• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    NUTRITIONAL COMPOSITION TO PROMOTE MUSCULOSKELETAL HEALTH IN PATIENTS WITH INFLAMMATORY INTESTINAL DISEASE (IBD). The present invention relates to a nutritional composition to promote musculoskeletal health in patients with inflammatory bowel disease that is disclosed. The nutritional composition comprises casein protein, vitamin K in a ratio of vitamin K1: vitamin K2 being between 3: 1 and 1: 3 and vitamin K providing between 3.5 and 20 (Mi) g / 100 kcal of the nutritional composition, vitamin D and alpha-linolenic acid. A pharmaceutical formulation, a nutritional formulation, a tube feeding formulation, a food supplement, a functional food, a beverage product or a combination thereof comprising the nutritional composition are also disclosed. A method for improving musculoskeletal health is also disclosed.
    公开号:BR112015001884B1
    申请号:R112015001884-0
    申请日:2013-07-30
    公开日:2020-12-01
    发明作者:Jalil Benyacoub；Viral Brahmbhatt；François-Pierre Martin；Eduardo Schiffrin
    申请人:Société des Produits Nestlé S.A.；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    [001] The present invention relates to a nutritional composition, in particular a nutritional composition for patients with inflammatory bowel disease. The present invention also relates to a method for improving musculoskeletal health in patients, in particular patients with inflammatory bowel disease. BACKGROUND OF THE INVENTION
    [002] Inflammatory bowel disease refers to a group of diseases that involve an inflammation of the gastrointestinal tract.
    [003] Crohn's disease is an example of an inflammatory bowel disease. Crohn's disease can affect the entire gastrointestinal tract from the mouth to the anus.
    [004] An exact cause of Crohn's disease is unknown. Crohn's disease is believed to be caused by a combination of genetic, non-genetic or environmental factors (for example, infections) that interact with the body's immune system and this affects the gastrointestinal tract.
    [005] Crohn's disease is a chronic inflammatory disorder in which the body's immune system mistakenly attacks and destroys healthy tissue in the gastrointestinal tract. The signs and symptoms of Crohn's disease involve chronic recurring periods of sudden outbursts and remission.
    [006] Crohn's disease can result in gastrointestinal, extra-intestinal and systemic complications. Gastrointestinal complications can include diarrhea, abdominal pain, fever and rectal hemorrhage. Extra-intestinal complications include problems with the eyes, bones, skin abnormalities and blood abnormalities. In addition, extra-intestinal complications of Crohn's disease lead to reduced bone density causing osteoporosis or increased bone weakness causing osteomalacia. Systemic complications associated with Crohn's disease include growth retardation in children, weight loss due to decreased food consumption and malabsorption of carbohydrates or lipids that further exacerbate weight loss.
    [007] There is no single cure for Crohn's disease. Where remission of Crohn's disease is possible, relapse can be prevented and symptoms controlled with medication, changes in lifestyle, intervention with nutritional compositions and in some cases surgery.
    [008] Treatment of Crohn's disease is only possible when symptoms are active. Treatment of Crohn's disease usually involves first treating the acute problem and then maintaining remission.1
    [009] There is a need to provide a nutritional composition that can correct metabolic changes in patients with Crohn's disease and prevent and correct changes associated with Crohn's disease in patients with Crohn's disease.
    [0010] There is a need to be able to monitor patients with Crohn's disease to be able to predict a likelihood of a relapse and remission of the effects of Crohn's disease before its occurrence during the remission period. Monitoring of patients with Crohn's disease in this way is achieved with so-called biomarkers. Biomarkers allow the possibility of an early nutritional intervention to maintain a state of remission. Thus, it is desirable to identify biomarkers in patients with Crohn's disease that can be used as a diagnostic tool.
    [0011] Nutritional compositions are known to provide a nutritional composition alone and / or supplementary nutritional composition to patients with inflammatory bowel disease (eg Crohn's disease). Nutritional compositions are a primary therapy for inflammatory bowel disease (e.g., Crohn's disease). Nutritional compositions can allow inflammatory activity to be controlled and can allow patients to be kept in a state of remission.
    [0012] A Modulen IBD nutritional composition manufactured by Nestlé is known. See for example the product information leaflet http://www.nestlenutrition.co.uk/healthcare/gb/products/Documents/Mo dulen% 20IBD-nutritionpanel.pdf downloaded and viewed on 01 June 2012. Modulen IBD is used for patients with inflammatory bowel disease (eg Crohn's disease). Modulen IBD is known to contain vitamin K in an amount of 27 pg / 100 g. Modulen IBD is known to contain vitamin D in an amount of 4.9 pg / 100 g. Modulen IBD is known to contain alpha-linolenic acid in an amount of 0.2 g / 100 g. Modulen IBD is a composition based on casein protein. The casein in Modulen IBD provides an anti-inflammatory cytokine transforming growth factor-p2. The transforming growth factor-p2 has been shown to induce remission in children with active inflammatory bowel disease (eg, Crohn's disease). The transforming growth factor-p2 promotes healing of the mucosa of the gastrointestinal tract since it controls inflammatory activity. In addition, the transforming growth factor-p2 has immunomodulatory properties.
    [0013] WO2011 / 031601 discloses a nutritional composition and a method of making and using the nutritional composition. The nutritional composition includes exogenous vitamin K2. The nutritional composition can also include an additional component selected from phosphorus, magnesium, zinc, iron, copper, manganese, calcium, vitamin D, osteopontin and combinations thereof. SUMMARY OF THE INVENTION
    [0014] There is a need to provide a nutritional composition that promotes musculoskeletal health in patients with inflammatory bowel disease (eg, Crohn's disease).
    [0015] There is a need to provide a nutritional composition that restores the metabolic profile in patients with inflammatory bowel disease (eg, Crohn's disease).
