JP2008063234A - Prophylactic/ameliorating composition for chronic renal failure - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a daily easily ingestible composition capable of efficiently carrying out prophylacticing/ameliorating chronic renal failure. <P>SOLUTION: The composition is obtained by including GABA (γ-aminobutyric acid) and α-lipoic acid and/or catechins as an active ingredient of the prophylactic/ameliorating composition for the chronic renal failure. The GABA is preferably a fermentation product of a lactic acid bacterium containing the GABA. The fermentation product of the lactic acid bacterium containing the GABA preferably contains 20-80 mass% of the GABA in terms of the solid content. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a composition that can not only prevent chronic renal failure but also improve its symptoms.

  The kidneys filter the body fluid and discharge the waste as urine, and also regulate the ratio of the components of the body fluid and blood pressure. When the kidney function decreases, the waste in the blood drains well. It becomes difficult to maintain the internal environment of the body.

  Renal failure refers to a condition in which renal function is reduced, and is divided into acute renal failure and chronic renal failure. Acute renal failure is a sudden decrease in kidney function between hours and days due to bleeding, rapid decrease in blood pressure, infection, dehydration associated with burns, etc. Most of the functions can be restored. Chronic renal failure, on the other hand, gradually loses kidney function over a long period of several years to over ten years due to immune system abnormalities, allergies to drugs, high blood pressure, diabetes, chronic nephritis, etc. Yes, once lost, it cannot be restored.

  At the end of renal failure, the kidneys almost fail, so ultimately, artificial dialysis or kidney transplantation that purifies blood instead of the kidneys is necessary, but currently there are about 250,000 patients who need dialysis in Japan. It is said that there are people, and it is thought that the number of patients will increase with the aging of society.

  By the way, γ-aminobutyric acid (hereinafter also referred to as “GABA”) is a kind of amino acid widely distributed in nature such as animals and plants, and in animals, it exists in the brain and spinal cord as a neurotransmitter. GABA is known to have various physiologically active effects such as an antihypertensive action, a tranquilizing action, a diabetes improving action and the like. As an action relating to renal function, for example, Non-Patent Document 1 describes prevention against acute renal failure.・ The improvement effect is reported. Non-Patent Document 2 reports the effect of anaerobic treatment tea (Gabalon tea) on blood pressure and renal function in salt-loaded rats. Patent Document 1 discloses a health food enriched in GABA content characterized by containing black wheat malt or a processed product thereof, and the health food has a function of activating kidney function. Is described.

On the other hand, α-lipoic acid (also known as thioctic acid) and catechins are widely known as substances having an antioxidant action. For example, Patent Document 2 discloses an anti-diabetic drug containing α-lipoic acid and vitamin E as active substances. As an indication of the diabetic drug, renal parenchymal degeneration is exemplified. Yes. Patent Document 3 discloses sequelae of diabetes mellitus characterized by containing R-(+)-α-lipoic acid, R-(-)-dihydrolipoic acid or metabolites and salts, esters, and amides thereof. And drugs for the treatment of late complications such as cataracts, neuropathy, nephropathy are disclosed. Patent Document 4 discloses the use of a lipoic acid component and a conjugate acid component for the treatment of diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, and atherosclerosis caused by diabetes. ing. Patent Document 5 discloses a renal function improving agent having a mesangial cell-specific growth inhibitory activity, which contains tea polyphenols extracted from tea as an active ingredient. It is disclosed. Patent Document 6 discloses a mesangial cell growth inhibitor containing (−)-epicatechin 3-O-gallate as an active ingredient. Patent Document 7 discloses a renal failure ameliorating agent containing (+)-catechin as an active ingredient. Patent Document 8 discloses a composition for reducing uremic substances characterized by containing (−)-epicatechin 3-O-gallate as an active ingredient.
JP 2001-213773 JP 2004-217669 A JP-A-7-206676 Special Table 2004-508399 JP-A-6-1222626 Japanese Patent Laid-Open No. 6-16549 JP-A-5-43459 Japanese Patent No. 2649296 Food and Chemical Toxicology 42 (2004) 2009-2014 Journal of Japanese Society of Home Economics Vol.51 No.4 265〜271 (2000)

  However, since there are various factors in chronic renal failure, there are many cases where a satisfactory effect cannot be obtained even if the above components are used alone. Further, α-lipoic acid and catechins have a bad taste, and it has been difficult to take a sufficient amount on a daily basis for a long period of time so that an effect can be expected.

