CH665126A5 - DIETETARY AGENT FOR REDUCING THE UREA CONCENTRATION IN BODY LIQUIDS AND ITS PRODUCTION. - Google Patents

Description

DESCRIPTION

The invention relates to a dietary agent for reducing the urea concentration in body fluids and its production.

With kidney diseases, kidney transplants and the like, there is the problem of urea removal from the organism. Normally, 70% of the urea formed in the liver during protein breakdown is excreted via the kidney, up to 30% is also released through the intestinal wall and split by bacteria there, depending on the prevailing pH of the intestine, either fixing in the intestine and Elimination takes place (with acidic pH values) or with alkaline pH values, the toxic ammonia is resorbed and transported back to the liver. In the case of kidney diseases, dialysis had to be carried out at regular intervals to remove the excess urea that was not removed via the intestine. If it were possible to remove a larger proportion of the urea via the intestine, there might be the possibility of reducing the frequency of dialysis or being able to bypass dialysis at all.

The prerequisite for this would be that the urea is continuously removed from the equilibrium that has to be established via the intestinal wall. This could be done by

A microorganism flora is produced in the intestine, which develops a strong urea-splitting activity.

Setelae and his colleagues at the University of Helsinki have already assumed that the residual nitrogen compounds in the body fluids are not only end products of the metabolic process that have to be eliminated, but are also partly useful for the resynthesis of proteins or amino acids and therefore should not be removed completely, only the excess must be removed. In order to achieve this, they have already proposed to change the conditions in the intestine in such a way that the biological decomposition of residual nitrogen there is increased and thus a shift in the biological balance through the intestine is achieved. At the same time, the patient should be kept on an appropriate diet. In order to change the conditions in the intestine in the desired sense, soil microorganisms of the species Serratia, Pseudomonas and Rhizobium or Agrobacterium, which are not identified in more detail, which contain adaptive, residual nitrogen-degrading enzymes such as urease, creatinase and the like and thus a breakdown of the residual nitrogen, such as e.g. of the urea in the intestine to a greater extent (Kidney International, Vol. 13, Suppl. 8 (1978), pp.194-202). However, it turned out that they no longer had the desired properties in the intestine (Proceeding Eur. Soc. For Artifical Organs (ESAO) Vol V, Zurich, 6-8.11.1978). They also need an approximately neutral pH in order to achieve good urease activity. Under such conditions, however, ammonia formed when the urea is cleaved is reabsorbed and has highly undesirable toxic effects on the liver. For this reason, Setelä's work was unsuccessful.

The object of the invention is to solve this problem. For this purpose, it is assumed that an intestinal flora would be required which has an urease which also shows strong activity in the acidic pH range and where possible has its maximum activity there. In addition, it should be a constitutively formed urease, not an urease that only arises adaptively due to the urea present.

It is known that the low pH in the intestine, which is aimed at removing ammonia, can be caused by a bifidus flora. It has now been found that there are certain strains of bifidus which constitutively form a urease which is highly active in the acidic pH range and which in turn can continuously split the urea passing through the intestinal wall and thus remove it from equilibrium.

The invention therefore relates to a dietary agent for reducing the urea concentration in body fluids, characterized by a content of bifidus bacteria of the species Bifidobacterium suis or / and Bifidobacterium infantis containing urease.

The bifidus bacteria of the species Bifidobacterium suis to be used according to the invention were found in pigs. An occurrence in humans has so far not become known. The strain Bifidobacterium suis DSM 20211 is preferably used in the context of the invention. DSM 2877 is preferred as the strain of the species Bifidobacterium infantis. This was deposited on February 10, 1984 with the German Collection of Microorganisms, Grisebachstrasse 8, 3400 Göttingen (FRG). It consists of gram-positive, pleomorphic, anaerobic rods that form acetate and lactic acid from glucose. The murein of the cell wall is of the Orn-Ser-Ala-Thr-Ala type. In addition to B. infantis, this type of murine also contains B. longum and B. suis. The genome of these three species is very closely related to5

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each other. The strain cannot ferment arabinose and melezitose and differs from B. infantis and B. longum B. suis.

The dietary agent according to the invention can contain the urease-containing bifidus strain of the species suis or infantis alone, but preferably it contains a combination with other bifidus strains which above all have a considerable ability to form acidity. Such bifid strains are e.g. Bifidobacterium adolescentis DSM 20083, 20086 and 20087; Bifidobacterium angulatum DSM 20098; Bifidobacterium bifidum DSM 20082; 20215 and 20456; Bifidobacterium breve DSM 20091, 20213; Bifidobacterium catenulatum DSM 20103; Bifidobacterium infantis DSM 20088, 20090 and 20223; Bifidobacterium longum DSM 20097 and 20219; Bifidobacterium sp DSM 20093. All of the above-mentioned Bifidobacterium strains are known and are available to the public at: German Collection of Microorganisms, Grisebachstrasse 8, 3400 Göttingen (FRG). "

In addition to the bifid strains mentioned, the dietetic agent according to the invention can also contain conventional additives such as flavors, colors, diluents and the like. Preferably, the agent additionally contains components of the culture medium, i.e. the solids contained in the culture medium in which the bacteria were grown. In particular, the dietary agent therefore contains milk components or soy milk solids and, if appropriate, additionally peptone and / or yeast extract.

