Nutritional Composition for Improving the Mammalian Immune System

• US 20150004130A1
• Filed: 09/15/2014
• Published: 01/01/2015
• Est. Priority Date: 06/23/2008
• Status: Active Grant

• Current Assignee: nv nutricia
• Original Assignee: nv nutricia
• Inventors: VAN HELVOORT, Adrianus Lambertus Bertholdus, VAN NORREN, Klaske, HAGEMAN, Robert Johan Joseph, FABER, Joyce, VOS, Arjan Paul, VAN LIMPT, Cornelus Johannes Petrus
• Granted Patent: US 10,449,248 B2
• Time in Patent Office: Days
• US Class Current: 424/85.1
• CPC Class Codes: A23L 33/12 Fatty acids or derivatives thereof
• CPC Class Codes: A23L 33/175 Amino acids
• CPC Class Codes: A23L 33/19 Dairy proteins
• CPC Class Codes: A23L 33/40 Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/324 having an effect on the immune system
• CPC Class Codes: A23V 2250/0628 Leucine
• CPC Class Codes: A23V 2250/1868 Docosahexaenoic acid
• CPC Class Codes: A23V 2250/187 Eicosapentaenoic acid
• CPC Class Codes: A23V 2250/28 Oligosaccharides
• CPC Class Codes: A23V 2250/54246 Casein
• CPC Class Codes: A23V 2250/54252 Whey protein
• CPC Class Codes: A61K 2039/55583 Polysaccharides
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/702 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
• CPC Class Codes: A61K 35/20 Milk; Whey; Colostrum
• CPC Class Codes: A61K 38/018 from milk
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 39/39 : characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/12 : Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/42 : Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants

Abstract

The invention relates to a nutritional composition comprising

(a) at least 18 en % of proteinaceous matter;
(b) at least 12 wt % of leucine, based on total proteinaceous matter;
(c) a lipid fraction comprising at least a ω-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid and docosapentaenoic acid;
(d) an immune modulator;
for improving the immune function in a mammal, preferably a human.

Claims

1. A method for improving an immune function in a mammal, comprising administering a nutritional composition to the mammal, said nutritional composition comprising:

(a) at least 18 en % of proteinaceous matter;

(b) at least 12 wt. % of leucine, based on total proteinaceous matter;

(c) a lipid fraction comprising at least 15 wt. % based on total lipid content of a ω

-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid and docosapentaenoic acid; and

(d) an immune modulator, and

improving immune function in the mammal.

2. The method according to claim 1, wherein improving the immune function comprises at least one effect selected from the group consisting of:

improving a Th1-mediated immune response;

increasing the activity or number of natural killer (NK) cells;

increasing pathogen-specific or tumor-specific IgA, IgG or IgM antibody production;

increasing IgA, IgG or IgM concentrations to normal range values in the blood of mammals with sub-normal levels of said antibodies;

increasing the total number of white blood cells in mammals with treatment- or disease-induced decreased number of white blood cells;

increasing the number or activity of phagocytic cells in mammals with treatment- or disease-induced decreased number of phagocytic cells;

improving cell-mediated cytotoxic responses against pathogens, pathogen-infected cells or tumor cells;

improving the barrier function of mucosal epithelia by increasing sIgA excretion, increasing intestinal mucus production, decreasing epithelial permeability or decreasing microbial translocation across the epithelia with the exception of non-infectious uptake of microbes by local immune cells;

improving the composition of the intestinal microbiota by increasing the number or activity of beneficial bacteria such as bifidobacteria or lactobacilli, by improving the colonization resistance of the intestinal microbiota, by decreasing the number of potential pathogenic organisms in the intestinal microbiota, or by decreasing the pH of the intestinal content; and

mounting effective immune responses against cancer cells, either as a primary treatment or as an adjuvant treatment to eradicate residual cancer cells.

3. The method according to claim 2, wherein improving a Th1-mediated immune response comprises at least one effect selected from the group consisting of:

improving cellular vaccination responses;

increasing Th1-induced production of IgG subclass antibody production in acute responses against pathogens or in anti-tumor immune responses;

decreasing antigen-specific or total IgE antibodies in serum;

improving cellular immune responses to viral or bacterial pathogens or pathogen-mimicking substances; and

increasing IL-2, IFN-gamma or IL-12 production in acute responses against pathogens, pathogen-mimicking substances or in local anti-tumor immune responses.

