CS230838B1 - Special amino acid complex for enteral nutrition - Google Patents

Abstract

The invention relates to a complex of amino acids (L-isoleucine, L-leucine, L-lysine.HCl, L-methionine, L-phenylalanine, L-threonine, L-tryptophan, L-valine, L-alanine, L-arginine, L-aspartic acid, L-glutamine, Glycine, L-histidine, L-proline, L-serine, L-tyrosine ethyl ester.HCl) with a special purpose for enteral nutrition_in the form of a powder, which is applied in the form of a suspension in an appropriate concentration containing carbohydrates and essential fatty acids, with the possible content of other minerals, trace elements, vitamins and related substances, including possible flavoring.

Description

The invention relates to an amino acid complex specifically intended for enteral nutrition in powder form, containing carbohydrates and essential fatty acids and optionally mineral salts, trace elements, vitamins, biofactors and/or taste enhancers; this complex is administered in the form of a suspension of appropriate concentration either orally or by means of a suitable probe.

The amino acid complex belongs to special dietetics and forms a transition between parenteral nutrition and a normal diet. It is a preparation that falls into the group of chemically defined diets without ballast substances. Its composition is original and differs substantially from known preparations already used clinically. It was compiled based on the authors' experience in preparing various mixtures of amino acids, supplemented by the latest clinical findings in this area. The amino acid complex contains mainly L-forms of pure amino acids, namely essential and assisting, with the exception of cystine. The ratio of essential amino acids to assisting amino acids is equal to 3, which is optimal based on previous experience and the complex has a high biological value. The amount of amino acids was chosen so that 1 g of dietary fiber accounts for 622 kJ, which is optimal for the use of amino acids. The carbohydrate content was adjusted so that the complex was palatable and its resorption was prolonged for a longer period. The supply of mineral salts and trace elements, including vitamins, was chosen in accordance with the latest knowledge to ensure daily needs.

The essence of the amino acid complex with special purpose for enteral nutrition according to the invention

rests in to, that it contains in percentage by weight 0.60 until 0.79 L-Isoleucine 0.36 until 0.48 L-alanine 0.94 until 1.24 L-leucine 0.34 until 0.46 glycine 0.68 until 0.90 L-valine 0.40 even 0.75 L-proline 0.94 until 1.24 L-phenylalanine 0.77 until 1.02 L-serine 0.20 until 0.27 B-tryptophan 0.42 until 0.56 ethyl hydrochloride 0.43 until 0.56 L-threonine L-tyrosine ester 0.94 until 1.24 Ir-methionine 7.6» until 0.25 maltose 0.69 until •0.91 L-lysine 3.85 until 4.62 sorbitol 0.65 until 0.85 L-arginine 11.40 until 13.90 starch 0.24 until 0.31 L-histidine 18.60 until 22.88 glucose 1.41 until 1.85 L-glutamine 3.78 until 4.43 fructose 1.05 until 1.37 L-Aspartic Acid 30.40 until 37.00 sucrose

0.24 to 0.30 safflower oil.

To prepare the amino acid complex, L-forms of pure amino acids or a sum of amino acids obtained by hydrolysis of a suitable protein source and supplemented with the necessary amount of pure amino acids can be used. Pure amino acids can be weighed directly, mixed and homogenized by repeated sieving. Mineral salts are processed in the same way; sugars are also weighed directly and homogenized by sieving. The oil component is processed by trituration. The final preparation of the required composition is obtained by mixing and homogenizing the individual parts, as detailed in the examples.

The amino acid complex according to the invention has been tested pharmacologically and clinically in all its alternatives. It does not require the enzymatic equipment of the digestive tract for its use and is well tolerated, especially when using a nasogastric or nasojejunal tube. In pharmacological testing, a clinically used preparation of similar composition was used for comparison.

Due to non-toxicity, it was not possible to perform an LD^ ₀ test, only a harmlessness test.

