CN107028985A - Application of the heavy wall mushroom probiotics in preventing and/or treating diabetes and its relevant disease - Google Patents
Application of the heavy wall mushroom probiotics in preventing and/or treating diabetes and its relevant disease Download PDFInfo
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- CN107028985A CN107028985A CN201610080172.3A CN201610080172A CN107028985A CN 107028985 A CN107028985 A CN 107028985A CN 201610080172 A CN201610080172 A CN 201610080172A CN 107028985 A CN107028985 A CN 107028985A
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- 235000011803 sesame oil Nutrition 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
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- 229960002622 triacetin Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/113—Acidophilus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention discloses a kind of application of heavy wall mushroom probiotics in prevention and treatment diabetes and its relevant disease, specifically, the heavy wall mushroom probiotics of the present invention is used to prepare composition or preparation, and the composition or preparation are used for the one or more purposes being selected from the group：(a) prevent and/or treat diabetes；(b) prevent and/or treat angiocardiopathy；And/or (c) prevention and/or treatment obesity.The heavy wall mushroom probiotics of the present invention can significantly inhibit increased weight, reduction serum level of glucose, reduction blood lipid level, improvement insulin resistance and/or reduction glycated hemoglobin levels, effectively mitigate diabetes and its illness of relevant disease.
Description
Technical field
The invention belongs to microbiological art, in particular it relates to heavy wall mushroom probiotics prevention and/
Or treatment diabetes and its relevant disease in application, be directed to comprising heavy wall mushroom probiotics composition and its
Using.
Background technology
There are a large amount of symbiotic microorganisms in human body, they are largely resided in the enteron aisle of people, and quantity exceedes
1000000000000000 (1014The order of magnitude), it is more than 10 times of human body cell sum.In very long evolutionary process, intestines
Road microorganism and the mankind have reached good cooperation, nutrition, metabolism to human body and immune all play to closing weight
The effect wanted, many researchers are more " the devices that human body intestinal canal microbiologic population is regarded as to human body
Official ", or the genome of human body second, wherein the magnanimity hereditary information and human health that contain are closely related.
By to diabetes, coronary heart disease, diabetes, colon cancer, etc. hundreds of nearly ten thousand kinds of samples of disease research send out
Existing, some specific species show significant association with disease, these results disease clinical evaluation and
The therapeutic intervention in diagnosis and later stage provides a brand-new direction.
Diabetes have become the 3rd serious people health of threatening after tumour, cardiovascular and cerebrovascular diseases in the world
Chronic disease.Meanwhile, it will have a strong impact on the cardiovascular and cerebrovascular and kidney of people.With economic fast-developing and life
The continuous improvement of mode living, the incidence of disease of the metabolic disease such as diabetes of China steeply rises, it has also become shadow
Ring the chief threat of human health.IDF's latest data shows, diabetes patient's incidence of disease 1994
Year is 2.5%, and 2002 growths were 5.5%, by 2008 up to 9.7%.At present, Chinese diabetes morbidity has been
Through suitable with the economically developed U.S., the incidence of disease of big city diabetes has reached 9-10%.2005,
Pointed out in the report of World Health Organization's issue, from 2005 to 2015, due to heart disease, apoplexy and sugar
Urine disease causes premature death and is about 3.9 trillion RMB by the national income of loss.Therefore, research causes
Diabetes Etiological, and set up onset diabetes in intervening measure that is strong and easily promoting, containment crowd
The ascendant trend of rate, it has also become problem in science urgently to be resolved hurrily in Chinese biomedical, alimentary field.
In the crowd with diabetes, 90% above is type ii diabetes.Type ii diabetes be due to blood glucose from
Dysequilibrium and the chronic synthetic disease for showing hyperglycemic symptoms, carbohydrate and fat in pathogenic process
Metabolic disorder, influences the normal physiological activity of each organ-tissue of whole body.The pathology origin cause of formation of type ii diabetes is more
Sample, it is considered that be due to that inborn inherent cause and posteriori environmental factor are coefficient.For this
The research of a little aspects has a lot, but can not all explain generation and the pathogenesis of type ii diabetes well.
Current this area is also without a kind of effective, prevention of Small side effects and/or treatment diabetes and its correlation
The method and medicine of disease.
Therefore this area in the urgent need to develop it is a kind of it is new, have no toxic side effect, for preventing and/or treating
The medicine of diabetes and its relevant disease.
The content of the invention
Preventing it is an object of the present invention to provide heavy wall mushroom probiotics and/or treating diabetes and its phase
Purposes in terms of related disorders.
Effectively had no toxic side effect it is a further object of the present invention to provide a kind of, for preventing and/or treat
Medicine, beverage, the food compositions of diabetes and its relevant disease, or animal feed composition.
It is a further object of the present invention to provide one kind reduction serum glucose, blood fat and/or glycosylated hemoglobin water
Flat method and its application.
First aspect present invention provides a kind of purposes of heavy wall mushroom probiotics (Firmicutes), for making
Standby composition or preparation, the composition or preparation are used for the one or more purposes being selected from the group：(a) it is pre-
Anti- and/or treatment diabetes；(b) prevent and/or treat angiocardiopathy；And/or (c) prevention and/or treatment
Obesity, wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus oris),
Megasphaera elsdenii (Megasphaera elsdenii) or its combination.
In another preference, the heavy wall mushroom probiotics includes Lactobacillus oris (Lactobacillus oris).
In another preference, the Lactobacillus oris (Lactobacillus oris) is selected from the group：Lactobacillus
Oris DSM 4864, Lactobacillus oris DSM 4865, Lactobacillus oris DSM 4866 or
It is combined.
