CN105012349A - Probiotic preparation for preventing and treating vascular dementia and preparation method of probiotic preparation - Google Patents
Probiotic preparation for preventing and treating vascular dementia and preparation method of probiotic preparation Download PDFInfo
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Abstract
The invention belongs to the field of life science, relates to an application of a probiotic preparation in treating and preventing vascular dementia, in particular to a new application of medicine for preventing and treating vascular dementia through clostridium butyricum. Vascular dementia is brain tissue damage existing on the basis of multiple cerebrovascular diseases and the syndrome with cognition impairment as main clinical manifestation. The probiotic preparation for preventing and treating vascular dementia comprises medicine, healthcare products and drinks. No toxic or side effect is found. Intestinal flora is creatively adopted as treatment target points, a new pattern for preventing and treating vascular dementia is created, disease symptoms are relieved, nerve cell damage is retarded, good social and economic benefits are achieved, and the probiotic preparation is worthy of being applied and popularized.
Description
Technical field
The present invention relates to the novelty teabag of Clostridium butyricum, be specifically related to Clostridium butyricum in preparation prevention and the application in treatment vascular dementia compositions, belong to field of biological pharmacy.
Background technology
Vascular dementia (vascular dementia, VaD) is the brain tissue damage that multiple cerebrovascular disease basis occurs, and then is the syndrome of main clinical manifestation with cognitive dysfunction.Research shows, VaD is the second largest dementia being only second to senile dementia (Alzheimer ' sdisease AD), account for the half of the whole dementia patients of China, the prevalence of China VaD is 1.1% ~ 3.0%, annual morbidity is 5 ~ 9/1000 people, and sickness rate is in the trend risen year by year, and in the patients with cerebral apoplexy of over-65s, the apoplexy patient of about 25% ~ 41% can develop into VaD in three months.Along with the arriving of Chinese society aging, patients with cerebrovascular disease will get more and more, and VaD number of the infected also constantly increases, and personal health in serious harm, and causes heavy economic pressures to society and family.At present, the pathogenesis with regard to VD proposes the pathogenesis such as apoptosis, oxidative stress, inflammatory reaction, excitotoxic amino acids, choline system.Find in research that VD and apoptosis also exist substantial connection really.Apoptosis (apoptosis) is also called programmed cell death (Programmed cell death, PCD), it is a kind of specific type of biosphere cell death, namely under some physiology or the induction of pathologic factor, activated membrane signaling system, start the program gene about regulating cell apoptosis, finally cause cell to control oneself by certain procedures and destroy and death.Can adjust the gene of dying and protein to be divided into two classes by participating in neuron according to its effect: a class inhibitory neuron is adjusted and died, another kind of promotion neuron tune is died.
VaD is multi-factor disease, relevant with factors such as hypertension, diabetes, hyperlipidemia, pathogenesis may be relevant with following factor: (1) central cholinergic system dysfunction, VaD is a kind of change relating to cholinergic nerve of centrum unit and the aspect such as synapse, mediator thereof caused by cerebrovascular, the syndrome of the acquired intelligence damage of chronic progressive external and cognitive disorder; (2) oxygen-derived free radicals generates increases.Oxygen-derived free radicals can affect the function of cell membrane, causes cell membrane to increase, particularly to Ca some ion permeabilities
2+permeability increases, Ca in cell
2+concentration raises, and causes Ca
2+overload, increases the weight of neural cell injury; (3) excitatory neurotransmitter, glutamic acid (Glu) is a kind of acidic amino acid, be distributed widely in central nervous system as cerebral cortex, Hippocampus etc., after brain tissue ischemia, energy metabolism occurs abnormal, cause ATP level in body to decline rapidly, enhance the antiport of Glu, in cell, Glu content sharply raises, with the receptors bind such as NMDA, increase Na
+and Ca
2+interior stream, causes cellular swelling, Ca
2+overload, the arachidonic acid of generation, oxygen-derived free radicals, disrupting biofilm, causes DNA, protein degradation, finally causes nerve cell death; (4) inflammatory reaction etc.But up to now, the pathogenesis of VaD is still not exclusively clear and definite, thus lacks effective medicine.Existing clinical treatment means or medicine (as cholinesterase inhibitor, N-methyl-D-aspartate receptor antagonist etc.) all can not completely control VaD all symptoms or delay even to reverse its process, therapeutic effect is undesirable, and have side effect, affect patient health, treatment and prevention VaD become a difficult problem medically, and probiotics preparation part of the present invention solves this difficult medical problem, effectively can prevent and treat VaD, and have no side effect, harmless to body, social meaning is huge.
