Functional Compositions and Their Uses

Abstract

This invention relates to functional compositions and their uses, the compositions comprising two essential components: a first component as shown in (i) and a second component as shown in (ii): the first component (i) is selected from one or more of N-acetylneuraminic acid, sialylated oligosaccharides, sialylated proteins, and sialylated lipids; the second component (ii) is selected from one or more of Bifidobacterium probiotics; and, in the composition, the mass ratio of the substance shown in the first component (i) to the number of probiotics shown in the second component (ii) is 1 mg: (0.16 × 10⁻⁶) / ( ... 7 ~0.4×10 10 CFU. Compared to sialic acid, sialylated substances, or Bifidobacterium probiotics alone, the composition provided by this invention can more effectively enhance immunity and prevent and / or treat viral respiratory diseases, and can also more effectively suppress inflammatory responses.

Description

Technical Field

[0001] This invention belongs to the field of functional nutrient research technology, specifically relating to functional compositions and their uses, and more specifically to functional compositions and their uses in helping to enhance immunity, fight influenza viruses, and reduce inflammatory responses. Background Technology

[0002] Influenza (flu) is an acute respiratory infectious disease that occurs seasonally, primarily caused by the influenza virus. It is characterized by rapid spread, high infectivity, and severe pathogenicity. The pathogen of influenza is an RNA virus belonging to the Orthomyxoviridae family. Based on differences in matrix protein antigens and viral nucleoproteins, it is classified into three types: type A, type B, and type C (or types A, B, and C). Hemagglutinin (HA) and neuraminidase (NA) are the main spike proteins on the envelope of type A influenza viruses. Mutations in HA do not result in new subtypes and often cause small, periodic or seasonal influenza outbreaks; however, mutations in NA can lead to new subtypes and often result in large-scale influenza outbreaks that spread rapidly and over a wide area. The H1N1 influenza A virus is currently the most widespread type of virus. This virus is a triple-recombined influenza A virus complex. The parent genes of gene segments PB2 and PA are avian influenza viruses, while MP, NP, HA, NA, and NS are derived from swine influenza viruses. PB1, which is involved in the rearrangement, is a human influenza virus gene segment. Because the H1N1 influenza A virus aggregates related gene segments from avian influenza, swine influenza, and human influenza viruses, it has undergone qualitative changes in its genetic material, making its virulence and ability to invade host cells significantly higher than its parent swine influenza virus, and easily causing a rapidly spreading global influenza pandemic with a high mortality rate.

[0003] After humans are infected with the H1N1 virus, the virus primarily replicates in the respiratory tract and lungs. The influenza virus can specifically bind to α-2,6-galactosialidase receptors (SAα2 and 6Gal) in the human upper respiratory tract and α-2,3-galactosialidase receptors (SAα2 and 3Gal) in avian cells, triggering continuous viral transcription and replication, leading to the spread of influenza between humans and birds. Susceptible populations such as infants, children, pregnant women, and the elderly may experience severe complications and sequelae after viral infection, posing a serious threat to their life and health.

[0004] Influenza vaccination is currently one of the most important means of preventing influenza. However, influenza vaccines still have their shortcomings. Firstly, there are material limitations. The preparation of influenza vaccines requires efficient replication in chicken embryos, and the process of producing influenza vaccines using chicken embryos is time-consuming and complex, making it impossible to meet the needs of influenza outbreaks. Secondly, while vaccines are more effective against infections of the same subtype of virus, their effectiveness against infections of different subtypes of viruses is poor.

[0005] In the treatment of viral infections, current main strategies include inhibiting viral replication, enhancing the body's immunity, or suppressing the inflammatory response. Drugs that inhibit viral replication include oseltamivir, zanamivir, and amantadine; traditional Chinese medicine formulas have shown some efficacy in enhancing the body's immune response to the virus. Although these drug preparations have demonstrated varying degrees of therapeutic effect in clinical practice, several drugs still present safety concerns and adverse reactions. In particular, there are few effective antiviral drugs for infants and children, and many cases of improper use exist. Doctors strictly control the dosage and route of administration, and families of infected children also maintain a cautious attitude towards drug use. Among them, IFN-a currently has no nebulized inhalation formulation; only injectable IFN-a is used as a nebulized inhalation formulation, which is currently considered "off-label use." Oseltamivir has relatively mild adverse reactions, but it can still cause adverse side effects on the gastrointestinal tract, liver, central nervous system, respiratory system, blood, and skin. Arbidol's main adverse reactions include nausea, diarrhea, dizziness, and elevated serum transaminase levels. Ribavirin has serious adverse reactions. Because it reacts within red blood cells, the most serious subjective adverse reaction is hemolytic anemia. Within 1-2 weeks of oral administration, infants / children may experience a decrease in hemoglobin, red blood cells, and white blood cells, which seriously affects the child's immunity.

[0006] Another direction in antiviral research is to suppress the generation of cytokine storms in the body. The inflammatory response itself is a protective reaction of the body against the invasion of pathogens, but if its effect is too strong, it can cause various harmful effects related to infection. Therefore, the inflammatory response in the body must be properly regulated to protect the body from serious damage caused by inflammation.

[0007] The use of probiotics is currently considered as a strategy for the prevention or treatment of viruses, and its efficacy in the prevention or treatment of enterovirus infections, such as rotavirus infection, has been clinically validated. Its molecular and cellular mechanisms in the clinical treatment of inflammatory intestinal diseases mainly involve three aspects: 1) Probiotics can produce antimicrobial substances and competitively adhere to the intestinal epithelium with pathogens, thereby preventing pathogen adhesion and colonization in the intestine; 2) Probiotics can improve the survival rate of intestinal epithelial cells and the barrier function of the intestinal epithelium, and stimulate protective responses to regulate the dynamic homeostasis of intestinal epithelial cells; 3) Probiotics can enhance innate immunity and regulate the inflammatory response caused by pathogens through the TLR signaling pathway. There are also some reports on the prevention and treatment of respiratory diseases with probiotics. For example, reference 1 discloses the application of Bifidobacterium animalis and its prepared compound bacterial preparations in the preparation of drugs for the treatment or prevention of avian influenza virus infection, but the mechanism of action is still unclear.

