "Bioavailability of omega-3 fatty acids: ethyl ester preparations are as suitable as triglyceride preparations." Akt.Ernãhr.-Med. 15: 123-5. Marten, B., M. Pfeuffer and J. Schrezenmeier (2006). "Medium-chain triglycerides." International Dairy Journal 16: 1374-82. Metges, C. C. and G. Wolfram (1991). "Medium- and long-chain triglycerides labeled with 13C: a comparison of oxidation after oral or parenteral administration in humans." J Nutr 121 (1): 31-6. Mozaffarian, D., A. Geelen, I. A. Brouwer, J. M. Geleijnse, P. L. Zock and M. B. Katan (2005). "Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials." Circulation 112 (13): 1945-52. Reaven, P., S. Parthasarathy, et al. (1993). "Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hyper-cholesterolemic subjects." J Clin Invest 91 (2): 668-76. Rodriguez, M., S. Funke, M. Fink, H. Demmelmair, M. Turini, G. Crozier and B. Koletzko (2003). "Plasma fatty acids and [13C] linoleic acid metabolism in pre-term infants fed a formula with medium-chain triglycerides." J Lipid Res 44 (1): 41-8. Sala-Vila, A., C. Campoy, A. I. Castellote, F. J. Garrido, M. Rivero, M. Rodríguez-Palmero and M. C. López-Sabater (2006). "Influence of dietary source of docosahexaenoic and arachidonic acids on their incorporation into membrane phospholipids of red blood cells in term infants." Prostaglandins Leukot Essent Fatty Acids 74 (2): 143- 8. Sala-Vila, A., A. I. Castellote, C. Campoy, M. Rivero, M. Rodriguez-Palmero and M. C. Lopez-Sabater (2004). "The source of long-chain PUFA in formula supplements does not affect the fatty acid composition of plasma lipids in fullterm in-fants." J Nutr 134 (4): 868-73. Schwellenbach, L. J., K. L. Olson, K. J. McConnell, R. S. Stoicpart, J. D. Nash and J. A. Merenich (2006). "The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone versus in combination with low dose eicosapentaenoic acid in patients with coronary artery disease and elevated triglycerides." J Am Coll Nutr 25 (6): 480-5. Serhan, C. N. (2006). "Novel chemical mediators in the resolution of inflammation: resolvins and protectins." Anesthesiol Clin 24 (2): 341-64. Sijben, J. W. and P. C. Calder (2007). "Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease." Proc Nutr Soc 66 (2): 237-59. Snook, J. T., S. Park, G. Wardlaw, R. Jandacek, D. Palmquist, M.-S. Lee and J. Hoover (1996). "Chylomicron fatty acid composition and serum lipid concentrations in subjects fed caprenin or palm oil / palm kernel oil as the major dietary fat." Nutrition Research 16 (6): 925-36. St-Onge, M.P., C. Bourque, P.J. Jones, R. Ross and W. E. Parsons (2003a). "Medium- versus long-chain triglycerides for 27 days increases fat oxidation and energy expenditure without resulting in changes in body composition in overweight women." Int J Obes Report Metab Disord 27 (1): 95-102. Tapiero, H., G. N. Ba, P. Couvreur and K. D. Tew (2002). "Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies." Biomed Pharmacother 56 (5): 215-22. Theobald, H. E., A. H. Goodall, N. Sattar, D. C. Talbot, P. J. Chowienczyk and T. A. Sanders (2007). "Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women." J Nutr 137 (4): 973-8. Williams, C. M. and G. Burdge (2006). "Long-chain n-3 PUFA: plant v. Marine sources." Proc Nutr Soc 65 (1): 42-50. Zampelas, A., D. B. Panagiotakos, C. Pitsavos, U. N. Das, C. Chrysohoou, Y. Skoumas and C. Stefanadis (2005). "Fish consumption among healthy adults is associated with decreased levels of inflammatory markers related to cardiovascular disease: the ATTICA study." J Am Coll Cardiol 46 (1): 120-4.