4. The method according to claim 1, wherein improving the immune function prevents or treats a reduced immune function due to, or resulting from, aging, disease, disorder or trauma.

5. The method according to claim 4, wherein the reduced immune function manifests itself as a symptom selected from the group consisting of infections, inflammations, vascular complications, bad wound healing, mucositis and stomatitis.

6. The method according to claim 4, wherein the disease or disorder is selected from the group consisting of cancer, tumor growth, diabetes, chronic obstructive pulmonary disease, HIV infections, renal disease, renal failure, heart failure, and a disease state characterized by one or both of a high plasma and a high serum level of pro-inflammatory cytokines.

7. The method according to claim 6, wherein the nutritional composition is administered to a mammal suffering from cancer.

8. The method according to claim 4, wherein the mammal has a trauma selected from the group consisting of surgery, drug treatment, chemotherapy and radiotherapy.

9. The method according to claim 1, wherein the nutritional composition is administered to a mammal receiving an anti-cancer immunotherapy or planning to start anti-cancer immunotherapy within a period of two months, and wherein the nutritional composition enhances the effectiveness of an immunotherapy.

10. The method according to claim 1, wherein the immune modulator is selected from the group consisting of immune system modulating indigestible carbohydrates, lactoferrin, glycine, immune system modulating drugs, and immune system modulating bacteria or fragments thereof.

11. The method according to claim 10, wherein the indigestible carbohydrate comprises a galactooligosaccharide

12. The method according to claim 10, wherein the indigestible carbohydrate comprises a fructooligosaccharide.

13. The method according to claim 11, wherein the indigestible carbohydrate comprises a galactooligosaccharide and a fructooligosaccharide and the molar ratio of galactooligo-saccharide to fructooligosaccharide ranges from 1:

1 to 20;

1.

14. The method according to claim 10, wherein the indigestible carbohydrate is selected from the group of galactomannans having a degree of polymerization (DP) between about 2 and about 50, xylans having a DP of between about 2 and about 60, oligomers having more than about 30 wt. % of galacturonic acid or glucuronic acid moieties having a molecular weight of between about 520 and about 2200 Daltons, and any combination thereof.

15. The method according to claim 10, wherein the indigestible carbohydrate comprises between about 1 wt. % and about 15 wt. %, based on total dry matter.

16. The method according to claim 10, wherein the immune system modulating drug is selected from the group consisting of:

growth factors suitable for preventing or treating neutropenia or treatment-related dysfunction of the immune system in cancer patients selected from the group consisting of granulocyte-colony stimulating factors and derivatives thereof, granulocyte macrophage-colony stimulating factors and stem cell factors; and

antibiotics suitable for preventing or treating infections in cancer patients with neutropenia or anti-cancer treatments that render them susceptible to infections.

17. The method according to claim 10, wherein the immune system modulating bacteria or derivatives thereof are selected from the group consisting of probiotic bacteria, bacterial fragments, CpG oligonucleotides and heat-shock proteins.

18. The method according to claim 1, wherein the nutritional composition is a liquid nutritional composition comprising at least 7 g/100 ml of proteinaceous matter.

19. The method according to claim 1, wherein the proteinaceous matter originates from at least one protein source selected from the group of whey protein, casein, caseinate, soy protein and wheat protein.

20. The method according to claim 1, wherein the proteinaceous matter comprises at least 15 wt. % whey protein.

21. The method according to claim 1, wherein the nutritional composition comprises leucine in the form of a free acid, a salt, a dipeptide or a conjugate with a conjugating compound other than an amino acid, a protein, or a peptide, which conjugate is capable of being split into the free amino acid or salt thereof.

22. The method according to claim 1, comprising between 12 wt. % and 23 wt. % of leucine, based on total proteinaceous matter.

23. The method according to claim 1, comprising between 4 wt. % and 20 wt. % of glutamine, based on total proteinaceous matter.

24. The method according to claim 1, wherein the nutritional composition comprises at least 0.7 wt. % of one or more of the group of cystine, cysteine and cysteine equivalents.