    [0016] Patients can be pediatric or adolescent patients. A pediatric patient is a patient aged between 0 and 18 years, 0 and 17 years, or 0 and 17 years. An age of 0 refers to the time of birth regardless of whether the birth was premature or not. An adolescent patient is a patient aged between 13 and 19, 13 and 18, or 13 and 17 years.
    [0017] In a first aspect, the present disclosure refers to a nutritional composition. The nutritional composition comprises acid casein protein, vitamin K in a ratio of vitamin K1: K2 being between 3: 1 to 1: 3 and vitamin K present in an amount between 17.5 and 100 pg / 100 g of the nutritional composition, vitamin D present in an amount between 2.5 and 75 pg / 100 g of the nutritional composition; and n6 / n3 fatty acids in a ratio of n6: n3 fatty acids between 5: 1 and 1: 5.
    [0018] In another aspect, the present disclosure relates to a pharmaceutical formulation, a nutritional formulation, a tube feeding formulation, a food supplement, a functional food, a beverage product or a combination thereof comprising a nutritional composition comprising casein acid protein, vitamin K in a ratio of vitamin K1: K2 being between 3: 1 to 1: 3 and vitamin K present in an amount between 17.5 and 100 pg / 100 g of the nutritional composition, vitamin D present in an amount between 2.5 and 75 pg / 100 g of the nutritional composition; and n6 / n3 fatty acids in a ratio of n6: n3 fatty acids between 5: 1 and 1: 5.
    [0019] In another aspect, the present disclosure refers to a method of improving musculoskeletal health in pediatric patients. The method comprises administering to pediatric patients in need of it a nutritional composition comprising acid casein protein, vitamin K in a ratio of vitamin K1: K2 being between 3: 1 to 1: 3 and vitamin K present in an amount between 17, 5 to 100 pg / 100 g of the nutritional composition, vitamin D present in an amount between 2.5 to 75 pg / 100 g of the nutritional composition; and n6 / n3 fatty acids in a ratio of n6: n3 fatty acids between 5: 1 to 1: 5. BRIEF DESCRIPTION OF THE DRAWINGS
    [0020] Figure 1 shows a Pediatric Crohn's Disease Activity Index (PCDAI) in children aged 6.6 to 17.7 years with Crohn's disease when administered with a nutritional composition in accordance with the present disclosure.
    [0021] Figure 2 shows the effects of the nutritional composition of the present disclosure on bone density and muscle cross-sectional area when administered to children aged between 6.6 and 17.7 years with Crohn's disease. DETAILED DESCRIPTION
    [0022] For a complete understanding of the present disclosure and its advantages, reference is made to the following detailed description, taken in combination with the attached figures.
    [0023] It should be appreciated that various aspects of the present disclosure disclosed herein are merely illustrative in specific ways to manufacture and use the disclosure and do not limit the scope of the disclosure when taken into account with the attached claims, the detailed description and the attached figures .
    [0024] It should be assessed that characteristics of an aspect of the disclosure will be evident to those skilled in the art from a consideration of the description or examples of the disclosure disclosed here and these characteristics can be combined with characteristics of other aspects / modalities of the present disclosure.
    [0025] As used in this disclosure and the appended claims, the singular forms "one", "one" and "o", "a" include references in the plural unless the context clearly specifies otherwise.
    [0026] The present inventors have developed a nutritional composition for inflammatory bowel disease (e.g., Crohn's disease).
    [0027] The term "nutritional composition" includes, but is not limited to, complete nutritional compositions, partial or incomplete nutritional compositions, and specific nutritional compositions for the disease or condition. A complete nutritional composition (that is, those that contain all the essential macro and micronutrients) can be used as a single source of nutrition for the patient. Patients can receive 100% of their nutritional needs from such a complete nutritional composition. A partial or incomplete nutritional composition does not contain all essential macro and micronutrients and cannot be used as a single source of nutrition for the patient. Partial or incomplete nutritional compositions can be used as a nutritional supplement. A specific nutritional composition for the disease or condition is a composition that releases nutrients or pharmaceuticals and can be a complete or partial nutritional composition.
    [0028] It has been found that the nutritional composition when used during an active phase of inflammatory bowel disease (eg, Crohn's disease): can induce remission (as indicated by a PCDAI count and endoscopic assessments, can infra-regulate the response inflammatory, promote healing of the intestinal mucosa, can promote weight gain, can promote linear growth and improve nutritional status as well as improve musculoskeletal changes.
    [0029] PCDAI counting is well known in the art and PCDAI refers to the Pediatric Crohn's Disease Activity Index. PCDAI is a reliable and validated multi-parameter measure that classifies disease activity among children and adolescents. It is found that the nutritional composition of the present disclosure significantly reduces the PCDAI in the first two weeks of treatment, reducing to the minimum value within 8 weeks as described in figure 1.
    [0030] The nutritional composition comprises acid casein protein, vitamin K in a ratio of vitamin K1: K2 being between 3: 1 and 1: 3 and vitamin K present in an amount between 17.5 and 100 pg / 100 g of the composition nutritional, vitamin D present in an amount between 2.5 and 75 pg / 100 g of the nutritional composition; and n6 / n3 fatty acids in a ratio of n6: n3 fatty acids between 5: 1 and 1: 5.
    [0031] The acidic casein is produced by acidifying the milk until the isoelectric point of the casein is reached (at pH 4.7). Subsequently, the so-called acid casein protein precipitates. The process is well established in the art (see fundamentals section of US4397926) Often, acidic casein is obtained in a continuous casein coagulation process from exactly skimmed milk under the influence of whey. However, other production methods are available.
    [0032] The acid casein protein is high in naturally occurring transforming growth factor Beta-2 (TGF-p2). Transforming growth factor Beta-2 (TGF-p2) is an anti-inflammatory cytokine that plays an important role in healing the intestinal mucosa.
