Probiotic and prebiotic composition as well as preparation method and application thereof

Abstract

The invention belongs to the field of foods or medicines, and particularly relates to a probiotic and prebiotic composition, a preparation process and application thereof. The composition comprises probiotics, resistant dextrin, xylooligosaccharide, fructo-oligosaccharide, stachyose, erythritol and cranberry powder, and is prepared by a fluidized bed spray granulation process. As an auxiliary preparation of antibiotics, animal and trial administration tests prove that the composition can synergistically treat upper / lower respiratory tract infection and urinary tract infection, shorten the symptom duration, accelerate the recovery of original diseases, maintain the diversity of intestinal flora, improve the abundance of beneficial bacteria such as bifidobacteria and reduce the incidence rate of adverse reactions, and can be used for preparing the medicine for treating the diseases. The antibiotic-related diarrhea is relieved. The invention provides a micro-ecological restoration scheme for antibiotic treatment, and has clear clinical value and process feasibility.

Description

Technical Field

[0001] The present invention relates to the field of food or medicine, and particularly to a composition, preparation process and application of a probiotic and prebiotic composition. Background Art

[0002] In recent years, the problem of drug resistance caused by the abuse of antibiotics has become increasingly severe globally. According to the 2024 report of the World Health Organization (WHO), antibiotic resistance directly causes more than 1.27 million deaths annually, and the number of indirectly related deaths reaches 4.95 million. Although β-lactam antibiotics (such as amoxicillin clavulanate potassium preparations) are widely used in the treatment of respiratory tract, urinary tract infections, etc., their overuse not only accelerates the evolution of drug-resistant strains but also significantly disrupts the balance of the intestinal flora, leading to side effects such as diarrhea and constipation. A survey of Chinese medical institutions shows that about 30% of antibiotic users will experience symptoms related to intestinal flora imbalance, and children and immunocompromised populations are at higher risk. Patients with related intestinal complications require additional treatment, increasing the burden on the medical system.

[0003] Traditional countermeasures such as the rotation of antibiotics and the research and development of new antibiotics have limited effectiveness. The WHO points out that only 4 antibiotics under research globally were effective against drug-resistant bacteria from 2017 to 2023, and the R & D investment continues to shrink due to low commercial returns. Against this background, the development of adjuvant preparations that can not only enhance the efficacy of antibiotics but also protect the intestinal microecology has become an important direction.

[0004] To alleviate the side effects of antibiotics, although the concept of the synergy of probiotics and prebiotics (synbiotics) has been widely recognized, there are significant defects: such as unreasonable strain selection and ratio, most preparations only contain 2 - 3 kinds of Lactobacillus or Bifidobacterium, lacking the ability of targeted repair for antibiotic-induced flora imbalance; the prebiotic combination is single, relying on traditional ingredients such as fructooligosaccharide or inulin, ignoring the synergistic effect of resistant dextrin and xylooligosaccharide; lacking synergistic components, without integrating prebiotics, unable to continuously promote the colonization of probiotics; process defects leading to a low viable cell rate, conventional tableting or freeze-drying processes result in the survival rate of probiotics in gastric acid being less than 10%, and the particle size is uneven, affecting the intestinal colonization efficiency; lacking clinical adaptability: few products are designed for combined drug use with specific antibiotics (such as Augmentin), unable to achieve precise synergy between flora regulation and anti-infection treatment.

[0005] Currently, solutions for microecological imbalance caused by antibiotics urgently need to be innovated. This composition provides a highly efficient and stable antibiotic adjuvant preparation for clinical use through multi-strain synergy, synbiotic synergism and process optimization, with significant scientific research value and application prospects. Summary of the Invention

[0006] Although there are already various probiotic compositions in the prior art, problems such as unreasonable strain selection and ratio, single prebiotic combination, lack of synergistic components, low viable bacteria rate caused by process defects, and lack of clinical adaptability have not been properly solved. The present invention overcomes the deficiencies of the prior art and provides an efficient and stable antibiotic adjuvant preparation for clinical use through multi-strain synergy, synbiotic synergism, and process optimization.

[0007] Specifically, the technical solutions and technical effects of the present invention are as follows:

[0008] One of the purposes of the present invention is to provide a probiotic and prebiotic composition, wherein the composition comprises probiotics, resistant dextrin, xylo-oligosaccharide, fructo-oligosaccharide, stachyose, erythritol, and vitamin C.

[0009] In some embodiments, the probiotics include Bifidobacterium animalis subsp. lactis BLa80, Pediococcus acidilactici CCFM7902, Lactobacillus acidophilus LA85, Lactiplantibacillus plantarum N13, Paracasei paracasei LC86, Bifidobacterium bifidum BBi32, Lactobacillus rhamnosus LRa05, and Lactobacillus casei LC89.

[0010] In a more preferred embodiment, the strains are in the following weight ratios:

[0011] Bifidobacterium animalis subsp. lactis BLa80 10%-20%

[0012] Pediococcus acidilactici CCFM7902 5%-15%

[0013] Lactobacillus acidophilus LA85 5%-15%

[0014] Lactiplantibacillus plantarum N13 10%-20%

[0015] Paracasei paracasei LC86 10%-20%

[0016] Bifidobacterium bifidum BBi32 5%-15%

[0017] Lactobacillus rhamnosus LRa05 10%-20%

[0018] Lactobacillus casei LC89 5%-15%.

[0019] Another purpose of the present invention is to provide the parts by weight of a probiotic and prebiotic composition, and to determine the optimal ratio of probiotics and prebiotics. The composition comprises the following components:

[0020] Probiotics 1-50 parts by weight

[0021] Resistant dextrin 5-100 parts by weight

[0022] 5 - 100 parts by weight of xylo - oligosaccharide

[0023] 1 - 50 parts by weight of fructo - oligosaccharide

[0024] 1 - 50 parts by weight of stachyose

[0025] 1 - 50 parts by weight of erythritol

[0026] 1 - 50 parts by weight of cranberry powder.

[0027] In a more preferred embodiment, the composition comprises the following components:

[0028] 5 - 20 parts by weight of probiotics

[0029] 10 - 50 parts by weight of resistant dextrin

[0030] 10 - 50 parts by weight of xylo - oligosaccharide

[0031] 3 - 10 parts by weight of fructo - oligosaccharide

[0032] 1 - 5 parts by weight of stachyose

[0033] 5 - 10 parts by weight of erythritol

[0034] 5 - 10 parts by weight of cranberry powder.

[0035] The third object of the present invention is to provide a probiotic and prebiotic composition containing vitamin C.

[0036] In some embodiments, the vitamin C comprises natural plant extracts and synthetic vitamin C and its derivatives.

[0037] In a more preferred embodiment, the vitamin C is natural vitamin C, and further the vitamin C is cranberry powder.

