CN107224584A - A kind of probiotic composition and its application - Google Patents
A kind of probiotic composition and its application Download PDFInfo
- Publication number
- CN107224584A CN107224584A CN201610176593.6A CN201610176593A CN107224584A CN 107224584 A CN107224584 A CN 107224584A CN 201610176593 A CN201610176593 A CN 201610176593A CN 107224584 A CN107224584 A CN 107224584A
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- CN
- China
- Prior art keywords
- lactobacillus
- bifidobacterium
- probiotic composition
- probiotics
- blood sugar
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
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- A—HUMAN NECESSITIES
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
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Abstract
The invention discloses a kind of probiotic composition, multi-joint probiotics of the said composition comprising effective dose and α glucosides enzyme levels.It is used for the application of medicine for preparing control postprandial blood sugar the invention also discloses the probiotic composition.Compared compared to the therapeutic scheme that α glucosides enzyme levels are used alone, the dosage of α glucosides enzyme level can be greatly reduced and play therapeutic effect in composition of the invention.On the other hand, the multi-joint probiotics in the composition of the present invention is used alone, postprandial blood sugar is not significantly reduced, and the composition of the present invention can then significantly reduce postprandial blood sugar, therefore with good application prospect.
Description
Technical field
The present invention relates to Remedies for diabetes technical field, specifically, be on a kind of probiotic composition and
It is applied.
Background technology
The definition that the World Health Organization (WHO) in 1999 and IDF (IDF) announce, diabetes
(DM) it is a kind of metabolic disease as caused by many reasons, its distinguishing feature is chronic hyperglycemia, but also meeting
Show as various metabolic disorders.Its type i diabetes for being broadly divided into insulin-dependent and non-insulin-depending type
Type II diabetes, other types and the type of gestational diabetes mellitus four, wherein type 2 diabetes patient account for more than 90%.
In the world, diabetes have turned into the chronic disease of the third-largest harm human life and health.According to international glycosuria
The data that disease connection is announced shows that global diabetic's number was about patient's number after 20 years more than 2.4 hundred million in 2006
It will steeply rise to 3.8 hundred million.In past 20 years, the diabetes prevalence of China also rises 4 times, 2007
Year, number of patients was up to 39,800,000.Therefore the prevention and treatment for diabetes have very urgent demand.
Type ii diabetes are because using hyperglycaemia as the metabolic of principal character caused by insulin secretion relative deficiency
Disease.Its main feature shows as insulin resistance, i.e., cell can not react to it after autologous generation insulin.
Type II diabetes is often accompanied by multiple complications, such as coronary heart disease, atherosclerosis, renal lesions, DPN,
PVR and foot lesion etc..The illness rate of China's diabetes has reached more than 15%, and type II diabetes
Patient has accounted for more than 95%.People's living standard is stepped up in recent years, causes the dietary structure of people also therewith
Have a very large change, based on the high confectionery thing of high fat, and lack enough motions, life stress is not in addition
Disconnected increase causes the illness rate of type II diabetes to increase year by year.
It is the most original method of control diabetes to keep on a diet with suitable exercise.But with living-pattern preservation, drink
Food and motion are increasingly difficult to achieve the effect of control diabetes.It is main at present to reduce blood glucose to reach treatment by medicine
The purpose of type II diabetes.These different classes of medicines are directed to age and the personal considerations of different diabetics
And other factorses.Primarily now there is the oral hypoglycemic medicine of four classes, wherein alpha-glucosidase restrainer can effectively drop
Low postprandial blood sugar.
Alpha-glucosidase restrainer, it is a kind of by delaying absorption of the enteron aisle to carbohydrate, so as to reach
The oral hypoglycemic drug of diabetes is treated, the various alpha-glucosidases of small intestine are located at by Reverse transcriptase, make carbon aquation
The speed that compound is decomposed into glucose in enteron aisle slows down, so as to slow down the absorption of glucose in enteron aisle, reduction is after the meal
Hyperglycaemia postpones the absorption of glucose.
Substantial amounts of clinical research shows that postprandial blood sugar can preferably reflect different blood glucose levels than fasting blood-glucose.Together
When postprandial hyperglycemia and the cardiovascular complication of diabetes have close correlation.Hyperglycaemia can promote high glycerine three
Ester mass formed by blood stasis makes lipid over oxidation small and dense LDL-C occur.Also result in increasing for blood pressure.