权利要求:
Claims (16)
[0001]
1. NET ENTERAL NUTRITIVE COMPOSITION, characterized by comprising: (i) a protein fraction comprising more than 25% by weight and up to 80% by weight of vegetable protein comprising at least one source of intact pea protein, in which the fraction of protein further comprises a milk protein selected from the casein group, including micellar casein and caseinate, and whey protein; (ii) a fat fraction comprising: (a) 8 to 15% by weight of linoleic acid (LA); (b) from 3.0 to 6.0% by weight of a combination consisting of polyunsaturated ω-3 fatty acids: alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in that the amount of ALA> 2.5% by weight and the combined amount of DHA and EPA <2.5% by weight; (c) 10 to 20% by weight of at least one medium chain fatty acid (MCFA); and (d) 35 to 79% by weight of at least one monounsaturated fatty acid (MUFA), in which all the relative amounts are calculated based on the total amount of fatty acids in the fat fraction.
[0002]
2. NET ENTERAL NUTRITIVE COMPOSITION, according to claim 1, characterized by additionally comprising one or more of a carbohydrate fraction, a dietary fiber fraction, and micronutrients.
[0003]
3. NET ENTERAL NUTRITIVE COMPOSITION according to either of Claims 1 or 2, characterized in that the protein fraction comprises 30 to 50% by weight, and more particularly 35 to 45% by weight of the vegetable protein in relation to the total protein in the protein fraction.
[0004]
4. NET ENTERAL NUTRITIVE COMPOSITION, according to any one of claims 1 to 3, characterized in that the protein fraction comprises from 5 to 60% by weight, particularly from 10 to 30% by weight, and more particularly from 15 to 25% in weight of pea protein, in relation to the total protein in the protein fraction.
[0005]
5. NET ENTERAL NUTRITIVE COMPOSITION, according to any one of claims 1 to 4, characterized in that the protein fraction additionally comprises a second vegetable protein, with the exception of said pea protein, preferably selected from the group of soy proteins, rice, and wheat, and more preferably soy.
[0006]
6. NET ENTERAL NUTRITIVE COMPOSITION according to any one of claims 1 to 5, characterized in that the protein fraction comprises from 50 to 70% by weight of at least one or more of said milk proteins, in relation to the total protein in the fraction of protein.
[0007]
7. NET ENTERAL NUTRITIVE COMPOSITION, according to any one of claims 1 to 6, characterized in that the protein fraction comprises pea, soy, casein and buttermilk protein, wherein the protein fraction consists of: - 20 to 40% by weight of casein, - from 20 to 40% by weight of whey protein, - from 13 to 25% by weight of soy protein, and - from 13 to 25% by weight of pea protein , in relation to the total protein in the protein fraction, where the sum of said proteins is equal to 100% by weight.
[0008]
8. NET ENTERAL NUTRITIVE COMPOSITION according to any one of claims 1 to 7, characterized in that the fat fraction comprises from 12.5 to 14.5% by weight, more preferably 13.5% to 13.9% by weight of linoleic acid (LA), calculated in relation to the total amount of fatty acids in the fat fraction.
[0009]
9. NET ENTERAL NUTRITIVE COMPOSITION according to any one of claims 1 to 8, characterized in that the fat fraction comprises from 4.0 to 5.0% by weight, and more preferably from 4.3 to 4.7% by weight a combination consisting of polyunsaturated ω-3 fatty acids: alpha linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), calculated in relation to the total amount of fatty acids in the fat fraction, and / or where the combined amount of DHA and EPA <1.0% by weight, calculated in relation to the total amount of fatty acids in the fat fraction.
[0010]
10. NET ENTERAL NUTRITIVE COMPOSITION, according to any one of claims 1 to 9, characterized in that the fat fraction comprises: (a) from 12.5 to 14.5% by weight of linoleic acid (LA); (b) from 4.0 to 5.0% by weight of a combination consisting of polyunsaturated ω-3 fatty acids: alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in that the amount of ALA> 2.7% by weight or varies between 2.5 and 4.0% by weight and the combined amount of DHA and EPA <1.0% by weight; (c) 14 to 18% by weight of at least one medium chain fatty acid (MCFA); and (d) 40 to 70% by weight of at least one monounsaturated fatty acid (MUFA), where all relative amounts are calculated based on the total amount of fatty acids in the fat fraction.
[0011]
11. NET ENTERAL NUTRITIVE COMPOSITION according to any one of claims 1 to 10, characterized by comprising: (i) a protein fraction comprising: (a) from 20 to 40% by weight of casein; (b) from 20 to 40% by weight of whey protein; (c) 13 to 25% by weight of soy protein; and (d) 13 to 25% by weight of pea protein; (e) relation to the total protein in the protein fraction, in which the sum of said proteins is equal to 100% by weight; (ii) a fat fraction comprising: (a) from 13.5 to 13.9% by weight of linoleic acid (LA); (b) from 4.3 to 4.7% by weight of a combination consisting of polyunsaturated ω-3 fatty acids: alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in that the amount of ALA> 2.7% by weight, or varies between 2.5 and 4.0% by weight and the combined amount of DHA and EPA <1.0% by weight; (c) from 15.7 to 16.2% by weight of at least one medium chain fatty acid (MCFA); and (d) 50 to 60% by weight of at least one monounsaturated fatty acid (MUFA); wherein all relative amounts are calculated based on the total amount of fatty acids in the fat fraction; (iii) a carbohydrate fraction; and (iv) optionally, a fraction of dietary fiber.
[0012]
12. NET ENTERAL NUTRITIVE COMPOSITION, according to claim 11, characterized by containing from 5 to 120 g / 1 of dietary fiber, wherein the fraction of dietary fiber consists of 15 to 50% by weight of polysaccharides other than soluble starch , 15 to 45% by weight of non-insoluble starch polysaccharides, 8 to 70% by weight of non-digestible oligosaccharides comprising at least 8% by weight, based on fiber, of hydrolyzed inulin, and comprising resistant starch.
[0013]
13. NET ENTERAL NUTRITIVE COMPOSITION according to any one of claims 1 to 12, characterized in that it comprises: (1) the protein fraction comprises at least 8En%, preferably at least 10En%, and more preferably at least 15En% of energy total composition; and / or (2) the fat fraction comprises between 30 and 50En%, and preferably between 30 and 40En% of the total energy of the composition; and / or (111) the carbohydrate fraction comprises between 30 and 62En% of the total energy of the composition.
[0014]
14. NET ENTERAL NUTRITIVE COMPOSITION according to any one of claims 1 to 13, characterized in that it has an energy content of at least 0.4 kcal / ml, preferably at least 0.7 kcal / ml, and more preferably of at least 0.9 kcal / ml of the composition.
[0015]
15. USE OF A NET NUTRITIVE COMPOSITION as defined in any one of claims 1 to 14, characterized in that it is in the preparation of a drug for the prevention and / or treatment of conditions of the upper and / or lower digestive tract in a patient fed via tube.
[0016]
16. USE OF A NET NUTRITIVE COMPOSITION, according to claim 15, characterized in that it is for tube feeding, particularly for use via tube of long duration.

