Oligosaccharide preparations that reduce the effects of respiratory diseases

Abstract

The present invention relates to oligosaccharide preparations for treating, alleviating, preventing, and / or delaying respiratory diseases, preferably infectious bronchitis, and / or their effects.

Description

Detailed Description of the Invention

[0001]

[0001] The present invention relates to oligosaccharide preparations for treating, remitting, preventing, and / or delaying respiratory diseases, preferably infectious bronchitis, and / or its effects.

[0002]

[0002] The global demand for poultry products continues to increase, and at the same time, farmers are facing continuous financial difficulties. Therefore, in poultry farming, it is of utmost importance to ensure animal welfare, sustainability, and animal health while optimizing animal performance and product quality.

[0003]

[0003] Infectious diseases, especially respiratory infectious diseases such as infectious bronchitis (IB) or Newcastle disease (ND), are known to occur in all regions and are one of the main causes of economic losses in poultry farming. Clinical symptoms of birds infected with infectious bronchitis virus (IBV) or Newcastle disease virus (NDV) include gasping, coughing, sneezing, damage to the respiratory epithelium, mucus accumulation, tracheal rales, conjunctivitis, rhinitis, dyspnea, asphyxia, etc. At the same time, feed consumption and weight gain, egg production, and egg quality decrease, and the feed conversion ratio (FCR) increases. In unvaccinated groups, the morbidity rate is typically 100%, and the mortality rate can be up to 60% depending on the specific virus strain infecting the group.

[0004]

[0004] As a countermeasure in current poultry farming, birds receive regular vaccination against NDV and IBV, for example, by spraying live attenuated IBV on chicks. However, the classification groups of IBV include several strains, and new IBV types and variants arise from mutation and recombination events. As a result, the currently applied IBV vaccines only provide cross-protection against some of these variants and cannot completely prevent the occurrence of IB in the population even after vaccination.

[0005]

[0005] In view of the prior art outlined above, an object of the present invention is to provide means and methods for treating, relieving, preventing and / or delaying respiratory diseases and the effects associated with and / or caused by said respiratory diseases.

[0006]

[0006] Surprisingly, this objective is achieved by using an oligosaccharide preparation to prevent and / or delay the effects of a respiratory disease, preferably infectious bronchitis, and / or the respiratory disease, preferably infectious bronchitis (i.e., infectious bronchitis caused by IBV), the oligosaccharide preparation comprising at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction comprising at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of anhydro subunit-containing oligosaccharides in relative abundance determined by mass spectrometry.

[0007]

[0007] In another aspect, the present invention relates to the use of an oligosaccharide preparation to improve the effectiveness of vaccination against respiratory diseases, preferably infectious bronchitis, wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry.

[0008]

[0008] In a further embodiment, the present invention relates to the use of an oligosaccharide preparation to reduce, prevent, and / or delay respiratory disease mortality in a flock of poultry attacked by a respiratory disease, preferably the respiratory disease being infectious bronchitis (particularly IB caused by IBV), and the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry.

[0009]

[0009] In another aspect, the present invention relates to the use of oligosaccharide preparations to reduce, alleviate, prevent and / or delay the incidence of respiratory disease (specifically, the incidence of respiratory disease in flocks of poultry that are under attack or at risk of being under attack by respiratory disease), preferably the respiratory disease being infectious bronchitis (particularly IB caused by IBV), and the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of anhydro subunit-containing oligosaccharides in relative abundance determined by mass spectrometry.

[0010]

[0010] In another aspect, the present invention relates to an oligosaccharide preparation for use in methods of treating, relieving, preventing and / or delaying the effects of a respiratory disease, preferably infectious bronchitis (particularly IB caused by IBV), the oligosaccharide preparation comprising at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction comprising at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry.

[0011]

[0011] In some embodiments, the present invention relates to an oligosaccharide preparation for use in a method of treating, relieving, preventing and / or delaying the effects of a respiratory disease, preferably infectious bronchitis, wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction comprises at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry, wherein the oligosaccharide preparation is administered to an individual (e.g., an animal such as a bird, poultry, or chicken) that has been vaccinated against a respiratory disease.

[0012]

[0012] In some embodiments, the oligosaccharide preparation is administered to an individual (for example, an animal such as a bird, poultry, or chicken) that is to be vaccinated against a respiratory disease.

[0013]

[0013] In some embodiments, the oligosaccharide preparation is administered to an individual (e.g., an animal such as a bird, poultry, or chicken) that has received at least one dose of the respiratory disease vaccine, and this individual will receive at least a second dose of the respiratory disease vaccine.

[0014]

[0014] In some embodiments, the oligosaccharide preparations of the present invention are included in nutritional compositions at a content exceeding 40 ppm, such as 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 600, 700, 800, 900, and over 1000 ppm.

[0015]

[0015] In some embodiments, n of the oligosaccharide preparation of the present invention is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 , 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100.

[0016]

[0016] In some embodiments, at least one fraction of the oligosaccharide preparation of the present invention comprises an anhydro subunit-containing oligosaccharide in relative abundance of 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2%. And / or, each fraction of the oligosaccharide preparation of the present invention contains, in relative abundance, 0.2%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 30%, 40%, 50%, 60%, 70%, or more than 80% anhydro subunit-containing oligosaccharides.

[0017]

[0017] In some embodiments, the oligosaccharide preparations of the present invention are approximately 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1300 g / mol, 400-1200 g / mol, 400-1100 g / mol, 500-1300 g / mol, 500-1200 The oligosaccharide preparation of the present invention has a weight-average molecular weight of g / mol, 500-1100 g / mol, 600-1300 g / mol, 600-1200 g / mol, or 600-1100 g / mol, and / or the oligosaccharide preparation of the present invention has a number-average molecular weight of approximately 1000-2000 g / mol, 1100-1900 g / mol, 1200-1800 g / mol, 1300-1700 g / mol, 1400-1600 g / mol, or 1450-1550 g / mol.

[0018]

[0018] In some embodiments, the relative abundance of oligosaccharides in each of the n fractions of the oligosaccharide preparation of the present invention decreases monotonically with increasing degree of polymerization.

[0019]

[0019] In some embodiments, the average DP of the oligosaccharide preparation of the present invention is at least 2. In some embodiments, the average DP of the oligosaccharide preparation of the present invention is at least 3.

[0020]

[0020] In some embodiments, the average DP of the oligosaccharide preparation of the present invention is less than 5.0.

[0021]

[0021] In some embodiments, the average DP of the oligosaccharide preparation of the present invention is 2 or more, for example, at least 3 or at least 4, and the average DP of the oligosaccharide preparation of the present invention is less than 5.0.

[0022]

[0022] In some embodiments, the average DP of the oligosaccharide preparation of the present invention is 1 to 5, for example, 2 to 5, or 2 to 4.94, or 3 to 5, or 3 to 3.94.

[0023]

[0023] In a preferred embodiment, the average DP of the oligosaccharide preparation of the present invention is determined based on the number-average molecular weight distribution of the oligosaccharide preparation of the present invention.

[0024]

[0024] The present invention is further characterized by the following items.

[0025]

[0025] Item 1. Use of an oligosaccharide preparation to treat, alleviate, prevent and / or delay respiratory diseases, preferably infectious bronchitis (particularly infectious bronchitis caused by IBV), and / or its effects (i.e., the effects of the respiratory disease, or the effects caused thereby, or the effects related thereto), wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry.

[0026]

[0026] Item 2. Use of an oligosaccharide preparation to treat, alleviate, prevent and / or delay the respiratory disease, preferably infectious bronchitis (in particular infectious bronchitis caused by IBV), and / or its effects (i.e., the effects of the respiratory disease, or the effects caused thereby, or the effects related thereto) in animals (preferably poultry, more preferably chickens) that have a respiratory disease, and / or are at risk of having the respiratory disease, wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of anhydro subunit-containing oligosaccharides in relative abundance determined by mass spectrometry.

