Compositions of 2'-fucosyllactose and probiotics, and uses and products thereof

Abstract

The application provides a composition of 2'-fucosyllactose and probiotics and application thereof, and belongs to the technical field of probiotics.The effective component of the composition is composed of 2'-fucosyllactose, Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63.The compounding of the probiotics and 2'-fucosyllactose has a good relieving effect on rhinitis and rhinitis sensitivity, and has a good market application prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of probiotics, and specifically relates to a composition of 2'-fucosyllactose and probiotics and application and products thereof. BACKGROUND

[0002] The main manifestations of rhinitis nasal sensitive patients are nasal congestion, nasal itching, sneezing, clear nasal discharge, and ocular dryness. The pathogenesis of rhinitis is diverse. For example, the pathogenesis of rhinitis disclosed in the prior art can be that foreign impurities such as pollen and dust invade the body as allergens, causing the body to produce specific antibodies and initial response. When the same allergen invades the body again, antigen presenting cells will recognize and process it, and the processed allergen induces the directional differentiation of initial T cells, so that Thl / Th2 and Th17 / Treg cells are biased, and then IL-4, TNF-α and other inflammatory cytokines are secreted, thereby causing rhinitis. Western medicine treatment is currently the main choice, but there is currently no drug that can prevent the recurrence of allergic rhinitis. The simple use of western medicine can effectively relieve symptoms and has good short-term efficacy, but the efficacy time is not long-lasting. The safety of western medicine needs to be considered.

[0003] Probiotics colonize in the human body, change the composition of the flora in a part of the host, and are beneficial to the host. By regulating the immune function of the host mucosa and the systemic immune function or by regulating the balance of intestinal flora, the single microorganism or the mixed microorganism with a clear composition that is beneficial to health is promoted to maintain intestinal health, thereby producing a beneficial effect on health. However, the application and development of probiotics for rhinitis nasal sensitivity in the prior art are still in the early stage.

[0004] Human milk oligosaccharides (HMOs) are a class of natural nutrients in human milk, and are the third largest nutrient in human milk, second only to fat and lactose. Its unique efficacy plays an important role in supporting the establishment of characteristic intestinal flora in infants and other populations, improving immunity, promoting brain development, and the like. However, there are few reports in the prior art on the application of HMOs for rhinitis nasal sensitivity.

[0005] A Chinese patent application with the application number CN202211358485.2 discloses a probiotic preparation and a prebiotic preparation for treating allergic rhinitis. Specifically, the probiotic preparation comprises Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus gasseri, Lactobacillus bifidus longum, Lactobacillus infantum, and Lactobacillus infantum. The prebiotic preparation comprises fructooligosaccharides and xylooligosaccharides. The probiotic preparation and the prebiotic preparation can synergistically enhance the effect of treating allergic rhinitis. However, the composition is relatively complex, and the application of some probiotics is limited. SUMMARY

[0006] To solve the above problems, the present application provides a composition based on the content of the prior art, comprising a specific probiotic combination and 2'-fucosyllactose. The probiotics selected by the present application include Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63, all of which are strains disclosed in the prior art and are commonly available on the market.

[0007] Bifidobacterium longum BB536 is a gram-positive, strictly anaerobic strain, which was first isolated from the intestinal tract of healthy breast-fed infants. BB536 is a human- friendly Bifidobacterium (HRB) probiotic strain. This strain has good food safety and meets the requirements of food probiotics.

[0008] Bifidobacterium breve M-16V is screened from the intestinal flora of infants and young children and is a strain related to healthy intestines. In particular, its immune system regulating effect and ability to promote intestinal health make it one of the standard probiotic strains commonly used in the art.

[0009] Bifidobacterium longum subsp. infantis M-63 mainly inhabits the intestinal tract of infants. Clinical studies have shown that it has a strong ability to utilize human milk oligosaccharides (HMOs) contained in breast milk and can improve the intestinal environment of healthy infants and young children. It is also known as a probiotic of the new era of HMOs. It can be used in infant formula milk powder and brings significant benefits to the development and health of infants and young children.

[0010] In the present application, 2'-fucosyllactose, as the component with the highest content in human milk oligosaccharides, is known to have the effects of enhancing immunity, resisting viruses, regulating intestinal flora and promoting the growth and development of infants and young children.

