CZ283569B6 - Nutrition mixture of a low-molecular type for treating malnutrient states of various 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

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Nutritional mixture Is a low-molecular-type dietetic containing mono to oligosaccharides, protein grafts of known molecular weight, resulting from hydrolysis of the starting proteins, fats composed of triglycerides with essential fatty acids, eventually. medium chain fatty acids (MCT), enriched with vitamins and minerals including trace elements. The nutritional mixture contains protein hydrolyzate, glucose, sucrose, safflower oil, respectively. oil containing MCT fats, sodium chloride, potassium chloride, calcium glycerophosphate, magnesium oxide, optimal trace elements, retlnol acetate, ascorbic acid, thiaminium dichloride, 5-riboflavln phosphoric acid sodium, pyrldoxolium chloride, nicotinamide, folic acid, calcium pantothenate , D-biotin, cyanocobalamin, lnosit, ergocalciferol, tocopherol acetate, phylloquinone. The composition may be flavored with suitable taste imitations. A nutritional composition of this composition serves to nutritionally support and treat malnutrition conditions of various etiologies, including conditions with altered GIT function.

Low-molecular-type nutritional mixture for the treatment of malnutrition states of different etiology

Technical field

The invention relates to a low molecular weight nutritional composition for the treatment of malnutrition conditions of various etiologies, 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, foreign literature reports about 25 to 50% (Sur. Gyn. Obst. 141, 1975, p. 512, Bistrian, RR et al .: Therapeutic Index of Nutritional Depletion in Hospitalized Patients, JPEN, 11, 5, 1987, p. 55, Quamieri, G. et al .: Direct Biochemical Analysis of Human Muscle Tissue 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, Quamieri, G .: Nutritional Assesment in Hospital Malnutrition). Malnutrice 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.Surg., 139, 1980, p. 1). 160, Buzby, GP et al .: Prognostic Nutritional Index in Gastrointestinal Surgery). The consequence of malnutrition is the susceptibility of patients to infections and their difficult suppression due to insufficient concentration of transport proteins (Regulators Peptides, 19, 1987, p. 281, Campos, RV: The Effect of Total Parenteral Nutrition on Gastrin Release in the Rat., Biol. Neonate, 51, 1987, pp. 286, Gall, DG et al .: Effect of Parenteral and Enteral Nutrition on Postnatal Development of the Smáli Intestine and Pancreas in the Rabbit, JPEN, 11, 6, 1987, p. 533, Heller, D. et al .: Free Amino Acid Formula: Nitrogen Utilization and Metabolic Effects in Normal Subjects., Ann. Surg., 170, 4, 1969, p. 642, Stephens, RV et al .: Use of Concentrated, Balanced, Liquid Elemental Diet for Nutritional Management of Catabolic States, JPEN, 12, 6, 1988, pp. 43, Wan, JMF et al .: Lipids and the Development of Immune Dysfunction and Infection, JPEN, 14, 4, 1990, pp. 362, Patterson, ML et al .: Enteral Feeding in the Hypoalbuminic 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, K. R. et al .: Comparison of Dietary Starch and Dietary Sucrose in the Pig, Gastroenterology, 74, 6, 1978, p. 1261, Thomas, FB et al .: Selective Release of Gastric Inhibitors Polypeptide by Introduodenal Amino Acid Perfusion in Man), Changes in Minerals and Trace Elements (Clin. Nutr., 6 1987, Suppl., P. 81, Bauman, V. et al .: Trace Elements in Newboms and Infants with Gastrointestinal Disease and Nutrition with a Samielemental Formula, JPEN, 10, 2, 1986, p. 223, Jacobson, S. : Serum Concentrations of Cobalamine during Total Parenteral Nutrition in Crohn's Disease, JPEN, 10, 2, 1986, p. 213, Martin, KD et al .: Selenium Content of Enteral Formulas, Gastroenterol., 78, 1980, p. 272, Mc Clain, C. et al .: Zinc Deficiency: A Complication of Crohn's Disease, JPEN, 10, 2, 1986, pp. 195, Takagi, Y. et al. : Clinical Studies on Zinc Metabolism during Total Parenteral Nutrition and Releated to Zinc Deficiency). For these reasons, it is necessary to balance the relationship between nutrient intake and expenditure and energy, between catabolism and anabolism by optimizing nutrition (JPEN, 11,1, 1987. p. 14, Popp, M. et al .: Energy Expediture and Mater Activity in Rats receiving Total Parenteral Nutrition, JPEN, 11, 1, 1987, pp. 1, Saito, H. et al .: Effect of Routes of Nutritient Administration on the Nutritional State, Catabolic Hormone Secretion and Gut Mucosal Integrity after Bum Injury, JPEN, 10 , 5, 1986, pp. 479, Smith, AE: Improved Nutritional Management Reduces Lenght of Hospitalization in Intractable Diarhea, JPEN, 11,5, 1987. p. 435, Abel, R. et al .: Guidelines for Use of Enteral Nutrition in the Adult Patient). This requirement can be practically realized by two basic routes of delivery - enteral, physiological and parenteral. Parenteral nutrition is accurately indicated in patients unable to take nutrients physiologically (Pharmacoter. Reports 28, 3, 1982,

