JP5051335B2 - Composition having intestinal environment improving action - Google Patents

Description

  The present invention relates to a composition that can effectively improve the intestinal environment when used by hemodialysis patients, constipation patients, and the like.

  In the recent satiety world, the bias in eating habits has been recognized, and conversely the need for various nutrients has been admired, and many dietary supplements containing various nutrients, so-called supplements, have been released. Yes.

  Among them, L-carnitine has been reported to act as a carrier of active fatty acids that cross the mitochondrial membrane since it was reported to be a substance that promotes fatty acid oxidation in the liver. It is an important nutrient that exists mainly and is closely related to lipid metabolism, especially fatty acid oxidation. Recently, it has been clarified that it is related not only to fatty acid formation but also to lipid metabolism such as fatty acid synthesis, ketone body formation, and glyceride synthesis. Furthermore, effects on ischemic heart and arrhythmia have been reported.

  L-carnitine is an important low-molecular substance that is effective not only for fatty acid metabolism but also for ischemic heart, arrhythmia, etc., and is also considered effective for adult diseases such as hyperlipidemia. It is said that L-carnitine deficiency is related to muscle spasms, feeling of fatigue, weakness, decreased cardiac function, etc. often seen in hemodialysis patients. However, the amount of biosynthetic L-carnitine has decreased with age, and it cannot be adequately supplemented with a normal diet in hemodialysis patients. Therefore, L-carnitine is effectively supplemented. There is a need to.

  By the way, it has been reported that hemodialysis patients generally have a higher concentration of trimethylamine in blood than healthy individuals. Trimethylamine is usually considered to be produced by the degradation of carnitine, choline and the like by intestinal bacteria, and the produced trimethylamine is absorbed from the intestinal tract and oxidized by the enzyme in the liver to produce odorless triethylamine N- It is excreted in urine as oxide. However, in hemodialysis patients, since there is no excretion in urine, trimethylamine stays in the blood, sometimes causing a fishy-like body odor.

  In 1984, Rebouche et al. Reported a study on carnitine absorption using rats (Non-patent Document 1). That is, carnitine was orally or intravenously administered to normal rats, the degradation rate was compared, and at the same time, carnitine was orally administered to rats sterilized and The decomposition rate is compared. According to this, the production rate of carnitine degradation product (trimethylamine N-oxide) in urine is in the order of “ordinary rat oral administration”> “normal rat intravenous administration”> “sterile rat oral administration”. It has been suggested that enterobacteria have a strong influence on the degradation of.

  Even in the same oral administration, administration of carnitine at a low dose (95 μg / kg) has a higher rate of migration into the tissue than administration of carnitine at a high dose (136 mg / kg). The excretion rate in feces was low.

In 1991, Rebouche et al. Conducted an experiment by orally administering human-labeled carnitine and observed the appearance of labeled carnitine in urine and feces for 11 days (non-patented). Reference 2). As a result, the excretion rates of the labeled body into urine and feces were 47% and 55%, respectively. The main metabolites are trimethylamine N-oxide (excreted in the urine, 8-48% of the dose) and γ-butyrobetaine (excreted from the stool, 0.44-45% of the dose). The total carnitine excreted was 16-23% of the intake, and the total carnitine excreted from the stool was only a very small amount (2% or less).
This means that carnitine administered orally is not absorbed in the living body, but passes through the intestine as it is and is decomposed by intestinal bacteria in the large intestine, absorbed as trimethylamine, oxidized in the liver to trimethylamine N-oxide, and urine It is excreted inside.

  Therefore, since urinary excretion is not performed in hemodialysis patients, in order to reduce the production of such nephrotoxic substances by reducing the blood trimethylamine concentration, the intestinal tract of administered carnitine It can be said that it is necessary to suppress degradation by enterobacteria in the plant as much as possible. In other words, it is necessary to improve the intestinal environment and suppress the degradation of carnitine.