Postprandial blood sugar is more high more be easily caused thrombosis to occur angina pectoris, the chance of myocardial infarction and apoplexy higher.With
Postprandial blood sugar increase total coronary heart disease incidence and lethal coronary heart disease incidence also gradually increases.Postprandial blood sugar is got over
The incidence of high diabetes Microalbuminuria and diabetic retinopathy is also higher.Hyperglycaemia can have influence on cognitive work(
Brain can be reduced reduces memory and notice to the disposal ability of information.Still further aspect hyperglycaemia can also be led
The change of mood is caused, can make one to feel deficient in energy, depressed etc..
Therefore, in the therapeutic strategy of existing diabetes, control and reduction postprandial hyperglycemia become particularly important.
The alpha-glucosidase inhibitor of current clinical practice has：Acarbose, Miglitol and voglibose.α-
In the clinical practice of glucosidase inhibitor class oral hypoglycemic drug, these three drug therapy dosage, which can be produced, to disappear
Change the even side effect such as ulcer of road dysfunction, long-term diarrhea, and it is continuous take after can produce drug resistance.
Probiotics is that a class is colonized in multiple positions such as body enteron aisle, reproductive system, oral cavity, can be produced definite strong
Kang Gongxiao improves host's microecological balance, plays the active microorganism of beneficial effect.Conventional probiotics is included but not
It is not limited to：Lactobacillus casei, lactobacillus acidophilus, two qi Bifidobacteriums, lactobacillus reuteri, bifidobacterium longum,
Bifidobacterium breve, bifidobacterium infantis, lactobacillus delbruockii subspecies bulgaricus, streptococcus thermophilus, youth bifid bar
Bacterium, Lactobacillus rhamnosus, Lactobacillus plantarum, bifidobacterium lactis, bacillus subtilis, streptococcus salivarius, lichens
Bacillus etc..
Existing literature shows, continuously takes probiotics, when it arrives certain amount in body accumulation, it is possible to decrease blood glucose.
Although its function of adjusting blood glucose has been confirmed that its mechanism has no final conclusion.
Meanwhile, still no document shows, probiotics is used alone, postprandial blood sugar can be effectively controlled.Experimental data
Also indicate that, individually take probiotics, postprandial hyperglycemia is not obviously improved.
In summary, although alpha-glucosidase inhibitor can effectively control postprandial hyperglycemia, but based on its side effect and not
Good reaction, clinically reduces composition and the method that its side effect occurs in the urgent need to finding.
The content of the invention
Present inventor is had found under study for action, and a variety of probiotics and alpha-glucosidase inhibitor are used in combination, can
To significantly reduce postprandial blood sugar concentration, therefore first purpose of the present invention, it is to provide a kind of probiotic composition,
The multi-joint probiotics comprising effective dose and alpha-glucosidase suppress in said composition.
According to the present invention, the probiotics of two or more, the probiotics choosing are included in the probiotic composition
From：It is Lactobacillus casei, lactobacillus acidophilus, two qi Bifidobacteriums, lactobacillus reuteri, bifidobacterium longum, short double
Discrimination bacillus, bifidobacterium infantis, lactobacillus delbruockii subspecies bulgaricus, streptococcus thermophilus, bifidobacterium adolescentis, mouse
Lee's sugar lactobacillus, Lactobacillus plantarum, bifidobacterium lactis and bacillus licheniformis.
It is preferred that, the Lactobacillus casei is Lactobacillus casei ATCC393；The lactobacillus acidophilus is the newborn bar of acidophilus
Bacterium ATCC4356；The two qis Bifidobacterium is two qi Bifidobacterium ATCC 29521；The lactobacillus reuteri
For lactobacillus reuteri ATCC23272；The bifidobacterium longum is bifidobacterium longum CICC6187；It is described short double
Discrimination bacillus is bifidobacterium breve ATCC 15701；The lactobacillus delbruockii subspecies bulgaricus are that Lactobacillus delbrueckii guarantor adds
Leah subspecies ATCC 11842；The streptococcus thermophilus is streptococcus thermophilus ATCC14485；The youth bifid
Bacillus is bifidobacterium adolescentis ATCC 15705；The Lactobacillus rhamnosus is Lactobacillus rhamnosus ATCC53103；
The Lactobacillus plantarum is Lactobacillus plantarum ATCC14917；The bifidobacterium lactis is DSM15954；Describedly
Clothing bacillus is bacillus licheniformis CICC20446.