    [0033] Vitamin K denotes a group of lipophilic, hydrophobic and essential vitamins having a common chemical ring structure (naphthoquinone). Vitamin K1 is a unique compound known as phylloquinone or phytomenadione and vitamin K2 is a series of vitamers known as menaquinones or menathetrenones.
    [0034] As noted, inflammatory bowel disease (eg Crohn's disease) is known to compromise bone growth, bone quality and basically bone density. An incidence of low bone mass in patients with inflammatory bowel disease (eg, Crohn's disease) varies from about 30 to 50%. Vitamin K is usually deficient in patients having inflammatory bowel disease (for example, Crohn's disease) and the consequent limited bioavailability can reduce osteocalcin carboxylation during bone mass formation as well as reduce bone strength, bone mineralization and bone microarchitecture. Consequently, patients having inflammatory bowel disease (eg Crohn's disease) benefit from a more effective dose of vitamin K. Low levels of vitamin K can lead to an increase in the rate of bone resorption, without a compensatory increase in the rate of formation. bone.
    [0035] Rather than trying to increase intake levels by means of higher vitamin K intake, vitamin K2 takes into account a more potent form of vitamin K without negatively impacting anticoagulation parameters. Vitamin K2, compared to vitamin K1, provides enhanced absorption and more stable serum levels through a longer half-life when compared to vitamin Kl. The enhanced absorption of vitamin K2 into extrahepatic tissue takes into account a greater impact to improve musculoskeletal health in patients with inflammatory bowel disease (for example, Crohn's disease).
    [0036] The present applicant surprisingly found that administering vitamin K in a ratio of vitamin K1: K2 being between 3: 1 and 1: 3 and vitamin K present in an amount between 17.5 to 100 pg / 100 g of the composition Nutritional as part of the nutritional composition improves the carboxylation of osteocalcin and improves bone health indexes during normal growth and development in children. In addition, vitamin K supplementation also promotes bone growth and bone quality in patients with inflammatory bowel disease (for example, Crohn's disease). Nutritional composition when administered increases bone density and improves bone tissue microarchitecture in patients with inflammatory bowel disease (eg, Crohn's disease), thereby reducing the incidence of fracture risk. The effects of vitamin K are directly observed on bone quality such that this form of vitamin K modulates the formation of proteins in the organic matrix of the bone involved in micro-architectural morphology, mineralization, density, elasticity and mechanical hardness, as measured by computed tomography peripheral quantitative ("pQCT") or Bone Densitometry by Dual Energy X-ray absorption ("DEXA").
    [0037] Bone density is expressed as the relationship between bone mass (expressed as the degree of photon attenuation through the bone, or bone mineral content (BMC)) and the image of the bone in a film (that is, the area) (expressed as BMC / cm2). Additionally, pQCT is a procedure that evaluates peripheral bone in 3 dimensions (volumetric) and is commonly applied to the forearm or tibia. A radiation source (typically X-rays) and a sensor revolves around the bone under examination, which is then reconstituted on the computer screen in a three-dimensional image. pQCT is an ideal technique to assess bone geometry even though sensitivity varies with the site under evaluation. Unlike most other techniques, pQCT measures true bone density (volumetric mineral bone density) because it normalizes bone mineral content derived not from the projected area but rather from the volume of the examined bone. pQCT can also be used to calculate SSI, an index of bone resistance to torsion. The index takes into account the bone geometry and the mineral characteristics of the bone. See, Geometry and bone density, Radetti, G., et al., Panminerva Med 2006; 48: 181 6.
    [0038] DEXA is based on X-ray spectrometry and its fundamental principle is based on the degree of attenuation of X-rays emitted from 2 different energy sources. DEXA is normally used to assess mineralization of the proximal lumbar or femoral bone. DEXA has an accuracy of 4 to 10% and a variation coefficient of 1 to 1.5%.
    [0039] In a preferred embodiment vitamin K is present in an amount of vitamin K in a vitamin K1: K2 ratio being between 2: 1 and 1: 2.
    [0040] In a preferred embodiment vitamin K is present in an amount of vitamin K in a ratio of vitamin K1: K2 being 1: 1.
    [0041] In a preferred embodiment, vitamin K is present in an amount between 20 and 50 pg / 100 g of the nutritional composition.
    [0042] In a preferred embodiment, vitamin K is present in an amount between 20 and 40 pg / 100 g of the nutritional composition.
    [0043] In a preferred embodiment, vitamin K is present in an amount between 22 and 30 pg / 100 g of the nutritional composition.
    [0044] In a preferred embodiment, vitamin K is present in an amount between 25 and 30 pg / 100 g of the nutritional composition.
    [0045] In a preferred embodiment, vitamin K is present in an amount between 26 and 28pg / 100 g of the nutritional composition.
    [0046] In a preferred embodiment, vitamin K is present in an amount of 27/100 g of the nutritional composition.
    [0047] Vitamin D is an important nutrient for the development of the inorganic bone matrix. Vitamin D is present in an amount between 2.5 and 75 pg / 100 g of the nutritional composition.
    [0048] In a preferred embodiment, vitamin D is present in an amount between 7.5 and 70 pg / 100 g of the nutritional composition.
    [0049] In a preferred embodiment vitamin D is present in an amount between 7.5 and 15 pg / 100 g of the nutritional composition.
    [0050] In a preferred embodiment vitamin D is present in an amount between 10 and 13 pg / 100 g of the nutritional composition.
    [0051] In a preferred embodiment vitamin D is present in an amount between 11 and 12 pg / 100 g of the nutritional composition.
    [0052] In a preferred embodiment vitamin D is present in an amount of 11.6 pg / 100 g of the nutritional composition.
    [0053] Figure 2 shows that administration of the traditional nutritional composition by enteral feeding for 12 weeks significantly improves bone density in children aged 6.6 to 17.7 years with inflammatory bowel disease (eg Crohn's disease) .