  Accordingly, an object of the present invention is to provide a composition that can be easily taken on a daily basis and can efficiently prevent and ameliorate chronic renal failure.

  To achieve the above object, the composition for preventing and improving chronic renal failure of the present invention comprises γ-aminobutyric acid, α-lipoic acid and / or catechins as active ingredients.

  In the composition for preventing / ameliorating chronic renal failure according to the present invention, the γ-aminobutyric acid is preferably a γ-aminobutyric acid-containing fermented lactic acid bacterium.

  The γ-aminobutyric acid-containing lactic acid bacteria fermented product preferably contains 20-80% by mass of γ-aminobutyric acid in terms of solid content.

  The composition for preventing and improving chronic renal failure of the present invention contains γ-aminobutyric acid and α-lipoic acid and / or catechins as active ingredients, so that a synergistic effect of these components can be expected, and chronic kidney can be efficiently produced. Can prevent or improve failure.

  ADVANTAGE OF THE INVENTION According to this invention, the composition which can be ingested daily as it is or by mix | blending with various food-drinks, and can prevent and improve chronic renal failure efficiently can be provided.

  The γ-aminobutyric acid (GABA) used as one of the active ingredients of the composition for preventing / ameliorating chronic renal failure of the present invention may be any one that can be used for pharmaceuticals and foods and beverages, and commercially available products may be used. Among them, GABA obtained by lactic acid bacteria fermentation is preferably used. GABA by lactic acid bacteria fermentation can be obtained, for example, according to the method described in JP-A-2003-70462. That is, a pre-culture solution of lactic acid bacteria (Lactobacillus hirugardi K-3 strain) is added to a culture solution (adjusted to pH 4.5 to 5.5) containing glutamic acid or sodium glutamate, glucose, yeast extract, emulsifier, etc. Incubate for 48-72 hours with readjustment. The obtained fermented liquor (preferably containing 70 to 80% by mass of GABA per solid content) is filtered and sterilized, and an appropriate excipient or the like is added to dry powder to obtain a GABA-containing lactic acid bacterium fermentation product (GABA content 20 to 80% by mass) can be obtained. In addition, you may further refine | purify, for example by desalinating the said fermented liquor.

  Commercially available α-lipoic acid used as another active ingredient can be used. α-Lipoic acid has R and S isomers (optical isomers). In the present invention, racemic or R isomers are preferably used.

  In addition, catechins used as another active ingredient are a kind of plant polyphenols, and are generally named as epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate, epicatechin, gallocatechin, (+) catechin and the like. Say.

  The catechins used in the present invention can be obtained according to known methods (for example, JP-A-59-219384, JP-A-60-13780, JP-A-61-130285, etc.). For example, an extract obtained by extracting tea leaves with hot water is fractionated with an organic solvent such as ethyl acetate and dried to obtain epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate, epi A powder containing 30 to 98% by mass of catechins such as gallocatechin, gallocatechin, epicatechin and (+) catechin can be obtained. Since such catechin powder is commercially available, it can also be used.

  1-70 mass% is preferable and, as for content of GABA in the chronic renal failure prevention and improvement composition of this invention, 2-20 mass% is more preferable. Moreover, 0.1-10 mass% is preferable and, as for content of alpha-lipoic acid, 0.5-5 mass% is more preferable. Moreover, 0.1-10 mass% is preferable and, as for content of catechin, 0.5-5 mass% is more preferable.

  The form of the composition for preventing / ameliorating chronic renal failure of the present invention can be appropriately selected from liquids, powders, granules, tablets, capsules and the like according to applications.

  In addition to the components described above, the composition for preventing and improving chronic renal failure of the present invention includes excipients, emulsifiers, stabilizers, sweeteners, flavors, pH adjusters, thickeners, proteins, protein hydrolysates, peptides Ingredients commonly used in foods such as amino acids, nucleic acids, lipids, saccharides, polysaccharides and oligosaccharides can be included.