The chronic toxicity test showed that the diet administered in the form of the complex according to the invention ensures higher weight gains than the standard diet used for rats. No pathological values were found in biochemical parameters, and histological examination of parenchymatous organs (liver, kidneys) also did not show any pathological changes. From a pharmacological point of view, the complex according to the invention was fully satisfactory, moreover, due to its advantageous composition, it achieves comparable results as with the standard preparation at half the dosage, which is also not negligible from an economic point of view.

Clinical testing was performed both directly per os and using a nasogastric tube. Per os testing confirmed the experience that a relative contraindication to oral administration of the amino acid complex according to the invention in the form of a suspension is persistent anorexia. Administration of the preparation did not lead to changes in blood pressure and pulse rate. There were also no changes in biological parameters. When using a nasogastric tube, tolerance was very good, the tube never clogged. In all patients with severe malnutrition, the clinical condition improved significantly.

When comparing the amino acid complex according to the invention with a clinically used preparation for the same indication, which did not contain L-methionine and L-tyrosine ethyl ester hydrochloride, the following results were obtained:

In the amino acid complex according to the invention, 1 g of nitrogen contains 615 kJ of energy, which is, according to experience, an optimal ratio. In the comparative preparation, 1 g of nitrogen contains 1,230 KJ, which is a lot.

The ratio of nitrogen of essential amino acids to total nitrogen in the preparation according to the invention is 3, which corresponds to high-quality egg protein; in the comparative preparation it is 2.3, which corresponds to low-quality protein, the usability of which is limited.

The preparation according to the invention contains 50% by weight of essential amino acids, of which 20% by weight are branched. This creates optimal conditions for protein synthesis, even in pathological conditions. The comparative preparation contains less essential amino acids, 36% by weight, and less branched amino acids, 16% by weight. Branched amino acids prevent proteinolysis.

The arginine/glycine index value of 1.87 in the preparation according to the invention is more advantageous than 1.12 in the comparative preparation, since the increased amount of arginine prevents possible hyperammonemia.

The phenylalanine/tyrosine index of 2.2 versus 0.9 confirms the increased content of L-tyrosine, which is desirable because in pathological conditions, an enzymatic block of L-phenylalanine/L-tyrosine very often occurs.

This comparison shows the advantages of the amino acid complex according to the invention. The composition of the sugar component allows the use of various metabolic pathways and thus increases the tolerability of the preparation.

In mineral supply, it is desirable to reduce the amount of sodium per 1 g of nitrogen. The preparation according to the invention contains 8.5 mmol of sodium/1 g of nitrogen, the comparative preparation 19.5 mmol/1 g.

Potassium accounts for 5.25 mmol/1 g of nitrogen, which is optimal, unlike the comparison product, where this ratio is 9.0 mmol/1 g of nitrogen. The trace elements manganese and zinc are present in higher amounts, because in pathological conditions there are increased losses of these elements.

The comparison clearly demonstrates that, based on basic experimental work and positive pharmacological and clinical results, a new amino acid complex formula was created, purposefully supplemented with carbohydrates, mineral salts, trace elements, vitamins, biofactors and/or flavorings, which represents a valuable enrichment of therapeutic options in an important clinical area.

Example 1

For a batch of 60 bags of 88 g (± 3 % by weight), the following ingredients are weighed (in g or mg):

Part 1:

39.5 L-isoleucine 62.4 L-leucine

45.6 L-lysine hydrochloride 62.4 L-methionine

24.0 L-alanine

42.6 L-arginine

69.0 L-aspartic acid 93.0 L-glutamine

230830

62.4 L-phenylalanine 28.2 L-threonine

13.8 L-Tryptophen 45.0 L-Valine

22.0 glycine 15.6 L-histidine 26.4 L-proline 51.0 L-serine

28.2 L-tyrosine ethyl ester hydrochloride

Part 2:

58.8 sodium chloride

46.8 potassium chloride 2.58 magnesium oxide

15.22 calcium phosphorylcholine chloride tetrahydrate

32.40 calcium glycerophosphate

Part 3:

444.6 meltose

222.3 sorbitol

672.0 soluble starch

Part 4: is created by combining, homogenizing and crosslinking parts 1, 2 and 3.