    [0054] In addition, the nutritional composition has improved anti-inflammatory activity for healing the mucosa due to the presence of n6 / n3 fatty acids and / or mixtures thereof. The n6 / n3 fatty acids are present in a ratio of n6: n3 fatty acids between 5: 1 and 1: 5. Since the nutritional composition promotes healing of the mucosa, there is an improvement in the absorption of nutrients in a patient with inflammatory bowel disease (for example, Crohn's disease).
    [0055] Examples of omega n3 fatty acids are hexadecatrienoic acid (HTA) C16: 3, alpha linolenic acid (ALA) C18: 3, stearidonic acid (SDA) C18: 4, eicosatrienoic acid (ETE) C20: 3, eicosatetraenoic acid (ETA) C20: 4, eicosapentaenoic acid (EPA) C20: 5, henicosapentaenoic acid (HPA) C21: 5, docosapentaenoic acid (DPA) C22: 5, docosahexaenoic acid (DHA) C22: 6, tetracosapentaenoic acid C24: 5 and tetracosaexaenoic C24: 6.
    [0056] In a preferred embodiment the omega 3 n3 fatty acids are eicosapentaenoic acid (EPA) C20: 5 and docosahexaenoic acid (DHA) C22: 6.
    [0057] Omega 3 n3 fatty acids can be derived from fish oils, algae oil, squid oil, and vegetable oils such as Echium oil and linseed oil and / or mixtures thereof.
    [0058] Examples of fatty acid omega 6, n6 are linolenic acid (LA) C18: 2, gamma-linolenic acid (GLA) C18: 3, eicosadienoic acid C20: 2, dihomo-gamma-linolenic acid (DGLA) C20: 3 , arachidonic acid (AA) C20: 4, docosadienoic acid C22: 2, adrenic acid C22: 4, docosapentaenoic acid C22: 5, tetracosatetraenoic acid C24: 4, tetracosapentaenoic acid C24: 5 and Calendic acid C18: 3.
    [0059] Omega 6 n6 fatty acids can be derived from poultry, eggs, avocado, nuts, cereals, durum wheat, whole grain, vegetable oils, onagrace oil, borage oil, cassis seed oil, flax oil / flaxseed, rapeseed oil, canola oil, hemp oil, soybean oil, cottonseed oil, sunflower seed oil, corn oil, safflower oil, pumpkin seeds, açaí, cashews and spirulina and / or mixtures thereof.
    [0060] In a preferred embodiment, omega 3 fatty acid, n3 is alpha-linolenic acid (ALA) C18: 3 and omega 6 fatty acid, n6 is linolenic acid (LA) C18: 2.
    [0061] Figure 2 shows that administration of the traditional nutritional composition by enteral feeding for 12 weeks significantly improves the area in muscle cross section in children aged 6.6 to 17.7 years with inflammatory bowel disease (for example, Disease Crohn's).
    [0062] The nutritional composition can also include one or more amino acids. Non-limiting examples of amino acids include Alanine, Arginine, Asparagine, Aspartate, Citrulline, Cysteine, Glutamate, Glutamine, Glycine, Histidine, Hydroxyproline, Hydroxyiserine, Hydroxytyrosine, Hydroxylysine, Isoleucine, Leucine, Lysine, Serine, Proline, Phenine, Phenine Threonine, Tryptophan, Tyrosine, Valine, HICA (Alpha-Hydroxy-isocaproic acid), HIVA (Alpha-Hydroxy-isovaleric acid), HIMVA (alpha-hydroxymethylvaleric acid) or a combination of these.
    [0063] In another embodiment the nutritional composition may comprise minerals such as sodium, potassium, calcium, phosphorus, magnesium, chloride, iron, zinc, copper, manganese, fluoride, chromium, molybdenum, selenium, iodine or any combination thereof.
    [0064] In another modality the nutritional composition includes other vitamins such as Vitamin A, Vitamin E, Vitamin C, Vitamin B1, Vitamin B2, Pantothenic acid, Vitamin B6, Vitamin B12, Niacin, Folic acid, Biotin and Choline or any combination of these.
    [0065] In another modality, the nutritional composition also includes one or more prebiotics. As used here, a prebiotic is a selectively fermented ingredient that allows for specific changes, both in composition and in activity in the gastrointestinal microflora, which confers benefits on the well-being and health of the host. Non-limiting examples of prebiotics include fructo-oligosaccharides, inulin, lactulose, galacto-oligosaccharides, acacia gum, soy oligosaccharides, xylo-oligosaccharides, isomalto-oligosaccharides, gentio-oligosaccharides, lactossaccharides, glyco-oligosaccharides, glyco-oligosaccharides, partially hydrolyzed, sugar alcohols, alpha glucan, beta glucan, or a combination of these.
    [0066] In another modality, the nutritional composition also includes one or more probiotics. Since probiotics are preferably microorganisms (live, including semi-viable or weakened, and / or non-replicating), metabolites, microbial cell preparations or microbial cell components that can confer health benefits on the host when administered in adequate amounts, more specifically that beneficially affect a host by improving its intestinal microbial balance, leading to effects on the health or well-being of the host. In general, these probiotics are believed to inhibit and / or influence the growth and / or metabolism of pathogenic bacteria in the intestinal tract. Probiotics can also activate the host's immune function. Non-limiting examples of probiotics include Saccharomyces, Debaromyces, Candida, Pichia, Torulopsis, Aspergillus, Rhizopus, Mucor, Penicillium, Bifidobacterium, Bacteroides, Clostridium, Fusobacterium, Melissococcus, Propionibacterium, Streptococcus, Staocococcus, Enteroccus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus, Lactobacillus or a combination of these.
