CA1239586A - Dialysis solution containing amino acids - Google Patents
Dialysis solution containing amino acidsInfo
- Publication number
- CA1239586A CA1239586A CA000464555A CA464555A CA1239586A CA 1239586 A CA1239586 A CA 1239586A CA 000464555 A CA000464555 A CA 000464555A CA 464555 A CA464555 A CA 464555A CA 1239586 A CA1239586 A CA 1239586A
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- Prior art keywords
- amino acids
- present
- percent
- essential
- weight
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/28—Peritoneal dialysis ; Other peritoneal treatment, e.g. oxygenation
- A61M1/287—Dialysates therefor
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A dialysis solution comprises physiological salts, and also contains a mixture of amino acids in specified proportions which are adapted to improve the metabolism of uremic patients to near normal state.
A dialysis solution comprises physiological salts, and also contains a mixture of amino acids in specified proportions which are adapted to improve the metabolism of uremic patients to near normal state.
Description
i23~3~86 Technical Field and Prior Art A growing number of patients who have end stage renal disk ease are maintained by dialysis procedures. While many are maintain-Ed by hemodialysis, others are maintained by peritoneal dialysis, and particularly continuous ambulatory peritoneal dialysis (CARD) as disk closed for example in U.S. Patent No. 4,239,041. This latter tech-unique is rapidly growing in clinical acceptance as a technique of choice for maintaining many patients with lost or compromised kidney function.
In peritoneal dialysis procedures, peritoneal dialysis soul-lion is inserted into the peritoneal cavity whereby diffusion ox-change takes place between the solution and the blood across the nay tubal body membranes, to remove by diffusion the waste products which are normally excreted through the kidneys, such as urea and creating ire, and also sodium and water.
The nature and rate of the materials removed from the body by either hemodialysis or peritoneal dialysis is generally a function of the solutes present in the dialysis solution. Physiological salts such as sodium chloride, sodium lactate, or acetate, are present in dialysis solutions generally at concentrations similar to those found in normal blood so that abnormal (high or low) concentrations of the ions forming such salts in the blood stream will equilibrate with the dialysis solution for removal.
However, dialysis procedures also result in the loss of some desirable materials from the blood, for example amino acids, D6-4414-]
with the result that patients on dialysis may suffer from problems no-suiting at least in part from low concentrations of amino acids in the blood stream or the body in general.
Also, it is discovered that uremia patients metabolize amino acids at different rates from the normal person. Accordingly, when normal mixtures of amino acids are given to a uremia patient, concentrations of certain amino acids in his blood will remain higher than would be normally expected, while the concentrations of other amino acids will fall lower than would be normally expected.
It has been previously proposed to use amino acid mixtures as an ingredient of peritoneal dialysis solutions. See in particular the article by Oreopoulos et at. entitled "Amino Acids as an Osmotic Agent (Instead of Glucose) in CARD, Proceedings of an International Symposium", Paris, November end and 3rd, 1979, Excerpt ~ledica (1980), pages 335-340. See also page 812 of the October 12, 1968 issue of The Lance. The preliminary communication from John Jesting there reports the addition of amino acids to dialysis fluids in patients under regular peritoneal dialysis regimens.
From the prior art one can infer that amino acids can be safely added to a dialysis solution. The teaching of this invention reveals that very special advantages can be achieved with their admix-istration through a dialysis solution in the case of uremia patients on dialysis by using a dialysis solution with an amino acid mixture according to this invention. The dialysis patient can absorb and use to his advantage the amino acid formulation of this invention ~239586 which has been augmented for his special needs without over burdening his system with excess amino acids that he does not require.
In accordance with this invention, a dialysis solution, and preferably a peritoneal dialysis solution, is provided which includes an amino acid formulation that successfully avoids the retention of excess amounts of certain of the amino acids in their blood stream for an excessive amount of time and also avoids unduly low concentra-lions of other amino acids in their blood stream. The concentrations of amino acids used herein provides, for uremia patients, each essential amino acid, and optionally other nonessential amino acids as well in a concentration that the uremia patient can use without suffering chronically elevated or reduced concentrations of any amino acid administered.
The presence of amino acids in the dialysis solution great-lye contributes to the blood stream thus maintaining the plasma amino acid level for the benefit and well being of the patient.
Description of Invention In this invention, a dialysis solution is proposed which comprises physiological salts in sufficient concentrations to be osmotically compatible with blood, and also containing from 0.5 to
In peritoneal dialysis procedures, peritoneal dialysis soul-lion is inserted into the peritoneal cavity whereby diffusion ox-change takes place between the solution and the blood across the nay tubal body membranes, to remove by diffusion the waste products which are normally excreted through the kidneys, such as urea and creating ire, and also sodium and water.