[0008] In addition, N-acetylneuraminic acid (Neu5Ac), also known as sialic acid, is widely found in mammalian tissues. It is a component of the oligosaccharide chains of mucins, glycoproteins, and glycolipids, occupying the non-reducing ends of complex carbohydrate oligosaccharide chains and connecting to the inner and outer surfaces of cell membranes in various ways, playing important physiological functions. Neu5Ac has a high concentration in the brain, with its content on nerve cell membranes being 20 times higher than in other cells. Neu5Ac participates in intercellular recognition, regulating neurogenesis, cell proliferation and migration, synapsis, cell adhesion, and axonal guidance, playing a crucial role in brain information transmission, nerve impulse conduction, and synapse formation. Behaviorally, it helps promote learning ability and memory function in infants and young children. Currently, existing technologies have reported the application of sialic acid and its oligosaccharides in the prevention and control of influenza viruses. For example, reference 2 discloses a method for inhibiting the growth of respiratory viruses in infants in need. The method includes: identifying an infant with at least one of respiratory syncytial virus, human parainfluenza type 3 virus, and influenza A virus; and administering an infant formula prepared by a nutrient delivery system to the infant. The nutrient delivery system includes (a) a pod container; and (b) a nutrient powder containing human milk oligosaccharides or their precursors. In addition, the nutrient powder may also contain probiotics.

[0009] References:

[0010] Reference 1: CN 111110703 B;

[0011] Reference 2: CN 106659218 A. Summary of the Invention

[0012] Problems to be solved by the invention

[0013] Based on the existing explorations of sialic acid or sialylated oligosaccharides and probiotics in the prior art, this invention, through extensive further research, unexpectedly discovered that sialic acid or sialylated substances, when combined with Bifidobacterium probiotics in a specific ratio, have a synergistic effect that helps enhance immunity, fight influenza viruses, or inhibit inflammatory responses.

[0014] It should be noted that although existing technologies, such as the study cited in Reference 2, mention that human milk oligosaccharides, alone or in combination with probiotics, can be used to control and alleviate many diseases, conditions, and symptoms related to the gut-brain-immune system, the primary aim of these studies is to provide a more convenient nutrient delivery system for delivering infant formula with a consistent formulation, thereby providing infants with the optimal amount of appropriate nutrients at the right temperature. They do not provide any empirical evidence regarding the efficacy of specific nutrient combinations in controlling and alleviating many diseases, conditions, and symptoms related to the gut-brain-immune system, and explicitly state that the nutrient powder contains probiotics to provide end-users with synergistic benefits in promoting the growth of the gut microbiota in infants.

[0015] Therefore, the object of the present invention is to provide a composition and its use, which combines sialic acid or sialylated substances and Bifidobacterium probiotics in appropriate proportions to achieve synergistic effects in enhancing immunity, fighting influenza viruses, or inhibiting inflammatory responses, for therapeutic or non-therapeutic purposes.

[0016] Solutions for solving problems

[0017] To address the aforementioned technical problems, the present invention provides the following technical solution:

[0018] [1]. A composition characterized in that the composition comprises two essential components, and, in a preferred embodiment, these two components are essential components or constitute the active component of the composition, wherein the activity is the ability to inhibit inflammatory responses and / or the activity to enhance immunity.

[0019] The first component is shown in (i) and the second component is shown in (ii):

[0020] The first component (i) is selected from one or more of N-acetylneuraminic acid, sialylated oligosaccharides, sialylated proteins, and sialylated lipids;

[0021] The second component (ii) is selected from one or more probiotics of the genus Bifidobacterium;

[0022] Furthermore, in the composition, the ratio of the mass of the substance represented by the first component (i) to the number of probiotics represented by the second component (ii) is 1 mg: (0.16 × 10⁻⁶) / (1 mg ≤ ... 7 ~0.4×10 10 CFU.

[0023] [2]. The composition according to [1] is characterized in that, in the first component (i), the sialylated oligosaccharide includes any one or more of 3'-sialylated lactose, 6'-sialylated lactose, sialylated-lactose-N-tetrasaccharide a, sialylated-lactose-N-tetrasaccharide b, sialylated-lactose-N-tetrasaccharide c, and disialyl-lactose-N-tetrasaccharide.

[0024] [3]. The composition according to [1] or [2] is characterized in that, in the second component (ii), the Bifidobacterium probiotic includes any one or more of Bifidobacterium adolescentis, Bifidobacterium animalis subsp. animalis, Bifidobacterium animalis subsp. lactis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum subsp. longis and Bifidobacterium longum subsp. infantis.

[0025] [4]. Use of the composition according to any one of [1] to [3] in the preparation of products having the ability to inhibit inflammatory responses and / or help enhance immunity.

[0026] [5]. According to the use described in [4], the inflammatory response includes an increase in the expression of inflammatory factors.

[0027] [6]. The product is characterized by comprising food, health food or medicine according to the use described in [4] or [5].

[0028] [7]. Use of the composition according to any one of [1] to [3] in the preparation of a medicament for the prevention and / or treatment of viral respiratory diseases.

[0029] [8]. According to the use described in [7], the virus is characterized in that it includes an influenza virus.

[0030] [9]. The use according to [7] or [8] is characterized in that the viral respiratory disease has symptoms that cause an inflammatory response.

[0031]

[10] . A product, characterized in that the product comprises a composition according to any one of [1] to [3] and any one or more of the following ingredients: plant product ingredients, animal meat product ingredients, animal dairy product ingredients, functional additives and any acceptable excipients.

[0032] The effects of the invention

[0033] By implementing the above technical solution, the present invention achieves the following technical effects:

[0034] This invention, through extensive screening studies, has developed a composition comprising a specific ratio of sialic acid or sialylated substances and Bifidobacterium probiotics. Compared to sialic acid, sialylated substances, or Bifidobacterium probiotics alone, the composition provided by this invention can more effectively enhance immunity, further more effectively prevent and / or treat viral respiratory infections, and more effectively suppress inflammatory responses. Furthermore, this composition can be taken long-term to help enhance immunity and can also be used after viral infection to suppress the symptoms caused by influenza virus invasion.

[0035] Furthermore, the present invention has unexpectedly discovered that, in some preferred embodiments, N-acetylneuraminic acid combined with Bifidobacterium probiotics has a more effective inhibitory effect on the damage of influenza virus to cells than sialylated oligosaccharides, and can play a better role in inhibiting the inflammatory response. Moreover, this effect is particularly significant when the content of N-acetylneuraminic acid is high and the content of Bifidobacterium probiotics is low. Attached Figure Description

[0036] Figure 1 Results of cytotoxicity assays on HEP-2 cells at different concentrations of functional active ingredients.

[0037] Figure 2 Example 9: Comparison of the effects of 9 functional substance combinations and BB536 at low, medium and high doses on the concentration of immune factors produced.