[0011] The present application uses scientific notation to represent the content of the bacteria, and the forms of "E+n" and "10 n " have the same meaning, as known by those skilled in the art, and are commonly used in the art, such as 2.5E+09 CFU / g and 2.5x10 9 CFU / g represent the same bacterial content.

[0012] In one aspect, the present application provides a composition of 2'-fucosyllactose and probiotics, characterized in that the active ingredients consist of 2'-fucosyllactose, Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63.

[0013] By weight, the active ingredients in the composition consist of 15-25 parts of 2'-fucosyllactose, 5-8 parts of Bifidobacterium longum BB536, 5-8 parts of Bifidobacterium breve M-16V and 1-5 parts of Bifidobacterium longum subsp. infantis M-63.

[0014] The content of 2'-fucosyllactose in the composition is 75-125 mg / g;

[0015] The ratio of the bacterial content of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 is 6-12:10-20:3-8;

[0016] The total bacterial content in the composition is >10 7 CFU / g.

[0017] The strains in the present application are all publicly known strains in the art, which can be purchased through conventional commercial channels, such as through Morinaga Milk Industry; or in some other ways, such as known to those skilled in the art, the Bifidobacterium longum BB536 has the accession number of ATCC BAA999; the Bifidobacterium breve M-16V has the accession number of LMG 23729. It should be noted that in the art, the strains selected in the present application are all star strains, and the corresponding strain numbers (BB536, M-16V, M-63) can be known by those skilled in the art to indicate which specific strain.

[0018] The content of 2'-fucosyllactose in the composition is selected from one or a combination of any of the following ranges: 75-100 mg / g, 100-125 mg / g, 75-80 mg / g, 75-90 mg / g, 75-95 mg / g, 75-105 mg / g, 75-110 mg / g, 75-120 mg / g, 80-120 mg / g, 90-120 mg / g, 80-125 mg / g, 95-125 mg / g, 105-125 mg / g, 110-125 mg / g, or a combination range of any of the above endpoint values;

[0019] Preferably, the ratio of the bacterial content of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 in the composition is 6-10:10-16:4-6; the total bacterial content in the composition is 10 9 CFU / g-10 11 CFU / g.

[0020] The ratio of the bacterial content of B. longum BB536, B. breve M-16V and B. longum subsp. infantis M-63 in the composition can be any of (8-10: 12-16: 5-6), (6-8: 10-16: 4-6), (6-10: 10-12: 4-5), (8-10: 10-16: 4-6), (8-10: 10-12: 5-6), (6-8: 12-16: 4-5), (6-8: 10-16: 4-6), (6-10: 10-16: 4-5), (6-10: 10-16: 5-6), (6-9: 12-15: 4-5), (7-8: 13-14: 4-5), or any combination of the end point values of the above ratio ranges.

[0021] The total bacterial content in the composition can be 10 9 CFU / g-10 11 CFU / g, preferably 10 9 CFU / g-10 10 CFU / g. Specifically, the total bacterial content in the composition can be: 2.5 x 10 9 CFU / g-7.5 x 10 9 CFU / g, 5 x 10 9 CFU / g-5 x 10 10 CFU / g, 3 x 10 9 CFU / g-8 x 10 10 CFU / g, 3.5 x 10 9 CFU / g-5 x 10 10 CFU / g, 3 x 10 9 CFU / g-4 x 10 10 CFU / g, 3 x 10 9 CFU / g-3.85 x 10 10 CFU / g, 3.85 x 10 9 CFU / g-4 x 10 10 CFU / g, 5 x 10 9 CFU / g-1 x 10 10 CFU / g, 4 x 10 9 CFU / g-1 x 10 10 CFU / g, or any combination of the end point values of the above.

[0022] Further preferably, the total bacterial content in the composition is 2.5E+09 CFU / g-7.5E+09 CFU / g.

[0023] Still further, the total bacterial content in the composition is:

[0024] Bifidobacterium longum BB536 is contained in an amount of 0.75E+09 CFU / g-2.5E+09 CFU / g;

[0025] Bifidobacterium breve M-16V is contained in an amount of 1.25E+09 CFU / g-4.0E+09 CFU / g;

[0026] Bifidobacterium longum subsp. infantis M63 is contained in an amount of 0.5E+09 CFU / g-1.5E+09 CFU / g.