" probiotic bacteria " is active microorganism, effectively can improve intestinal microflora, suppresses pathogen, produces good health effect, be prepared into the probiotics preparations such as medicine, health product or beverage at present.Regulate by improving intestinal microbial population and treat the common recognition that general disease more and more becomes scientific circles now, a lot of nervous system disease is found in clinical practice, as infantile autism, depression, all there is close contacting with enteric flora disturbance, there is close relationship with the brain-gut axis of human body, even have and to palliate a disease the successful examples of symptom by drinking Yoghourt.Brain-gut axis is one and is present in central nervous system and unifies the bi-direction interactive system of the complexity between intestinal microbial population, more and more known by people.But, have no relevant report both at home and abroad by probiotic bacteria regulating intestinal canal flora treatment of vascular dementia.
Clostridium butyricum belongs to (Clostridium butyricum) as important probiotic bacteria, previously should be used for prevention and therapy enteritis, constipation and other diseases widely.Clostridium butyricum genus is generally present in the intestinal of soil, animal and human's body, it is Gram-positive anaerobic bacillus(cillus anaerobicus), gastric acid can be tolerated and enter intestinal, the regeneration of secretion intestinal mucosa and the important nutrient butyric acid (butanoic acid) repaired, the intestinal mucosa of repairing damage, diminish inflammation, nutrition intestinal, has good curative effect to the intestinal tract disease that a variety of causes comprises enterobacterial infection, chemotherapy of tumors, surgical operation etc. caused.Clostridium butyricum is not only effective to the inflammatory bowel disease such as constipation, antibiotic-associated diarrhea, to intestinal disease of brain, as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and hepatic encephalopathy (HE) also have therapeutical effect.There are some researches prove, intestinal microbial population and cerebration can influence each other, and wherein brain-gut axis is important physiological foundation.Brain-gut axis is the interactional two-ways regulation axle of central nervous system and gastrointestinal function, it comprises the structure such as nervous system (ENS) in central nervous system (CNS), autonomic nervous system (ANS), hypothalamic-pituitary-adrenal (HPA) axle, intestinal, and functions is coordinated mutually.Brain is had an impact to GI tract activity and intestinal microbial population by brain-gut axis.At chronic stress mouse model small mouse except with except depressive symptom, its gastrointestinal tract often has low grade inflammation to infiltrate, and intestinal microbial population also can change simultaneously.Meanwhile, intestinal microbial population also has an impact to GI tract activity.And research proves that the growth of intestinal microbial population to cerebral nervous system is vital, even mature central nervous system, its effect is also very important.Can get muddled at chronic stress small mouse brain-gut axis, produce the emotions such as depression, anxiety, give probiotics agents treatment and mice behavior can be made again to recover normal.As can be seen here, intestinal microbial population, brain-gut axis, brain tight association, constitute intestinal microbial population-intestinal-brain axle, in human health mechanism, be in unique position.For this path, we can treat numerous disease.Therefore, we infer that intestinal microbial population and vascular dementia disease may also exist certain relation, and the research of the relation of intestinal microbial population and vascular dementia has no report.
Summary of the invention
The object of the invention is to the defect and the deficiency that overcome prior art, inventive application Clostridium butyricum in the control of vascular dementia, and then develops the probiotics preparation of prevention or treatment vascular dementia.The object of this invention is to provide a kind of Clostridium butyricum bacterial strain that is safe, effectively preventing vascular dementia and probiotics preparation and preparation method.
The invention provides Clostridium butyricum (Clostridium butyricum) the WZMC1016 bacterial strain that a strain has treatment of vascular dementia.