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235, Zadák, Z .: Treatment of Advanced Malnutrition by Parenteral Nutrition, Pharmacother. Reports, 28, 3, 1982, p. 227, Zitko, K. et al .: Parenteral Nutrition in Surgical Patients, Pharmacother. Reports, 28, 3, 1982, p. 199, Doberský, P .: Parenteral Nutrition Yesterday and Today). If at least a portion of the gastrointestinal tract is functional, it is preferable to select the enteral nutritional pathway, probe or stoma. Indeed, in total parenteral nutrition, intestinal mucosal hypoplasia and decreased secretion and function of the gastrointestinal tract enzymes (JPEN, 11, 6, 1987, p. 586) are shown. Karton, M. et al .: Effects of Parenteral Nutrition and Enteral Feeding on D-lactic Acidosis in a Patient with Short Bowel, JPEN, 13, 5, 1989, pp. 525. Bemer, Y. et al .: Vitamin Plasma Levels in Long Term Enteral Feeding Patients, JPEN, 12, 5, 1988, p. de Angelis, GL et al .: Gastric Pepsin and Acid Secretion during Total Parenteral 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, EJ et al .: Effect of Oral versus Intravenous Nutrition on Intestinal Adaptation after Smal Bowel Resection in the Dogs, JPEN, 11, 6, 1987, pp. 554, Roongpisuthipong, Ch et al .: Continuous Naso enteral Feeding: Inverse Relation Between Infusion Rate and Serum Levels of Bilirubin, JPEN, 12, 6, 1988, pp. 615, Sax, H. C. et al .: Hepatic Complications of Total Parenteral Nutrition.

Thus, the nutritional trend in patients in whom parenteral nutrition is indicated is in the fastest possible combination with enteral nutrition and a gradual transition to the enteral nutritional support pathway, which is less burdensome to the patient and less of a risk of secondary infection. Enteral nutrition can be applied to a greater amount of nutrients in a better balanced ratio, without overloading the patient with fluids. The steady-state relationship 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, Bufáno, G. et al .: Enteral Feeding in Anorexia Nervosa, JPEN, 14, 4, 1990, pp. 329, Bistrian, RR: Recent Advances in Parenteral and Enteral Nutrition).

For the combination of parenteral and enteral nutrition, or for single enteral nutrition by intragastric to intrajejunal gavage or direct stoma, pharmaceutically prepared and evaluated dietetics serve. They are balanced, chemically or biochemically defined preparations subject to pharmaceutical regulations.