The nature and rate of the materials removed from the body by either hemodialysis or peritoneal dialysis is generally a function of the solutes present in the dialysis solution. Physiological salts such as sodium chloride, sodium lactate, or acetate, are present in dialysis solutions generally at concentrations similar to those found in normal blood so that abnormal (high or low) concentrations of the ions forming such salts in the blood stream will equilibrate with the dialysis solution for removal.
However, dialysis procedures also result in the loss of some desirable materials from the blood, for example amino acids, D6-4414-]
with the result that patients on dialysis may suffer from problems no-suiting at least in part from low concentrations of amino acids in the blood stream or the body in general.
Also, it is discovered that uremia patients metabolize amino acids at different rates from the normal person. Accordingly, when normal mixtures of amino acids are given to a uremia patient, concentrations of certain amino acids in his blood will remain higher than would be normally expected, while the concentrations of other amino acids will fall lower than would be normally expected.
It has been previously proposed to use amino acid mixtures as an ingredient of peritoneal dialysis solutions. See in particular the article by Oreopoulos et at. entitled "Amino Acids as an Osmotic Agent (Instead of Glucose) in CARD, Proceedings of an International Symposium", Paris, November end and 3rd, 1979, Excerpt ~ledica (1980), pages 335-340. See also page 812 of the October 12, 1968 issue of The Lance. The preliminary communication from John Jesting there reports the addition of amino acids to dialysis fluids in patients under regular peritoneal dialysis regimens.
From the prior art one can infer that amino acids can be safely added to a dialysis solution. The teaching of this invention reveals that very special advantages can be achieved with their admix-istration through a dialysis solution in the case of uremia patients on dialysis by using a dialysis solution with an amino acid mixture according to this invention. The dialysis patient can absorb and use to his advantage the amino acid formulation of this invention ~239586 which has been augmented for his special needs without over burdening his system with excess amino acids that he does not require.
In accordance with this invention, a dialysis solution, and preferably a peritoneal dialysis solution, is provided which includes an amino acid formulation that successfully avoids the retention of excess amounts of certain of the amino acids in their blood stream for an excessive amount of time and also avoids unduly low concentra-lions of other amino acids in their blood stream. The concentrations of amino acids used herein provides, for uremia patients, each essential amino acid, and optionally other nonessential amino acids as well in a concentration that the uremia patient can use without suffering chronically elevated or reduced concentrations of any amino acid administered.
The presence of amino acids in the dialysis solution great-lye contributes to the blood stream thus maintaining the plasma amino acid level for the benefit and well being of the patient.
Description of Invention In this invention, a dialysis solution is proposed which comprises physiological salts in sufficient concentrations to be osmotically compatible with blood, and also containing from 0.5 to
2.5 percent by weight of a mixture of amino acids, at least one-thirdof the weight of amino acids present being essential amino acids, the following amino acids being present in the mixture in the following percentages by weight:
Safe Range Preferred Range Phenylalanine 1 to 4 of essential 2.5 to 2.8% of essential amino acids amino acids ~23~3S~36 Tarzan to 6.5% of essential to 6.5% of essential amino acids amino acids Isoleucine9 to 15% of essential to 12% of essential amino acids amino acids Lawson to 24% of essential to 17% of essential amino acids amino acids Allen to 24% of essential to 17% of essential amino acids amino acids Methionine6 to 10% of essential to 8% of essential amino acids amino acids Threonine9 to 18% of essential to 14% of essential amino acids amino acids Triptophan 1.5 to 4.5% of essential 2 to I of essential amino acids amino acids Lawson to 28% of essential to 18% of essential amino acids amino acids Histidine3 to 12% of essential to 9%. of essential amino acids amino acids The foregoing amino acids are considered essential amino acids to a uremia patient. Additionally, arginine in amounts of 1 to 7% of the essential amino acids in the mixture can be added as an essential amino acid The dialysis solution may also desirably contain other amino acids which are nonessential to a uremia patient, for example from 1 to 5 percent of Gleason, from 2 to 10 percent of ala nine, from 1 to 6 percent of praline, and/or from 1 to 5 percent shrine, all percents herein being by weight. Preferably 4 to 5 percent of ~39586 Gleason, 5 to 6 percent of praline, 4 to 5 percent of shrine, and 8 to 10 percent of ala nine may be used.
It is also to advantage to add up to 2% sustains.
