Composition of 2 '-fucosyllactose and probiotics as well as application and product thereof

Abstract

The invention provides a composition of 2 '-fucosyllactose and probiotics and application of the composition, and belongs to the technical field of probiotics. The effective components in the composition comprise the following components: 2 '-fucosyllactose, bifidobacterium longum BB536, bifidobacterium breve M-16V and bifidobacterium longum subsp. Infantis M-63. Through compounding of probiotics and 2'-fucosyllactose, the composition has a relatively good relieving effect in rhinitis and nasal allergy, and has a very good market application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of probiotics, and specifically relates to a composition of 2'-fucosyllactose and probiotics, and an application and product thereof. Background Art

[0002] Rhinitis and nasal allergy patients mainly show symptoms such as nasal obstruction, nasal itching, sneezing, runny nose, or with subjective symptoms such as dry eyes. Its pathogenesis is diverse. For example, the pathogenesis of rhinitis disclosed in the prior art can be: pollen, dust and other external impurities invade the body as allergens, so that the body-specific antibodies are produced and the initial response is made. When the same allergen invades the body again, antigen presenting cells will recognize and process it. The processed allergens induce the initial T cell tropism differentiation, so Thl / Th2, Th17 / Treg cell differentiation bias, and then secrete IL-4, TNF-α and other inflammatory cytokines, thereby causing the occurrence of rhinitis. Western medicine treatment is the main choice at present, but no medicine that can prevent the recurrence of allergic rhinitis has been developed yet. At present, the simple use of Western medicine treatment, although it can effectively relieve symptoms, has good short-term efficacy, but the efficacy time is not lasting. And the safety of Western medicine needs to be considered.

[0003] Probiotics colonize in the human body and change the composition of the host's flora in a certain part, which is beneficial to the host. They promote nutrient absorption and maintain intestinal health by regulating the host's mucosal and systemic immune functions or by regulating the balance of intestinal flora, thereby producing single microorganisms or mixed microorganisms with clear composition that are beneficial to health. However, the application and development of probiotics for rhinitis and nasal allergies in the prior art is still in its early stages.

[0004] Human milk oligosaccharides (HMOs) are a type of nutrient naturally present in breast milk and are the third largest nutrient in breast milk, second only to fat and lactose. Their unique efficacy plays an important role in supporting the establishment of characteristic intestinal flora in infants and other groups, improving immunity, and promoting brain development. However, there are few reports on the application of existing technologies in rhinitis and nasal allergies.

[0005] A Chinese patent application with application number CN202211358485.2 discloses a probiotic preparation and a prebiotic preparation for the treatment of allergic rhinitis. Specifically, the probiotic preparation contains Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus gasseri, Bifidobacterium longum, Bifidobacterium lactis, and Bifidobacterium infantis; the prebiotic preparation contains oligofructose and oligoxylose. The probiotic preparation and the prebiotic preparation can work synergistically to enhance the effect of treating allergic rhinitis. However, its composition is relatively complex, and the application population of some probiotics is limited. Summary of the invention

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

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

[0008] Bifidobacterium breve M-16V is selected from the flora in the intestines of infants and young children. It is a strain associated with healthy intestines. In particular, it has the ability to regulate the immune system and promote intestinal health, and is one of the standard probiotic strains commonly used in the field.

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

[0010] In the present invention, 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.

[0011] The present invention adopts scientific notation to express the bacterial content, in the form of "E+n" and "10 n " have equivalent meanings, as known to those skilled in the art, and are commonly used expressions in the art, such as 2.5E+09CFU / g and 2.5×10 9 CFU / g indicates the same bacterial content.

[0012] In one aspect, the present invention provides a composition of 2'-fucosyllactose and probiotics, characterized in that the effective ingredients consist of: 2'-fucosyllactose, Bifidobacterium longum BB536, Bifidobacterium breve M-16V, Bifidobacterium longum subspecies infantis M-63;

[0013] The effective ingredients in the composition are composed of the following by weight: 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 subspecies infantis M-63;

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

[0015] The bacterial content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 was 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 invention are all strains disclosed in the art and can be purchased through conventional commercial channels, such as through Morinaga Milk; or in some other ways, as known to those skilled in the art, the long Bifidobacterium BB536 has a deposit number of ATCC BAA999; the breve Bifidobacterium M-16V has a deposit number of LMG 23729. It should be noted that in the art, the strains selected in the present invention are all star strains, and the corresponding strain numbers (BB536, M-16V, M-63) can be known to those skilled in the art as to which specific strains they refer to.

