Method for extracorporeal carbon dioxide removal

Abstract

The present invention generally relates to a process suitable for extracorporeal lung support. The process relies on exposing blood, separated by a semipermeable membrane from the dialysis liquid. The dialysis liquid of the present invention comprises a buffering agent and has a high buffering capacity for H* ions. Carbon dioxide, bicarbonate and hydrogen cations can be efficiently transported across a semipermeable membrane to the dialysis liquid. The present invention also allows for the regeneration and recycling of the dialysis liquid, and thus for its recycling and repeated use. The versatility of the dialysis liquid allows to adjust the pH of the dialysis liquid, add fluids to the dialysis liquid and/or to the blood in the extracorporeal circuit and to remove substances from the blood in the extracorporeal circuit, depending on the conditions and needs. Thus, the present invention is versatile, and suitable for treating or preventing respiratory acidosis, metabolic acidosis, diseases associated with lung malfunction and/or kidney malfunction and/or liver malfunction. For example, when the kidney function is limited, the acid-base balance of the blood can be provided by the method of the present invention; and when the liver function is limited, toxins can be removed from blood by the method of the present invention.

1 . Process for removal of at least one undesired substance from blood, comprising the step of contacting blood to a dialysis liquid via a semipermeable membrane, wherein the dialysis liquid is characterized by:
 (i) a pH the range from pH 8.0 to pH 11.0;   (ii) comprising at least one buffering agent, wherein the buffering agent has at least one pKa value in the range from 7.0 to 11.0; and   (iii) a buffering capacity of 12 mmol/l or more for H +  ions.   
     
     
         2 . Process according to  claim 1 , wherein the buffering agent is a non-CO 2 -forming buffering agent. 
     
     
         3 . Process according to  claim 2 , wherein the non-CO 2 -forming buffering agent is selected from albumin, THAM, Tris and phosphate buffer. 
     
     
         4 . Process according to  claim 1 , wherein the dialysis liquid comprises albumin. 
     
     
         5 . Process according to  claim 1 , wherein the dialysis liquid comprises less than 10 mmol carbonate/bicarbonate. 
     
     
         6 . Process according to  claim 5 , wherein the dialysis liquid does not comprise carbonate/bicarbonate. 
     
     
         7 . Process according to  claim 5 , wherein the dialysis liquid does not comprise a CO 2 -forming buffering agent. 
     
     
         8 . Process according to  claim 1 , wherein said blood is present in a first chamber, and wherein said dialysis liquid is present in a second chamber, the chambers being separated by said semipermeable membrane. 
     
     
         9 . Process according to  claim 8 , wherein said blood flows through the first chamber, so that it enters, passes through and exits the first chamber. 
     
     
         10 . Process according to  claim 8 , wherein dialysis liquid flows through the second chamber, so that it enters, passes through and exits the second chamber. 
     
     
         11 . Process according to  claim 10 , wherein the dialysis liquid, when entering the second chamber, has a pH the range from pH 8.0 to pH 9.0 and comprises (i) 10 to 40 mmol/l carbonate/bicarbonate and (ii) 10 to 60 g/l albumin. 
     
     
         12 . Process according to  claim 8 , wherein the first chamber, the semipermeable membrane and the second chamber are comprised by one device. 
     
     
         13 . Process for removal of at least one undesired substance from blood, comprising the steps of:
 (i) introducing blood into a first chamber of a device,
 said device comprising a first chamber and a second chamber, wherein the first chamber and the second chamber are separated by a semipermeable membrane, 
   (ii) introducing a dialysis liquid into a second chamber of said device,
 wherein the dialysis liquid being introduced into the second chamber is characterized by: 
 (a) a pH the range from pH 8.0 to pH 11.0; 
 (b) comprising at least one buffering agent, wherein the buffering agent has at least one pKa value in the range from 7.0 to 11.0; and 
 (c) a buffering capacity of 12 mmol/l or more for H +  ions. 
   
     
     
         14 . Process according to  claim 12 , wherein the device is a dialysis unit or a dialyzer. 
     
     
         15 . Process according to  claim 1 , wherein the at least one undesired substance is selected from the group consisting of carbon dioxide (CO 2 ), hydrogen cation (H + ), hydrogen carbonate (HCO 3   − ) and solvates of any one thereof, or any combinations of these. 
     
     
         16 . Process according to  claim 1 , wherein the dialysis liquid comprises one or more buffering agents selected from the group consisting of: Tris(hydroxymethyl)aminomethane (Tris, THAM), carbonate/bicarbonate and a water-soluble protein, preferably albumin. 
     
     
         17 . Process according to  claim 16 , wherein the dialysis liquid comprises 10 to 40 mmol/l carbonate/bicarbonate, 10 to 60 g/l albumin and wherein the dialysis liquid has a pH the range from pH 8.0 to pH 11.0, preferably pH 8.0 to pH 9.0. 
     