[0027] Use of an oligosaccharide preparation for improving the effectiveness, efficacy, and / or efficiency of vaccination against respiratory diseases, preferably infectious bronchitis (especially infectious bronchitis caused by IBV), wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 - DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains anhydro-subunit-containing oligosaccharides in a relative abundance of at least about 0.5% to about 90%, such as 1% to 90%, or for example about 0.5% to about 15%, determined by mass spectrometry.

[0028] Use of an oligosaccharide preparation for reducing, preventing, and / or delaying death in a flock of poultry challenged with a respiratory disease, preferably infectious bronchitis (especially infectious bronchitis caused by IBV), wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 - DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains anhydro-subunit-containing oligosaccharides in a relative abundance of at least about 0.5% to about 90%, such as 1% to 90%, or for example about 0.5% to about 15%, determined by mass spectrometry.

[0029] Use of an oligosaccharide preparation for reducing, alleviating, preventing, and / or delaying the onset of a respiratory disease, preferably infectious bronchitis (especially infectious bronchitis caused by IBV), wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 - DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains anhydro-subunit-containing oligosaccharides in a relative abundance of at least about 0.5% to about 90%, such as 1% to 90%, or for example about 0.5% to about 15%, determined by mass spectrometry.

[0030] Item 6. Use according to any one of the preceding items, wherein the oligosaccharide preparation is contained in the nutritional composition at a content exceeding 40 ppm (for example, exceeding 40 ppm, 50 ppm, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200 ppm, etc.).

[0031]

[0031] Item 7. Use according to any one of the preceding items, wherein n of the oligosaccharide preparation is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, �3, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, %2, 93, 94, 95, 96, 97, 98, 99, or 100.

[0032]

[0032] Item 8. Use according to any one of the preceding items, wherein at least one fraction of the oligosaccharide preparation contains oligosaccharides containing anhydro subunits at a relative abundance of less than 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or 2%, and / or each fraction of the oligosaccharide preparation contains oligosaccharides containing anhydro subunits at a relative abundance of more than 0.2%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 30%, 40%, 50%, 60%, 70%, or 80%.

[0033]

[0033] Item 9. Oligosaccharide preparations are approximately 300-5000 g / mol, for example, approximately 2000-2800 g / mol, 2100-2700 g / mol, 2200-2600 g / mol, 2300-2500 g / mol, or 2320-2420 g / mol; 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1300 g / mol, 400-1200 g / mol, 400-1100 g / The use described in any one of the preceding items, wherein the oligosaccharide preparation has a weight-average molecular weight of moles, 500-1300 g / mol, 500-1200 g / mol, 500-1100 g / mol, 600-1300 g / mol, 600-1200 g / mol, or 600-1100 g / mol, and / or the oligosaccharide preparation has a number-average molecular weight of approximately 1000-2000 g / mol, 1100-1900 g / mol, 1200-1800 g / mol, 1300-1700 g / mol, 1400-1600 g / mol, or 1450-1550 g / mol.

[0034]

[0034] Item 10. The use described in any one of the preceding items, wherein the relative abundance of oligosaccharides in each of the n fractions of the oligosaccharide preparation decreases monotonically with the degree of polymerization.

[0035]

[0035] Item 11. The use according to any one of the preceding items, wherein the relative abundance of oligosaccharides in at least 5, 10, 20, or 30 DP fractions of the oligosaccharide preparation decreases monotonically with the degree of polymerization.

[0036]

[0036] Item 12. Use as described in any one of the preceding items, wherein the oligosaccharide preparation contains an anhydro subunit-containing oligosaccharide in relative amounts of 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2%.

[0037]

[0037] Item 13. The use described in any one of the preceding items, wherein each fraction of the oligosaccharide preparation contains, in relative abundance, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2% anhydro subunit-containing oligosaccharides.

[0038]

[0038] Item 14. Use according to any one of the preceding items, wherein at least one fraction of the oligosaccharide preparation contains, in relative abundance, more than 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 40%, 50%, 60%, 70%, or 80% anhydro subunit-containing oligosaccharide.

[0039]

[0039] Item 15. Use as described in any one of the preceding items, wherein the oligosaccharide preparation contains, in relative abundance, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or more than 25%, 30%, 40%, 50%, 60%, 70%, or 80% anhydro subunit-containing oligosaccharides.

[0040]

[0040] Item 16. The use according to any one of the preceding items, wherein each fraction of the oligosaccharide preparation contains, in relative abundance, more than 20%, 21%, 22%, 23%, 24%, or 25% anhydro subunit-containing oligosaccharide.

[0041]

[0041] Item 17. Use according to any one of the preceding items, wherein 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, or more than 30% of the anhydro subunit-containing oligosaccharides in the oligosaccharide preparation have only one anhydro subunit.

[0042]

[0042] Item 18. The use described in any one of the preceding items, wherein the oligosaccharide preparation has a DP1 fraction content of 1 to 40% in relative abundance.

[0043]

[0043] Item 19. The use of the oligosaccharide preparation having a DP2 fraction content of 1-35% in relative abundance, as described in any one of the preceding items.

[0044]

[0044] Item 20. The use of the oligosaccharide preparation having a relative abundance of 1-30% DP3 fraction as described in any one of the preceding items.

[0045]

[0045] Item 21. The use described in any one of the preceding items, wherein the oligosaccharide preparation has a DP4 fraction content of 0.1 to 20% in relative abundance.

[0046]

[0046] Item 22. The use described in any one of the preceding items, wherein the oligosaccharide preparation has a DP5 fraction content of 0.1 to 15% in relative abundance.

[0047]

[0047] Item 23. The ratio of the DP2 fraction to the DP1 fraction of the oligosaccharide preparation is 0.02 to 0.40 in terms of relative abundance, as described in any one of the preceding items.

[0048]

[0048] Item 24. The ratio of the DP3 fraction to the DP2 fraction of the oligosaccharide preparation is 0.01 to 0.30 in terms of relative abundance, as described in any one of the preceding items.

[0049]

[0049] Item 25. The use described in any one of the preceding items, wherein the total content of DP1 and DP2 fractions in the oligosaccharide preparation is less than 50, 30, or 10% in relative abundance.

[0050]

[0050] Item 26. Use according to any one of the preceding items, wherein the oligosaccharide preparation comprises at least 103, 104, 105, 106, or 109 different oligosaccharide species.

[0051]

[0051] Item 27. Use according to any one of the preceding items, wherein two or more independent oligosaccharides of the oligosaccharide preparation contain different anhydro subunits.

[0052]

[0052] Item 28. Use according to any one of the preceding items, wherein the oligosaccharide preparation comprises one or more anhydro subunits, which are reversible heat dehydration products of monosaccharides.

[0053]

[0053] Item 29. Use according to any one of the preceding items, wherein the oligosaccharide preparation comprises one or more anhydro-glucose, anhydro-galactose, anhydro-mannose, anhydro-allose, anhydro-altrose, anhydro-glucose, anhydro-indose, anhydro-talose, anhydro-fructose, anhydro-ribose, anhydro-arabinose, anhydro-rhamnose, anhydro-lyxose, or anhydro-xylose subunit.

[0054]

[0054] Item 30. Use as described in any one of the preceding items, wherein the oligosaccharide preparation comprises one or more anhydro-glucose, anhydro-galactose, anhydro-mannose, or anhydro-fructose subunits.

[0055]

[0055] Item 31. Use according to any one of the preceding items, wherein the oligosaccharide preparation comprises one or more 1,6-anhydro-β-D-glucofuranose subunits or 1,6-anhydro-β-D-glucopyranose subunits. In some embodiments, the oligosaccharide preparation comprises both 1,6-anhydro-β-D-glucofuranose anhydro subunits and 1,6-anhydro-β-D-glucopyranose anhydro subunits.

[0056]

[0056] Use as described in any one of the preceding items, item 32.1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose in the oligosaccharide preparation, wherein the ratio of 1,6-anhydro-β-D-glucopyranose to 1,6-anhydro-β-D-glucopyranose is approximately 10:1~1:10, 9:1~1:10, 8:1~1:10, 7:1~1:10, 6:1~1:10, 5:1~1:10, 4:1~1:10, 3:1~1:10, 2:1~1:10, 10:1~1:9, 10:1~1:8, 10:1~1:7, 10:1~1:6, 10:1~1:5, 10:1~1:4, 10:1~1:3, 10:1~1:2, or 1:1~3:1.

