CN102940652A - Eubacterium biforme preparation and use thereof - Google Patents

Eubacterium biforme preparation and use thereof Download PDF

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CN102940652A
CN102940652A CN2012102285637A CN201210228563A CN102940652A CN 102940652 A CN102940652 A CN 102940652A CN 2012102285637 A CN2012102285637 A CN 2012102285637A CN 201210228563 A CN201210228563 A CN 201210228563A CN 102940652 A CN102940652 A CN 102940652A
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eubacterium
treatment
group
biforme
disease
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CN102940652B (en
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崔云龙
李洪福
王发合
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BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd
QINGDAO EASTSEA PHARMACEUTICAL CO Ltd
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BEIJING PUERKANG MEDICAL HIGH TECHNOLOGY Co Ltd
QINGDAO EASTSEA PHARMACEUTICAL CO Ltd
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Abstract

The invention relates to a eubacterium biforme preparation. The eubacterium biforme preparation is a microecological preparation adopting eubacterium biforme as a main active ingredient. The invention also relates to a use of the eubacterium biforme preparation in treatment on related diseases. The eubacterium biforme preparation can be prepared into a drug composition, a health care product, a drink, a veterinary drug and a feed additive.

Description

Eubacterium biforme preparation and application thereof
The application divides an application, original application day: on 05 28th, 2008, and original applying number: 200810108889.X, former invention and created name: Eubacterium ventriosum and Eubacterium biforme preparation and application thereof.
Technical field
The present invention relates to Eubacterium ventriosum and Eubacterium biforme preparation and application thereof, be specifically related to Eubacterium ventriosum and Eubacterium biforme and make microbial ecological agent as main active ingredient alone or in combination, and the application of this microbial ecological agent in the treatment relevant disease, belong to the biological medicament field.
Background technology
At present, antimicrobial drug has drawn attention in the harm of the aspects such as clinical and aquaculture abuses, because microbial ecological agent is free from side effects, utilizes microbial ecological agent treatment relevant disease, health care and is used widely as veterinary drug and feed additive.Present microbial ecological agent Main Ingredients and Appearance comprises bacillus bifidus, lactobacillus, enterococcus, Bacillus licheniformis, bacillus subtilis etc., and treatment relevant disease curative effect is not ideal.Butanoic acid (butyric acid) has been proved to be the first-selection source of colon energy, and the energy of intestinal mucosa 70% is provided, and promotes intestinal mucosa cells proliferate and digestive system development ripe, and butanoic acid also is the important substance of regulating immunity simultaneously.Microbial ecological agent of the present invention enters intestinal owing to can secrete a large amount of butyric acid, and the treatment relevant disease is evident in efficacy, and can be used as health product, veterinary drug and feed additive application, and social meaning is huge, and has no the correlational study report, special this patent of invention of application.
Summary of the invention
The purpose of this invention is to provide a kind of novel microbial ecological agent, main active ingredient in this microbial ecological agent enters intestinal can produce a large amount of butanoic acid, repair intestinal mucosa, regulate immunity, the overexpression of the inflammation-inhibiting factor, this microbial ecological agent can also recover the intestinal microbial population balance and improve body and mucosal immunity simultaneously, effectively treats digestive system disease, nutrient malabsorption disease, autoimmune disease, cardiovascular and cerebrovascular disease, allergic disease, hand-foot-mouth disease and improves immunity and anticancer.Wherein said digestive system disease comprises diarrhoea, irritable bowel syndrome, cool and rush down, drink and rush down, ulcerative colitis, Crohn disease, antibiotic-associated diarrhea, pseudomembranous enteritis, infantile pneumonia Secondary cases diarrhoea, intestinal cancer, the tumor chemoradiotherapy auxiliary treatment, abdominal distention and dyspepsia, constipation, just smelly, just smelly poisoning syndrome, liver and gall diseases, viral diarrhea, feeding intolerance, necrotizing enterocolitis, jaundice, oral ulcer, thrush, promote children intestinal to reach maturity, facilitating digestion absorbs, nourishing healthy and growth promoter; Described nutrient malabsorption disease comprises rickets; Described autoimmune disease comprises rheumatoid arthritis, ankylosing spondylitis; Described cardiovascular and cerebrovascular disease comprises hyperlipemia, hypertension, cerebral thrombosis, cerebral embolism, cerebral ischemia, myocardial infarction, coronary heart disease, cerebral infarction, cerebral hemorrhage, angina pectoris, myocarditis, atherosclerosis; Described allergic disease comprises eczema; Described raising immunity comprises the treatment recurrent respiratory tract infection.
The preparation of microbial ecological agent of the present invention is preferably implemented by following step, but be not limited to this preparation technology, the known preparation technology that can realize all can: the sample of taking to contain Eubacterium ventriosum or Eubacterium biforme, preferred human or animal's feces, more preferably healthy babies feces, then sample is placed in the sterilization anaerobism bottle, being blown into nitrogen fully mixes simultaneously, therefrom getting rapidly 2 gram samples adds in the diluent of 18mL sterilization, be blown into the simultaneously abundant mixing of nitrogen, in aseptic operating platform, carry out 10 -1, 10 -2, 10 -3, 10 -4, 10 -5, 10 -6, 10 -7Gradient dilution gets 10 -5, 10 -6, 10 -7Three dilution gradients, coat respectively on Eubacterium ventriosum or the Eubacterium biforme selectivity list bacterium colony separating solids culture medium, place in the anaerobic jar, 37 ℃ of lower cultivations 48 hours of anaerobism, single bacterium colony that selection is grown fine is inoculated in respectively in the liquid amplification culture medium, place in the anaerobic jar 37 ℃ of lower amplification cultivation of anaerobism 48 hours.After gained medium centrifugal (12000rpm) isolated thalline, with the thalline lyophilisation, modulate the dry mycopowder of each strain, then carry out strain identification, produce butanoic acid experiment and toxicity test, with the avirulence Eubacterium ventriosum identified or the dry mycopowder of Eubacterium biforme alone or in combination desired proportions add adjuvant and make the various dosage forms such as tablet, capsule and powder or veterinary drug, feed additive.
Eubacterium ventriosum or Eubacterium biforme selectivity list bacterium colony separating solids medium optimization but be not limited to: purified water 100mL, tryptone 1g, yeast extract 0.5g, sodium hydrogen phosphate 0.4g, glucose 0.15g, soluble starch 0.05g, Cys 0.02g, Cys hydrochlorate 0.05g, agar 1.5g, 7.7,115 ℃ of adjust pHs, 20 minutes autoclavings.After being cooled to 60 ℃, add 5mL defiber horse blood, ES solution 4mL after the sterilization.
ES solution wherein: sodium propionate 30%, streptomycin sulfate 4%, paromomycin sulfate 2%, aerosporin 0.02%.
Eubacterium ventriosum or Eubacterium biforme liquid amplification culture medium are preferably but not limited to the beef 500g of rubbing, distilled water 11,1N NaOH 25.0mL with smart beef or Equus caballus (L.), rubs and removes fat and conjunctive tissue, mixing meat, water and sodium hydroxide boils, stir simultaneously, be cooled to room temperature, omit fat and the filtration on surface, keep filtrate, replenish enough distilled water filtrate and recover 1 liter of original volume.In every 100mL filtrate, add: peptone 2.0g, glucose 0.5g, yeast extract 1.0g, cysteine hydrochloride 0.05g, saline solution 4.0mL, vitamin K1 solution 0.1mL, 5mg/mL chlorhematin solution 0.5mL, transfer pH to 7.2 scholar 0.1, in the anaerobism pipe, pass into 97% nitrogen, 3% hydrogen, cover tightly the butyl rubber bottle stopper medicated cap, 121 ℃ of autoclaving 15min.Wherein: 1, the preparation of saline solution: take by weighing anhydrous calcium chloride 0.2g, magnesium sulfate 0.2g, dipotassium hydrogen phosphate 1g, potassium dihydrogen phosphate 1g, sodium bicarbonate 10g, sodium chloride 2g, adding distil water is to 1000mL; 2, the preparation of chlorhematin solution (5mg/mL): take by weighing chlorhematin 0.5g and be dissolved among the 1mol/L sodium hydroxide 1mL, adding distil water is to 100mL, 121 ℃ of autoclaving 15min, Refrigerator store; 3, vitamin K 1The preparation of solution: take by weighing vitamin K 11g adds dehydrated alcohol 99mL, and filtration sterilization lets cool the dark place and preserves.
Bacteriology's character of the Eubacterium ventriosum that the present invention preferably uses:
1, colonial morphology
Microscopic examination: long 1.5-2 micron, wide 0.5 micron, quarter butt, Gram-positive.
Dull and stereotyped form: thalline is rounded, protruding, periphery is neat, smooth; The color Lycoperdon polymorphum Vitt is opaque.
2, Physiology and biochemistry is identified
Litmus milk :-; Lipase :-; Gelatin liquefaction :-; Catalase :-; Arginine produces ammonia :-; The Esculin hydrolysis :+; Indole :-; Hydrogen sulfide :-; Voges-Proskauer test (V-P test) :-; Whether aerobic: anaerobic.
3, glycolysis experimental identification
Cellobiose :-; D-Fructose :+; The D-galactose :+; Glucose :+; D-MANNOSE :+; The D-Raffinose :-; Rhamnose :-; Sorbose :-; Melezitose :-; Sucrose :-; Trehalose :-; Xylose :+; Maltose :+; Starch :+; 6-(.alpha.-D-galactosido)-D-glucose. :+; Ribose :+; Glycerol :-; Esculin :+; Arabinose :-; Fructose :+.
Bacteriology's character of the Eubacterium biforme that the present invention preferably uses:
1, colonial morphology
Microscopic examination: long 2.0-5 micron, wide 1.0 microns, middle stock, Gram-positive.
Dull and stereotyped form: thalline is rounded, protruding, periphery is neat, smooth; The color Lycoperdon polymorphum Vitt is opaque.
2, Physiology and biochemistry is identified
Litmus milk :-; Lipase :-; Gelatin liquefaction :-; Catalase :-; Arginine produces ammonia :-; The Esculin hydrolysis :+; Indole :-; Hydrogen sulfide :-; The V-P test :-; Whether aerobic: anaerobic.
3, glycolysis experimental identification
Cellobiose :-; D-Fructose :+; The D-galactose :+; Glucose :+; D-MANNOSE :+; The D-Raffinose :-; Rhamnose :-; Sorbose :-; Melezitose :-; Sucrose :-; Trehalose :+; Xylose :-; Maltose :-; Starch :-; 6-(.alpha.-D-galactosido)-D-glucose. :-; Ribose :-; Esculin :+; Glycerol :-; Arabinose :-.
The inventor utilizes said method to go out Eubacterium ventriosum or Eubacterium biforme by Eubacterium ventriosum or Eubacterium biforme selectivity list bacterium colony separating solids culture medium isolation identification.
Eubacterium ventriosum of the present invention is preferred but be not limited to Eubacterium ventriosum (Eubacterium ventriosum), CGMCC, preservation numbering 2465.
Eubacterium biforme of the present invention is preferred but be not limited to Eubacterium biforme (Eubacterium biforme), CGMCC, preservation numbering 2466.
Eubacterium ventriosum of the present invention or Eubacterium biforme refer to that living organism is individual.
The present invention is alone or in combination as main medicament active composition with the above-mentioned Eubacterium ventriosum of effective dose or Eubacterium biforme, according to certain preparation process, add the excipient substances such as conventional excipient, flavoring agent, disintegrating agent, antiseptic, lubricant, wetting agent, adhesive, solvent, thickening agent, solubilizing agent, make any dosage form that is suitable for using clinically, such as dosage forms such as tablet, capsule, granule, powder, liquid preparation, enemas.
