Title:  Amino acid composition for hemodialysis

United States Patent:  6,787,039

Issued:  September 7, 2004

Inventors:  Drauz; Karlheinz (Freigericht, DE); Knaup; Guenter (Bruchkoebel, DE); Richet; Gerard (Saint-Quentin, FR); Kleophas; Werner (Duesseldorf, DE); Gruenert; Adolf (Ulm, DE)

Assignee:  Degussa AG (Duesseldorf, DE)

Appl. No.:  769397

Filed:  January 26, 2001

Abstract

The invention relates to a special amino acid mixture for hemodialysis as well as to the dialysis solution that can be prepared from the amino acid mixture. When the amino acid mixtures according to the invention are used for such purposes, the "shrinking men" phenomenon can be prevented. The present invention also relates to a hemodialysis process and apparatus. This aspect of the invention provides a closed dialysis system with a dialyzer solution containing the amino acid mixtures according to the invention.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide an amino acid composition which is capable of preventing the loss of amino acids/from the plasma of a patient undergoing hemodialysis.

It is another object of the present invention to provide an amino acid composition which can be used to compensate for pathological amino acid imbalances in the plasma of a patient undergoing hemodialysis.

It is an another object of the present invention to provide an amino acid composition which, as compared to known compositions, is capable, to a higher degree, of preventing the loss of amino acids from the plasma of a patient undergoing hemodialysis and which can be used to compensate for pathological amino acid imbalances in the plasma of a patient undergoing hemodialysis.

The objects of the invention, and others, may be accomplished with an amino acid composition comprising the following proportion of amino acids, based on the total weight of the amino acids, listed in Table 1:

The results of using this amino acid composition containing all relevant amino acids for hemodialysis are, on the one hand, that the amino acid concentration imbalances in the blood plasma of sick patients are compensated for and, on the other hand, that amino acid migration into the dialyzate due to lack of osmotic pressure is prevented.

Thus, the objects of the present invention may also be accomplished with a dialyzer fluid containing the proportions of the amino acids described above.

The objects of the present invention may also be accomplished with dialyzer fluid comprising amino acids at the concentrations listed in Table 2.

The objects of the present invention may also be accomplished with a method of hemodialysis by dialyzing a patient in need thereof using the inventive amino acid composition.

The objects of the present invention may also be accomplished with a method of hemodialysis by dialyzing a patient in need thereof with a dialyzer fluid containing the amino acid composition of the invention.

The objects of the present invention may also be accomplished with an apparatus for hemodialysis with a dialyzer, comprising:

a first flow path for the blood of a patient,

a second flow path for a dialyzer fluid,

a semipermeable membrane separating the first and second flow paths,

a vessel for containing the dialyzer fluid, wherein the vessel has a connection for withdrawal of dialyzer fluid to be supplied by the dialyzer and has a connection for the return to the vessel of the dialyzer fluid arriving from the dialyzer,

wherein the vessel is sufficiently thermally insulated from the ambient air that there is no need for a heating means to control the temperature of the dialyzer fluid and to keep it constant throughout the duration of the dialysis treatment,

wherein the connection for withdrawal of the dialyzer fluid discharges at the upper region of the vessel and the connection for return of the dialyzer fluid discharges in the lower region of the vessel,

wherein the vessel contains a dialyzer fluid containing the amino acid composition of the present invention.

The amino acid composition according to the invention may be added to a dialyzer solution in the proportion required to obtain a dialyzer fluid which corresponds in composition and concentration to the amino acid plasma level of a healthy person. The subject matter of the invention, therefore, also includes a dialysis solution having the amino acid composition described above.

DETAILED DESCRIPTION OF THE INVENTION

More preferred ranges for proportions of the amino acids in the composition of the present invention are set forth in Table 3 below:

The ranges for the proportion of the amino acids set forth in Tables 1 and 3 include all specific values and subranges therebetween, such as:

Amino Acid (wt %)

Gln: 14.2, 15, 18, 20, and 22;

Ala: 7.5, 8, 9, 10, and 11;

Pro: 6.5, 7, 8, 9, and 10;

Val: 5.5, 6, 7, 8,and 9;

Gly: 4.0, 4.5, 5.0, and 5.5;

Lys: 7.0, 8.0, 9.0, and 10.0;

Leu: 4.0, 4.5, 5.0, and 5.5;

Thr: 3.5, 4.0, 4.5, and 5.0;

Ser: 2.5, 3.0, and 3.5;

Arg: 4.5, 5.0, 5.5, and 6.0;

His: 3.0, 3.5, and 4.5;

Ile: 2.0, 2.5, and 2.8;

Tyr: 2.5, 2.8, 3.0, and 3.5;

Orn: 2.5, 2.8, 3.0, 3.5, and 4.0;

Glu: 1.8, 2.0, 2.5, 2.8, 3.0, and 3.2;

Phe: 2.2, 2.5, 2.8, 3.0, and 3.2;

Cys: 2.0, 2.2, 2.5, 2.8, 3.0, and 3.2;

Asn: 1.3, 1.5, 1.8, and 2.0;

Trp: 1.5, 1.8, 2.0, 2.2, and 2.5;

Cit: 1.2, 1.5, and 1.8;

Met: 0.8, 1.0, and 1.1;

Abu: 0.2 and 0.4;

Asp: 0.5, 0.6, and 0.8.