It is generally accepted that the normal diet requires at least 32.6 grams of essential amino acid per 100 grams of protein consumed, the balance comprising non-essential amino acids, in order to maintain health. As a further breakdown, Table 1 below discloses the minimum amounts per 100 grams of protein consumed of the various essential amino acid units of the protein which should be present in order to maintain health in children:
Isoleucine 3.7 grams/100 grams protein consumed Lawson 5.6 grams/100 grams protein consumed Lawson 7.5 grams/100 grams protein consumed Methionine 3.4 grams/100 grams protein consumed Phenylalanine 3.4 grams/100 grams protein consumed Threonine 4.4 grams/100 grams protein consumed Tryptophane 0.5 grams/100 grams protein consumed Valise 4.1 grams/100 grams protein consumed Total 32.6 grams/100 grams protein consumed As a specific embodiment, we propose that the dialysis soul-lion of this invention should contain from 1 to 2 percent by weight of an amino acid mixture having the following components:
~L~395~6 Phenylalanine 2.6 weight percent of essential amino acid mixture Tarzan 6.4 weight percent of essential amino acid mixture Isoleucine 10.3 weight percent of essential amino acid mixture Lawson 15.3 weight percent of essential amino acid mixture Valise 15.3 weight percent of essential amino acid mixture Methionine 7.7 weight percent of essential amino acid mixture Threonine 11.5 weight percent of essential amino acid mixture Tryptophane 2.6 weight percent of essential amino acid mixture Lawson 14.1 weight percent of essential amino acid mixture Histidine 7.7 weight percent of essential amino acid mixture Arginine 6.5 weight percent of essential amino acid mixture Non-essential amino acids may also be added as desired, but at least one half and preferably 70 to 90 percent of the weight of ~23~5~6 amino acids should be the amino acids listed immediately above.
The immediately preceding formulation has an amino acid con-tent that comprises amino acids considered essential to a uremia pa-tint. If there are nonessential amino acids added to the mixture the percentage of essential amino acids in the total amino acid mix-lure will be reduced for a given amount of essential amino acids.
The reduction will depend upon the amount of nonessentials. Consider a mixture of essentials and nonessentials where the amount of Essex-trial amino acids is the same as in the immediately preceding formula-lion but in which there are 23.3~ of nonessential amino acids. In such a case the composition of the amino acid content would be Final Solution with Non-Essentials Isoleucine 7.9 of amino acid mixture Lawson 11.8 of amino acid mixture Valise 11.8 of amino acid mixture Lawson 10.8 of amino acid mixture ~ethionine 5.9 of amino acid mixture ~henylalanine 2.0 of amino acid mixture Tarzan 4.9 of amino acid mixture Threonine 8.8 of amino acid mixture Tryptophan 2.0 of amino acid mixture ~istidine 5.9 of amino acid mixture Arginine 4.9 of amino acid mixture 76.7 of amino acid mixture Gleason 4.6 of amino acid mixture Praline 5.3 of amino acid mixture Ala nine 8.8 of amino acid mixture 100.00 of amino acid mixture D6-4414~ 39S~6 It can be seen by the general formulation of this invention on page 3 that no more than 4 weight percent, and preferably no more than 2.8 weight percent, of phenylalanine should be present in the essential amino acid mixture. However, to meet the special needs of uremia patients, from 4 to 6.5 percent of Tarzan is present.
Tarzan is, to a normal, healthy person, a nonessential amino acid. In the normal metabolic process phenylalarline is convert-Ed to Tarzan. A decrease of Tarzan levels relative to phenol-ala nine in the blood plasma of patients with uremia has been observe Ed This invention successfully overcomes the imbalance by adding the normally nonessential Tarzan to the mixture in greater quanta-ties rather than attempting to increase the phenylalanine with the in-tension that the patient produce the Tarzan deficit from a greater abundance of phenylalanine in the normal metabolic process.
At the same time, it has been observed that phenylalanine is metabolized quite slowly by uremia patients and is present in less than normal concentration in the solution. Thus, the patient's system is relieved of the task of converting phenylalanine and at the same time obtains a ready supply of Tarzan which, as a starting amino acid is not essential to a normal healthy person.
Valise is an amino acid that is required by body muscle.
Valise uptake by uremia patients is substantially reduced and their Dow ~23~58~j general well being can be improved by providing an elevated over nor-met concentration body muscle, Valise uptake-by uremia patients is substantially reduced and their general well being can be improved by providing an elevated over normal concentration of valise. Thus, valise has been increased in the formulation of this invention.
Isoleucine and Lawson are also elevated over normal concern-traction.
The preferred methionine retirement of 7 to 8 percent in a 100 percent essential amino acid mixture actually reflects a reduce lion in the methionine content with respect to the normal amino acid formulation of Table 1 containing only 32.6 percent of essential amino acids. sty the special needs of uremia patients, less Matthew-nine is required than in the case of a normal person.
Threonine is preferably added in essentially the concentra-lion called for by normal metabolism.