In another preference, the heavy wall mushroom probiotics includes Megasphaera elsdenii (Megasphaera
elsdenii)。
In another preference, the Megasphaera elsdenii (Megasphaera elsdenii) is selected from the group：
Megasphaera elsdenii DSM 20460、Megasphaera elsdenii ATCC 17752、
Megasphaera elsdenii ATCC 17753 or its combination.
In another preference, described heavy wall mushroom probiotics includes the one or more in table 3.
In another preference, described heavy wall mushroom probiotics is selected from table 3, and from identical or different category.
In another preference, the composition is selected from the group：Food compositions, health composition, medicine group
Compound, beverage composition for treating dental erosion, fodder compound or its combination.
In another preference, described composition is oral formulations.
In another preference, described composition is liquid formulation, solid formulation, semisolid preparations.
In another preference, the formulation of described composition is selected from the group：Powder agent, powder, tablet,
Sugar-coat agent, capsule, granule, suspending agent, solution, syrup, drops and sublingual lozenge.
In another preference, described food compositions include latex product, solution product, pulverulent product,
Or suspension product.
In another preference, described food compositions include dairy products, milk powder or emulsion.
In another preference, described liquid formulation is selected from the group：Solution product or suspension product.
Second aspect of the present invention provides a kind of purposes of heavy wall mushroom probiotics, for preparing composition or preparation,
The composition or preparation are used for the one or more purposes being selected from the group：(i) mammalian blood serum grape is reduced
Sugar level；(ii) mammalian islet element resistance is improved；And/or (iii) reduction mammal HbAle egg
(HbA1c) level in vain, wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus
Oris), Megasphaera elsdenii (Megasphaera elsdenii) or its combination.
In another preference, the composition or preparation are also independently or additionally used for one be selected from the group
Plant or multiple use：
(iv) body weight increase of mammal is suppressed；
(v) blood lipid level of mammal is reduced.
In another preference, the mammal includes people or non-human mammal.
In another preference, the non-human mammal includes rodent, such as rat, mouse.
In another preference, the blood lipid level of the reduction mammal includes reduction serum triglyceride water
It is flat.
Third aspect present invention provides a kind of composition for being used to treating and/or preventing diabetes, the combination
Thing includes：(i) the heavy wall mushroom probiotics of safe and effective amount；It is on (ii) food or pharmaceutically acceptable
Carrier；Wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus oris),
Megasphaera elsdenii (Megasphaera elsdenii) or its combination.
In another preference, the heavy wall mushroom probiotics includes Lactobacillus oris (Lactobacillus oris).
In another preference, the Lactobacillus oris (Lactobacillus oris) is selected from the group：Lactobacillus
Oris DSM 4864, Lactobacillus oris DSM 4865, Lactobacillus oris DSM 4866 or
It is combined.
In another preference, the heavy wall mushroom probiotics includes Megasphaera elsdenii (Megasphaera
elsdenii)。
In another preference, the Megasphaera elsdenii (Megasphaera elsdenii) is selected from the group：
Megasphaera elsdenii DSM 20460、Megasphaera elsdenii ATCC 17752、
Megasphaera elsdenii ATCC 17753 or its combination.
In another preference, the composition is selected from the group：Food compositions, health composition, medicine
Composition, beverage composition for treating dental erosion, fodder compound or its combination.
In another preference, the composition contains 1 × 10-1 × 1020Cfu/mL or cfu/g heavy wall mushroom
Probiotics, preferably 1 × 104-1×1015Cfu/mL or cfu/g heavy wall mushroom probiotics, with the composition
Cumulative volume or gross weight meter.
In another preference, in described composition, containing 0.0001-99wt%, preferably 0.1-90wt% institutes
The heavy wall mushroom probiotics stated, with the gross weight meter of the composition.
In another preference, described composition is unit dosage form (an a piece of, capsule or a bottle), each
The quality of composition described in unit dosage form is 0.05-5g, preferably 0.1-1g.
In another preference, described composition also contains other probiotics and/or prebiotics.
In another preference, other described probiotics are selected from the group：Lactic acid bacteria, Bifidobacterium, acidophilus
Lactobacillus or its combination.
In another preference, described prebiotics is selected from the group：FOS (FOS), galactooligosaccharide
(GOS), xylo-oligosaccharide (XOS), lactosucrose (LACT), soyabean oligosaccharides (SOS), inulin (Inulin),
Or its combination.
Fourth aspect present invention provides a kind of preparation method of composition described in third aspect present invention, including step：
By (i) heavy wall mushroom probiotics, with (ii) food or pharmaceutically acceptable carrier is mixed, from
And the composition described in third aspect present invention is formed, wherein, the heavy wall mushroom probiotics is selected from the group：
Lactobacillus oris (Lactobacillus oris), Megasphaera elsdenii (Megasphaera elsdenii) or its
Combination.
In another preference, described composition is oral formulations.
Fifth aspect present invention provides a kind of reduction serum glucose, blood fat and/or glycated hemoglobin levels
Method, apply (i) heavy wall mushroom probiotics or the composition described in third aspect present invention to the object,
Wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus oris), Erichsen are huge
Ball bacteria (Megasphaera elsdenii) or its combination.
In another preference, described administration includes oral.
In another preference, described application dosage is 0.01-5g/50kg body weight/days, it is preferred that
0.1-2g/50kg body weight/days.
In another preference, methods described is additionally operable to improve insulin resistance.
In another preference, described object includes mammal, such as people.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the invention and (such as implementation below
Example) in specifically describe each technical characteristic between can be combined with each other, so as to constitute new or preferred skill
Art scheme.As space is limited, no longer tire out one by one herein and state.
Brief description of the drawings
Fig. 1 shows the body weight increase situation of each group mouse after gavage Lactobacillus oris.