  The effective intake of the composition for preventing and improving chronic renal failure of the present invention is 0.05 to 1 g per day for adults, 0.01 to 0.4 g of α-lipoic acid, 0.01 to 0.4 g of catechins. It is.

  The composition for preventing and improving chronic renal failure of the present invention includes, for example, beverages (coffee beverages, tea beverages, carbonated beverages, sports beverages, fruit / vegetable beverages), dairy products (processed milk, milk beverages, lactic acid bacteria beverages, yogurt, cheese) ) And confectionery (jelly, chocolate, biscuit, gum, tablet confectionery, granule powder) and the like.

  EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not particularly limited thereto.

  2/3 of the left kidney of Wistar rats (male, body weight approximately 200 g) was excised, and the right kidney was ligated 7-10 days later to produce chronic renal failure model rats (7-10 after the right kidney ligation) Used for testing after days).

  Hereinafter, the test method will be described.

・ Grouping (10 per group)
Normal group (normal rat)
Control group (chronic renal failure model rat)
Test group 1 (chronic renal failure model rat)
Test group 2 (chronic renal failure model rat)

・ Administration sample (oral administration by stomach tube)
Normal group and control group: GABA non-administration Test group 1: GABA-containing lactic acid bacteria fermented product in terms of GABA 100 mg / kg body weight / day Test group 2: GABA-containing fermented lactic acid bacteria in terms of GABA 500 mg / kg body weight / day

  Using the lactic acid bacteria (Lactobacillus hilgardi K-3 strain) as the GABA-containing lactic acid bacteria fermented product, a fermentation broth is obtained by the method described in JP-A-2003-70462, and an excipient is added to this and sprayed. A dried product (GABA content: 21% by mass) was used.

  The animals were reared for 100 days under the above conditions (water and food were ingested freely). During the test period, water consumption, urine volume, urine protein, urinary albumin, urinary creatinine, creatinine clearance, blood urea nitrogen, blood creatinine, blood pressure, etc. were measured periodically. On the last day (100th day) of the test period, the kidneys of each group of rats were removed, and the expression level of fibronectin in the tissues was measured by Western blotting.

  First, FIG. 1 shows the results of measuring blood urea nitrogen, and FIG. 2 shows the results of measuring blood creatinine. Next, FIG. 3 shows the results of measuring the amount of drinking water, FIG. 4 shows the amount of urine, FIG. 5 shows the urine creatinine, FIG. 6 shows the creatinine clearance, FIG. 7 shows the urine protein, and FIG. FIG. 9 shows the result of measuring the systolic pressure of blood pressure, and FIG. 10 shows the result of measuring the diastolic pressure of blood pressure. Furthermore, the result of having measured the fibronectin expression level in a renal tissue in FIG. 11 is shown.

  1 and 2, it can be seen that blood urea nitrogen and blood creatinine are significantly increased in the control group compared with the normal group, and renal function is decreased. On the other hand, in the test group, it can be seen that blood urea nitrogen and blood creatinine are significantly decreased compared to the control group.

  From FIG. 3 and FIG. 4, a big difference was not seen between the control group and the test group about the amount of drinking water and the amount of urine. However, with regard to urinary creatinine and creatinine clearance, the test group significantly increased compared to the control group (see FIGS. 5 and 6), and for urine protein and urinary albumin, the test group compared to the control group. (See FIGS. 7 and 8).

  From FIG. 9 and FIG. 10, it can be seen that the blood pressure of the test group is significantly lower than that of the control group, and a high improvement effect is seen for renal hypertension.

  FIG. 11 shows that the test group (particularly test group 2) significantly suppressed the fibrosis of the renal tissue as compared to the control group.

  From these results, when GABA was orally administered, an effect of improving glomerular damage and an effect of suppressing renal sclerosis were observed, and the effect tended to depend on the dose of GABA.

  The effect of α-lipoic acid on cell damage when methylglyoxal (hereinafter abbreviated as “MG”) was added to porcine-derived renal epithelial cells (LLC-PK1 cells) was examined.

