Application of bacillus coagulans BC99 in preparation of probiotic preparation for assisting in reducing uric acid level

Abstract

The invention relates to application of bacillus coagulans BC99 in preparation of a probiotic preparation for assisting in reducing the uric acid level. The bacillus coagulans BC99 is a bacillus coagulans BC99 strain of which the preservation number is CGMCC (China General Microbiological Culture Collection Center) No. 21801, and the bacillus coagulans BC99 strain of which the preservation number is CGMCC No. 21801. The invention finds that the bacillus coagulans BC99 has a very remarkable effect in the aspect of assisting in reducing uric acid, and the effect is specifically shown as follows: the levels of serum uric acid, urea nitrogen and creatinine of a hyperuricemia rat are reduced; the xanthine oxidase activity of the hyperuricemia rats is improved; the serum inflammatory factor level of the hyperuricemia rats is regulated, and the inflammatory reaction caused by uric acid increase is inhibited; and the levels of glutamic oxalacetic transaminase and glutamic-pyruvic transaminase of high-uric-acid rats Meanwhile, the bacillus coagulans BC99 is used as a probiotic, so that the product is high in safety and not easy to generate resistance.

Description

Technical Field

[0001] The invention belongs to the technical field of microorganisms and relates to a new use of Bacillus coagulans BC99, and specifically relates to the use of Bacillus coagulans BC99 in the preparation of a probiotic preparation for assisting in reducing uric acid levels. Background Art

[0002] The cells in the human body undergo metabolism every day, and the nucleic acids in the body are destroyed to generate purines. These purines produced in the body and the purines ingested from food are decomposed by xanthine oxidase and adenosine deaminase in the body, and finally form uric acid. Uric acid is produced in the liver, muscle and adipose tissue. It is the end product of purine metabolism and the main antioxidant in human plasma, which can protect cells or neurons from oxidative damage. Under normal circumstances, a dynamic balance is maintained between the intestinal absorption of purines, the production of uric acid and the excretion of uric acid through the kidneys to maintain the normal physiological state of the body. Due to changes in dietary structure and lifestyle, the number of patients with hyperuricemia and gout has also increased, and it has become a common disease in modern society. The problems of drug dependence and difficulty in dietary control brought about by traditional drug treatment and diet control have also made measures to relieve hyperuricemia ineffective. Therefore, it is urgent to develop new effective methods to prevent and relieve the symptoms of hyperuricemia.

[0003] At present, a large number of studies have shown that increased uric acid levels are closely related to liver damage. Uric acid is produced in the liver, and high uric acid will cause the continuous production of pro-inflammatory factors and pro-oxidant mediators, further aggravating liver damage and forming a vicious cycle. Studies have shown that probiotics have shown great potential in preventing and treating liver damage and reducing inflammatory factors. As living microorganisms, probiotics can bring health benefits to the host in a variety of ways when consumed in sufficient amounts. The mechanism of action of probiotics in assisting in lowering uric acid mainly includes improving enzyme activity, reducing the production of pro-inflammatory factors, and improving the host's metabolic function.

[0004] The application of probiotics in assisting the reduction of uric acid is still in its early stages, and there are still few strategies. Therefore, developing more probiotics that assist in reducing uric acid can provide new ideas and methods for assisting in reducing uric acid and treating liver damage. Summary of the invention

[0005] In view of the deficiencies of the prior art, the object of the present invention is to provide a new use of Bacillus coagulans BC99, specifically to provide the use of Bacillus coagulans BC99 in the preparation of a probiotic preparation that assists in lowering uric acid levels.

[0006] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions: In a first aspect, the present invention provides the use of Bacillus coagulans BC99 in the preparation of a probiotic preparation that assists in reducing uric acid levels; The Bacillus coagulans BC99 is a Bacillus coagulans with a deposit number of CGMCC No. 21801. Bacillus coagulans BC99 strain.

