WO2016117654A1 - Promoteur de sécrétion d'insuline précoce - Google Patents

Promoteur de sécrétion d'insuline précoce Download PDF

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Publication number
WO2016117654A1
WO2016117654A1 PCT/JP2016/051732 JP2016051732W WO2016117654A1 WO 2016117654 A1 WO2016117654 A1 WO 2016117654A1 JP 2016051732 W JP2016051732 W JP 2016051732W WO 2016117654 A1 WO2016117654 A1 WO 2016117654A1
Authority
WO
WIPO (PCT)
Prior art keywords
insulin
lactic acid
cells
acid bacteria
initial
Prior art date
Application number
PCT/JP2016/051732
Other languages
English (en)
Japanese (ja)
Inventor
康人 吉田
栄一郎 内藤
智 國廣
幸司 宮崎
Original Assignee
株式会社ヤクルト本社
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 株式会社ヤクルト本社 filed Critical 株式会社ヤクルト本社
Priority to MYPI2017702472A priority Critical patent/MY191218A/en
Priority to SG11201705174WA priority patent/SG11201705174WA/en
Priority to CN201680006183.5A priority patent/CN107106619A/zh
Priority to KR1020177017045A priority patent/KR102497887B1/ko
Priority to JP2016570704A priority patent/JP6670256B2/ja
Publication of WO2016117654A1 publication Critical patent/WO2016117654A1/fr

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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