More preferred ranges for the concentrations of the amino acids in the dialyzer fluid of the present invention are set forth in Table 4 below:

The ranges for the proportion of the amino acids set forth in Tables 2 and 4 include all specific values and subranges therebetween, such as:

AminoAcid (concentration, .mu.mol/1)

Gln: 330, 350, 370, 400, 450, 500, 600, and 650;

Ala: 260, 270, 300, 350, 400, 450, 500, and 550;

Pro: 180, 190, 200, 250, 300, and 350;

Val: 170, 200, 250, and 275;

Gly: 160, 180, 200, 250, and 300;

Lys: 125, 130, 150, 180, 200, and 225;

Leu: 90, 100, 130, 150, and 175;

Thr: 100, 120, 150, and 170;

Ser: 80, 90, 100, 110, 120, and 130;

Arg: 70, 80, 90, 100, 110, 120, and 130;

His: 60, 70, 80, 90, 100, and 110;

Ile: 50, 60, 70, 80, and 90;

Tyr: 60, 70, 80, and 90;

Orn: 60, 70, 80, and 85;

Glu: 40, 50, 60, 80, and 80;

Phe: 50, 60, 70, and 75;

Cys: 30, 40, 50, 60, and 70;

Asn: 25, 30, 40, 50, and 60;

Trp: 20, 30, 40, and 50;

Cit: 20, 30, 35, and 40;

Met: 15, 20, 25, and 30;

Abu: 1, 5, 10, 15, 20, 25, and 30;

Asp: 15, 18, 20, and 22.

The amino acid concentrations occurring in the plasma of a healthy person are set forth in Table 5:

Heretofore an amino acid mixture for hemodialysis within the composition described above has not been used. The amino acid mixtures used for dialysis to date have never contained all amino acids cited hereinabove, or were originally designed for parenteral nutrition. Such solutions did not and still do not contain all amino acids listed in Table 1. Moreover, the concentration in those solutions is not adapted to the physiological plasma concentration, and so special imbalances not only are not compensated for but in some cases are further exacerbated, to the extent that pathological conditions as serious as hepatogenic encephalopathic coma can develop during continued dialysis.

Another aspect of the invention is the use of the amino acid composition for the preparation of a solution suitable for hemodialysis. In order to adjust the dialyzer fluid to the physiological concentrations listed in Table 2, preferably 0.43 to 0.37 g of the amino acid composition is added per liter of dialyzer solution.

As will be readily appreciated by those skilled in the art, the dialyzer fluid of the present invention may contain the inventive amino acid composition in a fluid medium that is suitable for use in dialysis treatments. The fluid medium may be any which are routinely used in dialysis. For a description of hemodialysis, see Kirk-Othmer Encyclopedia of Chemical Technology, Fourth Edition, Volume 8, pp. 64-74, incorporated herein by reference. The fluid medium is preferably an aqueous solution. The aqueous solution may contain appropriate buffers, electrolytes and/or nutrients.

Thus a system has been developed which permits the amino acid composition of the dialyzate to be equivalent to that of the plasma not only in the micromolar respect but also in percentage. This composition and concentration corresponds to the reference ranges of the individual amino acids measured in healthy blood donors (Table 2).

Another aspect of the invention is a hemodialysis method characterized by the use of the amino acid composition according to the invention or the dialyzer fluid according to the invention.

The suitability of the amino acid composition according to the invention as regards prevention of amino acid losses and correction of amino acid imbalances was proved in a 4-week open comparative study with 12 dialysis sessions on 10 patients with chronic kidney diseases of many years standing.

The dialyses were performed with the Genius dialysis system of Teerstegen and Endert (German Patent DE 3115665, incorporated herein by reference), which has a volumetric capacity of 75 liters of inlet solution.

The amino acid composition used had the absolute or relative composition set forth in Table 6:

In each case, 30.5 g of this amino acid mixture was dissolved in 75 liters of dialyzer solution.

Claim 1 of 12 Claims

What is claimed is:

1. An amino acid composition suitable for hemodialysis, comprising amino acids in the following proportions, based on the total weight of the amino acids:

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