[0027] The Bifidobacterium longum BB536 can be contained in an amount of 0.75E+09 CFU / g-2.5E+09 CFU / g, 2.0E+09 CFU / g-2.5E+09 CFU / g, 0.75E+09 CFU / g-2.0E+09 CFU / g, 0.8E+09 CFU / g-2.0E+09 CFU / g, 1E+09 CFU / g-2.0E+09 CFU / g, 1.5E+09 CFU / g-2.0E+09 CFU / g, 1.5E+09 CFU / g-2.5E+09 CFU / g, 1.5E+09 CFU / g-1.8E+09 CFU / g, 2.0E+09 CFU / g-2.3E+09 CFU / g, 2.3E+09 CFU / g-2.5E+09 CFU / g, or a combination of any of the above end point values.

[0028] The Bifidobacterium breve M-16V can be contained in an amount of 1.25E+09 CFU / g-4.0E+09 CFU / g, 1.25E+09 CFU / g-3.0E+09 CFU / g, 3.0E+09 CFU / g-4.0E+09 CFU / g, 1.5E+09 CFU / g-4.0E+09 CFU / g, 1.5E+09 CFU / g-3.0E+09 CFU / g, 1.25E+09 CFU / g-2.0E+09 CFU / g, 2.0E+09 CFU / g-4.0E+09 CFU / g, 2.0E+09 CFU / g-3.0E+09 CFU / g, 2.5E+09 CFU / g-3.5E+09 CFU / g, 3.5E+09 CFU / g-4.0E+09 CFU / g, 3.0E+09 CFU / g-3.5E+09 CFU / g, 3.5E+09 CFU / g-3.8E+09 CFU / g, 3.2E+09 CFU / g-3.6E+09 CFU / g, or a combination of any of the above end point values.

[0029] The content of B. longum infantis M63 can be in the range of 0.5E+09 CFU / g-1.5E+09 CFU / g, 0.5E+09 CFU / g-1.25E+09 CFU / g, 1.25E+09 CFU / g-1.5E+09 CFU / g, 0.5E+09 CFU / g-1E+09 CFU / g, 0.8E+09 CFU / g-1.25E+09 CFU / g, 1E+09 CFU / g-1.5E+09 CFU / g, 1E+09 CFU / g-1.25E+09 CFU / g, 1.2E+09 CFU / g-1.5E+09 CFU / g, 0.8E+09 CFU / g-1.2E+09 CFU / g, 1.3E+09 CFU / g-1.5E+09 CFU / g, 1.4E+09 CFU / g-1.5E+09 CFU / g, 1.25E+09 CFU / g-1.3E+09 CFU / g, 1.25E+09 CFU / g-1.45E+09 CFU / g, or a combination of any of the above end point values.

[0030] The content of each bacterium in the composition can be selected from the group consisting of any of the above single bacterium content, for example:

[0031] (1) 2+09 CFU / g-2.5+09 CFU / g of B. longum BB536, 3+09 CFU / g-4+09 CFU / g of B. breve M-16V, 1.25+09 CFU / g-1.5+09 CFU / g of B. longum infantis M63;

[0032] (2) 0.75+09 CFU / g-2+09 CFU / g of B. longum BB536, 1.25+09 CFU / g-4+09 CFU / g of B. breve M-16V, 0.5+09 CFU / g-1.5+09 CFU / g of B. longum infantis M63;

[0033] (3) 0.75+09 CFU / g-2.5+09 CFU / g of B. longum BB536, 1.25+09 CFU / g-3+09 CFU / g of B. breve M-16V, 0.5+09 CFU / g-1.25+09 CFU / g of B. longum infantis M63.

[0034] In some preferred embodiments, the content ratio of B. longum BB536, B. breve M-16V and B. longum infantis M-63 is 8-10:12-16:5-6; and the total content of bacteria in the composition is 6.75E+09 CFU / g-7.5E+09 CFU / g.

[0035] In more specific embodiments, the composition comprises:

[0036] 2'-fucosyllactose in an amount of 75-100 mg / g;

[0037] Bifidobacterium longum BB536 in an amount of 2.0E+09 CFU / g-2.5E+09 CFU / g;

[0038] Bifidobacterium breve M-16V in an amount of 3.0E+09 CFU / g-4.0E+09 CFU / g;

[0039] Bifidobacterium longum subsp. infantis M63 in an amount of 1.25E+09 CFU / g-1.5E+09 CFU / g.