With tryptophan, the concentration of 2 to 3 percent of the amino acids is substantially increased over its nutrient normal level of Table 1, when it is considered that only 32.6 percent of the amino acids in the nutrient normal mixture are essential amino acids.
The Lawson content of the mixture of this invention has been lowered to some extent from the nutrient normal concentration of Table 1, to make room for the increased amounts of other amino acids as specified. Lawson is an amino acid that tends to accumulate in the bloodstream of dialysis patients and it has been reduced.
D6-4414-Z ~395~6 Histidine is provided in substantial quantities because uremia patients appear to have a clear need for this amino acid.
The non-essential amino acids such as Gleason and others may also be provided as an additional source of nitrogen which is easily metabolizable, and also for other benefits.
The dialysis solution of this invention is one which avoids the further overburdening of the already overburdened system of a dialysis patient and provides for him the benefits of proper amino acid supplement.
The dialysis solution of this invention may comprise a water solution at a pi of 5.0 to 7.4, containing from 130 to 140 mEq/liter of sodium, 100 to 110 mEq/liter of chloride, 0 to 4 mEq/liter of calcium, 0 to 2 mEq/liter of magnesium, and, if desired, other ions, for example, 30 to 40 mEq/liter of bicarbonate precursors such as one or more of lactate, acetate, palate, and/or succinate owns .
The above ions may be provided by the addition of convent tonal physiological salts such as sodium chloride, calcium chloride, sodium lactate, sodium acetate, and traces of other salts such as pox Taoism chloride, magnesium chloride, and the like, added in accord dance with the known requirements for proper ion balance in a dimly-skis solution.
It is generally preferable for the osmolality of the soul-lions of this invention to be from 272 to 700 milliosmols per liter, preferably 279 to 480 milliosmols per liter.
D6-4414--l - ~3~586 The bicarbonate precursor acid ions mentioned above, as well as other acid ions of the Knobs cycle, may be added to also offer advantages in pi control of the peritoneal dialysis solution of this invention. The sodium or potassium salts of such ions, for exam-pie, may be used for this purpose, or the free acids.
Sulfhydryl-type antioxidant, for example azalea Sistine, may be also added to stabilize the amino acids in the peritoneal dial-Isis solution of this invention.
The solution of this invention may also contain osmotic agents for promoting ultrafiltration, for example, up to 4 grams per liter of glucose, or a suitable amount of a suitable, equivalent sugar or other osmotic agent. It may also be desirable to provide l to lo units of insulin per liter of the solution to assist in metal-holism of sugars present and amino acids, since both serve as nut tridents.
Also vitamins and mineral nutrients may be present in the solution, plus a source of fat nutrition, if desired.
The amino acids may be present in the form of short range polypeptides if desired, as long as they are short enough to avoid imp munological response by the body or other undesirable side effects.
Also, other equivalent materials may be used as amino acid subset-jutes, for example alpha veto derivatives of the amino acids.
The solution of this invention may be premixed, typically with a separate sterilization of different solution portions contain-in respectively the amino acids in one container and glucose present ~239~6 in another container in a separate, interconnected container system, followed by mixing without breaching the sterile conditions of the system. This avoids the known incompatibility problems encountered on sterilizing the mixture of sugar and amino acids in those in-stances where it is desired to have a sugar present in the dialysis solution of this invention.
Alternatively, glucose and amino acid solutions may be sop-irately sterilized in separate containers, and then brought together by the use of a sterile connector system similar to that shown in U.S. Patent 4,157,723 or the like, providing a reliably sterile con-section permitting the sterile mixing of the two solutions to form the dialysis solution of the invention.
It is specifically contemplated to use the solution of this invention as a peritoneal dialysis solution, and specifically in a CARD procedure. It would also be possible to use the solution of this invention in hemodialysis for similar benefit.
The amino acid mixture utilized in this invention may be added to commercially available dialysis solution formulations, for example Donnelly R dialysis solutions, a family of peritoneal dialysis solutions sold by Travenol Laboratories, Inc. of Deer field, Illinois.
Specifically 1.5 percent by weight of an amino acid formulation as described above may be added to Donnelly peritoneal dialysis solution containing 1.5 percent Betty of glucose, to provide a peritoneal dialysis solution having active ultrafiltration characteristics, while providing to the patient an increased amino acid content in the D6-4414-1 ~239~
blood, in which essential amino acid concentrations are distributed in a manner beneficial to the uremia patient.
The above has been offered for illustrative purposes only, and is not intended to limit the scope of the invention of this apply-cation, which is as defined in the claims below. A person skilled in the art would have no difficulty in formulating specific formulas within the scope of the invention.