Clostridium butyricum of the present invention is Clostridium butyricum (Clostridium butyricum) WZMC1016 bacterial strain, on October 22nd, 2014 at China Committee for Culture Collection of Microorganisms's common micro-organisms center, it is referred to as CGMCC (address: No. 3, Yard 1, BeiChen xi Road, Chaoyang District, Beijing City, Institute of Microorganism, Academia Sinica, postcode 100101) preservation, Classification And Nomenclature is Clostridium butyricum (Clostridium butyricum), and deposit number is CGMCC No.9831.
Clostridium butyricum of the present invention (Clostridium butyricum) WZMC1016 has following biological property:
(1) colonial morphology: be creamy white, circle is slightly convex, and edge is irregular, diameter 1 ~ 3mm, and surface is gloss slightly, has bubble to produce in fluid medium;
(2) individual morphology: be G
+bacillus cereus, thalline is in straight or knee shape, and 0.6 ~ 1.2 × 3.0 ~ 7.0 μm, end is round, single, paired, short chain, accidental long filament shape thalline;
(3) physiological and biochemical property: maltose (+); Mannitol (+); Raffinose (+); Lactose (+); Ribose (+); Starch (+).
Cultivate optimal condition: well-grown under anaerobism, does not grow in aerobic environment.Optimum growth temperature 35 ~ 40 DEG C; Minimum growth temperature 25 ~ 28 DEG C; The highest 43 ~ 45 DEG C; Growth optimum pH 6.5 ~ 7.0; PH 4.5 ~ 5.0 or 8.0 ~ 8.5 does not grow.
Another object of the present invention is to provide a kind of new pharmaceutical applications of Clostridium butyricum, i.e. the application of Clostridium butyricum in the dull-witted probiotics preparation compositions of preparation treatment of vascular, said composition can be medicine, health product and beverage etc.
The present invention is using the Clostridium butyricum WZMC1016 bacterial strain of effective dose as medicament active composition, according to certain preparation process, add the conventional adjuvant such as excipient, nutrient, make any one and be suitable for treatment and prevention vascular dementia probiotics preparation, the dosage form used clinically can be granule, powder, oral liquid, enema etc.
Indication effective dose of the present invention refers to can not lower than 1 × 10 according to total viable count that the solid live bacteria preparation made as active ingredient alone or in combination described in above comprises using Clostridium butyricum
7cFU/g.
Clostridium butyricum of the present invention refers to the form of living cells, and total viable count that probiotics preparation compositions comprises can not lower than 1 × 10
7cFU/g, generally 1 × 10
8more than CFU/g, can reach 1 × 10
12cFU/g or 1 × 10
12more than CFU/g.
The preferred preparation process of the present invention is, the preparation of Clostridium butyricum preparation: by Clostridium butyricum WZMC1016 bacterial strain seed liquor by weight 1% inoculum concentration access after sterilizing containing weight peptone 1%, Carnis Bovis seu Bubali cream 1%, yeast extract 0.5%, glucose 2%, K
2hP0
40.2%, MgSO
47H
2o 0.05%, MnSO
44H
2o 0.02%, oligofructose 0.3%, in dibasic ammonium citrate 0.2% fluid medium, through 36.DEG C ~ 38 DEG C of anaerobic fermentations after; centrifugalize thalline; thalline is added in sodium glutamate containing weight 5% and 5% greasiness milk powder frozen-dried protective liquid; clostridium butyricum active bacteria mycopowder can be obtained after mixed freezing drying; the dry mycopowder of gained; mix with pharmaceutical carrier, namely obtain described final dosage form probiotic composition.Preparation process is not limited to of the present invention, and other known preparation process is all passable.Pharmaceutical carrier can be oligofructose, glucose, trehalose etc.
Because the present invention makes public for the first time with Clostridium butyricum WZMC1016 bacterial strain as medicament active composition is in preparation treatment and the application in prevention vascular dementia medicine; therefore; with Clostridium butyricum WZMC1016 bacterial strain for active ingredient and auxiliary material combination make medicament; as long as this medicament is used for the treatment of and prevention vascular dementia, all belong to protection scope of the present invention.