Definitions

  • the present invention relates to an agent for improving the initial secretory ability of insulin.
  • Diabetes is a metabolic disease whose main feature is a hyperglycemic state.
  • Chronic hyperglycemia persistence is known not only to cause microvascular disorders such as nephropathy, retinopathy and neuropathy, but also to promote the onset of arteriosclerotic diseases such as myocardial infarction and cerebral infarction. That is, it can be said that diabetes is a disease that greatly affects not only QOL but also life expectancy.
  • type 2 diabetes has a relatively insufficient effect of insulin due to a decrease in insulin secretory ability of pancreatic ⁇ cells and a decrease in insulin sensitivity (insulin resistance) in target tissues such as liver, skeletal muscle, and fat. It becomes hyperglycemia by doing.
  • Diabetes mellitus as a lifestyle-related disease that is rapidly increasing at present is type 2 diabetes, and Western lifestyles such as overeating, high-fat diet, and lack of exercise are strongly influenced as environmental factors.
  • type 2 diabetes is mainly caused by a decrease in insulin secretion ability, particularly insulin secretion ability, which is necessary to suppress a rapid increase in blood glucose level after sugar intake, rather than insulin resistance. Therefore, a method for improving the initial secretory capacity is desired.
  • Non-patent Document 1 the cell wall polysaccharide-glycan complex of Gram-positive bacteria suppresses the increase of blood glucose level and urine sugar (Patent Document 1) and the Lactobacillus casei cell body (dead cell body) It has been reported that it has an inhibitory effect on elevation (Non-patent Document 1).
  • insulin secretagogues such as sulfonylurea drugs and glinide drugs are Not only early secretion (phase 1 additional secretion) but also late phase secretion (phase 2 additional secretion) and fasting basal secretion, in addition to the risk of hypoglycemia, causing fatigue of pancreatic ⁇ cells, There was a problem that the insulin secretion ability was further lowered and hyperglycemia was caused.
  • an object of the present invention is to provide a new agent for improving early secretory ability of insulin.
  • the present inventors have studied to solve the above-mentioned problems, and found that there is an action for improving the ability to secrete early insulin, which is specifically superior to viable bacteria, not dead lactic acid bacteria, and complete the present invention. It came to.
  • the present invention provides the following [1] to [9].
  • An insulin early secretory ability improving agent comprising a composition containing 1 ⁇ 10 10 cells or more of live lactic acid bacteria as an active ingredient.
  • the early insulin secretion capacity improving agent according to any one of [1] to [3], wherein the lactic acid bacterium is Lactobacillus casei.
  • a composition comprising 1 ⁇ 10 10 cells or more of live lactic acid bacteria for use in improving the initial secretory ability of insulin.
  • a method for improving the initial secretory ability of insulin comprising administering or ingesting an effective amount of a composition containing 1 ⁇ 10 10 cells or more of live lactic acid bacteria to a subject in need thereof.
  • the insulin early secretory capacity improving agent of the present invention has been found to have a particularly strong action of live bacteria of lactic acid bacteria. By improving only the initial secretory ability of insulin, the risk of hypoglycemia and further hyperglycemia induction due to exhaustion of pancreatic ⁇ cells is reduced.
  • the active ingredient of the insulin early secretory ability improving agent of the present invention is a composition containing 1 ⁇ 10 10 cells or more of live lactic acid bacteria.
  • lactic acid bacteria containing a large amount of dead bacteria did not have an effect of improving the initial secretion of insulin, and therefore the effects of the present invention are peculiar to live bacteria of lactic acid bacteria.
  • the viable bacteria mentioned here are, for example, a composition appropriately diluted in physiological saline or Ringer's solution, applied to a medium suitable for measurement of lactic acid bacteria such as BCP-added plate count agar medium or mupirocin-added TOS propionic acid medium It can be measured by counting colonies of lactic acid bacteria that appeared after holding at 37 ° C. for 3 days. In the case of obligate anaerobic bacteria, it is sufficient to degas and hold in an anaerobic jar filled with carbon dioxide and / or nitrogen.
  • Lactic acid bacteria are not particularly limited, and include Lactobacillus genus, Lactococcus genus, Enterococcus genus, Pediococcus genus, Leuconostoc genus, Bifidobacterium genus and the like. Among these, the genus Lactobacillus and the genus Bifidobacterium are preferable, and the genus Lactobacillus is more preferable.
  • Lactobacillus lactic acid bacteria examples include Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus zeae, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus gasseri, etc. .
  • Lactobacillus casei is preferable, and among Lactobacillus casei, Lactobacillus casei YIT9029 strain (FERM BP-1366) is more preferable.
  • the insulin initial secretion index is the initial insulin calculated from the fasting blood glucose before fasting glucose and the fasting blood insulin, blood glucose 30 minutes after glucose loading and blood insulin in the 75 g oral glucose tolerance test by the following formula: The secretory index.
  • the healthy human initial insulin secretion index is 0.4 or more, and the human initial insulin secretion index with abnormal insulin initial secretion ability is less than 0.4. It is said that humans with an initial insulin secretion index of less than 0.4 are likely to have diabetes.
  • the improvement of the initial insulin secretion ability means that the insulin initial secretion index is set to a healthy human level, for example, the insulin initial secretion index is 0.4 or more, preferably 0.4 to 5.0. Means that. In addition, it means that the additional secretion of insulin in the second phase is not increased, preferably the blood insulin concentration 60 minutes after glucose loading or the blood insulin concentration 120 minutes after glucose loading is not increased. To do. *
  • the subject who takes the agent for improving early insulin secretion ability of the present invention is not particularly limited, but is preferably a human having an early insulin secretion index of less than 0.4, that is, a type 2 diabetic patient or a type 2 diabetes preliminarily group. It is more preferable to target persons in the type 2 diabetes preparatory group.