[0038] The fourth object of the present invention is to screen erythritol as a binder for granulation and determine the optimal process. In the development of the formulation process, the screening of the binder and the optimization of granulation parameters are the keys to ensuring the stability and functionality of the probiotic composition.

[0039] First, the granulation performance of common binders on the market such as erythritol, dextrin and microcrystalline cellulose was compared through orthogonal experiments, and erythritol was determined to be the optimal binder for this scheme.

[0040] Secondly, through orthogonal experiments: inlet air temperature (50 / 60 / 70 °C) × atomization pressure (0.1 / 0.2 / 0.3 MPa) × fluidization velocity (1.5 / 2.0 / 2.5 m / s), the preparation process of the present invention is determined as follows: (1) Prepare erythritol into an adhesive solution; (2) Mix resistant dextrin and xylo-oligosaccharide, spray and add the adhesive in step (1) for granulation, and after sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0041] In a more preferred embodiment, the preparation process of the present invention is as follows: (1) Prepare erythritol into an adhesive solution with a concentration of 10-50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, spray and add the adhesive in step (1) for granulation, control the granule size to 0.3-1.0 mm, and after sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product. Further, the inlet air temperature during the granulation process is 50-70 °C, the atomization pressure is 0.1-0.3 MPa, and the fluidization velocity of the material is 1.5-3.0 m / s.

[0042] The fifth object of the present invention is to provide an application of a probiotic and prebiotic composition in the preparation of an antibiotic adjuvant preparation.

[0043] In some embodiments, the probiotic and prebiotic composition is used to relieve antibiotic-induced intestinal flora imbalance, diarrhea or constipation, and at the same time regulate the intestinal microecology.

[0044] In some embodiments, the composition is used in combination with an antibiotic preparation to treat related disease infections.

[0045] In a more preferred embodiment, the related disease infections include upper respiratory tract infection, lower respiratory tract infection, urinary tract infection, skin and soft tissue infection and other infections.

[0046] Compared with the prior art, the present invention has achieved the following remarkable technical effects:

[0047] (1) The probiotic and prebiotic composition provided by the present invention has a regulatory effect on the intestinal flora of mice in an antibiotic-induced diarrhea model, which is beneficial to the weight gain of mice, reduces the loose stool rate of mice, increases the levels of serum immunoglobulins IgA and IgG in mice, can significantly improve the low immune function of mice caused by AAD, has an obvious intestinal flora regulatory effect on AAD mice, and can relieve the symptoms of antibiotic-associated diarrhea.

[0048] (2) In the experiment of treating upper respiratory tract infection with the probiotic and prebiotic composition of the present invention combined with amoxicillin clavulanate tablets, the body weight of the mice increased, the lung index of the mice in each administration group decreased significantly, the levels of TNF-α and IL-8 decreased, and the combined administration could inhibit the inflammatory reaction of the mice and improve the lung tissue damage.

[0049] (3) The probiotic and prebiotic combination of the present invention can reduce the organ index of rats in the acute pyelonephritis model, reduce the levels of serum creatinine, urinary creatinine, serum IL-1β and CXCL-2 in rats, and significantly increase the levels of urinary SIgA and serum IL-10, suggesting that the combined medication can reduce the damage of renal function, inhibit the inflammatory reaction of rats, and enhance the local immune function of the rat urethra.

[0050] (4) Verified by the trial administration experiment, the probiotic composition of the present invention can reduce the incidence of adverse reactions, shorten the symptom duration, accelerate the recovery of the primary disease, and at the same time can maintain the diversity of the intestinal flora, increase the abundance of beneficial bacteria such as Bifidobacterium, relieve inflammation, and provide an effective solution for the precise intervention of antibiotic-related intestinal side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 Effect of taking probiotic and prebiotic composition on the level of serum immunoglobulin IgA in mice (compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01).

[0052] Figure 2 Effect of taking probiotic and prebiotic composition on the level of serum immunoglobulin IgG in mice (compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01).

[0053] Figure 3 Column stacked chart of species analysis at phylum level

[0054] Figure 4 Column stacked chart of species analysis at genus level SPECIFIC EMBODIMENTS

[0055] Example 1: A probiotic and prebiotic composition and its preparation method

[0056]

[0057]

[0058] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 20% (w / v); (2) Mix resistant dextrin and xylooligosaccharide, and spray and add them to the adhesive in step (1) for granulation. Control the granule size to be 0.7 mm, the inlet air temperature to be 60 °C, the atomization pressure to be 0.2 MPa, and the material fluidization speed to be 2.0 m / s. After sieving, mix with stachyose, fructooligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0059] Example 2: A probiotic and prebiotic composition and its preparation method

[0060]

[0061]

[0062] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 50% (w / v); (2) Mix resistant dextrin and xylooligosaccharide, and spray and add them to the adhesive in step (1) for granulation. Control the granule size to be 0.3 mm, the inlet air temperature to be 70 °C, the atomization pressure to be 0.1 MPa, and the material fluidization speed to be 1.5 m / s. After sieving, mix with stachyose, fructooligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0063] Example 3: A probiotic and prebiotic composition and its preparation method

[0064]

[0065]

[0066] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 30% (w / v); (2) Mix resistant dextrin and xylooligosaccharide, and spray and add them to the adhesive in step (1) for granulation. Control the granule size to be 0.8 mm, the inlet air temperature to be 50 °C, the atomization pressure to be 0.3 MPa, and the material fluidization speed to be 2.0 m / s. After sieving, mix with stachyose, fructooligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0067] Example 4: A probiotic and prebiotic composition and its preparation method

[0068]

[0069]

[0070] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 40% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the adhesive in step (1) for granulation. The granule size is controlled at 0.5 mm, the inlet air temperature is 65 °C, the atomization pressure is 0.25 MPa, and the material fluidization speed is 2.5 m / s. After sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0071] Example 5: A probiotic and prebiotic composition and its preparation method

[0072] Bifidobacterium animalis subsp. lactis BLa80 1.4 Pediococcus acidilactici CCFM7902 0.35 Lactobacillus acidophilus LA85 1.05 Lactiplantibacillus plantarum N13 0.7 Lactobacillus paracasei LC86 1.4 Bifidobacterium bifidum BBi32 0.35 Lactobacillus rhamnosus LRa05 1.4 Lactobacillus casei LC89 0.35 Resistant dextrin 36 Xylooligosaccharide 32 Fructooligosaccharide 5 Stachyose 4.5 Erythritol 8 Cranberry powder 7.5

[0073] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the adhesive in step (1) for granulation. The granule size is controlled at 0.6 mm, the inlet air temperature is 55 °C, the atomization pressure is 0.15 MPa, and the material fluidization speed is 3.0 m / s. After sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0074] Comparative Example 1: A probiotic and prebiotic composition and its preparation method