Part 5: 14.4 g of safflower oil is dispersed in 290 g of sucrose by trituration, then 1,488 g of sucrose is added, everything is homogenized and sieved.

Part 6: 486.0 mg of ferrous sulfate, 61.2 mg of manganese acetate monohydrate, 171.0 mg of manganese acetate tetrahydrate and 108.0 mg of zinc chloride are mixed in 124 g of fructose.

Part 7: in 98 g of fructose, 1.08 g of vitamin C, 128.4 mg of calcium D-pantothenate, 255.6 mg of vitamin E acetate, 1.2 g of inositol, 199.8 mg of nicotinamide are thoroughly ground and homogenized by sieving.

Part 8: is created by mixing, homogenizing and crosslinking parts 5, 6 and 7.

Part 9: 50 mg of vitamin _D2 and 25 mg of vitamin B12 are ground, homogenized and cross-linked in 50 g of glucose. Then 0.1 g is weighed as part 9.

Part 10: 430 mg of vitamin A acetate, 120 mg of vitamin A are mixed and ground in 99 g of glucose.

Bp 120 mg of vitamin B ₂ phosphate, 235 mg of pyridoxal chloride, 1.5 mg of folic acid, 19.5 mg of D-biotin, 120 mg of vitamin Kg, 16.5 mg of potassium iodide. The resulting mixture is ground with another 100 g of glucose, homogenized and cross-linked. The weighed amount of 20 g represents part 10.

Part 11: this part represents 1,075 g of glucose.

Part 12: will be created by combining and homogenizing parts 9, 10 and 11.

Part 13: is created by mixing, homogenizing and repeated crosslinking of parts 4 and 8.

Parts 12 and 13 are mixed, homogenized by repeated sieving through sieves No. 06, 125 and .40. The resulting final product is filled into 60 bags of 88 g each.

Example 2

As a raw material, 20 to 40% of the weight of the required amount of amino acids is taken in the form of a summary prepared by hydrolysis of casein or other protein substrate. After analytical determination and evaluation, it is supplemented with L-forms of pure amino acids to the amount specified in the recipe in example 1. The further procedure is the same as in this example.

Example 3

The procedure is the same as in example 1 or 2, except that the sugars contained in the recipe are omitted.

Example 4

The procedure is the same as in example 1 or 2, except that the vitamins contained in the recipe are omitted.

Example 5

The procedure is the same as in example 1 or 2, except that the trace elements contained in the recipe are omitted.

Claims (1)

Amino acid complex with special purpose for enteral nutrition in powder form, containing carbohydrates and essential fatty acids and optionally mineral salts, trace elements, vitamins, biofactors and/or taste enhancers, characterized in that it contains in percentages by weight 0.60 until 0.79 L-Isoleucine 0.34 until 0.46 glycine 0.94 aah ',24 L-leucine 0.40 until 0.75 L-proline 0.68 until 0.90 L-valine 0.77 until 1.02 L-serine 0.94 until 1.24 L-phenylalanine 0.42 until 0.56 hydrochloride ethyl ester- 0.20 until 0.27 L-tryptophan ru L-tyrosine 0.43 until 0.56 L-threonine 7.60 until 9.25 maltose 0.94 until ',24 L-methionine 3.85 until 4.62 sorbitol 0.69 until 0.91 L-lysine 1 i.40 until 13.90 starch 0.65 until 0.85 L-arginine 18.60 until 22.88 glucose 0.24 until 0.31 L-histidine 3.78 to 4.63 fructose 1.41 until 1.85 L-glutamine 30.40 to 37.00 sucrose 1.05 until ',37 L-Aspartic Acid 0.24 until 0.30 safflower oil dyeing 0.36 until 0.48 L-alanine