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    • 专利摘要:
    abstract use of i) a source of protein, ii) a prebiotic and iii) a probiotic for the manufacture of a nutritional composition for the treatment or prevention of infection in an allergic individual the invention concerns the use of prebiotics and probiotics for the treatment of infections in allergic patients. 1/1
    公开号:BR112015030389B1
    申请号:R112015030389-7
    申请日:2014-06-16
    公开日:2020-07-14
    发明作者:Leunis Forrinus Harthoorn
    申请人:N.V. Nutricia；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    [001] The present invention relates to nutritional compositions that comprise symbiotics for use in the treatment or prevention of infections in allergic patients. HISTORY OF THE INVENTION
    [002] Symbiotic combinations of probiotic lactic acid bacteria and prebiotic nondigestible fibers have been tested in models of inflammation and in studies with humans. Although the reduction in inflammatory responses has been demonstrated in several treatment protocols, the results are contradictory and not consistent, depending on the model or group of patients used. Allergy has been linked to better hygiene in the developed world. Based on this hygiene hypothesis, a large number of studies have been done, in which the treatment of allergy or the improvement of allergy symptoms, for example, atopic dermatitis, has been attempted. Allergic patients were treated with probiotic bacteria or dietary fibers, or both, but the results of allergy in prevention were inconsistent.
    [003] For example, in Allergy (2011) 66: 170-177, van der Aa et al. reported the effects on asthma symptoms, but the number of respiratory infections (lower and upper) during the intervention period did not differ between the symbiotic group and the placebo. The treatment product used in this study was an infant formula with galactooligosaccharides and inulin as prebiotics and B.breve as a probiotic.
    [004] Currently, probiotics or prebiotics are not normally used to treat infections in allergic patients.
    [005] Kukkonen et al. , J Allergy Clin Immunol (2007) 119: 192-198, described a study with the use of symbiotics that consisted of 4 probiotic strains and prebiotic galactooligosaccharides. Symbiotics were given in a double-blind manner to pregnant mothers and their healthy babies from birth to the age of 6 months. It is not reported whether the children were allergic. Kukkonen finds indications for an inverse association between the modification of the indigenous intestinal microbiota and the prevalence of eczema, especially when IgE is associated. This preventive study does not use a nutritional composition with symbiotics, but used capsules that must be eaten by the mother or mixed with liquids for the child. It is also not revealed what the effect of symbiotics would be when administered to allergic children.
    [006] WO 2010/033768 discloses compositions that include the infant formula comprising probiotics for reducing inflammation. Inflammation can be caused by allergy, chronic inflammatory disease, etc. An inflammation is an immune reaction that can result from an infection. Inflammation is, in general, an immune response of the body against a harmful stimulus, such as pathogenic microorganisms, chemicals, damaged tissues. The treatment or prevention of infections is therefore different from the treatment of an inflammation, and the document does not disclose the treatment or prevention of infections in allergic patients, but only the treatment of the inflammation.
    [007] Bõhme et al., In Acta Derm Venereol. (2002) 82 (2): 98-103, describe that during the first 2 years of life there is a significant association between atopic dermatitis and respiratory infections manifested in a higher rate of acute otitis media, pneumonia and use of antibiotics. It is known that these infections often exacerbate allergic manifestations, so there is a real need to limit the rate of microbial infection in allergic patients.
    [008] EP 1714660 discloses compositions containing probiotic bacteria and uronic acid oligosaccharides which are suitable as infant nutrition and advantageously reduce the incidence of infection. SUMMARY OF THE INVENTION
    [009] The inventors surprisingly found, for the first time, that a symbiotic, that is, a combination between a probiotic lactic acid bacterium and a non-digestible fiber significantly reduced the rate of microbial infection in allergic patients in the administration of a hypoallergenic formula; see the example. In addition, a statistically significant decrease in the use of antibiotics was found in the treatment group that received the symbiotic composition.