[0057]

[0057] Use according to any one of the preceding items, item 33.1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose, wherein the ratio of the oligosaccharide preparation is approximately 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:8, 1:9, or 1:10.

[0058]

[0058] The use described in any one of the preceding items, item 34.1, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose is approximately 2:1 in the oligosaccharide preparation.

[0059]

[0059] Use according to any one of the preceding items, item 35.1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose in each fraction of the oligosaccharide preparation, wherein the ratio is approximately 10:1 to 1:10, 9:1 to 1:10, 8:1 to 1:10, 7:1 to 1:10, 6:1 to 1:10, 5:1 to 1:10, 4:1 to 1:10, 3:1 to 1:10, 2:1 to 1:10, 10:1 to 1:9, 10:1 to 1:8, 10:1 to 1:7, 10:1 to 1:6, 10:1 to 1:5, 10:1 to 1:4, 10:1 to 1:3, 10:1 to 1:2, or 1:1 to 3:1.

[0060]

[0060] Use according to any one of the preceding items, item 36.1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose, wherein the ratio of 1,6-anhydro-β-D-glucopyranose in each fraction of the oligosaccharide preparation is approximately 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:8, 1:9, or 1:10.

[0061]

[0061] The use described in any one of the preceding items, item 37. The ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose is approximately 2:1 in each fraction of the oligosaccharide preparation.

[0062]

[0062] Item 38. Use according to any one of the preceding items, wherein at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the anhydro subunits in the oligosaccharide preparation are selected from the group consisting of 1,6-anhydro-β-D-glucofuranose and 1,6-anhydro-β-D-glucopyranose.

[0063]

[0063] Item 39. Use as described in any one of the preceding items, wherein the weight-average molecular weight of the oligosaccharide preparation is approximately 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1300 g / mol, 400-1200 g / mol, 400-1100 g / mol, 500-1300 g / mol, 500-1200 g / mol, 500-1100 g / mol, 600-1300 g / mol, 600-1200 g / mol, or 600-1100 g / mol.

[0064]

[0064] Item 40. Use as described in any one of the preceding items, wherein the number average molecular weight of the oligosaccharide preparation is approximately 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1000 g / mol, 400-900 g / mol, 400-800 g / mol, 500-900 g / mol, or 500-800 g / mol.

[0065]

[0065] Item 41. The degree of polymerization distribution is determined and / or detected by MALDI-MS, GC-MS, LC-MS, SEC, HPLC, and / or a combination thereof (e.g., MALDI-MS and SEC), as described in any one of the preceding items.

[0066]

[0066] Item 42. The degree of polymerization of the oligosaccharide preparation may be determined based on its molecular weight and molecular weight distribution, as described in any one of the preceding items.

[0067]

[0067] Item 43. Use as described in any one of the preceding items, wherein the oligosaccharide preparation is included in the nutritional composition at a concentration of at least 50 g per ton of feed (for example, at least 70 g, 100 g, 200 g, 300 g, 400 g, 500 g, 600 g, 700 g, 800 g, 900 g per ton of feed), and / or the oligosaccharide preparation is included in the nutritional composition at a content of at least 50 ppm (for example, at least 50, 70, 100, 150, 200, 300, 400, 500 ppm), and / or the oligosaccharide preparation is included in the nutritional composition at a concentration of at least 50 ppm (for example, at least 50, 70, 100, 150, 200, 300, 400, 500 ppm).

[0068]

[0068] Item 44. The oligosaccharide preparation is preferably subjected to at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73 ,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,1 41, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 2 The use described in any one of the preceding items, supplied over a period of 2, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, or 245 days, most preferably the nutritional composition is supplied continuously, i.e., without interruption.

[0069]

[0069] Item 44. The use according to any one of the preceding items, wherein the average DP of the oligosaccharide preparation is at least 2, or at least 3, or at least 4.

[0070]

[0070] Item 44. Use as described in any one of the preceding items, wherein the average DP of the oligosaccharide preparation is less than 5.0.

[0071]

[0071] Item 44. The use according to any one of the preceding items, wherein the average DP of the oligosaccharide preparation is 2 or greater, for example, at least 3 or at least 4, and / or the average DP of the oligosaccharide preparation is less than 5.0.

[0072]

[0072] Item 44. The use of the oligosaccharide preparation as described in any one of the preceding items, where the average DP is determined based on its number-average molecular weight distribution.

[0073]

[0073] Item 45. Oligosaccharide preparations for use in a manner to treat, induce remission, prevent and / or delay respiratory diseases, preferably infectious bronchitis (particularly infectious bronchitis caused by IBV), and / or their effects (i.e., the effects of the respiratory disease, or the effects caused thereby, or the effects related thereto), wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry.

[0074]

[0074] Item 46. Oligosaccharide preparations for use in a manner to treat, alleviate, prevent and / or delay the respiratory disease, preferably infectious bronchitis (particularly infectious bronchitis caused by IBV), and / or its effects (i.e., the effects of the respiratory disease, or effects caused thereby, or effects related thereto) in animals (preferably poultry, more preferably chickens) that have a respiratory disease and / or are at risk of having the respiratory disease, wherein the oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of anhydro subunit-containing oligosaccharides in relative abundance determined by mass spectrometry.

[0075]

[0075] Item 47. Oligosaccharide preparations for use as described in Item 45 or 46, administered in addition to vaccination against respiratory diseases.

[0076]

[0076] Item 48. An oligosaccharide preparation for use as described in any one of items 45 to 47, wherein the oligosaccharide preparation is included in a nutritional composition at a concentration exceeding 40 ppm (for example, 40 ppm, 50 ppm, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200 ppm, etc.).

[0077]

[0077] Item 49. n of the oligosaccharide preparation is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, Oligosaccharide preparations for use as described in any one of items 45 to 48, wherein the amount is 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100.

[0078]

[0078] Item 50. At least one fraction of the oligosaccharide preparation contains an anhydro subunit-containing oligosaccharide in relative abundance of 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2%, and / or each fraction of the oligosaccharide preparation is Oligosaccharide preparations for use as described in any one of items 45 to 49, comprising, in relative abundance, 0.2%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 30%, 40%, 50%, 60%, 70%, or more than 80% anhydro subunit-containing oligosaccharides.

[0079]

[0079] Item 51. Oligosaccharide preparations are approximately 300-5000 g / mol, for example, approximately 2000-2800 g / mol, 2100-2700 g / mol, 2200-2600 g / mol, 2300-2500 g / mol, or 2320-2420 g / mol; 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1300 g / mol, 400-1200 g / mol, 400-1100 g / mol, 5 Oligosaccharide preparations for use as described in any one of items 45 to 50, having a weight-average molecular weight of 00-1300 g / mol, 500-1200 g / mol, 500-1100 g / mol, 600-1300 g / mol, 600-1200 g / mol, or 600-1100 g / mol, and / or having a number-average molecular weight of approximately 1000-2000 g / mol, 1100-1900 g / mol, 1200-1800 g / mol, 1300-1700 g / mol, 1400-1600 g / mol, or 1450-1550 g / mol.

[0080]

[0080] Item 52. An oligosaccharide preparation for use according to any one of items 45 to 51, wherein the relative abundance of oligosaccharide in each of the n fractions of the oligosaccharide preparation decreases monotonically with the degree of polymerization.

[0081]

[0081] Item 53. An oligosaccharide preparation for use according to any one of items 45 to 52, wherein the relative abundance of oligosaccharides in at least 5, 10, 20, or 30 DP fractions of the oligosaccharide preparation decreases monotonically with the degree of polymerization.

[0082]

[0082] Item 54. Oligosaccharide preparations for use as described in any one of items 45 to 53, comprising an anhydro subunit-containing oligosaccharide in relative abundance of 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2%.

