DE3943424A1 - Solns. for intravenous nutrition - contg. alpha-keto acids, for patients with kidney conditions, avoids nitrogen cpd. build-up - Google Patents

Abstract

Aq. infusion or injection solns. for i.v. admin. contain one or more alpha-keto acids (I) selected from alpha-ketoglutarate (Ia), pyruvate (Ib), alpha-ketosuccinate (Ic), alpha-ketoadipate (Id), 3-methyl-alpha-ketobutyrate (Ie), 3-methyl-alpha-ketovalerate (If), 4-methyl-alpha-ketovalerate (Ig), 3-phenylpyruvate (Ih) and mercaptopyruvate (Ii) as nutrients in a concn. of 1-500 g/l. providing a calorific value of 100-10,00 kJ/l. USE/ADVANTAGE - The solns. are useful for parenteral nutrition, esp. for chronic nutrition of patients with renal insufficiency who cannot tolerate amino acid solns.. They provide efficient protein biosynthesis and energy supply and are simple to produce and administer.

Description

The present invention relates to the use of alpha-ketocarboxylic acids as nutriv active substance (= Nutrient) in aqueous infusion and injection solutions for intravenous administration in the parenteral nutrition.

The process of parenteral nutrition, that is, artificial nutrition bypassing the gastrointestinal Traktes, takes place worldwide in the most diverse Disease forms application. One understands under parenteral nutrition the intake of nutrients intravenous route, thus bypassing digestion and Absorption in the gastrointestinal tract. Because there are nutrients can get into the blood directly, it can be used parenterally Nutrition only the basic building blocks of the food use.

The goal of parenteral nutrition is the Provision of the necessary energy sources (fuels), ie of calories (1 kcal = 4.18 kJ) and the Preservation of protein content by infusion nutritive effective substances such. B. amino acids, fat or Fatty acids and carbohydrates. The amino acids serve while the protein buildup and only in an emergency of energy, usually via the pathway of gluconeogenesis, while the carbohydrates and the fat or the fatty acids the calories necessary for the life processes provide.  

The parenteral nutrition has become enormous Advances in medicine in recent years have contributed significantly, especially in the field of Surgery. Patients with insufficient oral food intake by resorption disorders, operations at the Gastrointestinal tract or in a coma can last for a long time only by infusion of nutrient solutions in qualitative sufficient composition to be kept alive.

Requirements for infusion and injection solutions for parenteral nutrition are that the ingredients as possible are physiological and enteral nutritional forms completely replace, that is the composition of Nutrients is designed so that the function of the Carbohydrate, fat and protein metabolism guaranteed is. Especially with regard to protein metabolism arise requirements in such a way that the ingredients in the form of essential amino acids that the organism can not synthesize available to ensure protein biosynthesis.

There are a large number of infusion devices on the market today. and injection solutions for complete parenteral Nutrition available, which, in the long term, Patients complete and calorally adequate intravenous can feed. However, to this day is an adequate one Parenteral nutrition in certain diseases, such as z. As in chronic renal failure, problematic.  

Due to the insufficient renal function is included Kidney disease of the organism with urinary substances, especially nitrogen-containing degradation products of Protein metabolism, especially burdened. at the complete parenteral nutrition of kidney patients Patients have always necessarily been mixtures essential amino acids in the infusion and injection solutions used to protein biosynthesis too guarantee. This has the consequence that the kidney-deficient Organism additionally with nitrogenous Substances (essential amino acids) is loaded, whose Degradation products, especially urea, the clinical picture Kidney insufficiency worsen.

Another significant technical disadvantage of amino acids and carbohydrate-containing (eg glucose) infusion and injection solutions for parenteral nutrition is that the amino groups of the amino acids with the Keto, aldehyde or carbonyl groups of carbohydrates (reducing sugars, such as glucose, galactose or Fructose) react chemically. This already 1912 through Maillard's reaction is called nonenzymatic Tanning reaction or Maillard reaction designated. It forms so-called melanoids, brown nitrogen-containing, partly toxic polymerization products with a molecular weight of up to 300,000 Dalton. Through the Maillard reaction, especially the destroys essential amino acids. The reaction is ongoing in aqueous solutions depending on the pH (alkaline: fast; acid: slows down) and the temperature (at 0 ° C very slow, over 90 ° C very fast). This has to Result that the inevitably necessary sterilization with Heat of Aqueous Amino Acid-Carbohydrate Mixtures not possible.  