On the other hand, it has become clear that certain oligosaccharides are assimilated by Bifidobacterium, which is an enteric bacterium beneficial to humans, and Lactobacillus, which is a lactic acid bacterium. Has been reported to increase the growth of bifidobacteria and improve the gut microbiota.
Bifidobacteria or Escherichia coli, which are the intestinal flora, were examined for culture by adding carnitine in the presence of oligosaccharides, but E. coli degraded carnitine, but Bifidobacterium itself did not degrade carnitine. .

In addition, when bifidobacteria and E. coli are mixed and cultured in a medium supplemented with xylooligosaccharides and carnitine, the growth of E. coli does not change, but bifidobacteria grow significantly compared to bifidobacteria alone without any addition. The tendency to do was recognized.
Furthermore, it was confirmed that when bifidobacteria and E. coli were mixed and cultured in a medium supplemented with xylooligosaccharides and carnitine, the degradation of carnitine added in the medium was suppressed more than when cultured in E. coli alone.

  When bifidobacteria and Escherichia coli were mixed and cultured in a medium not containing saccharides with the addition of carnitine, it was observed that Bifidobacteria did not grow but Escherichia coli grew. As the E. coli grew, carnitine in the medium was completely degraded. On the other hand, when only bifidobacteria were added to carnitine and cultured in a medium containing no saccharide, the growth of bifidobacteria was not observed, and the added carnitine was not degraded.

  Although these facts are assimilated by the addition of certain sugars for Bifidobacteria and Escherichia coli that are intestinal flora, there is no change in the growth of E. coli, but the growth of Bifidobacteria is markedly increased. It is none other than showing that the degradation of carnitine is suppressed.

  In addition, hemodialysis patients cannot take a sufficient amount of vegetables and fruits that are rich in dietary fiber due to restrictions on intake of potassium and water. In addition, there are many opportunities to take drugs that lower the levels of potassium and phosphorus in the blood, and constipation is exacerbated by the side effects of these drugs. For this reason, it is also important to improve the intestinal environment by supplementing dietary fiber in order to retain water in the intestine and increase the amount of stool.

Furthermore, coenzyme Q ₁₀ (CoQ ₁₀ ) is known as a substance that produces hydroquinone, ubichromenol, and the like under the general name: ubidecalenone. The coenzyme Q ₁₀ is not only having a biological activity as a coenzyme, known as vitamin-like substance having an action of improving the oxygen utilization efficiency. It is also a metabolic cardiotonic drug, and pharmacological effects such as mild and moderate congestive heart failure ameliorating drugs have been observed.

The Coenzyme Q ₁₀ is easily depleted with age, also often heart disease elderly, for example, the prevention of such ischemic heart disease, or for the relief of the symptoms, to replenish coenzyme Q ₁₀ as a nutrient Is desirable. Generally, Coenzyme Q ₁₀ fish, it has been known that are included in many meat and seaweed, has high content of coenzyme Q ₁₀ in a natural food material are very limited, therefore, usually it is difficult to supply the amount of coenzyme Q ₁₀ to compensate for the shortfall from natural food materials in the meal.

In this way, Coenzyme Q ₁₀ is also not only plays a very important role in the field of energy production, from exerting an antioxidant effect, rather than the patients who are exposed to oxidative stress by hemodialysis It is also an ingredient that must not be released.
Biochemistry, 23 (26): 6422-6426 (1984) Metabolism, 40 (12): 1305-1310 (1991)

Therefore, the present invention aims to provide an auxiliary nutritional composition for hemodialysis patients based on the above examination results, and particularly anaerobic intestinal environment of hemodialysis patients biased to anaerobic bacteria. It is an object of the present invention to provide a supplementary nutritional composition that improves constipation by creating an environment in which sex bacteria can easily grow.
Furthermore, this invention makes it a subject to provide the supplementary nutrition composition which can be used for a hemodialysis patient, a constipation patient, or a diet by the improvement of this intestinal environment.
Another object is to provide an agent for improving energy metabolism.