[0038] Figure 3 Example 9: Comparison of the effects of nine functional substance combinations on the concentration of immune factor production with three doses of SA (low, medium, and high).

[0039] Figure 4 Comparative results of the effects of three functional substance combinations on the expression levels of inflammatory factor mRNA. Detailed Implementation

[0040] The following describes embodiments of the present invention, but the present invention is not limited thereto. The present invention is not limited to the various configurations described below, and various modifications can be made within the scope of the claims. Embodiments and examples obtained by appropriately combining the technical means disclosed in different embodiments and examples are also included in the technical scope of the present invention.

[0041] In this specification, the range of values ​​referred to as "value A to value B" refers to the range including the endpoint values ​​A and B.

[0042] In this specification, the numerical range indicated by "above" or "below" refers to the numerical range that includes the stated number.

[0043] In this specification, the word "may" has two meanings: to perform a certain process and not to perform a certain process.

[0044] In this instruction manual, the term "infants and toddlers" refers to the human group under the age of 3 years.

[0045] In this manual, the term "children" refers to a group of humans who are older than 3 years and younger than 12 years and are in the period of growth and development.

[0046] In this manual, the term "adolescent" refers to a group of people aged 12 to 18 who are in the period of growth and development.

[0047] In this manual, the term "middle-aged and elderly" refers to human groups aged 45 years and older.

[0048] In this specification, the term "animal milk" is used to refer to the fluid obtained from the mammary glands of a mammal in the process of lactation. The term "animal milk" should be interpreted broadly and encompasses both raw milk (i.e., the fluid obtained directly from the mammary glands) and standardized dairy products (such as skim milk or whole milk).

[0049] In this specification, the terms "optional" or "optional" are used to indicate the use or omission of certain substances, components, procedures, application conditions, etc.

[0050] All unit names used in this manual are international standard unit names, and unless otherwise stated, the "%" used refers to weight or mass percentage content.

[0051] In this specification, references to "some specific / preferred embodiments," "other specific / preferred embodiments," "implementation," etc., refer to specific elements (e.g., features, structures, properties, and / or characteristics) related to that embodiment, which are included in at least one of the embodiments described herein and may or may not be present in other embodiments. Furthermore, it should be understood that these elements can be combined in any suitable manner in various embodiments.

[0052] In addition, unless otherwise defined, other technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0053] The technical solution of the present invention will be further described in detail below:

[0054] Composition

[0055] The present invention provides a composition comprising the components shown in the first component (i) and the second component (ii) below, and both being essential components of the composition:

[0056] The first component (i) is selected from one or more of N-acetylneuraminic acid, sialylated oligosaccharides, sialylated proteins, and sialylated lipids;

[0057] The second component (ii) is selected from one or more probiotics of the genus Bifidobacterium;

[0058] Furthermore, in the composition, the ratio of the mass of the substance represented by the first component (i) to the number of probiotics represented by the second component (ii) is 1 mg: (0.16 × 10⁻⁶) / (1 mg ≤ ... 7 ~0.4×10 10 CFU.

[0059] Compared to sialic acid, sialylated substances, or Bifidobacterium probiotics alone, the composition provided by this invention can more effectively enhance immunity and prevent and / or treat viral respiratory diseases, and can also more effectively suppress inflammatory responses.

[0060] In some preferred embodiments, the active ingredient of the composition comprises the components shown in the first component (i) and the second component (ii) below:

[0061] The first component (i) is selected from one or more of N-acetylneuraminic acid, sialylated oligosaccharides, sialylated proteins, and sialylated lipids;

[0062] The second component (ii) is selected from one or more probiotics of the genus Bifidobacterium;

[0063] Furthermore, in the composition, the ratio of the mass of the substance represented by the first component (i) to the number of probiotics represented by the second component (ii) is 1 mg: (0.16 × 10⁻⁶) / (1 mg ≤ ... 7 ~0.4×10 10 CFU.

[0064] (N-acetylneuraminic acid and sialylated substances)

[0065] N-Acetylneuraminic acid (NANA), also known as sialic acid, is an important component of gangliosides in the brain. Studies have shown that NANA is widely distributed in various biological tissues and is an important component of glycoproteins, oligosaccharides, and glycolipids. It is usually present at the terminal ends of glycoproteins and glycolipids in the form of glycosides, and is particularly abundant in the brain, nerve tissue, blood, submandibular glands, mucins, and colostrum of mammals. NANA has many beneficial effects, including promoting intellectual development, improving intestinal absorption, and enhancing immunity.

[0066] Currently, the main methods for producing N-acetylneuraminic acid include natural raw material extraction, chemical synthesis, polymer decomposition, enzyme and immobilized enzyme methods, and microbial fermentation. This invention does not impose specific limitations on the source and extraction process of N-acetylneuraminic acid. Typically, it can be prepared through microbial fermentation or enzymatic methods, or extracted from substances rich in sialic acid, such as eggs and bird's nest. Alternatively, finished N-acetylneuraminic acid can be obtained commercially.

[0067] Sialylation is a type of glycosylation involving the covalent addition of sialic acid to the terminal glycans of glycoproteins and glycolipids. This enzymatic process is tightly regulated by sialyltransferases (STs) and sialylases / neuraminidases (NEUs). Based on the type of glycosidic bond, sialylation can be classified into three types: α2-3-, α2-6-, and α2-8-sialylation. The sialylated substances described in this invention mainly include sialylated oligosaccharides, sialylated proteins, and sialylated lipids.

[0068] In some embodiments, the sialylated oligosaccharides of the present invention include any one or more of 3'-sialylated lactose, 6'-sialylated lactose, sialylated-lactose-N-tetrasaccharide a, sialylated-lactose-N-tetrasaccharide b, sialylated-lactose-N-tetrasaccharide c, and disialialic acid-lactose-N-tetrasaccharide. In some preferred embodiments, the sialylated oligosaccharide of the present invention is 3'-sialylated lactose.

[0069] To achieve more effective anti-influenza virus or anti-inflammatory effects, in some specific embodiments, the composition of the present invention comprises a first component as shown in (i) and a second component as shown in (ii), both of which are essential components of the composition: (i) N-acetylneuraminic acid or 3'-sialylated lactose; (ii) one or more Bifidobacterium probiotics. In some preferred embodiments, the active ingredient of the composition consists of the components shown in the first component (i) and the second component (ii): (i) N-acetylneuraminic acid or 3'-sialylated lactose; (ii) one or more Bifidobacterium probiotics.