    [010] Advantageously, the present symbiotic composition provides treatment for the infection and not the inflammation that can result from an infection. A beneficial consequence is that inflammation can be prevented and therefore there is no longer a need to treat inflammation at a later stage, for example, by administering analgesia or COX enzyme inhibitors such as ibuprofen. DETAILED DESCRIPTION OF THE INVENTION
    [011] The present invention thus relates to a method for the treatment or prevention of infection in an allergic individual, and said method comprises administering a composition comprising i) a source of protein consisting essentially of amino acids ii) at least one soluble non-digestible fiber selected from the group consisting of fructo-oligosaccharides, fucosyl-oligosaccharides not derived from milk and polydextrose, and iii) at least one lactic acid bacterium selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantil, Bifidobacterium lactis and Lactobacillus rhamnosus, to said allergic individual.
    [012] In other words, the invention relates to the use of i) a source of protein, ii) a prebiotic and iii) a probiotic for the manufacture of a nutritional composition for the treatment or prevention of infection in an allergic individual, where i) the protein source consists essentially of free amino acids, ii) the prebiotic comprises at least one soluble nondigestible fiber selected from the group consisting of non-milk-derived fructo-oligosaccharides, fucosyl-oligosaccharides and polydextrose, and iii) the The probiotic comprises at least one lactic acid bacterium selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantil, Bifidobacterium lactis and Lactobacillus rhamnosus.
    [013] The invention can also be formulated as a composition comprising i) a protein source consisting essentially of free amino acids, ii) at least one soluble nondigestible fiber selected from the group consisting of non-fructo-oligosaccharides, non-fucosyl-oligosaccharides milk derivatives and polydextrose, and iii) at least one lactic acid bacteria selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantil, Bifidobacterium lactis and Lactobacillus rhamnosus, for use in the treatment or prevention of infection in an allergic individual . Lactic acid bacteria
    [014] The fecal flora of breastfed infants is dominated by bifidobacteria due to the presence of oligosaccharides in human milk. They act as bifidogenic factors and stimulate the proliferation of these species in the infant intestine. Bifidobacteria are among the first colonizers of the human gastrointestinal tract, and their presence in large numbers in the intestines of breastfed children has been associated with improved health. Atopic children have been shown to have an altered intestinal microflora, with increased clostridia and decreased bifidobacteria. The bifidobacterial microflora of atopic children has been shown to be more similar to that of adults, with a decrease in B. bifidium and B. breve strains and an increase in B. adolescentis.
    [015] The composition for use according to the present invention comprises at least one lactic acid bacterium selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantil, Bifidobacterium lactis and Lactobacillus rhamnosus.Typically, these lactic acid bacteria are marketed by producers of lactic acid bacteria, but can also be isolated directly from faeces, identified, characterized and produced.
    [016] The composition for use according to the present invention comprises at least 1.0x109 of live lactic acid bacteria (colony forming units; CFU) per liter, preferably between 1.0x109 and 1x10 CFU per liter. Preferably, the composition for use according to the present invention comprises at least 10 x 10 7 live lactic acid bacteria (colony forming units; CFU) per liter, preferably between 1.0 x 10 7 and 1 x 10 9 CFU per liter.
    [017] It is important for the symbiotic effect of lactic acid bacteria and for prebiotic fiber that the concentration of the two ingredients is well balanced. Therefore, preferably, the concentration of lactic acid bacteria is at least 1.0 x 10 8 CFU of lactic acid bacteria per gram of prebiotic fiber, even more preferably between 2.0 x 10 8 and 2.0 x 10 10 CFU of lactic acid bacteria per gram of prebiotic fiber, more preferably between 1.0x10 and 1.0x10 CFU of lactic acid bacteria per gram of prebiotic fiber, more preferably between 1.0x10 and 5.0x10 CFU of lactic acid bacteria per gram of prebiotic fiber.