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同族专利:

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公开号 | 公开日

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WO2011093710A8|2011-10-06|

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EP2528456A1|2012-12-05|

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PL2528456T3|2014-09-30|

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RU2516782C2|2014-05-20|

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WO2011093693A1|2011-08-04|

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ES2478869T3|2014-07-23|

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US20130023468A1|2013-01-24|

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BR112012018842A2|2015-09-01|

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BR112012018842A8|2017-10-31|

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EP2528456B1|2014-04-23|

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RU2012136832A|2014-03-10|

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US8618047B2|2013-12-31|

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WO2011093710A1|2011-08-04|

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DK2528456T3|2014-07-14|

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SI2528456T1|2014-07-31|

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CN102843920A|2012-12-26|

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法律状态:
2017-10-24| B07D| Technical examination (opinion) related to article 229 of industrial property law|

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2018-03-27| B15K| Others concerning applications: alteration of classification|Ipc: A61K 36/47 (2006.01), A23L 33/115 (2016.01), A23L |

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2018-04-10| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

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2018-05-02| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa)|

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2019-05-14| B07A| Technical examination (opinion): publication of technical examination (opinion)|

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2019-05-14| B15K| Others concerning applications: alteration of classification|Free format text: AS CLASSIFICACOES ANTERIORES ERAM: A61K 36/47 , A23L 33/115 , A23L 33/12 , A23L 33/185 , A23L 33/19 , A23L 33/00 , A61K 35/20 , A61K 38/01 Ipc: A23L 33/00 (2016.01), A23L 33/115 (2016.01), A23L |

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2019-10-15| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application according art. 36 industrial patent law|

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2020-02-04| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application according art. 36 industrial patent law|

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2020-06-02| B09A| Decision: intention to grant|

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2020-11-10| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 31/01/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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PCT/NL2010/050041|WO2011093693A1|2010-01-29|2010-01-29|Liquid enteral nutritional composition suitable for tube feeding, minimizing lower and upper tract digestive conditions|

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NL10/050041|2010-01-29|

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PCT/NL2011/050060|WO2011093710A1|2010-01-29|2011-01-31|Liquid enteral nutritional composition suitable for tube feeding, minimizing lower and upper tract digestive conditions|

---