    [0067] In another modality, nutritional compositions also comprise a symbiotic. The symbiotic is a supplement that contains both prebiotic (s) and probiotic (s). The prebiotic (s) and probiotic (s) work together to improve the intestinal microflora. The symbiotic comprises any combination of the prebiotic (s) and the probiotic (s) mentioned above.
    [0068] In another embodiment, the nutritional composition comprises a pharmaceutically acceptable carrier and / or flavoring agent and / or coloring agent. The use of a flavoring agent provides a flavor to the nutritional composition that makes the nutritional composition more palatable to patients with inflammatory bowel disease (for example, Crohn's disease).
    [0069] In a preferred embodiment the nutritional composition is in the form of a powder that must be reconstituted with a liquid.
    [0070] The nutritional composition can be in a manageable form such as pharmaceutical formulations, nutritional formulations, tube feeding formulations, food supplements, functional foods, beverage products or a combination of these.
    [0071] As used here, a "feed by the bo" formulation is preferably a complete or incomplete nutritional product that is administered to a patient's gastrointestinal tract, except through oral administration, including but not limited to a nasogastric tube, tube orogastric, gastric tube, jejunostomy tube (J tube), percutaneous endoscopic gastrostomy (PEG), port, as well as a chest cavity port that provides access to the stomach, jejunum and other appropriate access ports.
    [0072] The nutritional composition of the present disclosure is advantageous in patients with inflammatory bowel disease (for example, Crohn's disease) who wish to avoid treatment with drug therapy and to avoid side effects that are associated with drug therapy.
    [0073] The nutritional composition of the present disclosure can be used in patients with inflammatory bowel disease (eg, Crohn's disease) as a supplement to drug therapy.
    [0074] The nutritional composition of the present disclosure is advantageous in patients with inflammatory bowel disease (for example, Crohn's disease) who fail to respond to medication. EXAMPLE
    [0075] The nutritional composition according to the present disclosure was manufactured according to table 1.
    [0076] The column "Example of nutritional composition per 100 g" shows an example of the nutritional composition based on the constituents of the nutritional composition per 100 g of the nutritional composition, when the nutritional composition is in the form of a powder.
    [0077] The column "Declared value per serving: 20.4 g of the nutritional composition (powder) per 84 ml of water to form 100 ml of reconstituted formula" shows the nutritional composition based on the constituents of the nutritional composition when 20.4 g of the nutritional composition example are reconstituted with 84 ml of water to form a 100 ml nutritional composition in the form of a liquid.




    [0078] The reconstituted nutritional formulation was administered to children aged 6.6 to 17.7 years with internal inflammatory disease (eg Crohn's disease) over a period of twelve weeks.
    [0079] After observing the comparative characteristics, children aged between 6.6 and 17.7 years with inflammatory bowel disease (eg Crohn's disease) were administered with the nutritional composition for 4 weeks as a unique nutritional support for obtain clinical remission. The administration was then continued for 8 weeks.
    [0080] Children aged between 6.6 and 17.7 years with inflammatory bowel disease (for example, Crohn's disease) were followed up at 4 and 12 weeks after the first visit. Muscle cross-sectional area and bone density were measured at the first visit and at 12 weeks.
    [0081] A plasma metabolic profile of children aged 6.6 to 17.7 years with inflammatory bowel disease (eg, Crohn's disease) was obtained at the first visit and after 4 weeks of nutritional intervention by a metabonomic method . The metabonomic method consisted of using a Biocrates Life Sciences AbsoluteIDQTM kit according to the manufacturer's instructions. The plasma metabolic profile of children aged 6.6 to 17.7 years with inflammatory bowel disease (eg, Crohn's disease) was processed with multivariate statistics to identify metabolic information (biomarkers). Metabolic information (biomarkers) is indicative of the physiological status of children aged between 6.6 and 17.7 years with inflammatory bowel disease (for example, Crohn's disease) in response to the intervention with the nutritional composition. Metabolic trajectories of the plasma metabolic profile have been observed over time, which have been associated with distinct differences in circulating amino acids and lipids.
    [0082] Significant differences were observed.
    [0083] It has been observed that a 4-week intervention with the nutritional composition is able to partially restore a metabolic profile in children aged between 6.6 and 17.7 years with inflammatory bowel disease (for example, Crohn's disease). The initial tilling of amino acids and lipids in children aged between 6.6 and 17.7 years with inflammatory bowel disease (for example, Crohn's disease) at the first visit compared to controls at the same age demonstrates a significant reduction in various metabolites.
    [0084] The 4-week intervention with the nutritional composition is not only able to induce the remission of an effect with an acute episode of inflammatory bowel disease, but also surprisingly restores the levels of threonine, histidine and tryptophan amino acids. In addition, definitive trends for the restoration of the amino acids proline and glutamine were also observed. Consequently, the nutritional composition may further comprise amino acids to reflect the restoration of the amino acid levels found in a patient in a state of remission from an acute episode effect of inflammatory bowel disease.
    [0085] In addition to a catabolic protein response, a reduction in several lipid species from the first visit was also observed when compared to controls of the same age. Similar to the amino acid response, the nutritional intervention is able to restore the response to multiple lipid metabolites after 4 weeks. The results indicate that the nutritional composition can change the catabolic response to an anabolic response.
    [0086] It was also found that the nutritional composition of the present disclosure significantly reduces the PCDAI (Pediatric Crohn's Disease Activity Index) in the first four weeks of treatment, reducing to the minimum value within 8 weeks as described in figure 1.
    [0087] Furthermore, since muscle destruction is considered to contribute to the concentration of plasma amino acids, the nutritional intervention that restores these amino acids as described above, will reduce the catabolic stress of the muscle. In order to demonstrate this effect, a Z count for the muscle cross-sectional area at the first visit and after 12 weeks was established. The Z count measures the change in area in muscle cross section when compared to a reference population. As shown in Figure 2, a 4-week intervention with the nutritional composition is able to alleviate the loss of area in muscle cross section and promote the area in muscle cross section within 12 weeks.