The dietetic agent according to the invention can be packaged in any form suitable for oral administration. It is preferably in lyophilized form and is slurried and drunk to a drinkable consistency before administration by adding a drinkable liquid such as water, milk, tea or the like. However, administration can also take other forms, e.g. in gelatin capsules.

Another object of the invention is a preferred method for producing the dietetic agent according to the invention. According to this preferred embodiment, at least one Bifidobacterium suis or infantis strain and, if appropriate, a further Bifidobacterium strain are grown in a suitable nutrient medium and the culture thus obtained is lyophilized.

Suitable nutrient media are all nutrient solutions suitable in physiological, dietary and taste terms, preferably milk products, such as. B. soy milk, which is preferred, or whey and especially skimmed milk. The nutrient media can be mixed with other additives, e.g. Yeast extract and / or peptons and / or other substances which promote digestion, preferably in amounts of 0.1 to 1% by volume, based on the finished nutrient medium. In particular when using skim milk, which is usually prepared from dry skimmed milk and water, an addition of yeast extract and or peptone has proven to be expedient. A mixture of two or more of the above-mentioned suitable nutrient media can also be used. Preferably 0.4 to 0.5% by weight of yeast extract and 0.4 to 0.6% by weight of peptone, based on the volume of the solution, are added.

As already mentioned, the dietetic agent according to the invention can also contain other conventional additives, in particular dietetically suitable additives such as e.g. Glucose, β-lactose and lactulose can be added. Based on the freeze-dried state, the agent preferably contains IO6 to 1010. In particular IO8 to 109 living bifidum bacterial cells per gram.

The microorganisms themselves are grown in the manner known and customary for this purpose.

The incubation time depends on the temperature. Incubation is preferably carried out at a temperature of 15 to 45 ° C. for 15 to 30 hours and in particular at 37 + 2: C for 24 hours. During the cultivation, the pH is preferably maintained between 5.7 and 5.9, suitably Addition of an alkali Lime milk (calcium hydroxide solution), which is usually added two to four times during cultivation, is particularly suitable.

The dietetic agent according to the invention creates the possibility of reducing the amount of urea in the body fluids much more than was previously possible via the intestine. This opens up the possibility, even in the case of kidney failure, to reduce the urea content to such an extent that the remaining amounts of residual urea are harmless or can be removed without or only with a few dialysis treatments, so that the distance between the individual dialyses can be considerably extended. This not only makes life much easier for the sick, it also prevents the nitrogen compounds required for resynthesis from being excessively removed from the body.

The following example further explains the invention.

example

A nutrient solution prepared from soy milk powder and water, to which 0.5% by weight of yeast extract and peptone, based on the finished nutrient solution, was added, is inoculated with a pure culture of Bifidobacterium infantis, DSM 2877. The culture is incubated at a temperature of 37 ° C for 24 hours. After approximately 8 hours, the pH is adjusted to 5.8 to 5.9 by adding the required amount of lime milk. The culture is then cooled and freeze-dried. The lyophilisate obtained in this way is stored in a cool place. For administration, the product is stirred with lukewarm water (approx. One teaspoon per '/ 41 water) and the suspension obtained is drunk immediately.

Instead of soy milk, skim milk and whey were also used.

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Claims (10)

665 126 1. Dietary agent for reducing the urea concentration in body fluids, characterized by a content of urease-containing bifidus bacteria of the species Bifidobacterium suis or infantis. 2. Composition according to claim 1, characterized in that it contains Bifidobacterium suis DSM 20211 or / and Bifidobacterium infantis DSM 2877. 2nd PATENT CLAIMS 3. Composition according to claim 1 or 2, characterized in that it additionally contains other types of bifidus. 4. Composition according to claim 3, characterized in that it additionally contains at least one of the strains Bifidobacterium adolescentis DSM 20083, 20086 and 20087; Bifidobacterium angulatum DSM 20098; Bifidobacterium bifidum DSM 20082, 20215 and 20456; Bifidobacterium breve DSM 20091, 20213; Bifidobacterium catenulatum DSM 20103; Bifidobacterium infantis DSM 20088, 20090 and 20223; Bifidobacterium longum DSM 20097 and 20219 or / and Bifidobacterium sp DSM 20093 contains. 5. Agent according to one of claims 1 to 4, characterized in that it additionally contains components of the culture medium of the bifid strains contained. 6. Composition according to claim 5, characterized in that it contains milk components or soy milk solids as culture medium components. 7. Composition according to claim 5 or 6, characterized in that it contains peptone or / and yeast extract. 8. Agent according to one of the preceding claims, characterized in that it is in lyophilized form. 9. A method for producing the dietary agent according to claim 1 to 8, characterized in that at least one Bifidobacterium suis or / and infantis strain is grown in a suitable nutrient medium and the culture obtained is lyophilized. 10. The method according to claim 9, characterized in that milk or soy milk is used as the nutrient medium with the addition of peptone and / or yeast extract.