[0083]

[0083] Item 55. Oligosaccharide preparations for use according to any one of items 45 to 54, wherein each fraction of the oligosaccharide preparation contains, in relative abundance, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2% anhydro subunit-containing oligosaccharides.

[0084]

[0084] Item 56. An oligosaccharide preparation for use according to any one of items 45 to 55, wherein at least one fraction of the oligosaccharide preparation contains, in relative abundance, more than 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 30%, 40%, 50%, 60%, 70%, or 80% anhydro subunit-containing oligosaccharide.

[0085]

[0085] Item 57. Oligosaccharide preparations for use as described in any one of items 45 to 56, comprising, in relative abundance, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or more than 25%, 30%, 40%, 50%, 60%, 70%, or 80% of anhydro subunit-containing oligosaccharides.

[0086]

[0086] Item 58. An oligosaccharide preparation for use according to any one of items 45 to 57, wherein each fraction of the oligosaccharide preparation contains, in relative abundance, more than 20%, 21%, 22%, 23%, 24%, or 25% anhydro subunit-containing oligosaccharide.

[0087]

[0087] Item 59. Oligosaccharide preparations for use according to any one of items 45 to 58, wherein 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, or more than 30% of the anhydro subunit-containing oligosaccharides of the oligosaccharide preparation have only one anhydro subunit.

[0088]

[0088] Item 60. An oligosaccharide preparation for use according to any one of items 45 to 59, having a DP1 fraction content of 1 to 40% in relative abundance.

[0089]

[0089] Item 61. An oligosaccharide preparation for use according to any one of items 45 to 60, having a DP2 fraction content of 1 to 35% in relative abundance.

[0090]

[0090] Item 62. An oligosaccharide preparation for use according to any one of items 45 to 61, having a DP3 fraction content of 1 to 30% in relative abundance.

[0091]

[0091] Item 63. An oligosaccharide preparation for use according to any one of items 45 to 62, having a DP4 fraction content of 0.1 to 20% in relative abundance.

[0092]

[0092] Item 64. An oligosaccharide preparation for use according to any one of items 45 to 63, having a DP5 fraction content of 0.1 to 15% in relative abundance.

[0093]

[0093] Item 65. An oligosaccharide preparation for use according to any one of items 45 to 64, wherein the ratio of the DP2 fraction to the DP1 fraction of the oligosaccharide preparation is 0.02 to 0.40 in relative abundance.

[0094]

[0094] Item 66. An oligosaccharide preparation for use according to any one of items 45 to 65, wherein the ratio of the DP3 fraction to the DP2 fraction of the oligosaccharide preparation is 0.01 to 0.30 in relative abundance.

[0095]

[0095] Item 67. An oligosaccharide preparation for use according to any one of items 45 to 66, wherein the total content of DP1 and DP2 fractions in the oligosaccharide preparation is less than 50, 30, or 10% in relative abundance.

[0096]

[0096] Item 68. Oligosaccharide preparation for use as described in any one of items 45 to 67, comprising at least 103, 104, 105, 106, or 109 different oligosaccharide species.

[0097]

[0097] Item 69. An oligosaccharide preparation for use according to any one of items 45 to 68, wherein two or more independent oligosaccharides of the oligosaccharide preparation contain different anhydro subunits.

[0098]

[0098] Item 70. Oligosaccharide preparation for use according to any one of items 45 to 69, comprising one or more anhydro subunits which are reversible heat dehydration products of monosaccharides.

[0099]

[0099] Item 71. Oligosaccharide preparation for use as described in any one of items 45 to 70, comprising one or more anhydro-glucose, anhydro-galactose, anhydro-mannose, anhydro-allose, anhydro-altrose, anhydro-glucose, anhydro-indose, anhydro-talose, anhydro-fructose, anhydro-ribose, anhydro-arabinose, anhydro-rhamnose, anhydro-lyxose, or anhydro-xylose subunit.

[0100]

[0100] Item 72. Oligosaccharide preparations for use as described in any one of items 45 to 71, comprising one or more anhydro-glucose, anhydro-galactose, anhydro-mannose, or anhydro-fructose subunits.

[0101]

[0101] Item 73. An oligosaccharide preparation for use according to any one of items 45 to 72, comprising one or more 1,6-anhydro-β-D-glucofuranose subunits or 1,6-anhydro-β-D-glucopyranose subunits. In some embodiments, the oligosaccharide preparation comprises both 1,6-anhydro-β-D-glucofuranose anhydro subunits and 1,6-anhydro-β-D-glucopyranose anhydro subunits.

[0102]

[0102] Oligosaccharide preparations for use as described in any one of items 45 to 73, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose in the oligosaccharide preparation is approximately 10:1 to 1:10, 9:1 to 1:10, 8:1 to 1:10, 7:1 to 1:10, 6:1 to 1:10, 5:1 to 1:10, 4:1 to 1:10, 3:1 to 1:10, 2:1 to 1:10, 10:1 to 1:9, 10:1 to 1:8, 10:1 to 1:7, 10:1 to 1:6, 10:1 to 1:5, 10:1 to 1:4, 10:1 to 1:3, 10:1 to 1:2, or 1:1 to 3:1.

[0103]

[0103] Oligosaccharide preparations for use as described in any one of items 45 to 74, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose in the oligosaccharide preparation is approximately 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:8, 1:9, or 1:10.

[0104]

[0104] Oligosaccharide preparation for use as described in any one of items 45 to 75, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose is approximately 2:1 in the oligosaccharide preparation.

[0105]

[0105] An oligosaccharide preparation for use as described in any one of items 45 to 76, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose in each fraction of the oligosaccharide preparation is approximately 10:1 to 1:10, 9:1 to 1:10, 8:1 to 1:10, 7:1 to 1:10, 6:1 to 1:10, 5:1 to 1:10, 4:1 to 1:10, 3:1 to 1:10, 2:1 to 1:10, 10:1 to 1:9, 10:1 to 1:8, 10:1 to 1:7, 10:1 to 1:6, 10:1 to 1:5, 10:1 to 1:4, 10:1 to 1:3, 10:1 to 1:2, or 1:1 to 3:1.

[0106]

[0106] Oligosaccharide preparations for use according to any one of items 45 to 77, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose in each fraction of the oligosaccharide preparation is approximately 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:8, 1:9, or 1:10.

[0107]

[0107] Oligosaccharide preparation for use as described in any one of items 45 to 78, wherein the ratio of 1,6-anhydro-β-D-glucofuranose to 1,6-anhydro-β-D-glucopyranose is approximately 2:1 in each fraction of the oligosaccharide preparation.

[0108]

[0108] Item 80. An oligosaccharide preparation for use according to any one of items 45 to 79, wherein at least 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the anhydro subunits in the oligosaccharide preparation are selected from the group consisting of 1,6-anhydro-β-D-glucofuranose and 1,6-anhydro-β-D-glucopyranose.

[0109]

[0109] Item 81. Oligosaccharide preparations for use as described in any one of items 45 to 80, wherein the weight-average molecular weight of the oligosaccharide preparation is approximately 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1300 g / mol, 400-1200 g / mol, 400-1100 g / mol, 500-1300 g / mol, 500-1200 g / mol, 500-1100 g / mol, 600-1300 g / mol, 600-1200 g / mol, or 600-1100 g / mol.

[0110]

[0110] Item 82. Oligosaccharide preparations for use as described in any one of items 45 to 81, wherein the number average molecular weight of the oligosaccharide preparation is approximately 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1000 g / mol, 400-900 g / mol, 400-800 g / mol, 500-900 g / mol, or 500-800 g / mol.

[0111]

[0111] Item 83. The degree of polymerization distribution is determined and / or detected by MALDI-MS, GC-MS, LC-MS, SEC, HPLC, and / or a combination thereof (e.g., MALDI-MS and SEC) for the oligosaccharide preparations for use as described in any one of items 45 to 82.

[0112]

[0112] Item 84. Oligosaccharide preparations for use as described in any one of items 45 to 83, the degree of polymerization of the oligosaccharide preparation may be determined based on its molecular weight and molecular weight distribution.