[0070] (Bifidobacterium probiotics)

[0071] This invention does not impose any particular limitation on the source of Bifidobacterium probiotics. Typically, they can be obtained through microbial fermentation or by directly purchasing commercially available finished products.

[0072] This invention does not specifically limit the species of Bifidobacterium. In some embodiments, the Bifidobacterium probiotics described in this invention include any one or more of the following: Bifidobacterium adolescentis, Bifidobacterium animalis subsp. animalis, Bifidobacterium animalis subsp. lactis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum subsp. longis, and Bifidobacterium longum subsp. infantis. In some preferred embodiments, the Bifidobacterium probiotics described in this invention are Bifidobacterium longum subsp. longis.

[0073] The present invention does not specifically limit the specific strains of the above-mentioned bacteria. For example, the animal Bifidobacterium lactis subsp. includes strains Bb-12, HN109, and Bi-07, etc., Bifidobacterium bifidum includes strain R0071, etc., the long subsp. infantis includes strain R0033, etc., and the long subsp. longis includes strain BB536, etc.

[0074] In order to achieve more effective immune enhancement and anti-influenza virus or anti-inflammatory effects, in some specific embodiments, the composition of the present invention comprises the components shown in (i) and (ii) below: (i) N-acetylneuraminic acid, or sialylated oligosaccharide, or sialylated protein, or sialylated lipid; (ii) Bifidobacterium longum subsp.

[0075] In some more specific embodiments, the composition of the present invention comprises a first component as shown in (i) and a second component as shown in (ii), and both are essential components of the composition: (i) N-acetylneuraminic acid or 3'-sialylated lactose; (ii) *Bifidobacterium longum* subsp. *longum*. In some preferred embodiments, the active ingredient of the composition consists of the components shown in the first component (i) and the second component (ii): (i) N-acetylneuraminic acid or 3'-sialylated lactose; (ii) *Bifidobacterium longum* subsp. *longum*.

[0076] Through extensive experimentation, this invention unexpectedly discovered that in some preferred embodiments, when the composition of this invention comprises the first component as shown in (i) and the second component as shown in (ii) as essential components of the composition, its efficacy in enhancing immunity, resisting influenza viruses, and inhibiting inflammatory responses is particularly prominent: (i) N-acetylneuraminic acid; (ii) *Bifidobacterium longum* subsp. *longum*. In some more preferred embodiments, the active ingredient of the composition consists of the components shown in the first component (i) and the second component (ii): (i) N-acetylneuraminic acid; (ii) *Bifidobacterium longum* subsp. *longum*.

[0077] Furthermore, in order to obtain better synergistic effects in enhancing immunity, suppressing inflammatory responses, or preventing and / or treating viral respiratory infections, in some specific embodiments, in the compositions of the present invention, the mass ratio of the substance shown in (i) to the number of probiotics shown in (ii) is 1 mg: (0.16 × 10⁻⁶) 7 ~0.4×10 10 CFU, for example, can be 1 mg: 0.16 × 10⁻⁶ 7 CFU, 1mg: 0.5×10 7 CFU, 1mg: 0.2×10 8 CFU, 1mg: 0.3×10 8 CFU, 1mg: 0.1×10 9 CFU, 1mg: 0.3×10 9 CFU, 1mg: 0.4×10 9 CFU, 1mg: 0.1×10 10 CFU or 1mg: 0.4×10 10 CFU, etc.

[0078] The present invention does not particularly limit the form of the composition; typically, it can be a liquid or a solid.

[0079] For consideration of the method of use of the composition and to meet the requirements of relevant laws and regulations, in some embodiments, the composition is a non-food composition. In some embodiments, the composition is a non-food and non-health food composition. In other embodiments, the composition is a food composition. In still other embodiments, the composition is a health food composition. In some embodiments, the composition is a pharmaceutical composition.

[0080] product

[0081] The present invention provides a product comprising the above-described composition.

[0082] In addition to the essential components described above, the product of this invention may also include other components as needed for the final product. Examples of such components include:

[0083] Plant-based ingredients include fruits such as fig, pomegranate, kiwi, orange, tangerine, pineapple, strawberry, apple, rubber, grape, pear, cherry, blueberry, blackberry, blackcurrant, cranberry, raspberry, melon, amla, and bilberry, or their extracts; fruits and vegetables such as onion, cucumber, tomato, cauliflower, carrot, spinach, kale, Brussels sprouts, garlic, basil, and oregano, or their extracts; grains such as rice (indica, japonica, glutinous rice), cereals (wheat, barley, oats, rye), corn, sorghum, millet, sorghum, yellow millet, buckwheat, soybean, broad bean, pea, mung bean, red bean, and kidney bean, or their extracts; nuts such as walnut, pistachio, cashew, hazelnut, almond, apricot kernel, pine nut, peanut, sunflower seed, chestnut, macadamia nut, and ginkgo, or their extracts; coffee or its extracts; and some medicinal and edible herbal medicines or their extracts.

[0084] Animal meat product ingredients, including meat products from pigs, cattle, sheep, aquatic products, or poultry.

[0085] Animal dairy products include fresh milk from cows, sheep, etc., as well as processed dairy products such as milk powder, whey protein, or cheese.

[0086] Functional additives include vitamins (one or more of vitamin A, beta-carotene, vitamin D3, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, pantothenic acid, folic acid, niacin, choline, inositol, biotin, L-carnitine, and lutein); starch; modified starch; amino acids (L-lysine-L-glutamic acid, L-glutamic acid, L-arginine, L-tryptophan, L-glutamine, taurine, L-valine, L-isoleucine, L-leucine, casein phosphopeptide, etc.); dietary fiber (inulin, konjac flour, galactooligosaccharides, fructooligosaccharides, raffinose, polydextrose, isomaltooligosaccharides, soybean polysaccharides, cyclodextrin, resistant dextrin, or other similar ingredients). Soy fiber, etc.); trace element supplements (which may include metal ion salts of organic acids, such as calcium citrate, L-calcium lactate, calcium hydrogen phosphate, potassium gluconate, sodium citrate, ferrous gluconate, potassium iodide, zinc gluconate, sodium selenite, copper gluconate, chromium sulfate, manganese gluconate, and magnesium gluconate, etc.); fat supplements (such as saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, OPO structured lipids, OPL structured lipids, LPL structured lipids, DHA, EPA, ARA, phospholipids, etc.); nucleotide supplements; human milk oligosaccharides (such as 2'-FL, 3-FL, DFL, LNFPI, LNFPII, LNT, LNnT, 3'-SL, 6'-SL, DSLNT, etc.), etc.

