CN106389479A - Application of bacillus coagulans in preparing preparation for preventing or treating autism - Google Patents

Application of bacillus coagulans in preparing preparation for preventing or treating autism Download PDF

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CN106389479A
CN106389479A CN201611060351.7A CN201611060351A CN106389479A CN 106389479 A CN106389479 A CN 106389479A CN 201611060351 A CN201611060351 A CN 201611060351A CN 106389479 A CN106389479 A CN 106389479A
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bacillus coagulans
cfu
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CN106389479B (en
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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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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/74Bacteria
    • A61K35/741Probiotics
    • A61K35/742Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/74Bacteria
    • A61K35/741Probiotics
    • A61K35/744Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745Bifidobacteria
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

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  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The invention discloses an application of bacillus coagulans in preparing a preparation for preventing and treating autism. The application is specifically characterized in that the bacillus coagulans is used for preventing or treating the autism and reducing symptoms of the autism.

Description

Application in preparation prevention or treatment autism preparation for the Bacillus coagulans
Technical field
The present invention relates to application in preparation prevention or treatment autism preparation for the Bacillus coagulans, specifically with condensing Bacillus cereuss prevention or treatment autism, reduce autistic symptoms.
Background technology
Autism, also known as infantile autism, is a kind of dysplasia class disease, is mainly shown as three major types core symptom, that is,:Society Meeting disorders,communication, communication disorder, the way of act of the narrow and mechanical repetition of interest, it is slow to there is Mental development in about 3/4 this disease infant Stagnant.Its course of disease sustainable all one's life is it is difficult to reverse, and prevalence raises year by year, give family and society cause huge economy and Burden on society.According to World Health Organization's statistics, the autistic children belong quantity of China's Mainland is about 60-180 ten thousand people, has scholar then to think real Border quantity is likely to be breached 260-800 ten thousand people.Autism has become as the important diseases that children's spirit class disables, with sickness rate Raise, bring huge society and financial burden and persistently to family and society.
The current remedy measures of autism mainly include behavior intervention and pharmaceutical intervention, and clinical adopt trains behavior intervention more With psychological cognition treatment, using medicine, symptomatic treatment is carried out to adjoint mental symptom simultaneously.However, medicine (as Risperidone, Ah Vertical piperazine azoles etc.) intervene and often bring various untoward reaction, affect Treatment Compliance and long term maintenance therapy.Lonely Solely disease patient's possessiveness is on the weak side, to untoward reaction sensitivity, therefore curative effect of medication and safety to Treatment Compliance with for a long time Maintaining treatment is particularly important.Therefore, find prevention that can be both safe and effective or treatment autism, reduce autistic symptoms Medicine be clinical in the urgent need to.The present inventor finds through research, and Bacillus coagulans can effectively be prevented or be treated lonely Disease, does not have safely any toxic and side effects, and effect is better than bacillus bifiduss, and has no that correlational study is reported, special this patent of invention of application.
Content of the invention
It is an object of the invention to provide one kind can be prevented or be treated autistic preparation, said preparation is by Bacillus coagulans system Become.
The preparation of the preparation of the present invention is implemented preferably through following step, but is not limited to this preparation technology, known The preparation technology enabling all permissible:Take the sample that may contain Bacillus coagulans, then sample be placed in sterilizing bottle, Therefrom take a certain amount of sample to add in the diluent of 18mL sterilizing during research, fully mix, in aseptic operating platform, carry out 10-1、10-2、10-3、10-4、10-5、10-6、10-7Gradient dilution, takes 10-5、10-6、10-7Three dilution gradients, are respectively coated in solidifying On knot bacillus cereuss selectivity single bacterium colony separation solid medium, it is placed in incubator, cultivates 48 hours at 37 DEG C, select growing way good Good single bacterium colony is inoculated in liquid amplification culture medium respectively, is placed in incubator, amplification cultivation 48 hours at 37 DEG C.By gained After medium centrifugal (12000rpm) isolates thalline, by thalline lyophilisation, modulate and mycopowder is dried, then basis 《The outstanding Bacteria Identification handbook of uncle》, Related Bacteria identification document or 16S rRNA sequence comparative analysis carry out Bacillus coagulans identification And toxicity test, avirulent Bacillus coagulans are dried mycopowder desired proportions interpolation adjuvant and make tablet, capsule, dissipate The various dosage form such as agent, powder or liquid preparation, also can add the oligosaccharide such as other viable bacterias or oligofructose to play synergism.