To solve this problem is in practice the Separation of the amino acid solution and the carbohydrate solution in individual containers and sterilization in these separate containers. Mixing the both separate solutions via one of the two solutions connecting connector takes place immediately before intravenous administration. This results in disadvantages in the technical handling and production of such Infusion and injection solutions. Alternatively, the alternating administration of amino acid-containing solutions to ensure protein biosynthesis and carbohydrate-containing Solutions to ensure energy supply. The thus, compared to infusion and Injection solutions in a container, associated higher technical effort, also results in higher production costs and thus higher prices.

Therefore, there is still a significant need for nutritionally effective infusion and injection solutions, the administered to renal insufficiency patients for a prolonged period which can be an effective nutritive Effect in the sense of ensuring protein biosynthesis and provide energy to patients, the kidney-deficient organism not additionally with nitrogen-containing substances, such as. B. Amino acids, and the other technically simple to produce and technically easy to handle of administration.  

The object underlying the invention is Nutritionally effective infusion and injection solutions for Provide long-term renal insufficiency Patients are administered intravenously can be attributed without affecting the nutritive ingredients Complications, especially in the form of nitrogen loads occur, with the previously known Infusion and injection solutions for the complete parenteral nutrition complications occurring Nitrogen pollution can be avoided and both sufficient effective nutritional contribution to the Patients in the form of adequate protein biosynthesis and adequate energy supply can be guaranteed, as also a simple technical production and handling ensure during administration.

This object is achieved by the infusion and injection solution for intravenous administration containing optionally further additives, such as. B. Electrolytes, carbohydrates or fats or fatty acids, solved, characterized by a Content of at least one physiologically metabolizable alpha-ketocarboxylic acid (synonym: alpha-keto acid) or a mixture of such alpha-ketocarboxylic acids as nutritive active substance selected from the group alpha Ketoglutarate, pyruvate, alpha-ketosuccinate, alpha Ketoadipate, alpha-keto (methyl) butyrate, alpha-keto (methyl) valerate, phenylpyruvate or mercaptopyruvate, preferably from the group alpha-ketoglutarate, pyruvate, alpha-ketosuccinate, in a concentration of 1 to 500 g / l and an energy content (calorific value) in the range of 100 to 10,000 kJ / l.  

When using a mixture of alpha-keto acids as Nutritionally active substances in infusion and injection solutions for complete parenteral nutrition in the concentration of 1 to 500 g / l, are the following alpha-keto acids preferably in the following relative Quantities include:

alpha-ketoglutarate 0 to 45 parts by weight Pyruvate (alpha-ketopropionate) 0 to 45 parts by weight alpha-Ketosuccinat 0 to 45 parts by weight 3-methyl-alpha-Ketovalerianat 6 to 9 parts by weight 4-methyl-alpha-Ketovalerianat 9 to 13.5 parts by weight 3-Phenylpyruvate 0 to 9.5 parts by weight 3-methyl-alpha-ketobutyrate 13.5 to 20.5 parts by weight alpha-Ketoadipat 0 to 10 parts by weight alpha-ketobutyrate 0 to 10 parts by weight

In the case of the alpha-keto acids used in accordance with the invention, Mixtures It is essential that according to the muscle amino acid pattern kidney deficient patients Ratios of 3-methyl-alpha-ketobutyrate: 4- Methyl alpha-keto valerate: 3-methyl-alpha-keto valerianat be respected. So should this Ratio be such that the concentration of 3- Methyl alpha-ketobutyrate greater than 4-methyl-alpha-keto valerianate is greater than 3-methyl-alpha-ketovalerianate. Preferably, the ratio of alpha-keto acids should be 3-methyl-alpha-ketobutyrate: 4-methly-alpha-keto valerianate: 3-methyl-alpha-ketovalerate 2.25: 1.5: 1 be.  

