CN110227085A - Application of the Akkermansia Muciniphila in preparation antidepressant or health care product - Google Patents
Application of the Akkermansia Muciniphila in preparation antidepressant or health care product Download PDFInfo
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- CN110227085A CN110227085A CN201910639110.5A CN201910639110A CN110227085A CN 110227085 A CN110227085 A CN 110227085A CN 201910639110 A CN201910639110 A CN 201910639110A CN 110227085 A CN110227085 A CN 110227085A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 230000001430 anti-depressive effect Effects 0.000 title description 6
- 239000000935 antidepressant agent Substances 0.000 title description 5
- 229940005513 antidepressants Drugs 0.000 title description 5
- 229940079593 drug Drugs 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 19
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- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
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- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/24—Antidepressants
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
The invention discloses a kind of application of Akkermansia Muciniphila bacterium in the drug or health care product of preparation prevention and treatment depression.The present invention has carried out internal pharmacodynamic study to effect of the AkkermansiaMuciniphila bacterium in depression morbidity and antidepression, and the AkkermansiaMuciniphila abundance in patients with depression enteron aisle is substantially reduced as the result is shown.Results of animal shows that depressed mouse intestinal Akkermansia Muciniphila abundance significantly reduces.The present invention gives the transplanting of Akkermansia Muciniphila bacterium to depressed mouse model, experiment shows, the transplanting of Akkermansia Muciniphila bacterium can promote the move distance of mouse and reduce the dead time of tail-suspention test and forced swim test, the significant depressive state for alleviating mouse, show good antidepression curative effect, and no side effects.
Description
Technical field
The present invention relates to a kind of probiotics, and in particular to Akkermansia Muciniphila in antidepressant or
New application in health care product, belongs to pharmaceutical technology field.
Background technique
Depression is with the persistently low mental disorder for main clinical characteristics of significant mental state.Its clinic is often accompanied by
Mental state is low, depression of feeling oneself inferior or even conamen or behavior, and most of patients has the tendency that recurrent exerbation.Therefore, depression
It is a kind of disease of high disability rate.According to the World Health Organization (WHO) report, in general population every 100 people just have 15 people by
Arrived the puzzlement of depression.The annual expense for treating depression accounts for the 12.3% of medical total expenditure.And in China, it is estimated to be
20000000-5,000 ten thousand patients with depression, and illness rate increases year by year, and not yet safely and effectively antidepression is biological for existing market
Preparation.
Although the factors such as the morbidity of depression and heredity, neuroendocrine, nerve immunity, body fluid are closely related,
The exact cause of disease is not known.A large number of studies show that, intestinal flora plays important during depression in recent years
Role.Intestinal flora affects the function and behavior of brain by " intestines-brain axis ".Clinical research discovery, patients with depression excrement
Middle actinomyces, lactobacillus, streptococcus, the bacteriums such as cercaria clostridium significantly increase and bacteroid, sour coccus, the bacteriums such as Veillonella
It significantly reduces, animal experiment study shows to transplant in the excrement of depressive patient to germfree mouse, and behavior depression is presented in mouse.
Akkermansiamuciniphila is a kind of 2004 identified strains come out, is universal in human gut
Existing fungal component, about accounting 3-5%.Akkermansiamuciniphila has been found and fat, type-II diabetes, solitarily
The chronic diseases such as disease are closely related.However it yet there are no its report in prevention and treatment depression.
Summary of the invention
Goal of the invention: the present invention passes through clinical detection on the basis of Akkermansiamuciniphila exercise use
Its clinical efficacy is screened in data analysis and zoopery, develops its newly answering in the drug or health care product of preparation prevention and treatment depression
With.
Technical solution: in order to achieve the goal above, the technical scheme adopted by the invention is as follows:
Akkermansia Muciniphila bacterium answering in the drug or health care product that preparation prevents and treats depression
With.
Akkermansia Muciniphila bacterium prevents and treats drug or the guarantor that intestines problem merges depression in preparation
Application in strong product.Preferably, the intestines problem includes enteritis, intestinal canal tumour.
Akkermansia Muciniphila bacterium prevents and treats drug or the health care of Patients with Diabetes Accompanied by Depression in preparation
Application in product.
Akkermansia Muciniphila bacterium prevents and treats drug or the health care of Patients with Diabetes Accompanied by Depression in preparation
Application in product.