Above-mentioned Eubacterium ventriosum or Eubacterium biforme with effective dose of the present invention made the viable bacteria microbial ecological agent as main medicament active composition alone or in combination, also can be above-mentioned Eubacterium ventriosum or Eubacterium biforme alone or in combination with the probiotic bacterias such as bacillus bifidus, Bacillus coagulans, lactobacillus, streptococcus, bacillus subtilis in one or more or the combination of other active ingredients make the viable bacteria microbial ecological agent, to play synergistic therapeutic action, improve therapeutic effect.
Microbial ecological agent among the present invention consumption clinically, because of the application method that patient age, body weight and symptom, medication purpose determine different with factors such as method, therapeutic effect and administration times, correct consumption should be decided by the doctor, and application dose also is that the clinician is easy to grasp and adjust according to the state of an illness.
Indication effective dose of the present invention refers to can not be lower than 1 * 10 with above-mentioned Eubacterium ventriosum or Eubacterium biforme according to total viable count that the top described solid live bacteria preparation of making as main medicament active composition alone or in combination comprises 6CFU/g is generally 1 * 10 7More than the CFU/g, can reach 1 * 10 12CFU/g or 1 * 10 12More than the CFU/g.
Indication effective dose of the present invention refers to can not be lower than 1 * 10 with above-mentioned Eubacterium ventriosum or Eubacterium biforme according to total viable count that the top described liquid active bacteria formulation of making as main medicament active composition alone or in combination comprises 6CFU/mL is generally 1 * 10 7More than the CFU/mL, can reach 1 * 10 12CFU/mL or 1 * 10 12More than the CFU/mL.
Because the present invention discloses Eubacterium ventriosum or Eubacterium biforme first in the application of making as main active ingredient in the microbial ecological agent, the medicament that therefore contains above-mentioned Eubacterium ventriosum or Eubacterium biforme all belongs to protection scope of the present invention.
Any one bacterial strain in Eubacterium ventriosum of the present invention or the Eubacterium biforme comprises Eubacterium ventriosum CGMCC2465 strain and Eubacterium biforme CGMCC2466 strain, when making any dosage form, all has the effect of the above-mentioned disease for the treatment of.Any medicament; if any one the bacterial strain composition that contains in its component in above-mentioned Eubacterium ventriosum or the Eubacterium biforme prepares patent medicine; on the signs such as its packing or description or at other any propaganda materials, need only effect dated or that prompting has the above-mentioned disease for the treatment of, then fall within protection scope of the present invention.
Any one bacterial strain in Eubacterium ventriosum of the present invention or the Eubacterium biforme comprises that Eubacterium ventriosum CGMCC2465 strain and Eubacterium biforme CGMCC2466 strain can make health product or beverage.Health product or beverage that any one bacterial strain in above-mentioned Eubacterium ventriosum or the Eubacterium biforme is made; have the effect for the treatment of above-mentioned disease if on the signs such as its packing or description or at other any propaganda materials, need only to indicate or point out, then fall within protection scope of the present invention.
Any one bacterial strain in Eubacterium ventriosum of the present invention or the Eubacterium biforme comprises that Eubacterium ventriosum CGMCC2465 strain and Eubacterium biforme CGMCC2466 strain can make veterinary drug or feed additive.Any one bacterial strain in above-mentioned Eubacterium ventriosum or the Eubacterium biforme is made veterinary drug or feed additive, then fall within protection scope of the present invention.
The specific embodiment
Medicine preparation example explanation: above-mentionedly the preparation of Eubacterium ventriosum and Eubacterium biforme is described, here by take Eubacterium ventriosum CGMCC2465 strain and Eubacterium biforme CGMCC2466 strain as example, Eubacterium ventriosum powder is described, the preparation method of Eubacterium biforme powder and Eubacterium ventriosum Eubacterium biforme bigeminy viable bacteria powder (hereinafter to be referred as the bigeminy viable bacteria), preparation method those skilled in the art of other Eubacterium ventriosums and Eubacterium biforme bacterial strain preparation are easy to grasp by present embodiment, preparation method those skilled in the art of other dosage forms are easy to grasp by this enforcement, narrate no longer one by one explanation at this.It is described that preparation method is not limited to the embodiment of the invention, and known can to reach the method for preparing purpose all passable, and the preparation explanation of embodiment is not limiting the scope of the invention just to explanation of the present invention.
The preparation of medicine Preparation Example 1 oral Eubacterium ventriosum viable bacteria powder, oral Eubacterium biforme viable bacteria powder and bigeminy viable bacteria powder
The preparation of 1 mycopowder and the evaluation of strain
Take Jiaonan City, Shandong Province one healthy babies feces, then feces is placed in the sterilization anaerobism bottle, be blown into nitrogen and fully mix simultaneously, therefrom getting rapidly 2 gram feces adds in the diluent of 18mL sterilization, be blown into the simultaneously abundant mixing of nitrogen, in aseptic operating platform, carry out 10 -1, 10 -2, 10 -3, 10 -4, 10 -5, 10 -6, 10 -7Gradient dilution gets 10 -5, 10 -6, 10 -7Three dilution gradients, coat on Eubacterium ventriosum or the Eubacterium biforme selectivity list bacterium colony separating solids culture medium, place in the anaerobic jar, 37 ℃ of lower cultivations 48 hours of anaerobism, two single bacterium colonies that selection is grown fine are inoculated into respectively in Eubacterium ventriosum or the Eubacterium biforme liquid amplification culture medium, place in the anaerobic jar 37 ℃ of lower amplification cultivation of anaerobism 48 hours.After gained medium centrifugal (12000rpm) isolated thalline, with the thalline lyophilisation, modulate the dry mycopowder of two strains, then carry out strain identification according to said method, through being accredited as Eubacterium ventriosum CGMCC2465 strain and Eubacterium biforme CGMCC2466 strain.
2 produce the butanoic acid experiment
The Eubacterium ventriosum and the Eubacterium biforme that are separated to are inoculated into respectively in the liquid amplification culture medium, place in the anaerobic jar, 37 ℃ of lower amplification cultivation of anaerobism 48 hours, centrifugal (12000rpm), get supernatant and be respectively 7.8mmol/L and 8.2mmol/L with vapor detection metabolite butanoic acid content, show and all can produce butanoic acid.
3 Physiology and biochemistries are identified through identifying and are not all produced the harmful substances such as hydrogen sulfide, indole, ammonia.
4 toxicity tests
4.1 30 SPF rank mices are got in animal and grouping, in 6～8 ages in week, body weight 16～19g is randomized into Eubacterium ventriosum group, Eubacterium biforme group and non-administered group, 10 every group.
To contain the bacterium number average be 1 * 10 4.2 preparation bacterium liquid is modulated to above-mentioned Eubacterium ventriosum mycopowder and Eubacterium biforme mycopowder with purified water 12The bacterium liquid of CFU/mL.
4.3 method Eubacterium ventriosum group, Eubacterium biforme group and non-administered group all give identical normal feedstuff, and the raising condition is all consistent, the Eubacterium ventriosum group gavages Eubacterium ventriosum bacterium liquid 0.5mL every day, the Eubacterium biforme group gavages Eubacterium biforme bacterium liquid 0.5mL every day, non-administered group gavages purified water 0.5mL every day, fed 6 months, and observed body weight and toxic reaction.
4.4 result
Each is organized mice and abnormal conditions all do not occurred, it is unusual that chatter, spasm, movement disorder, attitude do not occur, outstanding without eyeball, it is normal to urinate, and skin, breathing are normally, without death condition, and the body weight increase of Eubacterium ventriosum group, Eubacterium biforme group is significantly higher than non-administered group (P＜0.05), shows that Eubacterium ventriosum and Eubacterium biforme have the enhancing development effect, illustrates that two bacterial strains are respond well, have no toxic reaction, the results are shown in Table 1.
Table 1 Mouse Weight increases situation
5 are prepared into the dosage forms such as powder
Behind above-mentioned steps and method isolation identification Eubacterium ventriosum and Eubacterium biforme, produce butanoic acid, not toxin producing, avirulence through experimental check, just can be made into mycopowder, then add as required relevant auxiliary materials and make various dosage forms, preferably according to the viable count of Eubacterium ventriosum and Eubacterium biforme mycopowder, add defatted milk powder in proportion, glucose is made powder, makes total viable count be not less than 1 * 10 7CFU, then the mycopowder with two bacterium packs alone or in combination, makes oral Eubacterium ventriosum viable bacteria powder, oral Eubacterium biforme viable bacteria powder and bigeminy viable bacteria powder.
Effect embodiment explanation: although Eubacterium ventriosum and Eubacterium biforme have many bacterial strains, but the different strains that separates as stated above has identical biological characteristics, and the mechanism of action is identical, comprise and enter a large amount of butanoic acid of intestinal secretion, additional intestinal beneficial bacterium recovery intestinal microbial population balance, raising body and mucosal immunity etc., therefore to select the Eubacterium ventriosum and the Eubacterium biforme bacterial strain that separate as stated above be object of study in the present invention, introduces the effect of Eubacterium ventriosum and Eubacterium biforme.
Embodiment 1, Eubacterium ventriosum and Eubacterium biforme are to the repair research of intestinal mucosa
1 materials and methods
1.1 material
1.1.1 medicine Eubacterium ventriosum bacterium liquid (10 7CFU/mL); Eubacterium biforme bacterium liquid (10 7CFU/mL); Bigeminy viable bacteria bacterium liquid (10 7CFU/mL); Bacillus bifidus bacterium liquid (10 7CFU/mL); Dextrorotation dextran sulfate sodium (DSS, 10g/ bottle, Sino-American Biotec); Ai Er Xinlan (1g/ bottle, Sino-American Biotec).
1.1.2 70 of animal SD male white rats, body weight 80～100g, 2 grades of standards are available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute's Experimental Animal Center.
1.2 method
1.2.1 intestinal mucosal injury moulding and treatment
70 of rats, 10 rats are as Normal group, and 60 rats are given on an empty stomach rat oral gavage (1mL/100g) with 3%DSS solution in addition, every day 1 time, totally 7 days, annotate DSS 1mL/ only to internal rectum from anus for the last time.Then put to death wherein 10 (model control group), cut open the belly and get the knot rectum, measure knot rectum weight in wet base (g/100g. body weight), formaldehyde is fixed, with Ai Er Xinlan solution-dyed, the counting of naked-eye observation ulcer and rotten to the corn part dyed a little blued area (cm with kind of calliper indigo plant 2), behind the confirmation ulcer, all the other 50 rat models are divided into 5 groups at random, 10 every group, difference gavage normal saline, Eubacterium ventriosum bacterium liquid (10 7CFU/mL), Eubacterium biforme bacterium liquid (10 7CFU/mL), bigeminy viable bacteria bacterium liquid (10 7CFU/mL), bacillus bifidus bacterium liquid (10 7CFU/mL), 1mL/ time, every day 2 times, totally 21 days.Put to death whole rats after 21 days, process knot rectum specimen by upper method, detect corresponding index.
1.2.2 t-student ' t check is used in the significance,statistical check of the data difference between each group of statistical analysis, significance of difference boundary is p＜0.05.