Fig. 2 shows the body weight increase situation of each group mouse after gavage Megasphaera elsdenii.
Fig. 3 shows the body weight increase situation of each group mouse after gavage combination strain.
Fig. 4 shows shadow of the gavage Lactobacillus oris to the serum level of glucose of feeding food rich in fat mouse
Ring.
Fig. 5 shows serum level of glucose of the gavage Megasphaera elsdenii to feeding food rich in fat mouse
Influence.
Fig. 6 shows influence of the gavage combination strain to the serum level of glucose of feeding food rich in fat mouse.
Fig. 7 shows influence of the gavage Lactobacillus oris to the serum level of glucose of diabetic mice.
Fig. 8 shows shadow of the gavage Megasphaera elsdenii to the serum level of glucose of diabetic mice
Ring.
Fig. 9 shows influence of the gavage combination strain to the serum level of glucose of diabetic mice.
Figure 10 shows serum levels of triglyceride, pancreas islet of the gavage Lactobacillus oris to feeding food rich in fat mouse
The influence of element and glycosylated hemoglobin (HbA1c) level.
Figure 11 show gavage Megasphaera elsdenii to the serum levels of triglyceride of feeding food rich in fat mouse,
The influence of insulin and glycosylated hemoglobin (HbA1c) level.
Figure 12 shows serum levels of triglyceride, insulin of the gavage combination strain to feeding food rich in fat mouse
With the influence of glycosylated hemoglobin (HbA1c) level.
Figure 13 show gavage Lactobacillus oris to the serum levels of triglyceride of diabetic mice, insulin and
The influence of glycosylated hemoglobin (HbA1c) level.
Figure 14 shows serum levels of triglyceride, pancreas islet of the gavage Megasphaera elsdenii to diabetic mice
The influence of element and glycosylated hemoglobin (HbA1c) level.
Figure 15 shows serum levels of triglyceride, insulin and sugar of the gavage combination strain to diabetic mice
Change the influence of hemoglobin (HbA1c) level.
Embodiment
The present inventor is by in-depth study and experiment extensively, it has unexpectedly been found that, Lactobacillus oris
(Lactobacillus oris) and/or Megasphaera elsdenii (Megasphaera elsdenii) have prevention and/
Or the effect for the treatment of diabetes and its relevant disease, by the active compound containing above-mentioned heavy wall mushroom probiotics
Feeding food experimental subjects, it is found that said composition can suppress increased weight, reduction serum level of glucose, drop
Low levels of lipid, improve insulin resistance and/or reduction glycated hemoglobin levels, effectively mitigate diabetes and
The illness of its relevant disease (such as angiocardiopathy, obesity).The present invention is completed on this basis.
As used herein, term " containing " represents that various composition can be applied to the mixture or group of the present invention together
In compound.Therefore, term " mainly by ... constitute " and " consist of " are included in term " containing ".
The heavy wall mushroom probiotics of the present invention and its application
As used herein, described " heavy wall mushroom probiotics of the invention " refers to Lactobacillus oris and/or the huge ball of Erichsen
Multiple bacterium is one or more mixed in the mixing of one or more Pseudomonas of two kinds of Pseudomonas of shape bacterium or each Pseudomonas
Close.
Wherein, Lactobacillus oris is facultative anaerobic bacteria, and Gram's staining is positive, it is impossible to move.Cell is in bar
Single dispersing morphology can be presented in shape (0.8-1.0 × 2-4pm), cell, can also be rendered into pair or short chain form.
Megasphaera elsdenii is strict anaerobes, and Gram's staining is negative.A variety of volatility fat can be produced
Fat acid.
The invention provides heavy wall mushroom probiotics in terms of preventing and/or treating diabetes and its relevant disease
Application.Heavy wall mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its combination) has a) suppression
Increased weight processed；(b) serum level of glucose is reduced；(c) blood lipid level is reduced；(d) improve insulin to support
It is anti-；And/or (e) reduces the ability of glycated hemoglobin levels.
According to the preference of the present invention, through heavy wall mushroom probiotics, (such as Lactobacillus oris, Erichsen are huge spherical
Bacterium or its combination) carry out the C57BL/6J male mices for being fed high-fat food of gavage, with not receiving
The control group of gavage is compared, and its increased weight amplitude slows down, various and diabetes and its relevant disease (such as heart
Vascular diseases, obesity) the related increased amplitude of index is suppressed, such as serum level of glucose, blood fat water
Gentle glycated hemoglobin levels, and significantly improve insulin resistance.
According to another preference of the present invention, through heavy wall mushroom probiotics (such as huge ball of Lactobacillus oris, Erichsen
Shape bacterium or its combination) come the diabetes model C57BL/6J male mices treated, pair with not receiving treatment
Compared according to group, its index related to diabetes and its relevant disease (such as angiocardiopathy) is remarkably decreased,
Such as serum level of glucose, blood lipid level and glycated hemoglobin levels, and significantly improve insulin resistance.
Therefore, heavy wall mushroom probiotics of the invention (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
Can be to prevent and/or treat diabetes and its relevant disease (such as angiocardiopathy, obesity).
Composition and its application
Present invention also offers a kind of composition, it is preferable that is pharmaceutical composition.The composition includes
The heavy wall mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its combination) of effect amount, it is excellent at one
Select in example, the composition also includes the probiotics being selected from the group：The newborn bar of lactic acid bacteria, Bifidobacterium, acidophilus
Bacterium or its combination；And/or the prebiotics being selected from the group：FOS (FOS), galactooligosaccharide (GOS),
Xylo-oligosaccharide (XOS), lactosucrose (LACT), soyabean oligosaccharides (SOS), inulin (Inulin),
Or its combination.
In a preference, described composition is liquid formulation, solid formulation, semisolid preparations.