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

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

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

(a) molecular (1st generation) containing pure amino 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., Gonzales-Huix, F., Abad-Lacruz, A. et al .: Effect of total enteral nutrition on the short-term. outcome of severely malnourished cirrhotics: a randomized controlled trial, Gastroenterology 1990 , 98, pp. 715. Herskowitz, K. Souba, WW: Intestinal glutamine metabolism during criticalillness: a surgical perspective, Nutrition 6, 1990. pp. 199-206. Remedia 3, 1993, pp. 168, Zadák, Z .: Nutritional pharmacology and enteral nutrition in clinical practice).

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SUMMARY OF THE INVENTION

Low molecular weight dietetics do not require enzymatic assurance for their utilization. Amino acids and low molecular weight oligopeptides are absorbed directly by intestinal mucosa. The subject of the present invention is the balanced, biochemically defined low-molecular-weight 2-generation dietetics, the so-called oligopeptic nutrition.

The use of this type of dietetics utilizes the ability of short-chain peptides to be absorbed by the digestive tract without protease involvement, and thus can be administered to patients with limited enzymatic activity of GIT. Another advantage of oligopeptides compared to crystalline amino acids is the possibility of absorbing multiple amounts of nitrogenous substances through the same intestine and less osmotic load of GIT. At the same time, the size of the oligopeptide molecule makes it possible to prepare a stable colloid, sterilizable by conventional methods, and thus to prepare a liquid dosage form under industrial conditions.

The source of oligopeptides in low molecular weight peptide diets is an enzyme hydrolyzate of commercially 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 to 16.2 wt. 17.0 to 21.7% »1 30.7 to 33.1% 1 « 0.47 to 0.61% 11 28.8 to 31.3% - 0.99 to 1,26% »» 0.44 to 0.56% 11 0.67 to 0.86% ! 1 0.04 to 0.05% 11 7.6 to 9.8. 10 ^'J wt%. 2.5 to 3.2. 10 ' ⁵ % F! 0.96 to 1,2. 10 ' ³ % 2.7 to 3.5. 10 ' ³ % th 1.0 to 1.3. 10 ' ³ % »1 1.4 to 1.85. 10 *% ti 3.4 to 4.45. 10 ' ⁵ % 11 0.017 to 0.022 wt. 6.7 to 8,6.10- ⁴ % 11 1.5 to 2.0. 10 ' ⁶ % 11 4.0 to 5.0. 10 ' ³ % ft 1,8 to 2.45. 10 · ⁴ % ti 1,8 to 2.45. 10 ^u % Í1 3.6 to 4.7.10 ^-4 % t! 3.14 to 4.01. 10 ' ³ % tf 1.79 to 2.3. 10 ' ⁵ % It 2.02 to 2.6. IO ' ³ % rf 0.92 to 1.18. 10- ⁴ % tt 0.79 to 1.01. 10 ' ⁶ % II 1.89 to 2.4.1 θ ’*% tt 0.018 to 0,023% tt

egg white hydrolyzate glucose sucrose stabilized oil safflower (or soy or sunflower) enzyme starch hydrolyzate sodium chloride potassium chloride calcium glycerophosphate. 2 H ₂ O MgO ferrous sulfate. 7 H ₂ O potassium iodide copper (I) acetate. H ₂ O Manganese acetate. 4 H ₂ O zinc oxide potassium dichromate ammonium molybdenum. 4 H ₂ O ergocalciferol ascorbic acid tocopherol acetate thiaminium dichloride sodium salt of 5-riboflavin phosphoric acid pyridoxolia nicotinamide folic acid calcium pantothenate D-biotin cyanocobalamin phyloquininone inositu

The nutritional composition of the invention may contain up to 3.3 wt. oils containing triacylglycerols of fatty acids having 6 to 12 carbon atoms.

The nutritional composition of the invention is prepared by weighing and screening 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 introduced into the homogenizer by injection. The homogenized mixture is filled into sachets of special foil, preferably under a protective nitrogen atmosphere, in a microbiologically safe environment and sealed by heat sealing. Production is practically waste-free, ecologically advantageous, but it is demanding in terms of weighing accuracy, homogeneity and compliance with hygienic conditions to maintain the microbiological safety of the final product.