[0113]

[0113] Item 85. Oligosaccharide preparations for use as described in any one of items 45 to 84, wherein the oligosaccharide preparation is included in a nutritional composition at a concentration of at least 50 g per ton of feed (e.g., at least 70 g, 100 g, 200 g, 300 g, 400 g, 500 g, 600 g, 700 g, 800 g, 900 g per ton of feed), and / or the oligosaccharide preparation is included in a nutritional composition at a content of at least 50 ppm (e.g., at least 50, 70, 100, 150, 200, 300, 400, 500 ppm), and / or the oligosaccharide preparation is included in a nutritional composition at a concentration of at least 50 ppm (e.g., at least 50, 70, 100, 150, 200, 300, 400, 500 ppm).

[0114]

[0114] Item 86. The oligosaccharide preparation is preferably subjected to at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 7 4, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 11 1, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 14 2, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 1 73, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 2 An oligosaccharide preparation for use as described in any one of items 45 to 85, supplied over a period of 4, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, or 245 days, most preferably the nutritional composition is supplied continuously, i.e., without interruption.

[0115]

[0115] Item 87. An oligosaccharide preparation for use according to any one of items 45 to 86, wherein the average DP of the oligosaccharide preparation is at least 2, or at least 3, or at least 4.

[0116]

[0116] Item 88. An oligosaccharide preparation for use as described in any one of items 45 to 87, wherein the average DP of the oligosaccharide preparation is less than 5.0.

[0117]

[0117] Item 89. An oligosaccharide preparation for use according to any one of items 45 to 88, wherein the average DP of the oligosaccharide preparation is 2 or greater, for example, at least 3 or at least 4, and / or the average DP of the oligosaccharide preparation is less than 5.0.

[0118]

[0118] Item 90. The average DP of an oligosaccharide preparation is determined based on its number-average molecular weight distribution, as described in any one of items 45 to 89 for use.

[0119]

[0119] The oligosaccharide preparations of the present invention may also be provided in the form of a powder formulation comprising at least 20% (w / w) of the oligosaccharide preparations referred to herein; at least 25% (weight / weight) of a silica-based adsorbent having an average particle size D of 3000 μm or less (e.g., 100-500, 200-500, 200-300 μm, etc.) (e.g., diatomaceous earth, amorphous precipitated silica); and optionally 0-25% (weight / weight) of water and / or auxiliary agents, where % is based on the total weight of the powder formulation. For example, such a powder formulation may contain 30-70% (weight / weight) of the oligosaccharide preparations referred to herein; 30-70% (weight / weight) of a silica-based adsorbent (e.g., having an average particle size of at least 50 μm); and 0-21% (weight / weight) of water, where % is based on the total weight of the powder formulation. In some embodiments, the oligosaccharide preparation is formulated as described in any one of Examples 22-26 and 33 of International Publication No. 2020 / 097458.

[0120]

[0120] The method for producing the oligosaccharide preparation of the present invention is described in International Publication No. 2020 / 097458, International Publication No. 2016 / 007778, in particular the examples described therein, in particular any one of Examples 1-7 and 16-18 of International Publication No. 2020 / 097458A1, paragraph

[0317] of International Publication No. 2016 / 007778A1, and / or any one of Examples 73-77, 80-89, 97-99, and 101-110, and preferably the oligosaccharide preparation of the present invention is produced as described in Example 16 of International Publication No. 2020 / 097458A1. Specifically, the oligosaccharide preparation of the present invention is characterized by the step of heating an aqueous composition comprising one or more feed sugars and a catalyst to a temperature and time sufficient to induce polymerization. In some embodiments, the supplied sugars are glucose, mannose, galactose, lactose, fructose, sucrose, xylose, arabinose, glucosamine, N-acetylglucosamine, N-acetylgalactosamine, glucuronic acid, galacturonic acid, fucose, rhamnose, quinobose, or any combination thereof; glucose and mannose, glucose and galactose, glucose and lactose, glucose and fructose, glucose and arabinose, glucose and sucrose, glucose and xylose, glucose and galactose and arabinose, etc.In some embodiments, the catalyst is (+)-camphor-10-sulfonic acid; 2-pyridinesulfonic acid; 3-pyridinesulfonic acid; 8-hydroxy-5-quinoline sulfonic acid hydrate; α-hydroxy-2-pyridinemethanesulfonic acid; (β)-camphor-10-sulfonic acid; butylphosphonic acid; diphenylphosphinic acid; hexylphosphonic acid; methylphosphonic acid; phenylphosphinic acid; phenylphosphonic acid; tert-butylphosphonic acid; SS)-VAPOL hydrogen phosphate; 6-quino Phosphatesulfonic acid, 3-(1-pyridinio)-1-propanesulfonate; 2-(2-pyridinyl)ethanesulfonic acid; 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine-p,p'-disulfonic acid monosodium salt hydrate; 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate; bis(4-methoxyphenyl)phosphinic acid; phenyl(3,5-xylyl)phosphinic acid; L-cysteic acid monohydrate; poly(styrenesulfonic acid-co-divinylbenzene); lysine Ethane disulfonic acid; ethanesulfonic acid; isethionic acid; homocysteic acid; HEPBS (N-(2-hydroxyethyl)piperazine-N'-(4-butanesulfonic acid)); HEPES (4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid); 2-hydroxy-3-morpholinopropanesulfonic acid; 2-(N-morpholino)ethanesulfonic acid; methanesulfonic acid; metaniazide; naphthalene-1-sulfonic acid; naphthalene-2-sulfonic acid; perfluorobutanesulfonic acid The catalyst is any one of the following: nic acid; 6-sulfoquinovose; triflic acid; 2-aminoethanesulfonic acid; benzoic acid; chloroacetic acid; trifluoroacetic acid; caproic acid; enanthic acid; caprylic acid; pelargonic acid; lauric acid; palmitic acid; stearic acid; arachidic acid; aspartic acid; glutamic acid; serine; threonine; glutamine; cysteine; glycine; proline; alanine; valine; isoleucine; leucine; methionine; phenylalanine; tyrosine; or tryptophan. In some embodiments, the supply sugar is glucose, and the catalyst is (+)-camphor-10-sulfonic acid, (β)-camphor-10-sulfonic acid, butylphosphonic acid, HEPBS, naphthalene-1-sulfonic acid, naphthalene-2-sulfonic acid, or palmitic acid.In some embodiments, the supply sugars are glucose and mannose, and the catalyst is ethanedisulfonic acid, ethanesulfonic acid, trifluic acid, or lauric acid. In some embodiments, the supply sugar is galactose, and the catalyst is 2-(N-morpholino)ethanesulfonic acid, methanesulfonic acid, or metaniazide.

[0121]

[0121] For the sake of clarity, the term “oligosaccharide preparation” may refer to a preparation containing one or more oligosaccharides.

[0122]

[0122] As used herein, “oligosaccharide” or “oligomer” may refer to a compound containing a monosaccharide unit, or two or more monosaccharide subunits linked by glycosidic bonds to form an oligosaccharide. “Oligosaccharide” may also refer to a compound containing an anhydro monosaccharide unit, or two or more monosaccharide subunits in which at least one monosaccharide unit is substituted by an anhydro subunit. “Oligosaccharide” may be functionalized optionally. As used herein, the term “oligosaccharide” encompasses all species of oligosaccharides, where each monosaccharide subunit in the oligosaccharide is independently and optionally functionalized and / or substituted with its corresponding anhydro monosaccharide subunit.

[0123]

[0123] An anhydro subunit may be a reversible heat dehydration product of a monosaccharide or monosaccharide subunit, or a sugar caramelization product. For example, an anhydro subunit may be an anhydro monosaccharide such as anhydro glucose. As another example, an anhydro subunit may be linked to one or more ordinary monosaccharide subunits and / or one or more anhydro monosaccharide subunits via glycosidic linkages.