    [0088] Thus it is demonstrated that a nutritional intervention in children aged between 6.6 and 17.7 years with inflammatory bowel disease (for example, Crohn's disease) is able to correct a metabolic interruption and thus alleviate the response catabolic muscle and relieve musculoskeletal changes associated with inflammatory bowel disease (eg, Crohn's disease).
    [0089] Furthermore, it has been observed that the administration of the nutritional composition in maintenance therapy takes significantly longer time for relapse. Therefore, the nutritional composition promotes longer periods of remission with improved muscle cross-sectional area and improved bone density during a remission phase in patients with inflammatory bowel disease (for example, Crohn's disease).
    [0090] It has been surprisingly found that the amounts of the components used with ratios within the above ranges play an important role and are advantageous when the composition is used in patients with inflammatory bowel disease. The nutritional composition promotes and improves the area in muscle cross-section and bone density, the nutritional composition also takes significantly longer time for relapse in patients with inflammatory bowel disease.
    [0091] Having thus described the present disclosure in detail and the advantages of it, it should be understood that the preceding detailed description of the disclosure is not intended to limit the scope of its disclosure.
    [0092] The person skilled in the technique will be able to practice dissemination by combining various aspects and modalities. Disclosure is not limited to the detailed description and / or examples.
    [0093] What is desired to be protected by patent authorization is presented in the following claims.
    权利要求:
    Claims (15)
    [0001]
    1. Nutritional composition, characterized by the fact that it comprises: acid casein protein, vitamin K in a ratio of vitamin K1: K2 being between 3: 1 and 1: 3 and vitamin K present in an amount between 17.5 and 100 pg / 100 g of the nutritional composition, vitamin D present in an amount between 2.5 and 75 pg / 100 g of the nutritional composition; and n6 / n3 fatty acids in a ratio of n6: n3 fatty acids between 5: 1 and 1: 5 and mixtures thereof.
    [0002]
    2. Nutritional composition according to claim 1, characterized by the fact that omega 6, n6 fatty acids are selected from the group consisting of linolenic acid (LA) C18: 2, gamma linolenic acid (GLA) C18: 3, eicosadienoic acid C20: 2, dihomo-gamma-linolenic acid (DGLA) C20: 3, arachidonic acid (AA) C20: 4, docosadienoic acid C22: 2, adrenic acid C22: 4, docosapentaenoic acid C22: 5, tetracosatetraenoic acid C24: 4, tetracosapentaenoic acid C24: 5 and Calendic acid C18: 3 or mixtures thereof.
    [0003]
    3. Nutritional composition according to claim 1 or 2, characterized by the fact that omega 3, n3 fatty acid is selected from the group consisting of hexadecatrienoic acid (HTA) C16: 3, alpha-linolenic acid (ALA) C18: 3, stearidonic acid (SDA) C18: 4, eicosatrienoic acid (ETE) C20: 3, eicosatetraenoic acid (ETA) C20: 4, eicosapentaenoic acid (EPA) C20: 5, henicosapentaenoic acid (HPA) C21: 5, acid docosapentaenoic (DPA) C22: 5, docosahexaenoic acid (DHA) C22: 6, tetracosapentaenoic acid C24: 5 and tetracosahexaenoic acid C24: 6 or mixtures thereof.
    [0004]
    4. Nutritional composition according to any one of claims 1 to 3, characterized by the fact that it also comprises one or more amino acids selected from the group comprising Alanine, Arginine, Asparagine, Aspartate, Citrulline, Cysteine, Glutamate, Glutamine, Glycine, Histidine , Hydroxyproline, Hydroxyiserine, Hydroxytyrosine, Hydroxylysine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Taurine, Threonine, Tryptophan, Tyrosine, Valine, HICA (Alpha-Hydroxy-Isocaproic Acid) (HIV) , HIMVA (alpha-hydroxymethylvaleric acid) or a combination of these.
    [0005]
    5. Nutritional composition according to any one of claims 1 to 4, characterized by the fact that it also comprises one or minerals selected from the group consisting of sodium, potassium, calcium, phosphorus, magnesium, chloride, iron, zinc, copper, manganese , fluoride, chromium, molybdenum, selenium, iodine or any combination of these.
    [0006]
    6. Nutritional composition according to any one of claims 1 to 5, characterized by the fact that it also comprises one or more additional vitamins selected from the group consisting of Vitamin A, Vitamin E, Vitamin C, Vitamin B1, Vitamin B2, Pantothenic acid , Vitamin B6, Vitamin B12, Niacin, Folic acid, Biotin and Choline or any combination of these.
    [0007]
    7. Nutritional composition according to any one of claims 1 to 6, characterized by the fact that it also comprises one or more prebiotics selected from the group comprising fructo-oligosaccharides, inulin, lactulose, galacto-oligosaccharides, acacia gum, soy oligosaccharides, xylo-oligosaccharides, isomalto-oligosaccharides, gentio-oligosaccharides, lactosaccharose, glycooligosaccharides, pecticoligosaccharides, guar gum, partially hydrolyzed guar gum, sugar alcohols, alpha glucan, beta glucan, or a combination of these.
    [0008]
    8. Nutritional composition according to any one of claims 1 to 7, characterized by the fact that it further comprises one or more probiotics selected from the group comprising Saccharomyces, Debaromyces, Candida, Pichia, Torulopsis, Aspergillus, Rhizopus, Mucor, Penicillium, Bifidobacterium , Bacteroides, Clostridium, Fusobacterium, Melissococcus, Propionibacterium, Strep-tococcus, Enterococcus, Lactococcus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, or a combination of these.