[0018] In the composition, the content of 2'-fucosyllactose is selected from one or a combination 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 of any endpoint values ​​above;

[0019] Preferably, in the composition, the ratio of the bacterial content of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum infantis subspecies M-63 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 bacterial content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subspecies infantis M-63 in the composition can be any one 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 range of the endpoint 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: 2.5×10 9 CFU / g-7.5×10 9 CFU / g, 5×10 9 CFU / g-5×10 10 CFU / g, 3×10 9 CFU / g-8×10 10 CFU / g, 3.5×10 9 CFU / g-5×10 10 CFU / g, 3×10 9 CFU / g-4×10 10 CFU / g, 3×10 9 CFU / g-3.85×10 10 CFU / g, 3.85×10 9 CFU / g-4×10 10 CFU / g, 5×10 9 CFU / g-1×10 10 CFU / g, 4×10 9 CFU / g-1×10 10 CFU / g or the content range represented by a combination of any of the above endpoint values.

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

[0023] Furthermore, in the composition:

[0024] The content of Bifidobacterium longum BB536 is: 0.75E+09CFU / g-2.5E+09CFU / g;

[0025] The content of Bifidobacterium breve M-16V is: 1.25E+09CFU / g-4.0E+09CFU / g;

[0026] The content of Bifidobacterium longum subspecies infantis M63 is: 0.5E+09CFU / g-1.5E+09CFU / g.

[0027] Wherein, the content of Bifidobacterium longum BB536 can be: 0.75E+09CFU / g-2.5E+09CFU / g, 2.0E+09CFU / g-2.5E+09CFU / g, 0.75E+09CFU / g-2.0E+09CFU / g, 0.8E+09CFU / g-2.0E+09CFU / g, 1E+09CFU / g-2.0E+09CFU / g g, 1.5E+09CFU / g-2.0E+09CFU / g, 1.5E+09CFU / g-2.5E+09CFU / g, 1.5E+09CFU / g-1.8E+09CFU / g, 2.0E+09CFU / g-2.3E+09CFU / g, 2.3E+09CFU / g-2.5E+09CFU / g or the content range represented by a combination of any of the above endpoint values.

[0028] The content of the Bifidobacterium breve M-16V can be: 1.25E+09CFU / g-4.0E+09CFU / g, 1.25E+09CFU / g-3.0E+09CFU / g, 3.0E+09CFU / g-4.0E+09CFU / g, 1.5E+09CFU / g-4.0E+09CFU / g, 1.5E+09CFU / g-3.0E+09CFU / g, 1.25E+09CFU / g-2.0E+09CFU / g, 2.0E+09CFU / g -4.0E+09CFU / g, 2.0E+09CFU / g-3.0E+09CFU / g, 2.5E+09CFU / g-3.5E+09CFU / g, 3.5E+09CFU / g-4.0E+09CFU / g, 3.0E+09CFU / g-3.5E+09CFU / g, 3.5E+09CFU / g-3.8E+09CFU / g, 3.2E+09CFU / g-3.6E+09CFU / g or the content range represented by a combination of any of the above endpoint values.

[0029] The content of the Bifidobacterium longum subspecies infantis M63 can be 0.5E+09CFU / g-1.5E+09CFU / g, 0.5E+09CFU / g-1.25E+09CFU / g, 1.25E+09CFU / g-1.5E+09CFU / g, 0.5E+09CFU / g-1E+09CFU / g, 0.8E+09CFU / g-1.25E+09CFU / g, 1E+09CFU / g-1.5E+09CFU / g, 1E+09CFU / g-1.2 The content range represented by the combination of any endpoint values ​​above is 5E+09CFU / g, 1.2E+09CFU / g-1.5E+09CFU / g, 0.8E+09CFU / g-1.2E+09CFU / g, 1.3E+09CFU / g-1.5E+09CFU / g, 1.4E+09CFU / g-1.5E+09CFU / g, 1.25E+09CFU / g-1.3E+09CFU / g, 1.25E+09CFU / g-1.45E+09CFU / g or any combination of the above endpoint values.