When using alpha-keto according to the invention acidic infusion and injection solutions the following advantages:

Alpha keto acids (= alpha-ketocarboxylic acids) are the Keto analogues of essential and nonessential amino acids, that is, the amino groups of the amino acids by transamination reactions by a keto group are substituted. These reactions are physiological in the organism. The Alpha-keto acids are thus completely physiological Substances whose biochemical metabolic pathways are sufficient are known. In Table 1, those at use according to the invention as an individual or in the form of mixtures, coming nutritive effective alpha keto acids as keto analogues of their corresponding Associated amino acids.

Table 1, keto analogues (alpha-keto acids) of the amino acids amino acid alpha-ketoglutarate glutamate Pyruvate (alpha-ketopropionate) alanine alpha-Ketosuccinat arginine 3-methyl-alpha-Ketovalerianat isoleucine 4-methyl-alpha-Ketovalerianat leucine 3-Phenylpyruvate phenylalanine 3-methyl-alpha-ketobutyrate valine alpha-Ketoadipat lysine alpha-ketobutyrate threonine

Of importance is that not the essential amino acids solved as a whole molecule, but its corresponding Carbon skeleton is essential, so from the organism can not be synthesized. Because alpha-keto acids do not contain nitrogen, they can not arise nitrogen-containing degradation products. Alpha-keto acids help the organism, the nitrogenous To re-metabolize metabolites and make them vital again To synthesize protein. This leads to a full protein supply at minimized Nitrogen supply.

By endogenous amination are from Ketoanalogen, as Precursors of the amino acids, the corresponding amino acids, formed as needed. Surprisingly was also found to be endogenous essential amino acids from their analog alpha-keto acids, if these instead of the essential amino acids as liver or Muscle perfusion can be administered (See: Walser, McK., Lund, P., Rudermann, N.B. Coulter, A.W .: Synthesis of Essential Amino Acids from their alpha ketoanalogues by Perfused Rat Liver and Muscle. J. Clin. Invest., 52, 2865-2877, 1973).  

This effect, which has been known for years, is used therapeutically Success especially in kidney-deficient patients used orally administered with alpha-keto acids, which are converted endogenously into amino acids, which for used the protein biosynthesis, thereby endogenous Nitrogen binding, thereby reducing the burden of kidney insufficiency Organism with urinary, especially nitrogen-containing substances is reduced (see. z. B: Heidland, A .: Keto analogues for uremic treatment. Praxis-Kurier, 41, 17, 1975 or: Walser, McK .: Ketoacids in the Treatment of Uremia. Clin. Nephrology, 3, 180-186 or: Kopple, J.D., Swendseid, M.E .: Amino Acid and Keto Acid Diets for Therapy at Renal Failure. Nephron, 18, 1-12, 1977).

The same positive effect can also be seen in the case of intravenous Administration of alpha-keto acids can be achieved. From of particular importance here is that in kidney insufficiency Patients specifically the essential branched-chain Amino acids valine, leucine and isoleucine, but also lysine, tyrosine (synthesis of phenylalanine), Threonine and the non-essential amino acids serine, Glycine and alanine (synthesis from pyruvate), as well as ornithine and glutamine (both synthesized from glutamate) in the Ratio to the remaining amino acids in too low Concentration are present, that is, amino acid imbalances present, which is a protein biosynthesis inhibit.  

By the inventive use of the infusion and Injection solution with a mixture of those shown in Table 1 listed alpha-keto acids and those in Example 1 it is thus possible to all o. g. Balance amino acid deficiencies and thereby an effective nutritional contribution in the sense of a Ensuring adequate protein biosynthesis for kidney-deficient patients, without additional nitrogen pollution, to ensure. By adding z. B. one Carbohydrate like glucose to this solution, in one Concentration of z. B. 220 g / l, is also a sufficient Ensured energy supply to the patient.