  • the type 2 diabetes preparatory group means a person with an initial insulin secretion index of less than 0.4 and a fasting blood glucose level of 100 mg / dL or more and / or a glucose load of 120 minutes or more and a glucose level of 130 mg / dL or more. A person who falls within the border between healthy and healthy people.
  • the initial secretory ability improving agent for insulin of the present invention is preferably taken orally in 1 to 3 divided doses per day.
  • the intake period is preferably taken continuously for 1 week or longer, more preferably taken continuously for 4 weeks or longer, particularly preferably taken continuously for 8 weeks or longer.
  • the preparation of the insulin early secretory ability improving agent of the present invention is not limited as long as it is a composition containing 1 ⁇ 10 10 cells or more of live bacteria of lactic acid bacteria.
  • it can be a conventional pharmaceutical preparation.
  • preparations include solid agents such as tablets, granules, powders, and capsules, solutions such as solutions, suspensions, emulsions, freeze-dried agents, and the like. It can be prepared by mixing with a nontoxic pharmaceutical carrier as appropriate by conventional means.
  • non-toxic pharmaceutical carriers include, for example, glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acids, gelatin, albumin , Water, physiological saline and the like.
  • conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonic agents, excipients and the like can be appropriately added as necessary.
  • live bacteria of lactic acid bacteria in the form of a fermented product in terms of ease of intake, continuity of intake, and the like.
  • fermented milk fermented soymilk, fermented fruit juice, fermented plant fluid, etc. fermented with lactic acid bacteria, which are active ingredients, are preferably used as fermented products.
  • These fermented products can be produced according to a conventional method.
  • fermented milk is obtained by inoculating and cultivating live lactic acid bacteria in a sterilized milk medium and homogenizing it to obtain a fermented milk base.
  • a separately prepared syrup solution is added and mixed, homogenized with a homogenizer or the like, and flavor is further added to obtain a final product.
  • Saccharomyces genus Candida genus, Rhodotorula genus, Pichia genus, Schizosaccharomyces genus, Torula genus, Tigosaccharomyces genus yeast, Aspergillus genus, Penicillium genus, Eurothium Fermentation such as genus, Monascus genus, Micol genus, Neurospora genus, and Rhizopus genus may be used in combination, but it is preferable to ferment only with lactic acid bacteria.
  • Lactobacillus casei strain YIT9029 was inoculated, syrup was mixed with skim milk solution fermented at 37 ° C., flavor was added, homogenized and filled into a container to obtain the composition of the present invention. .
  • the number of viable bacteria of Lactobacillus casei in 100 mL of this fermented dairy product was 1 ⁇ 10 11 cells.
  • the composition which did not contain Lactobacillus casei and added the lactic acid equivalent to fermented dairy products and adjusted the flavor was used.
  • about another composition it is the same as this invention composition.
  • Test 1 (Example) (experimental method) 19 males with an initial insulin secretion index of less than 0.4 (the initial insulin secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose loading were 0.28, 107 mg / dL, and 172 mg / dL, respectively) And 17 patients (average insulin initial secretion index, fasting blood glucose level, and blood glucose level after 120 minutes of glucose loading were 0.29, 111 mg / dL and 178 mg / dL, respectively).
  • composition of the present invention A composition containing 1 ⁇ 10 11 cells of live casei (hereinafter referred to as “the composition of the present invention”) or a placebo containing no Lactobacillus casei was ingested once a day (100 mL) for 8 weeks.
  • the subjects were instructed not to change their lifestyle, such as eating, drinking, sleeping, etc. as much as possible during the study, and to avoid excessive exercise, food saving, and overeating that greatly deviated from the normal range.
  • Table 1 shows the initial secretion index of insulin before intake, 4 weeks, and 8 weeks. As shown in Table 1, it was confirmed that ingesting 1 ⁇ 10 11 cells per day of live Lactobacillus casei improved the initial insulin secretion compared with placebo. Although the results are not shown, in the group that ingested 1 ⁇ 10 11 cells per day of live Lactobacillus casei bacteria, there was almost no change in the fasting blood insulin concentration, which is an indicator of the basic secretory amount of insulin. There wasn't. Furthermore, the blood insulin concentration (Table 2) 60 minutes after loading 75 g glucose and the blood insulin concentration (Table 3) after 120 minutes, which are indicators of the amount of additional secretion in the second phase, are decreased.
  • composition of the present invention does not increase the basal secretion of insulin and the additional secretion of the second phase. From this, it was confirmed that the initial secretory ability of insulin was specifically improved by ingesting 1 ⁇ 10 11 cells per day of live Lactobacillus casei.
  • Test 2 (Comparative experiment) (experimental method) 8 males with an initial insulin secretion index of less than 0.4 (Insulin early secretion index, fasting blood glucose level, and average blood glucose level after 120 minutes of glucose load were 0.24, 117 mg / dL, and 173 mg / dL, respectively) And 7 people (Insulin initial secretion index, fasting blood glucose level, and average glucose level after 120 minutes of glucose loading are 0.16, 121 mg / dL and 189 mg / dL, respectively), Lactobacillus casei viable bacteria per 2 g 4 ⁇ 10 9 cells and 2 ⁇ 10 11 cells of dead bacteria, or a placebo containing no Lactobacillus casei was ingested once a day (2 g) for 8 weeks.
  • Table 4 shows the initial secretory index of insulin before intake and after 8 weeks.
  • the powder is prepared by adding a powder obtained by mixing skim milk powder and trehalose in a ratio of 2 to 1 to a freeze-dried powder containing live and dead bacteria of Lactobacillus casei YIT9029 strain to adjust the number of bacteria.
  • a placebo is a mixture of skim milk powder and trehalose in a 2 to 1 ratio.
  • the number of dead bacteria contained in the powder was determined by measuring the total number of Lactobacillus casei contained in the powder by the DAPI staining method and excluding the number of living bacteria therefrom.