Bacillus coagulans selectivity single bacterium colony separation solid medium is preferably but not limited to:Purified water 1000mL, egg White peptone 10g, beef leaches thing 10g, dibasic ammonium citrate 2g, sodium acetate 5g, yeast powder 5g, glucose 5g, potassium dihydrogen phosphate 2g, tells Warm 80 1.0ml, Calcium Carbonate 20g, magnesium sulfate 0.58g, manganese sulfate 0.25g, agar 15g, adjust pH 6.2-6.5,115 DEG C of high pressure go out Bacterium 20min.
Bacillus coagulans liquid amplification culture medium is preferably but not limited to:Purified water 1000mL, peptone 10g, beef Leaching thing 3g, sodium chloride 5g, glucose 5g, adjust 7,115 DEG C of autoclaving 20min of pH.
For being further elaborated with the present invention, inventor utilizes said method to pass through Bacillus coagulans selectivity single bacterium colony Separate solid medium isolation identification and gone out avirulent Bacillus coagulans, Bacillus coagulans of the present invention are not limited to In bacterium described to illustrate the invention, as long as avirulent Bacillus coagulans are all of the present invention, all in the guarantor of the present invention In the range of shield.
Bacillus coagulans of the present invention are preferably but not limited to Bacillus coagulans TBC169 deposit number CGMCC1207 Or Bacillus coagulans deposit number CGMCC1.2407.
The bacteriological quality of the Bacillus coagulans that the present invention preferably uses in implementing to illustrate:
1st, to illustrate the invention, the present invention utilizes the detached Bacillus coagulans of said method is Bacillus coagulans TBC169 deposit number CGMCC1207.
2nd, colonial morphology
Micro- sem observation:Shaft-like, Gram-positive.
Plate morphology:Bacterium colony is white, circular, neat in edge, size 2-3mm.
3rd, Physiology and biochemistry identification
Gelatin liquefaction:-;Catalase:+;VP tests:+;Phenylalanine deaminase test-.
4th, glycolysiss experimental identification
Glucose:+;Maltose:+;Sucrose:+;Xylose:-;Fructose:+;Rhamnose:-;Lactose:+;Inulin:+;Gala Sugar:+;Dextrin:+.
5th, detached bacterium carries out 16S rRNA gene sequencing, records in sequence BLAST and GenBank and RDP data base Gene order carry out similarity analysis, determine detached bacterium be Bacillus coagulans.
Bacillus coagulans of the present invention refer to the bion of work.
The present invention be using effective dose as stated above detached Bacillus coagulans as main active ingredient, according to one Fixed preparation process, add conventional excipient, flavoring agent, disintegrating agent, preservative, lubricant, wetting agent, adhesive, solvent, The adjuvants such as thickening agent, solubilizing agent, make any fit for service dosage form, such as tablet, capsule, granule, powder, liquid The dosage forms such as body preparation, powder.
Bacillus coagulans of the present invention make active bacteria formulation as key agents active ingredient.
Indication effective dose of the present invention refer to as stated above detached Bacillus coagulans according to described above individually or Combine the total viable count comprising as the solid live bacteria preparation that key agents active ingredient is made and cannot be below 1 × 106CFU/g, Typically 1 × 107More than CFU/g, can reach 1 × 1012CFU/g or 1 × 1012More than CFU/g.
Indication effective dose of the present invention refer to as stated above detached Bacillus coagulans according to described above individually or Combine the total viable count comprising as the liquid active bacteria formulation that key agents active ingredient is made and cannot be below 1 × 106CFU/mL, Typically 1 × 107More than CFU/mL, can reach 1 × 1012CFU/mL or 1 × 1012More than CFU/mL.
Preparation of the present invention include Bacillus coagulans be used alone or with other drugs use in conjunction, especially include coagulating Knot bacillus cereuss be used alone or with bacillus bifiduss use in conjunction.
Bacillus bifiduss of the present invention refer to the bion of work.