[0124]

[0124] Oligosaccharides may be characterized by containing two or more monosaccharide subunits linked by glycosidic bonds. In this regard, "gluco-oligosaccharide" may refer to a single glucose molecule or a compound containing two or more glucose monosaccharide subunits linked by glycosidic bonds. "Gluco-oligosaccharide" may also refer to a compound containing anhydro-glucose or two or more glucose monosaccharide subunits linked by glycosidic bonds in which at least one monosaccharide subunit is substituted by an anhydro-glucose subunit. Similarly, "galacto-oligosaccharide" may refer to a compound containing galactose or two or more galactose monosaccharide subunits linked by glycosidic bonds. "Galacto-oligosaccharide" may also refer to a compound containing anhydro-galactose or two or more galactose monosaccharide subunits linked by glycosidic bonds in which at least one monosaccharide subunit is substituted by an anhydro-galactose subunit. Similarly, a gluco-galactose oligosaccharide may be a compound containing one or more glucose monosaccharide subunits and one or more galactose monosaccharide subunits linked by glycosidic bonds. A gluco-galactose oligosaccharide may also refer to a compound in which at least one of the monosaccharide subunits is substituted with its respective anhydro monosaccharide subunit. A gluco-galactoxyl oligosaccharide may refer to a compound produced by the condensation reaction of glucose, galactose, and xylose. Oligosaccharide preparations containing gluco-galactose oligosaccharides may include gluco-galactose oligosaccharides, gluco-xyl oligosaccharides, galactoxyl oligosaccharides, gluco-galactoxyl oligosaccharides, and compounds containing one or more glucose monosaccharide subunits, one or more xylose monosaccharide subunits, and one or more galactose monosaccharide subunits linked by glycosidic bonds, as well as their anhydro monosaccharide subunits.

[0125]

[0125] As used herein, the terms “monosaccharide unit” and “monosaccharide subunit” may be used interchangeably unless otherwise specified. A “monosaccharide subunit” may refer to a monosaccharide monomer of an oligosaccharide. In the case of an oligosaccharide having a degree of polymerization (DP) of 1, the oligosaccharide may be referred to as a monosaccharide subunit or monosaccharide. In the case of an oligosaccharide having a degree of polymerization of 2 or more, its monosaccharide subunits are linked via glycosidic bonds.

[0126]

[0126] As used herein, the term "ordinary monosaccharide" may refer to a monosaccharide that does not contain an anhydro subunit. The term "ordinary disaccharide" may refer to a disaccharide that does not contain an anhydro subunit. Therefore, the term "ordinary subunit" may refer to a subunit that is not an anhydro subunit.

[0127]

[0127] The terms “relative abundance” or “abundance,” as used herein, may refer to the abundance of a species based on how common or rare the species is. For example, a DP1 fraction containing 10% anhydro subunit-containing oligosaccharides in relative abundance (i.e., a fraction having 1 DP) may refer to multiple DP1 oligosaccharides in which 10% are anhydro monosaccharides based on the number of DP1 oligosaccharides.

[0128] [Polymerization degree (DP) distribution]

[0128] The degree of polymerization distribution of oligosaccharide preparations can be determined by any suitable analytical method and instrument, including but not limited to end-group method, osmotic pressure (osmotic measurement), ultracentrifugation, viscosity measurement, light scattering method, size exclusion chromatography (SEC), SEC-MALLS, field flow fractionation (FFF), asymmetric flow field flow fractionation (A4F), high-performance liquid chromatography (HPLC), and mass spectrometry (MS). For example, the degree of polymerization distribution can be determined and / or detected by mass spectrometry such as MALDI-MS, LC-MS, or GC-MS. As another example, the degree of polymerization distribution can be determined and / or detected by SEC such as gel permeation chromatography (GPC). As yet another example, the degree of polymerization distribution can be determined and / or detected by HPLC, FFF, or A4F. As yet another example, the degree of polymerization of an oligosaccharide preparation can be determined based on its molecular weight and molecular weight distribution (see International Publication No. 2020 / 097458 for further details).

[0129] [Anhydrous subunit concentration]

[0129] The oligosaccharide preparation may contain n distinct fractions, each fraction having a distinct DP, where n is any integer, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc. In some embodiments, each of the n fractions of oligosaccharide in the oligosaccharide preparation described herein independently contains an anhydro subunit concentration. For example, in some embodiments, fraction DP1 contains 10% anhydro subunit-containing oligosaccharide in relative abundance, and fraction DP2 contains 15% anhydro subunit-containing oligosaccharide in relative abundance. In another example, in some embodiments, fractions DP1, DP2, and DP3 each contain 5%, 10%, and 2% anhydro subunit-containing oligosaccharide in relative abundance, respectively. In other embodiments, two or more fractions of oligosaccharide may contain the same concentration of anhydro subunit-containing oligosaccharide. For example, in some embodiments, the DP1 and DP3 fractions each contain approximately 5% of an anhydro subunit-containing oligosaccharide in relative abundance.

[0130]

[0130] The concentration of the anhydro subunit can be determined by any preferred analytical method such as nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, HPLC, FFF, A4F, or any combination thereof. In some embodiments, the concentration of the anhydro subunit is determined at least in part by mass spectrometry such as MALDI-MS. In some embodiments, the concentration of the anhydro subunit can be determined at least in part by NMR. In some embodiments, the concentration of the anhydro subunit can be determined at least in part by HPLC. For example, in some embodiments, the concentration of the anhydro subunit can be determined by MALDI-MS, as illustrated in more detail in International Publication No. 2020 / 097458.

[0131] [Glycoside linkage]

[0131] In some embodiments, the oligosaccharide preparations described herein include various glycosidic linkages. The type and distribution of glycosidic linkages may depend on the source and method of preparation of the oligosaccharide preparation. In some embodiments, the type and distribution of various glycosidic linkages may be determined and / or detected by any suitable method known in the art, such as NMR. For example, in some embodiments, glycosidic linkages are determined and / or detected by proton NMR, carbon NMR, 2D NMR, e.g., 2D JRES, HSQC, HMBC, DOSY, COSY, ECOSY, TOCSY, NOESY, or ROESY, or any combination thereof. In some embodiments, glycosidic linkages are determined and / or detected at least partially by proton NMR. In some embodiments, glycosidic linkages are determined and / or detected at least partially by carbon NMR. In some embodiments, glycosidic linkages are determined and / or detected at least partially by 2D HSQC NMR.

[0132]

[0132] In some embodiments, the oligosaccharide preparation may include one or more α-(1,2) glycoside linkages, α-(1,3) glycoside linkages, α-(1,4) glycoside linkages, α-(1,6) glycoside linkages, β-(1,2) glycoside linkages, β-(1,3) glycoside linkages, β-(1,4) glycoside linkages, β-(1,6) glycoside linkages, α-(1,1)-α glycoside linkages, α-(1,1)-β glycoside linkages, β-(1,1)-β glycoside linkages, or any combination thereof.

[0133]

[0133] In some embodiments, the oligosaccharide preparation is approximately 0-60 mol%, 5-55 mol%, 5-50 mol%, 5-45 mol%, 5-40 mol%, 5-35 mol%, 5-30 mol%, 5-25 mol%, 10-60 mol%, 10-55 mol%, 10-50 mol%, 10-45 mol%, 10-40 mol%, 10-35 mol%, 15-60 mol%, 15-55 mol%, 15-50 mol, It has a glycosidic bond distribution of α-(1,6) glycoside links in the following proportions: 15-45 mol%, 15-40 mol%, 15-35 mol%, 20-60 mol%, 20-55 mol%, 20-50 mol%, 20-45 mol%, 20-40 mol%, 20-35 mol%, 25-60 mol%, 25-55 mol%, 25-50 mol%, 25-45 mol%, 25-40 mol%, or 25-35 mol%.

[0134] [Molecular weight]

[0134] The molecular weight and molecular weight distribution of the oligosaccharide preparation can be determined by any suitable analytical means and instruments, such as end-group method, osmotic pressure (osmotic measurement), ultracentrifugation, viscosity measurement, light scattering method, SEC, SEC-MALLS, FFF, A4F, HPLC, and mass spectrometry. In some embodiments, the molecular weight and molecular weight distribution are determined by mass spectrometry, such as MALDI-MS, LC-MS, or GC-MS. In some embodiments, the molecular weight and molecular weight distribution are determined by size exclusion chromatography (SEC), such as gel permeation chromatography (GPC). In other embodiments, the molecular weight and molecular weight distribution are determined by HPLC. In some embodiments, the molecular weight and molecular weight distribution are determined by MALDI-MS.

