CN107616985A - Bacillus coagulans preparation and its application - Google Patents

Bacillus coagulans preparation and its application Download PDF

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Publication number
CN107616985A
CN107616985A CN201710924663.6A CN201710924663A CN107616985A CN 107616985 A CN107616985 A CN 107616985A CN 201710924663 A CN201710924663 A CN 201710924663A CN 107616985 A CN107616985 A CN 107616985A
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disease
bacillus coagulans
cfu
probiotics
bacillus
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崔云龙
赵婀姿
李洪福
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Qingdao Eastsea Pharmaceutical Co ltd
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Qingdao Eastsea Pharmaceutical Co ltd
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Abstract

The present invention relates to a kind of probiotics and its application, and in particular to main active includes the probiotics of bacillus coagulans, and application of the said preparation in preventing or treating relevant disease.

Description

Bacillus coagulans preparation and its application
Technical field
The present invention relates to a kind of probiotics and its application, and in particular to main active includes bacillus coagulans Probiotics, and said preparation prevent or treat relevant disease in application.
Background technology
Bacillus coagulans has the characteristics that high temperature resistant, acidproof and bile tolerance, can improve intestinal microflora, adjusts intestines Road dysfunction and maintenance intestinal flora balance, effectively facilitate nutrient metabolism and utilization, in prevention and treatment disease side Face plays an increasingly important role.At present, bacillus coagulans turns into the new food that can be used for by defending planning commission and examining Prebiotic strain, bacillus coagulans preparation research turn into new focus.Filter out the condensation with high activity, notable prebiotic effect Bacillus strain is the emphasis and difficult point of probiotics preparation research and development.
The present inventor has found that bacillus coagulans DH156 has high bioactivity, main active bag by research The probiotics of the DH156 containing bacillus coagulans can effectively adjust body microecological balance, prevention or treatment relevant disease, The no any toxic side effect of safety, has huge economic value and social value, and has no that correlative study is reported, spy applies for this Patent of invention.
The content of the invention
It is an object of the invention to provide a kind of probiotics, the main active of said preparation includes bacillus coagulans DH156, deposit number CGMCC No.13136, and application of the said preparation in preventing or treating relevant disease is provided.
What the preparation of the probiotics of the present invention was implemented preferably through following step, but be not limited to this and prepare work Skill, the known preparation technology that can be realized can be with:The sample of bacillus coagulans may be contained by taking, and be then placed in sample and gone out Therefrom take a certain amount of sample to add in the dilution of 18mL sterilizings in bacterium bottle, during research, fully mix, in aseptic operating platform It is interior, carry out 10-1、10-2、10-3、10-4、10-5、10-6、10-7Gradient dilution, take 10-5、10-6、10-7Three dilution gradients, respectively It is coated on bacillus coagulans selectivity single bacterium colony separation solid medium, is placed in incubator, is cultivated 48 hours at 37 DEG C, selected Select the single bacterium colony to grow fine to be inoculated in respectively in liquid amplification culture medium, be placed in incubator, amplification cultivation 48 is small at 37 DEG C When.After gained medium centrifugal (12000rpm) is isolated into thalline, by thalline vacuum freezedrying, dry bacterium powder is modulated, Then basis《The outstanding Bacteria Identification handbook of uncle》, Related Bacteria identification document or 16S rRNA sequence comparative analysis carry out condensation gemma Bacillus is identified and toxicity test, by avirulent bacillus coagulans dry bacterium powder desired proportions addition auxiliary material be made tablet, The various formulations such as capsule, powder, pulvis or liquid preparation, can also add the viable bacterias such as Bifidobacterium, Bacillus acidi lactici or FOS, The oligosaccharide such as xylo-oligosaccharide play synergy.Research shows that the oligosaccharide such as FOS, xylo-oligosaccharide can remarkably promote condensation Bacillus DH156 breeds, and assists bacillus coagulans DH156 preferably to play prebiotic effect.