Safe Range Preferred Range Phenylalanine 1 to 4 of essential 2.5 to 2.8% of essential amino acids amino acids ~23~3S~36 Tarzan to 6.5% of essential to 6.5% of essential amino acids amino acids Isoleucine9 to 15% of essential to 12% of essential amino acids amino acids Lawson to 24% of essential to 17% of essential amino acids amino acids Allen to 24% of essential to 17% of essential amino acids amino acids Methionine6 to 10% of essential to 8% of essential amino acids amino acids Threonine9 to 18% of essential to 14% of essential amino acids amino acids Triptophan 1.5 to 4.5% of essential 2 to I of essential amino acids amino acids Lawson to 28% of essential to 18% of essential amino acids amino acids Histidine3 to 12% of essential to 9%. of essential amino acids amino acids The foregoing amino acids are considered essential amino acids to a uremia patient. Additionally, arginine in amounts of 1 to 7% of the essential amino acids in the mixture can be added as an essential amino acid The dialysis solution may also desirably contain other amino acids which are nonessential to a uremia patient, for example from 1 to 5 percent of Gleason, from 2 to 10 percent of ala nine, from 1 to 6 percent of praline, and/or from 1 to 5 percent shrine, all percents herein being by weight. Preferably 4 to 5 percent of ~39586 Gleason, 5 to 6 percent of praline, 4 to 5 percent of shrine, and 8 to 10 percent of ala nine may be used.
It is also to advantage to add up to 2% sustains.
It is generally accepted that the normal diet requires at least 32.6 grams of essential amino acid per 100 grams of protein consumed, the balance comprising non-essential amino acids, in order to maintain health. As a further breakdown, Table 1 below discloses the minimum amounts per 100 grams of protein consumed of the various essential amino acid units of the protein which should be present in order to maintain health in children:
Isoleucine 3.7 grams/100 grams protein consumed Lawson 5.6 grams/100 grams protein consumed Lawson 7.5 grams/100 grams protein consumed Methionine 3.4 grams/100 grams protein consumed Phenylalanine 3.4 grams/100 grams protein consumed Threonine 4.4 grams/100 grams protein consumed Tryptophane 0.5 grams/100 grams protein consumed Valise 4.1 grams/100 grams protein consumed Total 32.6 grams/100 grams protein consumed As a specific embodiment, we propose that the dialysis soul-lion of this invention should contain from 1 to 2 percent by weight of an amino acid mixture having the following components:
~L~395~6 Phenylalanine 2.6 weight percent of essential amino acid mixture Tarzan 6.4 weight percent of essential amino acid mixture Isoleucine 10.3 weight percent of essential amino acid mixture Lawson 15.3 weight percent of essential amino acid mixture Valise 15.3 weight percent of essential amino acid mixture Methionine 7.7 weight percent of essential amino acid mixture Threonine 11.5 weight percent of essential amino acid mixture Tryptophane 2.6 weight percent of essential amino acid mixture Lawson 14.1 weight percent of essential amino acid mixture Histidine 7.7 weight percent of essential amino acid mixture Arginine 6.5 weight percent of essential amino acid mixture Non-essential amino acids may also be added as desired, but at least one half and preferably 70 to 90 percent of the weight of ~23~5~6 amino acids should be the amino acids listed immediately above.
The immediately preceding formulation has an amino acid con-tent that comprises amino acids considered essential to a uremia pa-tint. If there are nonessential amino acids added to the mixture the percentage of essential amino acids in the total amino acid mix-lure will be reduced for a given amount of essential amino acids.
The reduction will depend upon the amount of nonessentials. Consider a mixture of essentials and nonessentials where the amount of Essex-trial amino acids is the same as in the immediately preceding formula-lion but in which there are 23.3~ of nonessential amino acids. In such a case the composition of the amino acid content would be Final Solution with Non-Essentials Isoleucine 7.9 of amino acid mixture Lawson 11.8 of amino acid mixture Valise 11.8 of amino acid mixture Lawson 10.8 of amino acid mixture ~ethionine 5.9 of amino acid mixture ~henylalanine 2.0 of amino acid mixture Tarzan 4.9 of amino acid mixture Threonine 8.8 of amino acid mixture Tryptophan 2.0 of amino acid mixture ~istidine 5.9 of amino acid mixture Arginine 4.9 of amino acid mixture 76.7 of amino acid mixture Gleason 4.6 of amino acid mixture Praline 5.3 of amino acid mixture Ala nine 8.8 of amino acid mixture 100.00 of amino acid mixture D6-4414~ 39S~6 It can be seen by the general formulation of this invention on page 3 that no more than 4 weight percent, and preferably no more than 2.8 weight percent, of phenylalanine should be present in the essential amino acid mixture. However, to meet the special needs of uremia patients, from 4 to 6.5 percent of Tarzan is present.