Akkermansia Muciniphila bacterium prevents and treats the fat drug or health care product for merging depression in preparation
In application.
Akkermansia Muciniphila bacterium prevents and treats the drug or health care product that epilepsy merges depression in preparation
In application.
It is a kind of with prevention and treatment depression biological agent, it include Akkermansia Muciniphila bacterium or
Akkermansia Muciniphila fungus extract.
Preferably, above-described application, the Akkermansia Muciniphila bacterium bag is included
Bacterium after Akkermansia Muciniphila viable bacteria or pasteurization.
The utility model has the advantages that compared to the prior art, the present invention has the following advantages:
(1) present invention is screened on clinical detection data analysis foundation by a large amount of zoopery, is furtherd investigate, is mentioned
For new application of the Akkermansia Muciniphila in antidepressant.The present invention is knocked out using flora and caprophyl transplanting
Technology, the experimental results showed that, Akkermansia Muciniphila transplanting can promote the move distance of mouse and reduce outstanding tail
The dead time of experiment and forced swim test, the significant depressive state for alleviating mouse prompt Akkermansia
Muciniphila has good antidepression curative effect, clinically can be used for preparing the drug for the treatment of depression.
(2) the experimental results showed that Akkermansia Muciniphila, curative effect is reliable, use is safe, has no toxic side effect,
It can be used for preparing the drug or health food of prevention and treatment depression.
(3) it is a discovery of the invention that Akkermansia Muciniphila viable bacteria or pass through the dead bacterium of pasteurization, for metabolism
Disease shows preferably effective and safe.The present invention has found by comparison, equally safe for depressive patient, and
Viable bacteria and dead bacterium are equally effective.
Detailed description of the invention
Fig. 1 is that chronic restricted stress causes mouse depression sample state to flora and Akkermansia Muciniphila phase
To the influence diagram of abundance.
Fig. 2 is spacious field experimental result picture.(normal group is compared, P < 0.05 *;Compared with depressed group,#P<0.05)
Fig. 3 be tail-suspention test result figure (compared with normal group, P < 0.05 *;Compared with depressed group,#P<0.05)。
Fig. 4 be forced swim test result figure (compared with normal group, P < 0.05 *;Compared with depressed group,#P<0.05)。
Specific embodiment
According to following embodiments, the present invention may be better understood.However, as it will be easily appreciated by one skilled in the art that real
It applies specific material proportion, process conditions and its result described in example and is merely to illustrate the present invention, without that should will not limit
The present invention described in detail in claims processed.
Embodiment 1
1, the preparation method of Akkermansia Muciniphila bacterium solution:
The Akkermansia Muciniphila bacterium solution for taking 1ml, is added in the brain heart oxoid meat soup of 10ml, in 37 DEG C
After cultivating 72h under anaerobic environment, by bacterium solution centrifugation (6000rpm) 20 minutes, supernatant is separated, with sterile PBS solution by bacterium solution
Allotment obtains Akkermansia Muciniphila bacterium solution (abbreviation AKK bacterium solution) to OD600=1.
2, clinical fecal sample preparation method:
Each 5 parts of healthy and depressed volunteer's excrement collected are chosen, sample mixing processing is carried out for every group of fecal sample, it will
The excrement of sample mixing processing is dissolved in sterile PBS, and by bacterium solution centrifugation (1000rpm) 10 minutes, it is spare to take out supernatant.
3, intestinal flora knocks out modeling
6-8 weeks C57BL/6 male mice is taken routinely to drink broad-spectrum antibiotic daily, it is for 4 weeks.Broad-spectrum antibiotic includes ammonia
Benzyl XiLin (Ampicillin, 1g/l), metronidazole (Metronidazole, 1g/l), neomycin (Neomycin, 1g/l) or ten thousand
Ancient mycin (Vancomycin, 500mg/l).
4, caprophyl is transplanted
After intestinal flora knocks out modeling, by C57 mouse 30,3 groups is randomly divided into, every group 10, is positive respectively
Normal group, depressed group, AKK treatment group, normal group mouse give Healthy People caprophyl 0.1ml and sterile PBS solution 0.1ml daily;Suppression
Strongly fragrant group of mouse gives depressive patient caprophyl 0.1ml and sterile PBS solution 0.1ml daily;AKK treatment group mouse gives depression daily
Patient's caprophyl 0.1ml and AKK bacterium solution 0.1ml.Behaviouristics detection, behaviouristics inspection are carried out to mouse after caprophyl transplants modeling
Survey includes: spacious field experiment, tail-suspention test and forced swim test.