    [018] In an embodiment according to the method or use according to the present invention, the composition is administered in an amount that provides at least 1.0 x 10 7 CFU of lactic acid bacteria per day, preferably in an amount that provides at least less than 2.0xl07 to a maximum of 2.0x1o11 CFU of lactic acid bacteria per day, in an amount that provides at least 4.0x07 to a maximum of 1.2x1o11 CFU of lactic acid bacteria per day, even more preferably in an amount that provides at least 1.0x08 to a maximum of 6.0x1010 CFU of lactic acid bacteria per day.
    [019] Lactobacillus rhamnosus, in particular Lactobacillus rhamnosus GG, also referred to as Lactobacillus GG or LGG, is one of the best studied species in humans and is also found in high amounts in the infant's intestines. In a preferred embodiment, at least one lactic acid bacterium is selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantil, Bifidobacterium lactis and Lactobacillus rhamnosus GG. LGG is marketed and can be obtained from Valio Ltd.
    [020] Bifidobacterium is a genus of gram-positive, non-mobile, frequently branched anaerobic bacteria. Bifidobacteria are ubiquitous, endosymbiotic inhabitants of the gastrointestinal tract, vagina and mouth of mammals and other animals. Some bifidobacteria are used as probiotics. In a preferred embodiment, the lactic acid bacteria in the composition for use according to the present invention is Bifidobacterium breve, or in one embodiment consists of Bifidobacterium breve. According to a preferred embodiment, the composition for use according to the present invention comprises at least one B. breve selected from the group consisting of B. breve Bb-03 (Rhodia / Danisco), B. breve M-16V (Morinaga ), B. breve R0070 (Institute Roseli, Lallemand), B. breve BR03 (Probiotical), B. breve BR92) (Cell Biotech), DSM 20091, LMG 11613, YIT4065, FERM BP-6223 and CNCM 1-2219. More preferably, B. breve is selected from the group consisting of B. breve M-16V and B. breve CNCM 1-2219, more preferably M-16V. B. breve 1-2219 was published in WO 2004/093899 and deposited in the National Collection of Cultures of Microorganisms, Pasteur Institute, Paris, France on May 31, 1999 by Compagnie Gervais Danone. B. breve M-16V was deposited as BCCM / LMG23729, and is marketed by Morinaga Milk Industry Co., Ltd.
    [021] Preferably, the bacteria are alive. However, non-living lactic acid bacteria can also have beneficial effects on the immune system. Without limiting this theory, there is a hypothesis that dead lactic acid bacteria can be used to treat or prevent infection in allergic patients. In a preferred embodiment, at least part of the lactic acid bacteria present in the composition is dead or at least unable to multiply. Non-digestible fiber
    [022] Soluble nondigestible fiber is a term known in the art and refers to nondigestible carbohydrates that can be used by probiotic bacteria as a source of energy (fermentation) in the intestinal tract. Most of the formation and proliferation of probiotic bacteria occurs in the colon. Without limiting the theory, the inventors believe that the administration of live probiotic bacteria enterally results in a relatively high concentration of these microorganisms in the small intestine, where fermentation can begin, which results in fermentation products that are beneficial for stimulating the immune system and results in a lower rate of infection.
    [023] Thus, a soluble nondigestible fiber can be defined as a nondigestible carbohydrate that beneficially affects the host by selectively stimulating the growth and / or activity of one or a limited number of bacteria in the colon. The preferred nondigestible soluble fibers in the composition for use according to the present invention are not derived from milk. The preferred non-digestible soluble fibers in the composition for use according to the present invention include non-milk derived fructooligosaccharides, polydextrose and fucosyloligosaccharides, such as fucosillactoses, fucosylated lactosamine-lactoses, and the like, and sialylated oligosaccharides characterized by one or more of N-acetylneuraminic acid, such as 3'- and 6'-sialyl-lactose (SL) and sialyl-lacto-N-tetraose.
    [024] The term "oligosaccharide" as used in the present invention preferably refers to a saccharide with an average degree of polymerization (DP) of 2 to 100, more preferably an average DP of 2 to 60. It is understood that, in the context of the present invention, an oligosaccharide with a DP in a certain range can include a mixture of saccharides with different average DPs, for example, if an oligosaccharide with a DP between 2 and 100 is included in the present composition, it can include compositions containing oligosaccharides with an average SD between 2 and 5, an average SD between 50 and 70 and an average SD between 7 and 60.