According to the present invention, the alpha-glucosidase comprising one or more therapeutically effective amounts in the probiotic composition suppresses
Agent, the alpha-glucosidase inhibitor is selected from：Acarbose, voglibose and Miglitol.
Second object of the present invention, be to provide the probiotic composition be used for prepare control the medicine of postprandial blood sugar
The application of thing.
Third object of the present invention, is to provide and includes in a kind of medicine for controlling postprandial blood sugar, the medicine
The above-mentioned probiotic composition of effect amount and appropriate pharmaceutically acceptable excipient；The medicine can be to be available for orally
The formulation of administration, optional formulation includes tablet, capsule, pill, solution and suspension etc..
In a specific embodiment, in probiotic composition of the invention, the alpha-glucosidase inhibitor is
Acarbose, the probiotics is double by Lactobacillus acidophilus ATCC 4356, Lactobacillus rhamnosus ATCC393, length
The tetrad bacterium of discrimination bacillus CICC6187 and bacillus licheniformis CICC20446 compositions.
In another embodiment, the probiotics in the probiotic composition by Lactobacillus acidophilus ATCC 4356,
Lactobacillus rhamnosus ATCC393 and bifidobacterium longum CICC6187 compositions；
In one embodiment, the probiotics in the probiotic composition by Lactobacillus acidophilus ATCC 4356,
Lactobacillus rhamnosus ATCC393, bacillus licheniformis CICC20446；The alpha-glucosidase inhibitor is meter Ge Lie
Alcohol.
In one embodiment, the acarbose comprising therapeutically effective amount and by Lactobacillus acidophilus ATCC 4356,
Lactobacillus rhamnosus ATCC393, bifidobacterium longum CICC6187 and bacillus licheniformis CICC20446 groups
Into tetrad bacterium composition, can effectively reduce mouse postprandial blood sugar.
Compared compared to the therapeutic scheme that alpha-glucosidase suppression is used alone, alpha-glucosidase presses down in composition of the invention
The dosage of system can be greatly reduced and play therapeutic effect.On the other hand, four in the composition of the present invention are used alone
Join probiotics, postprandial blood sugar is not significantly reduced, and composition can then significantly reduce postprandial blood sugar, therefore is had
Good application prospect.
Embodiment
The present invention is described in more detail below by specific embodiment, for a better understanding of the present invention,
But following embodiments are not limit the scope of the invention.
In the context of the present invention, " probiotics " refers to that a class is colonized in body enteron aisle, reproductive system, mouth
Multiple positions such as chamber, can produce definite health efficacy improves host's microecological balance, plays the activity of beneficial effect
Microorganism.The probiotics includes：The newborn bar of Lactobacillus casei, lactobacillus acidophilus, two qi Bifidobacteriums, Luo Yishi
Bacterium, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, lactobacillus delbruockii subspecies bulgaricus, thermophilic chain
Coccus, bifidobacterium adolescentis, Lactobacillus rhamnosus, Lactobacillus plantarum, bifidobacterium lactis and lichens gemma bar
Bacterium.
In the context of the present invention, " the multi-joint probiotics " refers to that the probiotic combination of two or more is used.
Streptozotocin (Streptozotocin, STZ) used in following examples is a kind of Glucosamine
- nitroso ureas, the selective destruction of beta Cell of islet to certain kind animal can induce many animals and produce
Diabetes are general using rat and mouse manufacture diabetes animal model.
Embodiment 1：The foundation of diabetic mouse model
3 weeks male C57/BL mouse are bought, conventional feed, which is fed, makes adaptation environment 3 days.Feed is replaced by high fat
High sugar feed is fed 4 weeks, and mouse fasting be can't help after water 12h, and 150mg/kg Streptozotocin is injected intraperitoneally on an empty stomach
Recover high-sugar-fat-diet after (Streptozotocin, STZ) (dissolving of pH4.2 citrate buffer solutions), 1h to raise.
