JP2007022981A - Reducing agent for ammonia in blood and food and drink reducing ammonia in blood - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe and more inexpensive reducing agent for ammonia in blood having reducing effects on the ammonia in blood and more scarcely applying a load to the body and to provide a food and drink having the reducing effects on the ammonia in blood. <P>SOLUTION: The reducing agent for the ammonia in blood is characterized as comprising γ-PGA (γ-polyglutamic acid) as an active ingredient. The food and drink reducing the ammonia in blood is characterized as similarly adding the γ-PGA. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a blood ammonia reducing agent comprising γ-polyglutamic acid (hereinafter sometimes abbreviated as γ-PGA) as an active ingredient and a food and drink having a blood ammonia reducing effect.

  In order to maintain homeostasis in the living body, the liver metabolizes harmful substances and excess substances in the blood and normalizes the blood that is transported throughout the body. For this reason, if the above action is not performed due to a decrease in liver function, harmful substances and excess substances are carried over the blood to the whole body. As a result, the amount of ammonia in the peripheral blood is increased, causing serious results such as hepatic encephalopathy and hyperammonemia.

  Methods for reducing the amount of ammonia in the blood include adjusting the intestinal environment to suppress the amount of ammonia generated, excreting ammonia generated in the intestine early, or suppressing the absorption of ammonia in the intestine. Conceivable. Specifically, (1) a method of killing harmful bacteria that produce spoilage products in the intestine by administration of antibiotics such as neomycin and kanamycin, and (2) oligosaccharides such as lactulose (Bifido factor) as a supplement. ) Is used to make the useful bacteria such as bifidobacteria and lactobacilli predominate in the intestine and suppress the growth of harmful bacteria such as Escherichia coli and Clostridium perfringens and consequently suppress the production of spoilage products.

  However, the above-mentioned method by administration of antibiotics may kill not only harmful bacteria in the intestine but also other useful bacteria, and resistant bacteria may appear due to heavy use of antibiotics. It has also been reported that there are drawbacks that disrupt the bacterial flora and cause a decline in immune function.

On the other hand, oligosaccharides are known to reduce pH in the intestine by lactulose, raffinose, or sugar alcohol, lactitol, and to excrete ammonia early (Patent Documents 1 and 2). However, these need to be taken on a daily basis, but there is a pain for patients who have to drink large amounts. Furthermore, these substances have a strong sweet taste and it is difficult to take a large amount thereof, and some patients may not be able to exert a desired effect. In addition, diarrhea may occur due to a decrease in intestinal pH, which not only makes it difficult to absorb other necessary nutrients, but can also gradually weaken the intestinal tract. In addition, many of these products are expensive rather than daily consumption.
JP-A-10-194975 JP-A-11-189538

  Accordingly, an object of the present invention is to provide a safer and less expensive blood ammonia reducing agent that has a blood ammonia reducing effect and less burdens the body, and a food and drink having a blood ammonia reducing effect. There is.

  The present inventors have found that γ-PGA has an effect of lowering the ammonia concentration in blood without lowering the pH in the intestine, while studying the physiological function of γ-PGA. The present invention has been completed based on the knowledge.

  That is, the present invention relates to a blood ammonia reducing agent characterized by containing γ-PGA as an active ingredient, and to a food or beverage product having a blood ammonia reducing effect characterized by containing γ-PGA.

  According to the blood ammonia reducing agent or food / beverage product having the blood ammonia reducing effect of the present invention, containing γ-PGA brings about an effect that the blood ammonia concentration is lowered by taking this.

  Hereinafter, the present invention will be described in detail.

  Γ-PGA, which is an active ingredient of the blood ammonia reducing agent or blood ammonia reducing food or drink of the present invention, is a polypeptide secreted outside the cell by Bacillus bacteria such as Bacillus natto, and culture of Bacillus natto, etc. It can be obtained from the liquid. The molecular weight varies depending on the bacterial cell, the culture method, and the purification method from the culture solution, and is known to be several thousand to several million. As a commercially available product, for example, “Karutake” manufactured by Ajinomoto Co., Inc. is available.

  There is no particular limitation on the formulation of the blood ammonia reducing agent containing γ-PGA of the present invention as an active ingredient, and those skilled in the art can appropriately formulate the formulation using a conventional formulation technique as appropriate. If there is no problem, γ-PGA can be taken as it is in an extreme case. Conventional formulation technologies include cellulose and derivatives thereof such as crystalline cellulose, starches and derivatives thereof such as corn starch and dextrin, sugars and derivatives thereof such as lactose, glucose, mannitol, sorbitol, natural polymers such as gum arabic Compounds, inorganic substances such as calcium carbonate and sodium chloride, other excipients, amino acid sweeteners such as sucrose and aspartame, saccharin, acesulfame K, sucralose and other flavoring agents, binders, disintegrants, lubricants A combination with additives such as a bulking agent and a coating agent is included, and the dosage form can be appropriately formed into a capsule, liquid, granule, powder, tablet or the like.

  The production of blood ammonia-reducing food or drink containing the γ-PGA of the present invention as an active ingredient is not particularly limited, and prevention of hepatic encephalopathy or hyperammonemia or the like containing γ-PGA or It can be prepared in the form of a pathological diet for treatment.