Bacillus coagulans selectivity single bacterium colony separation solid medium is preferably but not limited to:Purified water 1000mL, egg White peptone 10g, beef leaching thing 10g, dibasic ammonium citrate 2g, sodium acetate 5g, dusty yeast 5g, glucose 5g, potassium dihydrogen phosphate 2g, tells Warm 801.0ml, calcium carbonate 20g, magnesium sulfate 0.58g, manganese sulfate 0.25g, agar 15g adjust pH 6.2-6.5, and 115 DEG C of high pressures are gone out Bacterium 20min.
Bacillus coagulans liquid amplification culture medium is preferably but not limited to:Purified water 1000mL, peptone 10g, beef Thing 3g, sodium chloride 5g, glucose 5g are leached, adjusts 7,115 DEG C of autoclaving 20min of pH.
To be further elaborated with the present invention, inventor passes through bacillus coagulans selectivity single bacterium colony using the above method Separation solid medium separation identifies avirulent bacillus coagulans, preferably DH156 bacterial strains, deposit number CGMCC No.13136。
The present invention implements the bacteriological quality of the bacillus coagulans preferably used in explanation:
1st, colonial morphology
Micro- sem observation:It is shaft-like, Gram-positive.
Plate morphology:Bacterium colony is white, circular, neat in edge, size 2-3mm.
2nd, Physiology and biochemistry is identified
Gelatin liquefaction:-;Catalase:+;VP is tested:+;Phenylalanine deaminase experiment-.
3rd, glycolysis experimental identification
Glucose:+;Maltose:+;Sucrose:+;Xylose:-;Fructose:+;Rhamnose:-;Lactose:+;Inulin:+;Gala Sugar:+;Dextrin:+.
4th, the bacterium of separation carries out 16S rRNA gene sequencing, measures in sequence BLAST and GenBank and RDP databases Gene order carry out similarity analysis, it is determined that separation bacterium be bacillus coagulans Bacillus coagulans.
Bacillus coagulans DH156 of the present invention is identified as bacillus coagulans Bacillus coagulans, coagulates The regulation body microecological balance that has of knot bacillus and prebiotic effect this bacterial strain are provided with, including but not limited to anti-inflammatory, anti- Allergy, it is antifatigue, improve immunity, promote digestion, promote absorption of nutrient ingredients, regulation spirit, skin maintenance, liver protection, nourishing the stomach, Clearing lung-heat, memory and notice, fat-reducing, nutrition and health care or enhancing development are improved, or prevent or treat disease of digestive system, Nutrient malabsorption disease, respiratory disease, psychosis, allergic disease, autoimmune disease, generation Thank systemic disease, cardiovascular and cerebrovascular disease, tumour or heavy metal poisoning, or the other diseases that prevention or treatment are triggered by these diseases Deng.Wherein described disease of digestive system includes but is not limited to diarrhoea, constipation, abdominal distension, indigestion, IBS, ulcer Property colitis, Crohn disease, pseudomembranous enteritis, necrotizing enterocolitis, intestinal cancer, tumor chemoradiotherapy auxiliary treatment, pylorus spiral shell Bacillus infection, disease in the liver and gallbladder, jaundice, canker sore, thrush, hand-foot-and-mouth disease, feeding intolerance promote children intestinal development It is ripe;The respiratory disease includes but is not limited to RRTI, chronic obstructive pulmonary disease or bronchial astehma;The spirit System disease includes but is not limited to anxiety disorder, depression, self-closing disease or Parkinson;The allergic disease includes but is not limited to Rheumatic arthritis or eczema;The autoimmune disease includes but is not limited to rheumatoid arthritis or rigid spine It is scorching;The metabolic system disease includes but is not limited to diabetes or gout;The cardiovascular and cerebrovascular disease includes but is not limited to high blood Fat disease.Further, the diarrhoea include but is not limited to cool rush down, drink rush down, antibiotic-associated diarrhea, infantile pneumonia it is secondary Property diarrhoea or virus diarrhea.