[0007] The present invention has developed a new use of Bacillus coagulans BC99, providing a research basis for its wide application, and also developed a new strategy for assisting in lowering uric acid levels. The present invention found that Bacillus coagulans BC99 is very effective in assisting in lowering uric acid, specifically in: (1) significantly reducing the levels of serum uric acid, urea nitrogen, and creatinine in rats with high uric acid levels; (2) significantly improving the activity of xanthine oxidase (XOD) in rats with high uric acid levels; (3) regulating the levels of serum inflammatory factors such as TNF-α, IL-6, and IL-1β in rats with high uric acid levels, and inhibiting the inflammatory response caused by increased uric acid levels; (4) effectively reducing the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats with high uric acid levels. At the same time, as a probiotic, Bacillus coagulans BC99 has high safety and is not prone to resistance.

[0008] Preferably, the dosage form of the probiotic preparation includes solution, powder, tablet, granule or capsule. The dosage form of the probiotic preparation involved in the present invention is not limited, including the most commonly used solution, powder, or further prepared capsule, tablet or granule.

[0009] Preferably, the number of viable bacteria in the probiotic preparation is not less than 1×10 9 CFU / mL or 1×10 9 CFU / g, for example 1×10 9 CFU / g (CFU / mL), 2×10 9 CFU / g (CFU / mL), 5×10 9 CFU / g (CFU / mL), 8×10 9 CFU / g (CFU / mL), 1×10 10 CFU / g (CFU / mL), 5×10 10 CFU / g (CFU / mL), 1×10 11 CFU / g (CFU / mL), 1×10 12 CFU / g (CFU / mL), 1×10 13 CFU / g (CFU / mL), etc. Other specific point values ​​within this numerical range can be selected and will not be described here one by one.

[0010] Preferably, the strains in the probiotic preparation also include Bifidobacterium bifidum with a preservation number of CGMCC No. 16923. Bifidobacterium bifidum BBi32 strain.

[0011] The above-mentioned Bacillus coagulans BC99 can not only be used alone to lower uric acid levels, but can also be combined with the Bifidobacterium bifidum BBi32 strain to lower uric acid levels.

[0012] The present invention has also developed a brand-new strategy for reducing uric acid levels, that is, Bacillus coagulans BC99 strain and Bifidobacterium bifidum BBi32 strain are compounded and used, and it is found that the two can cooperate with each other and promote each other, and synergize in reducing serum uric acid, urea nitrogen, creatinine levels of hyperuricemic rats, improving xanthine oxidase activity of hyperuricemic rats, regulating serum inflammatory factor levels of hyperuricemic rats, suppressing inflammatory reactions caused by elevated uric acid, etc., and when using consistent bacterial amounts, compared with a single BC99 strain or a single BBi32 strain intervention method, the compounding of the two bacteria is significantly improved in the above-mentioned effects. Therefore, the two probiotics are used to prepare probiotic preparations that assist in reducing uric acid levels and have good prospects. Meanwhile, the above-mentioned two bacteria are both probiotics, and the safety of the product is high, and it is not easy to produce resistance.

[0013] Preferably, the ratio of the number of viable bacteria of the BC99 strain to that of the BBi32 strain is 1:10-10:1, for example, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc. Other specific point values ​​within this numerical range can be selected, and they will not be described one by one here.

[0014] Based on the potential synergistic relationship between the above two strains, when they meet the above-mentioned specific ratio of live bacteria counts, their effects are even better in lowering the serum uric acid, urea nitrogen, and creatinine levels of hyperuricemia rats, improving the xanthine oxidase activity of hyperuricemia rats, regulating the levels of serum inflammatory factors in hyperuricemia rats, and inhibiting the inflammatory response caused by increased uric acid.

[0015] Preferably, the probiotic preparation is in the form of a solution, which is prepared by the following method: The relevant strains are inoculated into a culture medium for activation and fermentation to obtain a fermentation broth; the fermentation broth is centrifuged and then resuspended with a solvent to obtain a bacterial suspension or a mixed bacterial suspension.

[0016] Preferably, the probiotic is in the form of a freeze-dried powder, which is prepared by the following method: The relevant strains are inoculated into a culture medium for activation and fermentation to obtain a fermentation liquid; the fermentation liquid is centrifuged, mixed with a protective agent, and then freeze-dried to obtain bacterial powder or mixed bacterial powder.