[0075] Lactobacillus reuteri TSR-332 2.0 Lactobacillus fermentum TSF-331 1.6 Lactobacillus casei Zhang 0.9 Bifidobacterium lactis Probio-M8 1.3 Lactobacillus rhamnosus NM-94 1.2 Resistant dextrin 36 Xylooligosaccharide 32 Fructooligosaccharide 5 Stachyose 4.5 Erythritol 8 Cranberry powder 7.5

[0076] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 20% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the adhesive in step (1) for granulation. The granule size is controlled at 0.7 mm, the inlet air temperature is 60 °C, the atomization pressure is 0.2 MPa, and the material fluidization speed is 2.0 m / s. After sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0077] Comparative Example 2: A probiotic and prebiotic composition and its preparation method

[0078]

[0079]

[0080] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the adhesive in step (1) for granulation. The granule size is controlled at 0.3 - 1.0 mm, the inlet air temperature is 50 - 70 °C, the atomization pressure is 0.1 - 0.3 MPa, and the material fluidization speed is 1.5 - 3.0 m / s. After sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0081] Comparative Example 3: A probiotic and prebiotic composition and its preparation method

[0082] Bifidobacterium animalis subsp. lactis BLa80 1.0 Pediococcus acidilactici CCFM7902 0.8 Lactobacillus acidophilus LA85 0.8 Lactiplantibacillus plantarum N13 1.0 Lactobacillus paracasei LC86 0.9 Bifidobacterium bifidum BBi32 0.8 Lactobacillus rhamnosus LRa05 1.0 Lactobacillus casei LC89 0.7 Resistant dextrin 36 Inulin 41.5 Erythritol 8 Cranberry powder 7.5

[0083] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Spray-resistant dextrin and granulate it with the adhesive in step (1), control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70°C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix it with inulin, cranberry powder, and probiotic powder to obtain the product.

[0084] Comparative Example 4: A probiotic and prebiotic composition and its preparation method

[0085]

[0086]

[0087] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylooligosaccharide, spray and granulate it with the adhesive in step (1), control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70°C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix it with maltitol oligosaccharide, fructooligosaccharide, cranberry powder, and probiotic powder to obtain the product.

[0088] Comparative Example 5: A probiotic and prebiotic composition and its preparation method

[0089] Bifidobacterium animalis subsp. lactis BLa80 1.0 Pediococcus acidilactici CCFM7902 0.8 Lactobacillus acidophilus LA85 0.8 Lactiplantibacillus plantarum N13 1.0 Lactobacillus paracasei LC86 0.9 Bifidobacterium bifidum BBi32 0.8 Lactobacillus rhamnosus LRa05 1.0 Lactobacillus casei LC89 0.7 Resistant dextrin 36 Fructooligosaccharide 41.5 Erythritol 8 Cranberry powder 7.5

[0090] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Spray-resistant dextrin and granulate it with the adhesive in step (1), control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70°C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix it with fructooligosaccharide, cranberry powder, and probiotic powder to obtain the product.

[0091] Comparative Example 6: A probiotic and prebiotic composition and its preparation method

[0092] Bifidobacterium animalis subsp. lactis BLa80 1.0 Pediococcus acidilactici CCFM7902 0.8 Lactobacillus acidophilus LA85 0.8 Lactiplantibacillus plantarum N13 1.0 Lactobacillus paracasei LC86 0.9 Bifidobacterium bifidum BBi32 0.8 Lactobacillus rhamnosus LRa05 1.0 Lactobacillus casei LC89 0.7 Resistant dextrin 36 Xylooligosaccharide 6.5 Fructooligosaccharide 24 Stachyose 11 Erythritol 8 Cranberry powder 7.5

[0093] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the adhesive in step (1) for granulation. Control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70 °C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix with stachyose, fructooligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0094] Comparative Example 7: A probiotic and prebiotic composition and its preparation method

[0095]

[0096]

[0097] Preparation process: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix xylo-oligosaccharide and fructooligosaccharide, and spray and add them to the adhesive in step (1) for granulation. Control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70 °C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix with stachyose, cranberry powder and probiotic powder to obtain the product.

[0098] Comparative Example 8: A probiotic and prebiotic composition and its preparation method

[0099] Bifidobacterium animalis subsp. lactis BLa80 1.0 Pediococcus acidilactici CCFM7902 0.8 Lactobacillus acidophilus LA85 0.8 Lactiplantibacillus plantarum N13 1.0 Lactobacillus paracasei LC86 0.9 Bifidobacterium bifidum BBi32 0.8 Lactobacillus rhamnosus LRa05 1.0 Lactobacillus casei LC89 0.7 Resistant dextrin 36 Xylooligosaccharide 32 Fructooligosaccharide 5 Stachyose 4.5 Microcrystalline cellulose 8 Cranberry powder 7.5

[0100] Preparation process: (1) Prepare microcrystalline cellulose into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the adhesive in step (1) for granulation. Control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70 °C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix with stachyose, fructooligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0101] Comparative Example 9: A probiotic and prebiotic composition and its preparation method

[0102] Bifidobacterium animalis subsp. lactis BLa80 1.0 Pediococcus acidilactici CCFM7902 0.8 Lactobacillus acidophilus LA85 0.8 Lactiplantibacillus plantarum N13 1.0 Lactobacillus paracasei LC86 0.9 Bifidobacterium bifidum BBi32 0.8 Lactobacillus rhamnosus LRa05 1.0 Lactobacillus casei LC89 0.7 Resistant dextrin 36 Xylooligosaccharide 32 Fructooligosaccharide 5 Stachyose 4.5 Erythritol 8 L-Ascorbic acid 7.5

[0103] Preparation process: (1) Prepare a binder solution with microcrystalline cellulose at a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the binder in step (1) for granulation. Control the granule size to be 0.3 - 1.0 mm, the inlet air temperature to be 50 - 70 °C, the atomization pressure to be 0.1 - 0.3 MPa, and the material fluidization speed to be 1.5 - 3.0 m / s. After sieving, mix with stachyose, fructooligosaccharide, L-ascorbic acid and probiotic powder to obtain the product.

[0104] Comparative Example 10: A probiotic and prebiotic composition and its preparation method

[0105]

[0106]

[0107] Preparation process: (1) Prepare a binder solution with erythritol at a concentration of 60% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray and add them to the binder in step (1) for granulation. Control the granule size to be 1.5 mm, the inlet air temperature to be 80 °C, the atomization pressure to be 0.4 MPa, and the material fluidization speed to be 1.0 m / s. After sieving, mix with stachyose, fructooligosaccharide, cranberry powder and probiotic powder to obtain the product.