[0135]

[0135] In some embodiments, the weight-average molecular weight of the oligosaccharide preparation is approximately 100-10000 g / mol, 200-8000 g / mol, 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 900-5000 g / mol, 1100-5000 g / mol, 1300-5000 g / mol, 1500-5000 g / mol, 1700-5000 g / mol, 300-4500 g / mol, 500-4500 g / mol, 700-4500 g / mol, 900-4 500g / mol, 1100-4500g / mol, 1300-4500g / mol, 1500-4500g / mol, 1700-4500g / mol, 1900-4500g / mol, 300-4000g / mol, 500-4000g / mol, 700-4000g / mol, 900-4000g / mol, 1100-4000g / mol, 1300-4000g / mol, 1500-4000g / mol, 1700-4000g / mol, 1900-4000g / mol, 300-3000g / mol, 500-3000g / mol, 700-3000g / mol, 900-3000g / mol, 1100-3000g / mol, 1300-3000g / mol, 1500-3000g / mol, 1700-3000g / mol, 1900-3000g / mol, 2100-3000g / mol, 300-2500g / mol, 500-2500g / mol, 700-2500g / mol, 900-2500g / mol, 1100-2500g / mol, 1300-2500g / mol, 15 The ranges are 0-2500 g / mol, 1700-2500 g / mol, 1900-2500 g / mol, 2100-2500 g / mol, 300-1500 g / mol, 500-1500 g / mol, 700-1500 g / mol, 900-1500 g / mol, 1100-1500 g / mol, 1300-1500 g / mol, 2000-2800 g / mol, 2100-2700 g / mol, 2200-2600 g / mol, 2300-2500 g / mol, or 2320-2420 g / mol. In some embodiments, the weight-average molecular weight of the oligosaccharide preparation is approximately 2000-2800 g / mol, 2100-2700 g / mol, 2200-2600 g / mol, 2300-2500 g / mol, or 2320-2420 g / mol.

[0136] [Types of Oligosaccharides]

[0136] In some embodiments, the species of oligosaccharides present in the oligosaccharide preparations referenced herein may depend on one or more types of supply sugars. For example, in some embodiments, if the supply sugar contains glucose, the oligosaccharide preparation contains gluco-oligosaccharides. For example, in some embodiments, if the supply sugar contains galactose, the oligosaccharide preparation contains galacto-oligosaccharides. In another example, in some embodiments, if the supply sugar contains galactose and glucose, the oligosaccharide preparation contains gluco-galacto-oligosaccharides.

[0137]

[0137] In some embodiments, the oligosaccharide preparation comprises one or more types of monosaccharide subunits. In some embodiments, the oligosaccharide preparation may comprise oligosaccharides having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more different types of monosaccharide subunits.

[0138] [Method for producing oligosaccharide preparations]

[0138] A method for producing the oligosaccharide preparation of the present invention is described in detail in International Publication No. 2020 / 097458, the method comprising heating an aqueous composition containing one or more feed sugars and a catalyst to a temperature and time sufficient to induce polymerization, wherein the catalyst is (+)-camphor-10-sulfonic acid; 2-pyridinesulfonic acid; 3-pyridinesulfonic acid; 8-hydroxy-5-quinoline sulfonic acid hydrate; α-hydroxy-2-pyridinemethanesulfonic acid; (β)-camphor -10-Sulfonic acid; Butylphosphonic acid; Diphenylphosphinic acid; Hexylphosphonic acid; Methylphosphonic acid; Phenylphosphinic acid; Phenylphosphonic acid; Tert-butylphosphonic acid; SS)-VAPOL hydrogen phosphate; 6-Quinoline sulfonic acid, 3-(1-pyridinio)-1-propanesulfonate; 2-(2-pyridinyl)ethanesulfonic acid; 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine-p,p'-disulfonic acid monosodium salt hydrate; 1 ,1'-Binaphthyl-2,2'-Diyl Hydrogen Phosphate; Bis(4-Methoxyphenyl)phosphinic Acid; Phenyl(3,5-Xylyl)phosphinic Acid; L-Cysteic Acid Monohydrate; Poly(Styrene Sulfonic Acid-Co-Divinylbenzene); Lysine; Ethane Disulfonic Acid; Ethane Sulfonic Acid; Isethionic Acid; Homocysteic Acid; HEPBS (N-(2-Hydroxyethyl)piperazine-N'-(4-Butane Sulfonic Acid)); HEPES (4-(2-Hydroxyethyl)-1-Pipe Selected from the group consisting of: radinethanesulfonic acid; 2-hydroxy-3-morpholinopropanesulfonic acid; 2-(N-morpholino)ethanesulfonic acid; methanesulfonic acid; metaniazide; naphthalene-1-sulfonic acid; naphthalene-2-sulfonic acid; perfluorobutanesulfonic acid; 6-sulfoquinovose; trifric acid; 2-aminoethanesulfonic acid; benzoic acid; chloroacetic acid; trifluoroacetic acid; caproic acid; enanthic acid; caprylic acid; pelargonic acid; lauric acid; pamitic acid; stearic acid; arachidic acid; aspartic acid; glutamic acid; serine; threonine; glutamine; cysteine; glycine; proline; alanine; valine; isoleucine; leucine; methionine; phenylalanine; tyrosine; and tryptophan.

[0139]

[0139] In some embodiments, polymerization of the supply sugar is achieved by step growth polymerization. In some embodiments, polymerization of the supply sugar is achieved by polycondensation.

[0140] [Sugar supplied]

[0140] One or more feed sugars used in the method for producing the oligosaccharide preparations described herein may comprise one or more types of sugars. In some embodiments, one or more feed sugars comprise monosaccharides, disaccharides, trisaccharides, tetrasaccharides, or any mixture thereof.

[0141]

[0141] In some embodiments, one or more supply sugars include glucose. In some embodiments, one or more supply sugars include glucose and galactose. In some embodiments, one or more supply sugars include glucose, xylose, and galactose. In some embodiments, one or more supply sugars include glucose and mannose. In some embodiments, one or more supply sugars include glucose and fructose. In some embodiments, one or more supply sugars include glucose, fructose, and galactose. In some embodiments, one or more supply sugars include glucose, galactose, and mannose.

[0142]

[0142] As used herein, the singular forms “one,” “and,” and “it” include plural references unless the context specifically indicates otherwise. Thus, for example, “drugs” includes multiple such drugs, and “oligosaccharides” includes one or more oligosaccharides (or more oligosaccharides) and their equivalents known to those skilled in the art.

[0143]

[0143] When ranges are used herein for physical properties such as molecular weight or chemical properties such as chemical formulas, it is intended that all combinations and partial combinations of ranges, as well as specific embodiments thereof, be included. When the term “approximately” is used with respect to a numerical value or numerical range, it means that the referenced numerical value or numerical range is an approximation within experimental variation (or statistical experimental error), and therefore, in some cases, the numerical value or numerical range may vary by 1% to 15% of the stated numerical value or numerical range.

[0144]

[0144] The present invention will be described in more detail below by non-limiting embodiments.

[0145] [Examples]

[0145] The present invention disclosed herein is not limited to any specific embodiments, figures, methodologies, examples, protocols, etc. described herein, but is limited only by the claims.

[0146] [Example 1]

[0146] For the broiler feeding trial, 32,600 male Ross 308-day-old broilers were fed either a control diet or a test diet. 10,800 broilers were given the control diet and 21,800 broilers were given the test diet. The control diet was a broiler basal diet (corn, soybean meal). The test diet contained 0.9 kg / MT of the oligosaccharide preparation described herein in addition to the basal diet. Specifically, the oligosaccharide preparation contained more than two DP fractions and had an average DP of less than 5, as determined based on its number-average molecular weight distribution. Each DP fraction of the oligosaccharide preparation contained approximately 0.5% to 15% anhydro subunit-containing oligosaccharides in relative abundance as determined by mass spectrometry. Feeding was carried out according to general recommendations for the breed; no antibiotics, growth promoters, or ionophores were present in the feed.