    [025] In one embodiment, the composition for use according to the present invention does not comprise uronic acid oligosaccharides, preferably the composition for use according to the present invention does not comprise uronic acid oligosaccharides with a degree of polymerization from 2 to 250 The term uronic acid oligosaccharide, as used here, refers to an oligosaccharide in which at least 50% of the residues are selected from the group consisting of guluronic acid, manuronic acid, galacturonic acid and glucuronic acid.
    [026] In one embodiment, the soluble non-digestible fibers in the composition for use according to the present invention comprise polydextrose. Polydextrose is a soluble non-digestible fiber fermented favorably by Bifidobacteria and Lactobacilli. It has the additional advantage of distributing only 1 kcal per gram of fiber, compared to 2 kcal per g of fructo-oligosaccharides. It is widely used and can be obtained commercially , for example, under the trade names LITESSE, STA-LITE and TRIMCAL.
    [027] In a preferred embodiment, the soluble nondigestible fibers in the composition for use according to the present invention comprise fructooligosaccharides. The term "fructo-oligosaccharides", as used herein, refers to a soluble nondigestible fiber that comprises a chain of at least 2 p-linked fructose units. A fructo-oligosaccharide can comprise a terminal glucose unit. In a preferred embodiment, the average degree of polymerization of the fructo-oligosaccharides in the composition for use according to the present invention is in the range between 2 and 60, preferably the degree of polymerization of the fructo-oligosaccharides is in the range of 2 to 60.
    [028] Preferably, the soluble nondigestible fibers in the composition for use according to the present invention are a combination of short-chain fructo-oligosaccharides (scFOS) and long-chain fructo-oligosaccharides (IcFOS). Long-chain fructo-oligosaccharides are also called inulin. Preferably, the scFOS: IcFOS ratio is in the range between 95/5 to 10/90, even more preferably in the range between 95/5 to 40/60. In the context of the present invention, scFOS has an average DP between 2 and 6. In the context of the present invention, IcFOS means any fructo-oligosaccharide composition with an average DP greater than or equal to 7. A suitable source of scFOS is RAFTILOSE® (Orafti ). RARTILINE® HP (Orafti) is a particularly preferred source of IcFOS, and has an average SD> 20. Products commonly marketed as inulin comprise scFOS, and IcFOS generally has an average SD greater than 7.
    [029] The composition for use according to the present invention preferably comprises more scFOS than IcFOS. Preferably, the scFOS: IcFOS ratio is at least 1, preferably between 2 and 12, even more preferably between 3 and 10, most preferably the scFOS: IcFOS ratio is about 9. Both scFOS and IcFOS stimulate growth Bifidobacteria and Lactobacilli. ScFOS has been found to stimulate growth early in the colon, while IcFOS stimulates the growth of bacteria in the distal part of the colon.
    [030] The soluble non-digestible fiber is present preferably in the composition for use according to the invention in an amount sufficient to provide a dose of 0.1 to 7 g / day, more preferably of 0.2 to 6 g / day, even more preferably from 0.5 to 3 g / day. In an embodiment according to the method or use according to the present invention, the composition is administered in an amount that provides 0.1 to 7 g of soluble non-digestible fiber per day, more preferably 0.2 to 6 g of soluble non-digestible fiber per day, even more preferably from 0.5 to 3 g of soluble non-digestible fiber per day.
    [031] Soluble non-digestible fiber is preferably present in a concentration of at least about 15 mg per g of dry weight of the composition, or at least 3 g per liter of composition. More preferably, the concentration of soluble nondigestible fiber in the composition for use according to the present invention is 15 to 75 mg per g dry weight of the composition, and even more preferably 35 to 60 mg per g dry weight of the composition. composition.
