CN107106619A - Early secretion of insulin performance improving agent - Google Patents
Early secretion of insulin performance improving agent Download PDFInfo
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- CN107106619A CN107106619A CN201680006183.5A CN201680006183A CN107106619A CN 107106619 A CN107106619 A CN 107106619A CN 201680006183 A CN201680006183 A CN 201680006183A CN 107106619 A CN107106619 A CN 107106619A
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- Prior art keywords
- insulin
- secretion
- lactic acid
- early
- acid bacteria
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 140
- 102000004877 Insulin Human genes 0.000 title claims abstract description 70
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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
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- 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
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention provides a kind of Early secretion of insulin performance improving agent.The Early secretion of insulin performance improving agent is with the viable bacteria 1 × 10 containing lactic acid bacteria10Composition more than individual cell is active ingredient.
Description
Technical field
Improve the preparation of Early secretion of insulin performance the present invention relates to a kind of.
Background technology
Diabetes are the metabolic diseases using hyperglycemia state as cardinal symptom.Known lasting chronic hyperglycemia is not only simultaneously
The minute blood vessel obstacles such as nephrosis, PVR, neurosis are sent out, and the arteriosclerotics such as miocardial infarction, cerebral infarction can be promoted
The morbidity of disease.That is, diabetes can be described as not only left and right QOL but also be also the disease in significantly left and right life-span.Deposited in diabetes
In a variety of sick types, main sick type is type 1 diabetes and diabetes B.
Wherein, diabetes B is due to the reduction of the insulin secretion performance of beta Cell of islet and due to liver, bone
In the target tissues such as flesh, fat insulin receptivity reduction (insulin resistance) and cause insulin effect relative deficiency and
Cause hyperglycaemia.Now, the diabetes as lifestyle disease sharply increased are diabetes Bs, hyperphagia, higher fatty acid
The habits and customs of America and Europe's type such as food, lack of exercise influence it to fall ill strongly as environmental factor.
In addition, in Japanese, it is main former as a rule compared to insulin resistance for diabetes B
Early secretion of insulin required for because being insulin secretion performance, especially suppressing the rising of blood glucose value drastically after Sugar intake
The reduction of energy, it is desirable to have improve the method for the Early insulin secretion performance of insulin.
On the other hand, as the report on lactic acid bacteria, it was recently reported that the polysaccharide of the cell membrane of suppression gram-positive bacteria-
The rising (patent document 1) of glycan Complex Inhibition blood glucose value and glucose in urine and the thalline (dead thalline) of Lactobacillus casei have blood
Sugar rises inhibitory action (non-patent literature 1).
Prior art literature
Patent document
Patent document 1:Japanese Unexamined Patent Publication 8-59492 publications
Non-patent literature
Non-patent literature 1:Endocrine Journal 1997,44(3),357-365
The content of the invention
Invent problem to be solved
However, existing blood sugar value depressant too pays close attention to the improvement of hyperglycaemia on an empty stomach, and exist and cause low blood
The risk of sugar, wherein, using sulfonyl urea medicine, how (Glinide) medicine is not only improved row as the insulin secretion stimulators of representative
Early insulin secretion (the additional secretion of first phase) after diet, and improve later stage secretion (the additional secretion of the second phase) and empty
Basal secretion during abdomen, therefore outside risk of hypoglycemia, can also cause the fatigue of beta Cell of islet, exist and cause further
The problem of reduction of insulin secretion performance and hyperglycaemia.The problem of in order to solve such, due also to as described above, Japanese 2
Patients with type Ⅰ DM main cause is the reduction of Early secretion of insulin performance, it is desirable that developing only improves Early insulin secretion performance
Preparation.
Therefore, problem of the invention is to provide new Early secretion of insulin performance improving agent.
Method for solving problem
Therefore, the present inventor is studied to solve above-mentioned problem, as a result finds not only lactic acid bacteria
Dead thalline, and viable bacteria also has special excellent Early secretion of insulin performance improvement effect, so as to complete the present invention.
That is, the present invention provides following (1)~(9).
(1) a kind of Early secretion of insulin performance improving agent, it is with the viable bacteria 1 × 10 containing lactic acid bacteria10It is more than individual cell
Composition be active ingredient.
(2) the Early secretion of insulin performance improving agent as described in (1), wherein, every 1 day intake lactic acid bacteria viable bacteria 1 ×
1010It is more than individual cell.
(3) the Early secretion of insulin performance improving agent as described in (1) or (2), wherein, lactic acid bacteria is to belong to lactobacillus
Lactic acid bacteria.
(4) the Early secretion of insulin performance improving agent as any one of (1)~(3), wherein, lactic acid bacteria is cheese
Lactobacillus.