2 results
2.1 knot rectal ulcer (or rotten to the corn) is counted and area
Use the DSS gavage, add rectum and can form the damage of typical Intestinal Mucosa at whole knot rectum after to DSS, especially the intestinal specimen of colon lower end and rectum with the dyeing of Ai Er Xinlan after, intestinal mucosa visible obviously irregular ulcer point or the rotten to the corn point of engrain.Knot rectal ulcer (erosion) is counted and ulcer area Eubacterium ventriosum treatment group, the Eubacterium biforme treatment group, bigeminy viable bacteria treatment group and model control group, normal saline model control group or bacillus bifidus treatment group more all have very significant difference (P＜0.01), and the Eubacterium ventriosum treatment group, the Eubacterium biforme treatment group, there was no significant difference between the bigeminy viable bacteria treatment group (P＞0.05), the Eubacterium ventriosum treatment group, the Eubacterium biforme treatment group, passage of loose stools before bigeminy viable bacteria treatment group and the model control group treatment, be with once in a while blood, Eubacterium ventriosum treatment group after the treatment, the Eubacterium biforme treatment group, bigeminy viable bacteria treatment group is all arranged normally just, and model control group is passage of loose stools still.See Table 2.
The various bacterium of table 2 are to the repair of intestinal mucosa
Figure BSA00000744009900081
3 conclusions
Eubacterium ventriosum and Eubacterium biforme are owing to can secrete butanoic acid, the intestinal mucosa cells energy is provided, intestinal mucosa cells had good promotion proliferation function, the intestinal mucosa of energy repairing damage, change intestinal mucosal permeability, promote intestinal mucosa to reach maturity, facilitating digestion absorbs, the non-product butanoic acid probiotic bacteria such as bacillus bifidus that is better than evident in efficacy.Therefore, Eubacterium ventriosum and Eubacterium biforme can be treated the intestinal mucosal injury diseases such as diarrhoea, ulcerative colitis, Crohn disease, antibiotic-associated diarrhea, pseudomembranous enteritis, infantile pneumonia Secondary cases diarrhoea, tumor chemoradiotherapy auxiliary treatment, viral diarrhea, necrotizing enterocolitis alone or in combination, promote intestinal growth ripe, facilitating digestion absorbs, eliminate abdominal distention and dyspepsia and treatment feeding intolerance, enhancing development and nourishing healthy, the nutrient malabsorption disease also there is good therapeutical effect, comprises rickets.
Embodiment 2, Eubacterium ventriosum and Eubacterium biforme are regulated the research of immunity and inflammatory Cytokines Expression
1 experiment material and method
1.1 laboratory animal: male SD rat, 180-220g.
1.2 Experimental agents: mesalazine (200mg/mL); Eubacterium ventriosum bacterium liquid (10 7CFU/mL); Eubacterium biforme bacterium liquid (10 7CFU/mL); Bigeminy viable bacteria bacterium liquid (10 7CFU/mL); Bacillus bifidus bacterium liquid (10 7CFU/mL).Provided by Qingdao DongHai Pharmacy Co., Ltd.
1.3 experiment reagent: Freund's complete adjuvant (sigma), MTT (sigma); Concanavaline (ConA) (Sigma); Lipopolysaccharide (LPS) (Sigma); MTT (Sigma) is available from Beijing big chemical industry instrument of easypro uncle Co., Ltd; RPMI-1640 (Gibco); Cattle mucous membrane of colon protein freeze-dried powder (self-control); IL-8ELISA test kit (BD); TNF-α ELISA test kit (Ebioscience); Rat IgG reference serum; The Mus IgG of rabbit Chinese People's Anti-Japanese Military and Political College antiserum, outsourcing.
2 experimental techniques
2.1 the neonatal calf colon is got in the preparation of cattle mucous membrane of colon protein freeze-dried powder, scraping cattle mucous membrane of colon repeatedly freezes molten method and obtains cattle mucous membrane of colon albumen, and purification is concentrated, saves backup in 4 ℃ behind the vacuum freeze-drying.
2.2 cattle mucous membrane of colon albumen is got in the foundation of immunologic derangement disease model and complete Freund's adjuvant (1: 1) is made complete antigen, select body weight the SD of 200 ± 20g rat, the modeling rat is every interior injections of antigens 4mg of the sufficient sole of the foot first, in the 10th, 17,24,31 day respectively at the sufficient sole of the foot, back, groin, intraperitoneal injection antigen 6mg, last 1 injection does not add adjuvant, reaches necessarily to serum resistive connection intestinal antibody and tires.The 35th day model group rat amobarbital sodium intraperitoneal injection of anesthesia, and carry out respectively following processing (fasting 24h before processing), use first 2% formalin 1.5mL coloclysis, keep somewhere 1h, venting after cleaning with normal saline.Use again antigen liquid (4mg/mL does not add adjuvant) 2mL coloclysis, keep somewhere 2h, then clean venting.Behind the 3d, randomly draw 2 model group rats and put to death, get its colon specimen (upwards 10 centimetres in anus), pathologic finding confirms to have the pathological change of a series of inflammatory bowel such as hyperemia, edema, cell infiltration, ulcer.
2.3 Normal group (10) is established in animal grouping and treatment.After the modeling success, with modeling rat random packet, 1) model control group (10), give the normal saline gavage; 2) positive drug (mesalazine, 200mg/mL) treatment group (10); 3) Eubacterium ventriosum (10 7CFU/mL) treatment group (10); 4) Eubacterium biforme (10 7CFU/mL) treatment group (10); 5) the bigeminy viable bacteria (10 7CFU/mL) treatment group (10); 6) bacillus bifidus (10 7CFU/mL) treatment group (10).Each 1mL/100g body weight, 1 times/day, gavage is given normal saline or curative 21 days continuously.Claim weekly during this time body weight one time, and continue to observe animal ordinary circumstance and feces character.
2.4 index determining is to normal saline or medicine to the after 21 days, sacrificed by decapitation animal, rating model matched group and 5 indexs such as treatment group colon weight in wet base index, mucosal ulcer's index, mucosa injury index, mesentery lymhocyte transformation rate, IL-8, TNF-α and IgG.
2.4.1 colon weight in wet base index colon weight in wet base index=colon weight in wet base (g)/100g. body weight.
2.4.2 mucosal ulcer's index is with fresh colon intestinal tube longitudinal incision, remove intestinal contents, epimere in the colon and colon hypomere two parts are numbered respectively, be fixed on the hardboard, after fresh specimens is taken pictures, fixing in 10% formalin, with slice strand or linear hemorrhagic pathological changes on the kind of calliper mucous membrane of colon, measured with whole pathological changes total lengths.The calculating of ulcer index: focus length is 1 minute less than 1mm, and 1-2mm is two minutes, and 2-3mm is 3 minutes, and 3-4mm is 4 minutes, greater than 4mm, it is divided into some sections such as focus length, and every section by the score of upper method, and when focus width during greater than 2mm, its score doubles.The summation of each focus score of animal total colectomy is its ulcer index.
2.4.3 get the rat mesentery lymphocyte under the mesentery lymhocyte transformation rate gnotobasis, cross 200 order cells sieve, aseptic PBS washed twice, 1000rpm, 5min.Adjusting cell concentration with complete RPMI-1640 is 5 * 10 5Individual/mL, every hole 100 μ l are inoculated in the 96 hole circle floor cells plates, add simultaneously ConA (final concentration is 3 μ g/mL) or LPS (final concentration is 5 μ g/mL), 100 μ l/ holes.Other sets blank hole (not adding derivant), 37 ℃, 5%CO 2Hatch 72h, cultivate and finish front 4h, add MTT (5mg/ml) 20 μ l, after cultivation finishes, measure the 540nm place and measure the OD value, the calculating lymphocyte stimulation indices.The stimulating group OD value medicine of lymphocyte stimulation indices (SI)=stimulating group OD value/not.
2.4.4IL-8, TNF-α and IgG sacrificed by decapitation rat, get blood, 4 ℃ of hold over night, 3000rpm, 20min is centrifugal, gets supernatant, packing, be put in-20 ℃ to be measured.Use the ELISA test kit, to specifications, the content of rat IL-8 and TNF-α in the mensuration rat blood serum.Use simple immunodiffusion method to measure the content of I gG in the serum.
2.5 t-student ' t check is used in the significance,statistical check of the data difference between each group of statistical procedures, significance of difference boundary is p＜0.05.
3 experimental results
3.1 feces character, colon weight in wet base index
The model control group rat is arranged white mucus loose stool during moulding.The treatment group rat is also arranged white mucus loose stool before treatment, treat after 21 days and all arrange normally just.
Mesalazine treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, 21 days postcolon weight in wet base indexes of bigeminy viable bacteria treatment group treatment relatively are significance with model control group and bacillus bifidus treatment group and reduce (P＜0.05), but mesalazine treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group rat treatment postcolon weight in wet base index be there was no significant difference relatively, sees Table 3.
Table 3 immunologic derangement rat model colon weight in wet base index variation situation
Figure DEST_PATH_GSB00000996649600031
Figure BSA00000744009900102
3.2 mucosal ulcer's index (integration)
Mesalazine treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, the treatment of bigeminy viable bacteria treatment group after 21 days mucosal ulcer's index relatively be significance with model control group and bacillus bifidus treatment group and reduce (P＜0.05), but mucosal ulcer's index compares there was no significant difference after mesalazine treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, the treatment of bigeminy viable bacteria treatment group rat, sees Table 4.
Table 4 immunologic derangement rat model intestinal mucosa ulcer index situation of change
Figure DEST_PATH_GSB00000996649600041
Figure BSA00000744009900112
3.3 mesentery lymhocyte transformation rate
After setting up the success of immunologic derangement model, the bone-marrow-derived lymphocyte conversion ratio raises, the T lymhocyte transformation rate reduces, mesalazine treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, the treatment of bigeminy viable bacteria treatment group significantly reduced with model control group and bacillus bifidus treatment group comparison bone-marrow-derived lymphocyte conversion ratio after 21 days and the T lymhocyte transformation rate significantly raises (P＜0.05), but compare there was no significant difference (P＞0.05) between Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, the bigeminy viable bacteria treatment group, see Table 5.
Table 5 immunologic derangement rat model mesentery lymhocyte transformation rate situation of change
Figure DEST_PATH_GSB00000996649600043
Figure BSA00000744009900114
3.4 serum il-8 and TNF-alpha content
IL-8 in the model control group rat blood serum and TNF-alpha content are than the remarkable rising (P＜0.05) of Normal group, the mesalazine treatment group, the Eubacterium ventriosum treatment group, the Eubacterium biforme treatment group, bigeminy viable bacteria treatment group treatment after 21 days serum il-8 and TNF-alpha content relatively be significance reduction (P＜0.05) with model control group and bacillus bifidus treatment group, but Eubacterium ventriosum treatment group, the Eubacterium biforme treatment group, serum il-8 content and TNF-α compare there was no significant difference (P＞0.05) after the treatment of bigeminy viable bacteria treatment group rat, see Table 6.
Table 6 immunologic derangement rat model serum il-8 and TNF-alpha content situation of change
Figure DEST_PATH_GSB00000996649600051
Figure BSA00000744009900122
3.5 serum IgG content
IgG content in the model control group rat blood serum is than the remarkable rising (P＜0.05) of Normal group, mesalazine treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, the treatment of bigeminy viable bacteria treatment group after 21 days IgG content relatively be significance reduction (P＜0.05) with model control group and bacillus bifidus treatment group, but serum il-8 and TNF-alpha content compare there was no significant difference (P＞0.05) after Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, the treatment of bigeminy viable bacteria treatment group rat, see Table 7.