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

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

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

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

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

[0035] In a more specific embodiment, in the composition:

[0036] The content of 2'-fucosyllactose is 75-100 mg / g;

[0037] The content of Bifidobacterium longum BB536 is: 2.0E+09CFU / g-2.5E+09CFU / g;

[0038] The content of Bifidobacterium breve M-16V is: 3.0E+09CFU / g-4.0E+09CFU / g;

[0039] The content of Bifidobacterium longum subspecies infantis M63 is: 1.25E+09CFU / g-1.5E+09CFU / g.

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

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

[0042] (2) The content of 2'-fucosyllactose was 125 mg / g; the total bacterial content was 2.5E+09 CFU / g; the bacterial content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 was 6:10:4;

[0043] (3) The content of 2'-fucosyllactose was 75 mg / g; the total bacterial content was 7.5E+09 CFU / g; the bacterial content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 was 8:16:6.

[0044] Those skilled in the art should be aware that combinations of the above range values ​​are also within the scope of the technical solution of the present invention.

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

[0046] In another aspect, the present invention provides use of the composition in preparing a product for preventing and treating rhinitis or nasal allergy.

[0047] The rhinitis or nasal allergy symptoms include, but are not limited to, any one or more of nasal itching, sneezing, runny nose and nasal congestion; the nasal allergy symptoms selectively include or do not include any one or more of eye itching, red eyes and tearing.

[0048] Based on the characteristics of probiotics, the rhinitis or nasal allergy symptoms may also be accompanied by intestinal symptoms or psychiatric symptoms; the intestinal symptoms include but are not limited to intestinal bloating; the psychiatric symptoms include but are not limited to anxiety or sleep disorders.

[0049] Preferably, the rhinitis or nasal allergy symptoms may also be accompanied by fatigue or inattention.

[0050] The composition of the present invention can be applied to a variety of groups according to actual needs, including but not limited to infants (within 12 months of birth), toddlers (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), and the elderly (over 60 years old). It is particularly suitable for infants and children.

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

[0052] The products include but are not limited to food or food additives, medicines or medicine additives, health products or health product additives.

[0053] In some preferred conditions, the product may further include a freeze-drying protectant for protecting live bacteria.

[0054] Preferably, the product can be a food or a health product, and the food or health product also includes any one or more of the flavoring agents, fragrance agents, thickeners, antioxidants, preservatives, colorants, color retainers, enzyme preparations and emulsifiers required for the food or health product.

[0055] In some specific embodiments, the product is selected from: any one or more of biscuits, cakes, jelly candies, hard candies, marshmallows, functional drinks, juices, effervescent tablets, yogurt, cheese, ice cream, modulated milk powder, granules, solid drinks, chewable tablets, soft candies, and drops.

[0056] Preferably, the product may be a medicine, which may further include pharmaceutical excipients.

[0057] As is well known in the art, the pharmaceutical excipients include, but are not limited to, any one or more of excipients, disintegrants, emulsifiers, fillers, diluents, binders, lubricants, stabilizers, plasticizers, opacifiers, colorants, flavoring agents, cosolvents and surfactants.

[0058] In some specific embodiments, the medicine may be an oral medicine, including but not limited to any one or more of syrup, tablet, capsule, soft capsule, granule and oral liquid.

[0059] Beneficial effects of the present invention:

[0060] The present invention obtains a composition having the effect of relieving rhinitis and nasal sensitivity by compounding three probiotics in the prior art and further compounding with 2'-fucosyllactose. Through verification in an animal model, the composition of the present invention can significantly reduce the occurrence of nasal sensitivity symptoms (scratching the nose, sneezing), and can reduce the expression of inflammatory factors. In the population experiment, the test product has the following effects: relieving nasal sensitivity symptoms; relieving nasal congestion, nasal itching, sneezing, runny nose and mouth breathing symptoms; reducing the recurrence of nasal sensitivity symptoms; relieving intestinal flatulence symptoms; being more energetic, focused and happy; improving sleep quality and learning status; etc., and has a good practical application prospect. DETAILED DESCRIPTION

[0061] The present invention will be further described in detail below in conjunction with specific examples. The following examples are not intended to limit the present invention, but are only intended to illustrate the present invention. The experimental methods used in the following examples are generally conventional, unless otherwise specified, and the materials, reagents, etc. used in the following examples are commercially available, unless otherwise specified.