    [0009]
    Nutritional composition according to any one of claims 1 to 8, characterized in that it further comprises a pharmaceutically acceptable carrier, a flavoring agent and a dye or any combination thereof.
    [0010]
    10. Pharmaceutical formulation, nutritional formulation, tube feeding formulation, food supplement, functional food, beverage product or combination thereof, characterized by the fact that it comprises the nutritional composition, as defined in any one of claims 1 to 9.
    [0011]
    11. Use of a nutritional composition, as defined in any of claims 1 to 9, characterized by the fact that it is for the manufacture of a formulation, as defined in claim 10, to improve musculoskeletal health.
    [0012]
    12. Use, according to claim 11, characterized by the fact that the said formulation is to improve musculoskeletal health in patients, and the patients may optionally be pediatric or adolescent patients.
    [0013]
    13. Use, according to claim 12, characterized by the fact that said patient has at least one of delayed development, failure to thrive, inflammatory-intestinal disease, Crohn's disease, osteopenia associated with Crohn's disease, malnutrition or any combination of these.
    [0014]
    14. Use, according to claim 12 or 13, characterized by the fact that said improvement in musculoskeletal health is improved bone density.
    [0015]
    15. Use, according to any one of claims 12 to 14, characterized by the fact that said improvement in musculoskeletal health is an area in improved muscle cross section.
    类似技术:
    公开号 | 公开日 | 专利标题
    BR112015001884B1|2020-12-01|nutritional composition to promote musculoskeletal health in patients with inflammatory bowel disease |, its use, and pharmaceutical formulation, nutritional formulation, tube feeding formulation, food supplement, functional food or beverage product
    US11123407B2|2021-09-21|Nutritional composition for treating or preventing impaired mobility
    Todd et al.2008|Update on postinjury nutrition
    CA3030292C|2021-09-14|Compositions and methods for managing digestive disorders and a healthy microbiome
    CN107106653A|2017-08-29|Alimentation composition available for treatment IBD patient
    TWI639387B|2018-11-01|Galactooligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract
    AU2014253403B2|2018-03-01|Infant formula with a low content of medium-chain fatty acids in specific proportions, and its use in promoting and/or ensuring a balanced growth in infants
    BR112020009765A2|2020-11-03|compositions and methods that use a combination of autophagy inducer and high protein content for inducing autophagy
    WO2015085077A1|2015-06-11|Method of achieving memory and learning improvement by the administration of sialic acid
    US20200138838A1|2020-05-07|Composition comprising hmss/hmos and use thereof
    US20200138762A1|2020-05-07|Medium chain fatty acids for use in the prevention or treatment of cardiac enlargement and/or valvular heart disease
    ES2743468T3|2020-02-19|Compositions and methods using p-anisaldehyde
    ES2870568T3|2021-10-27|Nutritional Products to Promote Safe Swallowing for Individuals with Dysphagia
    BR112021007958A2|2021-07-27|mixed triglycerides
    Kartikey et al.2016|Effects of Oxidative Stress on Development of Osteoporosis, Carcinogenesis, Atherosclerosis and Brain Degeneration
    WO2021111422A1|2021-06-10|Composition comprising 2'-fl and dfl for use in a method for reducing pain
    BR112021007155A2|2021-07-20|human dietary supplement and method for treating digestive system and immune-related disorders
    BR112016030813B1|2021-11-03|NUTRITIONAL PRODUCT, ITS USE AND METHODS OF MANUFACTURING AND IMPROVEMENT OF A COHESIVE NATURE
    US20160129118A1|2016-05-12|Cohesive liquid bolus comprising bioactives
    同族专利:
    公开号 | 公开日
    US9763898B2|2017-09-19|
    WO2014020004A1|2014-02-06|
    EP2879523B1|2016-11-16|
    CN104582506B|2016-10-19|
    US9561194B2|2017-02-07|
    JP6368306B2|2018-08-01|
    JP2015530981A|2015-10-29|
    US20170079935A1|2017-03-23|
    BR112015001884A2|2017-07-04|
    EP2879523A1|2015-06-10|
    US20150174080A1|2015-06-25|
    CA2877811A1|2014-02-06|
    HK1209984A1|2016-04-15|
    CA2877811C|2019-07-23|
    AU2013298645B2|2016-11-03|
    CN104582506A|2015-04-29|
    AU2013298645A1|2015-01-15|
    DK2879523T3|2017-01-16|
    ES2609654T3|2017-04-21|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4397926A|1981-12-03|1983-08-09|Borden, Inc.|Preparation of cheese analogs from combinations of acid casein and rennet casein|
    EP0527283B1|1991-08-12|1997-11-26|Societe Des Produits Nestle S.A.|Food composition|
    EP0852913A1|1997-01-14|1998-07-15|Societe Des Produits Nestle S.A.|Composition and method for treatment of inflammatory conditions of the gastro-intestinal tract|
    CA2223198A1|1997-01-14|1998-07-14|Societe Des Produits Nestle S.A.|Composition and method for treatment of inflammatory conditions of the gastro-intestinal tract|
    DE69904257T2|1999-01-20|2003-04-17|Nutricia Nv|infant formula|
    US7759507B2|2003-09-05|2010-07-20|Abbott Laboratories|Lipid system and methods of use|
    CN101534807A|2006-07-14|2009-09-16|纳多制药股份公司|Pharmaceutical and nutraceutical products comprising vitamin k2|