    [032] Galacto-oligosaccharides (GOS) commonly used as the prebiotic fiber in nutritional composition, which includes infant formula, are not suitable for the purposes of the present invention. GOS is derived from lactose in milk and is normally polluted with small amounts of milk protein. This milk protein, although present in small amounts, can still trigger immune reactions in the allergic patient. Thus, in one embodiment, the composition for use according to the present invention does not comprise galacto-oligosaccharides. Protein source
    [033] Patients with allergies usually have an exaggerated immune response against protein allergens. In particular, food allergy is caused by many food-related proteins. Cow's milk proteins are the most common allergens in childhood, followed by chicken egg proteins. In order to be absolutely sure that the protein is not present in the composition for use according to the invention, the protein source is made up exclusively of free amino acids.
    [034] The present invention advantageously relates to the use of a composition in which the protein source provides 7 to 20% of the total calories of the composition, preferably the protein source provides 8 to 17% of the total calories, even more preferably the protein source provides 9 to 15% of the total calories in the composition.
    [035] Alternatively, in the composition for use according to the present invention, the protein source content is between 10 and 20% by weight of free amino acids based on the dry weight of the total composition, preferably between 11 and 18% in terms of weight, and even more preferably between 12 and 16% by weight of free amino acids based on the dry weight of the total composition. Thus, the composition for use according to the present invention comprises as the only source of proteins between 10 and 20% by weight of free amino acids, preferably between 11 and 18% by weight, and even more preferably between 12 and 16% by weight. weight of free amino acids, based on the dry weight of the total composition.
    [036] In one embodiment, the composition for use according to the present invention is a formula for infants. Therefore, in one embodiment, the protein source comprises all essential amino acids. The ideal amino acid profile for the infant formula is known in the art. A preferred embodiment of an amino acid composition is given in Table 2. Fat
    [037] The composition for use according to the present invention preferably comprises fat. The term "fat", as used in the present invention, includes all sources of fat commonly used in nutritional products, and can comprise a source of triglycerides, diglycerides, monoglycerides and free fatty acids. In particular, when the composition for use according to the invention is for the treatment of children, the composition preferably comprises long-chain polyunsaturated fatty acids (LCPUFAs). In a preferred embodiment, the composition for use according to the present invention comprises eicosapentaenoic acid (EPA), arachidonic acid (ARA) or docosahexaenoic acid (DHA), preferably the composition comprises ARA and DHA or both, more preferably a composition comprises ARA and DHA. In a preferred embodiment, the fat provides 30 to 50% of the total calories in the composition.
    [038] In a preferred embodiment according to the present invention, the composition comprises at least 0.05 g ARA and / or at least 0.05 g DHA per liter of composition, or even more preferably at least 60 mg up to a maximum of 420 mg of ARA per liter of final composition, and / or at least 60 mg to a maximum of 420 mg of DHA per liter of final composition, or even more preferably from at least 80 mg to a maximum of 240 mg of ARA per liter of final composition, and / or at least 80 mg to a maximum of 240 mg of DHA per liter of final composition. In one embodiment, the composition for use according to the present invention comprises at least 0.35 mg ARA per g dry weight of the composition, and / or at least 0.35 mg DHA per g dry weight of the composition. Preferably, the composition comprises at least 0.4 mg to a maximum of 10 mg ARA per g dry weight of the composition, and / or at least 0.4 mg to a maximum of 10 mg DHA per g dry weight of the composition, preferably at least 0.5 mg to a maximum of 6 mg ARA per g dry weight of the composition, and / or at least 0.5 mg to a maximum of 6 mg DHA per g dry weight of the composition composition, more preferably from at least 0.6 mg to a maximum of 3 mg ARA per g dry weight of the composition, and / or from at least 0.6 mg to a maximum of 3 mg DHA per g dry weight of the composition . Individuals
    [039] The present method or use is for allergic individuals. Allergic individuals include not only individuals who have been diagnosed with an allergy, but also individuals who are at an increased risk of developing an allergy, such as children of parents with an allergy. The present method or use is intended specifically for allergic babies and / or allergic children. Babies are aged 0 to 12 months, children are aged 12 to 36 months, even more preferably for babies. Thus, in an embodiment according to the present invention, the allergic individual is an allergic child and / or an allergic baby. Application and compositions
    [040] The present method or use is for treatment or prevention, preferably prevention of infections in individuals with an allergy.