[0017] Preferably, the probiotic preparation further contains excipients; the excipients include any one of fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, colorants, pH regulators, antioxidants, antibacterial agents or buffers, or a combination of at least two of them.

[0018] In a second aspect, the present invention provides the use of Bacillus coagulans BC99 in the preparation of a probiotic preparation for improving hyperuricemia; The Bacillus coagulans BC99 is a Bacillus coagulans with a deposit number of CGMCC No. 21801. Bacillus coagulans BC99 strain.

[0019] Based on the excellent efficacy of Bacillus coagulans BC99 in reducing uric acid levels, it can be used to prepare probiotic preparations for improving hyperuricemia.

[0020] Preferably, the number of viable bacteria in the probiotic preparation is not less than 1×10 9 CFU / mL or 1×10 9 CFU / g, for example 1×10 9 CFU / g (CFU / mL), 2×10 9 CFU / g (CFU / mL), 5×10 9 CFU / g (CFU / mL), 8×10 9 CFU / g (CFU / mL), 1×10 10 CFU / g (CFU / mL), 5×10 10 CFU / g (CFU / mL), 1×10 11 CFU / g (CFU / mL), 1×10 12 CFU / g (CFU / mL), 1×10 13 CFU / g (CFU / mL), etc. Other specific point values ​​within this numerical range can be selected and will not be described here one by one.

[0021] Preferably, the strains in the probiotic preparation further include the Bifidobacterium bifidum BBi32 strain with a preservation number of CGMCC No. 16923; the ratio of the number of viable bacteria of the BC99 strain to that of the BBi32 strain is 1:10-10:1.

[0022] The present invention has also developed a new strategy for improving hyperuricemia, that is, the Bacillus coagulans BC99 strain and the Bifidobacterium bifidum BBi32 strain are compounded and used together, and it is found that the two can cooperate with each other and promote each other, and synergize in improving the effect of hyperuricemia. When the amount of bacteria used is the same, compared with the intervention method of a single BC99 strain or a single BBi32 strain, the compounding of the two bacteria significantly improves the above effect. Therefore, the use of the two probiotics in the preparation of probiotic preparations for improving hyperuricemia has a good prospect.

[0023] Compared with the prior art, the present invention has the following beneficial effects: The present invention has developed a new use of Bacillus coagulans BC99, providing a research basis for its wide application, and also developed a new strategy for assisting in lowering uric acid levels. The present invention found that Bacillus coagulans BC99 is very effective in assisting in lowering uric acid levels, specifically in: (1) significantly reducing the levels of serum uric acid, urea nitrogen, and creatinine in rats with hyperuricemia; (2) significantly improving the activity of xanthine oxidase (XOD) in rats with hyperuricemia; (3) regulating the levels of serum inflammatory factors such as TNF-α, IL-6, and IL-1β in rats with hyperuricemia, and inhibiting the inflammatory response caused by increased uric acid; and (4) effectively reducing the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats with hyperuricemia.

[0024] The present invention has also developed a brand-new composite bacteria strategy for reducing uric acid levels, that is, Bacillus coagulans BC99 strain and Bifidobacterium bifidum BBi32 strain are compounded and used, and it is found that the two can cooperate with each other and promote each other, and synergize in reducing serum uric acid, urea nitrogen, creatinine levels of hyperuricemic rats, improving xanthine oxidase activity of hyperuricemic rats, regulating serum inflammatory factor levels of hyperuricemic rats, suppressing inflammatory reactions caused by elevated uric acid, etc., and when using consistent bacterial amounts, compared with a single BC99 strain or a single BBi32 strain intervention method, the compounding of the two bacteria is significantly improved in the above-mentioned effects. Therefore, the two probiotics are used to prepare probiotic preparations that assist in reducing uric acid levels and have good prospects. Meanwhile, the above-mentioned two bacteria are both probiotics, and the safety of the product is high, and it is not easy to produce resistance.

