CN109481473A - Application of the bacteroides fragilis extract in the drug or food of preparation prevention and treatment irritable bowel syndrome - Google Patents
Application of the bacteroides fragilis extract in the drug or food of preparation prevention and treatment irritable bowel syndrome Download PDFInfo
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- CN109481473A CN109481473A CN201710812676.4A CN201710812676A CN109481473A CN 109481473 A CN109481473 A CN 109481473A CN 201710812676 A CN201710812676 A CN 201710812676A CN 109481473 A CN109481473 A CN 109481473A
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- bacteroides fragilis
- capsular polysaccharide
- extract
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- drug
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Classifications
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- A23C19/09—Other cheese preparations; Mixtures of cheese with other foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
- A23G9/00—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor
- A23G9/32—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor characterised by the composition containing organic or inorganic compounds
- A23G9/36—Frozen sweets, e.g. ice confectionery, ice-cream; Mixtures therefor characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/163—Sugars; Polysaccharides
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- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
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- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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Abstract
The present invention relates to application of the bacteroides fragilis extract in the drug or food of preparation prevention and treatment irritable bowel syndrome, contain bacteroides fragilis capsular polysaccharide A in the bacteroides fragilis extract.The bacteroides fragilis capsular polysaccharide A that molecular weight is 5-70KD has unexpectedly been prepared in the present invention, and it is surprised to find that molecular weight is that the capsular polysaccharide A of 5~70KD has the function of preferably preventing and treating irritable bowel syndrome, effect is much better than the capsular polysaccharide A that the molecular weight extracted from bacteroides fragilis NCTC 9343 is 110KD.
Description
Technical field
The present invention relates to the applied technical fields of bacteroides fragilis, are making more particularly to a kind of bacteroides fragilis extract
The drug of standby prevention and treatment irritable bowel syndrome or the application in food.
Background technique
Irritable bowel syndrome (IBS) is clinically one of the most common type function of intestinal canal disorder disease, public in recent years
It is considered a kind of psychosomatic disease with special pathology, physiological foundation, is one group and shows as abdominal pain, abdominal distension, constipation, diarrhea, or
Constipation replaces with diarrhea, lacks morphology or biochemical abnormal syndrome.IBS global incidence is very high, and various regions disease incidence exists
Between 10%~15%.In western countries, IBS accounts for the 12% of family health care doctor's Number of Outpatients, account for gastrointestinal disease outpatient service 20%~
50%.The ratio that IBS symptom occurs in China is identical as foreign countries, and patient is based on young people and a middle-aged person, and the age is 20~50
Between year, First episode person is rarely found within 50 years old or more.Women is more than male, and male to female ratio is 1:5~1:2, has Familial aggregation to incline
To.Studies have shown that the medical resource spent in terms of IBS is quite huge, the quality of life of different degrees of influence patient.
The cause of disease and pathogenesis of IBS is now still unclear, may be with diet, enteric infection and psychiatric etc. because being known as
It closes, is the result of multifactor functioning.Its clinical symptoms multiplicity also with other symptoms, therefore treats ratio in addition to abdominal symptoms
It is more difficult, often need drug combination.There is also the psychiatrics problems such as depression and anxiety for some patientss, it is often necessary to psychotherapy.Cause
This, should be according to the severity of patient symptom, symptom type and seizure frequency when treating IBS, it then follows the treatment of individuation is former
Then, comprehensive remedy measures are taken.The selection for the treatment of method and drug should vary with each individual, comprising: base therapy, psychotherapy
And drug therapy.Currently, treatment IBS drug mainly include the following types:
One, the drug for adjusting function of intestinal canal, including antidiarrheic, antispasmodic, dynamics-promoting medicine and the medicine for adjusting visceral sensitivity
Object.
Antidiarrheic is usually used in the treatment of IBS patient's diarrhea.Common drug has Loperamide, diphenoxylate and dioctahedron to cover
De- stone.Loperamide (imodium) acts on intestinal wall opioid peptides receptor, prevents acetylcholine and prostaglandin release, inhibits intestines compacted
It is dynamic, extend the residence time of intestinal contents, enhance the absorption of moisture and ion in enteron aisle, and then alleviate diarrhea, abdominal pain etc..Ground is fragrant
Promise ester (Diphenoxylate) acts on intestinal smooth, increases intestinal segment and shrinks, extends intestinal contents and intestinal mucosa time of contact.
Moisture and pathogenic bacteria can be absorbed in dioctahedral smectite (dioctahedral smectite), improves alimentary canal mucous membrane protection, promotes Mucous rehabilitation,
It can also adjust and restore Colon Movement function simultaneously, reduce the sensibility of colon.
Antispasmodic is usually used in the treatment of IBS patient's abdominal pain, abdominal distension.3 classes, i.e. cholinolytic can be divided by its main mechanism
Energy drug, smooth muscle relaxant and calcium channel blocker, many drugs have multiple pharmacological action.
Anticholinergics medicine includes atropine, anisodamine, belladonna etc..Because it has atropine-like adverse reaction, limit
Its clinical application.The enteron aisle M3 selectivity nachr antagonist developed in recent years can inhibit the movement of postprandial enteron aisle, be expected to use
In the treatment of IBS.
Smooth muscle relaxant includes opium poppy bases drug (papaverine, dicyclomine, mebeverine) and multiple ion channels tune
It saves agent (Trimebutine).Opium poppy bases drug can be done directly on smooth muscle cell and certain enteron aisle excitatory neurons, inhibit
The release of excitatory neurotransmitter.Trimebutine generates depolarising, to improve smooth by inhibiting cell membrane potassium-channel
The excitability of myocyte；On the other hand by blocking calcium channel, flow of calcium ions is inhibited to make to inhibit cellular contraction
Gastrointestinal smooth muscular relaxation.In addition, Trimebutine also has dual regulation to smooth muscle nurve receptor: in harmonic motion state
Under act on adrenergic receptor, inhibit the release of norepinephrine, increase the movement rhythm and pace of moving things；When moving hyperfunction, effect
In cholinergic recepter and opiate receptor, inhibit acetylcholine release, to inhibit smooth muscle movement.
Calcium ion antagonist is selectively acting in colon calcium channel, blocks Ca2+ influx, plays the pine to smooth muscle
Relaxation effect, inhibits gastrocolic reflex, has adjustment effect to constipation and diarrhea, also there is certain curative effect to abdominal pain, such as dimension bromine
Amine, Spasmomen.
Dynamics-promoting medicine is usually used in the treatment of IBS tients with constipation.Serotonin (5-HT) is that gastrointestinal tract and the important of maincenter are passed
Matter, with extensive biological effect, 95% 5-HT is distributed in gastrointestinal tract in human body, and there are many 5- for distribution on intestinal mucosa
HT receptor and 5-HT transporter.In recent years, important function of the 5-HT4 receptor in gastroenteritic power and visceroceptory sensation are adjusted is by weight
Depending on it has the function of promoting gastroenteritic power, reduce gastrointestinal allergy and promoting chloride ion and hydrone secretion, thus becomes and control
Treat the novel targets of Functional Gastrointestinal Disease.5-HT4 receptor stimulating agent Cisapride can promote cholinergic nerve after Myenteric plexus section
Acetylcholine is discharged, the small intestinal transit with full gastrointestinal tract.But it because the medicine may cause QT interval prolongation, therefore should be used with caution.It replaces
Additive color sieve also known as Zelnorm are new 5-HT4 receptor stimulating agents, and partial selective acts on gastrointestinal tract 5-HT4 receptor subtype, right
IBS patient based on constipation has the function of accelerating small intestine and Colonic transit.Recent research also demonstrates that tegaserod is to internal organ
Sensibility has adjustment effect, and does not have cardiovascular adverse effects, is a kind of safely and effectively new drug.