In the preparation of bacillus bifiduss use in conjunction of the present invention, the total viable count of bacillus bifiduss that solid preparation comprises is not low In 1 × 106CFU/g, typically 1 × 107More than CFU/g, can reach 1 × 1012CFU/g or 1 × 1012More than CFU/g;Or The total viable count of bacillus bifiduss that liquid preparation comprises is not less than 1 × 106CFU/mL, typically 1 × 107More than CFU/mL, highest can Reach 1 × 1012CFU/mL or 1 × 1012More than CFU/mL.
Due to present invention firstly discloses Bacillus coagulans make preparation in prevention or treatment as main active ingredient Application in autism, the preparation therefore containing above-mentioned Bacillus coagulans is preventing or is treating the application in autism preparation all to belong to In protection scope of the present invention.
Bacillus coagulans of the present invention, when making any dosage form, are respectively provided with prevention or treatment are autistic Effect.If being prepared into preparation containing Bacillus coagulans composition in its component, in its packaging or the mark such as description or As long as indicating on other any propaganda materials or prompting having prevention or treats autistic effect, then fall into the protection of the present invention Within the scope of.
Bacillus coagulans of the present invention can make medicine, health food, food or beverage etc..
Specific embodiment
Preparation example explanation:The above-mentioned preparation to Bacillus coagulans preparation illustrates, here by condensation spore Bacillus TBC169 deposit number CGMCC1207 or Bacillus coagulans deposit number CGMCC1.2407 (Bacillus coagulans preservation Numbering CGMCC1.2407 be purchased from China Committee for Culture Collection of Microorganisms's common micro-organisms center) as a example carry out specifically Bright, preparation method those skilled in the art of other Bacillus coagulans strain preparations are easy to grasp by the present embodiment, its Preparation method those skilled in the art of his dosage form are easy to grasp by this enforcement, and here no longer describes explanation one by one.Preparation Method is not limited to described in the embodiment of the present invention, known can reach preparation purpose method all permissible, the system of embodiment Standby explanation is the description of the invention, is not limiting the scope of the invention.
The preparation of preparation embodiment 1 Bacillus coagulans powder
The preparation of 1 mycopowder and the identification of strain
Take the samples such as the feces of people, soil, haystack substrate, then sample is placed in sterilizing bottle, therefrom takes 2 grams of samples Add in the diluent of 18mL sterilizing, fully mix, in aseptic operating platform, carry out 10-1、10-2、10-3、10-4, 10-5, 10-6, 10-7Gradient dilution, takes 10-5, 10-6, 10-7Three dilution gradients, coat Bacillus coagulans selectivity single bacterium colony separation solid In culture medium, it is placed in incubator, cultivates 48 hours at 37 DEG C, select the single bacterium colony growing fine to be inoculated into Bacillus coagulans liquid In body amplification culture medium, amplification cultivation 48 hours at 37 DEG C.Gained medium centrifugal (12000rpm) is isolated after thalline, will Thalline lyophilisation, modulates and mycopowder is dried, and viable count is 1 × 109More than CFU/g, then carries out strain identification, warp Physiology and biochemistry and 16S rRNA sequence comparative analysis are accredited as Bacillus coagulans, are Bacillus coagulans TBC169 deposit number CGMCC1207.
Prepared by Bacillus coagulans deposit number CGMCC1.2407 mycopowder, by Bacillus coagulans deposit number CGMCC1.2407 is inoculated in Bacillus coagulans liquid amplification culture medium, amplification cultivation 48 hours at 37 DEG C.Gained is cultivated After liquid centrifugation (12000rpm) isolates thalline, thalline lyophilisation modulating and mycopowder is dried, viable count is 1 × 109More than CFU/g.
2 toxicity tests
2.1 animals and packet take 30 SPF rank mices, 6-8 week old, body weight 14-18g, random segregation junction bacillus cereuss CGMCC1207 group, 1.2407 groups of Bacillus coagulans CGMCC and non-administered group, every group 10.
Above-mentioned different Bacillus coagulans mycopowder is modulated to be 1 containing bacterium number by 2.2 preparation bacterium solution respectively with purified water ×109The bacterium solution of CFU/mL.