[0040] In specific embodiments, the components of the composition can be selected from any one or more of the following:

[0041] (1) 2'-fucosyllactose in an amount of 100 mg / g; total bacteria in an amount of 6.75E+09 CFU / g; Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 in a ratio of 10:12:5;

[0042] (2) 2'-fucosyllactose in an amount of 125 mg / g; total bacteria in an amount of 2.5E+09 CFU / g; Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 in a ratio of 6:10:4;

[0043] (3) 2'-fucosyllactose in an amount of 75 mg / g; total bacteria in an amount of 7.5E+09 CFU / g; Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 in a ratio of 8:16:6.

[0044] It will be appreciated by those skilled in the art that combinations of the above ranges are also within the scope of the present application.

[0045] Preferably, the probiotic bacteria are in any one or more of the forms of live bacteria, dead bacteria, fermentation broth, fermentation broth precipitate and freeze-dried powder.

[0046] In another aspect, the present application provides the use of the composition in the preparation of a product for preventing or treating rhinitis or rhinitis sensitivity.

[0047] The symptoms of rhinitis or rhinitis sensitivity include, but are not limited to, any one or more of itching of the nose, sneezing, runny nose and nasal congestion; the symptoms of rhinitis sensitivity optionally include or exclude any one or more of itching of the eyes, redness of the eyes and tearing.

[0048] Based on the characteristics of probiotics, the rhinitis or nasal sensitivity symptoms can also be accompanied by intestinal symptoms or mental symptoms; the intestinal symptoms include but are not limited to intestinal distension; the mental symptoms include but are not limited to anxiety or sleep disorders.

[0049] Preferably, the rhinitis or nasal sensitivity symptoms can also be accompanied by easy fatigue or inattention.

[0050] The population suitable for the composition of the present application can be selected according to actual needs, including but not limited to infants (within 12 months after birth), young children (1-4 years old), children (5-11 years old), adolescents (12-18 years old), young adults (19-35 years old), middle-aged people (36-59 years old), the elderly (over 60 years old) and the like. It is particularly suitable for infants and children.

[0051] In another aspect, the present application provides a product comprising the composition.

[0052] The product includes but is not limited to a drug or a drug additive.

[0053] In some preferred conditions, the product can further comprise a freeze-drying protective agent for protecting live bacteria.

[0054] Preferably, the product can be a drug, which can further comprise a pharmaceutical excipient.

[0055] As known in the art, the pharmaceutical excipient includes but is not limited to any one or more of excipients, disintegrants, emulsifiers, fillers, diluents, binders, lubricants, stabilizers, plasticizers, opacifiers, color correctors, flavoring agents, co-solvents and surfactants.

[0056] In some specific embodiments, the drug can be an oral drug, including but not limited to any one or more of syrup, tablet, capsule, soft capsule, granule and oral liquid.

[0057] Advantages of the present application:

[0058] The present application obtains a composition for relieving rhinitis and nasal sensitivity by compounding three strains of probiotics in the prior art and further compounding 2'-fucosyllactose. Through verification in animal models, the composition of the present application can significantly reduce the occurrence of nasal sensitivity symptoms (nose scratching and sneezing) and reduce the expression of inflammatory factors. In a human experiment, the test product has the effects of relieving nasal sensitivity symptoms, relieving symptoms of nasal congestion, nasal itching, sneezing, runny nose and mouth breathing, reducing recurrence of nasal sensitivity symptoms, relieving intestinal distension, being more energetic, having a focused mind and a happy mood, improving sleep quality and learning state, etc., and has a good practical application prospect. Detailed Implementation

[0059] The present invention will be further described in detail below with reference to specific embodiments. The following embodiments are not intended to limit the present invention, but only to illustrate the present invention. Unless otherwise specified, the experimental methods used in the following embodiments are generally performed under conventional conditions. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available.

[0060] Unless otherwise specified, the same markings in different positions in this invention have similar meanings, as can be understood by those skilled in the art.

[0061] The sources of some of the raw materials used in this invention are shown in Table 1 below:

[0062] Table 1

[0063] Raw material name Brand / manufacturer Article number / code 2'-fucosyllactose Glycom - Bifidobacterium longum BB536 Morinaga ATCC BAA999 Bifidobacterium breve M-16V Morinaga LMG 23729 Bifidobacterium longum subsp. infantis M-63 Morinaga - Ovalbumin Merck A5503 BALB / c mice Vitonlva - IgE test kit (ELISA method) Shanghai Enzyme-linked ml037602 OVA-sIgE test kit (ELISA method) Shanghai Enzyme-linked ml063583

[0064] The probiotics used in this invention, as an example, are provided in the form of freeze-dried powder. Those skilled in the art can refer to the cultivation or freeze-drying methods in the prior art to prepare the raw materials, ensuring the bacterial content for actual application. In fact, the composition of this invention can also be provided in the form of a liquid formulation.