The probiotics of the present invention can effectively prevent or treat relevant disease, including but not limited to anti-inflammatory, antiallergy, resist Fatigue, immunity is improved, promotes digestion, promotes absorption of nutrient ingredients, regulation spirit, skin maintenance, liver protection, nourishing the stomach, clearing lung-heat, carries High memory and notice, fat-reducing, nutrition and health care or enhancing development, or prevention or treatment disease of digestive system, nutrition are inhaled Receive obstacle disease, respiratory disease, psychosis, allergic disease, autoimmune disease, metabolic system Disease, cardiovascular and cerebrovascular disease, tumour or heavy metal poisoning, or prevention or the other diseases that are triggered by these diseases for the treatment of etc..Its Described in disease of digestive system include but is not limited to diarrhoea, constipation, abdominal distension, indigestion, IBS, ulcerative colitis Inflammation, Crohn disease, pseudomembranous enteritis, necrotizing enterocolitis, intestinal cancer, tumor chemoradiotherapy auxiliary treatment, Helicobacter pylori Dye, disease in the liver and gallbladder, jaundice, canker sore, thrush, hand-foot-and-mouth disease, feeding intolerance promote children intestinal to reach maturity;Institute State respiratory disease and include but is not limited to RRTI, chronic obstructive pulmonary disease or bronchial astehma;The psychosis Including but not limited to anxiety disorder, depression, self-closing disease or Parkinson;The allergic disease includes but is not limited to rheumatic Arthritis or eczema;The autoimmune disease includes but is not limited to rheumatoid arthritis or ankylosing spondylitis;It is described Metabolic system disease includes but is not limited to diabetes or gout;The cardiovascular and cerebrovascular disease includes but is not limited to hyperlipemia.Enter One step, it is described diarrhoea include but is not limited to cool rush down, drink rush down, antibiotic-associated diarrhea, infantile pneumonia Secondary cases diarrhoea Or virus diarrhea.
The probiotics of the present invention can also be applied as effect components to be used for preventing or controlling in compositions related Treat above-mentioned disease.
The present inventor is through repeatedly screening and cultivates, and isolated bacillus coagulans bacterial strain DH156, the bacterial strain is compared with it He has higher activity, more excellent regulation body microecological balance ability and prebiotic effect by bacterial strain.As used herein, " institute State bacillus coagulans ", " bacillus coagulans of the present invention " or " bacillus coagulans described in this probiotics " refer to it is solidifying Tie bacillus DH156 bacterial strains, deposit number CGMCC No.13136.It should be understood that these terms are also included derived from condensation bud Spore bacillus DH156 bacterial strain, especially with high activity, or there is excellent regulation body microecological balance ability and prebiotic work Derivative strain.Main active includes bacillus coagulans DH156 and its probiotics of derivative strain is each fallen within Protection scope of the present invention.
Probiotics of the present invention, main active include but is not limited to bacillus coagulans DH156, and preservation is compiled Number CGMCC No.13136, can also add the oligosaccharide such as other viable bacterias, FOS or other active components.
The probiotics of the present invention, is to be used as main active or main active using the bacillus coagulans One of, according to certain preparation process, add conventional excipient, flavor enhancement, disintegrant, preservative, lubricant, wetting agent, The auxiliary materials such as binder, solvent, thickener, solubilizer, the formulation that manufactured any one is adapted for use with, as tablet, capsule, The formulations such as granule, powder, liquid preparation, pulvis.
Probiotics of the present invention includes but is not limited to composite medicine, health products, food, veterinary drug or feed addition Agent.
Bacillus coagulans described in this probiotics refers to bion living.
Bacillus coagulans described in this probiotics has high bioactivity.
This probiotics, the total viable count of bacillus coagulans that solid pharmaceutical preparation includes are not less than 1 × 106CFU/g, typically 1 × 107More than CFU/g, it can reach 1 × 1012CFU/g or 1 × 1012More than CFU/g;Or the condensation that liquid preparation includes The total viable count of bacillus is not less than 1 × 106CFU/mL, typically 1 × 107More than CFU/mL, it can reach 1 × 1012CFU/mL or 1 × 1012More than CFU/mL.