The drug for adjusting visceral sensitivity includes 5-HT3 receptor antagonist and 5-HT4 receptor stimulating agent.Visceral sensitivity increases
Height is considered as one of IBS pathology, physiological important feature.Some researches show that there are visceroceptory sensations is different by, 61% IBS patient
Often, improving visceroceptory sensation is approach interesting in IBS treatment, and clinical research and animal experiment study show some drugs
There is adjustment effect to the visceral sensitivity increased.
5-HT3 receptor is present in enteric nervous member, promoted by being released to local 5-HT the movement of enteron aisle, secretion and
Visceral pain is caused to stimulate.To IBS patient, the especially decline of visceral pain threshold with abdominal pain person, 5-HT3 receptor antagonist can be tried out
Agent.As A Luosiqiong mainly inhibits the 5-HT3 receptor of non-selective ion channel in enteric nervous system, and inhibit visceral reflex,
Recently it is mainly used for the severe diarrhea type women IBS patient invalid through traditional treatment.There is also Ondansetrons, Ge Nixi ketone
Deng.
5-HT4 receptor stimulating agent tegaserod has motivator and reduces the double action of visceroceptory sensation sensibility, is applicable in
In the constipation type IBS patient with obvious colic symptoms.Human research's report, tegaserod can reduce the injury of rectum balloon expandable
The reaction of stimulation improves the visceroceptory sensation of human body.
Two, to constipation type patient in addition to 5-HT4 receptor stimulating agent, laxative also laxative: can be selected.It is now recognized that Ying Shen
With or as far as possible avoid using irritant purgative, and advocate and apply dilatancy purgatives.Dilatancy purgatives such as willow leaf Asiatic plantain etc. can increase
Add the capacity and moisture of excrement, promotes defecation.Permeability laxative polyethylene glycol is increased excrement and is contained by Hydrogenbond hydrone
Water and softer stool promote defecation.Because it is not absorbed, toxicity is minimum, suitable for the patient being hard and dry.Lactulose is being tied
Enteral forms lactic acid and acetic acid through bacterial decomposition, adjusts environment in enteric cavity, promotes intestinal motility, which is more suitable for the elderly.
Three, improve the drug of maincenter emotion: IBS patient is often accompanied by Behavioral disturbances, should include to the drug therapy of IBS
Antidepression, anti-keratin monoclonal antibody.Antidepressants have tricyclic antidepressant, as amitriptyline and selectivity 5-HT reuptake inhibit
Agent, such as Prozac and Paxil.Wherein, Fluoxetine in Treatment IBS plays the role of following 4 aspects: the improvement of mental psychology
It can induce the alleviation of gastrointestinal symptoms；Work of the 5-HT neurotransmitter activity and its receptor of the adjusting internal organ stomach and intestine pain sensation to gastrointestinal tract dynamia
With；Potential maincenter analgesic effect；Prevent mental handicape and it is physically different between vicious circle.To with severe anxiety essence
The IBS patient of refreshing symptom, in the treatment it is contemplated that cooperation anxiolytic drugs treatment.
Four, Chinese medicine: domestic some clinical observations confirm, the abdominal pain of IBS patient, diarrhea and just can be effectively relieved in some Chinese medicines
Secret symptom.
Five, probiotics: in recent years, the relationship of enteric flora disturbance and IBS are taken seriously.Some researches show that one
Divide the morbidity of patient related with intestinal bacilli illness, the symptom of patient can be improved to some extent to patient's probiotic supplemented.Its
Mechanism of action is not still fully aware of, it is considered that has biochemical to inhibit or facilitation, nutrient competition, immune clearance and glutinous
Attached Receptor Competition etc..But the type of common probiotics preparation and few, it mainly include that Birid Triple Viable, bifidoquater are living
Bacterium etc..
Currently, still lacking very effective treatment means for IBS, IBS cannot still be cured completely.It is necessary to study novel
The active drug that can treat IBS.
Bacteroides fragilis (Bacteroides fragilis) is the member of Bacteroides in Gram-negative anaerobic bacteria,
Belong to Bacteroidetes, is totally different from Bifidobacterium, lactic acid bacteria of Firmicutes etc..Bacteroides has 25 strains, is only from
The mankind's has 10 strains, and be only from animal has 10 strains, has 5 strains from humans and animals.Bacteroides fragilis is
A kind of obligate anaerobes, according to the difference of culture medium and the differences of growth phase, pleomorphism is presented in thalli morphology, under general condition
Thallus be rod-shaped, both ends blunt circle, color depth, Neutral colour is shallow and uneven, has pod membrane, without brood cell, unpowered, some have vacuole,
Thallus is different in size.According to can synthesize, secrete bacteroides fragilis enterotoxin (BFT) can be classified as produce enterotoxin type fragility intend
Bacillus (Enterotoxigenic Bacteroides fragilis, ETBF) and non-production enterotoxin type bacteroides fragilis
(NontoxigenicBacteroides fragilis, NTBF).Bacteroides fragilis is as people and animal intestinal tract normal flora
A part is primarily present in colon.In addition, respiratory tract, gastrointestinal tract and urogenital mucosa can also be colonized growth.Fragility is quasi-
Bacillus is as a kind of conditioned pathogen, when host mucosal is damaged, can invade submucosa, cause to infect, can also be through blood stream
It is dynamic, cause the other organs of body, such as enteron aisle, abdominal cavity, liver, lung, brain tissue, soft tissue, marrow pyogenic infection and occur together
Abscess.
Summary of the invention
Based on this, the present invention provides a kind of new opplications of bacteroides fragilis (bacteroidesfragilis) extract.
Specific technical solution is as follows:
Application of the bacteroides fragilis extract in the drug or food of preparation prevention and treatment irritable bowel syndrome, it is described fragile quasi-
Contain bacteroides fragilis capsular polysaccharide A in bacillus extract.
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 5~75KD.
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 15KD~65KD；
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 25KD~55KD.
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 35KD~45KD.
In wherein some embodiments, the content of bacteroides fragilis capsular polysaccharide A is in the bacteroides fragilis extract
60-75wt%.
In wherein some embodiments, the bacteroides fragilis is that the fragility that deposit number is CGMCC No.10685 intends bar
Bacterium ZY-312.
In wherein some embodiments, the preparation method of the bacteroides fragilis extract the following steps are included:
(1) by the bacteroides fragilis bacterium solution centrifugation after fermented and cultured, the first sediment is collected, takes first precipitating
65-72 DEG C of water is added in object, and phenol solution is added after dissolution, keeps 65-72 DEG C of stirring 25-35min, and centrifugation collects first
Supernatant；
(2) the first supernatant collected in step (1) ether is extracted into removal phenol, then removes remaining ether, received
Collect aqueous phase solution；
(3) the final concentration of 75-85v/ of dehydrated alcohol to ethyl alcohol is added in the aqueous phase solution being collected into step (2)
The second sediment is collected in v%, alcohol precipitation, centrifugation,
(4) second sediment is taken, water is added to be configured to suspension, then adjusting pH is 6.5-7.5, centrifugation collects second
Supernatant, desalination of dialysing, is freeze-dried to get the bacteroides fragilis extract.
In wherein some embodiments, the water that is added in first sediment in step (1), the phenol solution with
And the proportion of first sediment is 3-5mL:3-5mL:1g；The mass concentration of the phenol solution is 70-80%.