[0087] Any acceptable excipients, including but not limited to solvents, antioxidants, antibacterial agents, thickeners, diluents, cosolvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, food flavorings, food colorings, etc.

[0088] The present invention does not specifically limit the type of the aforementioned product. In some embodiments, the product is a food. In some embodiments, the product is a health food. In some embodiments, the product is a medicine. In other embodiments, the product is a non-food. In other embodiments, the product is a non-health food. In other embodiments, the product is a non-medicine.

[0089] For different product categories, the present invention does not particularly limit the specific form of the product. For example, it can be in solid or liquid form.

[0090] The present invention does not specifically limit the target population of the product. For example, the product can be used for infants, children, teenagers or adults.

[0091] In some specific implementations, the products described in this invention may be infant formula, baby food, children's formula, children's snacks, formula milk powder for pregnant women, milk powder for middle-aged and elderly people, or nutritional or dietary supplements.

[0092] In other specific embodiments, the products described in this invention may be beverages (carbonated beverages, fruit and vegetable juice beverages, functional beverages, tea beverages, milk beverages, alcoholic beverages, instant coffee, grain powder, nut powder or lotus root powder, etc.), candies (gel candies, hard candies, compressed candies, etc.), milk and dairy products (fresh milk, milk powder, whey powder, fermented milk, cheese or condensed milk, etc. derived from fresh cow (sheep) milk), pasta products (noodles, instant noodles, steamed buns, dumplings or wontons, as well as baked goods such as bread, cakes or biscuits), etc.

[0093] In some other specific embodiments, the product of the present invention is an oral preparation, which includes, but is not limited to, tablets, pills, granules, powders, sprays, teas, capsules, or oral liquids.

[0094] The product provided by this invention is suitable for all population groups in principle, especially for those with weakened immunity, those who need to enhance their immunity, or those who need to suppress inflammatory responses. The components of the product can also be adjusted accordingly for different population groups with different characteristics.

[0095] While enabling the product to effectively enhance immunity, suppress inflammatory responses, and prevent and / or treat viral respiratory diseases, the content of each substance in the product also meets the relevant market regulations or requirements.

[0096] Furthermore, the dosage of N-acetylneuraminic acid and Bifidobacterium probiotics in the product can be determined according to the relevant laws and regulations of different regions or countries. In some preferred embodiments, N-acetylneuraminic acid, an essential component of the composition, accounts for 0.01%-1% of the total mass of the product, preferably 0.05%-0.6%. In some preferred embodiments, sialylated oligosaccharides, an essential component of the composition, account for 0.06%-1.1% of the total mass of the product, preferably 0.15%-0.75%. In some preferred embodiments, Bifidobacterium probiotics, an essential component of the composition, account for 10% of the total mass of the product. 8 -10 13 CFU / g, preferably 10 9 -10 11 CFU / g.

[0097] Uses to help boost immunity

[0098] This invention proposes using sialic acid or sialylated substances in a specific ratio with Bifidobacterium probiotics to enhance immunity, and the two substances have a synergistic effect. Therefore, the composition provided by this invention can be used to prepare products that help enhance immunity, and the products described in this invention (such as food or health food) can also enhance immunity.

[0099] Uses of suppressing inflammatory responses

[0100] This invention proposes using sialic acid or sialylated substances in a specific ratio with Bifidobacterium probiotics to suppress inflammatory responses, with the two substances exhibiting a synergistic effect. Therefore, the composition provided by this invention can be used to prepare products capable of suppressing inflammatory responses, and the products described in this invention (e.g., food, health food, or pharmaceuticals) also possess the ability to suppress inflammatory responses.

[0101] In some embodiments, the inhibition of inflammatory responses described in this invention is not intended to prevent and / or treat disease, and the inflammatory response has not reached the level of becoming a disease. In this case, the composition or product with the ability to inhibit inflammatory responses can be a food or health food. Simultaneously, the inhibition of inflammatory responses described in this invention can be used to enhance immunity, and the products provided by this invention can also enhance immunity by inhibiting inflammatory responses. In other embodiments, the inhibition of inflammatory responses described in this invention is intended to prevent and / or treat disease. For example, after influenza virus infection, inhibiting the inflammatory response can prevent influenza from harming the body. In this case, the composition or product with the ability to inhibit inflammatory responses can be a drug.

[0102] The inflammatory response described in this invention includes an increase in the expression of inflammatory factors, and in some embodiments, the inflammatory factors include any one or more of TNF-α, IL-6, and iNOS.

[0103] The present invention also provides a method for suppressing an inflammatory response, the method comprising administering an appropriate amount of the composition or the product to a person in need. The administration includes oral, sublingual, or inhalation of the composition or the product by the person in need. Ingestion of the composition or the product can effectively suppress inflammatory responses, including inflammatory responses in disease states or non-disease states.

[0104] Used for the prevention and / or treatment of viral respiratory infections.

[0105] This invention proposes using sialic acid or sialylated substances in a specific ratio with Bifidobacterium probiotics for the prevention and / or treatment of viral respiratory infections, with the two substances exhibiting a synergistic effect. Therefore, the composition provided by this invention can be used to prepare a medicament for the prevention and / or treatment of viral respiratory infections, and the medicament described in this invention also possesses the ability to prevent and / or treat viral respiratory infections.

[0106] The viral respiratory diseases described in this invention include respiratory diseases caused by influenza virus infection, typically including respiratory diseases caused by H1N1 influenza A virus infection.

[0107] Furthermore, in some embodiments, the viral respiratory disease of the present invention has symptoms that cause an inflammatory response; further, the inflammatory response includes an increase in the expression of inflammatory factors; and even further, the inflammatory factors include any one or more of TNF-α, IL-6, and iNOS.

[0108] The present invention also provides a method for preventing and / or treating viral respiratory infectious diseases, the method comprising administering an appropriate amount of the composition or the drug to a person in need. The administration includes oral, sublingual, or inhalation of the composition or the drug by the person in need. Ingestion of the composition or the drug can effectively prevent and / or treat infectious respiratory diseases such as influenza viruses.

[0109] Example

[0110] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Unless otherwise specified, the reagents, methods, and equipment used in this invention are conventional in the art.