[0065] As is known to those skilled in the art, probiotics can be applied using live or dead bacteria. Dead bacteria do not affect the probiotic viability of the strain. This invention uses live bacteria powder as an example, but those skilled in the art can adjust the bacterial form according to actual circumstances. Based on the above, those skilled in the art should also understand that using fermentation broth containing live or dead bacteria, fermentation broth precipitate, freeze-dried powder, etc., are all possible applications of the composition of this invention.

[0066] Unless otherwise specified, the experimental schemes used for efficacy verification in this invention are all feasible for those skilled in the art using conventional techniques. For example, when it involves the detection of relative gene expression levels, the schemes in the existing technical literature “Yuan Xu. Effects of Linggui Zhugan Decoction combined with Pidotimod on the expression of TSLP, TNF-α, VCAM-1 and IL-4 in rats with spleen deficiency and dampness-predominant allergic rhinitis [D]. Inner Mongolia Medical University, 2020. DOI:10.27231 / d.cnki.gnmyc.2020.000190.” or targeted (e.g., for different animals) optimized schemes can be used. These methods are only set up to verify the efficacy of the technical solution of this invention and do not mean that the technical solution of this invention itself includes these efficacy verification methods.

[0067] Examples 1-3

[0068] The specific formulations involved in Examples 1-3 refer to Table 2:

[0069] Table 2

[0070]

[0071] In the selected raw material of the fungus, the addition amount is calculated according to the formula, so that the content of the fungus meets the requirements of the formula, and the other components in the formula are supplemented by non- effective component maltodextrin.

[0072] Comparative Examples 1-5

[0073] The specific formulations of Comparative Examples 1-5 refer to Table 3:

[0074] Table 3

[0075]

[0076] Effect verification of rhinitis mouse model in effect experiment example 1

[0077] The compositions of Examples 1-3 and Comparative Examples 1-7 were used to verify the effect of the animal model.

[0078] Experimental animals: SPF level BALB / c mice, female, body weight 20 ± 2 g, 6-8 weeks old. The mice were free to obtain food and water under the condition of 23-25℃ and humidity of 50%, and were adaptively fed for 1 week before the experiment.

[0079] Model construction method: from the first day of the experiment (marked as D1), the mice were injected intraperitoneally with 35 μg OVA (ovalbumin) + 4 mg Al (OH) 3 every other day, and the basic sensitization was completed after 5 injections. Starting from D10, the mice were given 3% OVA solution 1 μL per side per day for nasal instillation, and the instillation was continued for 7 days. On D17, the behavior of the mice was observed to determine the success of the model. The behavior evaluation method: within 15 min, more than 10 times of sneezing and more than 8 times of grabbing the nose were determined as successful model construction. From D18, the experiment was conducted by gavage.

[0080] The experimental animal grouping and treatment are as follows:

[0081] (1) Blank control group: the mice were not modeled, and the same amount of water was gavaged;

[0082] (2) Model group: model mice, gavaged with the same amount of water;

[0083] (3) Example group: the compositions of Examples 1-3 were respectively gavaged, and the mice were gavaged at a sample concentration (water soluble) of 5 g / L, twice a day, 1 mL each time, for 14 consecutive days;

[0084] (4) Comparative Example Group: The way of the Reference Example Group is adopted for gavage, the difference is that the composition of Comparative Example 1-5 is used as the sample, it should be noted that when the sample concentration should be adjusted according to different comparative examples, the standard for adjustment refers to the actual administration concentration of the active ingredient in the corresponding example, for example, the administration concentration of 2'-fucosyllactose in Comparative Example 2-5 should be the same as that of Example 1; the administration concentration of 2'-fucosyllactose in Comparative Example 6 should be the same as that of Example 2; Comparative Example 7 is the same as Example 3.

[0085] In each of the above groups, 7 parallels are set.