2.3 methods each Bacillus coagulans group and non-administered group all give identical normal feedstuff, and rearing conditions are homogeneous Cause, each Bacillus coagulans group gavages Bacillus coagulans bacterium solution 0.5mL daily, and non-administered group gavages purified water 0.5mL daily, Feeding 14 days, observes body weight and toxic reaction.
2.4 result
All abnormal conditions in each group mice, does not occur chatter, spasm, movement disorder, attitude abnormal, no eyeball is dashed forward Go out, urinate normal, skin, breathing are normal, no death condition has no toxic reaction.
3 are prepared into the dosage forms such as powder
After above-mentioned steps and method isolation identification, through experimental check avirulence so that it may by Bacillus coagulans strain Make mycopowder, then according to needing interpolation relevant auxiliary materials to make various dosage forms, preferably according to the viable count of Bacillus coagulans mycopowder, Add starch in proportion and make powder, make viable count be not less than 1 × 107CFU/g, then packs.
Application effect embodiment explanation:
The present invention is with Bacillus coagulans TBC169 deposit number CGMCC1207 or Bacillus coagulans deposit number CGMCC1.2407 is the application effect that representative illustrates Bacillus coagulans.Used in the present invention, bacillus bifiduss come from market Sell product, the bifidobacteria viable bacteria that the public can buy.
Application effect embodiment 1:Application in treatment autism for the Bacillus coagulans
1 model group preparation:
1.1 laboratory animals select adult Wistar rats (purchased from dimension tonneau China Experimental Animal Center):Adult SPF level Wistar female rats (weight 200-250g) 30, male rat (weight 300-350g) 30.Mus female, great and mighty or powerful mate The filial generation male rat (35d, weight 80-100g after birth) 50 given birth to afterwards.
1.2 preparation methods, with reference to the method for Schneider etc., Mus female, great and mighty or powerful are mated overnight, morning next day is to raettin Carry out vaginal smear examination, find that cloudy bolt person is designated as gestation the 1st day, and pregnant dams are individually raised.Pregnant dams press model group:Right According to group=4:1 quantity carries out random packet, and when the 12.5th day, it is disposable that the pregnant Mus of model group press 600mg/kg dosage abdominal cavity Injection Sodium Valproate (VPA), the normal saline of matched group pregnant Mus lumbar injection equivalent.The young Mus that the pregnant Mus of model group give birth to are orphan Solely disease model group, and the young Mus that the pregnant Mus of matched group give birth to are matched group.It is designated as P1 within 1st day after young Mus birth.Set up rat lonely Solely disease model.
1.3 model group preparation result modeling successes.
2 Drug therapy experiments:
2.1 experimental techniques randomly select 35 ages in days (P35) autism filial mice 40, matched group filial mice 10.Wherein compare Group filial mice is Normal group (n=10), and autism group filial mice is randomly divided into 1207 groups of Bacillus coagulans CGMCC, condensation Bacillus cereuss CGMCC1.2407 group, bacillus bifiduss group, 4 groups of model control group (n=10).Each treatment group and matched group all give Identical normal feedstuff, and rearing conditions are all consistent, each Bacillus coagulans group and bacillus bifiduss group using be 1 containing bacterium number × 106The bacterium solution of CFU/mL (modulating mycopowder with 0.9% normal saline) gavages 0.5mL, and model control group and matched group group fill daily Take 0.9% normal saline 0.5mL, continuous 2 weeks.Observe the impact to autism rat behavior for the Bacillus coagulans, and with double Bacillus is compared discrimination.
2.2 Behavior evaluations carry out Behavior evaluation to experimental mouse, and including social communication's behavioral value, (social behavior dives Fu Qi, persistent period, number of times), repeat behavioral value (reason hair cumulative time) and learning and memory test (Moirrs water maze survey Examination).Selection is identical with detection mice date of birth, weight difference is less than 15g, the male Mus of sub-cage rearing assist as strange Mus Carry out social communication's behavioral value.Data carries out statistical analysis using SPSS 21.0.