[0111] As described in the cited literature (Wang Qianwen. Screening and Mechanism Study of Probiotics for Alleviating Respiratory Viral Infections [D]. Jiangnan University, 2022.), after viral infection, the host activates the body's immune response to resist the infection and protect the body's health. However, although the immune response aims to eliminate the virus, the antiviral process can directly harm the body and ultimately aggravate respiratory inflammation and damage. Therefore, in order to screen suitable compositions that can synergistically enhance immunity and demonstrate their efficacy, this invention uses influenza virus-infected cells as an example model to demonstrate and verify the efficacy of the compositions in enhancing immunity from two aspects: antiviral and inhibition of inflammatory response.

[0112] 1. Experimental protocol for anti-influenza virus formulation composition

[0113] 1.1.1 Cells and Viruses

[0114] The cell line (HEP-2) was purchased from ATCC. The H1N1 influenza A virus was provided by the Chinese Center for Disease Control and Prevention and stored at -80°C.

[0115] 1.1.2 Experimental Materials and Reagents

[0116] Experimental materials: SA (N-acetylneuraminic acid), 3'-SL (3'-sialyl lactose), 6'-SL (6'-sialyl lactose), and Bifidobacterium longum BB536. Appropriate amounts of each substance were weighed and dissolved in DMSO to prepare a 20 mM stock solution. The H1N1 influenza virus solution was passaged twice in chicken embryos, and the viral titer was determined to be 2. -7 .

[0117] 96-well plates were purchased from Corning Costar (Cambridge, MA, USA); DMEM medium and fetal bovine serum (FBS) were purchased from Gibco, USA; and penicillin-streptomycin (10,000 U / mL) and its antibiotics (10,000 U / mL) were purchased from Beijing Solarbio Biotechnology Co., Ltd. Phosphate-buffered saline (PBS) and dimethyl sulfoxide (DMSO) were purchased from Sigma, USA.

[0118] Cell culture medium: DMEM medium containing 10% FBS and 1% penicillin antibiotics;

[0119] Cell maintenance medium: DMEM medium containing 2% FBS and 1% penicillin and antibiotics.

[0120] 1.1.3 Instruments

[0121] Cell culture incubator; optical microscope; clean bench; water bath; RT-PCR instrument; Western blot detection system.

[0122] 1.1.4 Experimental Methods

[0123] 1) H1N1 influenza virus TCID 50 Measurement

[0124] Influenza virus H1N1 cryopreservation solution was serially diluted 10-fold using serum-free DMEM medium. Each concentration of virus solution was then sequentially inoculated into 96-well plates containing a monolayer of cells at 100 μL / well, with 6 replicates per concentration. A normal cell control group was included. The 96-well plates containing the virus solution were incubated at 37°C in a 5% CO2 incubator for 2 hours. The virus dilution was then replaced with cell maintenance medium, and the plates were incubated for another 48 hours. Cell morphology was observed, and the number of wells and the degree of cytopathic effect were recorded. Wells with a cytopathic effect rate ≥50% in the control group were considered diseased wells. The median cell culture infection capacity (TCID) of the virus was calculated using the Reed-Muench method. 50 ).

[0125] 2) Cytotoxicity experiments of functional substances

[0126] HEP-2 cells were revived, passaged 3-4 times until good cell growth was observed, digested with trypsin, and diluted to a concentration of 1.5 × 10⁻⁶ cells with complete culture medium. 5 Cells / mL were mixed by pipetting and seeded into 96-well plates at 100 μL / well. The plates were incubated at 37°C with 5% CO2 for 24 h. The test sample was serially diluted 2-fold (maximum concentration 200 μM) with culture medium, and each concentration was added to 96-well plates at 100 μL / well, with 3 replicates per concentration. A blank control group was included. The plates were incubated at 37°C with 5% CO2 for 48 h. Cell morphology was observed, and the supernatant was discarded. A 10% CCK-8 solution was prepared with PBS, and 100 μL was added to each well. After incubation for 1 h, the absorbance of the cells was measured at 540 nm using a microplate reader. The cell viability % was calculated using the formula: Cell viability % = Absorbance value of the drug group (A) / Absorbance value of the cell control group (A) × 100%.

[0127] 3) Detection of the efficacy of functional compositions against H1N1 virus

[0128] Set up a normal cell control (negative control group), an influenza virus control group (positive control group), and a drug treatment group. Take a culture plate that has grown into a monolayer of cells, aspirate the culture medium, and add 100 TCID50. 50Influenza virus solution (influenza virus control group and drug treatment group) or culture medium (normal cell control group), 100 μL / well, was incubated at 37℃ and 5% CO2 for 4 h. After adsorption, the influenza virus solution was removed, and 100 μL of the appropriate dose of each compound was added. Each concentration was tested in triplicate, and the reaction was repeated 3 times. After 48 h, cell morphology was observed, the supernatant was discarded, and 100 μL of CCK-8 was prepared into a 10% solution with PBS and added to each well. After incubation for 1 h, the absorbance (A value) of the cells was measured at 540 nm using an ELISA reader. The inhibition rate (%) of the drug on virus-induced cell cytopathic effects was calculated according to the formula: Inhibition rate (%) = (Average A value of drug - Average A value of virus control group) / (Average A value of cell control - Average A value of virus control group) × 100%.

[0129] 4) Research on the anti-H1N1 virus mechanism of functional compositions

[0130] The following groups were set up: normal cell control (blank control group), influenza virus control group (model control group), and drug treatment group (see Table 4). Culture plates that had grown into monolayers of cells were taken, the culture medium was aspirated, and 100 mg TCID⁻¹ was added. 50 Influenza virus solution (influenza virus control group and drug-treated group) or culture medium (normal cell control group), 1.0 mL / well, was incubated at 37℃ in a 5% CO2 incubator for 4 h for adsorption. The influenza virus solution was then removed, and 1.0 mL of each appropriate dose of compound was added. Three replicates were performed for each concentration, and the results were repeated three times. After 48 h, the supernatant was collected and the levels of inflammatory factors TNF-α, iNOS, and IL-6 were detected using an ELISA kit.

[0131] The following groups were set up: normal cell control (blank control group), influenza virus control group (model control group), and drug treatment group (see Table 4). Culture plates that had grown into monolayers of cells were taken, the culture medium was aspirated, and 100 mg TCID⁻¹ was added. 50 Influenza virus solution (influenza virus control group and drug-treated group) or culture medium (normal cell control group), 1.0 mL / well, was incubated at 37℃ in a 5% CO2 incubator for 4 h. After adsorption, the influenza virus solution was aspirated, and 1.0 mL of each appropriate dose of compound was added, with 3 replicates per concentration, repeated 3 times. After 48 h, the supernatant was aspirated, and the cells were washed twice with pre-cooled PBS. Total RNA was extracted with Trizol, and after reverse transcription, the mRNA expression levels of inflammatory factors TNF-α, iNOS, and IL-6 were detected by real-time quantitative PCR.