(5) the Early secretion of insulin performance improving agent as any one of (1)~(4), wherein, lactic acid bacteria is cheese
YIT9029 plants of lactobacillus.
(6) viable bacteria 1 × 10 containing lactic acid bacteria10Composition more than individual cell is for manufacturing Early secretion of insulin
Use in energy improver.
(7) for Early secretion of insulin performance improvement, the viable bacteria 1 × 10 containing lactic acid bacteria10Group more than individual cell
Compound.
(8) a kind of Early secretion of insulin performance improvement method, wherein, by the viable bacteria 1 × 10 containing lactic acid bacteria10Individual cell
More than composition cast or absorb with effective dose to needing its object.
(9) the Early secretion of insulin performance improvement method as described in (8), wherein, the viable bacteria 1 of every 1 day intake lactic acid bacteria
×1010It is more than individual cell.
The effect of invention
The Early secretion of insulin performance improving agent of the present invention is that the viable bacteria for being found that lactic acid bacteria has especially strong effect
And obtain.By only improving the Early insulin secretion performance of insulin, enter caused by risk of hypoglycemia and fatigue by beta Cell of islet
One step induces the dangerous low of hyperglycaemia.
Embodiment
The active ingredient of the Early secretion of insulin performance improving agent of the present invention is the viable bacteria 1 × 10 containing lactic acid bacteria10It is individual
Composition more than cell.Shown in embodiment as be described hereinafter, in the lactic acid bacteria containing a large amount of dead bacterium, without insulin early stage point
The improvement secreted, thus the present invention effect be lactic acid bacteria viable bacteria it is distinctive.Viable bacteria mentioned here can for example pass through
The composition suitably diluted with physiological saline or ringer's solution is coated on to addition BCP plate count agar culture medium or addition
TOS propionic acid culture mediums of mupirocin etc. are suitable to the culture medium that lactic acid bacteria determines, in 37 DEG C of lactic acid bacterias occurred after being kept for 3 days
Bacterium colony counted and determined.In addition, in the case of obligate anaerobe, be put into deaerate and be filled with carbon dioxide and/or
Kept in the anaerobic jar of nitrogen.
As lactic acid bacteria, be not particularly limited, can enumerate lactobacillus, lactococcus, enterococcus spp, Pediococcus,
Leuconostoc, Bifidobacterium etc..Wherein, preferably lactobacillus, Bifidobacterium, more preferably lactobacillus.
And then, as the lactic acid bacteria of lactobacillus, can enumerate Lactobacillus casei, Lactobacillus rhamnosus, corn lactobacillus,
Lactobacillus bulgaricus, lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus gasseri etc..Wherein, preferred Lactobacillus casei, cheese breast
More preferably Lactobacillus casei YIT9029 plants (FERM BP-1366) in bacillus.
The viable bacteria of lactic acid bacteria, as be described hereinafter shown in embodiment, the effect with improvement Early secretion of insulin index.Wherein,
Early secretion of insulin index refers to, in the experiment of 75g oral glucose loads, from the blood glucose on an empty stomach before glucose load with
The insulin that insulin is calculated according to the following formula in the blood glucose of 30 minutes and blood after insulin, glucose load in blood on an empty stomach is early
Phase secretes index.
The Early secretion of insulin index of Healthy People is more than 0.4, the pancreas islet of the people of Early secretion of insulin property abnormality
Plain Early insulin secretion index is less than 0.4.The people that Early secretion of insulin index is less than 0.4 is thought suffering from the possibilities of diabetes
It is high.
In the present invention, Early secretion of insulin performance improvement is to instigate such Early secretion of insulin index to reach health
The level of people, for example, make Early secretion of insulin index for more than 0.4, be preferably 0.4~5.0.In addition, also meaning and not
Make the additional secretion increase of the insulin of the second phase, preferably do not make insulin in the blood after glucose load after 60 minutes dense
Insulin concentration increase in blood after degree or glucose load after 120 minutes.
Make every 1 day intake lactic acid bacteria 1 × 10 of people of the Early secretion of insulin index less than 0.411During individual cell, insulin is early
Phase secretion index is improved.On the other hand, in the case where the intake of the viable bacteria of lactic acid bacteria is few, it cannot get insulin early stage
Secrete the improvement of index.
It is therefore preferable that every 1 day viable bacteria 1 × 10 of the intake containing lactic acid bacteria10Composition more than individual cell, more preferably every 1
Its viable bacteria 1 × 10 of intake containing lactic acid bacteria11Composition more than individual cell, intake in more preferably every 1 day contains lactic acid bacteria
Viable bacteria 1 × 1011Individual cell~1 × 1012The composition of individual cell.