Table 7 immunologic derangement rat model serum IgG content situation of change
Figure DEST_PATH_GSB00000996649600053
Figure BSA00000744009900124
4 conclusions
The immunologic derangement that a variety of causes causes and inflammatory factor rising thereof can give rise to diseases, and make the enhancing of intestinal sensitivity, tolerance decline cause irritable bowel syndrome, cool and rush down, drink and rush down; Intestinal mucosal injury be can make, ulcerative colitis or Crohn disease caused; Autoimmune disease be can cause, rheumatoid arthritis, ankylosing spondylitis comprised; Inflammatory factor raises and can cause cardiovascular and cerebrovascular disease in the blood, comprise hyperlipemia, hypertension, cerebral thrombosis, cerebral embolism, cerebral ischemia, myocardial infarction, coronary heart disease, cerebral infarction, cerebral hemorrhage, angina pectoris, myocarditis, the struvite cytokines such as tumor necrosis factor (TNF-α), interleukin 8 (IL-8), interleukin-11 β (IL-1 β) have promoted generation and the development of atherosclerosis and cardiovascular and cerebrovascular disease, and the struvite cytokine levels such as TNF-α, the IL-8 in the Patients with Cardiovascular/Cerebrovascular Diseases serum, IL-1 β are apparently higher than Healthy People; Can cause allergic disease, comprise allergic skin disease, further comprise eczema.Originally studies show that Eubacterium ventriosum and Eubacterium biforme owing to can secrete butanoic acid, by regulating the expression of nuclear factor (NF-κ B), regulate immunologic balance, eliminate dysimmunity and suppress the inflammatory factor overexpressions such as TNF-α, IL-8, effectively treat the disease that above-mentioned various immunologic derangements and inflammatory factor thereof raise and cause, and effect is better than the non-product butanoic acid probiotic bacterias such as bacillus bifidus.
Embodiment 3, Eubacterium ventriosum and Eubacterium biforme promote the research of intestinal growth maturation
1 data and method
1.1 data is selected feeding intolerance children's 100 examples, diagnostic criteria: the performance of the gastrointestinal motility disorders such as clinical appearance vomiting, abdominal distention, gastric retention, in stomach tube, extract residual milk out before breast-feeding.All infants are all got rid of gastrointestinal tract congenital malformation, mechanical intestinal obstruction, anencephaly hepatic and kidney function obstacle and cardiac damage.Man's 60 examples, women 40 examples.By table of random number 100 routine children's are divided into five groups, A group (Eubacterium ventriosum treatment group), B group (Eubacterium biforme treatment group), C group (bigeminy viable bacteria treatment group), D organize (bacillus bifidus treatment group) and matched group.Every group of 20 routine infants, five groups of infant gestational ages, sex, body weight, severe extents are learned processing by statistics, and no significant difference ((P＞0.05)) has comparability.
1.2 all infants of method all give routine care, infusion pump fluid infusion, the conventional Comprehensive Treatments such as treatment protopathy and Parenteral nutrition.
The A group: give oral Eubacterium ventriosum viable bacteria powder (containing Eubacterium ventriosum is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional Comprehensive Treatment basis 7CFU/g) oral, 1 bag/time, 3 times/days, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
The B group: give oral Eubacterium biforme viable bacteria powder (containing Eubacterium biforme is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional Comprehensive Treatment basis 7CFU/g) oral, 1 bag/time, 3 times/days, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
The C group: give oral bigeminy viable bacteria powder (containing Eubacterium ventriosum and Eubacterium biforme total viable count is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional Comprehensive Treatment basis 7CFU/g) oral, 1 bag/time, 3 times/days, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
The D group: give Oral Bifidobacterium viable bacteria powder (containing bacillus bifidus is 1.0 * 10 for Qingdao DongHai Pharmacy Co., Ltd's production, 500mg/ bag on conventional Comprehensive Treatment basis 7CFU/g) oral, 1 bag/time, 3 times/days, the rear oral or nasal feeding of breast-feeding, the course for the treatment of is more than 7 days;
Matched group: conventional Comprehensive Treatment, the course for the treatment of is more than 7 days.
1.3 observation index is observed five groups of symptom variation such as abdominal distention, vomiting, gastric retention and borborygmus, physiological weight loss returns to the birth weight time, the milk amount increases situation and records the time that the intravenous nutrition of stopping using reaches complete enteral nutritional support, have or not jaundice complication and jaundice persistent period, and have no adverse reaction.
1.4 curative effect judging standard produce effects: treat 3～5 days abdominal distention, symptoms of emesis and disappear, borborygmus is normal, and nasal feeding is suckled every 2～3 hours 1 time, can tolerate, and stays without the gastric content storage; Take a turn for the better: treat 5～7 days abdominal distention, symptoms of emesis and alleviate, a little less than the borborygmus, nasal feeding is suckled every 2～3 hours 1 time, gastric content retention＜1/3; Invalid: treat 7 days abdominal distention, symptoms of emesis without improvement, a little less than the borborygmus, nasal feeding is suckled every 2～3 hours 1 time, and the gastric content storage stays＞and 1/3.Produce effects and improvement add up to effectively.
1.5 statistical procedures adopts SPSS11.0 software to carry out statistical procedures.Data all with
Figure BSA00000744009900141
X is relatively adopted in expression between group 2Check or t check have statistical significance take P＜0.05 as difference.
2 results
2.1 six groups of curative effects compare A group produce effects 15 examples, 5 examples that take a turn for the better, total effective rate 100%; B group produce effects 16 examples, 4 examples that take a turn for the better, total effective rate 100%; C group produce effects 14 examples, 6 examples that take a turn for the better, total effective rate 100%; D produce effects 10 examples, 2 examples that take a turn for the better, invalid 8 examples, total effective rate 60%; Matched group produce effects 5 examples, 4 examples that take a turn for the better, invalid 11 examples, total effective rate 45%.Learn by statistics check, A group, B group, C group total effective rate are significantly higher than D group and matched group, and difference has statistical significance (P＜0.01), total effective rate difference not statistically significant (P＞0.05) between A group, B group, the C group.
2.2 two groups of observation index relatively return to the birth weight time, reach the complete enteral nutritional support time, vomiting and abdominal distention extinction time, and the jaundice persistent period, A organizes, B organizes, the C group compares with D group and matched group, and difference has statistical significance (P＜0.05); Comparing difference not statistically significant (P＞0.05) between A group, B group, the C group sees Table 8.
Table 8 liang group treatment fore-and-aft observing index relatively
Figure DEST_PATH_GSB00000996649600061
Figure BSA00000744009900152
3 conclusions
Originally studies show that Eubacterium ventriosum and Eubacterium biforme owing to can secrete butanoic acid, the intestinal mucosa cells energy is provided, promotion intestinal mucosa propagation and intestinal growth are ripe, and the treatment feeding intolerance is evident in efficacy, and effectively treats vomiting, abdominal distention.Simultaneously, the secretion butanoic acid, the activity of reduction beta-glucuronidase enzyme stops conjugated bilirubin to be decomposed into unconjugated bilirubin competitively, reduces the liver sausage circulation; By producing butanoic acid, promote enterokinesia, promote defecation, increase bilirubinic discharge; Butanoic acid can promote to be decomposed into free cholic acid in conjunction with cholic acid in the intestinal, reduces in conjunction with the heavily absorption of cholic acid at intestinal wall, is conducive to eliminate cholestasis, therefore shortens the jaundice persistent period, effectively prevents and treat jaundice.Simultaneously, Eubacterium ventriosum and Eubacterium biforme secretion butanoic acid promote intestinal growth ripe, obviously shorten returning to the birth weight time and reaching the complete enteral nutritional support time, show and can absorb and growth promoter by facilitating digestion to have nutrition health-care functions.And the above-mentioned therapeutic effect of Eubacterium ventriosum and Eubacterium biforme significantly is better than the non-product butyrics such as bacillus bifidus.
Embodiment 4, Eubacterium ventriosum and Eubacterium biforme are to the preventive effect research of intestinal cancer
1 experimental technique
Selecting body weight is 100 of the female Kunming mouses of 18-20g, is divided at random Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group, bacillus bifidus treatment group and matched group (20 every group), and experimental period was 20 weeks.
Carcinogen is 1,2-Dimethylhydrazine (symmetrical 1,1-dimethylhydrazine, DMH), is white powdery crystallization, is made into 0.4% solution with physiological saline solution before facing injection at every turn, and uses NaHCO 3Its pH is transferred to 6.5.Weekly to mouse peritoneal injection DMH 20mg/kg (being 0.4%DMH solution 0.05ml/10g) once, continuous 20 weeks.After 1 week, add Dextran sodium sulfate (DSS) in lumbar injection DMH in the drinking-water, concentration is 20g/L, drinks continuously 7 days.
In the time of lumbar injection DMH, Eubacterium ventriosum bacterium liquid (10 7CFU/mL), Eubacterium biforme bacterium liquid (10 7CFU/mL), bigeminy viable bacteria bacterium liquid (10 7CFU/mL), bacillus bifidus bacterium liquid (10 7CFU/mL), 0.5mL/ time, 1 times/day, continuous 20 weeks.
Matched group, in the time of lumbar injection DMH, normal saline gavage, 0.5mL/ time, 1 times/day, continuous 20 weeks.
2 experimental results
After the 20th week that experiment finishes, after with ether mouse anesthesia being caused death, open the abdominal cavity, observe intestinal and change.The result shows 20 mices of matched group, and lesser tubercle appears in the large intestine intestinal wall, and the intestinal gauffer reduces or disappears, and the intestinal quality is hard, and 100% has generated the intestinal cancer; The bacillus bifidus treatment group has 14 mice large intestine intestinal wall lesser tubercle to occur, and the intestinal gauffer reduces or disappears, and the intestinal quality is hard, and 70% has generated the intestinal cancer; Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group all have 9 mice large intestine intestinal wall lesser tubercle to occur, and the intestinal gauffer reduces or disappears, and the intestinal quality is hard, and 45% has generated intestinal cancer, significantly is lower than matched group and bacillus bifidus treatment group.
3 conclusions
This experiment shows Eubacterium ventriosum and Eubacterium biforme owing to can secrete butanoic acid, and butanoic acid is a kind of deacetylase (HDAC) inhibitor, mainly changes chromatin Structure by the degree of acetylation that changes histone, regulation and control P 21Expression etc. several genes, the growth of termination colon-cancer cell, induce the ripe differentiation of colon-cancer cell, induce the colon-cancer cell apoptosis, can effectively prevent canceration, prevent intestinal cancer recurrence and diffusion transfer, the obviously canceration of prevention of ulcerative colitis, prevention rate has reached 55%, therefore can make relevant dosage form, be used for prevention intestinal cancer, be particularly useful for the intestinal chronic disease generation cancerations such as pre-anti-caking or rectal polyp, schistosomicide, bacillary dysentery, ameba, Crohn disease and ulcerative colitis, safeguard that the human intestine is healthy.Most of patients with bowel cancer is all died from postoperative recurrence and transfer, therefore Eubacterium ventriosum and Eubacterium biforme also can be used for the rear prevention of recurrence of intestinal cancer operation and transfer, take the healing that can promote wound after the operation simultaneously, harmful bacteria, antiinflammatory prevention infection can be suppressed, immunity of organisms can be improved.
The experimentation of embodiment 5, Eubacterium ventriosum and Eubacterium biforme treatment intestinal cancer
1 experimental technique
100 of BALB/c mouse, get the mouse junction cancer C26 tumor tissue that goes down to posterity under the animal skins, become suspension with normal saline by 1: 3 dilution proportion, it is subcutaneous only to be inoculated in mouse armpit by 0.2ml/, then mice is divided at random Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group, bacillus bifidus treatment group and model control group (20 every group).
Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group, bacillus bifidus treatment group are injected bacterium liquid (10 in inoculation respectively in tumor tissue after 72 hours, 144 hours 7CFU/mL) 0.1mL/ only.Injecting normal saline 0.1mL/ is only in tumor tissue after 72 hours, 144 hours in inoculation respectively for matched group.Test the gross tumor volume of measuring each treated animal on the 12nd day, observe tumour inhibiting rate.