Effective dose refers to can not lower than 1 × 10 according to total viable count that the solid live bacteria preparation made as active ingredient alone or in combination described in above comprises using Clostridium butyricum
7cFU/g.
The total viable count of Clostridium butyricum that clostridium butyricum preparation compositions of the present invention comprises can not lower than 1 × 10
7cFU/g, generally 1 × 10
8more than CFU/g, can reach 1 × 10
12cFU/g or 1 × 10
12more than CFU/g.
It is dull-witted that the present invention selects Clostridium butyricum WZMC1016 bacterial strain to carry out treatment of vascular, evident in efficacy, and with the increase of dosage, curative effect is strengthened, and does not find any toxic and side effects.
Advantage of the present invention and effect:
The present invention discloses the purposes of Clostridium butyricum WZMC1016 bacterial strain in treatment of vascular dementia first, and provides the preparation method of Clostridium butyricum preparation compositions.The Clostridium butyricum WZMC1016 bacterium source that the present invention selects is in human body, and through screening, domestication and checking, safety is high, has good ecological mutual aid.The present invention obviously can improve the alteration of intestinal flora caused by vascular dementia, and the present invention can improve the anti-neuronal apoptosis of cerebral tissue, improving studing ability.The metabolite of Clostridium butyricum has the short-chain fatty acid such as butanoic acid, by blood brain barrier, also can play the nerve injury effect of anti-angiogenic property dementia in brain.Therefore, Clostridium butyricum preparation compositions of the present invention as the medicine for the treatment of of vascular dementia, can have no side effect, easy to use, can be used as the auxiliary treatment that nutritional preparation and other nutrients one are used from clinical patients.
Detailed description of the invention
Clostridium butyricum mycopowder is first prepared in the preparation of Clostridium butyricum preparation compositions, then dose corresponding adjuvant as required and make corresponding dosage form, the present invention is specifically prepared as example with oral clostridium butyricum active bacteria powder, the preparation method of probiotic bacteria is described, the preparation method of other dosage form is omitted, illustrate no longer one by one, concrete preparation dosage form is not limited to method described below.If do not specialize, the conventional means that technological means used in embodiment is well known to those skilled in the art.
The Isolation and ldentification of embodiment 1 Clostridium butyricum (Clostridium butyricum) WZMC1016 bacterial strain
Using the feces of a healthy young people as sample separation, on modified MRS agar culture medium, under 37 DEG C of anaerobic conditions, 48h is coated with separation and Culture, obtain Clostridium butyricum of the present invention (Clostridium butyricum) WZMC1016, be accredited as Clostridium butyricum and belong to.
The formula of modified MRS culture medium: peptone 10g, Carnis Bovis seu Bubali cream 10g, yeast extract 5g, glucose 20g, K
2hPO
42g, MgSO
47 H
2o 0.5g, MnSO
44H
2o 0.2g, oligofructose 3g, dibasic ammonium citrate 2g, agar 15g, distilled water 1L, adjust pH to 7.0,115 DEG C of sterilizings 15 minutes.
Clostridium butyricum of the present invention (Clostridium butyricum) WZMC1016 has following microbial characteristic:
(1) colonial morphology: be creamy white, circle is slightly convex, and edge is irregular, diameter 1 ~ 3mm, and surface is gloss slightly, has bubble to produce in fluid medium.
(2) individual morphology: be G
+bacillus cereus, thalline is in straight or knee shape, and 0.6 ~ 1.2 × 3.0 ~ 7.0 μm, end is round, single, paired, short chain, accidental long filament shape thalline.
(3) physiological and biochemical property: maltose (+); Mannitol (+); Raffinose (+); Lactose (+); Ribose (+); Starch (+).
Cultivate optimal condition: well-grown under anaerobism, does not grow in aerobic environment.Optimum growth temperature 35 ~ 40 DEG C; Minimum growth temperature 25 ~ 28 DEG C; The highest 43 ~ 45 DEG C; Growth optimum pH 6.5 ~ 7.0; PH 4.5 ~ 5.0 or 8.0 ~ 8.5 does not grow.