[0132] 2 Experimental Results

[0133] This study first investigated the toxicity of several functional substances to HEP-2 cells, and the results were as follows: Figure 1As shown in Table 1, the figure shows that the cell viability of SA and the two sialic acid oligosaccharides (3'-SL and 6'-SL) reached 100% at a concentration of 200 μM, indicating that these three substances had no effect on cell viability. However, the cell viability of probiotic BB536 was less than 80% at a concentration of 2000 μg / mL, and close to 80% at 1000 μg / mL, indicating that the 2000 μg / mL dose had some toxicity to the cells. However, the median toxic concentration (TC) of BB536 was also found to be low. 50 The concentrations were still higher than the maximum dosage (see Table 1), further indicating that these four substances had little impact on cell survival within the dosage range. Based on these results, in the experiment to detect the antiviral efficacy of the drugs, the maximum concentrations of functional proteins and probiotics were set at 2000 μg / mL, with the probiotic activity at 2 × 10⁻⁶. 11 Therefore, the maximum concentration of probiotics is 4 × 10⁻⁶ CFU / g. 8 CFU / mL.

[0134] Table 1. Cytotoxicity of functional active ingredients to HEP-2 cells.

[0135] Compound <![CDATA[TC 50 ]]> SA >1000μM 3'-SL >2000μM 6'-SL >2000μM BB536 >2000μg / mL

[0136] Further investigation was conducted into the effects of these four functional substances on inhibiting virus-induced cytopathic effects. The results are shown in Table 2. The table shows that SA and sialylated oligosaccharide 3'-SL have significant inhibitory effects on H1N1 influenza virus-induced HEP-2 cytopathic effects. 50 The values ​​were 48.37±1.08μM and 54.32±2.05μM, respectively. The IC of BB536... 50A value greater than 1000 μg / mL indicates that its inhibitory effect on H1N1 influenza virus-induced HEP-2 cytopathic effect is not significant. Further investigation was conducted on the inhibitory effects of the three functional substances at different concentrations and in different ratios on virus-induced cytopathic effects. The low and high concentrations of SA and 3'-SL were set at 10 μM and 40 μM, respectively, and the units were converted to μg / mL according to molecular weight; the low and high concentrations of BB536 were 40 μg / mL and 160 μg / mL, respectively. The results are shown in Table 3. The table shows that SA and 3'-SL at high concentrations can achieve an inhibition rate of over 60% on virus-induced cytopathic effects, while BB536 at high concentrations only has an inhibition rate of 34%. However, when SA and 3'-SL are combined with BB536, the inhibition rate of cytopathic effects in the combination of SA and BB536 reaches 83.36%, indicating that the combination of the two substances has a synergistic effect. The combination of 3'-SL and BB536 showed an inhibition rate of 65.52% against cytopathic effects, which was 5.52% higher than that of high-concentration 3'-SL. The synergistic effect was less than that of the combination of SA and BB536.

[0137] Table 2. Inhibition results of functional components on virus-induced cytopathic effects.

[0138] Compound <![CDATA[IC 50 ]]> SA 48.37±1.08μM 3'-SL 54.32±2.05μM 6'-SL >200μM BB536 >1000μg / mL

[0139] Table 3. Inhibition rate of functional substance composition combinations against virus-induced cytopathic effects.

[0140]

[0141] Based on the preliminary research, further research was conducted on the mechanism of action of SA and BB536 in inhibiting H1N1 influenza virus. The specific implementation plan is shown in Table 4.

[0142] Table 4 Experimental design schemes for inhibiting H1N1 influenza virus with different doses of functional compositions.

[0143]

[0144] After influenza virus infects body cells, it activates the NF-κB pathway via the Toll-like receptor (TLR) pathway, causing an inflammatory response and leading to apoptosis. TLR activation stimulates the antiviral response and may result in the excessive secretion of pro-inflammatory mediators. In inflammation-induced immune responses, pro-inflammatory cytokines such as TNF-α and IL-6 play crucial regulatory roles. Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine produced by various cells in response to inflammatory responses and immune regulation, and it can induce apoptosis. IL-6 is a potent activator of acute-phase responses, contributing to systemic and local inflammatory responses. Excessive IL-6 can induce various chronic inflammatory diseases. NO free radicals are also crucial in inflammatory and immune responses. They are synthesized by enzymes such as NOS (eNOS) and iNOS via the L-arginine pathway. Under normal physiological conditions, iNOS in dormant cells remains dormant. However, under pathological conditions, it produces large amounts of NO and plays a dual role in chronic infection and inflammation. Reducing NO production may be an effective strategy for treating various inflammatory diseases. This study first used ELISA to detect the production of two pro-inflammatory factors, and then used PCR to further determine the expression levels of the mRNA of the inflammatory factors at the gene level.

[0145] As shown in Table 5, the levels of pro-inflammatory factors TNF-α, IL-6, and iNOS in the normal cell control group were 59.67±6.67 pg / mL, 246.39±8.24 pg / mL, and 2.87±0.09 pg / mL, respectively. However, in the model group after viral infection, the levels of the three factors reached 144.11±1.92 pg / mL, 417.62±6.46 pg / mL, and 5.14±0.25 pg / mL, respectively. All three inflammatory factors were significantly elevated (as shown in Tables 5 and 6), indicating that the model was successfully established. Intervention with low, medium, and high doses of functional substance SA and probiotic BB536 revealed a decrease in the levels of pro-inflammatory factors (Table 5). After significant difference analysis, it was found that, except for the low concentration of BB536 where there was no significant difference in TNF-α compared with the model group (p>0.05), the levels of three immune factors, TNF-α, IL-6, and iNOS, at medium and high concentrations of BB536 and at low, medium, and high concentrations of SA were all significantly lower than those in the model group (p≤0.0005) (as shown in Table 6).

[0146] Table 5. Production of inflammatory factors by functional substances and their different combinations during the anti-H1N1 virus process.