2 experimental results
Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group tumor weigh and model control group and the relatively significance reduction (P＜0.05) of bacillus bifidus treatment group, but Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group be there was no significant difference (P＞0.05) relatively, sees Table 9.
The antitumaous effect research of table 9 Eubacterium ventriosum and Eubacterium biforme
Figure BSA00000744009900171
3 conclusions
This experiment shows that Eubacterium ventriosum and Eubacterium biforme owing to can secrete butanoic acid, have significant antitumaous effect, studies show that at present butanoic acid is a kind of anticarcinogen.Therefore, Eubacterium ventriosum and Eubacterium biforme can be treated or auxiliary treatment intestinal cancer and other cancers alone or in combination.
Embodiment 6, Eubacterium ventriosum and Eubacterium biforme are to the anti-diarrhea effect research of experimental diarrhea mice
1 materials and methods
BALB/C mice, male, body weight (20 ± 1) g, 2 grades of standards.Eubacterium ventriosum bacterium liquid (10 7CFU/mL); Eubacterium biforme bacterium liquid (10 7CFU/mL); Bigeminy viable bacteria bacterium liquid (10 7CFU/mL); Bacillus bifidus bacterium liquid (10 7CFU/mL).Provided by Qingdao DongHai Pharmacy Co., Ltd.
Mice is divided into Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group and bacillus bifidus treatment group and matched group (20 every group) at random, and single cage is raised.Sodium ampicillin (adding the normal saline preparation) 0.15g gavage is used in moulding animal fasting in front 1 day feedwater subsequently, and 0.5mL/ only 2 times/days, causes diarrhea of mouse, draining sample or mushy stool.Mice is used respectively bacterium liquid gavage, and 0.5mL/ time, 2 times/days, the blank group is to the equal-volume normal saline, for three days on end.Before the moulding and get fresh stool after the treatment and do the faecal microbiota analysis.
2 results
2.1 anti-diarrhea effect
The anti-diarrhea effect of Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group significantly is better than model control group and bacillus bifidus treatment group (P＜0.05), but Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group be there was no significant difference (P＞0.05) relatively, sees Table 10.
The anti-diarrhea effect research of table 10 Eubacterium ventriosum and Eubacterium biforme
Figure BSA00000744009900181
2.2 analysis of intestinal microflora
The result shows that Eubacterium ventriosum and Eubacterium biforme have significant proliferation (P＜0.05) to intestinal beneficial bacterium, and quick-recovery intestinal microbial population balance sees Table 11 soon.
Table 11 analysis of intestinal microflora (Log 10CFUg -1, n=10)
Figure BSA00000744009900182
3 conclusions
This experiment shows that Eubacterium ventriosum and Eubacterium biforme have significant therapeutic effect to diarrhoea, and effect is better than bacillus bifidus (P＜0.05).And can promote intestinal beneficial bacterium propagation, fast quick-recovery intestinal microbial population balance, proof is to antibiotic-associated diarrhea, pseudomembranous enteritis, infantile pneumonia Secondary cases diarrhoea, tumor chemoradiotherapy auxiliary treatment, constipation, just the alteration of intestinal flora disease such as smelly has good treatment and preventive effect, disclose simultaneously rush down cooling, drinking to rush down with irritable bowel syndrome also has remarkable therapeutical effect.
Embodiment 7, Eubacterium ventriosum and Eubacterium biforme are to the therapeutical effect research of Experimental Constipation Model mice
1 materials and methods
BALB/C mice, male, body weight (20 ± 1) g, 2 grades of standards.Eubacterium ventriosum bacterium liquid (10 7CFU/mL); Eubacterium biforme bacterium liquid (10 7CFU/mL); Bigeminy viable bacteria bacterium liquid (10 7CFU/mL).Provided by Qingdao DongHai Pharmacy Co., Ltd.
Mice is divided into Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group, model control group and Normal group (10 every group) at random, and single cage is raised.Except Normal group, all the other each assembly moldings animal fasting in front 1 day feedwater, the oral 50mg/Kg of giving R-1132 brings out constipation subsequently.Mice is used respectively bacterium liquid gavage, and 0.5mL/ time, 2 times/days, model control group and Normal group be to the equal-volume normal saline, and 2 times/days, for three days on end.
2 results
Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group significantly are better than model control group (P＜0.05) to the therapeutical effect of constipation, but Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group be there was no significant difference (P＞0.05) relatively, sees Table 12.
Table 12 Eubacterium ventriosum and Eubacterium biforme are to the therapeutical effect research of constipation
Figure BSA00000744009900191
3 conclusions
Because Eubacterium ventriosum and Eubacterium biforme enter intestinal and can secrete a large amount of butanoic acid, promote intestinal peristalsis promoting, and the fast quick-recovery intestinal microbial population balance of energy, improve intestinal microenvironment, recover the intestinal normal function, therefore effectively treat constipation and constipation-predominant of irritable bowel syndrome.
Embodiment 8, Eubacterium ventriosum and Eubacterium biforme are to the just smelly and just therapeutical effect of smelly poisoning syndrome
1 method
Use the HP-6890 gas chromatograph, in the situation of informed consent, measure indole and scatol content in 15 routine volunteer's feces.After namely getting fresh excreta 0.5g and accurately weighing, put in the 50mL triangular flask, add ethanol 20mL supersound extraction 20 minutes, filter, mark liquid (0.1%p-Isopropylphenol) 3mL is settled in the 25mL measuring bottle, during mensuration in adding, getting 4 μ l solution injection chromatographic column (HP-INNO WAX glass capillary column, 30m * 0.53mm, filling 17%Silicone SE-30) analyzes.Condition determination is column temperature: 200 ℃; 230 ℃ of injector temperatures, 260 ℃ of detector temperatures, carrier gas flux N 290mL/min; H 2Flow: 58mL/min; Air mass flow: 60mL/min.
15 routine volunteers, man 5, woman 10, age 25-55 year, (containing Eubacterium ventriosum is 1.0 * 10 for oral Eubacterium ventriosum viable bacteria powder, 500mg/ bag to be divided at random the Eubacterium ventriosum treatment group 7CFU/g), (contain Eubacterium biforme is 1.0 * 10 to the Eubacterium biforme treatment group for oral Eubacterium biforme viable bacteria powder, 500mg/ bag 7CFU/g), (contain total viable count is 1.0 * 10 to bigeminy viable bacteria treatment group for oral Eubacterium ventriosum Eubacterium biforme bigeminy viable bacteria powder, 500mg/ bag 7CFU/g), in identical normal diet situation, take respectively after meal each preparation, each 3 bags, one day 3 times, be used in conjunction 14 days.Before and after taking medicine, adopt the content that feces is measured indole and scatol, carry out statistical analysis.
2 results
Indole after the administration among the human excrement and urine and the content of scatol all obviously descend (P＜0.05), see Table 13.
Table 13 Eubacterium ventriosum and Eubacterium biforme are eliminated just smelly effect research
Figure BSA00000744009900201
3 conclusions
Eubacterium ventriosum and Eubacterium biforme can obviously reduce the enterotoxin content such as indole and scatol, effectively eliminate the just smelly just smelly poisoning syndrome that reaches, skin maintenance, and can alleviate burden of liver, can be used as the adjuvant therapy medicaments of liver and gall diseases.
Embodiment 9, Eubacterium ventriosum and Eubacterium biforme improve immunity research
1 materials and methods
BALB/C mice, male, body weight (20 ± 1) g, 2 grades of standards.Eubacterium ventriosum bacterium liquid (10 7CFU/mL); Eubacterium biforme bacterium liquid (10 7CFU/mL); Bigeminy viable bacteria bacterium liquid (10 7CFU/mL); Levamisole (50mg/Kg).Provided by Qingdao DongHai Pharmacy Co., Ltd.
Mice is divided into Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group, Levamisole in Treating group, model control group and Normal group (10 every group) at random, and single cage is raised.Except Normal group, adopt the modeling of subcutaneous injection 25mg/Kg hydrocortisone.Mice is used respectively bacterium liquid gavage, 0.5mL/ time, 2 times/days, the Levamisole in Treating group, 50mg/Kg, 2 times/days, model control group and Normal group be to the equal-volume normal saline, and 2 times/days, continuous 21 days.After the last administration, the india ink method detects carbon clearance index (K value) and the phagocytic index (α value) of Mus blood, investigates simultaneously the variation of Mus thymus index (g/10g.B.W).
2 results
Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group are compared with model control group with the Levamisole in Treating group, significantly improve immunity (P＜0.05), but Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group be there was no significant difference (P＞0.05) relatively, sees Table 14.
Table 14 Eubacterium ventriosum and Eubacterium biforme are on the impact of immunologic function
Figure BSA00000744009900211
3 conclusions
This experiment shows that Eubacterium ventriosum and Eubacterium biforme can significantly improve immunity, so tumor patient can be used Eubacterium ventriosum or Eubacterium biforme improves immunity, when especially chemicotherapy immunity reduces, as adjuvant therapy medicaments; Eubacterium ventriosum and Eubacterium biforme can be repaired intestinal mucosa, fast quick-recovery intestinal microbial population balance, and can improve the immunity antiviral, therefore can effectively treat viral diarrhea; Eubacterium ventriosum and Eubacterium biforme also have significant therapeutic effect to oral ulcer, thrush, hand-foot-mouth disease and recurrent respiratory tract infection, and can be used as the adjuvant therapy medicaments of liver and gall diseases by improving immunity.
Embodiment 10, Eubacterium ventriosum and Eubacterium biforme are studied the irritable bowel syndrome therapeutical effect
1 object and method
1.1 the object of observation selects 2006～2008 years medical Rome clear and definite irritable bowel syndrome (IBS) patients of II diagnostic criteria diagnosis by proposition in 1999 to be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group.
1.2 observe the improvement situation for the treatment of front and back symptom.
1.3 safety evaluatio
Conscientiously observing in the treatment may the untoward reaction relevant with curative, record time of origin, symptom and persistent period, result.
1.4 statistical analysis
Adopt the SAS statistical analysis software, data represent with percentage rate or mean ± standard deviation that respectively χ is used in the significance of difference test before and after the treatment 2Check and accurate probabilistic method, or t check, the significance level of difference is P＜0.05.
2 results
Each organizes equal 30 routine patients, and the those benefits in detail observed result is as follows:
2.1 oral Eubacterium ventriosum viable bacteria powder treatment 30 cases of irritable bowel syndrome observation of curative effect result
2.1.1 clinical data male 16 examples, women's 14 examples, 36.8 years old mean age, average course of disease 21.9 months.The IBS typing, suffering from diarrhoea is principal mode 13 examples, constipation is principal mode 14 examples, alternating diarrhea and constipation type 3 examples.
2.1.2 the oral Eubacterium ventriosum viable bacteria of medication powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g) provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days, 60 days courses for the treatment of.
2.1.3 observation of curative effect result
The symptoms such as the diarrhoea of the doing well,improving comparison 30 routine IBS patients before and after the irritable bowel syndrome patients treatment and constipation all are significantly improved after the treatment (P＜0.05), see Table 15.
Doing well,improving before and after the treatment of table 15 irritable bowel syndrome patients relatively
※ is with X 2 test or accurate probabilistic method
2.2 oral Eubacterium biforme viable bacteria powder treatment 30 cases of irritable bowel syndrome observation of curative effect result
2.2.1 clinical data male 17 examples, women's 13 examples, 40.2 years old mean age, average course of disease 19.5 months.The IBS typing, suffering from diarrhoea is principal mode 20 examples, constipation is principal mode 6 examples, alternating diarrhea and constipation type 4 examples.