3 results
3.1 social communication's behavior evaluations
Compared with matched group, autism rat model Social behaviors number of times reduces (P < 0.01), and social incubation period increases (P < 0.01), the Social behaviors persistent period reduces (P < 0.01), and difference is statistically significant.With autism rat model phase After Bacillus coagulans CGMCC 1207 and CGMCC1.2407 treatment, rat Social behaviors number of times increases (P < 0.05) to ratio, society Bank of Communications is persistent period increase (P < 0.05), reduces (P < 0.05) social incubation period, difference has statistical significance.With Bacillus bifiduss treatment group rat is compared, and Bacillus coagulans CGMCC 1207 and CGMCC1.2407 group rat Social behaviors number of times increase Plus (P 0.05), social behavior's reduction incubation period (P < 0.05), social behavior's persistent period increases (P < 0.05), and difference has Statistical significance.1207 groups of Bacillus coagulans CGMCC and CGMCC1.2407 group between, rat Social behaviors number of times, social row For persistent period, social no difference of science of statistics incubation period (P > 0.05) occur.The social activity to autism rat for the Bacillus coagulans The behavior effect of being significantly improved, and it is significantly higher than bacillus bifiduss treatment group.It is shown in Table 1.
Table 1 different group rat social communications Behavioral change statistical analysiss
Group Number of cases Behavior occurrence number (secondary) Behavior incubation period (s) The persistent period (s) in behavior
Normal group 10 28.03±3.47 17.93±2.23 88.68±7.98
Model control group 10 18.77±2.16 32.18±3.44 70.62±6.23
Bacillus bifiduss group 10 21.39±2.50 25.85±3.36 73.46±4.02
1207 groups of Bacillus coagulans CGMCC 10 26.55±2.31 20.21±2.66 82.66±3.38
1.2407 groups of Bacillus coagulans CGMCC 10 26.83±2.79 19.87±2.56 82.13±4.05
3.2 repetition behavior evaluations
Compared with matched group, autism rat model reason hair accumulated time increases (P < 0.01), and difference has statistics to anticipate Justice;Compared with autism rat model, after Bacillus coagulans CGMCC 1207 and CGMCC1.2407 treatment, rat reason hair accumulation Time shortens (P < 0.05), and difference is statistically significant;Compared with bacillus bifiduss group rat, Bacillus coagulans CGMCC 1207 All shorten (P < 0.05) with CGMCC1.2407 group rat reason hair accumulated time, difference is statistically significant;Bacillus coagulans Between CGMCC1207 group and CGMCC1.2407 group, rat reason hair accumulated time no difference of science of statistics (P > 0.05).Condense spore Bacillus can substantially reduce the repetition behavior of autism rat, and its effect is significant is higher than bacillus bifiduss.It is shown in Table 2.
The different group rat of table 2 repeats Behavioral change statistical analysiss
Group Number of cases Reason hair cumulative time (s)
Normal group 10 67.83±11.20
Model control group 10 196.36±24.63
Bacillus bifiduss group 10 159.30±19.31
1207 groups of Bacillus coagulans CGMCC 10 126.98±19.76
1.2407 groups of Bacillus coagulans CGMCC 10 127.82±21.68
3.3 ability of learning and memory assessments
Compared with matched group, autism rat model ability of learning and memory poor (P < 0.01), difference has statistics to anticipate Justice;Compared with autism rat model, after Bacillus coagulans CGMCC 1207 and CGMCC1.2407 treatment, learning and memory in rats Ability improves (P < 0.05), and difference is statistically significant;Compared with bacillus bifiduss group rat, Bacillus coagulans CGMCC 1207 Improve (P < 0.05) with CGMCC1.2407 group learning and memory in rats ability, difference is statistically significant;Bacillus coagulans Between CGMCC1207 group and CGMCC1.2407, learning and memory in rats ability no difference of science of statistics (P > 0.05).Condense spore bar Bacterium can significantly improve the ability of learning and memory of autism rat, and its effect is significant is higher than bacillus bifiduss.It is shown in Table 3.