Tarzan is, to a normal, healthy person, a nonessential amino acid. In the normal metabolic process phenylalarline is convert-Ed to Tarzan. A decrease of Tarzan levels relative to phenol-ala nine in the blood plasma of patients with uremia has been observe Ed This invention successfully overcomes the imbalance by adding the normally nonessential Tarzan to the mixture in greater quanta-ties rather than attempting to increase the phenylalanine with the in-tension that the patient produce the Tarzan deficit from a greater abundance of phenylalanine in the normal metabolic process.
At the same time, it has been observed that phenylalanine is metabolized quite slowly by uremia patients and is present in less than normal concentration in the solution. Thus, the patient's system is relieved of the task of converting phenylalanine and at the same time obtains a ready supply of Tarzan which, as a starting amino acid is not essential to a normal healthy person.
Valise is an amino acid that is required by body muscle.
Valise uptake by uremia patients is substantially reduced and their Dow ~23~58~j general well being can be improved by providing an elevated over nor-met concentration body muscle, Valise uptake-by uremia patients is substantially reduced and their general well being can be improved by providing an elevated over normal concentration of valise. Thus, valise has been increased in the formulation of this invention.
Isoleucine and Lawson are also elevated over normal concern-traction.
The preferred methionine retirement of 7 to 8 percent in a 100 percent essential amino acid mixture actually reflects a reduce lion in the methionine content with respect to the normal amino acid formulation of Table 1 containing only 32.6 percent of essential amino acids. sty the special needs of uremia patients, less Matthew-nine is required than in the case of a normal person.
Threonine is preferably added in essentially the concentra-lion called for by normal metabolism.
With tryptophan, the concentration of 2 to 3 percent of the amino acids is substantially increased over its nutrient normal level of Table 1, when it is considered that only 32.6 percent of the amino acids in the nutrient normal mixture are essential amino acids.
The Lawson content of the mixture of this invention has been lowered to some extent from the nutrient normal concentration of Table 1, to make room for the increased amounts of other amino acids as specified. Lawson is an amino acid that tends to accumulate in the bloodstream of dialysis patients and it has been reduced.
D6-4414-Z ~395~6 Histidine is provided in substantial quantities because uremia patients appear to have a clear need for this amino acid.
The non-essential amino acids such as Gleason and others may also be provided as an additional source of nitrogen which is easily metabolizable, and also for other benefits.
The dialysis solution of this invention is one which avoids the further overburdening of the already overburdened system of a dialysis patient and provides for him the benefits of proper amino acid supplement.
The dialysis solution of this invention may comprise a water solution at a pi of 5.0 to 7.4, containing from 130 to 140 mEq/liter of sodium, 100 to 110 mEq/liter of chloride, 0 to 4 mEq/liter of calcium, 0 to 2 mEq/liter of magnesium, and, if desired, other ions, for example, 30 to 40 mEq/liter of bicarbonate precursors such as one or more of lactate, acetate, palate, and/or succinate owns .
The above ions may be provided by the addition of convent tonal physiological salts such as sodium chloride, calcium chloride, sodium lactate, sodium acetate, and traces of other salts such as pox Taoism chloride, magnesium chloride, and the like, added in accord dance with the known requirements for proper ion balance in a dimly-skis solution.
It is generally preferable for the osmolality of the soul-lions of this invention to be from 272 to 700 milliosmols per liter, preferably 279 to 480 milliosmols per liter.
D6-4414--l - ~3~586 The bicarbonate precursor acid ions mentioned above, as well as other acid ions of the Knobs cycle, may be added to also offer advantages in pi control of the peritoneal dialysis solution of this invention. The sodium or potassium salts of such ions, for exam-pie, may be used for this purpose, or the free acids.
Sulfhydryl-type antioxidant, for example azalea Sistine, may be also added to stabilize the amino acids in the peritoneal dial-Isis solution of this invention.
The solution of this invention may also contain osmotic agents for promoting ultrafiltration, for example, up to 4 grams per liter of glucose, or a suitable amount of a suitable, equivalent sugar or other osmotic agent. It may also be desirable to provide l to lo units of insulin per liter of the solution to assist in metal-holism of sugars present and amino acids, since both serve as nut tridents.
Also vitamins and mineral nutrients may be present in the solution, plus a source of fat nutrition, if desired.
The amino acids may be present in the form of short range polypeptides if desired, as long as they are short enough to avoid imp munological response by the body or other undesirable side effects.
Also, other equivalent materials may be used as amino acid subset-jutes, for example alpha veto derivatives of the amino acids.
The solution of this invention may be premixed, typically with a separate sterilization of different solution portions contain-in respectively the amino acids in one container and glucose present ~239~6 in another container in a separate, interconnected container system, followed by mixing without breaching the sterile conditions of the system. This avoids the known incompatibility problems encountered on sterilizing the mixture of sugar and amino acids in those in-stances where it is desired to have a sugar present in the dialysis solution of this invention.