The nutritional composition of the invention was used for pharmacological monitoring of chronic toxicity in rats. Since safety has been demonstrated in long-term (10-week exposure), clinical trials have been undertaken. In total, the nutritional composition of the invention was administered to 19 patients at 5 selected workplaces. The indicated area included patients predominantly in intensive (or metabolic) care units diagnosed with GIT with nutritional disorder (Crohn's, adeno-gastric CA, collical sprue), neurological (amyotrophic lateral sclerosis, apical sy) and nephrological (chronic renal failure) treated with hemodialysis).

Nutritional and clinical status of the patient was evaluated during the clinical trial, as well as the effect on protein metabolism (including serum amino acid kinetics, indicative nitrogen balance and short-term protein values), water and mineral balance of transaminases, eventually immunity parameters. The individual parameters were within the reference range of normal values during the application of the nutritional mixture, the pathological values at the initial examination were significantly changed towards the norm. The balance of water and minerals was balanced. Also, the nutritional status of patients was balanced, in most cases there was an improvement, which was usually reflected positively also in the clinical condition.

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

The nutritional composition of the invention serves for the dietary treatment of malnutrition conditions of various etiologies 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 13.40g glucose 18.00g sucrose 25.50g starch enzyme hydrolyzate KMS-X-50 23.10g safflower oil stabilized 0.50g sodium chloride 1.05g potassium chloride 0.47g calcium glycerophosphate. 2 H ₂ O 0.712 g magnesium oxide 0.043 g ferrous sulfate. 7 H ₂ O 8.1000 mg

Potassium iodide copper (I) acetate. H ₂ O Manganese acetate. 4 H ₂ O zinc oxide potassium dichromate ammonium molybdate. 4 H ₂ O ascorbic acid retinol acetate ergocalciferol tocopherol acetate thiamine dichloride sodium salt of 5-riboflavin phosphoric acid pyridoxolia chloride nicotinamide folic acid calcium pantothenate D-biotin cyanocobalamin phylochinone inosit

0,0270 mg 1,0200 mg 2,8500 mg 1,0800 mg 0,1527 mg 0,0367 mg 18,0000 mg

0,7110 mg 0,00165 mg 4,2600 mg 0,2000 mg 0,2000 mg 0,3900 mg 3,3300 mg 0,0190 mg 2,1400 mg 0,0981 mg 0,00084 mg 0,2000 mg 19, 5000 mg

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

Example 2

In this Example 1, the same amount of stabilized soybean oil is used in place of the stabilized dye safflower oil.

Example 3

In this Example 1, the same amount of stabilized sunflower oil is used in place of the stabilized oil of safflower.

Example 4

In this Example 1, the same amount of casein hydrolyzate is used instead of egg white hydrolyzate.

Example 5

In this Example 1, the same amount of soy hydrolyzate is used instead of egg white hydrolyzate.

Example 6

In this Example 1, wherein an equal amount of lactose hydrolyzate is used in place of the egg white hydrolyzate.

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Example 7

If necessary, to increase the energy input from fat, the nutritional mixture can be enriched by the addition of medium chain fatty acid oil with triglycerides. Their metabolism and mode of transport allows 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 individual ingredients according to the following recipe:

egg white hydrolyzate glucose sucrose enzyme starch hydrolyzate KMS-X-50 safflower oil stabilized miglyol 812 sodium chloride potassium chloride calcium glycerophosphate. 2 H ₂ O magnesium oxide ferrous sulphate. 7 H ₂ O Potassium iodide Copper acetate. H ₂ O Manganese acetate. 4 H ₂ O zinc oxide potassium dichromate ammonium molybdate. 4 H ₂ O ascorbic acid retinol acetate ergocalciferol tocopherol acetate thiamine dichloride sodium salt of 5-riboflavin phosphoric acid pyridoxolia chloride nicotinamide folic acid calcium pantothenate

D-biotin cyanocobalamin phylloquinone inosit

13,40 g

18,0 g

35,00 g

33,20 g

0.50 g

3,50 g

1.05 g

0.47 g

0.712 g

0.043 g

8,1000 mg

0,0270 mg

1,0200 mg

2,8500 mg

1.0800 mg

0.1527 mg

0,0367 mg

18,0000 mg

0,7110 mg

0.00165 mg

4,2600 mg

0,2000 mg

0,2000 mg

0.3900 mg

3,3300 mg

0.0190 mg

2.1400 mg

0.0981 mg

0.00084 mg

0,2000 mg

19,5000 mg

In this way, 106 g of a nutritional composition according to the invention with an energy value of 16-5 kJ (400 kcal) are prepared.