[0062] Unless otherwise specified, the same symbols in the present invention have similar meanings in different positions, which can be understood by those skilled in the art.

[0063] The sources of some raw materials used in the present invention are as follows:

[0064] Table 1

[0065] Raw material name Brand / Manufacturer Item No. / Serial No. 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 Vital River - IgE test kit (ELISA method) Shanghai ELISA ml037602 OVA-sIgE detection kit (ELISA method) Shanghai ELISA ml063583

[0066] The probiotics used in the present invention are provided in the form of freeze-dried powder as an example, and those skilled in the art can refer to the cultivation method or freeze-drying method in the prior art to prepare the raw materials to ensure the bacterial content in actual application. In fact, the composition of the present invention can also be provided in the form of a liquid preparation.

[0067] As known to those skilled in the art, probiotics can be used in the form of live bacteria or dead bacteria, and dead bacteria do not affect the probiotic activity of the strain. In the embodiments of the present invention, live bacteria powder is used as an example, but those skilled in the art can adjust the form of bacteria according to actual conditions. Based on the above, those skilled in the art should also know that the use of fermentation broth containing live or dead bacteria, fermentation broth precipitation, freeze-dried powder, etc. are all possible application methods of the composition of the present invention.

[0068] The experimental schemes for effect verification performed in the present invention, unless otherwise specified, can be implemented by those skilled in the art according to conventional technical means in the art. For example, when it comes to the detection of relative gene expression, reference can be made to the schemes in the prior art document "Yuan Xu. Effect of Ling Gui Zhu Gan Tang combined with Pidotimod on the expression of TSLP, TNF-α, VCAM-1, and IL-4 in rats with allergic rhinitis of spleen deficiency and dampness type [D]. Inner Mongolia Medical University, 2020. DOI: 10.27231 / d.cnki.gnmyc.2020.000190." or targeted (such as for different animals) optimization schemes. These methods are only set up to verify the effect of the technical scheme of the present invention, and do not mean that the technical scheme of the present invention itself includes these effect verification methods.

[0069] Examples 1-3

[0070] The specific formulas involved in Examples 1-3 refer to Table 2:

[0071] Table 2

[0072]

[0073] The purchased bacterial raw materials are used, and the added amount is calculated according to the formula so that the bacterial content meets the requirements of the formula. Other ingredients in the formula are supplemented with non-functional ingredient maltodextrin.

[0074] Comparative Examples 1-5

[0075] The specific formula of Comparative Examples 1-5 is shown in Table 3:

[0076] Table 3

[0077]

[0078]

[0079] Effect Experiment Example 1 Effect Verification of Rhinitis Mouse Model

[0080] The compositions of Examples 1-3 and Comparative Examples 1-7 were used to verify the effects on animal models.

[0081] Experimental animals: SPF BALB / c female mice, weighing 20±2g, 6-8 weeks old. Mice were given free access to food and water at 23-25℃ and 50% humidity, and the experiment was carried out after 1 week of adaptive feeding.

[0082] Model construction method: From the first day of the experiment (recorded as D1), 35μg OVA (ovalbumin) + 4mg Al(OH)3 were injected into the mouse peritoneum every other day. After 5 injections, the basic sensitization was completed. Starting from D10, 1μL of 3% OVA solution was dripped into each side of the mouse nasal cavity every day for nasal drip stimulation. After 7 days of continuous stimulation, the mice were behaviorally observed on D17 to determine the success of the model. Behavioral evaluation method: within 15 minutes, the number of sneezes was more than 10 times and the number of nose scratching was more than 8 times, and the model was successfully constructed. The gavage experiment started on D18.