25. The method according to claim 1, wherein the lipid fraction comprises less than 30 wt. % of a saturated fatty acid.

26. The method according to claim 1, wherein the lipid fraction further comprises at least one ω

-6 polyunsaturated fatty acid, and wherein the molar ratio of ω

-3 polyunsaturated fatty acids to ω

-6 polyunsaturated fatty acids is less than 1.0

27. The method according to claim 1, wherein the nutritional composition comprises proteinaceous matter, a lipid, and a digestible carbohydrate, wherein

a) the proteinaceous matter content provides between 18 en % and 50 en %;

b) the lipid content provides between 10 en % and 50 en % of the total composition;

c) the digestible carbohydrate content provides between 20 en % and 70 en %, of the total composition.

28. The method according to claim 1, wherein the nutritional composition is a liquid nutritional composition having an energetic value in the range of between 0.3 kcal/ml and 3.0 kcal/ml.

29. The method according to claim 1, wherein the nutritional composition is a liquid nutritional composition, having an energetic value in the range of between 0.2 kcal/ml and 1.0 kcal/ml.

30. The method according to claim 1, wherein the nutritional composition is a semi-liquid, gel or solid nutritional composition having an energetic value in the range of between 3.2 kcal/g and about 8.0 kcal/g.

31. The method according to claim 1, wherein the nutritional composition further comprises at least one component selected from the group consisting of sodium, potassium, chloride, fluoride, iodide, calcium, phosphorous, magnesium, vitamin A, vitamin D3, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, folic acid, vitamin B12, biotin, vitamin C, lipoic acid, zinc, iron, copper, manganese, molybdenum, selenium and chromium.

32. The method according to claim 1, wherein the mammal is a human.

33. The method according to claim 1, wherein the nutritional composition is administered orally.

34. The method according to claim 1, wherein the nutritional composition is administered enterally.

35. The method according to claim 1, wherein the nutritional composition is administered under supervision of a medical specialist.

36. The method according to claim 32, wherein the nutritional composition is self-administered.

37. The method according to claim 4, wherein improving the immune function prevents or treats a reduced immune function due to, or resulting from, disease, disorder or trauma.

38. The method according to claim 19, wherein the proteinaceous matter originates from at least one protein source selected from the group consisting of whey protein and casein.

39. The method according to claim 21, wherein the conjugate is capable of being split into the free amino acid or salt thereof in the gut or stomach or after absorption by the enterocytes or liver.

40. The method according to claim 1, wherein the nutritional composition comprises a digestible carbohydrate and the nutritional composition has a glycemic index of less than 55.

41. A method for therapeutically treating a mammal having cancer comprising administering a nutritional composition to the mammal having cancer, said nutritional composition comprising:

(a) at least t 18 en % of proteinaceous matter;

(b) at least 12 wt. % of leucine, based on total proteinaceous matter;

(c) a lipid fraction comprising at least a ω

-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid and docosapentaenoic acid; and

(d) an immune modulator,

and reducing or alleviating one or more symptoms associated with the cancer.

42. The method according to claim 41, wherein the nutritional composition comprises 1-15 wt. % of an immune modulator selected from the group of galactooligosaccharides and fructooligosaccharides, the composition further comprising a digestible carbohydrate and the composition having a glycemic index of less than 55.

43. A method for therapeutically treating a mammal having an infection comprising administering a nutritional composition to the mammal having the infection, said nutritional composition comprising:

(a) at least 18 en % of proteinaceous matter;

(b) at least 12 wt. % of leucine, based on total proteinaceous matter;

(c) a lipid fraction comprising at least a ω

-3 polyunsaturated fatty acid selected from the group of eicosapentaenoic acid, docosahexaenoic acid, eicosatetraenoic acid and docosapentaenoic acid; and

(d) an immune modulator,

and reducing or alleviating one or more symptoms associated with the infection.

44. The method according to claim 43, wherein the nutritional composition comprises 1-15 wt. % of an immune modulator selected from the group of galactooligosaccharides and fructooligosaccharides, the composition further comprising a digestible carbohydrate and the composition having a glycemic index of less than 55.