In a preference, described liquid formulation is selected from the group：Solution product or suspension product.
In a preference, the formulation of described composition is selected from the group：Powder agent, powder, tablet, sugar
Clothing agent, capsule, granule, suspending agent, solution, syrup, drops and sublingual lozenge.
Pharmaceutical composition of the present invention can be described with medicinal tablet, any form administration of injection or capsule
Pharmaceutical preparation includes the medium and carrier that excipient, medicine allow, and these materials can be carried out according to method of administration
Selection.Pharmaceutical formulations of the present invention can further include the active constituent of auxiliary.
Lactose, glucose, sucrose, D-sorbite, mannose, starch, Arabic gum, calcium phosphate, algae
Hydrochlorate, gelatin, calcium silicates, fine crystallization cellulose, polyvinylpyrrolidone (PVP), cellulose, water,
Syrup, methylcellulose, methyl hydroxybenzoate, nipasol, talcum, magnesium stearate or ore deposit
Thing oil etc. is used as the carrier of pharmaceutical composition, excipient or diluent etc. in the present invention.
In addition, the pharmaceutical composition of the present invention can further comprise lubricant, wetting agent, emulsifying agent, suspension
Liquid stabilizer, preservative, sweetener and spices etc..The pharmaceutical composition of the present invention can be by a variety of known
Method is produced with enteric-coated preparations, in order to the active component of pharmaceutical composition be microorganism can pass through stomach and
Do not destroyed by hydrochloric acid in gastric juice.
In addition, the capsule form that the microorganism of the present invention can prepare in conventional manner is used.For example, standard is assigned
The cold dry microorganism of shape agent and the present invention are mixed and made into bead pill, and pill then is packed into gelatine capsule
In.In addition, the microorganism and medicine of the present invention allow excipient such as liquid glue, cellulose, the silicic acid used
Suspension or dispersion liquid is made by mixing in salt or mineral oil etc., and this suspension or dispersion liquid can load soft gelatin
In capsule.
The pharmaceutical composition of the present invention can be made into casing piece for being administered orally.Term-" casing " in the application,
The coating for allowing to use including all conventional medicines, these are coated not by gastric acid degradation, but can be filled in small intestine
Decompose and quick release goes out microorganism of the invention.The casing of the present invention can be in synthesis hydrochloric acid in gastric juice such as pH=1
Maintained more than 2 hours at 36-38 DEG C in HCl solution, and preferably in synthesis intestinal juice such as pH=7.0 buffer solution
Decomposed in 1.0 hours.
The casing of the present invention is to be coated with every agreement that contracts a film or TV play to an actor or actress 16-30mg, preferably 16-25mg, more preferably
16-20mg is coated.Casing thickness is 5-100 μm in the present invention, and preferable thickness is 20-80 μm.Intestines
Clothing composition selects oneself open conventional polymer known.
Currently preferred casing is by cellulosic phthalic acetate polymer or trimellitic acid polyisocyanate polyaddition
The copolymer of thing and methacrylate is (for example, containing more than 40% methacrylate and contain methylcellulose neighbour's benzene
The copolymer of the methacrylate of dioctyl phthalate hydroxypropyl acrylate or its ester derivative) prepare.
The viscosity of cellulosic phthalic acetate used in casing is about 45-90cp, acetyl in the present invention
Content 17-26%, phthalate content 30-40%.Glued for the inclined ester of phthalic acid of cellulose acetate in casing
Degree is about 5-21cp, second phthalein content 17-26%.Cellulose acetate trimellitate is given birth to by Eastman Kodaks company
Production, the enteric materials that can be used in the present invention.
Cruel for the hydroxypropyl methyl cellulose phthalic acid in casing of the present invention, molecular weight is generally 20,
000-130,000 dalton, desired molecular weight is 80,000-100,000 dalton, and hydroxypropyl content is
5-10%, methoxyl content is 18-24%, and phthalyl content is 21-35%.
It is extremely HP50 for the hydroxypropyl methyl cellulose phthalic acid in casing of the present invention, by Japan
Shin-Etsu Chemidnl Co.Ltd. are produced.HP50 contains 6-10% hydroxypropyls, 20-24% methoxyl groups,
21-27% propyl group, its molecular weight is 84,000 dalton.Another Enteric materials are HP55, and HP55 contains
There are 5-9% HPMCP, 18-22% methoxyl groups, 27-35% O-phthalic
Acid, its molecular weight is 78,000 dalton.
Casing of the present invention is prepared as follows：Casing solution is sprayed in core using conventional method.The enteric coating
In method all solvents be alcohols (such as ethanol), ketone (such as acetone), halogenated hydrocarbon compound (such as dichloromethane),
Or its composition.Softening agent such as di-n-butyl phthalic acid ester and glyceryl triacetate are added to casing molten
In liquid, its ratio is 1 part of coatings to about 0.05 part or about 0.3 part of softening agent.Spray method is preferably continuously held
OK, the doses sprayed can be controlled according to used condition is coated.Atomisation pressure can be adjusted arbitrarily,
In general, preferable result can be obtained under average 1-1.5 handkerchiefs pressure.
In specification " medicine effective quantity " refer to that people and/or animal can be produced function or activity and can be by people
And/or the amount that animal is received.Such as, in the present invention, it can prepare containing 1 × 10-1 × 1020Cfu/ml or
Cfu/g (it is special, 1 × 10 can be contained4-1×1015Cfu/ml or cfu/g；More particularly, 1 × 10 can be contained6-1×
1011Cfu/ml or cfu/g) heavy wall mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
Preparation.