In wherein some embodiments, step (3) alcohol precipitation be 0-8 DEG C at a temperature of alcohol precipitation 8-16 hours.
In wherein some embodiments, step (4) includes: to take second sediment, adds water to be configured to mass concentration and is
The suspension of 8-12% adds the glacial acetic acid aqueous solution that mass concentration is 8-12%, is heated to boiling, is stirred to react 1.5-2.5
Hour, adjusting pH is 6.5-7.5, and the second supernatant is collected in centrifugation, and desalination of dialysing is freeze-dried to get the bacteroides fragilis
Extract.
In wherein some embodiments, the preparation method of the bacteroides fragilis extract further includes the steps that degradation: will
Bacteroides fragilis extract obtained in step (4) is degraded by the method for ultrasound, the condition of the ultrasound are as follows: 180-
210kHz, 15-25 DEG C.
In wherein some embodiments, the dosage form of the drug includes pill, tablet, granule, capsule, oral solution or pipe
Raise preparation.The drug includes people's medication or animal-use drug, can be used for human or animal.
The bacteroides fragilis extract can individually carry out preventative or therapeutic, can also with it is other prebiotic
Bacterium and/or prebiotic material are administered together.When combination medicine-feeding, can with single formulation or separated preparation, while or it is different when, make
It is administered with identical or different administration route.
The food includes milk powder, cheese, curdled milk, yoghourt, ice cream or fermented cereal food.The food can be with
It is animal foodstuff, such as feed etc..The food can also be baby food or pet food.
The present invention also provides a kind of bacteroides fragilis extract for preventing and treating irritable bowel syndrome or drugs or food.
Specific technical solution is as follows:
A kind of bacteroides fragilis extract or drug or food, the drug or food for preventing and treating irritable bowel syndrome
In contain bacteroides fragilis extract, bacteroides fragilis capsular polysaccharide A is contained in the bacteroides fragilis extract.
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 5~75KD.
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 15KD~65KD；
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 25KD~55KD.
In wherein some embodiments, the molecular weight of the bacteroides fragilis capsular polysaccharide A is 35KD~45KD.
In wherein some embodiments, the content of bacteroides fragilis capsular polysaccharide A is in the bacteroides fragilis extract
60-75wt%.
In wherein some embodiments, the bacteroides fragilis is that the fragility that deposit number is CGMCC No.10685 intends bar
Bacterium ZY-312.
In wherein some embodiments, the preparation method of the bacteroides fragilis extract the following steps are included:
(1) by the bacteroides fragilis bacterium solution centrifugation after fermented and cultured, the first sediment is collected, takes first precipitating
65-72 DEG C of water is added in object, and phenol solution is added after dissolution, keeps 65-72 DEG C of stirring 25-35min, and centrifugation collects first
Supernatant；
(2) the first supernatant collected in step (1) ether is extracted into removal phenol, then removes remaining ether, received
Collect aqueous phase solution；
(3) the final concentration of 75-85v/ of dehydrated alcohol to ethyl alcohol is added in the aqueous phase solution being collected into step (2)
The second sediment is collected in v%, alcohol precipitation, centrifugation；
(4) second sediment is taken, water is added to be configured to suspension, then adjusting pH is 6.5-7.5, centrifugation collects second
Supernatant, desalination of dialysing, is freeze-dried to get the bacteroides fragilis extract.
In wherein some embodiments, the water that is added in first sediment in step (1), the phenol solution with
And the proportion of first sediment is 3-5mL:3-5mL:1g；The mass concentration of the phenol solution is 70-80%.
In wherein some embodiments, step (3) alcohol precipitation be 0-8 DEG C at a temperature of alcohol precipitation 8-16 hours.
In wherein some embodiments, step (4) includes: to take second sediment, adds water to be configured to mass concentration and is
The suspension of 8-12% adds the glacial acetic acid aqueous solution that mass concentration is 8-12%, is heated to boiling, is stirred to react 1.5-2.5
Hour, adjusting pH is 6.5-7.5, and the second supernatant is collected in centrifugation, and desalination of dialysing is freeze-dried to get the bacteroides fragilis
Extract.
In wherein some embodiments, the preparation method of the bacteroides fragilis extract further includes the steps that degradation: will
Bacteroides fragilis extract obtained in step (4) is degraded by the method for ultrasound, the condition of the ultrasound are as follows: 180-
210kHz, 15-25 DEG C.
In wherein some embodiments, the dosage form of the drug includes pill, tablet, granule, capsule, oral solution or pipe
Raise preparation.The drug includes people's medication or animal-use drug, can be used for human or animal.
It may include one of following pharmaceutically acceptable auxiliary material or a variety of: diluent, excipient, bonding in the drug
Agent, lubricant, suspending agent, coating agent and solubilizer etc..The example of pharmaceutically acceptable auxiliary material includes: water, salting liquid, alcohol, silicon
Ketone, wax, vaseline, vegetable oil, polyethylene glycol, propylene glycol, liposome, carbohydrate, gelatin, lactose, amylose, magnesium stearate,
Talcum powder, surfactant, silicic acid, viscous paraffin, aromatic oil, mono fatty acid glyceride and difatty acid glyceride, petrochemical industry
(petroethral) aliphatic ester, hydroxymethyl cellulose, polyvinylpyrrolidone etc..
The drug can be administered by following any one or more of mode: with micropump or nasal mist or sucking
Type aerosol etc. carries out inhalation, is administered in the form of suppository or vaginal suppository, with lotion, solution, cream, ointment
Or the form local administration dusted, it is administered by using skin patch, with the tablet of the excipient containing such as starch or lactose
Form or individually or with excipient to be blended in the oral administration of the form in capsule or ovulum, or to contain flavoring agent
Or elixir, solution or the suspended form administration of colorant, or with parenteral injection, such as cavernous body is interior, intravenous, flesh
Interior or subcutaneous administrations.When parenteral injection is administered, the drug is preferably used with sterile aqueous solutions, can be contained
Other materials, such as enough salt or monosaccharide are so that the solution and blood are isotonic.When buccal or sublingual administration, the drug can
It is administered in the form of the tablet or pastille prepared in conventional manner.
The food includes milk powder, cheese, curdled milk, yoghourt, ice cream or fermented cereal food.The food can be with
It is animal foodstuff, such as feed etc..The food can also be baby food or pet food.
Bacteroides fragilis ZY-312 of the invention is preserved in Chinese microorganism strain preservation management on April 2nd, 2015
Committee's common micro-organisms center (CGMCC), deposit number are CGMCC No.10685, and preservation address is Chaoyang District, Beijing City
The institute 3 of North Star West Road 1.
The present inventor accumulates by protracted experience and a large amount of creative experiments researchs, obtains bacteroides fragilis
The preparation method of extract (main component is capsular polysaccharide A), finds that fragility of the invention intends bar by further experiment research
Fungus extract has the function of preventing and treating irritable bowel syndrome, equal to diarrhea-type irritability syndrome and constipation-predominant of irritable bowel syndrome
There is good preventive and therapeutic action, and it is much better than bacteroides fragilis itself to the control efficiency of irritable bowel syndrome.Into one
Step ground, inventor by molecular weight be 70KD bacteroides fragilis capsular polysaccharide A degrade, obtain molecular weight be 5~
The bacteroides fragilis capsular polysaccharide A of 70KD, and it is surprised to find that the capsular polysaccharide A that molecular weight is 5~70KD has preferably
The function of irritable bowel syndrome is prevented and treated, effect, which is much better than to extract from bacteroides fragilis NCTC 9343, to be obtained molecular weight and be
The capsular polysaccharide A of 110KD.Bacteroides fragilis capsular polysaccharide A provided by the invention it is good to the control efficiency of irritable bowel syndrome and
Be free from side effects to body, can individually carry out preventative treatability administration, or with other probiotics and/or prebiotic material
It is administered together.Bacteroides fragilis capsular polysaccharide A provided by the invention has edible and prospect in medicine well, provides for clinic
A kind of non-defective unit of the health care that suitable human body is taken and prevention and treatment irritable bowel syndrome.