Amino acid deficits are caused by the inventive Use of the infusion and injection solution not only by the synthesis of amino acids from the analogues balanced alpha-keto acids, but beyond there is a reduced degradation of existing amino acids by a sufficiently high concentration of the analog alpha-keto acids. The reason for this is that the Degradation of amino acids physiologically first in a transamination reaction to the analog alpha Keto acids takes place, which at a correspondingly high concentration, via a product inhibition customary in biochemistry, inhibit the further degradation of amino acids.

In addition to the already mentioned advantage of avoided additional nitrogen load in the inventive Use of alpha-keto acids compared to Amino acids as a nutritionally active substance in infusion and injection solutions for complete parenteral Nutrition, there are more benefits in the way  that by alpha-keto acids, in particular alpha- Ketoglutarate, pyruvate and alpha-ketosuccinate, none Aminosäurenimbalanzen be induced. This results from the metabolism of these substances. in the Citrate cycle (= Krebs cycle according to H. A. Krebs, Oxford, Nobel Prize 1954), in which the carbohydrate, protein or Amino acids and fat metabolism in the form of pyruvate or the activated acetic acid, take this alpha-keto acids dominate, by the intermediary metabolism of these nutrients thus via these alpha-keto acids as an intermediate expires. By the resulting bicarbonate degradation is the renal acidosis is favorably influenced. Furthermore also the dismantling of all the remaining ones takes place in Table 1 listed alpha-keto acids to pyruvate or to activated acetic acid. Because of the given diverse metabolic possibilities is a Aminierung thus only with appropriate need.

This physiological position of these alpha- Keto acids in the intermediary metabolism is the pharmacological guaranteed toxicological safety. The disadvantages of the induction of amino acid imbalances, their danger especially in kidney-deficient patients is increased, as well as the essential amino acids certain nonessential amino acids in not sufficient concentration are present, and at the use of previously known amino acid mixtures in Infusion and injection solutions occurred by the use of alpha-keto acids as amino acid substitutes avoided.  

A significant technical advantage arises in the use according to the invention alpha-ketosäurenhaltiger Infusion and injection solutions compared to amino acids Infusion and injection solutions, if usually a carbohydrate additive as an energy supplier desired in such infusion and injection solutions is because alpha-keto acids due to a missing Amino group, in contrast to amino acids, with carbohydrates no non-enzymatic browning reaction (Maillard reaction). Therefore, alpha- containing ketoacid infusion and injection solutions a carbohydrate portion are easily produced. The Ketosäurengemisch can easily along with the Carbohydrate mixture produced in a single container, heat sterilized (autoclaved) and stored become. The formation of toxic melanoids is avoided. Furthermore, the technical handling in the Administration of infusion and injection solutions simple and therefore safe to use, as in the Unlike amino acids with carbohydrate-containing Infusion and injection solutions, one immediately before the administration of two Compartments, not applicable.

Thus arise in the inventive use of alpha-keto acids as nutritive substance in Infusion and injection solutions instead of the previously All the amino acids used in this regard for the previously used amino acids known positive Properties without their disadvantages. The new infusion and solution for injection is excellent for intravenous Administration suitable.  

The new infusion and injection solutions include the same components as already known infusion and Injection solutions for intravenous administration, however with the exception that the amino acids to ensure an adequate protein biosynthesis partially until completely replaced by alpha-keto acids and in addition a carbohydrate for adequate energy supply may be included in the solution.

The manufacture of the new infusion and injection solutions can according to the known methods for Preparation of intravenously administered infusion and injection solutions for parenteral nutrition respectively.

The alpha-ketoacid concentrations used are dependent on the nutritional status of the Patients. They are in the range of 1 to 500 g / l, advantageously in the range of 5 to 250 g / l, in particular 10 to 100 g / l.

The energy content of the infusion and Injection solution is advantageously 100 to 10,000 kJ / l, in particular 2000 to 6000 kJ / l.

The pH of the solution according to the invention is in the range from 4.8 to 8.4.

Alpha-keto acids are readily available commercial products. In the chemicals trade are the mentioned alpha-keto acids available with a purity of more than 99%. The Recovery is technically or microbiologically.  