[0108] Verification test example

[0109] I. Regulatory effect of the probiotic and prebiotic composition of the present invention on the intestinal flora of mice with antibiotic-induced diarrhea model

[0110] 1 Materials and methods

[0111] 1.1 Materials

[0112] 1.1.1 Experimental drugs

[0113] Probiotic and prebiotic composition: Example 1, Example 2, Comparative Example 1, Comparative Example 3, Comparative Example 6, Comparative Example 7. Ampicillin sodium for injection (Shanghai Yuanye Bio-Technology Co., Ltd.); Bifico (Shanghai Shangyao Xinyi Pharmaceutical Factory Co., Ltd.).

[0114] 1.1.2 Experimental animals

[0115] 48 SPF-grade male BALB / c mice, 6 - 8 weeks old, weighing 18 - 20 g, provided by Shandong Pengyue Experimental Animal Technology Co., Ltd., animal certificate number: SCXK(Lu)20220006. The experimental animals were raised in a barrier environment animal room, with free access to water and food during the period, and the temperature was controlled at 20 - 23 °C, with a 12-hour light-dark cycle.

[0116] 1.2 Experimental methods

[0117] 1.2.1 Grouping and model construction

[0118] After 1 week of adaptive feeding, BALB / c mice were randomly divided into 9 groups of 8 mice each, namely the blank group, the model group, the positive group (Bifidobacterium triple viable capsules), the Example 1 group, the Example 2 group, the Comparative Example 1 group, the Comparative Example 3 group, the Comparative Example 6 group, and the Comparative Example 7 group.

[0119] Mice in the model group, the positive group and the probiotic groups were intragastrically administered ampicillin (22.4 g / kg) every day, in two divided doses, with each dose being (11.2 g / kg). Mice in the blank group were intragastrically administered the same volume of normal saline at the same time every day for 3 consecutive days. The criteria for judging the successful construction of the model: The mice curled up, had reduced activity, listlessness, perianal filth, obvious stains on the buttocks, or there were statistically significant differences in the diarrhea rate and diarrhea index between the model group and the blank group.

[0120] After the successful construction of the model, probiotic preparations were given. The blank group and the model group were intragastrically administered normal saline, the positive drug group was intragastrically administered Bifidobacterium triple viable capsules (8 g / kg, with the viable bacteria count per mouse not less than 1×10 7 CFU), and mice in each of the probiotic and prebiotic groups were given 5×10 6 CFU of the probiotic preparation for 14 consecutive days.

[0121] 1.2.2 Effects of probiotic and prebiotic compositions on the body weight of mice

[0122] On the first day of the experiment, that is, at 10:00 in the morning on the first day of the diarrhea model construction, the initial body weights of the mice in each group were recorded. Subsequently, ampicillin was given to the mice, and at 18:00 every day for the rest of the time, the body weights of the mice in each group were weighed and recorded.

[0123] 1.2.3 Effects of probiotic and prebiotic preparations on the loose stool rate of mice

[0124] Immediately after the model establishment, that is, on the 3rd day of the experiment, and 14 days after the administration of the probiotics, that is, on the 17th day of the experiment, the number of loose stools of the mice in each group was observed and recorded, and the loose stool rate of the mice was calculated: the ratio of the number of loose stools excreted by each animal to the total number of stools.

[0125] 1.2.4 Effects of probiotic and prebiotic compositions on the levels of serum immunoglobulin IgA and IgG in mice

[0126] 1 hour after the last administration of the probiotic preparation, blood was collected from the orbital cavities of the mice in each group, centrifuged at 3000 r / min for 10 min, and the serum was aliquoted and frozen at -80 °C for later measurement. The levels of serum IgA and IgG were detected using an ELISA kit.

[0127] 1.2.5 Effects of probiotic and prebiotic compositions on the intestinal flora of mice

[0128] At 30 min after model establishment and after the last administration of the probiotic preparation, mouse feces were aseptically collected. The samples were diluted 10-fold to 10-8, and appropriate dilution degrees were selected. The samples were respectively inoculated in BBL agar medium, MRS medium, TSC agar medium, and modified GAM agar medium. After cultivation, the numbers of Bifidobacterium, Lactobacillus, Clostridium perfringens, and Enterococcus in each gram of wet feces were calculated, and the results were expressed as the logarithm of the colony-forming units per unit mass of feces (lg CFU / g).

[0129] 1.2.6 Statistical analysis

[0130] The SPSS 26.0 statistical software was used. The experimental data were expressed as mean ± standard deviation For significant tests of data from two or more groups, the one-way analysis of variance method was used. A P value < 0.05 indicated a significant difference, and Sigmaplot 14 was used for plotting.

[0131] 2 Experimental results

[0132] 2.1 Effects of the probiotic and prebiotic composition on the body weight of mice

[0133] Table 1 Effects of the probiotic and prebiotic composition of the present invention on the body weight changes of each group of mice

[0134]

[0135]

[0136] Compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01.

[0137] As can be seen from Table 1, compared with the blank group, the body weight of each group of mice increased slowly during model establishment. Compared with the model group, there was no significant difference in the body weight increase of each probiotic preparation group of mice, indicating that the model was successfully constructed. After 14 days of administration of the probiotic preparation, compared with the blank group, there was no significant difference in the body weight increase of the model group. The body weight of the positive group increased by 46.38% (P < 0.01), the body weight of the Example 1 group increased by 54.35% (P < 0.01), and the body weight of the Example 2 group increased by 37.32% (P < 0.05); compared with the model group, the body weights of the positive group, Example 1, and Example 2 groups of mice increased by 60.96% (P < 0.01), 69.72% (P < 0.01), and 51% (P < 0.01), respectively. The effect of the Example 1 group was better than that of the positive group, and the effect of the Example 2 group was comparable to that of the positive group.

[0138] 2.2 Effects of probiotic and prebiotic preparations on the loose stool rate of diarrhea mice

[0139] Table 2 Effects of the probiotic and prebiotic composition of the present invention on the loose stool rate of diarrhea mice

[0140] Group After modeling / % After taking probiotic preparation / % Blank group 0.00±0.00 0.00±0.00 Model group <![CDATA[71.07±7.96 ** > <![CDATA[69.58±12.25 ** > Positive group <![CDATA[68.75±11.25 ** > <![CDATA[50.17±11.34 **## > Example 1 group <![CDATA[69.26±10.34 ** > <![CDATA[42.14±10.74 **## > Example 2 group <![CDATA[70.35±9.58 ** > <![CDATA[48.25±11.58 **## > Control group 1 <![CDATA[67.52±11.7 ** > <![CDATA[63.25±9.64 ** <!-- 14 -->]]> Control group 3 <![CDATA[66.94±8.69 ** > <![CDATA[54.32±9.88 **# > Control group 6 <![CDATA[73.43±8.32 ** > <![CDATA[55.86±9.71 **# > Control group 7 <![CDATA[70.13±9.97 ** > <![CDATA[59.47±8.62 ** >

[0141] Compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01.