Abstract

La présente invention concerne un promoteur de sécrétion d'insuline précoce. Le promoteur de sécrétion d'insuline précoce présente comme principe actif une composition contenant 1 × 1010 cellules ou plus de bactéries d'acide lactique vivantes.
PCT/JP2016/051732 2015-01-22 2016-01-21 Promoteur de sécrétion d'insuline précoce WO2016117654A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
MYPI2017702472A MY191218A (en) 2015-01-22 2016-01-21 Agent for improving early insulin secretory capacity
SG11201705174WA SG11201705174WA (en) 2015-01-22 2016-01-21 Agent for improving early insulin secretory capacity
CN201680006183.5A CN107106619A (zh) 2015-01-22 2016-01-21 胰岛素早期分泌性能改善剂
KR1020177017045A KR102497887B1 (ko) 2015-01-22 2016-01-21 인슐린 초기 분비능 개선제
JP2016570704A JP6670256B2 (ja) 2015-01-22 2016-01-21 インスリン初期分泌能改善剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015010024 2015-01-22
JP2015-010024 2015-01-22

Publications (1)

Publication Number Publication Date
WO2016117654A1 true WO2016117654A1 (fr) 2016-07-28

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PCT/JP2016/051732 WO2016117654A1 (fr) 2015-01-22 2016-01-21 Promoteur de sécrétion d'insuline précoce

Country Status (6)

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JP (1) JP6670256B2 (fr)
KR (1) KR102497887B1 (fr)
CN (1) CN107106619A (fr)
MY (1) MY191218A (fr)
SG (2) SG10201906475UA (fr)
WO (1) WO2016117654A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109922815A (zh) * 2016-10-28 2019-06-21 株式会社益力多本社 无病率降低抑制剂

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011193730A (ja) * 2010-03-17 2011-10-06 Yakult Honsha Co Ltd 多糖−ペプチドグリカン複合体保有乳酸菌の取得方法

Family Cites Families (1)

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Publication number Priority date Publication date Assignee Title
JPH0859492A (ja) 1994-08-26 1996-03-05 Yakult Honsha Co Ltd 抗糖尿病薬

Patent Citations (1)

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JP2011193730A (ja) * 2010-03-17 2011-10-06 Yakult Honsha Co Ltd 多糖−ペプチドグリカン複合体保有乳酸菌の取得方法

Non-Patent Citations (4)

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ASEMI, Z. ET AL.: "Effect of Multispecies Probiotic Supplements on Metabolic Profiles, hs-CRP, and Oxidative Stress in Patients with Type 2 Diabetes", ANN NUTR METAB, vol. 63, no. 1-2, 2013, pages 1 - 9, ISSN: 0250-6807 *
SIMON, M.C. ET AL.: "Intake of Lactobacillus reuteri improves incretin and insulin secretion in glucose-tolerant humans: a proof of concept", DIABETES CARE, vol. 38, no. 10, October 2015 (2015-10-01), pages 1827 - 34, ISSN: 0149-5992 *
TRIPOLT, N.J. ET AL.: "Short communication: Effect of supplementation with Lactobacillus casei Shirota on insulin sensitivity, beta- cell function, and markers of endothelial function and inflammation in subjects with metabolic syndrome - A pilot study", J DAIRY SCI, vol. 96, no. 1, 2013, pages 89 - 95, ISSN: 0022-0302 *
ZHANG, Y. ET AL.: "Lactobacillus casei reduces susceptibility to type 2 diabetes via microbiota-mediated body chloride ion influx", SCI REP, vol. 4, no. 5654, 2014, pages 1 - 10, ISSN: 2045-2322 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109922815A (zh) * 2016-10-28 2019-06-21 株式会社益力多本社 无病率降低抑制剂

Also Published As

Publication number Publication date
JPWO2016117654A1 (ja) 2017-11-02
JP6670256B2 (ja) 2020-03-18
CN107106619A (zh) 2017-08-29
KR102497887B1 (ko) 2023-02-08
KR20170103774A (ko) 2017-09-13
SG10201906475UA (en) 2019-08-27
MY191218A (en) 2022-06-09
SG11201705174WA (en) 2017-07-28

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