[0083] The experimental animals were grouped and treated as follows:

[0084] (1) Blank control group: mice were not modeled and gavaged with an equal amount of water;

[0085] (2) Model group: model mice were gavaged with an equal amount of water;

[0086] (3) Example group: The mice were gavaged with the compositions of Examples 1-3 at a sample concentration of 5 g / L (water soluble), twice a day, with a gavage volume of 1 mL each time, for 14 consecutive days;

[0087] (4) Comparative Example Group: Intragastric administration was performed in the same manner as in the Example Group, except that the compositions of Comparative Examples 1-5 were used as samples. It should be noted that during administration, the sample concentration should be adjusted according to the different comparative examples, and the adjustment standard should refer to the actual administration concentration of the active ingredient in the corresponding example. For example, the administration concentration of 2'-fucosyllactose in Comparative Examples 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; and Comparative Example 7 is the same as Example 3.

[0088] In each of the above groups, 7 parallels were set up.

[0089] During the administration period, except for the blank group, the other groups continued to maintain OVA nasal drops, and the blank group used an equal amount of saline nasal drops. Behavioral observations (number of nose scratching and sneezing) were performed on D25. On D36, the mice were anesthetized, and after orbital blood sampling (serum extraction), the mice were killed by dislocation of the neck, and the nasal mucosal tissue of the mice was obtained. The serum IgE and OVA-sIgE content were determined using commercial kits; the nasal mucosal tissue was determined using commercial kits and conventional detection methods to determine the gene expression of inflammatory factors (TNF-α, VCAM-1, IL-4).

[0090] The experimental results are as follows:

[0091] (1) The statistical results of D25 behavioral scores are shown in Table 4:

[0092] Table 4

[0093] Group Nose grabbing times (Mean±STD) Number of sneezes (Mean±STD) Blank control 3.1±1.3 1.6±0.5 Model Group <![CDATA[13.6±1.1 αα ]]> <![CDATA[12.0±0.8 αα ]]> Example 1 <![CDATA[2.1±1.1 ββ ]]> <![CDATA[1.6±0.5 ββ ]]> Example 2 <![CDATA[2.4±0.8 ββ ]]> <![CDATA[1.9±0.7 ββ ]]> Example 3 <![CDATA[2.0±1.0 ββ ]]> <![CDATA[1.7±0.8 ββ ]]> Comparative Example 1 <![CDATA[9.3±1.3 ββAA ]]> <![CDATA[7.7±1.1 ββAA ]]> Comparative Example 2 <![CDATA[11.9±1.1 βAA ]]> <![CDATA[10.6±1.3 βAA ]]> Comparative Example 3 <![CDATA[9.3±1.9 ββAA ]]> <![CDATA[8.3±1.6 ββAA ]]> Comparative Example 4 <![CDATA[9.7±1.4 ββAA ]]> <![CDATA[7.9±1.2 ββAA ]]> Comparative Example 5 <![CDATA[8.3±1.6 ββAA ]]> <![CDATA[7.6±1.5 ββAA ]]> Comparative Example 6 <![CDATA[7.4±2.0 ββBB ]]> <![CDATA[8.1±1.6 ββBB ]]> Comparative Example 7 <![CDATA[8.0±1.7 ββCC ]]> <![CDATA[7.3±1.8 ββCC ]]>

[0094] Significant difference mark: compared with the blank control, the model group, αα means P < 0.01; compared with the model group, Examples 1-3 and Comparative Examples 1-7, β means P < 0.05, and ββ means P < 0.01; compared with Example 1, AA means P < 0.01 for Comparative Examples 1-5; compared with Example 2, BB means P < 0.01 for Comparative Example 6; compared with Example 3, CC means P < 0.01 for Comparative Example 7.

[0095] In addition, since the statistical values ​​of the number of nose-scratching and sneezing are both integers, the probability of duplicate data in the statistical results is increased. Therefore, the statistical results of the number of sneezes in Comparative Example 3 and the number of nose-scratching in Comparative Example 5 in Table 4 are the same, but the original data of the two are different. The original data of the number of sneezes in Comparative Example 3 are: 6, 9, 7, 10, 7, 9, 10; the original data of the number of nose-scratching in Comparative Example 5 are: 10, 7, 7, 8, 7, 8, 11.