Clostridium butyricum of the present invention (Clostridium butyricum) WZMC1016, on October 22nd, 2014 at China Committee for Culture Collection of Microorganisms's common micro-organisms center, it is referred to as CGMCC (address: No. 3, Yard 1, BeiChen xi Road, Chaoyang District, Beijing City, Institute of Microorganism, Academia Sinica, postcode 100101) preservation, Classification And Nomenclature is that Clostridium butyricum belongs to, and deposit number is CGMCC No.9831.
The preparation of embodiment 2 Clostridium butyricum (Clostridium butyricum) WZMC1016 probiotics preparation compositions
1. seed liquor preparation: the mono-bacterium colony of picking Clostridium butyricum (Clostridium butyricum) WZMC1016, be inoculated in 50mL MRS liquid culture medium, pH is 7.0 ± 0.5,37 DEG C, and Anaerobic culturel 24h, is seed liquor;
The formula of modified MRS culture medium: peptone 10g, Carnis Bovis seu Bubali cream 10g, yeast extract 5g, glucose 20g, sodium acetate 5g, K
2hPO
42g, MgSO
47 H
2o 0.5g, MnSO
44H
2o 0.2g, oligofructose 3g, dibasic ammonium citrate 2g, distilled water 1L, adjust pH to 7.0,115 DEG C of sterilizing 15min.
2. fermentation culture: the seed liquor of getting step 1, is seeded in new modified MRS culture medium with 1% inoculum concentration, 37 DEG C, Anaerobic culturel 24h, terminates to cultivate;
3. collect thalline: get step 2 fermentation liquid, with 12,000rpm, 10min condition, remove fermented supernatant fluid, centrifugalize goes out thalline;
4. mycopowder preparation: get thalline that step 3 collects and add in sodium glutamate containing weight 5% and 5% greasiness milk powder frozen-dried protective liquid and can obtain Clostridium butyricum mycopowder after mixed freezing drying.
5. finished product preparation: get the dry mycopowder of step 4 gained, according to the viable count of Clostridium butyricum, mix with pharmaceutical carrier (oligofructose, glucose, trehalose etc.) in proportion, prepare Clostridium butyricum preparation compositions finished product, the viable count of finished product is not less than 1 × 10
7cFU/g or 1 × 10
7cFU/mL.
The treatment zoopery of embodiment 3 vascular dementia
Object: observe the impact of Clostridium butyricum preparation of the present invention on the learning and memory of fourth ventricle in mice with vascular dementia, intracerebral oxidation index and neurocyte morphological change.
One, materials and methods:
1. medicine: Clostridium butyricum (Clostridium butyricum) WZMC1016 mycopowder is 1 × 10 containing viable count
8cFU/g, concrete preparation method, detailed in Example 2.
2. laboratory animal: ICR mice is male, body weight 18-22 gram.
3. the preparation of vascular dementia (VaD) mouse model and animal grouping: adopt the one-sided common carotid artery obturation (rUCCAO) in the permanent right side, after mouse anesthesia, be fixed on operating-table, be separated and sew up and carry out right carotid with permanent little silk thread, the body temperature of mice remains on 37 DEG C of constant temperature.The successful mice of vascular dementia model is divided into model group and Clostridium butyricum WZMC1016 treatment group.Only open skin, do not connect bundle and be classified as Sham-operated control group,
Start after rUCCAO to treat, by concentration 1 × 10 to clostridium butyricum WZMC1016
9cFU/mL dosage 0.2mL gavage, once a day, administration in continuous 4 weeks, the normal saline of negative control group and vascular dementia model group mouse stomach equivalent.Whole mice all gives standard mouse food routine feeding.Experiment terminates the last week and carries out the test of water maze neuroethology to whole mice, and after neuroethology test terminates, Mice brain tissues carries out perfusion to be fixed, and the pathology of HE dyeing, TUNEL dyeing detect, Electronic Speculum Ultrastructural observation.
4. ability of learning and memory test
The experiment of spacious field and Morris water maze carry out ability of learning and memory test, comprise constant-bearing navigation and space exploration experiment.Experimental facilities is made up of video acquisition system, data analysis system and four ring tanks resembling line, the Spatial learning ability of test experience animal and spatial memory capacity.
