SK35694A3 - Nutritive mixture of low molecular type for healing of malnutritive states of different etiology - Google Patents

Abstract

This nutrition mixture is a dietetic preparation of low-molecular type containing mono- to oligosaccharides, protein fragments with a known molecular weight produced by the hydrolysis of initial proteins, fats consisting of triacylglycerols with essential fatty acids or fatty acids with a medium length chain (MCT) enriched with vitamins and mineral substances, including trace elements. The nutrition mixture contains protein hydrolysate, glucose, saccharose, saffron thistle oil or oil containing MCT fats, sodium chloride, potassium chloride, calcium glycerophosphate, the optimum quantity of trace elements, retinol acetate, ascorbic acid, thiaminium dichloride, the sodium salt of riboflavine 5-phosphoric acid, pyridoxolium chloride, nicotinamide, folic acid, calcium pantothenate, D-biotin, cyanocobalamin, inosite, ergocalcipherol, tocopherol acetate, fytoquinone. The mixture may be flavoured with suitable flavouring imitations. The nutrition mixture of this composition is used for the nutritive support and treatment of malnutrition conditions of various etiology, including the condition with a changed GIT function.

Description

Nutritional mixture of low molecular weight malnutrition states of different etiology of type

1iečenie

Technical field

The invention relates to a nutritionally low-molecular-type composition for the treatment of malnutrition conditions of various etiology, including conditions with limited enzymatic activity of the gastrointestinal tract (GIT).

BACKGROUND OF THE INVENTION

Malnutrition is the result of a number of serious diseases and is now considered a significant risk factor. A significant percentage of hospitalized patients are in a state of moderate or severe protein malnutrition, while foreign patients report about 25 to 50% (Sur. Gyn. Obst.

iterary sources 141, 1975, p. 512.

Bistrian, Depletion

R. R. et al., Therapeutic Index of Nutritional in Hospitalized Patients, JPEN. 11, 5 (1987), p.

55, Quarnieri, G. et al. Direct Biochemical Analysis

Human Musele Tisue in Hospital Malnutrition, JPEN, 11, 5, 1987, p. 122, Mobarhan, S. et al. Determinant of Nutritional Status in Hospital Patients in Italy, JPEN, 11, 5, 1987. p.

36, Quarnieri. G. = Nutritional Assistance in Hospital Malnutrition. Malnutricia is a major contributor to the failure of properly selected surgical and conservative treatments (Clin. Nutr., 4, Suppl., 1985, p. 133, Vinnars, E. = "Postoperative"

Nutrition, Am. J. Sugr., 139, 1980, p. 160, Buzby, G. P. et al. Prognostic Nutritional Index in Gastrointestinal Surgery. The consequence of malnutrition is the susceptibility of patients to infections and their severe suppression due to insufficient concentration (Regulators Peptides, 19, 1987, p.

Effect of Total Parenteral Nutntion Transport Proteins 281, Campos, R.V. on Gastrin Release in the Rat.

Biol. Neonate, 51, 1987, p.

286, Gali, D.G. et al. Effect of Parenteral and Enteral Nutrition on Postnatal Development of Small Intenstine and Pancreas in the Rabbit, JPEN, 11, fc>, 1987, p. 533, Heller, D. et al. Free Amino Acid Formula: Nitrogen Utilization

Metaboli c Effects in Normal Subjects. 4969, p. 642, Stephens, R.V. et al. Balanced, Liquid Dietary Diet

Ann. Surg., 170, 4,

Use of Concentrated for Nutritional Management

Catabolic States, JPEN, 12.6.1988, p. 43. Wan, J.M.F. et al. Lipids and the DEVELOPMENT of Imune Dysfunction and Infection. JPEN, 14, 4, 1990, p. 362, Patterson, M.L. et al. Enteral Feeding in the Hypoalbuminemic Patient). Protein malnutrition also affects changes in the metabolism of other substances, such as reduced availability of carbohydrates (Nutr. Metabol., 19, 1975, p. 225, Bruckdorfer, KR et al. Comparison of Dietary Starch and Dietary Sucrose in the Pig, Gastroenterology. 74 6, 1978, pp. 1261, Thomas, FB et al., Selective Release of Gastric Inhibitors Polypeptide by Introduodenal Amino Acid Perfusion in Man), changes in levels of minerals and trace elements (Clin, Nutr., 6, 1987, Suppl., 81, Bauman, V. et al., Trace Elements in Nevborns and Infants vith Gastrointestinal Disease and Nutrition vith and Samielemental Formula ', JPEN, 10, 2, 1986, p. 223, Jacobson, S. Serum Concentratíons of Cobalamine during Total Parenteral Nutrition in Crohn with Disease, JPEN, 10, 2, 1986, p. 213, Martin, KF et al., Selenium Content of Enteral Formulas, Gastroenterol., 78, 1980, p. 272, Mc Clain, C. et al. Zinc Deficiency: A Complication of Crohn with Disease, JPEN, 10, 2, 1986, pp. 195, Takagi, Y. et al. Clinical Studies on Zinc Metabolism during Total Parenteral Nutrition as Released to Zinc Deficiency). For this reason, the relationship between nutrient intake and expenditure and energy, between catabolism and anabolic nutritional optimization (JPEN, 11, 1, 1987, p. 14, Popp,