2.2.2 the oral Eubacterium biforme viable bacteria of medication powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days, 60 days courses for the treatment of.
2.2.3 observation of curative effect result
Doing well,improving before and after the irritable bowel syndrome patients treatment compares, and the symptoms such as 30 routine IBS patients' diarrhoea and constipation all are significantly improved after the treatment (P＜0.05), see Table 16.
Doing well,improving before and after the treatment of table 16 irritable bowel syndrome patients relatively
Figure BSA00000744009900231
※ is with X 2 test or accurate probabilistic method
2.3 oral bigeminy viable bacteria powder treatment 30 cases of irritable bowel syndrome observation of curative effect result
2.3.1 clinical data male 18 examples, women's 12 examples, 35.6 years old mean age, average course of disease 26.2 months.The IBS typing, suffering from diarrhoea is principal mode 16 examples, constipation is principal mode 9 examples, alternating diarrhea and constipation type 5 examples.
2.3.2 the oral bigeminy viable bacteria of medication powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days, 60 days courses for the treatment of.
2.3.3 observation of curative effect result
Doing well,improving before and after the irritable bowel syndrome patients treatment compares, and the symptoms such as 30 routine IBS patients' diarrhoea and constipation all are significantly improved after the treatment (P＜0.05), see Table 17.
Doing well,improving before and after the treatment of table 17 irritable bowel syndrome patients relatively
Figure BSA00000744009900232
※ is with X 2 test or accurate probabilistic method
3 conclusions
Irritable bowel syndrome is one group and comprises that stomachache, abdominal discomfort, bowl evacuation habit change and the clinical syndrome of the performances such as character is unusual of defecating, the non-organic disease.Symptom or the above sx↑s such as the diarrhoea that cool, drinking property diarrhoea refers to suffer from cold, eat cool food or the rear appearance of drinking, stomachache, abdominal discomfort are diagnosed as diarrhea type irritable bowel syndrome clinically, belong to a kind of of diarrhea type irritable bowel syndrome.At present medical research shows that IBS (comprising cools rush down and drink rush down) is because intestinal immunity is disorderly, the inflammatory factor overexpression descends the intestinal tolerance, and sensitivity strengthens and causes.Eubacterium ventriosum and Eubacterium biforme are regulated immunologic balance owing to can secrete butanoic acid, and the overexpression of the inflammation-inhibiting factor strengthens the intestinal tolerance, reduces sensitivity, recovers the intestinal normal function, effectively treats IBS, cools to rush down and drink and rush down.
Embodiment 11, Eubacterium ventriosum and Eubacterium biforme are to the therapeutical effect research of oral ulcer
1 object and method
1.1 case-data is oral ulcer patient's 15 examples of recurrence often, male 10 examples, women 5 examples, 35 years old mean age.Ulcer recurrence history 2～13 years, the each patient is recurred more than 6 times every year on average.During the oral ulcer outbreak, be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 5 routine oral ulcer patients, the curative effect of observing the recurrence for the treatment of oral ulcer and preventing canker sore.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Be for 2 weeks the above course for the treatment of.
1.3 observational technique is established own control, observes the recurrence time for the treatment of front and back ulcer area, pain degree and taking 2 all oral cavities ulcer.
1.4 treatment oral ulcer efficacy assessment standard (Zhou Pingxiu, Meng Xiangyong. the clinical observation of drug combination treatment recurrent aphtha. Huabei Coal Medical Sciences College's journal, 2006,8:81-82)
Produce effects: ulcer healing or obviously dwindle in 3 days, pain disappears;
Effectively: ulcer healing or obviously dwindle and pain disappears in 5 days;
Invalid: ulcer healing or obviously dwindle all after 7 days.
1.5 prevention oral cavity recurrence evaluation criteria
Produce effects: oral ulcer outbreak, take 2 all medicines after, recurrence in 3 months.
Effectively: oral ulcer outbreak, take 2 all medicines after, recurrence in 2 months.
Invalid: oral ulcer outbreak, take 2 all medicines after, recurrence in 2 months.
2 results
2.1 all ulcer healing, pain disappearances in 5 days of all patients of therapeutic effect, three groups for the treatment of oral ulcer effective percentage are 100%.
, followed up a case by regular visits to 3 months after 2 weeks 2.2 all patients of preventing canker sore recurrence effect take medicine, oral ulcer is not recurrence all, and three groups of preventing canker sore recurrence effective percentage have all reached 100%.And do not find any side effect.
3 conclusions
Oral ulcer is one of modal disease of cari oris mucosa.Someone occurs once in a while, someone frequently shows effect, the somebody finally develops into the behcets disease syndrome and has caused mouth neoplasm from oral ulcer, and brainstrust is suffered from the oral squamous cell carcinomas sickness rate the patient of clinical middle discovery recurrent oral ulceration the trend that increases year by year.Although the Therapeutic Method to oral ulcer is a lot, but all be symptomatic treatment basically, purpose mainly eases the pain, be difficult to complete Control in recurring, traditional medicine thinks and wants to avoid its recurrence fully that probability is little, and medicinal usage of the present invention is by recovering the intestinal microbial population balance, strengthen the mucosal immunity function, treatment and the recurrence of control oral ulcer are become a reality.And by the oral medication oral ulcer, the medicine that has solved most for the treatment of oral ulcer is local application, the difficult problem of medication inconvenience, and without any side effect.
Embodiment 12, Eubacterium ventriosum and Eubacterium biforme treatment Crohn disease observation of curative effect
1 object and method
1.1 case-data is diagnosed as cd patient through inspections such as clinical, colonoscope, histology or x-ray barium meals, totally 15 examples, and male 9 examples, women 6 examples, all have the symptoms such as stomachache, diarrhoea at 35 years old mean age.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 5 routine patients.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3～4 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3～4 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3～4 times/days.
Be for 6～8 weeks the above course for the treatment of.
1.3 observational technique is established own control, observes the improvement situation of clinical symptoms such as treating front and back stomachache, diarrhoea and inflammation.
1.4 treatment Crohn disease efficacy assessment standard (digesting the suggestion to diagnosis status of inflammatory bowel disease and treatment standard that disease credit meeting is revised with reference to Chinese Medical Association in 2000)
Clinical remission: clinical symptom disappearance after treatment, x-ray or colonoscopy find that inflammation tends towards stability;
Effectively: clinical symptom relief after treatment, x-ray or colonoscopy find that inflammation alleviates;
Invalid: clinical symptoms, x-ray, scope and pathological examination results are without improvement after treatment.
2 results
After the treatment, 15 routine patient clinical symptoms and inflammation all have improvement in various degree.The Eubacterium ventriosum group has the clinical symptom disappearance such as 4 example stomachache, diarrhoea, has reached clinical remission; 1 routine stomachache, diarrhoea, inflammation alleviate, and treatment is effective, total effective rate 100%.The Eubacterium biforme group has the clinical symptom disappearance such as 3 example stomachache, diarrhoea, has reached clinical remission; 2 routine stomachache, diarrhoea, inflammation alleviate, and treatment is effective, total effective rate 100%.Bigeminy viable bacteria group has the clinical symptom disappearance such as 3 example stomachache, diarrhoea, has reached clinical remission; 2 routine stomachache, diarrhoea, inflammation alleviate, and treatment is effective, total effective rate 100%.Curative effect compares there was no significant difference (P＞0.05) between three groups
3 conclusions
Crohn disease is a kind of of inflammatory bowel, belong to the autoimmune disease that excessive immunoreation causes, the inflammatory factor overexpression, Eubacterium ventriosum and Eubacterium biforme are because can secretory immune regulator butanoic acid, the adjusting immune restoration is normal, the overexpression of the inflammation-inhibiting factor, and can repair intestinal mucosa, Crohn disease is had significant therapeutical effect, and without any toxic and side effects.
Embodiment 13, Eubacterium ventriosum and Eubacterium biforme treatment Theatment of ulcerative
1 object and method
1.1 case-data is diagnosed as patients of ulcerative colitis through inspections such as clinical, colonoscope, histology or x-ray barium meals, totally 30 examples, male 18 examples, women 12 examples, 27～65 years old, 46.4 years old mean age.The shortest 6 months of the course of disease, the longest 15 years, average 4 years.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 10 routine patients.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3～4 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3～4 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3～4 times/days.
Be for 8 weeks the above course for the treatment of.
1.3 observational technique is established own control, observes the improvement situation of clinical symptoms such as treating front and back stomachache, diarrhoea, Mucous Stool, hemafecia and intestinal mucosa.
1.4 treatment ulcerative colitis efficacy assessment standard (digesting the suggestion to diagnosis status of inflammatory bowel disease and treatment standard that disease credit meeting is revised with reference to Chinese Medical Association in 2000)
Alleviate fully: clinical symptom disappearance after treatment, colonoscopy find that mucosa is roughly normal;
Effectively: clinical symptoms disappears substantially after treatment, and colonoscopy finds that mucosa mild inflammation or pseudopolyp form;
Invalid: clinical symptoms, scope and pathological examination results are without improvement after treatment.
2 results
After the treatment, 30 routine patient clinical symptoms and inflammation all have improvement in various degree.The Eubacterium ventriosum group has the clinical symptom disappearance such as 6 example stomachache, diarrhoea, has reached and has alleviated fully; 4 routine stomachache, diarrhoea, inflammation alleviate, and treatment is effective, total effective rate 100%.The Eubacterium biforme group has the clinical symptom disappearance such as 5 example stomachache, diarrhoea, has reached and has alleviated fully; 5 routine stomachache, diarrhoea, inflammation alleviate, and treatment is effective, total effective rate 100%.Bigeminy viable bacteria group has the clinical symptom disappearance such as 7 example stomachache, diarrhoea, has reached and has alleviated fully; 3 routine stomachache, diarrhoea, inflammation alleviate, and treatment is effective, total effective rate 100%.Curative effect is not relatively found any untoward reaction in there was no significant difference (P＞0.05) the 2.3 untoward reaction therapeutic processes between three groups.
3 conclusions
Ulcerative colitis is a kind of of inflammatory bowel; pathological changes mainly is confined to intestinal mucosa; belong to the autoimmune disease that excessive immunoreation causes, the inflammatory factor overexpression makes intestinal mucosa ulcer occur; Eubacterium ventriosum and Eubacterium biforme are because can secretory immune regulator butanoic acid; it is normal to regulate immune restoration, the overexpression of the inflammation-inhibiting factor, and can repair intestinal mucosa; ulcerative colitis is had significant therapeutical effect, and without any toxic and side effects.
Embodiment 14, Eubacterium ventriosum and Eubacterium biforme treatment Rheumatoid Arthritis are observed
1 object and method
1.1 case-data
Be the patient of rheumatoid arthritis through clinical clarifying a diagnosis, totally 15 examples, 36 years old mean age, medical history was at 2 years～10 years.Clinical symptoms is: arthroncus, pain, morning are stiff or joint crepitus arranged.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 5 routine patients.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Be for 12～24 weeks the above course for the treatment of.
1.3 observational technique is established own control, observes arthroncus before and after the treatment, pain, morning deadlock or the improvement situation of joint crepitus.
1.4 efficacy assessment standard (by " diagnostic criteria of traditional Chinese medical science disease " of State Administration of Traditional Chinese Medicine's issue in 1994).
Recovery from illness: arthralgia swelling disappears, stiff elimination in morning;
Take a turn for the better: arthralgia swelling disappears, and it is stiff that idol has pain, morning to rise slightly to have;
Invalid: before arthralgia swelling, the stiff together treatment in morning.