[0147] Grouping TNF-α (pg / mL) IL-6 (pg / mL) iNOS (pg / mL) Comparative Example 1 C 59.67±6.67 246.39±8.24 2.87±0.09 Comparative Example 2 M 144.11±1.92 417.62±6.46 5.14±0.25 Comparative Example 3 SA-H 80.89±7.56 300.65±1.01 3.63±0.30 Comparative Example 4 BB536-H 97.11±10.09 302.39±2.70 3.86±0.14 Comparative Example 5 SA-M 87.11±5.89 306.42±8.88 4.10±0.08 Comparative Example 6 BB536-M 101.89±8.39 326.18±5.54 4.13±0.13 Comparative Example 7 SA-L 104.78±10.46 321.75±3.25 4.17±0.05 Comparative Example 8 BB536-L 125.22±1.92 346.95±5.79 4.43±0.39 Example 1 SA+BB LL 100.78±6.94 297.31±5.99 3.80±0.03 Example 2 SA+BB LM 91.44±4.29 297.98±9.01 3.51±0.05 Example 3 SA+BB LH 79.33±6.51 290.85±2.91 3.84±0.12 Example 4 SA+BB ML 67.11±8.00 273.01±2.58 3.71±0.07 Example 5 SA+BB MM 72.67±3.38 288.70±2.23 3.40±0.19 Example 6 SA+BB MH 65.33±4.51 288.44±7.79 3.24±0.10 Example 7 SA+BB HL 43.00±5.77 287.95±8.00 3.23±0.02 Example 8 SA+BB HM 47.44±3.85 299.01±2.59 3.21±0.09 Example 9 SA+BB HH 54.84±5.72 285.26±3.26 3.23±0.26

[0148] Table 6 Comparison of differences in inflammatory factor production among groups

[0149]

[0150] Further analysis was conducted to compare the efficacy of nine functional compositions in inhibiting the H1N1 influenza virus with that of two single substances. The results are as follows: Figure 2 and Figure 3 As shown.

[0151] from Figure 2 The results show that the concentrations of the three inflammatory factors produced by combining BB536 with SA were all lower than those produced by BB536 alone. In particular, the synergistic effect of SA combined with BB536 at medium to high doses was more significant. Table 7 shows the results after one-way ANOVA. As shown in the table, compared with the low concentration of BB536, the three immune factors TNF-α, IL-6, and iNOS were all significantly reduced (p < 0.01) in the nine functional substance combinations. Compared with the medium dose of BB536 alone, except for the LL and LM groups where there was no significant difference in TNF-α concentration (p > 0.05) and the LL, ML, and MM groups where there was no significant difference in iNOS concentration, the three immune factors were significantly reduced in all other groups (p < 0.01). Compared with the high dose of BB536, the TNF-α concentration was significantly reduced (p < 0.01) after SA was combined with BB536 at low, medium, and high doses, and the iNOS production concentration was significantly reduced (p < 0.01) after SA was combined with BB536 at high doses.

[0152] from Figure 3 It can be seen that the combination of the nine functional substances also showed a synergistic effect compared with the individual effects of the three concentrations of SA (low, medium, and high). Specifically, after testing with one-way ANOVA (as shown in Table 7), it was found that the production of the three inflammatory factors (TNF-α, IL-6, and iNOS) in the combination of high-dose SA with the three doses of BB536 (HL group, HM group, and HH group) was significantly lower than that in the low-dose SA group (SA-L); compared with the medium-dose SA group (SA-M), except that there was no significant difference in IL-6 factor between the HM group and the SA-M group (p>0.05), the other indicators were significantly reduced (p<0.01); compared with the high-dose SA group, there was no significant difference in inflammatory factors IL-6 and iNOS (p>0.05), but the TNF-α production concentration in the HL group, HM group, and HH group was significantly lower than that in the SA-H group (p<0.01).

[0153] The above analysis shows that the SA+BB(HL), SA+BB(HM), and SA+BB(HH) groups were significantly more effective than SA and BB536 alone in inhibiting the production of inflammatory factors of H1N1 influenza virus.

[0154] Furthermore, this study compared the production of inflammatory factors at the gene level among the three combinations (HL group, HM group, and HH group) using mRNA expression levels. The results are as follows: Figure 4 As shown in the figure, the mRNA expression levels of the three inflammatory factors in the SA+BB(HL) group were lower than those in the SA+BB(HM) and SA+BB(HH) groups. Two-way ANOVA revealed that the TNF-α mRNA expression level in the HL group was not significantly different from that in the HH group (p > 0.05), but significantly lower than that in the HM group (p < 0.05). For IL-6, the HL group showed significantly lower levels than both the HM and HH groups (p < 0.05), while there was no significant difference between the HM and HH groups (p > 0.05). For the inflammatory factor iNOS, there was no significant difference among the three groups (p > 0.05). Therefore, the above analysis indicates that the combination of sialic acid (SA) and probiotic BB536 at high and low doses (i.e., SA / BB536 = 1:0.16 × 10⁻⁶) is effective. 7 When combined with mg / CFU, it exhibits optimal inhibition of the inflammatory response caused by H1N1 virus-induced cell infection.

[0155] Table 7 Comparison of differences in inflammatory factor production among groups

[0156]

[0157]

[0158]

[0159] Industrial availability

[0160] The composition provided by this invention can be widely used in many fields such as food, health food, and pharmaceuticals.

Claims

1. Use of a composition in the preparation of a product having the ability to inhibit an inflammatory response and / or contributing to enhanced immunity by inhibiting an inflammatory response, characterized in that, The composition comprises the following two essential components: (i) Component 1 and (ii) Component 2: The first component (i) is N-acetylneuraminic acid; The second component (ii) is Bifidobacterium longum subsp. BB536; Furthermore, in the composition, the mass ratio of N-acetylneuraminic acid to the quantity of *Bifidobacterium longum* subsp. BB536 is 1 mg: 0.16 × 10⁻⁶. 7 CFU; The inflammatory response includes an increase in the expression of inflammatory factors; The inflammatory factors include any one or more of TNF-α, IL-6, and iNOS.

2. The use according to claim 1, characterized in that, The products include pharmaceuticals.

3. Use of a composition in the preparation of a medicament for the prevention and / or treatment of viral respiratory infectious diseases; wherein, The composition comprises the following two essential components: (i) Component 1 and (ii) Component 2: The first component (i) is N-acetylneuraminic acid; The second component (ii) is Bifidobacterium longum subsp. BB536; Furthermore, in the composition, the mass ratio of N-acetylneuraminic acid to the quantity of *Bifidobacterium longum* subsp. BB536 is 1 mg: 0.16 × 10⁻⁶. 7 CFU; The viral respiratory diseases include respiratory diseases caused by H1N1 influenza A virus infection; The viral respiratory infections described above have symptoms that cause an inflammatory response; The inflammatory response includes an increase in the expression of inflammatory factors; The inflammatory factors include any one or more of TNF-α, IL-6, and iNOS.

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