CS230838B1 - Aminoacid complex esp for enternal sustenance - Google Patents

Abstract

The invention relates to an amino acid complex (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 for enteral nutrition in the form powder which is applied as a suspension at a reasonable concentration containing carbohydrates and essential fatty acids, with optional other minerals, trace elements, vitamins and their relatives substances, especially flavoring.

Description

The invention relates to a complex of amino acids with a special purpose for enteral nutrition in the form of a powder comprising carbohydrates and essential fatty acids and optionally mineral salts, trace elements, vitamins, biofactors and / or taste corrections; this complex is applied in the form of a suspension of appropriate cell concentration orally or by means of a suitable probe.

The complex of amino acids is one of the special dietetics and forms the transition between parenteral nutrition and normal diet. It is a preparation that belongs to the group of chemically defined diets without ballast substances. Its composition is original and substantially different from known formulations already clinically used. It was compiled on the basis of the authors' experience in the preparation of various mixtures of amino acids, supplemented by the latest clinical knowledge in this field. The amino acid complex contains mainly L-forms of pure amino acids, essential and assisting, with the exception of cystine. The ratio of essential amino acids to assistants is 3, so based on experience, it is optimal and the complex has a high biological value. The amount of amino acids was chosen to be 622 kJ per g of dd, which is optimal for amino acid utilization. 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, has been chosen in accordance with the latest knowledge to ensure daily needs.

Essence of a complex of amino acids with special purpose for enteral nutrition according to the invention

hears in tom, % by weight 0.60 to 0.79 L-isoleucine 0.36 to 0.48 L-alanine 0.94 to 1.24 L-leucine 0.34 to 0.46 glycine 0.68 to 0.90 L-valine 0.40 áž 0.75 Of L-proline 0.94 to 1.24 L-phenylalanine 0.77 to 1,02 L-lilac 0.20 to 0.27 B-tryptophan 0.42 to 0.56 ethyl- 0.43 to 0.56 Of L-threonine L-tyrosine ester 0.94 to 1.24 Ir-methionine 7,6 » to 0.25 maltose 0.69 to • 0.91 L-lysine 3.85 to 4.62 sorbitol 0.65 to 0.85 L-arginine 11.40 to 13.90 starch 0.24 to 0.31 L-histidine 18.60 to 22.88 glucose 1.41 to 1.85 Of L-glutamine 3.78 to 4.43 fructose 1.05 to 1.37 L-aspartic acids 30.40 to 37.00 sucrose

0.24 to 0.30 safflower oil.

The L-forms of pure amino acids or the 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 to prepare the amino acid complex. Pure amino acids can be weighed directly, mixed and homogenized by repeated cross-linking. The same applies to the mineral salts; also sugars are weighed directly and homogenized also by sieving. The oil component is triturated. The final formulation of the desired composition is obtained by mixing and homogenizing the individual parts as detailed in the Examples.

The amino acid complex of the invention has been tested pharmacologically and clinically in all its alternatives. It does not need the digestive tube enzymatic equipment to be used well, especially when using nasogastric or nasojejunal probes. In pharmacological testing, a clinically used formulation of close composition was used for comparison.

Because of non-toxicity, it was not possible to perform the LD ^ ₀ test, only the harmless test.

The chronic toxicity test has shown that the diet administered in the form of the complex of the invention provides higher weight gains than the standard diet used in rats. No pathological values were found in the biochemical parameters, nor did the histological examination of the parenchymatous organs (liver, kidney) show any pathological changes. From a pharmacological point of view, the complex according to the invention is fully satisfactory, moreover, in view of the advantageous composition, comparable results to that of a standard preparation are obtained at half-dosage, which is also not negligible from an economic point of view.

Clinical trials were performed either directly orally using a naeogastric probe. Per os testing has confirmed the experience that the relative hontraindication of oral administration of the amino acid complex of the invention in the form of a suspension is intense appetite. Administration of the product did not result in changes in pressure and pulse rate. Also, there were no changes in biological parameters. When using a nasogastric probe, the tolerance was very good, the probe never clogged. In all patients with severe nutritional disorder, the clinical condition improved significantly

When comparing the amino acid complex of the invention with a clinically used preparation of the same indication but without L-methionine and L-tyrosine ethyl ester hydrochloride, the following results were obtained:

With the amino acid complex of the invention, 6 g of energy per 1 g of nitrogen is used, which is, in experience, an optimal ratio. For the comparative preparation, 1 230 KJ per g of nitrogen is much, which is many.

The ratio of essential amino acid nitrogen to total nitrogen in the composition of the invention is 3, which corresponds to a high quality egg protein; for the comparator product it is 2.3, which corresponds to a poor quality protein, the usefulness of which is limited.