5, chronic restricted stress model is constructed
It constructs chronic restricted stress depression mouse model (Chronic restraint stress, CRS).CRS is current
More generally acknowledged depression model both at home and abroad, specific modeling method are as follows: take male C57BL/6 mouse, the age was at 6-8 weeks.It adapts to
Property feed 1 week after, mouse is seated in 0.5mm diameter daily, 3h in the centrifuge tube of 50ML continues 30 days.It was recorded at the 30th day
Performance testing result.During CRS modeling, remaining each group limits mouse feeding and water supply;Experiment terminates to carry out all mouse
Behaviouristics detection, behaviouristics detection include: spacious field experiment, tail-suspention test and forced swim test.
6, mice behavior detects
(1) spacious field is tested
Mouse is put into black wooden case to the corner of the cell (45cm ╳ 45cm ╳ 45cm), after adapting to 1 minute, with video meter
All spontaneous activities in 5 minutes after calculation machine tracking system record.Using total move distance as the index of motor activity.
(2) tail-suspention test
Adhesive tape is placed on away from about 2 centimeters of tail end, and mouse is suspended at the 50cm of ground.Every mouse is placed
6min, and the mouse dead time is recorded in seconds in last 4min.Dead time is defined as not escaping the row of guiding
For.When mouse does not have any body kinematics, they be considered as it is static, passively and completely fixedly hang over together.
(3) forced swim test
Mouse is placed in 30cm ╳ 45cm water tank, and water temperature is maintained at 27 DEG C.Every mouse places 6min, and last
4min records the mouse dead time in seconds.Dead time refers to that animal is floated in water without struggling, and need to only do
Movement is just able to maintain the time that head is higher than the water surface.Then, experiment mice is placed under warming lamp and dries.
7, Akkermansia Muciniphila flora sample extraction
According to the explanation of manufacturer, applicationExtracting tool (Omega Bio-tek, Norcross, GA,
U.S.), clinical fecal sample and mouse cecal content sample are subjected to DNA extraction.Light is divided using Nano-Drop 1000
Degree meter (Thermo Scientific Inc., Wilmington, DE, USA) determines DNA concentration.Pass through F338 (5 '-
ACTCCTACGGGAGGCAGCA-3 ') and R806 (5 '-GGACTACHVGGGTWTCTAAT-3 ') primer pair bacterium 16s rRNA base
Because V3-V4 Variable Area is expanded.3 repetitions of each sample, by the polymerase chain reaction (Polymerase of same sample
Chain Reaction, PCR) product mixing after with 2% agarose gel electrophoresis detect, use AxyPrepDNA gel recycling examination
Agent box (AXYGEN company) gel extraction PCR product, Tris_HCl elution;The detection of 2% agarose electrophoresis.Amplicon is from 2% fine jade
It is extracted in lipolysaccharide glue.All PCR products pass through AxyPrep DNA gel extraction equipment (Axygen Biosciences company)
It is purified.Referring to the preliminary quantitative result of electrophoresis, by PCR product QuantiFluorTM- ST blue-fluorescence quantitative system
(Promega company) detect quantitatively, later according to the sequencing amount requirement of each sample, carries out the mixing of corresponding proportion.?
Equal molecules, 250bp both-end sequencing analysis are carried out to the PCR product of extraction on Illumina MiSeq platform.Original pyrophosphoric acid is surveyed
Sequence sequence uploads to the database SRA (Sequence Read Archive) of NCBI data center.
7, Akkermansia Muciniphila flora is analyzed
The sequence of high quality merges overlapping and generates fastq file.It will be exported by QIIME (version 1.9.1) software
Fastq file carry out multipath decoding and Quality Control filtering.Quality Control filter criteria are as follows: (1) filter 20 or less read Quality of Tail value
Base, the window of 50bp is set, if the average mass values in window be lower than 20, rear end base, mistake are clipped since window
50bp read below after filtering medium control;(2) according to the overlap relationship between PE reads, pairs of reads is spliced
(merge) at a sequence, minimum overlap length is 10bp;(3) splice the maximum mispairing that the area overlap of sequence allows
Ratio is 0.2, and screening does not meet sequence;(4) sample is distinguished according to the barcode at sequence head and the tail both ends and primer, and adjusts sequence
Column direction, the mispairing number that barcode allows are 0, and maximum primer mispairing number is 2;Chimera sequence is gone using UCHIME software
It removes, and is gathered the section of 97% similitude by UPARSE (version 7.1http: //drive5.com/uparse/) software
Symphysis is at OUTs.Pass through RDA classifier (http://rdp.cme.msu.edu/) and and silva (SSU115) 16S rRNA number
It is compared according to library and classification is compared in each OUT (door level and category are horizontal).