[0025] The BC99 strain involved in the present invention is classified as Bacillus coagulans Bacillus coagulans The depository is the General Microbiology Center of China Microbiological Culture Collection Administration. The deposit date is February 1, 2021. The deposit number is CGMCC No. 21801. The address is: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing.

[0026] The BBi32 strain involved in the present invention is classified and named as Bifidobacterium bifidum Bifidobacterium bifidum The depository is the General Microbiology Center of China Microbiological Culture Collection Administration. The deposit date is December 10, 2018. The deposit number is CGMCC No. 16923. The address is: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is the statistical result diagram of the weight change of rats in each group; Figure 2 This is the statistical result diagram of serum uric acid content in each group of rats; Figure 3 is the statistical result diagram of serum xanthine oxidase (XOD) activity of rats in each group; Figure 4 This is the statistical result of serum aspartate aminotransferase (AST) content of rats in each group; Figure 5 This is the statistical result of serum alanine aminotransferase (ALT) in rats of each group; Figure 6 This is the statistical result of the serum inflammatory factor TNF-α level of rats in each group; Figure 7 This is the statistical result of the serum inflammatory factor IL-6 level of rats in each group; Figure 8 This is the statistical result of the serum inflammatory factor IL-1β level of rats in each group; Fig. 9 This is the statistical result graph of serum creatinine content of rats in each group; Fig.10 This is a statistical graph of serum urea nitrogen content in each group of rats. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0029] The BC99 strain referred to in the following content is named Bacillus coagulans Bacillus coagulans The deposit date is February 1, 2021, and the deposit number is CGMCC No. 21801.

[0030] The BBi32 strain involved in the following content is named Bifidobacterium bifidum Bifidobacterium bifidum The deposit date is December 10, 2018, and the deposit number is CGMCC No. 16923.

[0031] The SPF-grade SD male rats involved in the following content were purchased from Shanghai Experimental Animal Center; ordinary feed was purchased from Shanghai Slake Company.

[0032] The preparation method of the BC99 or BBi32 bacterial suspension involved in the following experiment is as follows: the desired strain is inoculated into MRS liquid culture medium, cultured at 37°C for 18 hours for activation, and activated twice in succession to obtain an activated solution; the activated solution is inoculated into MRS liquid culture medium at an inoculum amount of 3% (v / v), and cultured at 37°C to obtain a bacterial solution; the bacterial solution is centrifuged at 4°C and 4000 rpm for 5 min, filtered to obtain bacterial bodies, and the bacterial bodies are resuspended in PBS.

[0033] MRS medium: peptone 10g / L, beef extract 10g / L, glucose 20g / L, sodium acetate 2g / L, yeast powder 5g / L, diammonium hydrogen citrate 2g / L, K2PO4·3H2O 2.6g / L, MgSO4·7H2O 0.1g / L, MnSO4 0.05g / L, Tween 801mL / L, cysteine ​​hydrochloride 0.5g / L. Example

[0034] This example explores the improvement effect of probiotic preparations on the hyperuricemia rat model: (1) Rearing and screening conditions: Healthy male SPF SD rats, 8 weeks old, were raised in a controlled environment, with room temperature maintained at 23-27°C, humidity at 45-55%, and a 12h light / dark cycle. They were free to eat and drink. The litter was changed 1-2 times a week. 0.4 mL of blood was collected from the tail vein on an empty stomach and placed in a 1.5 mL EP tube, placed in a 4°C refrigerator for 1 hour, centrifuged at 4°C and 3000 r / min for 15 minutes, and serum was collected. The uric acid value was determined using a uric acid determination kit to exclude experimental rats with unstable uric acid. 70 rats with normal uric acid values ​​were selected and adaptively raised for one week.