The intake object of the Early secretion of insulin performance improving agent of the present invention is not particularly limited, and preferably insulin is early
Phase secretion index is less than 0.4 people, i.e. the people of diabetes B patient or diabetes B preparation group, particularly preferably with 2 type glycosurias
The artificial object of disease preparation group.Wherein, diabetes B preparation group refers to Early secretion of insulin index less than 0.4 and on an empty stomach
120 minutes more than blood glucose value 130mg/dL of more than blood glucose value 100mg/dL and/or glucose load people, refers to equivalent to glycosuria
The people of the borderline region of patient and healthy person.
Preferably every 1 natural gift, 1~3 orally ingestible of Early secretion of insulin performance improving agent of the present invention.In addition, as taking the photograph
During taking, continuous intake in preferably more than 1 week, continuous intake in more preferably more than 4 weeks, continuous intake in particularly preferred more than 8 weeks.
As long as viable bacteria 1 × 10 of the Early secretion of insulin performance improving agent containing lactic acid bacteria of the present invention10Individual cell with
On composition, then its dosage form do not limit, can for example be set to usual pharmaceutical preparations.As such preparation,
The solid formulation such as tablet, granule, powder, capsule can be enumerated;The liquors such as solution, suspending agent, emulsion;It is freeze-dried
Agent etc., these preparations can be mixed to prepare by the conventional method on preparation with appropriate pharmaceutical non-toxic carrier.As
Such pharmaceutical non-toxic carrier, can enumerate such as glucose, lactose, sucrose, starch, mannose, dextrin, aliphatic acid sweet
Grease, polyethylene glycol, HES, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, white egg
In vain, water, physiological saline etc..In addition, stabilizer, wetting agent, emulsifying agent, bonding agent, tonicity can also be properly added as needed
The usual additive such as agent, excipient.
In addition, easiness, the continuation in terms of of intake from intake, the viable bacteria of lactic acid bacteria is preferably with fermentate
Form is used.
Here, as fermentate, it is adapted to use acidified milk, the hair obtained by the viable lactic acid bacteria fermentation as active ingredient
Ferment soymilk, fermented juice, fermenting plant liquid etc..The manufacture of these fermentates can be manufactured according to conventional methods.Such as acidified milk,
Inoculated and cultured viable lactic acid bacteria on newborn culture medium after sterilization, is carried out homogenize process, obtains acidified milk base-material.This
When, the syrup solution that then addition mixing is prepared in addition is homogenized with homogenizer etc., then adds spices, and final system can be made
Product.
In addition, in culture, can also be in lactic acid bacteria and with other microorganisms, for example, saccharomyces, Candida
The yeast classes such as category, Rhodotorula, pichia category, Schizasaccharomyces, torulopsis, detection of zygosaccharomyces;Eurotium,
Der Pilzs such as Penicillium, Eurotium, Monascus, Mucor, Neurospora Pseudomonas, Rhizopus etc. are fermented,
But it is preferred that only use lactobacillus-fermented.
Embodiment
Next, enumerating embodiment, the present invention is illustrated in more detail.
Production Example 1 (manufacture of the present composition)
Skimmed milk powder after YIT9029 plants of Lactobacillus casei (Lactobacillus casei), 37 DEG C of fermentations are vaccinated with
After mixing molasses in solution, addition spices, homogenized, filling in a reservoir, obtains the present composition.The acidified milk system
The viable count of Lactobacillus casei in product 100mL is 1 × 1011Individual cell.
In addition, as placebo, wind is have adjusted using without Lactobacillus casei, addition and the equal lactic acid of fermented dairy product
The composition of taste.In addition, on others composition, it is identical with the present composition.
Test 1 (embodiment)
(experimental method)
It is less than 0.4 male 19 (Early secretion of insulin index, on an empty stomach blood glucose for Early secretion of insulin index
Value, glucose load after 120 minutes the average value of blood glucose value be respectively 0.28,107mg/dL and 172mg/dL) and 17 (pancreases
Island element Early insulin secretion index, on an empty stomach blood glucose value, glucose load after 120 minutes the average value of blood glucose value be respectively 0.29,
111mg/dL and 178mg/dL), make what its 1 day 1 (100mL) absorbed 8 weeks Production Examples 1 to contain Lactobacillus casei viable bacteria 1 respectively
×1011The composition (the hereinafter referred to as present composition) of individual cell or the placebo without Lactobacillus casei.In addition, right
In measured, the habits and customs indicate not change in test the diet before experiment is participated in as far as possible, drink, sleep etc.;Avoid big
Width depart from the overexercise of usual scope, go on a diet, overfeeding.