When the infusion and injection solutions of the invention in addition to alpha-keto acids also amino acids and / or peptides and / or proteins as further optional, nutriv effective substances that inhibit protein biosynthesis influence, contains, so is the quantity ratio advantageously 1: 3 to 3: 1. The infusion and Injection solution can not but if desired only amino acids, but z. As fats, fatty acids and Carbohydrates such as. As glucose, fructose or others Sugar, sorbitol, xylitol, mannitol or other sugar alcohols, Glycerol, sugar polymers, gelatin, glycols, Glycerophosphates, carbohydrate polymers, hydroxyethyl starch or dextrans as further, optionally nutritive active substance (s) serving as energy suppliers, contain.

The electrolyte salts can be prepared in a known manner in the form of Acetate, lactate, carbonate, bicarbonate, sulfate, Hydroxides and / or chloride are present.

The electrolyte additives, preferably sodium, potassium, Magnesium, calcium and zinc can be used in, for infusion solutions be contained in conventional concentrations.

Furthermore, the solution can be up to 250 mmol / l ions selected from the group lactations, acetate ions and contain up to 1500 mmol / l Bicarbonationen.

The alpha-keto acids may also be in the form of their sodium, Potassium, magnesium and / or calcium salts used become. By using such alpha-ketoacid salts decreases in the final dialysis solution of necessary proportion of chloride ions (corresponding to the cation electrolyte additives).  

This is particularly advantageous in relation to that different publications not the sodium per se, but the chloride salt of sodium for favoring responsible for hypertension. Furthermore Kidney diseases are common with hyperchloremia associated.

The use of the described electrolyte salts of alpha-keto acids, resulting in a lower Chloride ion requirement in the finished dialysis solution, thus reduces the high blood pressure in accordance with endangered patients. Unlike traditional ones Infusion and injection solutions, with one Chloride content of 98 to 107 mmol / l, it is through the inventive use of the new infusion and Injection solution possible, not only those used so far But to use chloride concentrations also any lower chloride concentrations, to chloride-free infusion and injection solutions.

In addition, the new infusion and injection solutions other carboxylic acids or their salts, preferably selected from the group succinate, lactate, acetate, Fumarate, malate, citrate or isocitrate, in one Concentration of 0.5 to 30 g / l included.

The new infusion and injection solution can also additionally alpha-hydroxycarboxylic acids or their sodium, Contain potassium, magnesium or calcium salts, preferably selected from the group hydroxyphenylpyruvate, Hydroxybutyrate and hydroxypropionate, in particular DL-2-hydroxy-4-methyl-thiobutyrat.

The infusion and injection solution according to the invention can if desired, also customary additives and auxiliaries  contained in pharmacologically effective amounts. Examples of common additives and auxiliaries are Hormones, such as insulin or erythropoietin, vitamins, Antioxidants or preservatives.

The new infusion and injection solutions are suitable except for use in kidney-deficient patients Also excellent in other forms of disease in which the applications of certain amino acids contraindicated or nitrogen metabolic disorders.

The following examples serve for further explanation of the present invention:

example 1

In one liter of water of injection quality becomes one produced according to the invention infusion and injection solution. This solution contains 15 g in 1 liter of water alpha-ketoglutaric acid and 7.5 g of pyruvate as nutritive effective substances for protein biosynthesis, glucose as Energy supplier and electrolyte salts in the form of Chloride.

Composition: Na + 50.0 mmol / l Ca ⁺⁺ 2.5 mmol / l Mg ⁺⁺ 2.5 mmol / l K + 15.0 mmol / l Zn ⁺⁺ 0.04 mmol / l Cl ^- 75.04 mmol / l alpha-ketoglutaric acid 15.0 g / l pyruvate 7.5 g / l glucose 220.0 g / l

The theoretical calorific value of this solution is 4138 kJ.

The acidic pH of this solution may, if desired by partial substitution of NaCl by NaOH or be adjusted exactly by adding HCl, for. B. to pH 7.4. This may cause a corresponding minor Change the chloride ion concentration done. The way The solution prepared is used for the production of Infusion and injection solutions known methods sterile filtered in plastic bags, plastic bottles or Glass bottle bottled and heat sterilized.