    [041] The composition according to the present use is preferably administered enterally, more preferably orally.The present composition is preferably a nutritional formula, preferably a formula for children. The present composition can be advantageously applied as a complete nutrition for children. The present composition preferably comprises lipids, proteins, and carbohydrates, and is preferably administered in liquid form. The present invention includes dry compositions, for example, powders, which are accompanied by instructions on how to administer said dry compositions, in particular the nutritional formula, with a suitable liquid, for example, water.
    [042] In a preferred embodiment of the composition for use according to the present invention, the soluble nondigestible fibers comprise fructooligosaccharides, and the lactic acid bacterium is Bifidobacterium breve.
    [043] In an embodiment in the composition for use according to the present invention, the soluble nondigestible fiber comprises a mixture between a short-chain fructo-oligosaccharide with an average degree of polymerization from 2 to 6 and a short-fruiting oligosaccharide long with an average degree of polymerization of at least 7, and the weight ratio between short-chain fructo-oligosaccharides: long-chain fructo-oligosaccharides is at least 1; preferably the weight ratio between scFOS: IcFOS is between 2 and 12, even more preferably between 3 and 10, most preferably the scFOS: IcFOS ratio is about 9.
    [044] In one embodiment, the composition for use according to the present invention comprises i) a protein source, ii) a prebiotic and iii) a probiotic, in which i) the protein source consists of free amino acids and is present between 10 and 20% by weight based on the dry weight of the total composition, ii) the prebiotic comprises a mixture of short-chain fructo-oligosaccharides with an average degree of polymerization from 2 to 6 and a long-chain fructo-oligosaccharide with a average degree of polymerization of at least 7, and the weight ratio between short-chain fructo-oligosaccharides: long-chain fructo-oligosaccharides is at least 1, and iii) the probiotic comprises at least one lactic acid bacterium selected from the group that consists of Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantil, Bifidobacterium lactis and Lactobacillus rhamnosus.
    [045] In a preferred embodiment, the composition for use according to the present invention is a nutritional composition that comprises an allergen-free protein source, and consists essentially of free amino acids, and Bifidobacteria, preferably Bifidobacterium breve, and a source of non-digestible carbohydrates comprising fructo-oligosaccharides with an average SD of 2 to 60.
    [046] In yet another preferred embodiment, the composition for use according to the present invention is a nutritional composition, preferably an infant formula, comprising a source of protein, a source of fat, soluble nondigestible fiber and lactic acid bacteria , where the protein source consists essentially of free amino acids and provides 7 to 20% of the total calories in the nutritional composition, the fat source comprises at least arachidonic acid (AA) and docosahexaenoic acid (DHA), percentage of energy , the soluble nondigestible fiber comprises fructooligosaccharides with an average SD of 2 to 60 at a concentration of 15 to 75 mg per g dry weight of the nutritional composition and the live lactic acid bacteria are selected from the group consisting of Bifidobacteriae Lactobacillus rhamnosus, preferably selected from the group consisting of Bifidobacterium breve and Lactobacillus rhamnosus LGG, preferably lactic acid bacteria comprise Bifidobacterium breve.