Alternatively, glucose and amino acid solutions may be sop-irately sterilized in separate containers, and then brought together by the use of a sterile connector system similar to that shown in U.S. Patent 4,157,723 or the like, providing a reliably sterile con-section permitting the sterile mixing of the two solutions to form the dialysis solution of the invention.
It is specifically contemplated to use the solution of this invention as a peritoneal dialysis solution, and specifically in a CARD procedure. It would also be possible to use the solution of this invention in hemodialysis for similar benefit.
The amino acid mixture utilized in this invention may be added to commercially available dialysis solution formulations, for example Donnelly R dialysis solutions, a family of peritoneal dialysis solutions sold by Travenol Laboratories, Inc. of Deer field, Illinois.
Specifically 1.5 percent by weight of an amino acid formulation as described above may be added to Donnelly peritoneal dialysis solution containing 1.5 percent Betty of glucose, to provide a peritoneal dialysis solution having active ultrafiltration characteristics, while providing to the patient an increased amino acid content in the D6-4414-1 ~239~
blood, in which essential amino acid concentrations are distributed in a manner beneficial to the uremia patient.
The above has been offered for illustrative purposes only, and is not intended to limit the scope of the invention of this apply-cation, which is as defined in the claims below. A person skilled in the art would have no difficulty in formulating specific formulas within the scope of the invention.
Claims (14)
1. A peritoneal dialysis solution which comprises physio-logical salts in sufficient concentrations to be osmotically compat-ible with blood, and also containing from 0.5 to 2.5 percent by weight of a mixture of amino acids, at least one-third of the weight of amino acids present being essential amino acids, the following essential amino acids being present in said mixture in the following percentages by weight:
phenylalanine 1 to 4 % of essential amino acids present tyrosine 4 to 6.5% of essential amino acids present isoleucine 9 to 15% of essential amino acids present leucine 12 to 24% of essential amino acids present valine 12 to 24% of essential amino acids present methionine 6 to 10% of essential amino acids present threonine 9 to 18% of essential amino acids present triptophan 1.5 to 4.5% of essential amino acids present lysine 12 to 28% of essential amino acids present histidine 3 to 12%. of essential amino acids present
phenylalanine 1 to 4 % of essential amino acids present tyrosine 4 to 6.5% of essential amino acids present isoleucine 9 to 15% of essential amino acids present leucine 12 to 24% of essential amino acids present valine 12 to 24% of essential amino acids present methionine 6 to 10% of essential amino acids present threonine 9 to 18% of essential amino acids present triptophan 1.5 to 4.5% of essential amino acids present lysine 12 to 28% of essential amino acids present histidine 3 to 12%. of essential amino acids present
2. The dialysis solution of Claim 1 in which from 1 to 5 percent by weight of glycine is present in said mixture.
3. The dialysis solution of Claim 1 in which from 1 to 7 percent of arginine is present in said mixture.
4. The dialysis solution of Claim 1 in which from 1 to 6 percent by weight of proline is present in said mixture.
5. The dialysis solution of Claim 1 in which from 1 to 5 percent by weight of serine is present in said mixture.
6. The dialysis solution of Claim 1 in which from 2 to 10 percent by weight of alanine is present in said mixture.
7. The dialysis solution of Claim 1 in which from 1 to 7 percent of arginine, 1 to 5 percent of glycine, 1 to 6 percent of proline, 1 to 5 percent of serine, and 2 to 10 percent of alanine are present in said mixture, all percentages being by weight.
8. The dialysis solution of Claim 1 in which the weight percent of tyrosine present is at least twice the weight percent of phenylalanine present.
9. A dialysis solution which comprises physiological salts in sufficient concentration to be osmotically compatible with blood and also containing essentially 1 to 2 percent by weight of a mixture of amino acids, at least one-third of the weight of amino acids pre-sent being essential amino acids, the following essential amino acids being present in said mixture in the following percentages by weight:
Phenylalanine 2.5 to 2.8% of essential aminio acids present Tyrosine 5 to 6.5% of essential aminio acids present Isoleucine 10 to 12% of essential aminio acids present Leucine 14 to 17% of essential aminio acids present Valine 14 to 17% of essential aminio acids present Methinonine 7 to 8% of essential aminio acids present Threonine 10 to 14% of essential aminio acids present Triptophan 2 to 3% of essential aminio acids present Lysine 13 to 18% of essential aminio acids present Histidine 7 to 9% of essential aminio acids present Arginine 5 to 7% of essential aminio acids present
Phenylalanine 2.5 to 2.8% of essential aminio acids present Tyrosine 5 to 6.5% of essential aminio acids present Isoleucine 10 to 12% of essential aminio acids present Leucine 14 to 17% of essential aminio acids present Valine 14 to 17% of essential aminio acids present Methinonine 7 to 8% of essential aminio acids present Threonine 10 to 14% of essential aminio acids present Triptophan 2 to 3% of essential aminio acids present Lysine 13 to 18% of essential aminio acids present Histidine 7 to 9% of essential aminio acids present Arginine 5 to 7% of essential aminio acids present
