CS260950B1 - Complex of aminoacids as combination solution for parenteral nutrition - Google Patents

Abstract

The solution relates to a complex of amino acids for parenteral combination therapy infusion solution with optional by adding additional effective and / or auxiliary components, especially vitamins, cations and anions, energy sources, stabilizers and / or antioxidants; the complex contains L-forms of the following amino acids: valine, leucine, isoleucine and water for injection up to 1000 ml and has a pH of 5.0 to 7.

Description

The invention relates to a complex of branched amino acids in the form of an infusion solution for combined parenteral nutrition, i.e. enrichment of basic and specialized amino solutions with L-valine, L-leucine and L-isoleucine, or in the form of isolated administration only. This triple combination makes it possible to increase the plasma levels of these amino acids both in the substitution form (in the case of a lack of these amino acids especially in malnutrition) and to utilize some pharmacodynamic properties at multiple levels. This increase makes it possible to normalize the pathological increase in some groups of amino acids, in particular those containing sulfur such as L-methionine and L-cystine, and in the group of aromatic amino acids in particular L-phenylalanine and L-tyrosine. These results are achieved through proteosynthesis and thus by means of a positive nitrogen balance. Elevated levels of these three amino acids allow them to be used for oxidation and hence energy recovery wherever glucose and fatty acid utilization are compromised, such as sepsis, liver failure, burn trauma, severe polytrauma or hepatocerebral coma. We have found that in hyperosmolar coma, branched-chain amino acids are the only drug that is vital indicated.

An example of the substitution and proteosynthetic effect of the proposed triple combination of branched amino acids is the following table:

Table

Effect of the Judicial Balance (N g / 24 h) n = 4 Patients with decompensated liver containing 25 g of protein cirhosou on a basic diet before administration Day 3 of administration 5th day of administration Neutramine C (400 mL) + Nutramine VLI (1,200 ml) - 3,1 - 1,4 - 0,3

An example of the pharmacodynamic action of the proposed triple combination is the following aminogram in a patient with hepatic coma when used initially with a pure Nutramine VLI solution, later in combination with Nutramine C, which does not affect the aminogram spectrum due to normalization.

Odaje v umol / 1

Normal values of amino acids Without amino solutions 29.12. VLI (1200 ml) 30.12. VLI + C (800 ml VLI) 7.1. Only C 10. 1 L-VAL 259 320 553 • 350 253 L-LEU 160 218 390 235 57 L-ISO 84 134 235 115 125 R total 503 672 1 178 700 420 L-TRE 146 340 320 160 160 L-MET 32 450 460 55 62 L-TRY 60 325 252 120 90 L-ARG 101 142 270 107 76 L-PRO 241 400 425 175 125 L-TYR 72 132 120 120 100 ALIGN! L-CYS / 2 118 152 136 tracks 30 % VAL 10% 6.8% 11% 9.7% 5.8 % % TRY 2.4% 6.9% 5 »  3.3% 3.0 % % MET 1.3% 9.6% 9.1% 1.5% 2.1 F INDEX 2.7 1.3 3.5 2.7 2.04 Ammonia 60 200 170 65 60

In the aminogram without the application of the amine solution in liver failure, we see high levels of methionine (14-fold), high levels of aromatic amino acids such as tryptophan (5-fold) and tyrosine (1.8-fold). The Fišer index is highly positive. Application of pure Nutramine VLI (3.12) causes a marked increase in branched-chain amino acids (2.3-fold), but at the same time decreases in L-TRE, L-TRY, L-TIR, L-CYS / 2, ammonia and Fišer index normalization. 10.1. when Nutramine VLX is discontinued, amino acid levels are close to normal.

The composition of the preparation is original and there is no similar product anywhere in the world.