Embodiment
Preparation example explanation:The above-mentioned preparation to bacillus coagulans preparation illustrates, here by condensing gemma It is specifically described exemplified by bacillus DH156 deposit number CGMCC No.13136, the system of other bacillus coagulans strain preparations Preparation Method those skilled in the art are easy to grasp by the present embodiment, and preparation method those skilled in the art of other formulations are led to Cross this implementation to be easy to grasp, no longer describe explanation one by one herein.Preparation method is not limited to described in the embodiment of the present invention, public The method that can reach preparation purpose known can be so that the preparation explanation of embodiment is the description of the invention, is not pair The limitation of the scope of the present invention.
Prepare the preparation of the bacillus coagulans pulvis of embodiment 1
The preparation of 1 bacterium powder and the identification of strain
The samples such as the excrement, soil, haystack substrate of people are taken, then sample is placed in sterilizing bottle, therefrom take 2 grams of samples Add in the dilution of 18mL sterilizings, fully mix, in aseptic operating platform, carry out 10-1、10-2、10-3、10-4, 10-5, 10-6, 10-7Gradient dilution, take 10-5, 10-6, 10-7Three dilution gradients, it is coated on bacillus coagulans selectivity single bacterium colony separation solid On culture medium, incubator is placed in, is cultivated 48 hours at 37 DEG C, the single bacterium colony for selecting to grow fine is inoculated into bacillus coagulans liquid In body amplification culture medium, amplification cultivation 48 hours at 37 DEG C., will after gained medium centrifugal (12000rpm) is isolated into thalline Thalline vacuum freezedrying, modulates dry bacterium powder, and viable count is 1 × 1010More than CFU/g, then carry out strain idenfication.Through Physiology and biochemistry and 16S rRNA sequence comparative analysis are accredited as bacillus coagulans, are bacillus coagulans DH156 deposit numbers CGMCC No.13136。
2 toxicity tests
2.1 animals and packet take 20 SPF rank mouse, 6-8 week old, body weight 14-18g, are randomly divided into and condense gemma bar Bacterium group and non-administered group, every group 10.
Above-mentioned bacillus coagulans bacterium powder is modulated to containing bacterium number be 1 × 10 by 2.2 preparation bacterium solutions with purified water9CFU/mL Bacterium solution.
2.3 method bacillus coagulans groups and non-administered group give identical basal feed, and rearing conditions are consistent, Bacillus coagulans group gavages bacillus coagulans bacterium solution 0.5mL daily, and non-administered group gavages purified water 0.5mL daily, feeding 14 days, observe body weight and toxic reaction.
2.4 result
Each group mouse does not occur abnormal conditions, and chatter, spasm, ataxia, posture exception do not occur, and no eyeball is dashed forward Go out, urination is normal, and skin, breathing are normal, no death condition, have no toxic reaction.
3 are prepared into the formulations such as pulvis
It is non-toxic through experimental check, so that it may by bacillus coagulans strain after above-mentioned steps and method separation identification Bacterium powder is made, then various formulations are made in addition relevant auxiliary materials as required, preferably according to the viable bacteria of bacillus coagulans bacterium powder Number, starch is added in proportion pulvis is made, viable count is not less than 1 × 107CFU/g, then pack.
The present inventor uses above-mentioned separation and preparation method, while also separation obtains bacillus coagulans DH147 and coagulated Tie bacillus DH154.
Application effect embodiment explanation:
The present invention is using probiotics made of bacillus coagulans DH156 deposit number CGMCC No.13136 as representative Illustrate the application effect of bacillus coagulans preparation.It should be understood that these embodiments are merely to illustrate the present invention rather than limitation The scope of the present invention.To better illustrate the application effect of the present invention, the present inventor also uses bacillus coagulans DH147, coagulated Probiotics made of bacillus DH154 and commercial bacillus coagulans is tied to carry out comparative illustration.Used in the present invention Commercial bacillus coagulans come from the active bacillus coagulans product of market sale.With reference to specific embodiment, enter One step illustrates the present invention.