[0142] As can be seen from Table 2, compared with the blank group, there were significant differences in the loose stool rate of the mice in the other groups after modeling (P < 0.01). After taking probiotics for 14 days, compared with the blank group, there were significant differences in the loose stool rate of the mice in the other groups (P < 0.01). Compared with the model group, the loose stool rate of the mice decreased significantly in the positive group and Examples 1 and 2 groups, and the decrease in Example 1 group was the most obvious, suggesting that its effect might be better than that of the positive control group, and the effect of Example 2 group was equivalent to that of the positive group.

[0143] 2.3 Effects of probiotic and prebiotic preparations on the levels of serum immunoglobulins IgA and IgG in mice

[0144] From Figure 1 , Figure 2 it can be seen that after taking probiotics and prebiotics for 14 days, compared with the blank group, the levels of IgA and IgG in the model group decreased significantly (P < 0.01). Compared with the model group, the levels of IgA and IgG in the positive control group and Comparative Examples 1 and 2 groups increased significantly (P < 0.05). The increase in the levels of serum immunoglobulins IgA and IgG in mice can significantly improve the low immune function of mice caused by AAD.

[0145] 2.4 Effects of the probiotic and prebiotic composition on the intestinal flora of mice in each group

[0146] Table 3 Changes in intestinal flora of mice in each group before and after taking the probiotic and prebiotic composition of the present invention

[0147]

[0148] Note: * P < 0.05, ** P < 0.01, compared with day 0.

[0149] The changes in the intestinal flora of mice in each group before and after taking probiotics are shown in Table 3. At the 14th day, compared with the blank group, the numbers of Bifidobacterium and Lactobacillus in the model group were significantly reduced, while the numbers of Enterococcus and Clostridium perfringens were significantly increased, indicating intestinal flora imbalance in the model mice. Compared with before taking (0d), on the 14th day in the model group, each flora in the model group had a certain degree of recovery, but none reached the healthy level. In the positive group and the groups of Example 1 and Example 2, Bifidobacterium, Lactobacillus, Enterococcus and Clostridium perfringens all recovered to a certain extent (P<0.05), among which the positive group and the group of Example 1 had the greatest degree of recovery, reaching the level of the blank group. The symbiotic bacteria Bifidobacterium and Lactobacillus in the intestine are one of the dominant bacteria in the human or animal intestine, enhancing the intestinal barrier function through various ways. When the intestinal flora is imbalanced, the relative abundances of Bifidobacterium and Lactobacillus decrease, while the relative abundances of opportunistic pathogens such as Enterococcus and the main pathogenic bacterium Clostridium perfringens causing AAD increase significantly, thus inducing intestinal diseases. The experimental results show that the probiotic and prebiotic composition of the present invention has an obvious effect on regulating the intestinal flora of AAD mice and can relieve the symptoms of antibiotic-associated diarrhea.

[0150] II. Study on the adjuvant treatment of upper respiratory tract infection with probiotic and prebiotic composition and amoxicillin clavulanate potassium

[0151] 1 Materials and methods

[0152] 1.1 Materials

[0153] 1.1.1 Experimental drugs

[0154] Probiotic and prebiotic composition: Example 1, Example 3, Example 5, Comparative Example 2, Comparative Example 4, Comparative Example 5. Amoxicillin clavulanate potassium tablets (Lunan Bait Pharmaceutical Co., Ltd.).

[0155] 1.1.2 Experimental animals and grouping

[0156] BALB / c mice, 4-6 weeks old, weighing 14-18 g, half male and half female. After 1 week of adaptive feeding, the mice were randomly divided into 9 groups, with 8 mice in each group, namely blank group, model group, amoxicillin clavulanate potassium tablet group, amoxicillin clavulanate potassium + Example 1 group, amoxicillin clavulanate potassium + Example 3 group, amoxicillin clavulanate potassium + Example 5 group, amoxicillin clavulanate potassium + Comparative Example 2 group, amoxicillin clavulanate potassium + Comparative Example 4 group, amoxicillin clavulanate potassium + Comparative Example 5 group.

[0157] 1.2 Experimental methods

[0158] 1.2.1 Model construction

[0159] Hydrocortisone 0.1 ml (0.5 mg) was intraperitoneally injected every morning, and cyclophosphamide 0.2 ml (0.5 mg) was intraperitoneally injected every afternoon. Such repeated administration was carried out for a total of 3 days. About 1 - 2 h after the last administration of cyclophosphamide to the immunosuppressed mice, a pediatric scalp acupuncture needle was inserted about 0.5 cm at the upper right part of the front back, about 1 cm away from the right ear root (after disinfection), and the bacterial solution MRSA (methicillin-resistant Staphylococcus aureus) was injected: the number of bacteria inoculated into each mouse was 6×10 8 CFU. Those that died within 5 h after injection were non-infectious deaths and were discarded. The modeled animals showed inactivity, anorexia, slow response to the outside world, slightly arched back, erected back hair about 5 - 12 h after infection, and then the limbs became limp (the two hind limbs often extended backward) and could not support the body; when the lung lesions were severe, the breathing was shallow and rapid, and some mice also showed symptoms such as diarrhea during the laboratory observation period.

[0160] 1.2.2 Grouping and Administration

[0161] Blank group: Not infected with MRSA + gavaged with normal saline

[0162] Model group: Infected with MRSA + gavaged with normal saline

[0163] Amoxicillin and Clavulanate Potassium Group (AMX): MRSA + Amoxicillin and Clavulanate Potassium Tablets

[0164] Amoxicillin and Clavulanate Potassium + Example 1 Group (AMX + S1): MRSA + Amoxicillin and Clavulanate Potassium Tablets + Probiotic and Prebiotic Composition of Example 1

[0165] Amoxicillin and Clavulanate Potassium + Example 3 Group (AMX + S3): MRSA + Amoxicillin and Clavulanate Potassium Tablets + Probiotic and Prebiotic Composition of Example 3

[0166] Amoxicillin and Clavulanate Potassium + Example 5 Group (AMX + S5): MRSA + Amoxicillin and Clavulanate Potassium Tablets + Probiotic and Prebiotic Composition of Example 5

[0167] Amoxicillin and Clavulanate Potassium + Comparative Example 2 Group (AMX + D2): MRSA + Amoxicillin and Clavulanate Potassium Tablets + Probiotic and Prebiotic Composition of Comparative Example 2

[0168] Amoxicillin and Clavulanate Potassium + Comparative Example 4 Group (AMX + D4): MRSA + Amoxicillin and Clavulanate Potassium Tablets + Probiotic and Prebiotic Composition of Comparative Example Group

[0169] Amoxicillin and Clavulanate Potassium + Comparative Example 5 Group (AMX + D5): MRSA + Amoxicillin and Clavulanate Potassium Tablets + Probiotic and Prebiotic Composition of Comparative Example 5

[0170] The dosage of amoxicillin and clavulanate potassium tablets is as follows: After grinding the amoxicillin and clavulanate potassium tablets, dissolve them in physiological saline to a concentration of 5.35 mg / mL. The volume of each gavage is 0.2 mL, three times a day. Each group of mice in the probiotic and prebiotic groups was given 5×10 6 CFU, and the blank group and the model group were given an equal amount of physiological saline for 7 days.