M. et al. Energy Expedition and Mater Activity in Rasts Receiving Total Parenteral Nutrition, JPEN, 11, 1, 1987, p. 1, Saito, H. et al. The Effect of Route of Nutritient Ionate on Nutritional State, Catabilic Hormone Secretion and Gut Musical Integrity after Burn Injury, JPEN, 10, 5, 1986, p. 479, Smith, A. E .: "Improved Nutritional Management Reduces Lenght of Hospitalization in Intractable Diarrhea", JPEN, 11, 5, 1987, p. 435. Abel, R. et al .: “Guidelines for Use of Enteral Nutrition in the Adult Patient”). This requirement can practically be accomplished by two basic delivery routes - the enterial, physiological and parenterial routes. Parenteral nutrition is strictly indicated in patients nutrients physiologically with 235, Zadák, Z. Nutrition Treatment, Pharmacotherapist. The investigators are unable to receive (Pharmacoter. Reports. 28, 3, 1982, Advanced Small-Parenteral You, 28 March 1982. p. 227, Zitko, K. et al. Parenteral Nutrition of Surgical Patients, Pharmacother. Reports, 28 March , 1982,

with. 199, Doberský, P ^.: Parental Nutrition Yesterday and Cines ”). If at least a portion of the gastrointestinal tract is functional, it is preferable to select the enteral nutritional pathway, probe or stoma. In total parenteral nutrition, intestinal mucosal hypoplasia and decreased secretion and function of the gastrointestinal enzymes of the intestinal tract are reduced (JPEN, 11, 6, 1987, p. 586, Karton, M. et al .: Effect of Parenteral Nutrition and Enteral Feeding on D- Acidosis in a Patient vith Short Bowel, JPEN, 13, 5, 1989, pp. 525, Berner, Y, et al., Vitamin Plasma Levels in

Long Term Enteral 505, de Angel is G., et al

Nasoenteral Feeding with annual nutrition support,

Feeding Patients, JPEN, 12, 5, 1988, p.

L. et al .: Gastric Pepsin and Acid Secre Transparent Nutrition and Constant-Rate

Enteral Nutrition in Infancy), which makes it difficult to later convert to a normal diet (Farmakoter. Reports, 28, 3, 1982, p.

207, Brodan, V. Pathophysiological Aspects of Parenteral Nutrition Gastroenterology, 70, 1976, p. 712, Feldman, E.J. et

Effect of Oral versus Intravenous Nutrition on Intestinal Adaptation after August 11 Bowel Resection in the Dogs, JPEN, 11, 6, 1987, p. Roongpisuthipong, CH. et al. Continuous Inverse Relation Betveen Infusion Rate and Serum Levels of Bil i rubi n, JPEN, 12, 6, 1988, p. 615.

Sax, H. C. et al. Hepatic Complicatlons of Total Parenteral Nutrion.

Thus, the nutritional trend of patients with indicated parenteral nutrition is as quickly as possible in combination with the entea of gradual transfer to the enteric pathway, less burdensome to the patient and less of a risk of secondary infection. Enteric nutrition can be applied to a greater amount of nutrients in a better balanced ratio, without overloading the patient with fluids. The steady-state ratio between parenteral and enteral nutrition is, according to US statistics 1 1.2, in favor of enteral nutrition, of course, depending on the type and nature of the disease (JPEN, 14, 4, 1990, p.

404, Bufano, G. et al. Entering Feeding in Anorexia Hervosa, JPEN. 14, 4 1990, p. 329, Bistrian, R. R., Recent Advances in Parenteral and Enteral Nutrition).

Pharmaceutically prepared and evaluated dietetics serve as a combination of paraenteral and enteric nutrition or for single entenal nutrition by intragastric to intratracheal tube or direct stoma. They are balanced, chemically or biochemically defined, and subject to pharmaceutical prescriptions.