Example 2

Example 1 was repeated with the exception that additionally 2 g of alpha-ketosuccinate as further nutritive effective substance were used.

Composition: Na + 50.0 mmol / l Ca ⁺⁺ 2.5 mmol / l Mg ⁺⁺ 2.5 mmol / l K + 15.0 mmol / l Zn ⁺⁺ 0.04 mmol / l Cl ^- 75.04 mmol / l alpha-ketoglutaric acid 15.0 g / l pyruvate 7.5 g / l alpha-Ketosuccinat 2.0 g / l glucose 220.0 g / l

The theoretical calorific value of this solution is 4171 kJ.

Example 3

Example 1 was repeated with the exception that as nutritionally active substances that the Protein biosynthesis positively influence the following alpha- Ketocarbonsäuren were used:

alpha-ketoglutaric acid 7.5 g g / l Pyruvate (alpha-ketopropionic acid) 10.0 g / l alpha-Ketosuccinat 4.5 g / l 3-methyl-alpha-ketovaleric acid 4.0 g / l 4-methyl-alpha-ketovaleric acid 6.0 g / l 3-Phenylpyruvate 4.0 g / l 3-methyl-alpha-ketobutyric acid 8.75 g / l alpha-Ketoadipinsäure 4.5 g / l alpha-ketobutyric acid 4.5 g / l Hydroxy-phenylpyruvate 5.0 g / l

Composition: Na + 50.0 mmol / l Ca ⁺⁺ 2.5 mmol / l Mg ⁺⁺ 2.5 mmol / l K + 15.0 mmol / l Zn ⁺⁺ 0.04 mmol / l Cl ^- 75.04 mmol / l alpha-ketoglutaric acid 7.5 g / l Pyruvate (alpha-ketopropionic acid) 10.0 g / l alpha-Ketosuccinat 4.5 g / l 3-methyl-alpha-ketovaleric acid 4.0 g / l 4-methyl-alpha-ketovaleric acid 6.0 g / l 3-Phenylpyruvate 4.0 g / l 3-methyl-alpha-ketobutyric acid 8.75 g / l alpha-Ketoadipinsäure 4.5 g / l alpha-ketobutyric acid 4.5 g / l Hydroxy-phenylpyruvate 5.0 g / l glucose 220.0 g / l

The theoretical calorific value of this solution is 4743 kJ.

Example 4

Example 1 was repeated with the exception that as nutritive substances that inhibit protein biosynthesis positively influence the following Ketocarbonsäuren were used:

3-methyl-alpha-keto valerate ^- | 2.0 g / l 4-methyl-alpha-ketovalerate ^- 3.0 g / l 3-methyl-alpha-ketobutyrate ^- 4.5 g / l

Glucose and electrolyte concentration the information in Example 1.

The theoretical calorific value of this solution is 3921 kJ.  

Example 5

In one liter of water of injection quality becomes one Inventive infusion and injection solution manufactured. This solution contains in 1 liter of water the following alpha-keto acids and additionally amino acids as Nutritionally active substances for protein biosynthesis and Electrolyte salts in the form of the chloride. This solution is excellent, long-term protein biosynthesis in case of parenteral nutrition strong in contrast to conventional amino acid solutions reduced nitrogen content (of a total of 11 amino acids 8 were substituted by their keto analogues). The solution is thus excellent for z. B. kidney-deficient patients.

Composition: Na + 50.0 mmol / l Ca ⁺⁺ 2.5 mmol / l Mg ⁺⁺ 2.5 mmol / l K + 15.0 mmol / l Zn ⁺⁺ 0.04 mmol / l Cl ^- 75.04 mmol / l 3-methyl-alpha-ketovalerate ^- 4.0 g / l 4-methyl-alpha-ketovalerate ^- 6.0 g / l 3-methyl-alpha-ketobutyrate ^- 9.0 g / l alpha-Ketoadipat 6.6 g / l 3-Phenylpyruvate 5.1 g / l alpha-ketobutyrate 4.4 g / l alpha-Ketosuccinat 12.0 g / l pyruvate 15.0 g / l L-tryptophan 2.0 g / l L-histidine 3.0 g / l L-methionine 4.2 g / l malate 6.2 g / l

The theoretical calorific value of this solution is 1390 kJ.