When for preparing pharmaceutical composition, (such as Lactobacillus oris, Erichsen is huge for heavy wall mushroom probiotics used
Ball bacteria or its combination), and/or the effective dose of its metabolite can be with the pattern of administration and to be treated
The order of severity of disease and change.Suitable for dosage form for oral administration, comprising can pharmaceutically be connect with solid-state or liquid
Intimately mixed about 1 × 10-1 × 10 of carrier received20Cfu/ml or cfu/g (particularly, can contain 1 × 104-1×
1015Cfu/ml or cfu/g；More particularly, 1 × 10 can be contained6-1×1011Cfu/ml or cfu/g) active firmicutes
Class probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its combination), or the active component that fermentation is produced.
This dosage is can adjust to provide optimal treatment response.For example, by an urgent demand for the treatment of situation, can be daily
Dosage separated several times is given, or dosage is reduced pari passu.
Described heavy wall mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its combination) can pass through
The approach such as oral is given.Solid-state carrier includes：Starch, lactose, Dicalcium Phosphate, microcrystalline cellulose, sucrose and
White bole, and liquid carrier includes：Culture medium, polyethylene glycol, nonionic surface active agent and edible oil are (such as
Corn oil, peanut oil and sesame oil), as long as being adapted to heavy wall mushroom probiotics (such as huge ball of Lactobacillus oris, Erichsen
Shape bacterium or its combination) characteristic and required specific administration mode.It is usually used in pharmaceutical composition is prepared
Adjuvant also can be advantageously included, such as flavor enhancement, pigment, preservative and antioxidant such as vitamin E, dimension
Raw element C, BHT and BHA.
In terms of easily prepared and administration position, pharmaceutical composition preferably is solid-state composition, especially tablet
The capsule filled with solid-filling or liquid.Oral administration is preferred.
The present composition is administered to the individual, is administered once daily or repeatedly.Dosage unit table
Show that it can be separated and suitable for the mankind or the dosage of other all mammalian subjects in form.Per unit contains
There are the carrier of medicine permission and the microorganism of the present invention of effective therapeutic dose.Dosage with patient body weight and glycosuria
The sick order of severity, included supplement active constituent and used microorganism and change.It is in addition such as possible,
It can separate and be administered, and if desired for can successive administration.Therefore, the dosage will not cause limit to the present invention
System.In addition, " composition " in the present invention does not mean only that medicine and expression can be as functional food
With healthy supplement.In a preference, the composition includes：It is beverage, food, medicine, dynamic
Thing feed etc..
In the preference of the present invention, a kind of food compositions are additionally provided, it contains the heavy wall of effective dose
Mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its combination), and can on the food of surplus
The carrier of receiving, the formulation of described food composition be selected from solid, dairy products, solution product, pulverulent product,
Or suspension product.
In a preference, the formula of the composition is as follows：
1×10-1×1020Cfu/mL heavy wall mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its
Combination)；And on food or pharmaceutically acceptable carrier, and/or excipient.
In another preference, the formula of the composition is as follows：
1×106-1×1011Cfu/mL heavy wall mushroom probiotics (such as Lactobacillus oris, Megasphaera elsdenii or its
Combination)；And on food or pharmaceutically acceptable carrier, and/or excipient.
The method for reducing serum glucose, blood fat and/or glycated hemoglobin levels
In another preference, methods described includes：Absorb the present invention pharmaceutical composition, food compositions,
Beverage composition for treating dental erosion or its combination.The experimental subjects is behaved.
In another preference, methods described includes：Absorb the present invention pharmaceutical composition, food compositions,
Or animal feed, or its combination.The experimental subjects is animal, preferably muroid, Lagomorpha.
In another preference, methods described is additionally operable to improve insulin resistance.
Main advantages of the present invention include：
(a) heavy wall mushroom probiotics of the invention (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
Increased weight can be significantly inhibited.
(b) heavy wall mushroom probiotics of the invention (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
The rise of serum level of glucose, blood lipid level and/or glycated hemoglobin levels can be significantly inhibited, is improved
Insulin resistance, so as to prevent diabetes and its relevant disease (such as angiocardiopathy, obesity).
(c) heavy wall mushroom probiotics of the invention (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
Elevated serum level of glucose, blood lipid level and/or glycated hemoglobin levels can be significantly reduced, are improved
Insulin resistance, so as to treat diabetes and its relevant disease (such as angiocardiopathy, obesity).
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are only used for
The bright present invention rather than limitation the scope of the present invention.The experiment side of unreceipted actual conditions in the following example
Method, generally according to normal condition such as Sambrook et al., molecular cloning：Laboratory manual (New York：
Cold Spring Harbor Laboratory Press, 1989) described in condition, or according to《Microorganism：
Laboratory manual》(James Cappuccino and Natalie Sherman are compiled, Pearson Education publishing houses)
Described in condition, or according to the condition proposed by manufacturer.
The probiotics of mushroom containing heavy wall of embodiment 1 (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
Food compositions
Raw material proportioning such as table 1.
The Combined food composition formula of table 1
| Raw material | Mass percent (%) |
| Bacterium component | 0.5 |
| Milk | 90.0 |
| White sugar | 9.5 |
Be formulated 1-6 in bacterium component be single bacteria component, respectively containing Lactobacillus oris DSM 4864,
Lactobacillus oris DSM 4865、Lactobacillus oris DSM 4866、Megasphaera elsdenii
DSM 20460、Megasphaera elsdenii ATCC 17752、Megasphaera elsdenii ATCC
17753。
For any two kinds of the mixtures of above-mentioned 6 kinds of bacterium, (weight ratio is 1 to bacterium component in formula 7:1).
According to above-mentioned formula rate mixing milk, white sugar, stirring is preheated, 20Mpa pressure to being thoroughly mixed
Homogeneous, 90 DEG C or so are sterilized 5-10 minutes, are cooled to 40-43 DEG C, are inoculated with 1-100 × 106Cfu/g bacterium component,
The food compositions of component containing bacterium (such as Lactobacillus oris, Megasphaera elsdenii or its combination) are made.