(1) Cell viability
LLC-PK1 cells were seeded on a petri dish, and 24 hours later, α-lipoic acid was added at 0 to 50 μM. Further, after culturing for 24 hours, 500 μM of MG was added, and the cell viability (%) was examined after 6 hours. Cell viability was determined by trypan blue staining and MTT method (Carmichael, J., DeGraff, WG, Gazdar, AF, Minna, JD, and Mitchell, JB, Evaluation of a tetrazolium-based semiautomated colorimetric assay:
Assessment of chemosensitivity testing. Cancer Res., 47, 936-942 (1987)). The results are shown in FIGS. From FIG. 12 and FIG. 13, it can be seen that the cell viability is increased depending on the concentration of α-lipoic acid, regardless of whether the trypan blue staining or the MTT method is used.

(2) Effect on intracellular reactive oxygen species Cells are cultured under the same conditions as in (1) above, MG is added, and dichlorofluorescein assay (Wang, H., and Joseph, JA, Quantifying cellular) is performed for 6 hours. oxidative stress
by dichlorofluorescein assay using microplate reader. Free Radic. Biol. Med., 27,
612-616 (1999)), intracellular reactive oxygen species were measured. The result is shown in FIG. FIG. 14 shows that the intracellular reactive oxygen species are reduced depending on the concentration of α-lipoic acid.

(3) Effect on nitric oxide (NO) Cells are cultured under the same conditions as in (1) above, and MG is added for 6 hours.
Han, SH, Kim, BY, Hwang, SG, Park, KK, Yang, KH, and Chung, AS, Chlorophyllin
suppression of lipopolysaccharide-induced nitric oxide production in RAW 264.7
cells. Toxicol. Appl. Pharmacol., 166, 120-127 (2000)). The result is shown in FIG. FIG. 15 shows that the amount of NO is reduced depending on the concentration of α-lipoic acid.

  From these results, it can be seen that α-lipoic acid effectively suppresses oxidative stress in renal epithelial cells.

  The composition for preventing and improving chronic renal failure of the present invention has high safety because it contains an ingredient used as a food material as an active ingredient. And it can prevent chronic renal failure effectively and improve the symptoms by taking it as it is or by mixing it with various foods and drinks on a daily basis.

It is a figure which shows the result of having measured blood urea nitrogen in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the blood creatinine in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the amount of drinking in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the urine volume in the GABA oral administration test using the chronic renal failure model rat. It is a figure which shows the result of having measured the urine creatinine in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the creatinine clearance in the GABA oral administration test using the chronic renal failure model rat. It is a figure which shows the result of having measured the urine protein in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the urinary albumin in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the systolic pressure of the blood pressure in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the diastolic pressure of the blood pressure in the GABA oral administration test using the chronic renal failure model rat. It is a figure which shows the result of having measured the fibronectin expression level in a renal tissue in the GABA oral administration test using a chronic renal failure model rat. It is a figure which shows the result of having measured the cell viability (%) by the trypan blue dyeing | staining when (alpha) -lipoic acid and methylglyoxal were added to a pig origin renal epithelial cell (LLC-PK1 cell). It is a figure which shows the result of having measured the cell survival rate (%) by the MTT method when (alpha) -lipoic acid and methylglyoxal are added to a pig origin renal epithelial cell (LLC-PK1 cell). It is a figure which shows the result of having measured the influence on intracellular reactive oxygen species when (alpha) -lipoic acid and methylglyoxal are added to a pig origin renal epithelial cell (LLC-PK1 cell). It is a figure which shows the result of having measured the influence on nitric oxide (NO) at the time of adding (alpha) -lipoic acid and methylglyoxal to a pig origin renal epithelial cell (LLC-PK1 cell).

Claims (3)

A composition for preventing and / or improving chronic renal failure, comprising γ-aminobutyric acid, α-lipoic acid and / or catechins as active ingredients. The composition for preventing or improving chronic renal failure according to claim 1, wherein the γ-aminobutyric acid is a lactic acid bacterium-containing fermented product containing γ-aminobutyric acid. The composition for preventing or improving chronic renal failure according to claim 1 or 2, wherein the fermented lactic acid bacterium containing γ-aminobutyric acid contains 20 to 80% by mass of γ-aminobutyric acid in terms of solid content.

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