2 results
Treat in 5 examples with oral Eubacterium ventriosum viable bacteria powder, 2 examples of fully recovering, 3 examples that take a turn for the better, invalid 0 example, total effective rate 100%, and have no any untoward reaction.
Treat in 5 examples with oral Eubacterium biforme viable bacteria powder, 1 example of fully recovering, 4 examples that take a turn for the better, invalid 0 example, total effective rate 100%, and have no any untoward reaction.
Treat in 5 examples with bigeminy viable bacteria powder, 4 examples of fully recovering, 1 example that takes a turn for the better, invalid 0 example, total effective rate 100%, and have no any untoward reaction.
3 conclusions
Rheumatoid arthritis belongs to autoimmune disease, the medicine for the treatment of rheumatoid arthritis is a lot of at present, but all there is the clinical application of various side effect restrictions, the side effect that has even can cause death, especially patient with rheumatoid arthritis need to be taken medicine for a long time, and patient is difficult to the tolerance side effect.Eubacterium ventriosum and Eubacterium biforme play a role by regulating immunity and the many aspects such as inflammatory Cytokines Expression, prevention infection, evident in efficacy, and without any toxic and side effects, patient can take for a long time, and Eubacterium ventriosum and Eubacterium biforme can also be made health product or beverage application for the treatment of rheumatoid arthritis except making the medicine.Embodiment 15, Eubacterium ventriosum and Eubacterium biforme treatment ankylosing spondylitis observation of curative effect
1 object and method
1.1 case-data
Be the patient of ankylosing spondylitis through clinical clarifying a diagnosis, totally 15 examples, 37 years old mean age, medical history was at 1 year～13 years.Clinical symptoms is: lumbar vertebrae pain, meet cold increasing the weight of, and spinal column is stiff, and pitching is unfavorable, or two hip pains, both legs limitation of activity, aversion to cold and cold limbs, weak hyperhidrosis are arranged.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 5 routine patients.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 2 times/days.
Be for 12～24 weeks the above course for the treatment of.
1.3 observational technique is established own control, observes the improvement situation of the clinical symptoms such as treatment front and back lumbar vertebrae pain, two hip pain.
1.4 the criterion of therapeutical effect that efficacy assessment standard is discussed revision in August, 1987 according to national combination of Chinese and Western medicine rheumatism Professional Committee of research association is formulated.
Significantly take a turn for the better: the position pain of getting involved after treatment disappears, and movable function improves or recovers normal, and it is normal that erythrocyte sedimentation rate recovers, and x-ray shows that bone lesion is improved or without development, recovers daily work;
Take a turn for the better: the position pain relief of getting involved, range of activity increases, and erythrocyte sedimentation rate reduces;
Invalid: through treating more than 3 courses for the treatment of (90 days), the position symptom of getting involved is without improvement.
2 results
Treat in 5 examples with oral Eubacterium ventriosum viable bacteria powder, 3 examples that significantly take a turn for the better, 2 examples that take a turn for the better, invalid 0 example, total effective rate 100%, and have no any untoward reaction.
Treat in 5 examples with oral Eubacterium biforme viable bacteria powder, 3 examples that significantly take a turn for the better, 2 examples that take a turn for the better, invalid 0 example, total effective rate 100%, and have no any untoward reaction.
Treat in 5 examples with oral bigeminy viable bacteria powder, 1 example that significantly takes a turn for the better, 4 examples that take a turn for the better, invalid 0 example, total effective rate 100%, and have no any untoward reaction.
3 conclusions
The ankylosing spondylitis course of disease is long, the state of an illness is heavy, need to take medicine for a long time, there is no the way of radical cure, treats at present main relief of symptoms, keeps good posture and slows down disease progression.Though at present medicine is a lot, all there is the clinical application of various side effect restrictions, the side effect that has even can cause death, therefore good effect and the medicine of being free from side effects are clinical needing most at present.Thinking that at present ankylosing spondylitis is due to inherited genetic factors and intestinal factors interact, is that the factors such as intestinal infection and intestinal mucosal permeability increase cause that on the basis of inherited genetic factors dysimmunity brings out ankylosing spondylitis and make disease progression.Eubacterium ventriosum and Eubacterium biforme are regulated the normal and downward modulation inflammatory Cytokines Expression of immune restoration, relief of symptoms on the one hand; On the other hand, the secretion butanoic acid is repaired intestinal mucosa, changes intestinal mucosal permeability, recovers intestinal health, eliminates the risk factor of ankylosing spondylitis and disease progression.Evident in efficacy, and without any toxic and side effects, patient can take for a long time, and Eubacterium ventriosum and Eubacterium biforme can also be made health product or beverage application for the treatment of ankylosing spondylitis except making the medicine.
Embodiment 16, Eubacterium ventriosum and Eubacterium biforme treatment and prevention hand-foot-mouth disease observation of curative effect
1 object and method
1.1 clarifying a diagnosis by the hand-foot-mouth disease diagnostic criteria, case-data is 30 routine patients of hand-foot-mouth disease, male 25 examples, women 15 examples, 1.6 one full year of life of mean age, maximum 3 one full year of life.Case is all generated heat, 37.5～40 ℃.Hand-foot-mouth disease all has the grain of rice to the circle of Semen phaseoli radiati size, oval-shaped herpes.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 10 routine patients observe Eubacterium ventriosum and Eubacterium biforme to the therapeutic effect of hand-foot-mouth disease.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Be 7 days the above course for the treatment of.
1.3 observational technique is established own control, observes treatment front and back body temperature, erythra and diet situation.
1.4 treatment hand-foot-mouth disease efficacy assessment standard (Liu Suqin. the curative effect of Therapeutic effect of ganciclovir Children. Applied Clinical Pediatrics magazine, 2006,21 (24): 1731-1732)
Produce effects: body temperature is normal, and erythra disappears substantially, and diet is normal;
Take a turn for the better: temperature decline, erythra partly disappears, and can take food on a small quantity;
Invalid: body temperature, erythra or diet are without improvement.
Produce effects reaches and transfers to effectively, observes simultaneously untoward reaction.
2 results
2.1 therapeutic effect
The Eubacterium ventriosum group, produce effects 6 examples, 4 examples that take a turn for the better, total effective rate 100%.
The Eubacterium biforme group, produce effects 5 examples, 5 examples that take a turn for the better, total effective rate 100%.
Bigeminy viable bacteria group, produce effects 7 examples, 3 examples that take a turn for the better, total effective rate 100%.
Total effective rate no difference of science of statistics (P＞0.05) between each group
2.2 the untoward reaction clinical observation has no any untoward reaction.
3 conclusions
Because the multiple infant of being born in of hand-foot-mouth disease, this and infant intestinal mucosa undeveloped mature, permeability is high, intestinal microbial population barrier also imperfection and immunity is low etc. relevant, Eubacterium ventriosum and Eubacterium biforme enter intestinal can secrete a large amount of butanoic acid, repair intestinal mucosa, promote intestinal mucosa to reach maturity, the intestinal microbial population barrier of while Erecting and improving and raising body, mucosal immunity, evident in efficacy aspect treatment and prevention infection hand-foot-mouth disease, this selects case all is infant, but it is effective equally to predict above child or adult's hand-foot-mouth disease of 3 one full year of life for the treatment of, and needed dosage is that the clinician can be easy to grasp according to the state of an illness and age.Simultaneously, clinical efficacy and the mechanism of action according to Eubacterium ventriosum and Eubacterium biforme, in the time of can being easy to predict the hand-foot-mouth disease outbreak of epidemic, oral Eubacterium ventriosum and Eubacterium biforme preparation can the prevention infection hand-foot-mouth disease, reduce the sickness rate of hand-foot-mouth disease.
Embodiment 17, Eubacterium ventriosum and Eubacterium biforme treatment pseudomembranous enteritis observation of curative effect
1 object and method
1.1 clarifying a diagnosis by the pseudomembranous enteritis diagnostic criteria, case-data is 15 routine patients of pseudomembranous enteritis, male 10 examples, women 5 examples, 38 one full year of life of mean age.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group, every group of 5 routine patients observe Eubacterium ventriosum and Eubacterium biforme to the therapeutic effect of pseudomembranous enteritis.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
15 days above courses for the treatment of.
1.3 observational technique is established own control, observes treatment front and back diarrhoea, intestinal mucosa reparation, pathogenic bacteria disappearance situation.
2 results
2.1 after treatment in 15 days, 15 routine patients all cure, transference cure is just examined clostridium difficile and is turned out cloudy, enteroscopy mucosa foci disappearance.
2.2 the untoward reaction clinical observation has no any untoward reaction.
3 conclusions
Pseudomembranous enteritis is owing to behind a large amount of use antimicrobial drug, cause alteration of intestinal flora, causes intestinal mucosal injury after the merging C. difficile infection, causes pseudomembrane.Eubacterium ventriosum of the present invention and Eubacterium biforme owing to can secrete a large amount of butanoic acid, are repaired injured intestinal mucosa, and suppress harmful bacteria, promote the probiotics growth, fast quick-recovery intestinal microbial population balance, and can improve immunity, therefore pseudomembranous enteritis is had significant therapeutical effect.
Embodiment 18, Eubacterium ventriosum and Eubacterium biforme are to thrush therapeutical effect observation of curative effect
1 object and method
1.1 clarifying a diagnosis by the thrush diagnostic criteria, case-data is 40 routine patients of thrush, male 30 examples, women 10 examples, 1.5 one full year of life of mean age.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group and matched group, every group of 10 routine patients observe Eubacterium ventriosum and Eubacterium biforme to the therapeutic effect of thrush.
1.2 medication
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Matched group gives partial smearing 10～200,000 U/mL nystatin-oleum morrhuae suspensions, 2 times/days.
Be 15 days the above course for the treatment of.
1.3 efficacy determination: transference cure, the oral cavity tunica albuginea disappears, and it is normal that mucosa recovers.
2 each treatment group and matched group there was no significant differences (P＞0.05) relatively as a result see Table 18.
Table 18 thrush curative effect relatively
Figure BSA00000744009900321
3 conclusions
Thrush is by the oral mucosa inflammation due to the Candida albicans.Candida albicans can be parasitic at the Healthy People digestive tract, when diarrhoea, can make the normal flora imbalance when using wide spectrum antibiosis rope or hormone, malnutrition and immunity of organisms to descend and fall ill, Eubacterium ventriosum of the present invention and Eubacterium biforme have significant therapeutical effect owing to can improve immunity, recovery colony balance, promotion absorption of nutrient ingredients and antiinflammatory to thrush.
Embodiment 19, Eubacterium ventriosum and Eubacterium biforme are to the therapeutical effect observation of curative effect of eczema
1 object and method
1.1 clarifying a diagnosis by the eczema diagnostic criteria, case-data is 40 routine patients of eczema, male 25 examples, women 15 examples, 1.5 one full year of life of mean age.Be randomized into oral Eubacterium ventriosum viable bacteria powder treatment group, oral Eubacterium biforme viable bacteria powder treatment group, oral bigeminy viable bacteria powder treatment group and matched group, every group of 10 routine patients observe Eubacterium ventriosum and Eubacterium biforme to the therapeutic effect of eczema.
1.2 medication
Matched group is coated with the affected part with carbamide ointment, and every day 3 times, 10 days is a course for the treatment of.Treatment group adds usefulness on the basis of matched group:
Oral Eubacterium ventriosum viable bacteria powder, the 500mg/ bag (contains the Eubacterium ventriosum viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral Eubacterium biforme viable bacteria powder, the 500mg/ bag (contains the Eubacterium biforme viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Oral bigeminy viable bacteria powder, the 500mg/ bag (contains total viable count and is not less than 1.0 * 10 7CFU/g), provided by Qingdao DongHai Pharmacy Co., Ltd.3 bags/time, 3 times/days.