Embodiment 2
The pharmaceutical composition of the probiotics of mushroom containing wall (such as Lactobacillus oris, Megasphaera elsdenii or its combination)
Raw material proportioning is shown in Table 2.
The drug regimen composition formula of table 2
Be formulated 1-6 in bacterium component be single bacteria component, respectively containing Lactobacillus oris DSM 4864,
Lactobacillus oris DSM 4865、Lactobacillus oris DSM 4866、Megasphaera elsdenii
DSM 20460、Megasphaera elsdenii ATCC 17752、Megasphaera elsdenii ATCC
17753。
For any two kinds of the mixtures of above-mentioned 6 kinds of bacterium, (weight ratio is 1 to bacterium component in formula 7:1).
Proportionally lactose, dusty yeast, peptone are well mixed with pure water, 60-65 DEG C is preheating to,
20Mpa pressure homogeneous, 90 DEG C or so are sterilized 20-30 minutes, are cooled to 36-38 DEG C, access bacterium component
(1-50×106Cfu/mL), 36-38 DEG C of fermentation to pH value is 6.0, centrifugation, freeze-drying to water content
Less than 3%, that is, prepare the freeze-drying thing of the component containing bacterium.Weigh the freeze-drying thing of 0.5 gram of component containing bacterium with
It is fitted into after maltodextrin mixed in equal amounts in capsule, that is, component containing bacterium is made, and (such as Lactobacillus oris, Erichsen are huge spherical
Bacterium or its combination) pharmaceutical composition.
The zoopery of embodiment 3 is verified
Experiment material:
Mouse：C57BL/6J male mices (4 week old, purchased from Zhongshan University's Experimental Animal Center) are bought,
Mouse growth process is in same environment, and feeds same food.
Inventor obtains 6 plants of heavy wall mushroom probiotics from preservation mechanism, and is stored in Shenzhen Hua Da gene studies
Institute.Meanwhile, lactobacillus reuteri (Lactobacillus reuteri GMNL-89) is chosen, purchased from Chinese allusion quotation
Type culture collection (CCTCC), deposit number is CCTCC NO:M207154, is used as control
Group (LR groups), in MRS nutrient solutions, 37 DEG C of culture 24-48h.
Wherein, the source-information of above-mentioned 6 plants of heavy walls mushroom probiotics is as shown in table 3.Bacterium 1-3 is cultivated in MRS
In liquid (DSMZ Medium 11), 37 DEG C of Anaerobic culturel 24-48h.Bacterium 4-6 is in improvement PYG nutrient solutions
In (DSMZ Medium 104), 37 DEG C of Anaerobic culturel 24-48h.All bacterial strains are sequenced through 16S rDNA and reflected
It is fixed it is errorless after start experiment.
Bacterial strain information is shown in Table 3.
The bacterial strain information of table 3
ATCC:American Type Culture Collection, American type culture collection；
DSMZ:Leibniz-Institute DSMZ-Deutsche Sammlung von Mikroorganismen
Und Zellkulturen GmbH, Germany Microbiological Culture Collection Center.
Food rich in fat (HF)：Containing 60% fat, 20% carbohydrate and 20% albumen, purchased from the U.S.
Research Diets companies (D12492).
It is common to maintain feed：Purchased from Zhongshan University's Experimental Animal Center.
Experimental method：
Experiment one：
In order to verify influence of the bacterial strain to the mouse of the different foods of feeding, normal male C57BL/6J mouse (4 are taken
Week old, purchased from Zhongshan University's Experimental Animal Center) to raise in mouse cage, mouse cage is placed in controllable environment：Often
Day illumination 12h, 22 DEG C of keeping temperature.Mouse can ad lib and drinking-water, adaptability raise 2 weeks after divide at random
Group, respectively control group (CK), test microbial inoculum group (1 group of bacterium, 2 groups of bacterium, 3 groups of bacterium, 4 groups of bacterium, bacterium 5
Group, 6 groups of bacterium, 2 groups of bacterium 1+ bacterium, 6 groups of bacterium 5+ bacterium, 4 groups of bacterium 1+ bacterium), control microbial inoculum group (LR, Lactobacillus
Reuteri GMNL-89) and food rich in fat group (HF), every group 10.LR groups, HF groups and experimental bacteria
Agent group feeding food rich in fat, CK group feedings commonly maintain feed.Experiment microbial inoculum group and LR groups use stomach respectively
The corresponding bacterial strain bacterium solution (10 of pipe gavage8CFU/0.2ml)；HF groups and CK group gavage normal salines, hold
It is continuous 8 weeks, a body weight is measured weekly (result is shown in Fig. 1-3 and table 4-6).
Experiment two：
In order to verify influence of the bacterial strain to diabetic mice, normal male C57BL/6J mouse are taken (4 weeks
Age, purchased from Zhongshan University's Experimental Animal Center) to raise in mouse cage, mouse cage is placed in controllable environment：Daily
Illumination 12h, 22 DEG C of keeping temperature.Mouse can ad lib and drinking-water, adaptability raise change within 2 weeks feed it is higher fatty acid
Food, continues 8 weeks.At the 4th week, continuous two days peritoneal injection alloxans (60mg/kg alloxan),
Herein after ensuing 4 weeks, the mouse that fasting blood glucose content is higher than 10.0mmol/L is chosen, it is random to be grouped,
Respectively control group (CK), experiment microbial inoculum group (1 group of bacterium, 2 groups of bacterium, 3 groups of bacterium, 4 groups of bacterium, 5 groups of bacterium,
6 groups of bacterium, 2 groups of bacterium 1+ bacterium, 6 groups of bacterium 5+ bacterium, 4 groups of bacterium 1+ bacterium), control microbial inoculum group (LR) and diabetes mould
Type group (DM), every group 10.Test microbial inoculum group and LR the groups corresponding bacterial strain bacterium solutions (10 of gavage 0.2ml respectively6~
108CFU/0.2ml)；DM groups and CK group gavage normal salines, continue 8 weeks, all mouse feedings
Identical food rich in fat, and under identical living environment.