It is the hypoglycemia phase to inject 6-10h after STZ, monitors mouse state, and the G/W of gavage 2% is to avoid blood if necessary
The too low death of sugar.
Random blood sugar is determined after 3 days, what it is higher than 16.7mmol/L is Glycemia Decline success mouse, while considerable
Observe mouse amount of drinking water, urine volume significantly raised.
Embodiment 2：Acarbose reduces the effective dose of diabetic mice postprandial blood sugar
Diabetic mice is divided into 5 groups and is designated as 1.~5. group respectively, overnight fast can't help water 16h, determines empty during experiment
After abdomen blood glucose (FBG), each group mouse stomach adds the 2g/kg starch solutions of various concentrations acarbose, uses blood
Sugared instrument detects 1h, 2h blood glucose (PBG) value after the meal.Each group gavage A Kabo dosage sets as follows：①0mg/kg、
②30mg/kg、③40mg/kg、④50mg/kg、⑤60mg/kg.1h, 2h blood glucose after the meal is detected with blood glucose meter
(PBG) value.
The influence of table 1, various dose acarbose to diabetic mice postprandial blood sugar (mmol/L)
* there are significant difference, p with model group<0.05；* has pole significant difference, p with model group<0.01
The fasting blood-glucose of diabetic mice is 17.15-22.03mmol/L, and postprandial blood sugar is significantly increased；In administration Ah Ka
After ripple sugar, higher level is still kept in low dosage (30-40mg/kg) postprandial blood sugar；Increase the agent of acarbose
Measure 1 hour still higher after the meal to 50mg/kg, but reduce 6.12mmol/L in 2 hours；Dosage is brought up to
60mg/kg, postprandial blood sugar is compared control group and significantly reduced；Low dosage (30-40mg/kg) level of postprandial blood sugar without
It is obviously improved.Acarbose just shows to reduce the effect of postprandial blood sugar when being at least 50~60mg/kg.
Embodiment 3：Multi-joint probiotics promotes acarbose antidiabetic drug to reduce the effect of postprandial blood sugar
Multi-joint probiotics includes the following strain of tetrad：Lactobacillus acidophilus ATCC 4356 1.0 × 109Cfu/ agent, rhamnose
Lactobacillus ATCC393 1.0 × 109Cfu/ agent, bifidobacterium longum CICC6187 1.0 × 109Cfu/ agent, lichens gemma bar
Bacterium CICC20446 1.0 × 109Cfu/ agent.
The male C57/BL mouse of 3 weeks adapt to environment 4 days, are randomly divided into two groups：It is normal to feed mouse (commonly
Forage feed) and Glycemia Decline mouse (high-sugar-fat-diet nursing), normal group, Glycemia Decline are small after 4 weeks
Mouse difference intraperitoneal injection of saline, Streptozotocin (STZ).The successful mouse of Glycemia Decline is divided into gavage
Probiotics and two groups of gavage physiological saline, probiotics mouse continuous gavage probiotics, normal group and physiological saline group are every
Day isometric physiological saline of gavage.12 mouse of physiological saline group are randomly divided into two groups after 3 weeks, mould is designated as respectively
12 mouse of probiotic group are randomly divided into two groups, are designated as respectively prebiotic by type group D and acarbose control group A
Bacterium group P and acarbose+probiotic group (A+P), detection probiotics reduce diabetic mice after the meal with acarbose
The effect of blood glucose.
Test the previous day, mouse overnight fast is determined after fasting blood-glucose (FBG) before can't help water 16h, experiment, respectively
Group mouse stomach different solutions, 1h, 2h blood glucose (PBG) value after the meal is detected with blood glucose meter.Each group gavage solution is set
It is as follows：
Normal group：2g/kg starch solutions+physiological saline；Model group：2g/kg starch solutions+physiological saline；A Ka
Ripple sugar group：2g/kg starch solutions+acarbose 30mg/kg；Probiotic group：2g/kg starch solutions+prebiotic bacterium solution
4×109Cfu/ is only；Acarbose+probiotic group：2g/kg starch solutions+prebiotic the bacterium solutions of acarbose 30mg/kg+
4×109Cfu/ is only.