The present invention for solving such a problem has the following configuration as a basic aspect.
(1) A supplemental nutritional composition comprising L-carnitine, oligosaccharide and dietary fiber;
(2) The compositions according to the above (1) by containing coenzyme _{Q 10;}
(3) The composition as described in (1) or (2) above, which is used for hemodialysis patients, constipation patients or diets;
(4) The composition according to the above (1) or (2) as an agent for improving energy metabolism;
(5) The composition according to (1) or (2) above as an agent for improving the intestinal environment;
(6) The composition according to any one of (1) to (5) above, further comprising bifidobacteria;
It is.

According to the present invention, a supplemental nutritional composition for improving the intestinal environment is provided, and is particularly effective as a supplemental nutritional composition for hemodialysis patients, constipation patients or diets.
Specifically, the auxiliary nutritional composition provided by the present invention, especially in vivo ingested L- carnitine, i.e. suppressing the degradation in the gut, also improve the energy metabolism by coenzyme Q _10, hemodialysis patients It has the advantage of avoiding the oxidative stress seen in
It also supplements dietary fiber, which is often deficient in hemodialysis patients, ensuring water retention in the intestines and increasing stool volume, and is therefore extremely effective as a dietary supplement. It is.

  As described above, the present invention is basically a supplementary nutritional composition for hemodialysis patients, constipation patients or diets characterized by containing L-carnitine, oligosaccharides and dietary fiber. In particular, it is a supplementary nutritional composition that effectively supplements various nutrients that hemodialysis patients lack.

  L-carnitine constituting the above composition includes alkanoyl L-carnitine selected from L-carnitine or acetyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine or isovaleryl L-carnitine or pharmacologically thereof Mention may be made of acceptable salts. Examples of such salts include tartrate, fumarate, magnesium citrate, hydrochloride, etc. Among them, L-carnitine tartrate itself is not hygroscopic and should preferably be used. Can do.

  In the supplementary nutritional composition provided by the present invention, it is preferable to blend so that about 10 to 500 mg of such L-carnitine is ingested.

Further, in the dietary supplement of the present invention, in order to suppress the degradation of L-carnitine in the intestine, the growth of bifidobacteria in the intestine is increased. For this purpose, oligosaccharide is ingested together with L-carnitine. It is essential to blend such.
The oligosaccharide referred to in the present invention is a general term for a combination of about 2 to 10 monosaccharides such as glucose and fructose. Therefore, disaccharides such as sucrose, lactose and maltose are also oligosaccharides from the molecular structure. Among them, in the present invention, it is preferable to use xylo-oligosaccharides mainly composed of xylobiose.

  This oligosaccharide strongly grows intestinal bifidobacteria and, when fermented by intestinal bacteria in the intestine, produces organic acids such as acetic acid and lactic acid, and makes the intestinal environment acidic. In addition, organic acids such as acetic acid and lactic acid produced are thought to stimulate the intestines, activate peristaltic movement, and improve constipation.

The greatest action of the oligosaccharide in the composition of the present invention is to grow Bifidobacterium, which is an enteric bacterium, in the intestine and thereby suppress the degradation of L-carnitine.
In addition, as described above, since urinary excretion is not performed in hemodialysis patients, the intestinal tract of administered carnitine is reduced in order to reduce blood triethylamine concentration and reduce production of such nephrotoxic substances. It is to suppress the degradation by enterobacteria in as much as possible.

This point was confirmed by the following test examples.
Test Example 1: Examination of the effect of bifidobacteria on the degradation of L-carnitine by E. coli

[the purpose]
It has been reported that L-carnitine taken orally is absorbed in the small intestine, but unabsorbed L-carnitine is metabolized by intestinal bacteria and the degradation product is absorbed from the intestinal tract.
Xylooligosaccharides are known to be assimilated by Bifidobacteria in the large intestine, and it is examined whether the growth of E. coli is suppressed when mixed culture with E. coli in the presence of xylooligosaccharides.