Blood parameters
Mouse after 16 hours, extracts blood from after eyeball and in intra capillary respectively, existed side by side on an empty stomach
It is put into 4 DEG C of refrigerator preservations.Extremely -20 DEG C of preservation is standby after separated plasma.(Roche is purchased from using glucose meter
Diagnose (Roche Diagnostics)) determine serum glucose baseline values；Utilize enzyme reaction-light splitting temperature
Meter determines lotus root connection kit measurement serum levels of triglyceride level；Using ELISA kit, (biology is built up in Nanjing
Graduate School of Engineering) determine serum insulin level and glycosylated hemoglobin (HbA1c) level.
Data statistic analysis
Data result is represented with average value ± standard error.Analysis of variance (ANOVA) is more using Tuckey afterwards
Weight comparative approach (GraphPad softwares, Santiago, CA, USA) (GraphPad Software, San Diego,
CA, USA) carry out significance analysis, p<0.05 thinks statistically significant difference.
Experimental result：
(1) Lactobacillus oris, Megasphaera elsdenii or its influence of combination to mouse body weight.
The body weight increase situation (Fig. 1) of each group mouse after the gavage Lactobacillus oris of table 4
Note：Data are mean+SD in table, for any two groups of data of each row, do not have same letter to represent poor behind numeral
Different significantly (p<0.05), table 5-18 is identical with this.
The body weight increase situation (Fig. 2) of each group mouse after the gavage Megasphaera elsdenii of table 5
The body weight increase situation (Fig. 3) of each group mouse after the gavage combination strain of table 6
As a result as shown in table 4-6 and Fig. 1-3.As a result show, in the growth curve of mouse, pass through 8 weeks feed
Support, the body weight of only feeding food rich in fat mouse is significantly higher than the body weight that feeding commonly maintains feed mouse
(p<0.05).Feeding bacterium (Lactobacillus oris, Megasphaera elsdenii or its combination) is and higher fatty acid simultaneously
The mouse weight of food is substantially less than the mouse (p of only feeding food rich in fat<0.05).And also below LR
Group.
As a result show, Lactobacillus oris, Megasphaera elsdenii or its combination can effectively control mouse obesity hair
Raw rate simultaneously helps to prevent type ii diabetes.
(2) serum of Lactobacillus oris, Megasphaera elsdenii or its combination to feeding food rich in fat mouse
The influence of glucose level.
Influence (Fig. 4) of the gavage Lactobacillus oris of table 7 to the serum level of glucose of feeding food rich in fat mouse
Influence of the gavage Megasphaera elsdenii of table 8 to the serum level of glucose of feeding food rich in fat mouse
(Fig. 5)
Influence (Fig. 6) of the gavage combination strain of table 9 to the serum level of glucose of feeding food rich in fat mouse
As a result as shown in table 7-9 and Fig. 4-6.Before experiment one is carried out, the serum of each group mouse (6 week old)
Glucose content is without difference (p>0.05).As a result show, experiment process keeps common dimension after 8 weeks
Holding the CK group mice serum glucose contents of feed feeding does not have significant change.And feeding food rich in fat
HF group mice serum glucose contents are increased considerably.At Lactobacillus oris, Megasphaera elsdenii or its combination
Although reason group mice serum glucose content is higher than CK group mouse, substantially less than only feeding food rich in fat
HF group mouse (p<0.05).
As a result show, Lactobacillus oris, Megasphaera elsdenii or its combination can significantly reduce the higher fatty acid food of feeding
The serum level of glucose of thing mouse.
(3) Lactobacillus oris, Megasphaera elsdenii or its combination are to diabetic mice serum glucose
The influence of level.
Influence (Fig. 7) of the gavage Lactobacillus oris of table 10 to diabetic mice serum level of glucose
Influence (Fig. 8) of the gavage Megasphaera elsdenii of table 11 to diabetic mice serum level of glucose
Influence (Fig. 9) of the gavage combination strain of table 12 to diabetic mice serum level of glucose
As a result as shown in table 10-12 and Fig. 7-9.Before diabetic mice experiment (experiment two) is carried out,
The serum glucose of all groups of mouse (14 week old) is without difference.As a result show, experiment process is after 4 weeks,
The serum glucose level of diabetic model group (DM groups) mouse is significantly raised, and adds microbial inoculum simultaneously
The serum glucose level of mouse is less than DM groups.After 8 weeks, while (Lactobacillus oris, Erichsen are huge for feeding microbial inoculum
Ball bacteria or its combination) mice serum glucose content be substantially less than DM groups (p<0.05).
As a result show, Lactobacillus oris, Megasphaera elsdenii or its combination can significantly reduce diabetes model
Mice serum glucose content.
(4) serum of Lactobacillus oris, Megasphaera elsdenii or its combination to feeding food rich in fat mouse
The influence of triglyceride, insulin and glycosylated hemoglobin (HbA1c) level.