8, it statisticallys analyze
Data useIt indicates, is tested using one-way analysis of variance (ANOVA), p < 0.05 is that difference has system
Meter learns meaning.
9, experimental result
(1) the above flora analysis method is pressed, the Akkermansia of healthy population and depressive patient is tested and analyzed
Muciniphila relative abundance.As shown in table 1, depressive patient Akkermansia Muciniphila is equal compared with healthy population abundance
Value significantly reduces, and prompting Akkermansia Muciniphila to reduce is pathogenic one of the factor of depression in patients.
Influence of 1. depression of table to Akkermansia Muciniphila relative abundance in flora
* p < 0.05 is compared with healthy population
(2) as shown in Table 2 and Fig. 1, chronic restricted stress experiment duplication mouse depressive state, bacteria detection discovery
Akkermansia Muciniphila bacterium abundance significantly lowers, and further verifying Akkermansia Muciniphila reduction can
It can be one of pathogenic principal element of depression in patients.
2 chronic restricted stress of table causes mouse depression sample state opposite to flora and Akkermansia Muciniphila
The influence of abundance
* p < 0.05 is compared with blank group
(3) depressive patient caprophyl transplantation experiments are found, depressive state occurs in transplanting mouse, and intestinal flora and depression is prompted to close
System closely, but after taking orally above-mentioned AKK bacterium, can effectively improve the depressive state of mouse.
As shown in Fig. 2, spacious field experiment in, compared with normal group, depression group mouse mobile total distance significantly reduce (P <
0.05) after, AKK bacterium is intervened by oral administration, the mobile total distance of mouse significantly increases (P < 0.05).
As shown in figure 3, in tail-suspention test, compared with normal group, the dead time of depression group mouse significantly increase (P <
0.05) after above-mentioned AKK bacterium is intervened, but by oral administration, the dead time of mouse significantly reduces (P < 0.05).
As shown in figure 4, compared with normal group, the dead time of depression group mouse is significantly increased in forced swim test
(P < 0.05), after AKK bacterium is intervened by oral administration, the dead time of mouse significantly reduces (P < 0.05).
(4) safety detection prompts strain transplanting safety before and after mouse transplanting Akkermansia Muciniphila bacterium
Effectively.
The present invention transplants front and back mouse blood routine, liver function, renal function, spleen to Akkermansia Muciniphila bacterium
Popular name for reason, hepatic pathology are detected, and do not find toxic side effect.
The experimental results showed that, the depressive patient excrement that AKK bacterium lacks is transplanted and knocks out mouse, mouse to intestinal flora as above-mentioned
In depressed sample state.By oral administration after the treatment of AKK bacterium, the depressive state of mouse is significantly improved.The above result shows that the present invention provides
AKK bacterium have effects that well it is antidepressant.
Dead bacterium of the present invention by Akkermansia Muciniphila after pasteurization, is equally cooked the above experiment, experiment
The result shows that all having antidepressant effect.Therefore, the Akkermansia Muciniphila bacterium or pasteurization that the present invention screens
Dead bacterium afterwards acts not only as food, uses in health care product, can be used for preparing drug, existing therapeutic effect also has pre-
Anti- effect.
The present invention is studies have shown that Akkermansia Muciniphila bacterium is not only effective to patients with depression, but also to one
As crowd's depressive state it is effective.
The present invention is according to the above method studies have shown that the extract of Akkermansia Muciniphila bacterium presses down prevention and treatment
Strongly fragrant disease is equally effective.
The technical concepts and features of embodiment of above only to illustrate the invention, its object is to allow be familiar with technique
People understands the content of present invention and is implemented, and it is not intended to limit the scope of the present invention, and all spirit according to the present invention is real
The equivalent change or modification that matter is done, should be covered by the scope of protection of the present invention.