[Method]
(1) E. coli or bifidobacteria were inoculated into 10 mL of PYF medium to which glucose was added to a final concentration of 0.5%, and anaerobically cultured at 37 ° C. for 18 to 24 hours.
(2) The culture medium of Group 1, Group 2 and Group 3 of the experimental group was mainly composed of 10 mL of PYF medium (containing no glucose), and L-carnitine was added to a final concentration of 0.4 mg / mL, Xylooligosaccharide was added to a final concentration of 0.5%.
In addition, the culture media of groups 4, 5 and 6 of the experimental group were mainly composed of 10 mL of PYF medium (containing no glucose), and L-carnitine was added to a final concentration of 0.4 mg / mL. No addition was made.
The Escherichia coli (1) was diluted 10,000 times with PYF medium (containing no glucose), and 0.1 mL each was added to Group 1, Group 3, Group 4, and Group 6.
Moreover, 0.1 mL of bifidobacteria of said (1) was added to 1st group, 2nd group, 4th group, and 5th group.
Table 1 below summarizes these conditions.

＋：添加あり
−：添加なし

+: With addition-: Without addition

The culture medium of each experimental group was cultured at 37 ° C. for 20 to 24 hours under anaerobic conditions. The test was conducted with each group n = 3.
(3) After culturing for 20 to 24 hours, the viable count of E. coli and bifidobacteria in each culture solution is cultured at 37 ° C./24 hours under aerobic conditions using TS agar medium; Then, the cells were cultured at 37 ° C./48 hours under anaerobic conditions using a BL agar medium, and the number of each colony was measured.
(4) The remaining culture solution was centrifuged, divided into cells and supernatant, the pH of the supernatant was measured, and then the L-carnitine concentration in the supernatant was measured.

[result]
The results are summarized in Tables 2 and 3 below.
Table 2: Number of viable bacteria in culture (bacteria count / mL)

Table 3: pH and total carnitine concentration in the medium, and pH and total carnitine concentration of the supernatant after culture

As is clear from the above results, Escherichia coli grew regardless of the presence or absence of xylooligosaccharides and decomposed all the added L-carnitine. Bifidobacteria metabolize xylo-oligosaccharides in the presence of xylooligosaccharides, produce acids and proliferate, but cannot grow in the absence of xylooligosaccharides, and there is no degradation of L-carnitine under any conditions It was.
In the case where E. coli and bifidobacteria were mixed and cultured under the condition where xylooligosaccharide was added, the growth of bifidobacteria was increased by the xylooligosaccharide, and the growth of E. coli was suppressed due to the acidic side of the medium. -It is well understood that the degradation of carnitine was suppressed.

  On the other hand, in the case where E. coli and bifidobacteria are mixed and cultured under the condition where no xylooligosaccharide is added, since bifidobacteria cannot grow, the growth of E. coli is not suppressed, and L-carnitine is degraded by the grown E. coli. It was made. From this, the importance of growing Bifidobacteria that specifically assimilate xylo-oligosaccharides can be understood.

From the above test results, as the greatest action of the oligosaccharide in the present invention, the characteristics of growing bifidobacteria in the intestine and thereby suppressing the degradation of L-carnitine were well clarified.
What is necessary is just to contain 300-3000 mg of xylo-oligosaccharides as an oligosaccharide in that case.

In addition, the supplementary nutrition composition provided by the present invention is characterized by blending dietary fiber. Such dietary fiber formulation increases the growth of lactic acid bacteria and bifidobacteria in the intestine, which is beneficial together with the oligosaccharides taken together, and reduces the degradation rate of carnitine.
As such dietary fiber, preferably indigestible dextrin can be mentioned, and its intake is said to be insufficient among 15 to 21 g of dietary fiber to be taken per day. Since it is 9g, it is good to contain 2000-8000mg as an amount per day.

In the auxiliary nutritional compositions provided herein may further contain a coenzyme Q _10. In the take Coenzyme _{Q 10,} only to be formulated to 1~100mg ingestion. That is, coenzyme Q _10, as described above, a deficiency likely component with age, and in hemodialysis patients, since loss of coenzyme Q ₁₀ by hemodialysis often compensates for these lack the energy metabolism What is necessary is just to mix | blend so that 1-100 mg may be ingested as an amount sufficient for using for such a purpose.