Depending on the content of active substances and the nature of the contained nutrients, dietetics can be divided into two basic groups:

1) high molecular weight dietetics. containing high molecular weight polysaccharide and protein substances requiring an enzymatic apparatus for utilization;

2) low molecular weight dietetics. chemically defined, containing mono to oligosaccharides; according to the crude protein content they are further divided into:

(a) molecular (1st generation) containing pure anino acids

(b) oligopeptidic (2nd generation), containing protein grafts of known molecular weight (max. 1 500) resulting from enzymatic or acid hydrolysis of the starting proteins; (c) Literature (Gabre, E.,

A. et al., Effect of

Gonzales-Huix, F. Abad-Lacruz, total enteral nutrition on the short-team. Outcome of Northern Malnourished Cirrhotics: A Randomized Controlled Lrial, Castroenterology, 1990, 98, p. 715. Herskovits, K., Souba, H.V. Intestinal glutamine metabolism during enticali lness: a surgical perspective. Nutrition 6, 1990, p. 199 to 206. Remedia

3, 1993, p. 168, Zadák, Z ^.: Nutritional Pharmacology and Enteral Nutrition in Clinical Practice).

SUMMARY OF THE INVENTION

Dietetic n isomolecular types do not require enzymatic assurance for their utilization. Amino acids and low molecular weight oligopeptides are absorbed directly by intestinal mucosa. It is an object of the present invention to provide balanced, biochemically defined, low molecular weight targets, the so-called oligopeptide nutrition.

In the application of this type of dietetic drug, the second generase diet utilizes the ability of the digestive tract to absorb this type of nutrient-free short chain peptide without the protease involvement and therefore can be administered to patients with limited GIT enzymatic activity. A further advantage of oligopeptides compared to crystalline amino acids is that they can absorb multiple amounts of crude protein through the same intestinal section and, at the same time, allows less gastrointestinal oligopeptides to be sterilized by conventional GIT methods. Molecule size preparation of a stable colloid and thus preparation of a liquid dosage form under industrial conditions.

The source of oligopeptides in low molecular weight dietary diets is an enzyme hydrolyzate of commonly available proteins, such as casein, bovine albumin, soy protein, or egg white.

Peptidic preparations represent a complete defined and balanced diet, because in addition to the peptide component, they also contain carbohydrates, lipids, minerals, trace elements and vitamins in the following proportions:

12, 6 17, 0 30, 7 to 16.2 % % % materials.  1 ii egg white hydrolyzate glucose sucrose until until 21.7 1/1 0, 47 until 0, 61 II stabilized oil dye lights (or soy or sunflower) 28.8 until 31.3 % • I an enzyme starch hydrolyzate 0.99 until 1.26 % I sodium chloride 0, 44 until 0, 56 % potassium chloride 0. 67 until 0.86 % · calcium glycerophosphate

0.04 to 0.052. 2 H 2 O% magnesium oxide

6. 6 until 9.8.ΙΟ ' ³ % · ferrous sulfate. 7 HzO 2. 5 until 3,2.10- ⁵ % Of potassium potassium 0. 9b until 1.2% ³ % copper acetate. IísO 2. 7 until 3,5.10-3 sž • 1 manganese acetate 4 KsO 1.0 until 1.3 ³ ' ³ sj zinc oxide 1.4 until 1,85.10 ' ⁴ % - potassium dichromate 3.4 until 4, 45, 10-10 ammonium molybdate 4 K2C 0.017 to 0,022% ascorbic acid 6. 7 until 8,6.10 ' ⁴ % retino1acetátu 1.5 until 2.0.10- *% · · ergocal ferol 4, 0 until 2.5 Sí ' ³ • 1 tocopherol 1. with until 2,45.10 ' ⁴ % · thiamine dichloride 1.8 until 2, 45.10 ' ⁴ % sodium salt of 5-R 1bof vinfosforečnéj 3, b until 4,7.10 ' ⁴ % pyridoxol chloride 14/14 until 4,01.10-3% 1 · nikotlnamidu 1.79 until 2.3.ΙΟ ' ⁵ % 1 · kyse1 i ny 11 stove j 2, 02 until 2,6.ΙΟ ³ % n calcium pantothenate 0.92 until 1,18.10- ⁴ % II D-biotin 0. 79 until 1,01.10 ' ⁶ % cyanocobalamin 1.89 until 2.4.10 ' ⁴ % phylloquinone 0.018 to 0.023% and knives here

The nutritional composition of the invention may contain up to 3.3% by weight. An oil containing triacylglycerols of C 6 -C 12 fatty acids.