[0096] The data in Table 4 show that the compositions of Examples 1-3 of the present invention can significantly reduce the number of nose scratching and sneezing in the model animals, which is basically close to that of the blank control, and significantly alleviates the symptoms of rhinitis and nasal allergy; the data of Comparative Examples 1-7 are not as good as Example 1, indicating that the components of the present invention have a certain synergistic effect.

[0097] (2) Serum test results are shown in Table 5

[0098] Table 5

[0099] Group IgE (ng / mL, Mean±STD) OVA-sIgE (ng / mL, Mean±STD) Blank control 196.6±8.3 42.5±4.2 Model Group <![CDATA[490.7±15.6 αα ]]> <![CDATA[168.4±9.5 αα ]]> Example 1 <![CDATA[188.4±14.4 ββ ]]> <![CDATA[64.3±6.1 ββ ]]> Example 2 <![CDATA[192.1±15.2 ββ ]]> <![CDATA[69.7±8.4 ββ ]]> Example 3 <![CDATA[185.5±17.5 ββ ]]> <![CDATA[66.4±6.7 ββ ]]> Comparative Example 1 <![CDATA[254.2±8.9 ββAA ]]> <![CDATA[135.5±9.1 ββAA ]]> Comparative Example 2 <![CDATA[377.2±7.1 ββAA ]]> <![CDATA[159.8±12.8 AA ]]> Comparative Example 3 <![CDATA[287.0±16.7 ββAA ]]> <![CDATA[142.9±4.9 βAA ]]> Comparative Example 4 <![CDATA[265.3±9.0 ββAA ]]> <![CDATA[134.6±12.4 ββAA ]]> Comparative Example 5 <![CDATA[232.8±6.7 ββAA ]]> <![CDATA[106.0±10.3 ββAA ]]> Comparative Example 6 <![CDATA[257.7±14.5 ββBB ]]> <![CDATA[148.2±7.8 βBB ]]> Comparative Example 7 <![CDATA[274.5±16.4 ββCC ]]> <![CDATA[157.1±9.6 CC ]]>

[0100] Significant difference mark: compared with the blank control, the model group, αα means P < 0.001; compared with the model group, Examples 1-3 and Comparative Examples 1-7, β means P < 0.05, and ββ means P < 0.01; compared with Example 1, AA means P < 0.01 for Comparative Examples 1-5; compared with Example 2, BB means P < 0.01 for Comparative Example 6; and compared with Example 3, CC means P < 0.01 for Comparative Example 7.

[0101] It can be seen from the data in Table 5 that the composition of the present invention can reduce the levels of IgE and OVA-sIgE in serum in relieving rhinitis and nasal allergy, indicating that it has a positive effect, and the dosage of the ingredients in the formula has a certain synergistic effect.

[0102] (3) The results of the detection of inflammatory factor expression levels in nasal mucosal tissue (relative expression levels, no unit, internal reference gene is GAPDH) are as follows:

[0103] Table 6

[0104]

[0105]

[0106] Significant difference mark: compared with the blank control, the model group, αα means P < 0.01; compared with the model group, Examples 1-3 and Comparative Examples 1-7, β means P < 0.05, and ββ means P < 0.01; compared with Example 1, AA means P < 0.01 for Comparative Examples 1-5; compared with Example 2, BB means P < 0.01 for Comparative Example 6; compared with Example 3, CC means P < 0.01 for Comparative Example 7.

[0107] It can be seen from the data in Table 6 above that the composition of the present invention can reduce the expression of inflammatory factors in relieving rhinitis and nasal allergy, and there is a certain synergistic effect between the components.

[0108] Effect Experiment Example 2: Population Effect Verification

[0109] According to the results of animal experiments, it can be seen that Example 1 has the best effect. Further product testing was carried out using the composition of Example 1, and 56 subjects aged 6 months to 14 years (inclusive) who reported having nasal allergy symptoms in the past 2 weeks (the main symptoms of nasal allergy include nasal itching, sneezing, runny nose, nasal congestion, accompanied by itchy eyes, red eyes and tearing, etc.) were retained for a 3-month trial.