Example 8

In this Example 7, where an equal amount of stabilized soybean oil is used instead of the stabilized dye oil.

Example 9

In this example 7, where the same amount of sunflower oil is used instead of the stabilized dye oil.

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Example 10

In this example 7, wherein the same amount of casein hydrolyzate is used instead of egg white hydrolyzate.

Example 11

In this example 7, wherein the same amount of soy hydrolyzate is used instead of egg white hydrolyzate.

Example 12

In this Example 7, wherein an equal amount of lactosol hydrolyzate is used in place of the egg white hydrolyzate.

Industrial applicability

The nutritional composition of the invention serves (as has been proven in practice) to nutritionally support and treat malnutrition conditions of various etiologies, including conditions with altered GIT function.

Claims (2)

PATENT CLAIMS A nutritional composition for the treatment of malnutrition conditions of various etiologies, including conditions with altered GIT activity, solved on the basis of low molecular weight substances, with precise microbiological and chemical parameters, characterized in that it comprises: 12.6 to 16.2 % wt. 17.0 to 21.7 % rt 30.7 to 33.1 % π 0.47 to 0.61 % n 28.8 to 31.3 % t < 0.99 to 1.26 % II 0.44 to 0.56 % at 0.67 to 0.86 % n 0.04 to 0.052 % π 7.6 to 9.8. 10 ' ³ % wt. 2.5 to 3.2. 10 ' ⁵ % ti 0.96 to 1,2. 10 ' ³ % II 2.7 to 3.5. 10 ' ³ % II 1.0 to 1.3. 10 ' ³ % »1 1.4 to 1.85. 10 · ⁴ % »1 3.4 to 4.45. 10 ' ⁵ % II 0.017 to 0,022 % wt. egg white hydrolyzate, or soy hydrolyzate, or casein hydrolyzate, or lactoser glucose hydrolyzate of sucrose stabilized oil of safflower, or soy or sunflower enzyme hydrolyzate of sodium chloride potassium chloride sodium chloride calcium glycerophosphate. 2 H ₂ O MgO ferrous sulfate. 7 H ₂ O potassium iodide copper (I) acetate. H ₂ O Manganese acetate. 4 H ₂ O zinc oxide potassium dichromate ammonium molybdenum. 4 H ₂ O ascorbic acid - 7 GB 283569 B6 6.7 to 8.6. 10 · ⁴ % 1.5 to 2.0. 10 · ⁶ % »1 4.0 to 5.2. 10 ' ³ % »» 1,8 to 2.45. 10 “ ⁴ % II 1,8 to 2,45.W ⁴ % ti 3.6 to 4.7. 10 ^-4 % 11 3.14 to 4.01. 10 ' ³ % ti 1.79 to 2.3. 10 ' ⁵ % »1 2.02 to 2.6. 10 ' ³ % 11 0.92 to 1.18. 10 ⁴ % ti 7.92 to 1.01. ío · ⁶ % tt 1.89 to 2.4. 10 · ⁴ % ti 0.018 to 0,023 % tt erginalciferol retinol acetate tocopherol acetate thiamine dichloride sodium salt of 5-riboflavin phosphoric acid pyridoxolia nicotinamide folic acid calcium pantothenate D-biotin cyanocobalamin phylloquinone inositos Nutritional composition according to claim 1, characterized in that it contains up to 3.3 wt. oils containing triacylglycerol of C 6 -C 12 fatty acids.