Detailed description of the invention
Fig. 1 is the colony characteristics figure of the bacteroides fragilis ZY-312 of embodiment 1；
Fig. 2 is that the bacteroides fragilis ZY-312 of embodiment 1 carries out the micro- sem observation figure after Gram's staining.
Fig. 3 is the 1H spectrum that the capsular polysaccharide A nuclear magnetic resonance chemical analyser of embodiment 1 is analyzed；
Fig. 4 is the 13C spectrum that the capsular polysaccharide A nuclear magnetic resonance chemical analyser of embodiment 1 is analyzed；
Fig. 5 is the COSY spectrum that the capsular polysaccharide A nuclear magnetic resonance chemical analyser of embodiment 1 is analyzed；
Fig. 6 is the hsqc spectrum that the capsular polysaccharide A nuclear magnetic resonance chemical analyser of embodiment 1 is analyzed；
Fig. 7 is the HMBC spectrogram that the capsular polysaccharide A nuclear magnetic resonance chemical analyser of embodiment 1 is analyzed；
Fig. 8 is the chemical structural formula for the bacteroides fragilis capsular polysaccharide A that embodiment 1 is prepared.
Specific embodiment
The present invention is described in further details below by specific embodiment, these embodiments are only used to illustrate this hair
It is bright, it does not limit the scope of the invention.
Bacteroides fragilis used in following embodiment is bacteroides fragilis ZY-312 (bacteroidesfragilis
ZY-312), China Committee for Culture Collection of Microorganisms's common micro-organisms center is preserved on April 2nd, 2015
(CGMCC), deposit number is CGMCC No.10685, and preservation address is Yard 1, BeiChen xi Road, Chaoyang District, Beijing City 3.
The preparation of 1 bacteroides fragilis extract of embodiment
(1) fermented and cultured of bacteroides fragilis
By strain streak inoculation in blood plate, Anaerobic culturel 48h.Observe colony morphology characteristic, dyeing property, size, ball
Rod-shaped and distribution situation etc..
Colony characteristics: after bacteroides fragilis ZY-312 cultivates 48h on blood plate, round dimpling, translucent, white is presented
Color, surface be smooth, not haemolysis, colony diameter between 1-3 mm, referring to Fig. 1.
Form under microscope: bacteroides fragilis ZY-312 carries out gram stain microscopy, is gram-negative bacteria, allusion quotation is presented
Rod-shaped, both ends blunt circle and the dense dye of type, not colored part is shaped like vacuole among thallus, referring to fig. 2.
It chooses single bacterium colony to be inoculated in tryptone meat soup progress fermented and cultured 8 hours (temperature is 37 DEG C), gained bacterium
Liquid centrifugation, revolving speed 3000r/min are centrifuged 15min, remove supernatant, collect sediment.
(2) preparation of bacteroides fragilis extract
1) bacteroides fragilis bacterium mud (sediment that above-mentioned steps (1) obtain) 200g is taken, 68 DEG C of ultrapure water 750mL are added,
After dissolution, adding volume fraction is 75% phenol solution 750mL, is uniformly mixed, and keeps 68 DEG C of stirring extraction 30min,
15000g is centrifuged 20min, takes supernatant liquor.
2) supernatant liquor extracts removal phenol with isometric ether (1.5L), collects supernatant liquor, and repetition is extracted to no benzene
Phenol residual.Heating water bath removes ether, collects water phase.
3) water phase 15000g measures volume after being centrifuged 20min, dehydrated alcohol is added, until the final concentration of 80% (volume of ethyl alcohol
Score), overnight (12 hours), 15000g is centrifuged 20min to 4 DEG C of alcohol precipitations, takes precipitating.
4) quality of the precipitating in step 3) is weighed, precipitating is configured to mass concentration by the deionized water that certain volume is added
It for 10% suspension, is uniformly mixed, the glacial acetic acid aqueous solution that mass concentration is 10% is added, is heated to boiling, persistently stir
After mixing reaction 2h, adjusts pH to 7.0,15000g and be centrifuged 20min, collect supernatant.By gained supernatant dialysis desalination, (10KD is saturating
Analyse bag), freeze-drying obtains bacteroides fragilis extract.
5) bacteroides fragilis extract described in 30mg step 4) is weighed, 0.5mL D is dissolved in2O, 1 μ l acetone of addition (1H,
2.22；13C, 30.89) calibration.1H, 13C, COSY, HSQC, HMBC are analyzed using 500MHz Bruker nuclear magnetic resonance chemical analyser
It composes (Fig. 3-Fig. 7), the bacteroides fragilis extract that confirmation step 4) is collected is capsular polysaccharide A, and purity is about 70%.Pass through GPC
(gel permeation chromatography) analysis, the repetitive unit molecular weight of above-mentioned capsular polysaccharide A is 781 as the result is shown, unit repetition number n value
It is 89, molecular weight is about 70KD, and molecular formula is-[C31N3O20H47]91, chemical structure is shown in Fig. 8.
(3) preparation of different molecular weight size capsular polysaccharide A
By degrading to the capsular polysaccharide A prepared in (2), the biodegrading process includes but is not limited to the present embodiment
Chemical degradation method, physical degradation methods and biological degradation method.For the present embodiment using the method for ultrasound, the ultrasonic method is by pod membrane
In 195kHz, 20 DEG C of condition is handled 3 hours, 2 hours, 0.5 hour and 0 hour Polysaccharide A respectively, collects obtain molecular weight respectively
Size is the capsular polysaccharide A of 2KD, 5KD, 40KD, 70KD.Use the method for (2) from bacteroides fragilis NCTC 9343 (purchased from beauty
State ATCC) in extract obtain molecular weight be 110KD capsular polysaccharide A.
2 bacteroides fragilis capsular polysaccharide A of embodiment causes the influence of diarrhea-type IBS to folium sennae
One, experimental design
In order to verify the bacteroides fragilis extract (main component is capsular polysaccharide A) of the offer of embodiment 1 for preventing/controlling
The effect of irritable bowel syndrome is treated, the present embodiment selects 60 C57BL/6 mouse to be tested.60 C57BL/6 mouse male and female
Fifty-fifty, every laboratory mice is assigned with a unique number.It, should be on the label of mouse cage before being grouped to animal
Mark project number, kind/strain, gender, cage number and animal number.Using BioBook software according to the initial of C57BL/6 mouse
Weight is grouped at random, is divided into 6 groups, i.e., and normal group (Group1), model group (Group2), Loperamide Capsules group
(2.4mg/kg) (Group3), bacteroides fragilis capsular polysaccharide A low (Group4), in (Group5), high (Group6) dosage group,
Every group C57BL/6 mouse 10.The present embodiment is by taking molecular weight is the capsular polysaccharide A of 5KD as an example.