We use our own experience in the field of amino acids, including the latest clinical findings in this field. By combining Nutramine VLI and Nutramine NEO (base solution), as well as Nutramines specialized as Nutramine U, C (renal failure, detoxidation in liver failure), or Nutramine N and P (premix and neonate), an optimal supply of branched amino acids in relation to individual clinical conditions, which has not been possible so far. It is possible to add other active and / or auxiliary components, in particular vitamins, eg ascorbic acid or B-group vitamins, minerals characterized by cations, eg sodium, potassium or magnesium, and anions, eg phosphates or chlorides, carbohydrates, eg sorbitol or xylitol, stabilizers or antioxidants, e.g., sodium bisulfite. The composition of the branched-chain amino acid combination solution to ensure optimum composition in terms of branched-amino acid content of the individual amino acid solutions, both basic and specialized, is as follows:

Table

Ingredients

Aminoacid Content % representation L-valine 10.00 g per 30 g amino acids 33,33% L-leucine 12.77 g per 30 g amino acids 42,57% L-isoleucine 7.23 g to 30 g amino acids 24,10 i

Total branched amino acids 30, Q0 g per 30 g amino acids 100%

Total nitrogen content 4.80 g per 30 g amino acids

Only pure L-forms of these amino acids can be used to prepare a difierized branched amino acid complex solution. The solution is usually prepared by dissolving the individual components without special order in water for injection at a temperature of at least 80 ° C, under stirring with a high speed stirrer, under a protective nitrogen atmosphere. After dissolution of the amino acids, 0.10 to 0.20 g per liter, e.g. sodium bisulfite, is generally added to the resultant solution.

After exhaustion, make up to the final volume with water for injection. The pH of the solution is in the range of 5.0 to 7.0, adjusted if necessary with dilute hydrochloric acid or sodium hydroxide solution or another pharmaceutically acceptable base or acid. The treated solution is filtered through an antimicrobial filter and filled into infusion bottles under a nitrogen atmosphere, under laminar air flow at 20 ° C to 65 ° C. After bottling, the solution is sterilized in an autoclave at 120 ° C for 25 to 30 minutes.

Further details of the composition of the amino acid complex of the invention are illustrated in the following examples.

Example 1

Weigh the L-forms of pure amino acids and other components according to the following recipe (in g per liter of solution)

L-valine

L-leucine

................................... 10,00 g / l

........................................... 12.77 g / l

L-isoleucine ........................................

Sodium bisulphite ................................

Water for injections ..................................

Total nitrogen content .............................

PH .................................................

kJ .................................................

7,22 g / 1 0,20 g / 1 000 ml 4,80 g / 1 5 to 7 523,00 kJ / 1

Said components are dissolved without particular order in redistilled water at a temperature of at least 80 ° C with vigorous stirring and under a nitrogen atmosphere. After dissolution, the solution is clarified twice with an addition of 0.5 to 3 wt. activated carbon, based on the weight of the active ingredients.

The solution is then filtered through an antimicrobial filter and filled under a laminar air flow under a nitrogen atmosphere at 20 to 65 ° C infusion bottles. Sterilize in an autoclave at 120 ° C for 25 minutes.

Example 2

The same procedure as in Example 1 except that only sorbitol in an amount of 50 to 100 g / l or only xylitol in an amount of 50 to 100 g / l, or both, are used simultaneously. The solution may be prepared without both of these sugars for administration, e.g. in pediatric practice.

Example 3

The procedure as in Examples 1 and 2, except that sodium bisulfite in an amount of 0.2 g to 1.00 g / l was used as the antioxidant.

Example 4

The procedure is the same as in the previous examples except that the following components are added in g per liter of solution:

ascorbic acid ................................ 0.4 g inosit ........... ................................. -0,5 § nicotinamide ........... ............................ 0,060 g pyridoxine.HCl ................. .................... 0,040 g riboflavin-5-phosphatnatrium 2,5 .................... 0.002 5 g

Ascorbic acid acts not only as a vitamin but also as a stabilizer and antioxidant.

Example 5

The same procedure as in the previous examples except that the following cations and anions in mmol per liter of solution are added:

Na + ....................... . . ...................... 48,00 K + .......................... ...................... 25,00 Mg2 + ........................ ...................... 2,6 η _λ ροΤ ....................... ...................... 9.0 Cl ......................... ...................... 14.0

Claims (1)

A complex of amino acids for combined parenteral nutrition in all conditions in the form of an infusion solution which can be combined not only with the basic solutions but also with solutions specialized with the optional addition of other active and / or auxiliary components, especially vitamins, minerals, carbohydrates, stabilizers and / or antioxidants, characterized in that the content by weight is 30.33 to 36.66 L-VALIN, 38.25 to 46.75 L-LEUCIN 21.69 to 26.51 L-ISOLEUCIN and water for injection up to 100% by weight . and has a pH of 5.0 to 7.0.