[0086] During the administration period, the OVA nasal challenge is continued in the groups other than the blank group, and the blank group is given an equal amount of normal saline for nasal instillation. On D25, behavioral observation statistics (number of nose scratching and sneezing) are performed. On D36, the mice are anesthetized, blood is taken from the eye orbit (serum is extracted), and the mice are sacrificed by decapitation, and the mouse nasal mucosa is obtained. The serum is subjected to IgE and OVA-sIgE content determination using a commercially available kit; the nasal mucosa is subjected to gene expression determination of inflammatory factors (TNF-α, VCAM-1, IL-4) using a commercially available kit and conventional detection method.

[0087] The experimental results are as follows:

[0088] (1) The D25 behavioral score statistics are as shown in Table 4:

[0089] Table 4

[0090] Group Scratch nose times (Mean ± STD) Sneeze times (Mean ± STD) Blank control 3.1±1.3 1.6±0.5 Model group 13.6 ± 1.1 αα ]] 12.0 ± 0.8 αα ]] Example 1 2.1 ± 1.1 ββ ]] 1.6 ± 0.5 ββ ]] Example 2 2.4 ± 0.8 ββ ]] 1.9 ± 0.7 ββ ]] Example 3 2.0 ± 1.0 ββ ]] 1.7 ± 0.8 ββ ]] Comparative example 1 9.3 ± 1.3 ββAA ]] 7.7 ± 1.1 ββAA ]] Comparative example 2 11.9 ± 1.1 βAA ]] 10.6 ± 1.3 βAA ]] Comparative example 3 9.3 ± 1.9 ββAA ]] 8.3 ± 1.6 ββAA ]] Comparative example 4 9.7 ± 1.4 ββAA ]] 7.9 ± 1.2 ββAA ]] Comparative example 5 8.3 ± 1.6 ββAA ]] 7.6 ± 1.5 ββAA ]] Comparative example 6 7.4 ± 2.0 ββBB ]] 8.1 ± 1.6 ββBB ]] Comparative example 7 8.0 ± 1.7 ββCC ]] 7.3 ± 1.8 ββCC ]]

[0091] Significant difference mark: model group compared with blank control, αα represents P<0.01; Examples 1-3, Comparative Examples 1-7 compared with model group, β represents P<0.05, ββ represents P<0.01; Comparative Examples 1-5 compared with Example 1, AA represents P<0.01; Comparative Example 6 compared with Example 2, BB represents P<0.01; Comparative Example 7 compared with Example 3, CC represents P<0.01.

[0092] In addition, since the values of the number of nose scratching and sneezing are all integer values, the probability of repeated data in the statistical results is increased, so the sneezing frequency of Comparative Example 3 and the nose scratching frequency of Comparative Example 5 in Table 4 are the same, but their original data are different, wherein the original data of the sneezing frequency of Comparative Example 3 is: 6, 9, 7, 10, 7, 9, 10; the original data of the nose scratching frequency of Comparative Example 5 is: 10, 7, 7, 8, 7, 8, 11.

[0093] The data in Table 4 show that the compositions of Examples 1-3 of the present application can significantly reduce the number of nose scratching and sneezing of the modeling animals, and are basically close to the blank control, and obviously relieve the symptoms of rhinitis and nasal sensitivity; the data of Comparative Examples 1-7 are all not as good as Example 1, indicating that the components of the present application have certain synergistic effect.

[0094] (2) The serum test results are as follows in Table 5

[0095] Table 5

[0096]

[0097]

[0098] Significant difference mark: the model group compared with the blank control, αα represents P < 0.001; Examples 1-3, Comparative Examples 1-7 compared with the model group, β represents P < 0.05, ββ represents P < 0.01; Comparative Example 1-5 compared with Example 1, AA represents P < 0.01; Comparative Example 6 compared with Example 2, BB represents P < 0.01; Comparative Example 7 compared with Example 3, CC represents P < 0.01.

[0099] The above Table 5 data can show that the composition of the present application can reduce the content of IgE, OVA-sIgE in serum in relieving rhinitis and nasal sensitivity, indicating that it has a positive effect, and the component dosage in the formula has certain synergistic effect.

[0100] (3) The expression amount (relative expression amount, no unit, internal reference gene is GAPDH) of inflammatory factors in nasal mucosa tissue is as follows in Table 6:

[0101] Table 6

[0102]

[0103]

[0104] Significant difference mark: the model group compared with the blank control, αα represents P < 0.01; Examples 1-3, Comparative Examples 1-7 compared with the model group, β represents P < 0.05, ββ represents P < 0.01; Comparative Example 1-5 compared with Example 1, AA represents P < 0.01; Comparative Example 6 compared with Example 2, BB represents P < 0.01; Comparative Example 7 compared with Example 3, CC represents P < 0.01.