Application effect embodiment 1:The bioactivity of bacillus coagulans
The preparation of 1 bacterium powder has been prepared bacillus coagulans DH156, has been condensed bud using the preparation method of above-mentioned bacterium powder Spore bacillus DH147, bacillus coagulans DH154 and commercial bacillus coagulans bacterium powder.According to the work of bacillus coagulans bacterium powder Bacterium number, starch is added in proportion pulvis is made, viable count is not less than 1 × 107CFU/g, then pack.
It is 1 × 10 that above-mentioned bacterium powder is diluted to containing bacterium number by 2 fermented and cultureds6CFU/mL bacterium solution, use liquid amplification cultivation Base, amplification cultivation 48 hours (3 parallel) at 37 DEG C.Detect the coagulated bacillus living number in nutrient solution.
Through 48h amplification cultivations, in bacillus coagulans DH156 nutrient solutions, viable count is significantly higher than 3 results condenses gemma bar Viable count (P < 0.05) in bacterium DH147, bacillus coagulans DH154 and commercial bacillus coagulans nutrient solution, is shown in Table 1.
Coagulated bacillus living number (the Log of table 110CFU·mL-1, n=10)
4 discussion are above-mentioned test result indicates that bacillus coagulans DH156 is substantially compared with other bacterial strains and business under equal conditions It is vigorous with strain growth.Probiotic active is high, breeding is that it plays the basis of prebiotic effect and ensured soon.It is test result indicates that solidifying Knot bacillus DH156 has higher bioactivity compared with other coagulating bacillus strains, has very high prebiotic value.
Application effect embodiment 2:Adjustment effect of the bacillus coagulans to gut flora
1 materials and methods
BALB/C mice, male, body weight (20 ± 1) g, 2 grades of standard.Preparation method prepares as described in above-described embodiment Bacillus coagulans DH156 bacterium solutions (1 × 107CFU/mL);Bacillus coagulans DH147 bacterium solutions (1 × 107CFU/mL);Condense Bacillus DH154 bacterium solutions (1 × 107CFU/mL);Commercial bacillus coagulans bacterium solution (1 × 107CFU/mL)。
Mouse is randomly divided into bacillus coagulans DH156 groups, bacillus coagulans DH147 groups, bacillus coagulans DH154 groups, commercial bacillus coagulans group, model control group and Normal group (every group 20), single cage raising.Except normal right It is outer according to group, the feedwater of animal fasting in 1 day before remaining each group modeling, then with ampicillin sodium (adding normal saline) 0.15g Gavage, 0.5mL/ only, 2 times/day, cause diarrhea of mouse, draining sample or mushy stool.Mouse is used into bacterium solution gavage, 0.5mL/ respectively Secondary, 2 times/day, model control group and Normal group give isometric physiological saline, for three days on end.Taken after moulding and after treatment fresh Stool makees faecal microbiota analysis.
2 results
2.1 mouse defecation situations
Compared with model control group, diarrhea of mouse situation significantly takes a turn for the better ((P < 0.05), wherein condensing bacillus coagulans each group Bacillus DH156 anti-diarrhea effect is considerably better than other each groups (P < 0.05), is shown in Table 2.
The different group mouse defecation situations of table 2
2.2 analysis of intestinal microflora
As a result show that bacillus coagulans has significant proliferation (P < 0.05) to intestinal beneficial bacterium, to enteron aisle Harmful bacteria has the effect (P < 0.05) that significantly inhibits, can fast quick-recovery gut flora balance.Wherein bacillus coagulans DH156 Effect it is more notable, its promote beneficial bacterium propagation, suppress harmful bacteria, adjust gut flora ability be considerably better than condensation gemma Bacillus DH147, bacillus coagulans DH154 and commercial bacillus coagulans (P < 0.05), are shown in Table 3.