[0171] 1.2.3 Body weight and lung index

[0172] After the mice were given the medicine, they were prohibited from drinking water and eating one day before dissection. After weighing the feces and body weight, they were anesthetized by intraperitoneal injection of pentobarbital sodium and sacrificed. Collect the blood from the heart, excise the entire lung and remove the connective tissue. Weigh the mass using a ten-thousandth electronic balance and calculate the lung index according to formula (1).

[0173] Lung index = wet lung mass / body weight (1)

[0174] 1.2.4 Detection of inflammatory factor levels in mouse lung tissue by enzyme-linked immunosorbent assay (ELISA)

[0175] Detect the levels of TNF-α and IL-8 in mouse lung tissue according to the steps of the ELISA kit instructions.

[0176] 1.2.5 Statistical analysis

[0177] Apply SPSS 26.0 statistical software. The experimental data are expressed as mean ± standard deviation For significant tests of data from two or more groups, the one-way analysis of variance method is used. P < 0.05 indicates a significant difference.

[0178] 2 Experimental results

[0179] 2.1 Body weight and lung index of mice in each group

[0180] Table 4 Effects of drug administration in each group on body weight and lung index of mice

[0181] Group Body weight / g <![CDATA[Lung index / g·g -1 > Blank group 31.46±2.44 0.45±0.04 Model group <![CDATA[18.83±4.05 ** > <![CDATA[1.26±0.22 ** > AMX <![CDATA[25.95±2.91 ## > <![CDATA[0.63±0.16 ## > AMX + S1 <![CDATA[28.15±2.15 ## > <![CDATA[0.56±0.18 ## > AMX + S3 <![CDATA[27.26±3.14 ## > <![CDATA[0.64±0.07 ## > AMX + S5 <![CDATA[24.02±2.00 ## > <![CDATA[0.72±0.11 # > AMX + D2 21.94±2.12 0.77±0.14 AMX + D4 20.10±3.26 <![CDATA[0.81±0.09 # > AMX + D5 23.59±3.05 0.79±0.12

[0182] Compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01.

[0183] As can be seen from Table 4, compared with the control group, the body weight of the mice in the model group decreased (P<0.01); compared with the model group, the body weight of the mice in the amoxicillin clavulanate potassium group and the dose groups of Examples 1, 3, and 5 increased (P<0.01). Compared with the control group, the lung index of the rats in the model group increased significantly (P<0.01); compared with the model group, the body weight of the mice in the amoxicillin clavulanate potassium group and the dose groups of Examples 1, 3, and 5 increased, and the lung index of the mice in each administration group decreased significantly (P<0.05, P<0.01), indicating that amoxicillin clavulanate potassium tablets and the combined administration with the probiotic and prebiotic compositions in each Example group can improve lung tissue damage in mice.

[0184] 2.2 Levels of inflammatory factors TNF-α and IL-8 in lung tissues of mice in each group

[0185] Table 5 Changes in levels of inflammatory factors TNF-α and IL-8 in lung tissues of mice after administration in each group

[0186]

[0187]

[0188] Compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01.

[0189] As can be seen from Table 5, compared with the control group, the levels of TNF-α and IL-8 in the lung tissues of the mice in the model group increased significantly (P<0.01). Compared with the model group, the levels of TNF-α and IL-8 in the lung tissues of the mice in the amoxicillin clavulanate potassium group and its combined administration groups with Examples 1, 3, and 5

[0190] decreased significantly (P<0.05, P<0.01).

[0191] III. Effects of probiotic and prebiotic compositions on inflammatory factors and local immune function in rats with acute pyelonephritis model 1 Materials and methods

[0192] 1.1 Materials

[0193] 1.1.1 Experimental animals

[0194] 60 SPF-grade SD rats, male, with a body weight of (180±20) g, provided by Lunan Pharmaceutical Group Co., Ltd., license number SYXK(Lu)20230023. Breeding environment: temperature 18 - 28°C, relative humidity 40% - 70%, light 12h, alternating light and dark.

[0195] 1.1.2 Experimental drugs

[0196] Probiotic and prebiotic compositions: Example 1, Example 4, Comparative Example 8, Comparative Example 9, Comparative Example 10. Levofloxacin Hydrochloride Tablets, Heilongjiang Nuojie Pharmaceutical Co., Ltd.

[0197] 1.2 Experimental methods

[0198] 1.2.1 Construction of acute pyelonephritis (APN) model

[0199] After the rats were deprived of water for 18 h, they were anesthetized intraperitoneally with 2% sodium pentobarbital, fixed supine, the abdomen was depilated and disinfected, a 2-cm midline incision was made in the lower abdomen, the abdominal wall was incised layer by layer, after finding the left ureter, a No. 4 suture was passed through both sides of the left ureter, the penis was clamped, 0.5 mL of Escherichia coli liquid was injected into the bladder, the abdominal wall was sutured layer by layer, and water and food intake were restored. The ureteral ligation thread was removed 24 h after the operation to open the ureter. The sham operation group was injected with 0.5 mL of normal saline. The modeling time was 3 d. The success criterion for establishing the APN model: the number of urinary white blood cells ≥ 100 per cubic millimeter.

[0200] 1.2.2 Grouping and administration

[0201] Blank group: Sham operation + normal saline

[0202] Model group: Normal saline

[0203] Positive group: Levofloxacin Hydrochloride Tablets

[0204] Levofloxacin Hydrochloride Tablets + Example 1 group (ZYFSX + S1): Levofloxacin Hydrochloride Tablets + probiotic and prebiotic composition of Example 1

[0205] Levofloxacin Hydrochloride Tablets + Example 4 group (ZYFSX + S4): Levofloxacin Hydrochloride Tablets + probiotic and prebiotic composition of Example 4

[0206] Levofloxacin Hydrochloride Tablets + Comparative Example 8 group (ZYFSX + D8): Levofloxacin Hydrochloride Tablets + probiotic and prebiotic composition of Example 8

[0207] Levofloxacin Hydrochloride Tablets + Comparative Example 9 group (ZYFSX + D9): Levofloxacin Hydrochloride Tablets + probiotic and prebiotic composition of Example 9

[0208] Levofloxacin Hydrochloride Tablets + Comparative Example 10 group (ZYFSX + D10): Levofloxacin Hydrochloride Tablets + probiotic and prebiotic composition of Example 10

[0209] The positive group was given levofloxacin hydrochloride tablets at a dose of 21 mg / (kg·d) plus 2 mL of normal saline by gavage. The sham operation group and the model group were given an equal volume of normal saline by gavage. The combined medication group was given levofloxacin hydrochloride tablets at a dose of 21 mg / (kg·d) plus 2 mL of the probiotic and prebiotic composition (probiotic preparation 5×10 6 CFU) by gavage for 14 days.