Claims (10)
- Application of the 1.Akkermansia Muciniphila bacterium in the drug or health care product that preparation prevents and treats depression.
- 2.Akkermansia Muciniphila bacterium prevents and treats drug or the health care that intestines problem merges depression in preparation Application in product.
- 3.AkkermansiaMuciniphila bacterium prevents and treats the drug or health care product of Patients with Diabetes Accompanied by Depression in preparation In application.
- 4.AkkermansiaMuciniphila bacterium prevents and treats the drug or health care product of Patients with Diabetes Accompanied by Depression in preparation In application.
- 5.AkkermansiaMuciniphila bacterium prevents and treats in the fat drug or health care product for merging depression in preparation Application.
- 6.AkkermansiaMuciniphila bacterium is in the drug or health care product that preparation prevents and treats that epilepsy merges depression Application.
- 7.AkkermansiaMuciniphila bacterium answering in the drug or health care product that preparation prevents and treats post-natal depression With.
- 8. Akkermansia Muciniphila bacterium according to claim 2 prevents and treats intestines problem in preparation and closes And depression drug or the application in health care product, which is characterized in that the intestines problem includes enteritis, intestinal canal tumour.
- 9. application according to any one of claims 1 to 8, which is characterized in that the Akkermansia Muciniphila bacterium bag includes the bacterium after Akkermansia Muciniphila viable bacteria or pasteurization.
- 10. a kind of biological agent with prevention and treatment depression, which is characterized in that it includes Akkermansia Muciniphila Bacterium or extract based on Akkermansia Muciniphila bacterium.
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CN201911126003.9A CN110693917B (en) | 2019-07-16 | 2019-11-18 | Application of Akkermansia Muciniphila in preparation of antidepressant or health-care product |
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CN111938158A (en) * | 2020-08-18 | 2020-11-17 | 王意 | Composition for preventing reduction of abundance of Akkermansia muciniphila bacteria in intestinal tract |
WO2021008149A1 (en) * | 2019-07-16 | 2021-01-21 | 江苏省中医院 | Application of akkermansia muciniphila in preparation of antidepressant drug or health care product |
CN113322202A (en) * | 2021-05-31 | 2021-08-31 | 君维安(武汉)生命科技有限公司 | Ackermanella, culture method and application thereof |
WO2023123613A1 (en) * | 2021-12-30 | 2023-07-06 | 浙江大学 | Bipolar affective disorder biomarker and use thereof |
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KR101740893B1 (en) * | 2014-05-20 | 2017-06-13 | 주식회사 엠디헬스케어 | COMPOSITION COMPRISING EXTRACELLULAR VESICLES DERIVED FROM Akkermansia muciniphila AS AN ACTIVE INGREDIENT FOR TREATING OR PREVENTING METABOLIC DISEASE |
EA201700507A1 (en) * | 2015-05-06 | 2018-05-31 | Университе Католик Де Лувен | COMPOSITION, CELLS, METHODS OF OBTAINING POLYPEPTIDE, APPLICATION OF POLYPEPTIDE AND CELLS, METHOD OF TREATMENT |
CN105030841A (en) * | 2015-08-24 | 2015-11-11 | 上海交通大学医学院附属瑞金医院 | Application of Akkermansia muciniphila BAA-835 strain |
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AU2017370681A1 (en) * | 2016-12-06 | 2019-06-27 | Pendulum Therapeutics, Inc. | Methods and compositions relating to isolated and purified microbes |
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WO2021008149A1 (en) * | 2019-07-16 | 2021-01-21 | 江苏省中医院 | Application of akkermansia muciniphila in preparation of antidepressant drug or health care product |
CN111938158A (en) * | 2020-08-18 | 2020-11-17 | 王意 | Composition for preventing reduction of abundance of Akkermansia muciniphila bacteria in intestinal tract |
CN113322202A (en) * | 2021-05-31 | 2021-08-31 | 君维安(武汉)生命科技有限公司 | Ackermanella, culture method and application thereof |
CN113322202B (en) * | 2021-05-31 | 2022-03-01 | 君维安(武汉)生命科技有限公司 | Ackermanella, culture method and application thereof |
WO2023123613A1 (en) * | 2021-12-30 | 2023-07-06 | 浙江大学 | Bipolar affective disorder biomarker and use thereof |
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