[0110] 1. The basic information of the subjects is as follows:

[0111]

[0112]

[0113] 2. The test indicators are as follows:

[0114] Evaluation content Indicator name Evaluation population Rating system Symptoms of nasal allergy (1) Improvement of nasal allergy symptoms All subjects 0-10 Symptoms of nasal allergy (2) Symptom distress level All subjects 0-10 Symptoms of nasal allergy (3) Duration of nasal allergy symptoms All subjects Level 4 Symptoms of nasal allergy (4) Changes in the recurrence frequency of nasal allergies All subjects Level 5 Bowel movement (5) Frequency of intestinal flatulence All subjects Level 5 Quality of Life (6) Psychological status score All subjects 1-10 Quality of Life (7) Score of impact on daily life All subjects 1-10

[0115] 3. The method of using the test product is as follows:

[0116] 175 mg of the composition was taken with water for 4 weeks, and statistical data was followed up after the end of the period. The activity of probiotics decreased above 40°C, and it was best to use warm water at 37°C. The use of antibiotics was suspended during the test process.

[0117] 4. Data statistical methods:

[0118] Descriptive statistics: percentage / mean; Difference statistics: percentage was tested for significance using T test; mean was tested for significance using repeated measures ANOVA; P < 0.05: at a 95% confidence level, the data were significantly different. P < 0.1: at a 90% confidence level, the data were significantly different.

[0119] The statistical results are as follows:

[0120] (1) Improvement of nasal allergy symptoms

[0121]

[0122] The score range is 0-10, with 0 indicating no improvement and 10 indicating a very significant improvement. The larger the mean value, the greater the degree of improvement. Significance annotation method: capital letters indicate P < 0.05; lowercase letters indicate P < 0.1.

[0123] (2) Level of bother of nasal allergy symptoms (score)

[0124]

[0125] The score range is 0-10, with 0 indicating no distress at all and 10 indicating extreme distress. The smaller the mean value, the less distress. Significance annotation method: capital letters indicate P < 0.05; lowercase letters indicate P < 0.1.

[0126] (3) Duration of nasal allergy symptoms

[0127]

[0128] The smaller the mean value, the shorter the duration of nasal allergy symptoms. Significance annotation method: capital letters indicate P < 0.05; lowercase letters indicate P < 0.1.

[0129] (4) Changes in the recurrence frequency of nasal allergies (statistics of the proportion of people)

[0130]

[0131] Significance marking method: capital letters indicate P < 0.05; lowercase letters indicate P < 0.1.

[0132] (5) Frequency of intestinal flatulence (population statistics)

[0133]

[0134] The smaller the mean value, the lower the frequency of intestinal flatulence. Significance annotation method: capital letters indicate P < 0.05; lowercase letters indicate P < 0.1.

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

[0136]

[0137] In summary:

[0138] According to the evaluation results of the 3-month trial of 56 subjects aged 6 months to 14 years (not included) who reported experiencing nasal allergy symptoms in the last 2 weeks (the main symptoms of nasal allergy include nasal itching, sneezing, runny nose, nasal congestion, accompanied by itchy eyes, red eyes and tears, etc.), the test product has the following effects:

[0139] Relieve nasal allergy symptoms: 100% of the subjects agreed that it can relieve nasal allergy symptoms.

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

[0141] Reduce the recurrence of nasal allergy symptoms: 52% of the subjects agreed that it can reduce the duration of nasal allergy symptoms, 25% of the subjects agreed that it can reduce the number of days per week with obvious nasal allergy symptoms, 95% of the subjects agreed that it can reduce the frequency of nasal allergy recurrence, and 90% of the subjects agreed that it can shorten the duration of nasal allergy.

[0142] Relieve intestinal gas symptoms: 41% of the subjects agreed that it can relieve intestinal gas.

[0143] More energy, more focused, and happier: 55% of the subjects agreed that they felt more "energetic", 70% agreed that they felt more "focused", and 50% agreed that they felt more "happier".

[0144] Improve sleep quality and learning status: 63% of the subjects agreed that it could improve "sleep quality", and 61% of the subjects agreed that it could improve "learning status".

[0145] The above embodiments are only used to illustrate the present invention, not to limit the present invention. Without departing from the technical concept of the present invention, those skilled in the art can adjust, optimize, upgrade and iterate the technical solutions developed, all of which are within the scope of protection of the present invention.