In other words, Coenzyme Q ₁₀ is a substance that plays a very important role in the field of energy production, from exerting an antioxidant effect, it must be for patients who have been exposed to oxidative stress by hemodialysis It is also an ingredient. However, hemodialysis patients by hemodialysis three times per week, is a low molecular substance L- carnitine, but the fact that losing components such as coenzyme Q _10, these components, their biosynthesis with aging The amount has also decreased, and hemodialysis patients cannot be adequately supplemented with a normal diet and therefore need to be supplemented effectively.

The nutritional supplement provided by the present invention suppresses the degradation of L-carnitine in the intestine by increasing the growth of bifidobacteria and lactic acid bacteria in the intestine and improving the intestinal environment. Therefore, it is blended so as to ingest oligosaccharide and dietary fiber together with L-carnitine. As a further purpose of improving energy metabolism, but further contain a coenzyme Q _10. As a result, intestinal bifidobacteria and lactic acid bacteria are strongly proliferated, and organic acids such as acetic acid and lactic acid are produced by fermentation by beneficial intestinal bacteria, irritating the intestine and activating peristalsis to improve constipation Is done.

As described above, the nutritional supplement composition provided by the present invention is to supplement the intestinal bifidobacteria with the growth of the intestinal bifidobacteria in the intestine and thereby suppressing the degradation of L-carnitine. Therefore, bifidobacteria can be further contained.
That is, it is known that the intestinal flora of hemodialysis patients have very few beneficial bifidobacteria and lactic acid bacteria compared to healthy people, and very much E. coli compared to healthy people. Therefore, for hemodialysis patients, beneficial bifidobacteria are supplemented, the degradation of L-carnitine is suppressed, the intestinal tract is inclined to the acidic side, peristaltic movement is activated, and constipation is improved. .

As described above, in the auxiliary nutritional composition of the present invention, basically, L- carnitine, and characterized in that it contains oligosaccharides and dietary fibers further contains a coenzyme Q ₁₀ or bifidobacteria It is a dietary supplement for hemodialysis patients, constipation patients or diets, and is a nutritional supplement composition that effectively supplements various nutrients that hemodialysis patients lack. When taken such compositions in vivo ingested L- carnitine, i.e. suppressing the degradation in the gut, and also, to avoid oxidation stress seen in hemodialysis patients with coenzyme Q _10.
It also supplements dietary fiber, which is often deficient in hemodialysis patients, ensuring water retention in the intestine and increasing stool volume. Therefore, it is extremely effective as a dietary supplement composition for dieting. Is.

Example 1: Dietary supplement formulation as a tablet:
L-carnitine 200mg
Coenzyme Q ₁₀ 30mg
Bifidobacterium 1 billion Xylooligosaccharide 700mg
Indigestible dextrin 3000mg
Tablets as dietary supplements taken three times a day were prepared according to the above formulation.

Examples 2-7:
Tablets as dietary supplements taken three times a day were prepared according to the formulation shown in Table 4 below.

単位：ｍｇ（１日分量を示す）

Unit: mg (indicating daily dose)

The present invention uniquely To supplement the L- carnitine or Coenzyme Q ₁₀ is insufficient for the patient hemodialysis, elevated lipid energy metabolism, skeletal muscle, improves the motion of the heart muscle, are exposed to stress oxide Provided is a supplemental nutritional composition having an effect of enhancing the antioxidant effect of hemodialysis patients.
The nutritional supplement composition of the present invention is a composition that improves constipation by making the intestinal environment of hemodialysis patients biased toward facultative anaerobes easy to grow obligate anaerobes, and blood It also improves constipation not only in dialysis patients but also in constipation patients.
It is also a supplement for dietary fiber, which ensures water retention in the intestine and increases the amount of stool, and is therefore effective as a dietary supplement composition.

Claims (4)

L- carnitine, xylo-oligosaccharides, containing dietary fiber and coenzyme Q _10, the auxiliary nutritional composition characterized in that for use in hemodialysis patients.   The composition according to claim 1 as an agent for improving energy metabolism.   The composition according to claim 1 as an agent for improving the intestinal environment.   The composition according to any one of claims 1 to 3, further comprising bifidobacteria.