A) constant-bearing navigation experiment: mice is put into water from 4 place of entry respectively towards pool wall, record mice finds platform required time, i.e. escape latency (escape latency), follow-on test 5 days.
B) space exploration experiment: remove platform on the 6th day, measures mice and resembles the line time of staying in target.
5. pathologic examination: the paraformaldehyde with 4% carries out cardiac perfusion to be fixed, and gets brain, paraffin embedding, section.
5.1 HE dyeing: paraffin section is carried out conventional H E dyeing, the dewaxing of paraffin section routine comes downwards in distilled water to be waited to contaminate; Haematoxylin dyeing 5min is put in section, and tap water washes away unnecessary dyestuff; Cut into slices in hydrochloride alcohol and break up the several seconds; Tap water fully washes section; In 1% Yihong aqueous solution 5 minutes, wash away unnecessary Yihong; Gradient alcohol dehydration, mounting.
5.2 TUNEL dyeing: TUNEL dying operation by specification carries out, and TUNEL positive cell core dyes brown color.
6. apply the change of PCR-DGGE technical measurement intestinal microbial population, calculate species abundance index, Shannon-Wiener index, species evenness index.After performance testing, by sacrifice, take out cecal content rapidly.Fresh specimens is transferred to ice chest laboratory immediately and is stored in-80 DEG C, extracts the genomic DNA of antibacterial in the fecal specimens of DNA extraction agent box.16S rRNAV3 district pcr amplification product carries out DGGE, software analysis DGGE finger printing, and rubber tapping reclaims band and cloning and sequencing, and sequence is carried out homology analysis in GenBank data base.
7. statistical analysis: experimental data represents with mean ± standard deviation, SPSS 18.0 statistical software is adopted to carry out one factor analysis of variance (One-Way ANOVA) statistical analysis, group difference adopts q inspection, and p < 0.05 indicates significant difference.
Two, experimental result:
1. water maze laboratory result
Neuroethology result shows: the decline of obvious ability of learning and memory and judgement appears in vascular dementia model mice; Clostridium butyricum treatment group obviously improves the learning memory disorder of vascular dementia model mice, and constant-bearing navigation achievement (escape latency) obviously shortens, and has significant difference (P < 0.01) with model group ratio.Above result shows that clostridium butyricum WZMC1016 group effect of the present invention is the most obvious, and tool has clear improvement the learning and memory function of fourth ventricle in mice with vascular dementia.Experimental result is in table 1.
Table 1 is on the impact of mice constant-bearing navigation achievement (escape latency)
2. spacious experimental result
Total Distance geometry free activity time of model group fourth ventricle in mice with vascular dementia motion is obviously few than sham operated rats (P < 0.05), and having obvious rising (P < 0.05) through the total Distance geometry of the mouse movement free activity time that clostridium butyricum WZMC1016 treats, mice activeness obviously takes a turn for the better.
3. hippocampal tissue morphological change
3.1 Ultrastructural observation
Sham operated rats hippocampal tissue neuronal structure is normal, and oval core and clearly chromosome, structure of mitochondria is normal.On the contrary, model group Hippocampus of Mice neuronal cell core is irregular, and chromatin is uneven cuts mitochondrial swelling, and neuron is obviously impaired.Clostridium butyricum WZMC1016 treatment group intact mitochondria number is more, and neuromal ultrastructure is impaired to be alleviated.
3.2 HE dyeing
Sham operated rats CA 1 Zone of Hippocampus in Mouse Granule Neurons marshalling, visible circle or oval forming core and obvious kernel.And Model group CA 1 Zone of Hippocampus in Mouse neuron becomes circle, kytoplasm solidifies, karyopycnosis, and kernel disappears, and pathological change is obvious.After clostridium butyricum WZMC1016 treats, neuronal damage alleviates.
3.3 TUNEL dyeing
The visible many sepia cells in model group CA 1 Zone of Hippocampus in Mouse, represent apoptosis.After clostridium butyricum WZMC1016 treats, almost lose the apoptotic cell of labelling, above result shows that clostridium butyricum of the present invention has obvious Anti-G value.。
4. the intestinal microbial population of vascular dementia is affected
Clostridium butyricum WZMC1016 treatment group significance on intestinal microbial population abundance index, Shannon-Wiener index (H ') and species evenness index is better than vascular dementia model mice.