(result)
By the Early secretion of insulin exponential representation before intake, after 4 weeks, after 8 weeks in table 1.As shown in table 1, every 1 is passed through
Its intake Lactobacillus casei viable bacteria 1 × 1011Individual cell, compared with placebo, confirms Early secretion of insulin improvement.Separately
Outside, although do not represent result, but in the group of every 1 day intake Lactobacillus casei viable bacteria, be used as the basal secretion amount of insulin
Index blood on an empty stomach in insulin concentration have almost no change.In addition, the index of the addition secretory volume as the second phase
, insulin concentration (table in insulin concentration (table 2) and blood after 120 minutes in blood after 75g glucose loads after 60 minutes
3) reducing, therefore confirm the present composition does not make the basal secretion of insulin and the additional secretion increase of the second phase.By
This, confirms by absorbing Lactobacillus casei viable bacteria 1 × 10 daily11Individual cell, can specifically improve the early stage of insulin
Secernment property.
[table 1]
(unit (μ U/ml)/(mg/dl))
※ values are average value
[table 2]
(unit μ U/ml)
[table 3]
(unit μ U/ml)
Test 2 (comparative experiments)
(experimental method)
It is less than 0.4 male 8 (Early secretion of insulin index, on an empty stomach blood glucose for Early secretion of insulin index
Value, glucose load after 120 minutes the average value of blood glucose value be respectively 0.24,117mg/dL and 173mg/dL) and 7 (pancreas islet
Plain Early insulin secretion index, on an empty stomach blood glucose value, glucose load after 120 minutes the average value of blood glucose value be respectively 0.16,
121mg/dL and 189mg/dL), bag (2g) intake in its every 1 day 1 is contained Lactobacillus casei viable bacteria 4 × 10 per 2g in 8 weeks respectively9It is individual
Cell and dead bacterium 2 × 1011The powder of individual cell or the placebo without Lactobacillus casei.By the pancreas islet before intake, after 8 weeks
Plain Early insulin secretion exponential representation is in table 4.Wherein, powder refer to relative to the viable bacteria containing YIT9029 plants of Lactobacillus casei and
The freeze-dried powder of dead bacterium, adds the powder for being mixed to get skimmed milk powder and trehalose with 2 to 1, is adjusted to above-mentioned bacterium number
Powder, placebo refers to the preparation for being mixed to get skimmed milk powder and trehalose with 2 to 1.In addition, the dead bacterium number contained by powder
By the total bacteria count as the Lactobacillus casei contained by DAPI Determination Staining powder, remove after viable count and try to achieve therefrom.
(result)
As shown in table 4, in intake Lactobacillus casei viable bacteria 4 × 10 daily9In the case of individual cell, confirm at the 8th week
Early secretion of insulin index decreased, Early secretion of insulin performance does not improve.
[table 4]
(unit (μ U/ml)/(mg/dl))
※ values are average value
Claims (9)
1. a kind of Early secretion of insulin performance improving agent, it is characterised in that:
With the viable bacteria 1 × 10 containing lactic acid bacteria10Composition more than individual cell is active ingredient.
2. Early secretion of insulin performance improving agent as claimed in claim 1, it is characterised in that:
The viable bacteria 1 × 10 of every 1 day intake lactic acid bacteria10It is more than individual cell.
3. Early secretion of insulin performance improving agent as claimed in claim 1 or 2, it is characterised in that:Lactic acid bacteria is to belong to breast
The lactic acid bacteria of Bacillus.
4. such as Early secretion of insulin performance improving agent according to any one of claims 1 to 3, it is characterised in that:Lactic acid bacteria
For Lactobacillus casei.
5. such as Early secretion of insulin performance improving agent according to any one of claims 1 to 4, it is characterised in that:Lactic acid bacteria
For YIT9029 plants of Lactobacillus casei.
6. the viable bacteria 1 × 10 containing lactic acid bacteria10Composition more than individual cell changes for manufacturing Early secretion of insulin performance
Use in kind agent.
7. for Early secretion of insulin performance improvement, the viable bacteria 1 × 10 containing lactic acid bacteria10Composition more than individual cell.
8. a kind of Early secretion of insulin performance improvement method, it is characterised in that:
By the viable bacteria 1 × 10 containing lactic acid bacteria10Composition more than individual cell is cast or absorbed with effective dose to needing its pair
As.
9. Early secretion of insulin performance improvement method as claimed in claim 8, it is characterised in that:Every 1 day intake lactic acid bacteria
Viable bacteria 1 × 1010It is more than individual cell.
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YONG ZHANG等: "Lactobacillus casei reduces susceptibility to type 2 diabetes via microbiota-mediated body chloride ion influx", 《SCIENTIFIC REPORTS》 * |
范文娅等: "乳酸菌的降血糖作用研究进展", 《天然产物研究与开发》 * |
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