[0210] 1.2.3 Organ indices of rats. After intraperitoneal anesthesia, the kidney and bladder tissues were excised and weighed wet.

[0211] Ratio of left and right kidneys = mass of left kidney / mass of right kidney × 100%;

[0212] Kidney (bladder) index (mg / g) = mass of kidney (bladder) (mg) / body mass (g) × 100%.

[0213] 1.2.4 Detection of biochemical indices.

[0214] Blood was collected from the abdominal aorta, centrifuged at 3000 r / min for 15 min, and the supernatant was taken. Serum creatinine and urinary creatinine were detected by the sarcosine oxidase method, and IL-1β, IL-10, and CXCL-2 were detected by ELISA. Rat urine was collected, and urinary creatinine was detected by the sarcosine oxidase method, and urinary SIgA was detected by ELISA.

[0215] 1.2.5 Statistical analysis

[0216] SPSS 26.0 statistical software was used. Experimental data were expressed as mean ± standard deviation When performing a significance test on data from two or more groups, one-way analysis of variance was used. P < 0.05 indicated a significant difference, and Sigmaplot 14 was used for plotting.

[0217] 2 Experimental results

[0218] 2.1 Comparison of organ indices of rats in each group

[0219] Table 6 Effects of medications in each group on the organ indices of rats

[0220]

[0221]

[0222] Compared with the blank group * P < 0.05, ** P < 0.01; compared with the model group # P < 0.05, ## P < 0.01.

[0223] As can be seen from Table 6, compared with the blank group, the left and right kidney ratio, kidney index, and bladder index of the rats in the model group were significantly increased (P<0.05). Compared with the model group, the left and right kidney ratio, kidney index, and bladder index of the positive group and the combined medication groups of Examples 1, 4, and 8 were significantly decreased (P<0.05).

[0224] 2.2 Comparison of urine SIgA, serum creatinine, and urine creatinine levels in rats of each group

[0225] Table 7 Effects of medications in each group on urine SIgA, serum creatinine, and urine creatinine levels in rats

[0226]

[0227] Compared with the blank group * P<0.05, ** P<0.01; compared with the model group # P<0.05, ## P<0.01.

[0228] As can be seen from Table 7, compared with the blank group, the serum creatinine and urine creatinine levels of the rats in the model group were significantly increased, and the urine SIgA level was significantly decreased (P<0.05); compared with the model group, the serum creatinine and urine creatinine levels of the rats in the positive group and each group of Examples were significantly decreased, and the urine SIgA level was significantly increased (P<0.05).

[0229] 2.3 Comparison of serum IL-1β, IL-10, and CXCL-2 levels in rats of each group

[0230] Table 8 Effects of medications in each group on serum IL-1β, IL-10, and CXCL-2 levels in rats

[0231]

[0232]

[0233] Compared with the blank group * P<0.05, ** P<0.01; compared with the model group # P<0.05, ## P<0.01.

[0234] As can be seen from Table 8, compared with the blank group, the serum IL-1β and CXCL-2 levels of the rats in the model group were significantly increased, and the IL-10 level was significantly decreased (P<0.05); compared with the model group, the serum IL-1β and CXCL-2 levels of the rats in the positive group and each group of Examples were significantly decreased, and the IL-10 level was significantly increased (P<0.05).

[0235] In summary, the combined use of the probiotic and prebiotic composition of the present invention and levofloxacin hydrochloride tablets can inhibit the inflammatory response of APN rats, improve local immune function, and inhibit bacterial growth.

[0236] IV. Trial Administration Experiment

[0237] 1. Subjects and Methods

[0238] 1.1 General Information

[0239] Sixty patients with primary urinary or respiratory tract infections were recruited, with an average age of 36.45 ± 15.75 years, 39 males and 21 females. The baseline characteristics of each group were balanced. The trial product was a probiotic solid beverage.

[0240] Exclusion Criteria: 1. Subjects with a history of chronic diseases or serious diseases in the neuropsychiatric system, respiratory system, cardiovascular system, digestive system, blood and lymphatic system, liver and kidney functions, endocrine system, etc. 2. Patients in the active stage of peptic ulcer. 3. For any other reason, the researcher deems it inappropriate for the subject to participate in the trial.

[0241] 1.2 Methods

[0242] 1.2.1 Grouping

[0243] Group A (n = 20): Amoxicillin and Clavulanate Potassium Dispersible Tablets + Composition of Example 1 (prepared according to the formula of Example 1, 3 g / bag, with no less than 50 billion CFU of probiotics per bag)

[0244] Group B (n = 20): Amoxicillin and Clavulanate Potassium Dispersible Tablets + Composition of Comparative Example 1 (prepared according to the formula of Comparative Example 1, 3 g / bag, with no less than 50 billion CFU of probiotics per bag)

[0245] Group C (n = 20): Amoxicillin and Clavulanate Potassium Dispersible Tablets.

[0246] 1.2.2 Administration and Detection

[0247] The trial subjects took 1 bag of probiotics orally each time, 3 times a day, either directly or after being dissolved in an appropriate amount of warm water or milk with a temperature not higher than 37°C. They took it orally for 7 days, and adverse reactions (incidence rate, severity, duration) were monitored through questionnaires every day. Fecal samples were collected at 0, 3, and 7 days for 16S rDNA sequencing to analyze the changes in intestinal flora diversity (Alpha / Beta diversity) and species composition.

[0248] 2. Results

[0249] 2.1 Overall Administration Situation

[0250] Table 9 Results of each group's medication

[0251] Group Incidence of adverse reactions Duration (days) Recovery time of primary disease (days) Group A 20％ ＜1 6.11±1.76 Group B 50％ 5.25 ＞7 Group C 60％ 3.5±0.71 ＞7

[0252] As can be seen from Table 9, the incidence of adverse reactions in Group A was the lowest (20%), and the duration of symptoms was the shortest (<1 day). The recovery time of the primary disease in Group A was significantly better than that of other groups.