Analysis of intestinal microflora (the Log of table 310CFU·g-1, n=10)
3 conclusions
This experiment shows that bacillus coagulans can effectively recover gut flora balance, has significant treatment to make to diarrhoea With wherein bacillus coagulans DH156's is better, is considerably better than other bacillus coagulanses (P < 0.05).Condense gemma Bacillus DH156 can remarkably promote intestinal beneficial bacterium propagation, suppress harmful bacteria growing, fast quick-recovery gut flora balance, it was demonstrated that its To diarrhoea, constipation, IBS, abdominal distension and indigestion, disease in the liver and gallbladder, feeding intolerance or promote children intestinal development There are the intestinal bacilli illness disease such as maturation good treatment and prevention to act on, while disclose to nutrient malabsorption disease Or heavy metal poisoning etc. also has obvious therapeutic action.
Application effect embodiment 3:The aperient effects of bacillus coagulans
1 materials and methods
BALB/C mice, male, body weight (20 ± 1) g, 2 grades of standard.Bacillus coagulans DH156 bacterium solutions (1 × 107CFU/ mL);Bacillus coagulans DH147 bacterium solutions (1 × 107CFU/mL);Bacillus coagulans DH154 bacterium solutions (1 × 107CFU/mL);Business With bacillus coagulans bacterium solution (1 × 107CFU/mL)。
Mouse is randomly divided into bacillus coagulans DH156 groups, bacillus coagulans DH147 groups, bacillus coagulans DH154 groups, commercial bacillus coagulans group, model control group and Normal group (every group 10), single cage raising.Except normal right It is outer according to group, the feedwater of animal fasting in 1 day before remaining each assembly molding, then orally give 50mg/Kg R-1132s and induce just It is secret.Mouse is used into bacterium solution gavage respectively, 0.5mL/ times, 2 times/day, model control group and Normal group give isometric physiology salt Water, 2 times/day, for three days on end.2 results
Bacillus coagulans DH156 groups compared with model control group, mice with constipation situation significantly take a turn for the better ((P < 0.05), and condense Bacillus DH156 defecating feces excretion is considerably better than other bacillus coagulans groups (P < 0.05), is shown in Table 4.
The different group mouse defecation situations of table 4
3 conclusions
This experiment shows that bacillus coagulans DH156 has significant therapeutic effect to constipation, and it is solidifying to be considerably better than other Bacillus (P < 0.05) is tied, further confirms the fast quick-recovery gut flora balance of bacillus coagulans DH156 energy, Ke Yiyou Effect treatment constipation and constipation-predominant of irritable bowel syndrome etc..
Microorganism fungus kind of the present invention used in implementation process is on October 21st, 2016 in China Microbiological bacterium Kind preservation administration committee common micro-organisms center (grind by Yard 1, BeiChen xi Road, Chaoyang District, Beijing City 3 Chinese Academy of Sciences microorganism Study carefully institute's postcode 100101) preservation.Classification And Nomenclature:Bacillus coagulans Bacillus coagulans, deposit number CGMCC No.13136.For above-mentioned strain through the microorganism Spot detection, testing result is survival.

Claims (10)

1. a kind of probiotics, it is characterised in that said preparation main active includes bacillus coagulans, the condensation bud Spore bacillus includes bacillus coagulans DH156, deposit number CGMCC No.13136.
2. the probiotics as described in claim 1, it is characterised in that bacillus coagulans refers to bion living.
3. the probiotics as described in claim 1, it is characterised in that the preparation includes composite medicine, health products, food Product, veterinary drug or feed addictive.
4. probiotics described in claim 1 prepare anti-inflammatory, antiallergy, it is antifatigue, improve immunity, promote digestion, Promote absorption of nutrient ingredients, regulation spirit, skin maintenance, liver protection, nourishing the stomach, clearing lung-heat, raising memory and notice, fat-reducing, battalion Support the application in health care or enhancing development composition.