Claims

1. A composition of 2'-fucosyllactose and probiotics, characterized in that: The active ingredients are composed of: 2'-fucosyllactose, Bifidobacterium longum BB536, Bifidobacterium breve M-16V, Bifidobacterium longum subsp. infantis M-63; In the composition: the content of 2'-fucosyllactose is 75-125 mg / g; The bacterial content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subsp. infantis M-63 was 6-12:10-20:3-8; The total bacterial content in the composition is >10 7 CFU / g.

2. The composition according to claim 1, characterized in that In the composition, the content ratio of Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum infantis subspecies M-63 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 according to claim 2, characterized in that The total bacterial content in the composition is 2.5E+09CFU / g-7.5E+09CFU / g.

4. The composition according to claim 3, characterized in that In the composition: The content of Bifidobacterium longum BB536 is: 0.75E+09CFU / g-2.5E+09CFU / g; The content of Bifidobacterium breve M-16V is: 1.25E+09CFU / g-4.0E+09CFU / g The content of Bifidobacterium longum subspecies infantis M63 is: 0.5E+09CFU / g-1.5E+09CFU / g.

5. The composition according to claim 4, characterized in that The bacterial content ratio of the Bifidobacterium longum BB536, Bifidobacterium breve M-16V and Bifidobacterium longum subspecies infantis M-63 is 8-10:12-16:5-6; the total bacterial content in the composition is 6.75E+09CFU / g-7.5E+09CFU / g.

6. The composition according to claim 5, characterized in that In the composition: The content of 2'-fucosyllactose is 75-100 mg / g; The content of Bifidobacterium longum BB536 is: 2.0E+09CFU / g-2.5E+09CFU / g; The content of Bifidobacterium breve M-16V is: 3.0E+09CFU / g-4.0E+09CFU / g The content of Bifidobacterium longum subspecies infantis M63 is: 1.25E+09CFU / g-1.5E+09CFU / g.

7. The composition according to claim 1, characterized in that The probiotics are in the form of any one or more of live bacteria, dead bacteria, fermentation liquid, fermentation liquid precipitation and freeze-dried powder.

8. Use of the composition according to any one of claims 1 to 7 in the preparation of products for preventing and treating rhinitis or nasal allergies.

9. The use according to claim 8, characterized in that: The rhinitis or nasal allergy symptoms include: any one or more of nasal itching, sneezing, runny nose and nasal congestion; the nasal allergy symptoms selectively include or exclude any one or more of eye itching, red eyes and tearing.

10. The use according to claim 9, characterized in that: The rhinitis or nasal allergy symptoms are accompanied by intestinal symptoms or psychiatric symptoms; the intestinal symptoms include intestinal flatulence; the psychiatric symptoms include anxiety or sleep disorders.

11. The use according to claim 10, characterized in that: The rhinitis or nasal allergy symptoms are accompanied by fatigue or difficulty concentrating.

12. A product comprising the composition according to any one of claims 1 to 7, characterized in that The products include food or food additives, medicines or medicine additives, health products or health product additives.

13. The product according to claim 12, characterized in that The product also includes a freeze-drying protective agent for protecting live bacteria.

14. The product according to claim 12, characterized in that The product is a food or a health product, and the food or the health product also includes any one or more of the flavoring agents, flavoring agents, thickeners, antioxidants, preservatives, colorants, color retainers, enzyme preparations and emulsifiers required for the food or the health product.

15. The product according to claim 14, characterized in that The product is selected from: any one or more of biscuits, cakes, jelly candies, hard candies, marshmallows, functional drinks, juices, effervescent tablets, yogurt, cheese, ice cream, modulated milk powder, granules, solid drinks, chewable tablets, soft candies, and drops.

16. The product according to claim 12, characterized in that The product is a medicine, which also includes pharmaceutical excipients.

17. The product according to claim 16, characterized in that The pharmaceutical excipients include: any one or more of excipients, disintegrants, emulsifiers, fillers, diluents, adhesives, lubricants, stabilizers, plasticizers, opacifiers, colorants, flavoring agents, cosolvents and surfactants.

18. The product according to claim 17, characterized in that The medicine is an oral medicine, including any one or more of syrup, tablet, capsule, soft capsule, granule and oral liquid.

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