[0105] The above Table 6 data can show that the composition of the present application can reduce the expression of inflammatory factors in relieving rhinitis and nasal sensitivity, and there is certain synergistic effect between the components.

[0106] Effect experiment example 2 crowd effect verification

[0107] According to the animal experiment results, it can be seen that Example 1 has the best effect, and further product testing is carried out using the composition of Example 1 for testing, and 56 cases of 6 months-14 years old (not included) are tested for 3 months by using the composition of Example 1 for 3 months.

[0108] 1. The basic information of the subjects is as follows:

[0109]

[0110] 2. The detection indexes are as follows:

[0111]

[0112]

[0113] 3. The method for using the test product is as follows:

[0114] 175mg composition is taken with water, and is used for 4 weeks, and after the end of the taking period, the statistical data is continued to follow up. The activity of probiotics is reduced above 40℃, and the most suitable is to use 37℃ warm water to brew, and the use of antibiotics is suspended in the test process.

[0115] 4. The data statistical method is as follows:

[0116] Descriptive statistics: percentage / average value; difference statistics: percentage uses T test for significance test; average value uses repeated measurement analysis of variance for significance test; P<0.05: at the confidence level of 95%, there is a significant difference in the data. P<0.1: at the confidence level of 90%, there is a significant difference in the data.

[0117] The statistical results are as follows:

[0118] (1) Improvement of nasal sensitivity symptoms

[0119]

[0120] The score range is 0-10, 0 means no improvement at all, and 10 means very great improvement. The greater the mean value, the greater the degree of improvement. The significance marking method: capital letters represent P<0.05; small letters represent P<0.1.

[0121] (2) Degree of nasal sensitivity symptom disturbance (score)

[0122]

[0123]

[0124] Score range 0-10, 0 means no disturbance at all, 10 means very disturbed. The smaller the mean value, the less the degree of disturbance. Significant annotation method: capital letters represent P<0.05; lowercase letters represent P<0.1.

[0125] (3) Duration of nasal sensitivity symptoms

[0126]

[0127] The smaller the mean value, the shorter the duration of nasal sensitivity symptoms. Significant annotation method: capital letters represent P<0.05; lowercase letters represent P<0.1.

[0128] (4) Change in nasal sensitivity recurrence frequency (number of people)

[0129]

[0130]

[0131] Significant annotation method: capital letters represent P<0.05; lowercase letters represent P<0.1.

[0132] (5) Intestinal gas frequency (number of people)

[0133]

[0134] The smaller the mean value, the lower the intestinal gas frequency. Significant annotation method: capital letters represent P<0.05; lowercase letters represent P<0.1.

[0135] (6) Mental state score (score statistics)

[0136]

[0137] In summary:

[0138] According to the evaluation results of 56 cases of 6 months-14 years old (not included) who self-reported that they had nasal sensitivity symptoms (main nasal sensitivity symptoms include nasal itching, sneezing, runny nose, nasal congestion, accompanied by eye itching, red eyes and tearing, etc.) in the past two weeks through 3-month in-dwelling test of the product, the test product has the following effects:

[0139] Relieve nasal sensitivity symptoms: 100% of the subjects recognized that the product could relieve nasal sensitivity symptoms.

[0140] Relief of nasal congestion, nasal itching, sneezing, runny nose and mouth breathing symptoms: 84% of subjects recognized that they could relieve the symptoms of nasal congestion, 88% of subjects recognized that they could relieve the symptoms of nasal itching, 86% of subjects recognized that they could relieve the symptoms of sneezing, 80% of subjects recognized that they could relieve the symptoms of runny nose, and 83% of subjects recognized that they could relieve the symptoms of mouth breathing.

[0141] Reduction of recurrence of nasal sensitivity symptoms: 52% of subjects recognized that they could reduce the duration of nasal sensitivity symptoms, 25% of subjects recognized that they could reduce the number of days of nasal sensitivity symptoms per week, 95% of subjects recognized that they could reduce the frequency of recurrence of nasal sensitivity, and 90% of subjects recognized that they could shorten the cycle of nasal sensitivity.

[0142] Relief of intestinal flatulence symptoms: 41% of subjects recognized that they could relieve intestinal flatulence.

[0143] More energetic, more focused and more cheerful: 55% of subjects recognized that they were more "energetic", 70% of subjects recognized that they were more "focused", and 50% of subjects recognized that they were more "cheerful".