Corresponding drug is given to every group of intragastric administration on mice, normal group and model group give the physiological saline of equivalent, and daily 1
It is secondary, continuous 5 days.All C57BL/6 mouse fasting for 24 hours, in 1h after the last administration, remove normal group (Group1) and gavage normal
Outside salt water, remaining each group C57BL/6 mouse gavaging 1g/mL folium sennae water decoction.By C57BL/6 mouse sub-cage rearing, every cage 1
Only, it is lined with filter paper under cage and does muck counting, how much diarrhoea degree is indicated with muck, is changed filter paper 1 time every 1h.It observes and counts 6h
Total just number, loose stools sum and the loose stools series of interior mouse.
Two, judgment criteria
Determine that (Zhou Gannan, Hu Zhihua, Wang Yaxian wait preparation and the abdomen of diarrhea of mouse model to loose stools series according to Zhou Shi method
Rush down application [J] Chinese herbal medicine of index, 1994,250 (4): 195-196.).Stain diameter < lcm is 1 grade, and 1~1.9cm is 2
Grade, 2~3cm are 3 grades, and > 3cm is 4 grades.The loose stool rate (%) of every animal=loose stools sum/always just counts × 100%, diarrhea refers to
Number (ID)=loose stool rate × loose stools series.
Three, result and analysis
All data are indicated with x ± s, for statistical analysis using 17.0 software of SPSS, and comparison among groups use single factor test
Variance analysis, P < 0.05 are to have statistical significance.Concrete outcome is as shown in table 1.
Influence of the 1 bacteroides fragilis capsular polysaccharide A of table to folium sennae induced mice diarrhea-type IBS
Note: compared with normal group, * P < 0.01；Compared with model group, ▲ P < 0.01.
From 1 result of table as it can be seen that model group (Group2) refers to the loose stools sum of normal group (Group1), loose stool rate, diarrhea
Number more has significant difference (P < 0.01), illustrates folium sennae induced mice diarrhea IBS model modeling success.With model group
Compare, the low, middle and high dose groups for the bacteroides fragilis capsular polysaccharide A that Loperamide group and embodiment 1 provide can significantly inhibit small
The degree (P < 0.01) of mouse diarrhea, shows bacteroides fragilis capsular polysaccharide A provided by the invention to diarrhea-type caused by folium sennae
IBS has apparent inhibiting effect.
Influence of the 3 bacteroides fragilis capsular polysaccharide A of embodiment to diarrhea-type IBS caused by castor oil
One, experimental design
In order to verify the bacteroides fragilis extract (main component is capsular polysaccharide A) of the offer of embodiment 1 for preventing/controlling
The effect of irritable bowel syndrome is treated, the present embodiment selects 60 C57BL/6 mouse to be tested.60 C57BL/6 mouse male and female
Fifty-fifty, every laboratory mice is assigned with a unique number.It, should be on the label of mouse cage before being grouped to animal
Mark project number, kind/strain, gender, cage number and animal number.Using BioBook software according to the initial of C57BL/6 mouse
Weight is grouped at random, is divided into 6 groups, i.e., and normal group (Group1), model group (Group2), Loperamide Capsules group
(2.4mg/kg) (Group3), bacteroides fragilis capsular polysaccharide A low (Group4), in (Group5), high (Group6) dosage group,
Every group C57BL/6 mouse 10.The present embodiment is by taking molecular weight is the capsular polysaccharide A of 40KD as an example.
Corresponding drug is given to every group of intragastric administration on mice, normal group and model group give the physiological saline of equivalent, and daily 1
It is secondary, continuous 5 days.All C57BL/6 mouse fasting for 24 hours, in 1h after the last administration, remove normal group (Group1) and gavage normal
Outside salt water, remaining each group C57BL/6 mouse gavaging castor oil 1 time (20mL/kg).By C57BL/6 mouse sub-cage rearing, every cage 1
Only, it is lined with filter paper under cage and does muck counting, how much diarrhoea degree is indicated with muck, is changed filter paper 1 time every 1h.It observes and counts 6h
Total just number, loose stools sum and the loose stools series of interior mouse.
Two, judgment criteria
With the judgment criteria of embodiment 2.
Three, result and analysis
All data withIt indicates, for statistical analysis using 17.0 software of SPSS, comparison among groups use Dan Yin
Plain variance analysis, P < 0.05 are to have statistical significance.Concrete outcome is as shown in table 2.
Influence of the 2 bacteroides fragilis capsular polysaccharide A of table to castor oil induced mice diarrhea-type IBS
Note: compared with normal group, * P < 0.01；Compared with model group, ▲ P < 0.01.
From 2 result of table as it can be seen that model group (Group2) refers to the loose stools sum of normal group (Group1), loose stool rate, diarrhea
Number more has significant difference (P < 0.01), illustrates castor oil induced mice diarrhea IBS model modeling success.With model group
Compare, Loperamide group can significantly inhibit 6h loose stools sum, loose stool rate and the Scours index (P of diarrhea mice caused by castor oil
< 0.05).The bacteroides fragilis capsular polysaccharide A of low dosage (0.125g/kg) is compared with model group, 6h loose stools sum, loose stool rate
There is certain inhibiting effect with Scours index, but there was no significant difference (P > 0.05)；But in middle and high dosage, the quasi- bar of fragility
Bacterium capsular polysaccharide A can significantly inhibit 6h loose stools sum, loose stool rate and Scours index (the P < of diarrhea mice caused by castor oil
0.05)。
Influence of the 4 bacteroides fragilis capsular polysaccharide A of embodiment to neostigmine induced mice intestinal motility hyperfunction
One, experimental design
In order to verify the bacteroides fragilis extract (main component is capsular polysaccharide A) of the offer of embodiment 1 in preventing/treating
The effect of irritable bowel syndrome, the present embodiment select 60 C57BL/6 mouse to be tested.60 C57BL/6 mouse male and female are each
Half, every laboratory mice is assigned with a unique number.It, should be in the label subscript of mouse cage before being grouped to animal
Infuse project number, kind/strain, gender, cage number and animal number.Using BioBook software according to the first initial body of C57BL/6 mouse
It is grouped at random again, is divided into 6 groups, i.e., normal group (Group1), model group (Group2), Pinaverium Bromide (0.1g/kg) group
(Group3), bacteroides fragilis capsular polysaccharide A low (Group4), in (Group5), high (Group6) dosage group, every group of C57BL/
6 mouse 10.The present embodiment is by taking molecular weight is the capsular polysaccharide A of 70KD as an example.
Corresponding drug is given to every group of intragastric administration on mice, normal group and model group give the physiological saline of equivalent, and daily 1
It is secondary, continuous 5 days.1h after the last administration, except for the normal group, remaining 5 groups are subcutaneously injected neostigmine 0.15mg/kg, cause small
Intestines are excited, and normally organize subcutaneous injection same amount of normal saline.After 15min, each group is filled with the suspension containing 5% active carbon powder
Stomach, cervical dislocation is put to death after 20min, is opened abdomen separation small intestine, is measured the small intestinal length that total small intestinal length and carbon powder promote, and calculate carbon
Last ink propulsive rate.Carbon powder ink propulsive rate=(small intestinal length/total small intestinal length that carbon powder promotes) × 100%.
Two, result and analysis
All data withIt indicates, for statistical analysis using 17.0 software of SPSS, comparison among groups use Dan Yin
Plain variance analysis, P < 0.05 are to have statistical significance.Concrete outcome is as shown in table 3.
Influence of the 3 bacteroides fragilis capsular polysaccharide A of table to castor oil induced mice diarrhea-type IBS
Note: compared with normal group, * P < 0.01；Compared with model group, ▲ P < 0.01.