The nutritional composition of the invention is prepared by weighing and sieving the individual components. These are combined with separately prepared, homogeneous triturations of vitamins and trace elements in a stirrer homogenizer. The stabilized oil phase with lipophilic vitamins and optionally the aromatic liquid additive are mixed into the homogenizer by injection. The homogenized mixture is filled into bags of special foil, preferably for a protective nitrogen atmosphere, in a microbiologically safe environment, and sealed by heat sealing. The production is practically waste-free, ecologically advantageous, but it is demanding in terms of weighing accuracy, homogeneity and compliance with hygiene conditions to maintain the microbiological safety of the final product.

suck weekly) Total was

The nutritional composition of the invention was used to pharmacologically monitor chronic toxicity in rats. As safety has been demonstrated in the long term (clinical trials have been made), the nutritional composition according to the invention was administered to 19 patients at 5 selected workplaces in the indicated area, patients were predominantly in units: intensive (or metabolic) care with GIT diagnosis nutrition (m.Crohn. adeno CA stomach, colic sprue), neurological (amyotrophic lateral sclerosis, apathetic sy) and nephrological (chronic renal failure treated by hemodialysis).

The nutritional and clinical status of the patient was evaluated in the clinical trial, the effect on protein metabolism (including serum amino acid kinetics, indicative nitrogen balance and short-term protein values) was evaluated, the transcaine water and mineral balance and immune parameters were monitored. During the nutritional use of the mixture, the individual parameters were within the reference range of normal values, the pathological values at the initial examination were adjusted significantly towards the standard. Balances of water and minerals were balanced. Also, the nutritional status of patients was balanced, in most cases there was an improvement, which was usually positively reflected also in the clinical condition.

Production technology guarantees two years of stability without loss of biological value and chemical identity of contained substances, which has been proven.

The nutritional composition of the invention serves for the dietary treatment of malnutrition conditions of various etiology, including patients with altered gastrointestinal tract function.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Weigh, sieve and mix the ingredients according to the following recipe:

egg white hydrolyzate 13.40 g glucose 18.00 g sucrose 25.50 g

starch enzyme hydrolyzate KMS-X-50 23. 10 g oil flares dye stabilized 00:50 g sodium chloride 1.5 g Potassium chloride 0. 47 g calcium glycerophosphate. 2 HaO 0,712 g magnesium oxide 0. 043 g ferrous sulphate. 7 HaO 8,1000 mg Potassium iodide 0.0270 mg copper acetate. H2O 1.0200 mg manganese acetate 4 H2O 2,8500 mg 21-stearous oxide 1.0800 mg potassium dichromate .1527 mg ammonium molybdate. 4 H2O 0.0367 mg ascorbic acid 18,0000 mg lip inolacetate .7110 mg ergoka1c i f ero1 0.00165 mg tocopherol acetate 4.2600 mg thiamine dichloride 0,2000 mg 5-riboflavin phosphoric acid sodium salt 0.2000 mg ch1or i d pyr i doxo1 i a C 3900 mg nicotinamide 3.3300 mg acid 0.0190 mg calcium pantothenate 2, 1400 mg D-biotin 0,0981 mg kyanokoba1am i n 0.00084 mg phylloquinone 0,2000 mg i noz i t 19.5000 mg

In this way, 83 g of a nutritional composition according to the invention with an energy value of 1254 kJ (300 kcal) are prepared.

Example 2

For example 1, where the same amount of stabilized soybean oil is used in place of the stabilized dye oil.

Example 3

In this Example 1, where the same amount of stabilized sunflower oil is used instead of the stabilized dye oil.

Example 4

Detto Example 1. wherein the egg white is used in the same amount instead of the egg case casein hydrolyzate hydrolyzate.

Example 5

For example 1, wherein the same amount of soy hydrolyzate is used instead of egg white hydrolyzate.

Example 6

For example 1, wherein the same amount of lactose hydrolyzate is used instead of egg white hydrolyzate.