Serum levels of triglyceride, insulin and sugar of the gavage Lactobacillus oris of table 13 to feeding food rich in fat mouse
Change the influence (Figure 10) of hemoglobin (HbA1c) level
Serum levels of triglyceride, insulin of the gavage Megasphaera elsdenii of table 14 to feeding food rich in fat mouse
With the influence (Figure 11) of glycosylated hemoglobin (HbA1c) level
Serum levels of triglyceride, insulin and saccharification of the gavage combination strain of table 15 to feeding food rich in fat mouse
The influence (Figure 12) of hemoglobin (HbA1c) level
As a result as shown in table 13-15 and Figure 10-12.Before experiment one is carried out, normal mouse (6 week old)
Serum levels of triglyceride, insulin and HbA1c levels are in all groups without difference.As a result show, test
Handle after 8 weeks, keep the common mouse blood parameter for maintaining feed feeding to remain unchanged no difference；And feeding is high
Mouse (HF groups) serum levels of triglyceride, insulin and the HbA1c levels of fat food significantly increase；With
Lactobacillus oris, the serum levels of triglyceride of Megasphaera elsdenii or its combined treatment group mouse, insulin and
HbA1c levels are substantially less than only feeding food rich in fat mouse (p<0.05).
As a result show, Lactobacillus oris, Megasphaera elsdenii or its combination can significantly reduce the higher fatty acid food of feeding
The serum levels of triglyceride and HbA1c levels of thing mouse, and insulin resistance can be significantly improved.
(5) the serum glycerine of Lactobacillus oris, Megasphaera elsdenii or its combination to diabetic mice
The influence of three fat, insulin and glycosylated hemoglobin (HbA1c) level.
Serum levels of triglyceride, insulin and HbA1c of the gavage Lactobacillus oris of table 16 to diabetic mice
The influence (Figure 13) of level
The gavage Megasphaera elsdenii of table 17 to the serum levels of triglyceride of diabetic mice, insulin and
The influence (Figure 14) of HbA1c levels
The gavage combination strain of table 18 is to the serum levels of triglyceride of diabetic mice, insulin and HbA1c levels
Influence (Figure 15)
As a result as shown in table 16-18 and Figure 13-15.As a result show, with Lactobacillus oris, Megasphaera elsdenii,
Or mouse of its combined treatment after 8 weeks, its serum levels of triglyceride, insulin and HbA1c levels are substantially less than
DM group mouse (p<0.05).
As a result show, Lactobacillus oris, Megasphaera elsdenii or its combination can significantly reduce diabetes model
The serum levels of triglyceride and HbA1c contents of mouse, and significantly improve insulin resistance.
All documents referred in the present invention are all incorporated as reference in this application, just as each document
It is individually recited as with reference to such.In addition, it is to be understood that after the above-mentioned instruction content of the present invention has been read,
Those skilled in the art can make various changes or modifications to the present invention, and these equivalent form of values equally fall within this Shen
Please appended claims limited range.
Claims (10)
1. a kind of purposes of heavy wall mushroom probiotics (Firmicutes), it is characterised in that for preparing group
Compound or preparation, the composition or preparation are used for the one or more purposes being selected from the group：(a) prevention and
/ or treatment diabetes；(b) prevent and/or treat angiocardiopathy；And/or (c) prevention and/or treatment obesity,
Wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus oris), Erichsen are huge
Ball bacteria (Megasphaera elsdenii) or its combination.
2. purposes as claimed in claim 1, it is characterised in that the heavy wall mushroom probiotics includes mouth breast
Bacillus (Lactobacillus oris).
3. purposes as claimed in claim 2, it is characterised in that the Lactobacillus oris (Lactobacillus oris)
It is selected from the group：Lactobacillus oris DSM 4864、Lactobacillus oris DSM 4865、
Lactobacillus oris DSM 4866 or its combination.
4. a kind of purposes of heavy wall mushroom probiotics, it is characterised in that described for preparing composition or preparation
Composition or preparation are used for the one or more purposes being selected from the group：(i) mammalian blood serum G/W is reduced
It is flat；(ii) mammalian islet element resistance is improved；And/or (iii) reduction mammal glycosylated hemoglobin
(HbA1c) level, wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus
Oris), Megasphaera elsdenii (Megasphaera elsdenii) or its combination.
5. purposes as claimed in claim 4, it is characterised in that the composition or preparation also independently or
It is additionally utilized for the one or more purposes being selected from the group：
(iv) body weight increase of mammal is suppressed；
(v) blood lipid level of mammal is reduced.
6. a kind of composition for being used to treating and/or preventing diabetes, it is characterised in that the composition bag
Include：(i) the heavy wall mushroom probiotics of safe and effective amount；On (ii) food or it is pharmaceutically acceptable carry
Body；Wherein, the heavy wall mushroom probiotics is selected from the group：Lactobacillus oris (Lactobacillus oris), angstrom
Family name's Megasphaera (Megasphaera elsdenii) or its combination.
7. composition as claimed in claim 6, it is characterised in that the composition contains 1 × 10-1 × 1020
Cfu/mL or cfu/g heavy wall mushroom probiotics, preferably 1 × 104-1×1015Cfu/mL or cfu/g firmicutes
Class probiotics, with the cumulative volume or gross weight meter of the composition.
8. composition as claimed in claim 6, it is characterised in that in described composition, contain 0.0001-99wt
%, the preferably heavy wall mushroom probiotics described in 0.1-90wt%, with the gross weight meter of the composition.
9. composition as claimed in claim 6, it is characterised in that described composition also contains other benefits
Raw bacterium and/or prebiotics.
10. the preparation method of composition described in a kind of claim 6, it is characterised in that including step：
By (i) heavy wall mushroom probiotics, with (ii) food or pharmaceutically acceptable carrier is mixed, from
And the composition described in claim 6 is formed, wherein, the heavy wall mushroom probiotics is selected from the group：Mouth breast
Bacillus (Lactobacillus oris), Megasphaera elsdenii (Megasphaera elsdenii) or its combination.
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