Be 10 days the above course for the treatment of.
1.3 efficacy determination: produce effects: erythra is cured in the medication 10 days; Effectively: the erythra major part disappears in the medication 10 days; Invalid: 10 days erythra of medication do not disappear or increase.
2 results
Treatment group and matched group are relatively learned by statistics and are processed, and there is significant difference P＜0.05, illustrate that Eubacterium ventriosum of the present invention and Eubacterium biforme treatment eczema is effective, see Table 19.
Table 19 Eubacterium ventriosum and Eubacterium biforme treatment eczema curative effect are relatively
Figure BSA00000744009900331
3 conclusions
Eczema belongs to allergic disease, is the immunologic derangement that alteration of intestinal flora causes, the skin injury that causes.Eubacterium ventriosum of the present invention and Eubacterium biforme are regulated immunologic balance, and can be recovered the intestinal microbial population balance owing to can secrete butanoic acid, and allergic disease is had good therapeutical effect, especially to allergic skin disease, comprise that eczema is evident in efficacy.
Embodiment 20, Eubacterium ventriosum and Eubacterium biforme are to the regulating action research of atherosclerosis (AS) the rat cell factor and blood fat
1 materials and methods
1.1 the male Sprague-Dawley of laboratory animal, medicine and reagent (SD) rat, 180-220g.Eubacterium ventriosum bacterium liquid (10 7CFU/mL); Eubacterium biforme bacterium liquid (10 7CFU/mL); Bigeminy viable bacteria bacterium liquid (10 7CFU/mL); Bacillus bifidus bacterium liquid (10 7CFU/mL), produced by Qingdao DongHai Pharmacy Co., Ltd.Rat TNF-α, IL-1 β, IL-10ELISA test kit.
1.2 rat AS model set up rat at the lumbar injection vitamin D 3(behind 600,000 units/Kg), give high lipid food (3% cholesterol, 0.5% sodium cholate, 0.2% propylthiouracil, 5% white sugar, 10% Adeps Sus domestica, 81.3% basic feedstuff) and fed for 8 weeks, can form typical AS pathological changes.
1.3 grouping and medication are divided into 6 groups at random with rat, i.e. Normal group, model control group, bacillus bifidus treatment group, Eubacterium ventriosum treatment group, Eubacterium biforme treatment group, bigeminy viable bacteria treatment group, 6 every group.Except Normal group feed normal feedstuff, all the other each groups are all at the lumbar injection vitamin D 3After give high lipid food, simultaneously medication therapy groups gives bacterium liquid gavage, each 1mL/100g (body weight), 1 times/day.Normal group and model control group give the water with volume.After 8 weeks, the lumbar injection chloral hydrate anesthesia is got aortic blood and is carried out index determining.
1.4 index determining
1.4.1TNF-the ratio that α, IL-1 β, IL-10 measure in the 4mL/g tissue adds normal saline, uses glass homogenizer homogenate, draws supernatant behind the centrifugal 10min of homogenate 3000r/min, adopts the ELISA method to measure, and is undertaken by the test kit explanation.
1.4.2 measure according to a conventional method the serum lipids parameter, comprising: T-CHOL (TC), triglyceride (TG) and HDL-C (HDL-C).
2 results
2.1TNF-α, IL-1 β, IL-10 and Normal group are relatively, all significantly risings (P＜0.01) of TNF-α, IL-1 β, IL-10 level in the model control group tremulous pulse; Eubacterium ventriosum of the present invention and Eubacterium biforme can significantly reduce TNF-α in the tremulous pulse, IL-1 β level, significantly increase IL-10 level (P＜0.01), and effect is better than bacillus bifidus (P＜0.05) and sees Table 20.
Table 20 Eubacterium ventriosum and Eubacterium biforme are on the impact of AS rat TNF-α, IL-1 β, IL-10
Figure DEST_PATH_GSB00000996649600161
Figure BSA00000744009900342
2.2 serum lipids parameter model matched group TC, TG are significantly higher than Normal group (P＜0.05), model control group HDL-C significantly is lower than Normal group (P＜0.05); Compare TC, TG with model control group after the treatment of Eubacterium ventriosum of the present invention and Eubacterium biforme and significantly reduce (P＜0.05), HDL-C significantly raises (P＜0.05), and effect is better than bacillus bifidus (P＜0.05), sees Table 21.
Table 21 Eubacterium ventriosum and Eubacterium biforme are on the impact of AS rat TC, TG, HDL-C
Figure DEST_PATH_GSB00000996649600171
Figure BSA00000744009900352
3 conclusions
Atherosclerosis (AS) is the main pathological basis of cardiovascular and cerebrovascular disease morbidity, and hyperlipidemia is atherosclerotic main inducing.AS is similar to other diseases associated with inflammation such as rheumatoid arthritis, psoriasis, asthma and inflammatory bowel disease, unusual with inflammatory and immune response, the struvite cytokine overexpressions such as TNF-α, IL-8, IL-1 β, accelerate generation and the development of AS, and then accelerated generation and the development of cardiovascular and cerebrovascular disease.
Studies show that the struvite cytokine levels such as Patients with Cardiovascular/Cerebrovascular Diseases TNF-α, IL-1 β such as hyperlipemia, hypertension, cerebral thrombosis, cerebral embolism, cerebral ischemia, myocardial infarction, coronary heart disease, cerebral infarction, cerebral hemorrhage, angina pectoris, myocarditis all significantly raise.TNF-α as an apoptotic intracellular signal can the induction of vascular endothelial apoptosis, promote the generation of endothelin level (ET-1) and increase the weight of the damage of blood vessel wall, and the effect of promotion interleukin 6 (IL-6) secretion is arranged, also can control the liposoluble enzymatic activity, suppress lipoprotein lipase (LPL) activity, suppress the generation of the local LPL of speckle, thereby be unfavorable for the lipid dissolving, and be easy to be deposited on blood vessel wall, promote arteriosclerosis to form, cause the generation of various cardiovascular and cerebrovascular diseases.TNF-α can bring out myocarditis, lowers cardiac function and causes myocardium cell necrosis by necrosis or apoptosis, causes angina pectoris and arrhythmia etc.The positive detection rate of Patients with Cardiovascular/Cerebrovascular Diseases IL-1 β is along with the also corresponding rising of rising of TNF-α verification and measurement ratio, two kinds of cytokines of TNF-α, IL-1 β are by reciprocal induction, interaction, jointly participate in the pathophysiological process of the cardiovascular and cerebrovascular diseases such as hyperlipemia, hypertension, cerebral thrombosis, cerebral embolism, cerebral ischemia, myocardial infarction, coronary heart disease, cerebral infarction, cerebral hemorrhage, angina pectoris, myocarditis, thereby caused generation and the development of cardiovascular and cerebrovascular disease.
IL-10 is a kind of anti-inflammatory cytokines with strong immunoregulation effect, brings into play protective effect in cardiovascular and cerebrovascular disease.Eubacterium ventriosum of the present invention and Eubacterium biforme are by the secretion butanoic acid; can make unusual cytokine-expressing recover normal or improve; to stoping struvite cytokine that the infringement of cardiovascular and cerebrovascular vessel and cell is played a good role, can effectively prevent, treat cardiovascular and cerebrovascular disease.
Blood fat mainly refers to cholesterol and the triglyceride in the serum.No matter be that cholesterol level increases, or the increased content of triglyceride, or both all increase, and are referred to as hyperlipemia.Hyperlipemia is the key factor that atherosclerosis, cardiovascular and cerebrovascular disease and microcirculation disturbance occur.Clinical data shows that the incidence rate of cardiovascular and cerebrovascular disease increases with the concentration rising of serum cholesterol and triglyceride.It is the apodeictic fact that blood fat reducing can obviously reduce coronary heart disease danger, and serum cholesterol reduces by 1%, and risk of coronary heart disease reduces by 2%.Therefore, the early discovery of hyperlipemia and active treatment have very important meaning to the control of cardiovascular and cerebrovascular disease.One of function of high density lipoprotein (HDL) is that transportation endogenous cholesterol to liver is processed, so study of anti-atherogenic effect is arranged.In inspection, indirectly reflect the level of HDL by the content that checks HDL-C.HDL-C reduces during atherosclerosis, shows that HDL reduces.Eubacterium ventriosum of the present invention and Eubacterium biforme reach the effect of blood fat reducing by reducing TC, TG and rising HDL, and can reduce the struvite cytokine overexpressions such as TNF-α, IL-1 β, thereby effectively prevent and treat atherosclerosis, cardiovascular and cerebrovascular disease and microcirculation disturbance.
The present invention in implementation process employed microorganism fungus kind respectively at 2008 04 year 25 days in (Datun Road, Chaoyang District, Beijing City, China Committee for Culture Collection of Microorganisms common micro-organisms center, Institute of Microorganism, Academia Sinica's postcode 100101) preservation, totally two following microorganism fungus kinds, but Eubacterium ventriosum of the present invention and Eubacterium biforme are not limited to this two kinds of microbial strains.
(1) Classification And Nomenclature: Eubacterium ventriosum Eubacterium ventriosum, preserve numbering CGMCC No.2465.
(2) Classification And Nomenclature: Eubacterium biforme Eubacterium biforme, preserve numbering CGMCC No.2466.
Above-mentioned two microorganism fungus kinds are through this microorganism Spot detection, and testing result is survival.

Claims (11)

1. a novel microbial ecological agent is characterized in that this microbial ecological agent is to make preparation with Eubacterium biforme as active ingredient.
2. by the described microbial ecological agent of claim 1, it is characterized in that the Eubacterium biforme of effective dose is made composite medicine, health product, beverage, veterinary drug and feed additive as active ingredient.
3. by the described application of claim 1, it is characterized in that Eubacterium biforme refers to the bion that lives.
4. by the described application of claim 1, it is characterized in that Eubacterium biforme QE-01 deposit number CGMCC2466.
5. by the described microbial ecological agent of claim 1, it is characterized in that the application in preparation treatment digestive system disease, nutrient malabsorption disease, autoimmune disease, cardiovascular and cerebrovascular disease, allergic disease, raising immunity, anticancer, hand-foot-mouth disease compositions.
6. by the described application of claim 5, it is characterized in that digestive system disease comprises diarrhoea, irritable bowel syndrome, cool and rush down, drink and rush down, ulcerative colitis, Crohn disease, antibiotic-associated diarrhea, pseudomembranous enteritis, infantile pneumonia Secondary cases diarrhoea, intestinal cancer, the tumor chemoradiotherapy auxiliary treatment, abdominal distention and dyspepsia, constipation, just smelly, just smelly poisoning syndrome, skin maintenance, liver and gall diseases, viral diarrhea, feeding intolerance, necrotizing enterocolitis, jaundice, oral ulcer, thrush, promote children intestinal to reach maturity, facilitating digestion absorbs, nourishing healthy and growth promoter.
7. by the described application of claim 5, it is characterized in that the nutrient malabsorption disease comprises rickets.
8. by the described application of claim 5, it is characterized in that autoimmune disease comprises rheumatoid arthritis, ankylosing spondylitis.
9. by the described application of claim 5, it is characterized in that cardiovascular and cerebrovascular disease comprises hyperlipemia, hypertension, cerebral thrombosis, cerebral embolism, cerebral ischemia, myocardial infarction, coronary heart disease, cerebral infarction, cerebral hemorrhage, angina pectoris, myocarditis, atherosclerosis.
10. by the described application of claim 5, it is characterized in that allergic disease comprises allergic skin disease, further comprise eczema.
11. by the described application of claim 5, it is characterized in that improving immunity and comprise the treatment recurrent respiratory tract infection.
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