Body fluid expanders comprising n-substituted aminosulfonic acid buffers

Abstract

A buffered body fluid expander solution, in which the buffer is a physiologically acceptable buffer that is not an inorganic phosphate buffer, comprises calcium ions and magnesium ions at a concentration ratio of 5:1 to 1:1. The non-phosphate buffer may be a physiologically acceptable N-substituted aminosulfonic acid buffers, especially those having a pKa value in aqueous solution of from 7.1 to 7.5 at 2O0C, and most preferably N-tris(hydroxymethyl) methyl-2-aminoethanesulfonic acid (TES), 3-(N-morpholino) propanesulfonic acid (MOPS), N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES) and combinations thereof. Preferred components include from 100 to 150 (preferably about 135) mmoles / L sodium ions, from 2.5 to 6.2 (preferably about 5) mmoles / L potassium ions, from 0.1 to 2.5 (preferably about 1.25) mmoles / L calcium ions, from 0.4 to 25.0 (preferably about 0.45) mmoles / L magnesium ions, from 96 to 126 (preferably about 118) mmoles / L chloride ions, 2 to 11 mmoles / L (preferably about 10) glucose (preferably D-glucose), from 50 to 150 (preferably about 110) μmoles / L glycerol, from 7 to 15 (preferably about 10) μmoles / L choline, from 5 to 400 (preferably about 300) μmoles / L glutamate (preferably L-glutamate), from 5 to 200 (preferably about 20) μmoles / L aspartate (preferably L-aspartate), from 100 to 2000 (preferably about 400) μmoles / L glutamine (preferably L-glutamine), from 15 to 215 (preferably about 60) μmoles / L pyroglutamate, from 20 to 200 (preferably about 100) μmoles / L arginine (preferably L-arginine), from 1 to 120 (preferably about 40) nmoles / L thiamine pyrophosphate (TPP), from 40 to 70 (preferably about 50) μmoles / L D- or DL or L-carnitine (preferably L-carnitine), and from 5 to 200 (preferably about 28) ml.U. / L porcine or human insulin (preferably human insulin). The solutions are useful for the manufacture of medicaments and blood volume expanders, for treating hypovolemia or for treating the loss of extracellular and interstitial fluid in subjects suffering with burns, for treating respiratory and / or metabolic acidosis in a subject, for perfusion of the abdominal cavity during peritoneal dialysis of a subject with acute renal failure or an acute toxicity condition, for preventing and / or ameliorating reperfusion injury, and for delivering a therapeutic, test and / or synergistic agent to a subject, including a biological agent, such as at least one stem cell, peptide or genomic derived protein.

Description

FIELD OF THE INVENTION[0001]The invention relates generally to body fluid expanders. In particular, the invention relates to physiological liquid media for use in expanding, maintaining or replacing blood or extravascular body fluid volume. It is envisaged that the invention will find use in various medical applications, including in intravenous and extravascular (e.g. peritoneal) infusion procedures.BACKGROUND ART[0002]Loss of blood volume, also known as hypovolemia, can result, for example, from a number of causes including physical injury, surgery, internal haemorrhaging or burns. Hypovolemia can also be induced by the intake of drugs such as diuretics and vasodilators.[0003]A significant loss of blood volume resulting from hypovolemia can be fatal unless treated rapidly. Such blood loss leads to a drop in blood pressure and a reduction in the necessary supply of blood (and with it oxygen) to essential organs and tissues. Consequently hypovolemia can result in ischemia, multiple ...

AI Technical Summary

Benefits of technology

[0007]We have identified a need to develop further solutions which are capable of compensating for the loss of blood and the loss of interstitial and extracellular fluid resulting from hypovolemia and severe burns. There is also a need to develop treatments which are effective at preventing or lowering the incidence of reperfusion injury in hypovolemic subjects.

[0008]In addition to the above, there is also a need to maintain a sufficient volume of extravascular, interstitial fluid. This fluid, which bathes and surrounds cells, is essential to maintaining the homeostasis of tissues and organs, and functions, inter alia, as a means of delivering materials to cells, removing metabolic waste, and facilitating effective intercellular communication.

[0009]The present invention also addresses the significant and important problem of replacement fluid treatments resulting in oedematous conditions within body organs, thereby simply augmenting the incidences of reperfusion injury. The invention is concerned to provide a physiological balanced fluid that complies with the composition of the interstitial fluid in all aspects, but most importantly in terms of tonicity and osmolality, and would facilitate a more natural dynamic fluid exchange between the extravascular space and interstitial phase in conjunction with the lymphatic system, thereby preventing the occurrence of oedema in surrounding tissues.

[0025]The invention also provides the use of a solution as defined herein for the manufacture of a medicament for (a) treating the loss of interstitial fluid in a subject suffering with burns, (b) treating respiratory and / or metabolic acidosis in a subject, (c) perfusion of the abdominal cavity during peritoneal dialysis of a subject with acute renal failure or an acute toxicity condition, or (c) preventing and / or ameliorating reperfusion injury.

Problems solved by technology

A significant loss of blood volume resulting from hypovolemia can be fatal unless treated rapidly.

Such blood loss leads to a drop in blood pressure and a reduction in the necessary supply of blood (and with it oxygen) to essential organs and tissues.

Consequently hypovolemia can result in ischemia, multiple organ failure, kidney damage, brain damage, and ultimately death.

Despite their ability to restore blood volume, the current blood volume expanders are ineffective at preventing a severe and often fatal condition known as reperfusion injury.

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