[0144] Improvement of sleep quality and learning state: 63% of subjects recognized that they could improve "sleep quality", and 61% of subjects recognized that they could improve "learning state".

[0145] The above examples are only used to illustrate the present application, not to limit the present application, and the technical solutions developed by the technical personnel in the art without departing from the technical concept of the present application, adjusting, optimizing, upgrading and iterating the technical solutions are within the protection scope of the present application.

Claims

1. A composition of 2'-fucosyllactose and probiotic bacteria, characterized in that, The effective component consists of 2'-fucosyllactose, Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63. The content of 2'-fucosyllactose in the composition is 75-125 mg / g. The content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 is 6-12:10-20:3-8. The total bacteria content in the composition is > 10 7 CFU / g.

2. The composition of claim 1, wherein, The proportion of the bacterial content of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 in the composition is 6-10: 10-16: 4-6; the total bacterial content in the composition is 10 9 CFU / g-10 11 CFU / g.

3. The composition of claim 2, wherein, The total bacteria content in the composition is 2.5 x 10 9 CFU / g-7.5 x 10 9 CFU / g.

4. The composition of claim 3, wherein, The composition further comprises one or more of the following components: Bifidobacterium longum BB536 at a content of 0.75 x 10 9 CFU / g-2.5 x 10 9 CFU / g; Bifidobacterium breve M-16V in an amount of: 1.25 x 10 9 CFU / g-4.0 x 10 9 CFU / g; Bifidobacterium longum subsp. infantis M63 in an amount of: 0.5 x 10 9 CFU / g-1.5 x 10 9 CFU / g.

5. The composition of claim 4, wherein, The proportions of the Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 are 8-10:12-16:5-6; the total bacterial content in the composition is 6.75x10 9 CFU / g-7.5x10 9 CFU / g.

6. The composition of claim 5, wherein, The composition further comprises one or more of the following components: The content of 2'-fucosyllactose is 75-100 mg / g. Bifidobacterium longum BB536 at a content of 2.0 x 10 9 CFU / g-2.5 x 10 9 CFU / g; Bifidobacterium breve M-16V in an amount of: 3.0 x 10 9 CFU / g-4.0 x 10 9 CFU / g; Bifidobacterium longum subsp. infantis M63 in an amount of: 1.25 x 10 9 CFU / g-1.5 x 10 9 CFU / g.

7. The composition of claim 1, wherein, The form of the probiotic bacteria is any one or more of the following: live bacteria, fermentation broth and freeze-dried powder.

8. Use of the composition of any one of claims 1-7 in the preparation of a product for preventing or treating rhinitis or rhinitis sensitivity.

9. Use according to claim 8, characterized in that, The symptoms of rhinitis or rhinitis sensitivity include any one or more of the following: nasal itching, sneezing, rhinorrhea and nasal congestion; the symptoms of rhinitis sensitivity optionally include or exclude any one or more of the following: eye itching, eye redness and tearing.

10. Use according to claim 9, characterized in that, The symptoms of rhinitis or rhinitis sensitivity are accompanied by intestinal symptoms or mental symptoms; the intestinal symptoms include intestinal flatulence; the mental symptoms include anxiety or sleep disorders.

11. Use according to claim 10, characterized in that, The symptoms of rhinitis or rhinitis sensitivity are accompanied by easy fatigue or lack of concentration.

12. A product comprising the composition according to any one of claims 1 to 7, characterized in that, The product includes a pharmaceutical product or an additive for a pharmaceutical product.

13. The product of claim 12, wherein, The product further comprises a freeze-drying protective agent for protecting the live bacteria.

14. The product of claim 12, wherein, The product is a pharmaceutical product, and the pharmaceutical product further comprises a pharmaceutical excipient.

15. The product of claim 14, wherein, The pharmaceutical excipient includes an excipient and / or a diluent.

16. The product of claim 14, wherein, The pharmaceutical excipient includes any one or more of the following: a disintegrant, an emulsifier, a filler, a binder, a lubricant, a stabilizer, a plasticizer, an opacifier, a color corrector, a flavoring agent, a solubilizer and a surfactant.

17. The product according to claim 15 or 16, characterized in that, The pharmaceutical product is an oral pharmaceutical product, and the oral pharmaceutical product includes any one or more of the following: a tablet, a capsule, a granule and an oral liquid.

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