The different group learning and memory in rats ability statistical analysiss of table 3
Group Number of cases Ability of learning and memory (s)
Normal group 10 22.60±9.62
Model control group 10 43.35±15.55
Bacillus bifiduss group 10 37.12±13.97
1207 groups of Bacillus coagulans CGMCC 10 24.71±12.53
1.2407 groups of Bacillus coagulans CGMCC 10 24.99±11.73
4 discussion
The Social behaviors that autism model group compares rat with Normal group substantially reduce, and repetition behavior dramatically increases, Ability of learning and memory is poor, and after Bacillus coagulans treatment, Social behaviors number of times increases (P < 0.05), and social incubation period drops Low (P < 0.05), grooming accumulated time reduces (P < 0.05), and ability of learning and memory improves (P < 0.05), and curative effect shows Work is better than bacillus bifiduss treatment group.Show that Bacillus coagulans intervention can substantially reduce the autistic symptoms of autism rat.
Bacillus coagulans preparation can effectively prevent or treat autism hence it is evident that reducing lonely symptom, and no any poison Side effect, application compliance is good, is prevention or the autistic new method for the treatment of, new breakthrough.
Microorganism fungus kind used in implementation process for the present invention is in August in 2004 23 days in Chinese microorganism strain Preservation administration committee common micro-organisms center (Datun Road, Chaoyang District, Beijing City, Institute of Microorganism, Academia Sinica's postcode 100101) preservation.Classification And Nomenclature:Bacillus coagulans bacillus coagulans, deposit number 1207.Bacillus coagulans TBC169 deposit number CGMCC1207 is voluntarily separated by the present patent application unit and obtains, and sells in commercial channel, and Granted patent protects (patent No. 200410098660.4), and according to the regulation of Guidelines for Patent Examination, the public can be from commercial channel Buy or authorized, without preservation, proved, therefore, the present invention does not provide Bacillus coagulans without offer preservation TBC169 deposit number CGMCC1207 preservation proves.
Bacillus coagulans CGMCC 1.2407 is purchased from China Committee for Culture Collection of Microorganisms's common micro-organismss The heart.

Claims (10)

1. application in preparation prevention or treatment autism preparation for the Bacillus coagulans.
2. as described in claim 1 application it is characterised in that described preparation include Bacillus coagulans be used alone or and other Drug combination.
3. apply it is characterised in that described preparation includes medicine, health food, food, beverage as described in claim 1.
4. apply as described in claim 1 it is characterised in that described Bacillus coagulans refer to the bion of work.
5. apply as described in claim 1 it is characterised in that described Bacillus coagulans include Bacillus coagulans TBC169 guarantor Hide numbering CGMCC1207 or Bacillus coagulans deposit number CGMCC1.2407.
6. as described in claim 2 application it is characterised in that described preparation includes Bacillus coagulans is used alone or and bifid Bacillus use in conjunction.
7. apply as described in claim 6 it is characterised in that described bacillus bifiduss refer to the bion of work.
8. as described in claim 1, application, it is characterised in that prevention or treatment autism, reduces autistic symptoms.
9. as described in claim 1 preparation it is characterised in that the total viable count of Bacillus coagulans that solid preparation comprises is not less than 1 ×106CFU/g, typically 1 × 107More than CFU/g, can reach 1 × 1012CFU/g or 1 × 1012More than CFU/g;Or liquid The total viable count of Bacillus coagulans that body preparation comprises is not less than 1 × 106CFU/mL, typically 1 × 107More than CFU/mL, highest Can reach 1 × 1012CFU/mL or 1 × 1012More than CFU/mL.
10. as described in claim 6 preparation it is characterised in that the total viable count of bacillus bifiduss that solid preparation comprises be not less than 1 × 106CFU/g, typically 1 × 107More than CFU/g, can reach 1 × 1012CFU/g or 1 × 1012More than CFU/g;Or liquid The total viable count of bacillus bifiduss that preparation comprises is not less than 1 × 106CFU/mL, typically 1 × 107More than CFU/mL, can reach 1×1012CFU/mL or 1 × 1012More than CFU/mL.
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CN107854495A (en) * 2017-08-04 2018-03-30 青岛东海药业有限公司 Bacillus coagulans is preparing the application in reducing blood urine acid supplement
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WO2019046444A3 (en) * 2017-08-29 2019-05-31 Flaask, Llc Compositions and methods for diagnosing susceptibility to autism spectrum disorder (asd), reducing the likelihood of developing asd, and/or treating asd
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