[0253] 2.2 Intestinal flora analysis

[0254] 2.2.1 Alpha diversity

[0255] Table 10 Alpha diversity indices of samples in each group

[0256] Group observed_otus shannon simpson chao1 goods_coverage pielou_e A1 319.11±91.03 5.02±1.13 0.90±0.09 322.51±91.41 1 0.61±0.12 A2 289.78±87.73 4.55±1.04 0.86±0.12 293.61±89.83 1 0.56±0.12 A3 312.78±91.44 5.01±0.67 0.91±0.06 318.27±93.83 1 0.61±0.08 B1 387.75±84.81 5.85±0.40 0.95±0.03 390.88±85.83 1 0.68±0.06 B2 346±113.48 5.62±0.98 0.95±0.04 355.22±117.57 1 0.67±0.09 B3 377.13±96.93 5.53±1.41 0.92±0.12 382.77±95.50 1 0.64±0.15 C1 353±44.08 5.36±0.32 0.93±0.03 355.29±43.73 1 0.63±0.04 C2 339±73.76 5.59±1.21 0.93±0.07 341.68±73.19 1 0.66±0.13 C3 268.75±33.54 5.01±0.76 0.91±0.05 272.41±35.96 1 0.62±0.08

[0257] As can be seen from the above table, Observed OTUs: The richness of the flora in Group C decreased significantly (Δ = 84.25), and the decrease in Group A was smaller (Δ = 6.33 / 10.62). Shannon index: The diversity in Group A remained stable (Δ = 0.01), and that in Group C decreased significantly (Δ = 0.32 / 0.35).

[0258] 2.2.2 Species composition at the phylum level

[0259] See Figure 3 、 Figure 4 。Bacteroidetes / Firmicutes (F / B value): The F / B value in Group A decreased from 1.22 to 0.67 (inflammation remission), and that in Group C remained 1.09 (residual inflammation); Proteobacteria (pro-inflammatory bacteria): The relative abundance in Group A increased (5.54% → 12.86%), which may be related to the clearance of pathogenic bacteria by antibiotics.

[0260] 2.2.3 Changes in key flora at the genus level

[0261] Table 11 Composition table of major genera in each group

[0262]

[0263] As can be seen from Table 11, beneficial bacteria: The abundances of Bifidobacterium (4.42% → 4.88%) and Bacteroides (18.19% → 21.44%) in Group A increased. Harmful bacteria: The abundance of Dialister in Group A decreased significantly (4.23% → 0.82%).

[0264] In summary, the probiotic composition of the present invention can reduce the incidence of adverse reactions, shorten the duration of symptoms, accelerate the recovery of the primary disease, and at the same time maintain the diversity of the intestinal flora, increase the abundances of beneficial bacteria such as Bifidobacterium, and reduce the F / B value (inflammation remission), providing an effective solution for the precise intervention of antibiotic-related intestinal side effects.

Claims

1. A probiotic and prebiotic composition, characterized in that, The described composition contains probiotics, resistant dextrin, xylo-oligosaccharide, fructo-oligosaccharide, stachyose, erythritol and vitamin C. Among them, the probiotics include Bifidobacterium animalis subsp. lactis BLa80, Pediococcus acidilactici CCFM7902, Lactobacillus acidophilus LA85, Lactiplantibacillus plantarum N13, Paracasei paracasei LC86, Bifidobacterium bifidum BBi32, Lactobacillus rhamnosus LRa05, and Lactobacillus casei LC89.

2. The probiotic and prebiotic composition according to claim 1, characterized in that, The described vitamin C contains natural plant extracts and synthetic vitamin C and its derivatives. Preferably, the vitamin C is natural vitamin C. More preferably, the vitamin C is cranberry powder.

3. The probiotic and prebiotic composition according to any one of claims 1-2, characterized in that, The described composition includes the following components: Probiotics 1 - 50 parts by weight Resistant dextrin 5 - 100 parts by weight Xylo-oligosaccharide 5 - 100 parts by weight Fructo-oligosaccharide 1 - 50 parts by weight Stachyose 1 - 50 parts by weight Erythritol 1 - 50 parts by weight Cranberry powder 1 - 50 parts by weight.

4. The probiotic and prebiotic composition according to claim 3, characterized in that, The described composition includes the following components: Probiotics 5 - 20 parts by weight Resistant dextrin 10 - 50 parts by weight Xylo-oligosaccharide 10 - 50 parts by weight Fructo-oligosaccharide 3 - 10 parts by weight Stachyose 1 - 5 parts by weight Erythritol 5 - 10 parts by weight Cranberry powder 5 - 10 parts by weight Among them, the weight ratios of each strain are as follows: Bifidobacterium animalis subsp. lactis BLa80 10% - 20% Pediococcus acidilactici CCFM7902 5% - 15% Lactobacillus acidophilus LA85 5% - 15% Lactiplantibacillus plantarum N13 10% - 20% Paracasei paracasei LC86 10% - 20% Bifidobacterium bifidum BBi32 5% - 15% Lactobacillus rhamnosus LRa05 10% - 20% Lactobacillus casei LC89 5% - 15%.

5. The probiotic and prebiotic composition according to any one of claims 1-2, characterized in that It includes the following steps: (1) Prepare erythritol into an adhesive solution; (2) Mix resistant dextrin and xylo-oligosaccharide, and spray them into the adhesive in step (1) for granulation. After sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product.

6. The composition according to claim 5, wherein It includes the following steps: (1) Prepare erythritol into an adhesive solution with a concentration of 10 - 50% (w / v); (2) Mix resistant dextrin and xylo-oligosaccharide, and spray them into the adhesive in step (1) for granulation. Control the granule size to be 0.3 - 1.0 mm. After sieving, mix with stachyose, fructo-oligosaccharide, cranberry powder and probiotic powder to obtain the product. Further, the inlet air temperature during the granulation process is 50 - 70°C, the atomization pressure is 0.1 - 0.3 MPa, and the material fluidization speed is 1.5 - 3.0 m / s.

7. Use of the probiotic and prebiotic composition according to claim 1 in the preparation of an antibiotic adjuvant preparation.

8. Use of the probiotic and prebiotic composition according to claim 7 in the preparation of an antibiotic adjuvant preparation, characterized in that, The described composition is used to relieve antibiotic-induced intestinal flora imbalance, diarrhea or constipation, and at the same time regulate the intestinal microecology.

9. Use of the probiotic and prebiotic composition according to claim 7 in the preparation of an antibiotic adjuvant preparation, characterized in that, The described composition is used in combination with an antibiotic preparation for the treatment of related disease infections.

10. Use of the probiotic and prebiotic composition according to claim 9 in the preparation of an antibiotic adjuvant preparation, characterized in that, The described related disease infections include upper respiratory tract infection, lower respiratory tract infection, urinary tract infection, skin and soft tissue infection and other infections.

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