From table 3 it can be seen that neostigmine can cause mouse small intestine hyperkinesia, and compared with model group, dimension
Bromine ammonium group can significantly reduce carbon powder propulsion rate, inhibit mouse small intestine hyperkinesia (P < 0.01) caused by neostigmine；
The bacteroides fragilis capsular polysaccharide A of middle and high dosage also can significantly reduce carbon powder propulsion rate (P < 0.05), inhibit neostigmine institute
The mouse small intestine hyperkinesia of cause.
Influence of the 5 bacteroides fragilis capsular polysaccharide A of embodiment to constipation type IBS
One, experimental design
In order to verify the bacteroides fragilis extract (main component is capsular polysaccharide A) of the offer of embodiment 1 for preventing/controlling
The effect of constipation-predominant of irritable bowel syndrome is treated, the present embodiment selects 60 SD rats to be tested.60 SD rat half male and half females,
Every experiment is assigned with a unique number with rat.Before being grouped to animal, it should be marked on the label of mouse cage
Project number, kind/strain, gender, cage number and animal number.It is carried out using BioBook software according to the original body mass of SD rat
6 groups are randomly divided into, i.e., normal group (Group1), model group (Group2), Tijiaseluo maleate (prepare: the Malaysia 1.2mg by solution
10ml sterile saline is added in sour tegaserod) group (Group3), bacteroides fragilis capsular polysaccharide A low (Group4), in
(Group5), high (Group6) dosage group, every group SD rat 10.The present embodiment is for the capsular polysaccharide A of 70KD with molecular weight
Example.
According to (Peng L H, Yang Y S, Sun G, et al.A new model of constipation-
predominant irritable bowel syndrome in rats[J].World Chinese Journal
OfDigestology, 2004,12 (1): 112-116.) method construct SD rat constipation type IBS model.Except normal group
(Group1) outside, remaining each group is per daily primary with ice physiological saline (0~4 DEG C) stomach-filling, each 2ml, continuous 14 days, establishes just
Secret type IBS model rat.Each group rat can free diet drinking-water during modeling.
After 14th day, corresponding drug is given in each test group stomach-filling, wherein normal group and model group give 10ml's respectively
Room temperature sterile saline；Positive controls (Group3) stomach-filling Tijiaseluo maleate；Group4~6 give respectively it is low, in
With the bacteroides fragilis capsular polysaccharide A of high dose, specific experiment and dosage regimen are shown in Table 4:
4 experimental group of table and dosage regimen
Two, result and analysis
Respectively at the 1st day, the 14th day and the 28th day collection each group Rat 24 h excrement particles number, if any diarrhea, with one
A pollution trace is one (see Table 5 for details).The excrement weighing being collected into, drying calculate excrement water content (see Table 6 for details).
5 SD rat of table excrement particles number situation of change () for 24 hours
| Test group | 1st day | 14th day | 28th day |
| Group1 | 49.13±6.34 | 48.53±6.48 | 48.10±5.43◆ |
| Group2 | 47.37±5.27 | 33.07±5.32*▲ | 32.44±6.23 |
| Group3 | 48.22±7.34 | 32.46±5.72*▲ | 47.43±6.35★◆ |
| Group4 | 47.78±5.39 | 32.73±4.39*▲ | 40.04±7.94★◆ |
| Group5 | 48.05±7.91 | 34.07±5.83*▲ | 43.90±8.06★◆ |
| Group6 | 47.88±6.54 | 33.77±5.60*▲ | 49.03±5.71★◆ |
Note: each group tests the * P < 0.01 compared with first day；14th day, Group2~6 and Normal group ratio, ▲ P <
0.01；Each group tests the 28th day and the 14th day ratio, ★ P < 0.01；28th day, each experimental group compared with model group, ◆ P <
0.01。
Table 6SD rat excrement change of moisture content situation
| Test group | 1st day | 14th day | 28th day |
| Group1 | 0.51±0.04 | 0.49±0.08 | 0.48±0.07◆ |
| Group2 | 0.47±0.07 | 0.39±0.04*▲ | 0.35±0.06 |
| Group3 | 0.48±0.08 | 0.37±0.07*▲ | 0.56±0.06★◆ |
| Group4 | 0.49±0.10 | 0.38±0.09*▲ | 0.44±0.07★◆ |
| Group5 | 0.46±0.05 | 0.40±0.05*▲ | 0.47±0.05★◆ |
| Group6 | 0.47±0.06 | 0.39±0.06*▲ | 0.53±0.09★◆ |
Note: each group tests the * P < 0.05 compared with first day；14th day, Group2~6 and Normal group ratio, ▲ P <
0.05；Each group tests the 28th day and the 14th day ratio, ★ P < 0.05；28th day, each experimental group compared with model group, ◆ P <
0.05。
As seen from Table 5, in Group1~6, the difference of first day 24 hours excrement particles number of each group rat is little；Except normal
Group is outer, remaining the 14th day excrement particles number of each group rat significantly reduces compared with first day, and difference is anticipated with statistics
Adopted (P < 0.05)；14th day, Group2~6 significantly reduced, difference compared with normal group (Group1) of excrement particles number
With statistical significance (P < 0.05), illustrate that the present embodiment successfully constructs constipation type IBS rat model.28th day, Group2
~6 excrement particles number obviously increases compared with the 14th day, and difference has statistical significance (P < 0.05).Illustrate the present invention
The bacteroides fragilis capsular polysaccharide A of the basic, normal, high dosage provided can effectively increase the excrement particles of the IBS rat of constipation type
Number.
As seen from Table 6, in Group1~6,24 hours first day excrement water content difference of each group rat are little；Except normal group
Outside, remaining the 14th day excrement water content of each group rat significantly reduces compared with first day, and difference has statistical significance
(P < 0.05), the 14th day, Group2~6 significantly reduced compared with normal group (Group1) of excrement water content, difference tool
Statistically significant (P < 0.05).28th day, the excrement water content of Group2~6 obviously increased compared with the 14th day, difference
With statistical significance (P < 0.05).Illustrate the bacteroides fragilis capsular polysaccharide A of basic, normal, high dosage provided by the invention
Effectively increase the excrement water content of the IBS rat of constipation type.
It can be seen from the results above that bacteroides fragilis capsular polysaccharide A provided by the invention has very the IBS of constipation type
Good therapeutic effect.
The therapeutic effect of 6 bacteroides fragilis of embodiment and bacteroides fragilis capsular polysaccharide A
One, experimental design
The bacteroides fragilis extract (main component is capsular polysaccharide A) provided for comparing embodiment 1 and fragile quasi- bar
Bacterium itself for preventing/treating irritable bowel syndrome effect, the present embodiment select 60 C57BL/6 mouse tested.60
C57BL/6 mouse half male and half female, every laboratory mice are assigned with a unique number.It is being grouped to animal
Before, project number, kind/strain, gender, cage number and animal number should be marked on the label of mouse cage.Use BioBook software root
It is grouped at random according to the original body mass of C57BL/6 mouse, is divided into 6 groups, is i.e. folium sennae causes diarrhea-type IBS model group
(Group1), castor oil causes diarrhea-type IBS model group (Group2) high dose bacteroides fragilis capsular polysaccharide A to cause abdomen to folium sennae
Rush down treatment group (Group3), the high dose bacteroides fragilis itself (10 of type IBS10CFU/ml diarrhea-type IBS's) is caused to folium sennae
Treatment group (Group4), high dose bacteroides fragilis capsular polysaccharide A are to the treatment group of diarrhea-type IBS caused by castor oil
(Group5) and high dose bacteroides fragilis itself (1010CFU/ml the treatment group of diarrhea-type IBS) is caused to castor oil
(Group6), every group C57BL/6 mouse 10.The molecular weight of capsular polysaccharide A described in the present embodiment is 40KD, and concentration is
0.5mg/mL；The concentration of bacteroides fragilis is 1010CFU/ml。
Corresponding drug is given to every group of intragastric administration on mice, model group (Group1, Group2) gives the physiological saline of equivalent,
1 time a day, continuous 5 days.All C57BL/6 mouse fasting for 24 hours, in 1h after the last administration, Group1, Group3 and
Group4C57BL/6 mouse gavaging 1g/mL folium sennae water decoction, Group2, Group5 and Group6C57BL/6 mouse gavaging castor
Sesame oil 1 time (20mL/kg).By C57BL/6 mouse sub-cage rearing, 1, every cage is lined with filter paper under cage and does muck counting, with muck
It is how many to indicate diarrhoea degree, it is changed filter paper 1 time every 1h.Observe and count total just number, loose stools sum and the loose stools grade of mouse in 6h
Number.