Table 2, probiotics reduce the facilitation of postprandial blood sugar to acarbose
1h and 2h after model group, acarbose group, probiotic group and acarbose+probiotic group mouse stomach
It is poor to postprandial blood sugar metabolic capability that postprandial blood sugar is all remarkably higher than normal group mouse, i.e. diabetic mice；Individually take
Acarbose or one multi-joint probiotics with sub-doses, diabetic mice postprandial blood sugar is with model group mouse without notable
Difference, illustrates that the two does not show to reduce the effect of postprandial blood sugar；And the two combination group (A+P groups) 1h after the meal
And 2h blood glucose is significantly lower than model group, with significant difference.It can be seen that multi-joint probiotics can significantly reduce acarbose
Dosage, with promote acarbose reduce postprandial blood sugar effect.
The specific embodiment of the present invention is described in detail above, but it is intended only as example, and the present invention is not
It is limited to particular embodiments described above.To those skilled in the art, it is any to the present invention carry out etc.
With modifications and substitutions also all among scope of the invention.Therefore, institute without departing from the spirit and scope of the invention
The impartial conversion and modification of work, all should be contained within the scope of the invention.
Claims (8)
1. a kind of probiotic composition, it is characterised in that the multi-joint benefit of effective dose is included in the probiotic composition
Raw bacterium and alpha-glucosidase suppress.
2. probiotic composition as claimed in claim 1, it is characterised in that included in the probiotic composition
The probiotics of two or more, the probiotics is selected from：Lactobacillus casei, lactobacillus acidophilus, two qi bifid bars
Bacterium, lactobacillus reuteri, bifidobacterium longum, bifidobacterium breve, bifidobacterium infantis, Lactobacillus delbrueckii Bao Jiali
Subspecies, streptococcus thermophilus, bifidobacterium adolescentis, Lactobacillus rhamnosus, Lactobacillus plantarum, bifidobacterium lactis,
And bacillus licheniformis.
3. probiotic composition as claimed in claim 2, it is characterised in that the Lactobacillus casei is cheese breast
Bacillus ATCC393；The lactobacillus acidophilus is Lactobacillus acidophilus ATCC 4356；The two qis Bifidobacterium is two
Qi Bifidobacterium ATCC 29521；The lactobacillus reuteri is lactobacillus reuteri ATCC23272；The length
Bifidobacterium is bifidobacterium longum CICC6187；The bifidobacterium breve is bifidobacterium breve ATCC 15701；Institute
Lactobacillus delbruockii subspecies bulgaricus are stated for lactobacillus delbruockii subspecies bulgaricus ATCC 11842；The thermophilus
Bacterium is streptococcus thermophilus ATCC14485；The bifidobacterium adolescentis is bifidobacterium adolescentis ATCC 15705；Institute
Lactobacillus rhamnosus is stated for Lactobacillus rhamnosus ATCC53103；The Lactobacillus plantarum is Lactobacillus plantarum
ATCC14917；The bifidobacterium lactis is DSM15954；The bacillus licheniformis is bacillus licheniformis
CICC20446。
4. probiotic composition as claimed in claim 2, it is characterised in that the multi-joint probiotics includes four kinds
Probiotics, be respectively：Lactobacillus acidophilus, Lactobacillus rhamnosus, bifidobacterium longum and bacillus licheniformis.
5. probiotic composition as claimed in claim 1, it is characterised in that included in the probiotic composition
The alpha-glucosidase inhibitor of one or more therapeutically effective amounts, the alpha-glucosidase inhibitor is selected from：Acarbose,
Voglibose and Miglitol.
6. probiotic composition as claimed in claim 1, it is characterised in that the alpha-glucosidase inhibitor for Ah
Card ripple sugar.
7. as probiotic composition according to any one of claims 1 to 6 is used to prepare the medicine for controlling postprandial blood sugar
The application of thing.
8. a kind of medicine of control postprandial blood sugar, it is characterised in that claim 1 of the medicine comprising effective dose~
Probiotic composition and appropriate pharmaceutically acceptable excipient any one of 6.
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| CN115137757A (en) * | 2022-07-29 | 2022-10-04 | 承葛健康科技(广东)有限公司 | Probiotic composition assisting in reducing blood sugar |
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