5. probiotics described in claim 1 is preventing or is treating disease of digestive system, nutrient malabsorption disease, exhales Desorption system disease, psychosis, allergic disease, autoimmune disease, metabolic system disease, cardiovascular and cerebrovascular disease Application in disease, tumour or heavy metal poisoning.
6. the probiotics as described in claim 1, it is characterised in that bacillus coagulans has high bioactivity.
7. applied as described in claim 5, it is characterised in that the disease of digestive system includes diarrhoea, constipation, abdominal distension, digestion not Good, IBS, ulcerative colitis, Crohn disease, pseudomembranous enteritis, necrotizing enterocolitis, intestinal cancer, tumour are put Chemotherapy auxiliary treatment, helicobacter pylori infections, disease in the liver and gallbladder, jaundice, canker sore, thrush, hand-foot-and-mouth disease, feeding intolerance Or children intestinal is promoted to reach maturity;The respiratory disease includes RRTI, chronic obstructive pulmonary disease or bronchial astehma; The psychosis include anxiety disorder, depression, self-closing disease or Parkinson;The allergic disease includes rheumatic Arthritis or eczema;The autoimmune disease includes rheumatoid arthritis or ankylosing spondylitis;The metabolic system Disease includes diabetes or gout;The cardiovascular and cerebrovascular disease includes hyperlipemia.
8. applied as described in claim 7, it is characterised in that it is described diarrhoea include cool rush down, drink rush down, antibiotic associated abdomen Rush down, infantile pneumonia Secondary cases is suffered from diarrhoea or virus diarrhea.
9. the probiotics as described in claim 1, it is characterised in that the bacillus coagulans includes bacillus coagulans DH156 and its derivative strain.
10. the probiotics as described in claim 1, it is characterised in that the total viable bacteria of bacillus coagulans that solid pharmaceutical preparation includes Number is not less than 1 × 106CFU/g, typically 1 × 107More than CFU/g, it can reach 1 × 1012CFU/g or 1 × 1012CFU/g More than;Or the total viable count of bacillus coagulans that liquid preparation includes is not less than 1 × 106CFU/mL, typically 1 × 107CFU/mL More than, it can reach 1 × 1012CFU/mL or 1 × 1012More than CFU/mL.
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CN111518720A (en) * 2020-04-30 2020-08-11 吉林省农业科学院 Bacillus coagulans (Bacillus coagulons) JA845 and application thereof
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CN113181342A (en) * 2021-05-19 2021-07-30 天津市宝恒生物科技有限公司 Bacillus coagulans preparation for treating depression
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CN113528367A (en) * 2020-04-15 2021-10-22 青岛蔚蓝生物股份有限公司 Bacillus coagulans with functions of preventing diarrhea and degrading cholesterol
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CN111254088A (en) * 2019-12-30 2020-06-09 杭州保安康生物技术有限公司 Bacillus coagulans strain and application thereof
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CN111518720B (en) * 2020-04-30 2021-01-05 吉林省农业科学院 Bacillus coagulans (Bacillus coagulons) JA845 and application thereof
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WO2022068273A1 (en) * 2020-09-29 2022-04-07 青岛蔚蓝生物股份有限公司 Bacillus coagulans having blood glucose reduction efficacy, and application thereof
CN112915108A (en) * 2021-01-21 2021-06-08 吉林省农业科学院 Application of bacillus coagulans JA845 in preparation of medicines for preventing and/or treating Alzheimer disease
CN113181342A (en) * 2021-05-19 2021-07-30 天津市宝恒生物科技有限公司 Bacillus coagulans preparation for treating depression
CN113181342B (en) * 2021-05-19 2022-11-08 天津市宝恒生物科技有限公司 Depression treating bacillus coagulans preparation
CN113789290A (en) * 2021-11-12 2021-12-14 山东中科嘉亿生物工程有限公司 Bacillus coagulans BCN019 with anti-fatigue effect and microbial inoculum and application thereof

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