[0035] (2) Animal grouping: After one week of adaptive feeding, the rats were randomly divided into 8 groups, with 10 rats in each group: blank group, model group, BC99 group (intervention with BC99 bacterial solution), BBi32 group (intervention with BBi32 bacterial solution), ATCC31284 group (intervention with commercially available Bacillus coagulans ATCC31284 bacterial solution), composite group 1 (combined intervention with BC99 bacterial solution and BBi32 bacterial solution, with a live bacteria count ratio of 10:1), composite group 2 (combined intervention with BC99 bacterial solution and BBi32 bacterial solution, with a live bacteria count ratio of 1:10), and control composite group (combined intervention with commercially available Bacillus coagulans ATCC31284 bacterial solution and commercially available Bifidobacterium bifidum ATCC29521 bacterial solution, with a live bacteria count ratio of 10:1).

[0036] (3) Animal modeling method: After one week of adaptive feeding, the rats were fasted for 12 h and deprived of water for 4 h. Then, potassium oxonate (300 mg / kg) and hypoxanthine (300 mg / kg) were gavaged once a day for 7 consecutive days. After 7 days, blood was collected from the tail tip of the rats, and the serum uric acid content was detected using a uric acid determination kit. Rats with serum uric acid content higher than 120 μmol / L were determined to have successfully established the model.

[0037] (4) Animal intervention methods: Blank group: Rats in the blank group (healthy rats) were gavaged with 10 mL of normal saline every day for 21 days; Model group: Rats in the model group (model rats) were gavaged with 10 mL of normal saline every day for 21 days; BC99 group: Rats in the BC99 group (model rats) were intragastrically administered with 10 mL BC99 bacterial suspension (concentration of 2×10 9 CFU / mL) for 21 days; BBi32 group: Rats in the BBi32 group (model rats) were intragastrically administered with 10 mL of BBi32 bacterial suspension (concentration of 2×10 9 CFU / mL) for 21 days; ATCC31284 group: Rats in the ATCC31284 group (model rats) were intragastrically administered with 10 mL of ATCC31284 bacterial suspension (concentration of 2×10 9 CFU / mL) for 21 days; Combined group 1: Rats in the combined group 1 (model rats) were intragastrically administered with 10 mL of BC99 and BBi32 mixed bacterial suspension (total concentration of 2×10 9 CFU / mL) for 21 days; Combined group 2: Rats in the combined group 2 (model rats) were intragastrically administered with 10 mL of BC99 and BBi32 mixed bacterial suspension (total concentration of 2×10 9 CFU / mL) for 21 days; Comparative composite group: Rats in the comparative composite group (model rats) were intragastrically administered with 10 mL of a mixed bacterial suspension of commercially available Bacillus coagulans ATCC31284 and commercially available Bifidobacterium bifidum ATCC29521 (total concentration of 2×10 9 CFU / mL) for 21 days.

[0038] (5) Indicator analysis: (5.1) During the experiment, the rats’ body weights were measured weekly and their diet and drinking water records were recorded. The dynamic body weight data of rats in each group are as follows: Figure 1 As shown. Figure 1It can be seen that the weight of rats in each group began to increase after the gavage. After the experiment, the weight of rats in each group increased to about 300g, indicating that the symptoms of hyperuricemia had no significant effect on the weight of rats, and the intervention of probiotics had no significant effect.

[0039] (5.2) Effects of probiotic intervention on serum uric acid levels in hyperuricemic rats: After the last intragastric administration, the rats were fasted for 12 h, blood was collected from the tail tip, centrifuged at 3500 r / min at 4°C for 20 min, and serum was collected in an EP tube. The serum uric acid content was detected using a uric acid determination kit; the serum uric acid content of rats in each group was as follows: Figure 2 shown.

[0040] Figure 2 The results showed that compared with the blank group, the uric acid level in the model group was much higher than that in the blank group; compared with the model group, after the intervention of probiotics in each group, the uric acid level in the serum of rats decreased to varying degrees. The uric acid content in the BC99 group, compound 1 group, and compound 2 group was significantly lower than that in the model group, and the compound 1 group and compound 2 group reduced the uric acid level most significantly, indicating that the two groups cooperate and promote each other in reducing the serum uric acid of rats with high uric acid.