Claims (11)

1. aqueous infusion and injection solution for intravenous administration, characterized by a content of at least one physiologically metabolizable alpha-ketocarboxylic acid or a mixture of such alpha-ketocarboxylic acids as a nutritionally active substance selected from the group alpha-ketoglutarate, pyruvate, alpha-ketosuccinate, alpha Ketoadipate, 3-methyl-alpha-ketobutyrate, 3-methyl-alpha-keto-valerianate, 4-methyl-alpha-keto-valerianate, 3-phenylpyruvate or mercaptopyruvate, preferably from the group alpha-ketoglutarate, pyruvate or alpha-ketosuccinate, in a concentration of 1 to 500 g / l and a calorific value in the range of 100 to 10,000 kJ / l and optionally further additives. 2. Solution according to claim 1, characterized characterized in that the alpha-ketocarboxylic acids as a nutritionally active substance in the form of calcium, potassium, magnesium or sodium salts these ketocarboxylic acids, preferably sodium salts, be used. 3. Solution according to one of the claims 1 to 2, characterized in that the alpha-ketocarboxylic acids in an amount of 5 to 250 g / l, preferably 10 to 100 g / l. 4. Solution according to one of the claims 1 to 3, characterized in that the pH is 4.8 to 8.4.   5. Solution according to one of the claims 1 to 4, characterized in that additionally electrolytes, preferably sodium, potassium, Magnesium, calcium and zinc, in for infusion solutions usual concentrations, and up to 250 mmol / l ions selected from the group lactations and acetate ions, and up to 1500 mmol / l bicarbonate ions and the contains corresponding residual chloride ions. 6. Solution according to one of claims 1 to 5, characterized in that when using a mixture, the alpha-keto acid mixture of the concentration of 1 to 500 g / l contains the following alpha-keto acids in the following relative amounts: alpha-ketoglutarate 0 to 45 parts by weight Pyruvate (alpha-ketopropionate) 0 to 45 parts by weight alpha-Ketosuccinat 0 to 45 parts by weight 3-methyl-alpha-Ketovalerianat 6 to 9 parts by weight 4-methyl-alpha-Ketovalerianat 9 to 13.5 parts by weight 3-Phenylpyruvate 0 to 9.5 parts by weight 3-methyl-alpha-ketobutyrate 13.5 to 20.5 parts by weight alpha-Ketoadipat 0 to 10 parts by weight alpha-ketobutyrate 0 to 10 parts by weight wherein the ratio of the alpha-keto acids is 3-methyl-alpha-ketobutyrate: 4-methyl-alpha-keto-valerianate: 3-methyl-alpha-keto-valerianate 2.25: 1.5: 1. 7. Solution according to one of the claims 1 to 6, characterized in that additionally a carboxylic acid salt selected from Group succinate, fumarate, lactate, acetate, malate, Citrate or isocitrate, in a concentration of 0.5 to 80 g / l.   8. Solution according to one of the claims 1 to 7, characterized in that additionally an alpha-hydroxycarboxylic acid salt, preferably selected from the groups hydroxyphenylpyruvate, Hydroxybutyrate and hydroxypropionate, in particular DL-2-hydroxy-4-methyl-thiobutyrate contains. 9. Solution according to one of the claims 1 to 8, characterized in that additionally contains 0.5 to 20 wt .-% amino acids. 10. Solution according to one of the claims 1 to 9, characterized in that additionally from 0.2 to 40% by weight of water-soluble Carbohydrates as further nutritive effective Substances, preferably glucose, fructose, Galactose, sorbitol, xylitol, mannitol, hydroxyethyl starch, Dextrans or glucose polymers contains. 11. Solution according to one of the claims 1 to 10, characterized in that additionally 10 to 500 mg / l vitamins, the protein metabolism affecting hormones in physiological effective amount and / or fats or fatty acids in a concentration of 0 to 300 g / l and / or Peptides in a concentration of 0 to 200 g / l contains.