    [047] In a preferred embodiment in the composition for use according to the present invention, the protein source provides 10 to 20% of the total calories of the composition, the concentration of soluble nondigestible fiber is 15 to 75 mg per g of dry weight of the composition and the concentration of lactic acid bacteria, preferably Bifidobacterium breve, is 2.0x08 and 2.0x1010 CFU of lactic acid bacteria, preferably Bifidobacterium breve, per gram of soluble nondigestible fiber, more preferably between 1, 0x109 el, 0x1010 CFU of lactic acid bacteria, preferably Bifidobacterium breve, per gram of soluble non-digestible fiber, more preferably between 1.0x09 and 5.0x10 CFU of lactic acid bacteria, preferably Bifidobacterium breve, per gram of non-soluble fiber digestible. Preferably, the soluble nondigestible fiber is a mixture between a short-chain fructo-oligosaccharide with an average degree of polymerization from 2 to 6 and a long-chain fructo-oligosaccharide with an average degree of polymerization of at least 7, and a weight ratio between short-chain fructo-oligosaccharides: Long-chain fructo-oligosaccharides is at least 1. Preferably the scFOS: IcFOS by weight ratio is between 2 and 12, even more preferably between 3 and 10, most preferably the ratio scFOS: IcFOS is about 9. Preferably, the composition further comprises fat which provides 30 to 50% of the total calories of the composition, and the composition comprises DHA or ARA or both in a concentration of at least 0.35 mg per g dry weight of the composition, preferably at least 0.4 mg to a maximum of 10 mg ARA per g dry weight of the composition, and / or at least 0.4 mg to a maximum of 10 mg DHA per g dry weight of the composition, preferably at least 0.5 mg up to a maximum of 6 mg ARA per g dry weight of the composition, and / or at least 0.5 mg to a maximum of 6 mg DHA per g dry weight of the composition, more preferably at least 0.6 mg up to a maximum of 3 mg ARA per g dry weight of the composition, and / or at least 0.6 mg to a maximum of 3 mg DHA per g dry weight of the composition. EXAMPLES Example 1. Clinical study showing the anti-inflammatory effects of a mixture of symbiotic prebiotic fibers with Bifidobacterium breve in a population of allergic patients.
    [048] Pre- and probiotics (symbiotics) have been investigated for potential beneficial effects on human health. This study describes the functional effects of a formula based on amino acids (AAF) with symbiotics in children with allergy to cow's milk (CMA). Methods
    [049] In a prospective, randomized, double-blind, controlled study, children with IgE-mediated and / or non-IgE-CMA were randomly assigned either a commercially available AAF (NEO; n = 56) or an AAF with symbiotics (NEO- SYN; n = 54) for 16 weeks. First, the child's growth and tolerance to the formula were monitored. Second, the dermatological (including the severity of atopic manifestations by SCORAD) and respiratory characteristics and stool characteristics were recorded in the individuals' diaries and / or evaluated by a doctor. The NEO-SYN group was fed exclusively with a commercially available AAF supplement with a Bifidobacterium breve free of milk protein and a mixture of prebiotic fiber comprising short-chain fructo-oligosaccharides (scFOS, with an average degree of polymerization less than 6) and IcFOS (with an average degree of polymerization above 7) in a scFOS: .IcFOS weight ratio of about 9: 1 at a concentration of about 45 mg scFOS + IcFOS per g dry weight of the composition. briefly used was the commercially available strain M-16V from Morinaga. B. breve was used in a concentration of 1.9x09 colony forming units (CFU) per gram of prebiotic fiber. Results
    [050] The mean age of children at inclusion was 4.58 ± 2.45 months. Overall, NEO-SYN and NEO were equally well tolerated and both supported normal growth. Both formulas reduced allergic symptoms and there were no significant differences between groups. The NEO-SYN group was reported to have fewer individuals suffering from infections (p = 0.008) and fewer individuals receiving medication for functional gastrointestinal (GI) disorders (p = 0.029) when compared to the NEO group. In addition, the NEO-SYN group had fewer children using antibiotics (p = 0.049), especially amoxicillin (p = 0.004), compared to the NEO group. The results are summarized in Table 1. Table 1: Reported infections and use of antibiotics in the 16-week window
    Conclusion
    [051] This study shows that an AAF with symbiotics is equally well tolerated, supports normal growth and has a similar effectiveness in managing the symptoms of AMC compared to an AAF without symbiotics. The addition of symbiotics improves resistance to infections and reduces the use of specific medication in children who have received AAF. Example 2. Composition for use according to the invention
    (UFC) per gram of prebiotic fiber * 14.7 g of powder are dissolved in 100 ml of water Table 2: Composition of the protein source

    权利要求:
    Claims (9)
    [0001]
    1. USE OF i) A SOURCE OF PROTEIN, ii) A PREBIOTIC AND iii) A PROBIOTIC FOR THE MANUFACTURE OF A NUTRITIONAL COMPOSITION FOR THE TREATMENT OR PREVENTION OF INFECTION IN AN ALLERGIC INDIVIDUAL, characterized i. the protein source consists essentially of free amino acids, ii. for the prebiotic to understand a mixture between. a short-chain fructo-oligosaccharide with an average degree of polymerization from 2 to 6, and b. a long-chain fructooligosaccharide with an average degree of polymerization of at least 7, and the weight ratio of short-chain fructo-oligosaccharide: long-chain fructo-oligosaccharide to be at least 1, iii. probiotic is Bifidobacterium breve.