  According to the present inventors, even when the intake of γ-PGA is less than 0.5 g per kg of body weight per day, the blood ammonia reducing effect has been confirmed. The content of γ-PGA may be appropriately determined according to the intended preparation and food and drink, and the amount of γ-PGA to be taken in order to obtain the blood ammonia reducing effect is not particularly limited.

Test example 1
(1) Test method Seven-week-old SD male rats (32 rats) were preliminarily raised for one week to acclimatize to the breeding environment, and confirmed that there was no problem with their health condition and were subjected to the test. In addition, tap water and a commercially available solid feed were freely ingested throughout the preliminary breeding and test breeding periods.

  32 mice were randomly selected from 3 groups of 10 or 11 γ-PGA administration group (γ-PGA group) (10 mice), lactulose administration group (lactulose group) (11 mice), and control group (11 mice). Divided into groups.

  For rats in the γ-PGA group, γ-PGA powder (Ajinomoto Co., Ltd. “Karutake”, Glu equivalent purity 82%) was adjusted to 1.0 g per kg of body weight per day, and equal to twice a day. Divided and administered repeatedly for 7 days.

  On the other hand, for the rats of the lactulose group, lactulose powder (manufactured by Sigma-Ardrich, lactulose purity 95% or more) was divided into equal amounts twice a day so as to be 3.0 g per kg of body weight per day, and repeated for 7 days. Administered.

  In the control group, ultrapure water was repeatedly administered for 7 days by dividing 10 g / kg body weight per day into equal parts twice a day.

  In the γ-PGA group and the lactulose group, no diarrhea symptoms or side effects such as a decrease in feed intake were observed.

  On the 8th day, several hours after the end of the first administration, portal blood was collected from all rats under anesthesia, plasma was separated by centrifugation, and the ammonia concentration in the portal blood was measured. It was measured using “Wako” (manufactured by Wako Pure Chemical Industries, Ltd.).

  Further, in order to measure the pH of the cecum contents, 1 g of cecal contents was suspended in 2 mL of distilled water, the suspension was centrifuged, and the resulting supernatant was measured with a pH meter.

(2) Measurement Results The serum ammonia concentration measurement results are shown in Table 1 below as the mean value (Mean) and standard error (SEM) of each group. From Table 1, the lactulose group tended to have a lower blood ammonia concentration than the control group. In the γ-PGA group, the blood ammonia concentration tended to be lower than that in the control group and the lactulose group. From this, it can be seen that γ-PGA has an action of suppressing an increase in blood ammonia concentration.

  The results of measurement of cecal pH are shown in Table 2 below as the mean value and standard error of each group. From Table 2, a marked decrease in cecal pH was observed in the lactulose group compared to the control group. In contrast, it was found that the pH in the cecum was decreased in the γ-PGA group as compared with the control group, but the degree was smaller than that in the lactulose group.

Test example 2
(1) Test method 10 weeks old SD female rats (23 rats) were preliminarily raised on a commercial solid feed for one week to acclimatize to the breeding environment, and then ovariectomy was performed. The observation period after ovariectomy and sham operation was set for 1 week, and the “AIN93-G” composition diet, which is a standard diet for growing small animals, was ingested. During the test period, tap water and feed were freely consumed.

  Thereafter, each group was randomly divided into 3 groups, 6 mice per group, 1% γ-PGA administration group (1% γ-PGA group), 2% γ-PGA administration group (2% γ-PGA group) and control group, The study was conducted for 4 weeks.

  During this study, rats in the control group were replaced with the “AIN 93-G” composition diet, and rats in the γ-PGA group (Group 2) were replaced with corn starch in the “AIN 93-G” composition diet, Feeds to which γ-PGA (Ajinomoto Co., Ltd. “Karutake”, Glu equivalent purity 88%) was added 1% and 2% each were ingested freely.

  During the study period, no side effects such as diarrhea symptoms or reduced intake were observed in any group.

  Abdominal aortic blood was collected from all rats under anesthesia, and plasma was separated by centrifugation, and then the ammonia concentration was measured using a measurement kit “Ammonia Test Wako” (manufactured by Wako Pure Chemical Industries, Ltd.).

(2) Measurement Results The serum ammonia concentration measurement results are shown in Table 3 below with the mean value (Mean) and standard error (SEM) of each group. From Table 3, the 1% γ-PGA group tended to have a lower blood ammonia concentration than the control group, and the 2% γ-PGA group was found to be significantly lower than the control group. From this, it can be seen that γ-PGA has an action of suppressing an increase in blood ammonia concentration.

  At this time, the daily dietary intake of rats was about 15 g, that is, the γ-PGA intake was 0.15 g and 0.3 g in the 1% and 2% γ-PGA groups, respectively. Further, the weight of the rat on the day of necropsy is about 350 g, that is, the dose of γ-PGA per kg body weight is 0.429 g and 0.857 g, respectively. In Test Example 1, it was confirmed that the increase in blood ammonia concentration was suppressed by an intake test of 3.0 g per day of body weight, but in the test of Test Example 2, the blood ammonia concentration of γ-PGA was increased at a lower level. The inhibitory effect was confirmed.

ADVANTAGE OF THE INVENTION According to this invention, the blood ammonia reducing agent and blood ammonia reduction food-drinks which are safe and have the outstanding blood ammonia reduction effect with little load with respect to a body can be provided cheaply.

Claims (2)

  A blood ammonia reducing agent comprising γ-polyglutamic acid as an active ingredient. A blood ammonia-reducing food or drink characterized by adding γ-polyglutamic acid.