[0041] (5.3) Effect of probiotic intervention on serum xanthine oxidase (XOD) activity in rats with hyperuricemia: After the last intragastric administration, the rats were fasted for 12 h, blood was collected from the tail tip, centrifuged at 3500 r / min at 4°C for 20 min, and serum was collected in an EP tube. XOD activity was detected using a XOD activity assay kit; the serum XOD content of rats in each group was as follows: Figure 3 shown.

[0042] Uric acid in the human body is mainly derived from nucleic acids and other purine compounds decomposed by cell metabolism, as well as purine in food, which are decomposed by enzymes. Uric acid is the final product of the decomposition of adenine and guanine, the components of nucleic acids, in the human body. Hypoxanthine and xanthine are the direct precursors of uric acid. Under the action of xanthine oxidase (XOD), hypoxanthine is oxidized to xanthine, and xanthine is oxidized to uric acid. Figure 3 The results showed that compared with the blank group, the XOD activity in the model group was higher than that in the blank group; compared with the model group, after intervention with probiotics in each group, the serum XOD activity of rats decreased to varying degrees, thereby reducing uric acid production and further harm to the body. The serum XOD activity of rats in the BC99 group, compound 1 group, and compound 2 group was significantly lower than that in the model group, and the serum XOD activity of rats in the compound 1 group and compound 2 group decreased most significantly, indicating that the two groups cooperated and promoted each other in reducing the serum XOD activity of rats with hyperuricemia.

[0043] (5.4) Effects of probiotic intervention on serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in rats with hyperuricemia: After the last intragastric administration, the rats were fasted for 12 h, blood was collected from the tail tip, centrifuged at 3500 r / min at 4°C for 20 min, and serum was collected in an EP tube. The AST and ALT detection kits were used to detect the content of AST and ALT respectively; the serum AST and ALT levels of rats in each group were as follows: Figure 4 , Figure 5 shown.

[0044] Studies have shown that uric acid is produced in the liver, muscle and adipose tissue, and patients with high uric acid levels also suffer from severe liver damage. Aspartate aminotransferase (AST) is mainly distributed in the myocardium, followed by tissues such as the liver, skeletal muscle and kidney. Under normal circumstances, the AST content in serum is low, but when the corresponding cells are damaged, the cell membrane permeability increases, and the AST in the cytoplasm is released into the blood, so its serum concentration can increase. Alanine aminotransferase (ALT) is a biological enzyme that is mainly present in the cytoplasm of liver cells, and the intracellular concentration is 1000-3000 times higher than that in serum. As long as 1% of liver cells are destroyed, the serum enzyme can be doubled. Therefore, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are recommended by the World Health Organization as the most sensitive detection indicators for liver function damage.

[0045] Depend on Figure 4 , Figure 5 It can be seen that compared with the blank group, the AST and ALT contents in the model group were much higher than those in the blank group; compared with the model group, after the intervention of probiotics in each group, the serum AST and ALT contents of rats decreased to varying degrees. The serum AST and ALT contents of rats in BC99 group, compound group 1 and compound group 2 were lower than those in the model group, and the serum AST and ALT contents of rats in compound group 1 and compound group 2 decreased most significantly, indicating that the two cooperated and promoted each other in reducing the serum AST and ALT contents of rats with hyperuricemia.

[0046] (5.5) Effects of probiotic intervention on serum inflammatory factor levels in rats with hyperuricemia: After the last oral administration, the rats were fasted for 12 h, anesthetized by intraperitoneal injection of 4% chloral hydrate solution, blood was collected from the eyeballs, centrifuged at 4°C 3500r / min for 20 min, and serum was collected in EP tubes. The content of TNF-α, IL-6, and IL-1β was detected according to the detection kit methods; the content of serum inflammatory factors in rats in each group was as follows: Figure 6-Figure 8 shown.

[0047] Depend on Figure 6-Figure 8It can be seen that compared with the blank group, the levels of TNF-α, IL-6, and IL-1β in the model group were higher than those in the blank group; compared with the model group, after intervention with probiotics in each group, the levels of TNF-α, IL-6, and IL-1β in serum of rats were reduced to varying degrees, and the effects of reducing the levels of TNF-α, IL-6, and IL-1β in serum of rats in the BC99 group, compound group 1, and compound group 2 were more significant, and the compound group 1 and compound group 2 were better, indicating that the two groups have synergistic effects in reducing the levels of serum inflammatory factors in rats with hyperuricemia.