    [0002]
    USE, according to any one of claims 1, characterized in that the protein source provides 7 to 20% of the total calories of the composition.
    [0003]
    USE, according to any one of claims 1 to 2, characterized in that the content of the protein source is between 10 and 20% by weight of free amino acids based on the dry weight of the total composition.
    [0004]
    USE, according to any one of claims 1 to 3, wherein the composition is characterized by further comprising DHA or ARA or both.
    [0005]
    USE, according to any one of claims 1 to 4, characterized in that the protein source provides 10 to 20% of the total calories of the composition, the concentration of soluble nondigestible fiber being 15 to 75 mg per g dry weight of the composition and the concentration of lactic acid bacteria be 2.0x08 and 2.0x1010 CFU of lactic acid bacteria per gram of soluble non-digestible fiber.
    [0006]
    6. USE, according to claim 5, wherein the composition is further characterized by fat which provides 30 to 50% of the total calories of the composition, and the composition comprises DHA or ARA or both in a concentration of at least 0 , 35 mg per g dry weight of the composition.
    [0007]
    USE, according to any one of claims 1 to 6, wherein the composition is characterized in that it does not comprise uronic acid oligosaccharides.
    [0008]
    8. USE, according to any one of claims 1 to 7, characterized in that the allergic individual is a child.
    [0009]
    USE, according to any one of claims 1 to 8, characterized in that the composition is a formula for children.
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    同族专利:
    公开号 | 公开日
    WO2014200351A1|2014-12-18|
    CN105283195A|2016-01-27|
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    AU2014278835B2|2019-10-03|
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    ES2665603T3|2018-04-26|
    BR112015030389A2|2017-07-25|
    WO2014200334A1|2014-12-18|
    EP3010521A1|2016-04-27|
    NO3010521T3|2018-06-09|
    US20220016186A1|2022-01-20|
    AU2014278835A1|2016-01-07|
    EP3010521B1|2018-01-10|
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    GB201306536D0|2013-04-10|2013-05-22|Gt Biolog Ltd|Polypeptide and immune modulation|
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    法律状态:
    2018-02-27| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2018-03-06| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|
    2018-03-27| B15K| Others concerning applications: alteration of classification|Ipc: A61K 38/00 (2006.01), A61K 31/702 (2006.01), A61K |
    2019-07-02| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]|Free format text: NOTIFICACAO DE DEVOLUCAO DO PEDIDO POR NAO SE ENQUADRAR NO ART. 229-C DA LPI. |
    2019-12-03| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-05-12| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2020-07-14| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 16/06/2014, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    NLPCT/NL2013/050423|2013-06-14|
    PCT/NL2013/050423|WO2014200334A1|2013-06-14|2013-06-14|Synbiotic composition for treatment of infections in allergic patients|
    PCT/NL2014/050392|WO2014200351A1|2013-06-14|2014-06-16|Synbiotic composition for treatment of infections in allergic patients|
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