10. The dialysis solution of Claim 9 in which from 5% to 7% of arginine is present in siad mixture.
11. The dialysis solution of Claim 9 which also includes from 4 to 5 percent of glycine, 5 to 6 percent of proline, 4 to 5 per-cent of serine and 8 to 10 percent of alanine, all percentages being by weight.
12. The dialysis solution of Claim 11 which is a peritoneal dialysis solution.
13. A dialysis solution which comprises physiological salts in sufficient concentration to be osmotically compatible with blood, and also containing from 0.5 to 2.5 percent by weight of a mixture of amino acids, said mixture of amino acids including at least 1 percent by weight of phenylalanine and from 4 to 6.5 percent by weight of ty-rosine, there being at least twice as much tyrosine present as phenyl-alanine, the balance of the amino acids comprising a mixture of the remaining essential amino acids with nonessential amino acids being optionally present.
14. The dialysis solution of Claim 13 in which 1 to 2 per-cent by weight of the mixture of amino acids is present.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000464555A CA1239586A (en) | 1984-10-02 | 1984-10-02 | Dialysis solution containing amino acids |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000464555A CA1239586A (en) | 1984-10-02 | 1984-10-02 | Dialysis solution containing amino acids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1239586A true CA1239586A (en) | 1988-07-26 |
Family
ID=4128823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000464555A Expired CA1239586A (en) | 1984-10-02 | 1984-10-02 | Dialysis solution containing amino acids |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1239586A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0347714A2 (en) * | 1988-06-22 | 1989-12-27 | Fresenius AG | Dialysing and rinsing solution for intraperitoneal dispensing |
| WO1991008008A2 (en) * | 1989-11-30 | 1991-06-13 | Baxter International Inc. | Histidine buffered peritoneal dialysis solution |
| EP0555087A1 (en) * | 1992-02-04 | 1993-08-11 | Baxter International Inc. | Peritoneal dialysis solutions containing at least one dipeptide |
| WO1994014430A1 (en) * | 1992-12-22 | 1994-07-07 | Baxter International Inc. | Improved amino acid solutions for treatment of peritoneal dialysis patients |
-
1984
- 1984-10-02 CA CA000464555A patent/CA1239586A/en not_active Expired
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0347714A2 (en) * | 1988-06-22 | 1989-12-27 | Fresenius AG | Dialysing and rinsing solution for intraperitoneal dispensing |
| EP0347714A3 (en) * | 1988-06-22 | 1990-12-27 | Fresenius AG | Dialysing and rinsing solution for intraperitoneal dispensing |
| WO1991008008A2 (en) * | 1989-11-30 | 1991-06-13 | Baxter International Inc. | Histidine buffered peritoneal dialysis solution |
| WO1991008008A3 (en) * | 1989-11-30 | 1991-09-19 | Baxter Int | Histidine buffered peritoneal dialysis solution |
| EP0555087A1 (en) * | 1992-02-04 | 1993-08-11 | Baxter International Inc. | Peritoneal dialysis solutions containing at least one dipeptide |
| US5597805A (en) * | 1992-02-04 | 1997-01-28 | Baxter International Inc. | Peritoneal dialysis solutions |
| EP0804931A2 (en) * | 1992-02-04 | 1997-11-05 | Baxter International Inc. | Peritoneal dialysis solutions and their use to minimize injury to mesothelial cells |
| EP0804931A3 (en) * | 1992-02-04 | 2001-04-11 | Baxter International Inc. | Peritoneal dialysis solutions and their use to minimize injury to mesothelial cells |
| WO1994014430A1 (en) * | 1992-12-22 | 1994-07-07 | Baxter International Inc. | Improved amino acid solutions for treatment of peritoneal dialysis patients |
| US5670176A (en) * | 1992-12-22 | 1997-09-23 | Baxter International Inc. | Amino acid solutions for treatment of peritoneal dialysis patients |
| US5698230A (en) * | 1992-12-22 | 1997-12-16 | Baxter International Inc. | Amino acid solutions for treatment of peritoneal dialysis patients |
| US5776503A (en) * | 1992-12-22 | 1998-07-07 | Baxter International Inc. | Amino acid solutions for treatment of peritoneal dialysis patients |
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