The composition according to the invention contains 50 wt. essential amino acids, of which 20 wt. branched. This creates optimal conditions for proteosynthesis. «Even under pathological conditions. The comparative formulation contains less essential amino acids, 36 wt. % and less branched amino acids, 16 wt. Branched amino acids prevent ppoteolysis.

An arginine / glycine index value of 1.87 for the formulation of the present invention is more preferred than 1.12 for the comparator formulation, since the increased amount of arginine prevents possible hyperammonemia.

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

These comparisons show the advantages of the amino acid complex of the invention.

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

For potassium, 5.25 mmol / 1 g of nitrogen is optimal, which is optimal in contrast to the comparative formulation, where the ratio is 9.0 mmol / 1 g of nitrogen. The trace elements manganese and zinc are present in higher amounts, because under pathological conditions there are increased losses of these elements.

The comparison clearly demonstrates that based on basic experimental work, positive pharmacological and clinical results, a recipe for a new amino acid complex has been created, effectively supplemented with carbohydrates, mineral salts, trace elements, vitamins, biofactors, or tasteful corrections. important clinical areas.

Example 1

For a batch of 60 sachets of 88 g (± 3% by weight), weigh the following components (expressed in g or mg):

Episode 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-tryptophene 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

Episode 2:

58.8 sodium chloride

46.8 potassium chloride 2.58 magnesium oxide

15,22 calcium phosphorylcholine chloride tetrahydrate

Calcium glycerophosphate

Episode 3:

444.6 meltoses

222.3 sorbitol

672.0 soluble starch

Part 4: is created by joining, homogenizing and sieving part 1, 2 and 3.

Part 5: 14.4 g of safflower oil are dispersed in 290 g of sucrose by trituration, then 1,488 g of sucrose are added, homogenized and cross-linked.

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

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

Part 8: produced by mixing, homogenizing and crosslinking part 5, 6 and 7.

Part 9: In 50 g of glucose, it is triturated, homogenized and cross-linked with 50 mg of vitamin D ₂ and 25 mg of vitamin B, g. Then weigh 0.1 g as part 9.

Part 10: mix and spread 430 mg of vitamin A acetate, 120 mg of vitamin A in 99 g of glucose

Bp 120 mg vitamin B ₂ phosphate, 235 mg pyridoxolium chloride, 1.5 mg folic acid, 19.5 mg D-biotin, 120 mg vitamin Kg, 16.5 mg potassium iodide. The resulting mixture is triturated with an additional 100 g of glucose, homogenized and crosslinked. A weighed quantity of 20 g represents part 10.

Lot 11: This portion represents 1,075 g of glucose.

Part 12: created by joining and homogenizing part 9, 10 and 11.

Part 13: produced by mixing, homogenizing and repeating screening parts 4 and 8.

The sections 12 and 13 are mixed, homogenized by repeated sieves No. 06, 125 and 40. The resulting end product is filled into 60 sachets of 88 g.

Example 2

20 to 40% by weight of the required amount of amino acids in the form of a summary prepared by hydrolysis of casein or other protein substrate is taken as raw material. After analytical determination and evaluation, they are supplemented with L-forms of pure amino acids to the amount indicated in the recipe in Example 1. The 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)

Aminoalkyl seli.o complex with a special purpose for enteral nutrition in the form of powder, containing carbohydrates and essential fatty acids and optionally mineral salts, trace elements, vitamins, biofactors and / or taste corrections, characterized in that it contains in percent by weight 0.60 to 0.79 L-isoleucine 0.34 to 0.46 glycine 0.94 aá ', 24 L-leucine 0.40 to 0.75 Of L-proline 0.68 to 0.90 L-valine 0.77 to 1,02 L-serine 0.94 to 1.24 L-phenylala.ninu 0.42 to 0.56 hydrochloride ethyl- 0.20 to 0.27 L-tryptophan % of L-tyrosine 0.43 to 0.56 Of L-threonine 7.60 to 9.25 maltoses 0.94 to ', 24 L-methionine 3.85 to 4.62 sorbitol 0.69 to 0.91 L-lysine 1 i, 40 to 13.90 starch 0.65 to 0.85 L-arginine 18.60 to 22.88 glucose 0.24 to 0.31 L-histidine 3.78 to 4.63 fructose 1.41 to 1.85 Of L-glutamine 30.40 toŽ 37.00 sucrose 1.05 to ', 37 L-aspartic acids 0.24 to 0.30 oil flares dyeing 0.36 to 0.48 L-alanine