Two, judgment criteria
With the judgment criteria of embodiment 2.
Three, result and analysis
All data withIt indicates, for statistical analysis using 17.0 software of SPSS, comparison among groups use Dan Yin
Plain variance analysis, P < 0.05 are to have statistical significance.Concrete outcome is as shown in table 6.
Influence of the 6 bacteroides fragilis capsular polysaccharide A of table to diarrhea of mouse type IBS
Note: Group3, Group4 are respectively compared with Group1, * P < 0.05；Group5, Group6 respectively with Group2,▲
P < 0.05；Group3 compared with Group4, Group5 compared with Group6,★P < 0.05.
From 6 result of table as it can be seen that Group3 and Group4 refers to the loose stools sum of model group (Group1), loose stool rate, diarrhea
Number more has significant difference (P < 0.05), illustrates bacteroides fragilis itself and bacteroides fragilis capsular polysaccharide A to folium sennae
Induced mice diarrhea IBS has treatment and prevention effect.Group5 and Group6 and the loose stools of model group (Group2) are total, dilute
Just rate, Scours index more have significant difference (P < 0.01), illustrate that bacteroides fragilis itself and bacteroides fragilis pod membrane are more
Sugared A has treatment and prevention effect to castor oil induced mice diarrhea IBS.Compared with Group4, Group3 loose stools sum, loose stools
Rate, Scours index are intended to small, have significant difference (P < 0.05), illustrate bacteroides fragilis capsular polysaccharide A to small caused by folium sennae
The treatment and prevention effect of mouse diarrhea IBS is better than bacteroides fragilis itself；Compared with Group6, Group5 loose stools is total, dilute
Just rate, Scours index are intended to small, there is significant difference (P < 0.05), illustrate bacteroides fragilis capsular polysaccharide A to caused by castor oil
The IBS treatment and prevention effect of diarrhea of mouse is better than bacteroides fragilis itself.
It is also confirmed by experiment, for neostigmine induced mice intestinal motility hyperfunction and constipation type IBS, the present invention
The treatment and prevention effect of the bacteroides fragilis capsular polysaccharide A of offer is equally better than bacteroides fragilis itself.
Therapeutic effect of the bacteroides fragilis capsular polysaccharide A of 7 different molecular weight of embodiment to IBS
The fragility containing 2KD, 5KD, 40KD and 70KD that the present embodiment is prepared using the embodiment of the present invention 1 respectively is quasi-
The bacteroides fragilis extract of bacillus capsular polysaccharide A carries out preventing/treating to constipation type IBS rat model, detects different molecular
Therapeutic effect of the bacteroides fragilis capsular polysaccharide A of amount to constipation type IBS.The present embodiment with 2KD, 5KD, 40KD of high dose and
For the bacteroides fragilis capsular polysaccharide A of 70KD.
One, experimental design
Referring to embodiment 5 experimental group method, by mouse be divided into Normal group, model group, 2KD group, 5KD group,
40KD group, 70KD group and 110KD group.
According to (Peng L H, Yang Y S, Sun G, et al.A new model of constipation-
predominant irritable bowel syndrome in rats[J].World Chinese Journal
OfDigestology, 2004,12 (1): 112-116.) method construct SD rat constipation type IBS model.Except normal group
(Group1) outside, remaining each group is per daily primary with ice physiological saline (0~4 DEG C) stomach-filling, each 2ml, continuous 14 days, establishes just
Secret type IBS model rat.Each group rat can free diet drinking-water during modeling.
After 14th day, corresponding drug is given in each test group stomach-filling, wherein normal group and model group give 10ml's respectively
Room temperature sterile saline；It is 2KD (Group3), 5KD (Group4), 40KD that molecular weight is given in Group3~7 respectively
(Group5), the capsular polysaccharide A of 70KD (Group6) and 110KD (Group7), specific experiment and dosage regimen are shown in Table 7:
7 experimental group of table and dosage regimen
Two, result and analysis
Respectively at the 1st day, the 14th day and the 28th day collection each group Rat 24 h excrement particles number, if any diarrhea, with one
A pollution trace is one (see Table 8 for details).The excrement weighing being collected into, drying calculate excrement water content (see Table 9 for details).
8 SD rat of table excrement particles number situation of change () for 24 hours
| Test group | 1st day | 14th day | 28th day |
| Group1 | 49.35±5.47 | 48.60±6.08 | 49.00±5.51◆ |
| Group2 | 48.39±5.27 | 32.20±3.12*▲ | 31.48±5.93 |
| Group3 | 48.22±4.83 | 32.54±2.99*▲ | 35.07±5.46★◆ |
| Group4 | 48.50±6.94 | 32.06±6.02*▲ | 45.83±5.95★◆ |
| Group5 | 48.35±6.03 | 31.43±5.39*▲ | 46.04±6.91★◆ |
| Group6 | 48.16±6.81 | 33.17±5.03*▲ | 47.90±7.17★◆ |
| Group7 | 47.92±5.97 | 32.93±5.72*▲ | 41.03±6.03★◆ |
Note: each group tests the * P < 0.01 compared with first day；14th day, Group2~7 and Normal group ratio, ▲ P <
0.01；Each group tests the 28th day and the 14th day ratio, ★ P < 0.01；28th day, each experimental group compared with model group, ◆ P <
0.01。
9 SD rat excrement change of moisture content situation of table
Note: each group tests the * P < 0.05 compared with first day；14th day, Group2~6 and Normal group ratio, ▲ P <
0.05；Each group tests the 28th day and the 14th day ratio, ★ P < 0.05；28th day, each experimental group compared with model group, ◆ P <
0.05。
As seen from Table 8, in Group1~7, the difference of first day 24 hours excrement particles number of each group rat is little；Except normal
Outside, remaining the 14th day excrement particles number of each group rat significantly reduces group (Group1) compared with first day, and difference is extremely aobvious
It writes (P < 0.01), there is statistical significance；14th day, Group2~7 compared with normal group (Group1) of excrement particles number,
It significantly reduces, difference is extremely significant (P < 0.01), has statistical significance.Illustrate that the present embodiment successfully constructs constipation type IBS
Rat model.28th day, in addition to Group3, the excrement particles number of Group4~7 obviously increased compared with the 14th day, difference pole
Significantly (P < 0.01) has statistical significance.Illustrate the bacteroides fragilis capsular polysaccharide of different molecular weight provided by the invention
A can effectively increase the excrement particles number of the IBS rat of constipation type.Meanwhile passing through the excrement between Group3~7 to 28 days
Grain number is compared discovery, and the excrement particles number of Group4, Group5 and Group6 are obviously more than Group2, Group7,
Difference is extremely significant (P < 0.05), has statistical significance.