Example 7

Increase the amount of fat-fed energy if necessary. it is possible to enrich the nutritional mixture with a medium-chain fatty acid triacylglycerol preparation. Their metabolism and mode of transport allow maximum utilization of this energy even in pathologically altered fat metabolism and dysfunction of transport mechanisms. The mixture is prepared by weighing, sieving and intermixing the ingredients according to the following recipe:

egg white hydrolyzate 13, 40 g glucose 18,00 9 sucrose 35, 00 g starch enzyme hydrolyzate KMS-X-50 33. 20 g oil flares dye stabilized 0, 50 9 miglyol 812 3. 50 g sodium chloride 1.05 g Potassium chloride 0. 47 g calcium glycerophosphate. 2 H2O 0. 712 g magnesium oxide 0, 043 9 sulphate of forestry 7 H2O 8,1000 mg Potassium iodide 0.0270 mg copper acetate. H2O 1,0200 mg manganese acetate 4 H2O 2,8500 mg zinc oxide 1.0800 mg

potassium dichromate .1527 mg ammonium molybdate. 4 HzO 0.0367 mg ascorbic acid 18.0000 mg retinol acetate .7110 mg ergokalci ferol O, 00165 mg tocopherol acetate 4.2600 mg thiamine dichloride 0.2000 mg sodium salt of 5-riboflavin phosphoric acid 0.2000 mg pyrodoxole chloride 0,3900 mg nikot i namid 3.3300 mg 11st 0.0190 mg calcium pantothenate 2.1400 mg D-biotin 0,0981 mg kyanokoba1am i n 0.00084 mg phylloquinone 0,2000 mg i knives t 19.5000 mg

In this way, they are prepared with an energy value

106 g of the nutritional composition of the invention is 1675 kJ (400 kcal).

Example 8

For example 7, where soybean oil is used.

Example 9

In this example 7, where the oil is used.

Example 10

For example 7, in which the same amount of white is used

Example 11

For example 7, where the egg white is used the same amount instead of the stabilized oil the same amount stabilized instead of the stabilized oil the same amount of sunflower instead of the hydrolyzate of the egg case and the other hydrolyzate.

instead of egg soy hydrolyzate.

Example 12

For example 7, where the same amount of lactoserine hydrolyzate is used instead of egg white hydrolyzate.

Industrial. exploitability

The nutritional composition of the invention is used (as in the practice _of Rene ove) nutríSnej the support and the treatment of conditions malnutrí & Nycha different etiolúgie, including conditions with altered gastrointestinal function.

Claims (2)

PATENT CLAIM Nutritional tolerability for the treatment of malnutrition conditions of various etiologies, including conditions with altered GIT activity. solved on the basis of n isomeric substances with precise microbiological and chemical parameters. characterized t>  m. that it contains ^: 12, 6 until 16th 2 J: materials. egg white hydrolyzate, or a soy hydrolyzate; a case of the hydrolyzate of the invention; a lactose hydrolyzate 17, 0 until 21, 7 % glucose 30, 7 until 33rd 1 % T sucrose 0. 47 until 0 61 % stabilized oil or soya or sunflower 28.8 until 31, 3 The an enzyme starch hydrolyzate 0, 99 until 1, 2b %  1 sodium chloride 0, 44 until 0 56 % potassium chloride 0. 67 until 0 86 3S calcium glycerophosphate . 2 H2O 0, 04 until 0 052 <0 magnesium oxide 7, ô until 9th S.10 ' ³ % ferrous sulfate. 7 II2O 2.5 until 3 2.10- '· % potassium iodide 0, 96 until 1. 2.ΙΟ ' ³ % · copper acetate. H2O 2, 7 until 3 5.10 ' ³ manganese acetate. 4 HaO 1, o until 1. 3.10-3 % zinc oxide 1.4 until 1. 85.10 ' ⁴ x potassium dichromate 3, 4 until 4. 45.1O- * "% ammonium molybdate. 4 HzO 0.017 to O. 022 % ascorbic acid 6.7 until 8th 6.10 ^-4 % · retinol 1.5 until Second 0.ío- * % ll ergokac1 f ero1 u 4.0 until 5th 2.ΙΟ ³ % tocopherol 1.8 until 2 45.1O- 4% thiamine dichloride 1.8 until Second 45.10- 4% sodium salt of 5-ribofla- vinfosforečnej 3, Ď until 4. 7.10 ' ⁴ % pyridoxolia chloride 3, 14 until 4,01.10 nicotinamide 1.79 until 2.3 .10- ⁵ % kyse1 iny 1 i stove j 2. 02 until 2.b .10 ' ³ % calcium pantothenate 0. 92 until í. 1S. 1 0 · * '4 D-biotin 0, 792 until 1.01.10- °% cyanocoba1 amine 1.89 until 2,4.10 ' ⁴ %' phylloquinone 0,018 until 0,023 4 inositol 2. The mixture according to claim 1, characterized in that it contains up to 3.3% by weight. an oil containing three acylglycerols of C 6 -C 12 fatty acids.