    CN101537170B|2008-03-17|2012-05-30|哈药集团制药六厂|Compound for preventing osteoporosis and osteoarthrosis|
    US20130052274A1|2009-09-14|2013-02-28|Nestec S.A.|Nutritional compositions including exogenous vitamin k2|
    CN102485709B|2010-12-01|2014-10-22|天津康鸿医药科技发展有限公司|Preparation method of vitamin K2 compound|GB201112091D0|2011-07-14|2011-08-31|Gt Biolog Ltd|Bacterial strains isolated from pigs|
    GB201117313D0|2011-10-07|2011-11-16|Gt Biolog Ltd|Bacterium for use in medicine|
    US11179427B2|2013-01-21|2021-11-23|Eth Zurich|Baby food composition comprising viable propionic acid-producing bacteria|
    GB201306536D0|2013-04-10|2013-05-22|Gt Biolog Ltd|Polypeptide and immune modulation|
    WO2015048334A2|2013-09-25|2015-04-02|Pronutria, Inc.|Edible species nutritive polypeptides and methods of production and use thereof|
    DK3212198T3|2014-10-29|2021-03-29|Glycom As|Synthetic composition and method for promoting mucosal healing|
    ITPD20140288A1|2014-10-30|2016-04-30|Fusaro Maria|L-INTEGRA|
    PT3193901T|2014-12-23|2018-06-29|4D Pharma Res Ltd|Pirin polypeptide and immune modulation|
    WO2016116583A1|2015-01-23|2016-07-28|Nestec S.A.|Method for determining the distinctive nutritional requirements of a patient|
    EP3294308A4|2015-05-14|2019-03-06|University of Puerto Rico|Methods for restoring microbiota of newborns|
    SI3307288T1|2015-06-15|2019-11-29|4D Pharma Res Ltd|Compositions comprising bacterial strains|
    MA41060B1|2015-06-15|2019-11-29|4D Pharma Res Ltd|Compositions comprising bacterial strains|
    MA41010B1|2015-06-15|2020-01-31|4D Pharma Res Ltd|Compositions comprising bacterial strains|
    MA51639A|2015-06-15|2020-04-15|4D Pharma Res Ltd|COMPOSITIONS CONTAINING BACTERIAL STRAINS|
    AU2016278072B2|2015-06-15|2020-07-23|4D Pharma Research Limited|Compositions comprising bacterial strains|
    WO2017004564A1|2015-07-02|2017-01-05|Cambrooke Therapeutics, Inc.|Nutritional compositions|
    GB201520497D0|2015-11-20|2016-01-06|4D Pharma Res Ltd|Compositions comprising bacterial strains|
    CN112569262A|2015-11-20|2021-03-30|4D制药研究有限公司|Compositions comprising bacterial strains|
    GB201520631D0|2015-11-23|2016-01-06|4D Pharma Res Ltd|Compositions comprising bacterial strains|
    GB201520638D0|2015-11-23|2016-01-06|4D Pharma Res Ltd|Compositions comprising bacterial strains|
    JP6441536B2|2016-03-04|2018-12-19|フォーディー ファーマ ピーエルシー４Ｄ Ｐｈａｒｍａ Ｐｌｃ|Composition comprising a bacterial strain|
    GB201612191D0|2016-07-13|2016-08-24|4D Pharma Plc|Compositions comprising bacterial strains|
    TW201821093A|2016-07-13|2018-06-16|英商４Ｄ製藥有限公司|Compositions comprising bacterial strains|
    DK3436054T3|2016-09-13|2019-11-11|Allergan Inc|STABILIZED NON-PROTEIN CLOSTRID TOXIN COMPOSITIONS|
    EP3529379A4|2016-10-24|2020-05-13|Habit, LLC|System and method for implementing meal selection based on vitals, genotype, and phenotype|
    GB201621123D0|2016-12-12|2017-01-25|4D Pharma Plc|Compositions comprising bacterial strains|
    TW201834645A|2016-12-19|2018-10-01|美商胺細拉健康公司|Amino acid compositions and methods for the treatment of liver diseases|
    JP2020520911A|2017-05-22|2020-07-16|フォーディー ファーマ リサーチ リミテッド４Ｄ Ｐｈａｒｍａ Ｒｅｓｅａｒｃｈ Ｌｉｍｉｔｅｄ|Composition comprising a bacterial strain|
    WO2018215782A1|2017-05-24|2018-11-29|4D Pharma Research Limited|Compositions comprising bacterial strain|
    WO2018229188A1|2017-06-14|2018-12-20|4D Pharma Research Limited|Compositions comprising bacterial strains|
    RS60910B1|2017-06-14|2020-11-30|4D Pharma Res Ltd|Compositions comprising a bacterial strain of the genus megasphaera and uses thereof|
    SG11202001142VA|2017-08-14|2020-03-30|Axcella Health Inc|Amino acid compositions for the treatment of liver disease|
    US10596136B2|2018-06-20|2020-03-24|Axcella Health Inc.|Compositions and methods for the treatment of fat infiltration in muscle|
    RU2737196C1|2019-06-25|2020-11-25|Федеральное государственное бюджетное образовательное учреждение высшего образования "Уральский государственный экономический университет" |Specialized food product for maintaining body reserve forces and method for production thereof|
    CN112790278A|2021-01-22|2021-05-14|乖宝宠物食品集团股份有限公司|A complete pet canned food for maintaining bone health|
    法律状态:
    2018-05-02| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-07-23| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2019-10-01| B25A| Requested transfer of rights approved|Owner name: SOCIETE DES PRODUITS NESTLE S.A. (CH) |
    2020-05-05| B15K| Others concerning applications: alteration of classification|Free format text: AS CLASSIFICACOES ANTERIORES ERAM: A23L 1/29 , A23L 1/30 , A23L 1/302 , A23L 1/304 , A23L 1/305 Ipc: A23L 33/00 (2016.01), A23L 33/19 (2016.01), A23L 3 |
    2020-05-05| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|
    2020-08-11| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2020-12-01| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 30/07/2013, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    EP12178573.7|2012-07-31|
    EP12178573|2012-07-31|
    PCT/EP2013/065948|WO2014020004A1|2012-07-31|2013-07-30|Nutritional composition for promoting musculoskeletal health in patients with inflammatory bowel disease |
    [返回顶部]