As seen from Table 9, in Group1~7,24 hours first day excrement water content difference of each group rat are little；Except normal group
Outside, remaining the 14th day excrement water content of each group rat significantly reduces compared with first day, and difference has statistical significance
(P < 0.05), the 14th day, Group2~7 significantly reduced compared with normal group (Group1) of excrement water content, difference tool
Statistically significant (P < 0.05).28th day, in addition to Group3, the excrement water content of Group4~7 was bright compared with the 14th day
Aobvious to increase, difference has statistical significance (P < 0.05).Meanwhile passing through the excrement water content between Group3~7 to 28 days
It is compared discovery, the excrement water content of Group4, Group5 and Group6 are obviously more than Group3, Group7, and difference is extremely aobvious
It writes (P < 0.05), there is statistical significance.
These results suggest that the bacteroides fragilis capsular polysaccharide A that molecular weight provided by the invention is 5KD~70KD can have
Effect increases the excrement particles number and excrement water content of the IBS rat of constipation type, has treatment effect well to the IBS of constipation type
Fruit.Also illustrate simultaneously, by degrading to bacteroides fragilis capsular polysaccharide A, the molecular weight and viscosity of reduction capsular polysaccharide A,
Its therapeutic effect to constipation-predominant of irritable bowel syndrome can be enhanced.
Meanwhile the present invention be also experimentally confirmed molecular weight be 5KD~70KD bacteroides fragilis capsular polysaccharide A for
The effect for reducing the Scours index of diarrhea-type IBS is also much better than the bacteroides fragilis capsular polysaccharide A that molecular weight is 2KD or 110KD.
Curative effect of the 8 difference bacteroides fragilis bacterial strain capsular polysaccharide A of embodiment to the IBS of constipation type
The ultrasonic method that the present embodiment is recorded using embodiment 1 degrades to the capsular polysaccharide A that molecular weight is 110KD
(ultrasound condition: 195kHz, 25 DEG C, 0.5 hour), and the capsular polysaccharide A that molecular weight is 70KD is collected, it is denoted as NCTC 9343-
70KD group, and the capsular polysaccharide A (being denoted as ZY-312-70KD group) for being 70KD with the molecular weight extracted from ZY-312 is carried out
Comparison, evaluates its curative effect to the IBS of constipation type.The method that the present embodiment reference implementation example 7 is recorded, detects excrement particles respectively
Number situation of change, rat excrement change of moisture content situation, concrete outcome are as follows:
10 SD rat of table excrement particles number situation of change () for 24 hours
Note: each group tests the * P < 0.01 compared with first day；Each group tests the 28th day and the 14th day ratio, ★ P < 0.01.
11 SD rat excrement change of moisture content situation of table
Note: each group tests the * P < 0.01 compared with first day；Each group tests the 28th day and the 14th day ratio, ★ P < 0.01.
It can be seen from the results above that obtaining the capsular polysaccharide that molecular weight is 110KD for extracting from 9343 bacterial strain of NCTC
A degrades, therapeutic effect similar in IBS of the capsular polysaccharide A that may be implemented to extract with ZY-312 bacterial strain to constipation type.
By the result of above embodiments as it can be seen that bacteroides fragilis capsular polysaccharide A provided by the invention is to diarrhea-type, constipation type
IBS have good preventive and therapeutic action, have the function of bidirectional modulation.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. application of the bacteroides fragilis extract in the drug or food of preparation prevention and treatment irritable bowel syndrome, which is characterized in that
Contain bacteroides fragilis capsular polysaccharide A in the bacteroides fragilis extract.
2. application according to claim 1, which is characterized in that the molecular weight of the bacteroides fragilis capsular polysaccharide A be 5~
75KD。
3. application according to claim 1, which is characterized in that the molecular weight of the bacteroides fragilis capsular polysaccharide A is
35KD~45KD.
4. application according to claim 1-3, which is characterized in that the bacteroides fragilis is that deposit number is
The bacteroides fragilis ZY-312 of CGMCC No.10685.
5. application according to claim 1-3, which is characterized in that the preparation side of the bacteroides fragilis extract
Method the following steps are included:
(1) by the bacteroides fragilis bacterium solution centrifugation after fermented and cultured, the first sediment is collected, first sediment is taken to add
Enter 65-72 DEG C of water, phenol solution is added after dissolution, keep 65-72 DEG C of stirring 25-35min, the first supernatant is collected in centrifugation
Liquid；
(2) the first supernatant collected in step (1) ether is extracted into removal phenol, then removes remaining ether, collect water
Phase solution；
(3) final concentration of 75-85v/v% of the dehydrated alcohol to ethyl alcohol, alcohol are added in the aqueous phase solution being collected into step (2)
Heavy, the second sediment is collected in centrifugation；
(4) second sediment is taken, water is added to be configured to suspension, then adjusting pH is 6.5-7.5, the second supernatant is collected in centrifugation
Liquid, desalination of dialysing, is freeze-dried to get the bacteroides fragilis extract.
6. application according to claim 5, which is characterized in that the water that is added in first sediment in step (1),
The phenol solution and the proportion of first sediment are 3-5mL:3-5mL:1g；The mass concentration of the phenol solution is
70-80%.
7. application according to claim 5, which is characterized in that step (3) alcohol precipitation is the at a temperature of alcohol precipitation at 0-8 DEG C
8-16 hours.
8. application according to claim 5, which is characterized in that step (4) includes: to take second sediment, and water is added to match
The suspension that mass concentration is 8-12% is made, adds the glacial acetic acid aqueous solution that mass concentration is 8-12%, is heated to boiling, stir
Mix reaction 1.5-2.5 hour, adjustings pH be 6.5-7.5, centrifugation, collect the second supernatant, dialysis desalination, be freeze-dried to get
The bacteroides fragilis extract.
9. application according to claim 5, which is characterized in that the preparation method of the bacteroides fragilis extract further includes
The step of degradation: bacteroides fragilis extract obtained in step (4) is degraded by the method for ultrasound, the ultrasound
Condition are as follows: 180-210kHz, 15-25 DEG C.
10. a kind of bacteroides fragilis extract for preventing and treating irritable bowel syndrome or drug or food, which is characterized in that described
Contain bacteroides fragilis extract in drug or food, contains bacteroides fragilis capsular polysaccharide in the bacteroides fragilis extract
A。
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| CN201710812676.4A CN109481473B (en) | 2017-09-11 | 2017-09-11 | Application of bacteroides fragilis extract in preparation of medicine for preventing and treating irritable bowel syndrome |
| CN202110977532.0A CN113730443B (en) | 2017-09-11 | 2017-09-11 | Application of bacteroides fragilis and extract thereof in preparation of medicine for preventing and treating irritable bowel syndrome |
| PCT/CN2017/120112 WO2019047439A1 (en) | 2017-09-11 | 2017-12-29 | Use of bacteroides fragilis extract in preparation of drug or food for preventing and treating irritable bowel syndrome |
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| CN116004486A (en) * | 2023-03-24 | 2023-04-25 | 广东省科学院微生物研究所(广东省微生物分析检测中心) | Bacteroides fragilis BFS17 for relieving irritable bowel syndrome and intestinal tract hypersensitivity and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115252652A (en) | 2022-11-01 |
| WO2019047439A1 (en) | 2019-03-14 |
| CN109481473B (en) | 2023-03-21 |
| CN113730443B (en) | 2022-10-04 |
| CN113730443A (en) | 2021-12-03 |
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