Conclusion:
The present invention is creatively therapy target with intestinal microbial population, start the new model for the treatment of of vascular dementia, the medicine for the treatment of of vascular dementia have developed a kind of good effect, having no side effect, prove through animal experiment study, the obvious ability of learning and memory improving fourth ventricle in mice with vascular dementia, alleviates apoptotic pathological change.It is dull-witted that the present invention selects Clostridium butyricum WZMC1016 bacterial strain to carry out treatment of vascular, evident in efficacy, and do not find any toxic and side effects, can be used as the auxiliary treatment that nutritional preparation and other nutrients one are used from clinical patients.
Claims (6)
1. the application of Clostridium butyricum in the dull-witted compositions of preparation treatment of vascular, is characterised in that described compositions comprises medicine, health product and oral liquid.
2. apply according to claim 1, it is characterized in that Clostridium butyricum is Clostridium butyricum WZMC1016 bacterial strain, this bacterial strain is deposited in China Committee for Culture Collection of Microorganisms's common micro-organisms center, deposit number: CGMCCNo.9831 on October 22nd, 2014.
3. apply according to claim 1, it is characterized in that described Clostridium butyricum is form of viable cells.
4. apply according to claim 1, it is characterized in that compositions is the compositions made using Clostridium butyricum as active ingredient.
5. apply according to claim 1, it is characterized in that the viable count that described compositions comprises Clostridium butyricum is not less than 1 × 10
7cFU/g.
6. Clostridium butyricum is in the preparation method of the dull-witted compositions for the treatment of of vascular, comprise the steps: by Clostridium butyricum WZMC1016 bacterial strain seed liquor by weight 1% inoculum concentration access after sterilizing containing weight peptone 1%, Carnis Bovis seu Bubali cream 1%, yeast extract 0.5%, glucose 2%, K
2hPO
40.2%, MgSO
47H
2o 0.05%, MnSO
44H
2o 0.02%; oligofructose 0.3%; in dibasic ammonium citrate 0.2% fluid medium; after 36 DEG C ~ 38 DEG C anaerobic fermentations, centrifugalize thalline, adds in sodium glutamate containing weight 5% and 5% greasiness milk powder frozen-dried protective liquid by thalline; clostridium butyricum active bacteria mycopowder can be obtained after mixed freezing drying; the dry mycopowder of gained, mixes with pharmaceutical carrier, namely obtains described final dosage form probiotic composition.
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| CN106420840A (en) * | 2016-11-23 | 2017-02-22 | 青岛东海药业有限公司 | Application of Clostridium butyricum in preparation of preparations for preventing or treating depression |
| CN106389479A (en) * | 2016-11-28 | 2017-02-15 | 青岛东海药业有限公司 | Application of bacillus coagulans in preparing preparation for preventing or treating autism |
| CN108186686A (en) * | 2017-12-31 | 2018-06-22 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | It is a kind of based on brain-gut axis resist it is chronic it is unpredictable stress Depression Induced drug and its application |
| CN108186686B (en) * | 2017-12-31 | 2020-11-13 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Medicine for resisting depression caused by chronic unpredictable stress based on brain-intestinal axis and application thereof |
| CN111202754A (en) * | 2019-03-11 | 2020-05-29 | 江苏佰澳达生物科技有限公司 | Probiotic composition for preventing and improving senile dementia and application thereof |
| CN111743934A (en) * | 2020-06-23 | 2020-10-09 | 江苏省中医院 | Traditional Chinese medicine composition for regulating intestinal flora and application thereof |
| CN113832069A (en) * | 2020-11-30 | 2021-12-24 | 河南农业大学 | Clostridium butyricum and application thereof, medicine, food, health product, veterinary drug, feed additive and microecological preparation |
| CN113832069B (en) * | 2020-11-30 | 2024-01-30 | 河南农业大学 | Clostridium butyricum and application thereof |
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