[0147]

[0147] All birds were vaccinated against Newcastle disease, infectious bronchitis, NB, and IBQX. Feed and water were provided freely. Starter (days 0-10) crumble, grower (days 11-22) pellets, finisher (days 23-35) pellets. The total trial period was 38 days.

[0148]

[0148] Despite vaccination, IBV infected birds and caused an outbreak on day 20 in birds fed the control diet. Surprisingly, in birds fed the test diet, the disease developed on day 29. Furthermore, FCR and weight gain were significantly improved in the test birds compared to the control birds (1.58 compared to 1.69 and 2615g compared to 2534g, respectively). In addition, mortality was significantly lower in birds fed the test diet compared to birds fed the control diet. Specifically, the mortality rate from day 23 to 35 was 14.48% in the control group and 2.965% in the test group. In comparison, there was no significant difference in mortality from day 0 to 10 between the two groups of birds. Therefore, the oligosaccharide preparation was found to enhance the resilience of birds, reduce the impact of the disease, and delay the IB outbreak.

[0149] [Example 2]

[0149] For another feeding trial using layered chickens, eight Bovans white hens were fed either a control feed (containing phytase and non-starch polysaccharide xylanase), a first test feed (a control feed containing an additional 450 ppm of the oligosaccharide preparation described in Example 1 of the present invention), or a second test feed (a control feed containing an additional 900 ppm of the oligosaccharide preparation described in Example 1 of the present invention) in 24 replicates. All birds were vaccinated against IBV and NDV.

[0150]

[0150] The experiment began when the birds were 22 weeks old and continued until they were 60 weeks old. Housing conditions, feed consumption, egg production, egg weight, Haugh units, yolk color, eggshell breaking strength, fertilizer moisture, and mortality were monitored weekly.

[0151]

[0151] With respect to egg production, egg mass, and FCR, birds administered one of the test feeds performed better than birds administered the control feed throughout the experiment. Outbreaks of IB and ND occurred at 26 weeks of age. Another outbreak of ND was recorded at 36 weeks of age. Consistent with the findings of Example 1, disease outbreaks were less affected in birds administered one of the test feeds compared to the control group of birds.

[0152]

[0152] At 22–25 weeks of age, the mean Hendy egg production rate (HDEP) was 1.39% and 4.13% higher in birds administered 450 ppm and 900 ppm of the oligosaccharide preparation compared to the control group. This improved productivity was even more pronounced at 26–30 weeks, i.e., at the time of disease outbreak, where HDEP was 7.66% and 11.34% higher in birds administered 450 ppm and 900 ppm of the oligosaccharide preparation compared to birds administered the control diet. In terms of mean egg mass, the performance of birds administered either of the test diets was at least 2.2% higher than that of the control birds in mean egg mass (g / d). Here again, this improvement was particularly pronounced at 26–30 weeks, with birds administered 450 ppm or 900 ppm of the oligosaccharide preparation of the present invention yielding an average egg mass that was 12.2% or 11.9%, respectively, higher than birds administered the control diet. Furthermore, regarding average FCR, the test birds were 1–1.5% lower (i.e., more efficient) than the control birds at 22–26 weeks of age, 9.9–11.2% lower at 26–30 weeks, 2.8–6.3% lower at 30–34 weeks, and 1.6–4.9% lower at 34–38 weeks. In addition, the average eggshell shattering strength was found to be improved by approximately 1% in eggs produced by the test birds in the weeks prior to the disease outbreak, and by approximately 3–11% compared to the control birds during or after the disease outbreak. In particular, pO2 and pCO2 as blood biomarkers indicated that the severity of respiratory stress experienced by birds in the test group was lower than that of birds in the control group during disease outbreaks.

Claims

1. The use of oligosaccharide preparations to prevent and / or delay respiratory diseases, preferably infectious bronchitis, and / or their effects, The oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of anhydro subunit-containing oligosaccharides, in relative abundance determined by mass spectrometry.

2. The use of oligosaccharide preparations to improve the effectiveness of vaccination against respiratory diseases, preferably infectious bronchitis, The oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of anhydro subunit-containing oligosaccharides, in relative abundance determined by mass spectrometry.

3. The use of oligosaccharide preparations to reduce, prevent, and / or delay mortality in flocks of poultry attacked by respiratory diseases, preferably infectious bronchitis, The oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of anhydro subunit-containing oligosaccharides, in relative abundance determined by mass spectrometry.

4. The use of oligosaccharide preparations to reduce, alleviate, prevent, and / or delay the incidence of respiratory diseases, preferably infectious bronchitis, The oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) having different degrees of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15% of anhydro subunit-containing oligosaccharides, in relative abundance determined by mass spectrometry.

5. Oligosaccharide preparations for use in methods of treating, alleviating, preventing, and / or delaying respiratory diseases, preferably infectious bronchitis, and / or their effects, The oligosaccharide preparation comprises at least n fractions of oligosaccharides (DP1 to DPn fractions) each having a different degree of polymerization selected from 1 to n, where n is an integer of 2 or more, and each fraction contains at least about 0.5% to about 90%, for example 1% to 90%, or for example about 0.5% to about 15%, of an anhydro subunit-containing oligosaccharide in relative abundance determined by mass spectrometry.

6. An oligosaccharide preparation for use in a method for treating, relieving, preventing, and / or delaying a respiratory disease, preferably infectious bronchitis, and / or its effects, as described in claim 5, which is administered to an individual vaccinated against the respiratory disease.

7. An oligosaccharide preparation for use according to any one of claims 1 to 4, or for use according to any one of claims 5 to 6, wherein the oligosaccharide preparation is contained in a nutritional composition at a concentration of 40 ppm or more.

8. n is at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, Oligosaccharide preparations for use according to any one of claims 1 to 4, 7, or for use according to any one of claims 5 to 7, wherein the values ​​are 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100.

9. At least one fraction of the oligosaccharide preparation contains an anhydro subunit-containing oligosaccharide in relative abundances of 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, or less than 2%, and / or each fraction of the oligosaccharide preparation contains, in relative abundance, 0.2%, Oligosaccharide preparations for use according to any one of claims 1 to 4, 7 to 8, or for use according to any one of claims 5 to 8, comprising an anhydro subunit-containing oligosaccharide in amounts of 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 30%, 40%, 50%, 60%, 70%, or more than 80%.

10. The aforementioned oligosaccharide preparations are approximately 300-5000 g / mol, 500-5000 g / mol, 700-5000 g / mol, 500-2000 g / mol, 700-2000 g / mol, 700-1500 g / mol, 300-1500 g / mol, 300-2000 g / mol, 400-1300 g / mol, 400-1200 g / mol, 400-1100 g / mol, 500-1300 g / mol, 500-1200 g / mol, 500-1100 g / mol, 600-1300 g / mol, 600- An oligosaccharide preparation for use according to any one of claims 1 to 4, 7 to 9, or for use according to any one of claims 5 to 9, wherein the oligosaccharide preparation has a weight-average molecular weight of 1200 g / mol or 600 to 1100 g / mol, and / or the oligosaccharide preparation has a number-average molecular weight of about 1000 to 2000 g / mol, 1100 to 1900 g / mol, 1200 to 1800 g / mol, 1300 to 1700 g / mol, 1400 to 1600 g / mol, or 1450 to 1550 g / mol.

11. The oligosaccharide preparation for use according to any one of claims 1 to 4, 7 to 10, or for use according to any one of claims 5 to 10, wherein the relative amount of oligosaccharide in each of the n fractions of the oligosaccharide preparation decreases monotonically with the degree of polymerization.

12. An oligosaccharide preparation for use according to any one of claims 1 to 4, 7 to 11, or for use according to any one of claims 5 to 11, wherein the average DP of the oligosaccharide preparation is at least 2, and / or the average DP of the oligosaccharide preparation is less than 5.0.

Images