[0048] (5.6) Effects of probiotic intervention on serum creatinine and urea nitrogen levels in rats with hyperuricemia: After the last oral administration, the rats were fasted for 12 h, anesthetized by intraperitoneal injection of 4% chloral hydrate solution, blood was collected from the eyeballs, centrifuged at 4°C 3500 r / min for 20 min, and serum was collected in EP tubes. Serum creatinine and urea nitrogen were tested according to the methods of serum creatinine and urea nitrogen test kits; the serum creatinine and urea nitrogen contents of rats in each group were as follows: Figure 9-10 shown.

[0049] Long-term hyperuricemia can lead to further aggravation of renal function damage, which is manifested by further increases in creatinine and urea nitrogen. Figure 9-10 It can be seen that compared with the blank group, the serum creatinine and urea nitrogen contents in the model group were higher than those in the blank group; compared with the model group, after the intervention of probiotics in each group, the serum creatinine and urea nitrogen contents of rats were improved to varying degrees, and the effects of reducing serum creatinine and urea nitrogen contents in rats in the BC99 group, compound 1 group, and compound 2 group were more significant, and the compound 1 group and compound 2 group were better, indicating that the two groups have synergistic effects in reducing serum creatinine and urea nitrogen levels.

[0050] The applicant declares that the present invention illustrates the technical solution of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0051] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0052] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. Application of Bacillus coagulans BC99 in the preparation of probiotic preparations for assisting in lowering uric acid levels; The Bacillus coagulans BC99 is a Bacillus coagulans with a deposit number of CGMCC No. 21801. Bacillus coagulans BC99 strain.

2. The use according to claim 1, characterized in that: The dosage form of the probiotic preparation includes solution, powder, tablet, granule or capsule.

3. The use according to claim 1, characterized in that: The number of viable bacteria in the probiotic preparation is not less than 1×10 9 CFU / mL or 1×10 9 CFU / g.

4. The use according to claim 1, characterized in that: The strains in the probiotic preparation also include Bifidobacterium bifidum with a preservation number of CGMCC No. 16923 Bifidobacterium bifidum BBi32 strain.

5. The use according to claim 4, characterized in that: The ratio of the number of viable bacteria of the BC99 strain to that of the BBi32 strain is 1:10-10:

1.

6. The use according to claim 1, characterized in that: The dosage form of the probiotic preparation is a solution, which is prepared by the following method: Inoculating the relevant strains into a culture medium for activation and fermentation to obtain a fermentation broth; centrifuging the fermentation broth and resuspending it with a solvent to obtain a bacterial suspension or a mixed bacterial suspension; The dosage form of the probiotic is a freeze-dried powder, which is prepared by the following method: The relevant strains are inoculated into a culture medium for activation and fermentation to obtain a fermentation liquid; the fermentation liquid is centrifuged, mixed with a protective agent, and then freeze-dried to obtain bacterial powder or mixed bacterial powder.

7. The use according to claim 1, characterized in that: The probiotic preparation also contains excipients; the excipients include any one of fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, colorants, pH regulators, antioxidants, antibacterial agents or buffers, or a combination of at least two of them.

8. Application of Bacillus coagulans BC99 in the preparation of probiotic preparations for improving hyperuricemia; The Bacillus coagulans BC99 is a Bacillus coagulans with a deposit number of CGMCC No. 21801. Bacillus coagulans BC99 strain.

9. The use according to claim 8, characterized in that: The number of viable bacteria in the probiotic preparation is not less than 1×10 9 CFU / mL or 1×10 9 CFU / g.

10. The use according to claim 8, characterized in that: The strains in the probiotic preparation also include Bifidobacterium bifidum with a preservation number of CGMCC No. 16923 Bifidobacterium bifidum BBi32 strain; the ratio of the number of viable bacteria of the BC99 strain to that of the BBi32 strain is 1:10-10:1.

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