     
         18 . Process according to  claim 16 , wherein the dialysis liquid comprises 5 to 20 mmol/l Tris, 10 to 60 g/l albumin and wherein the dialysis liquid has a pH the range from pH 8.0 to pH 11.0. 
     
     
         19 . Process according to  claim 8 , wherein the dialysis liquid exits from the second chamber, is subjected to at least one treatment step, and subsequently re-enters (is recycled) into (to) the second chamber. 
     
     
         20 . Process according to  claim 19 , wherein said at least one treatment step of the dialysis liquid is selected from the group consisting of (i) exposure to an adsorber and/or (ii) contact with a (preferably semipermeable) membrane, preferably for removal of carbon dioxide, and/or (iii) acidic pH and/or basic pH exposure. 
     
     
         21 . Process according to  claim 20 , wherein said treatment step includes acidification of the dialysis liquid to acidic pH, for formation of carbon dioxide, and subsequent removal of carbon dioxide. 
     
     
         22 . Process according to  claim 1 , additionally comprising a step of measuring at least one parameter of the blood and/or of the dialysis liquid, the parameter being selected from the group consisting of pH, carbon dioxide partial pressure, bicarbonate (HCO 3   − ) concentration, buffering capacity and deoxyhemoglobin (HHb) concentration or saturation. 
     
     
         23 . Process according to  claim 16 , wherein the albumin is selected from human serum albumin and/or bovine serum albumin. 
     
     
         24 . Process according to  claim 1 , wherein the dialysis liquid comprises more than 1.7 mmol/l calcium (Ca 2+ ) ions, preferably 2 to 4 mmol/l calcium (Ca 2+ ) ions, more preferably 2.4-2.6 mmol/l calcium ions. 
     
     
         25 . Process according to  claim 8 , wherein the dialysis liquid is recycled, and re-introduced into the second chamber, and wherein the step of re-introduction into the second chamber is preceded by a step of adjusting pH and/or buffering capacity. 
     
     
         26 . Method for extracorporeal treatment of blood from a human or animal subject, wherein the method comprises the steps of:
 (i) removing blood from the vein or artery of said subject;   (ii) subjecting blood of step (i) to a process according to  claim 1 ;   (ii) reintroducing blood of step (ii) into an artery or vein of said subject, preferably into a vein.   
     
     
         27 . Dialysis liquid for use in a method of treating a human or animal subject by therapy,
 wherein the dialysis liquid is characterized by:   (i) a pH in the range of pH 8.0 to pH 11.0;   (ii) comprising at least one buffering agent, wherein the buffering agent has at least one pKa value in the range from 7.0 to 11.0; and   (ii) a buffering capacity of 12 mmol/l or more for H +  ions.   
     
     
         28 . Dialysis liquid for use according to  claim 27 , wherein said use preferably comprises the process as defined in  claim 1 . 
     
     
         29 . Dialysis liquid for use according to  claim 27 , wherein said use preferably comprises the steps of:
 (i) removing blood from the vein or artery of a human or animal subject;   (ii) subjecting blood of step (i) to a process according to  claim 1 ;   (iii) reintroducing blood of step (ii) into an artery or vein of said subject, preferably into the vein.   
     
     
         30 . Dialysis liquid characterized by:
 (i) a pH in the range of pH 8.0 to pH 11.0;   (ii) comprising at least one buffering agent, wherein the buffering agent has at least one pKa value in the range from 7.0 to 11.0; and   (iii) a buffering capacity of 12 mmol/l or more for H +  ions,   for use in the medical treatment of a human or animal subject.   
     
     
         31 . The dialysis liquid for use according to  claim 30 , wherein said use comprises the process as defined in  claim 1 . 
     
     
         32 . The dialysis liquid for use according to  claim 30 , wherein said use preferably comprises the steps of:
 (i) removing blood from the vein or artery of a human or animal subject;   (ii) subjecting blood of step (i) to a process of  claim 1 ; and   (iii) reintroducing blood of step (ii) into an artery or vein of said subject, preferably into the vein.   
     
     
         33 . The dialysis liquid for use according to  claim 30 , wherein the dialysis liquid is used to prevent and/or treat one or more diseases selected from respiratory acidosis, metabolic acidosis, lung failure, liver failure, and kidney failure. 
     
     
         34 . The dialysis liquid for use according to  claim 30 , wherein the buffering agent is a non-CO 2 -forming buffering agent. 
     
     
         35 . The dialysis liquid for use according to  claim 34 , wherein the non-CO 2 -forming buffering agent is selected from albumin, THAM, Tris and phosphate buffer. 
     
     
         36 . The dialysis liquid for use according to  claim 30 , wherein the dialysis liquid comprises albumin. 
     
     
         37 . The dialysis liquid for use according to  claim 36 , wherein the albumin is selected from human serum albumin and/or bovine serum albumin. 
     
     
         38 . The dialysis liquid for use according to  claim 30 , wherein the dialysis liquid comprises less than 10 mmol carbonate/bicarbonate. 
     
     
         39 . The dialysis liquid for use according to  claim 38 , wherein the dialysis liquid does not comprise carbonate/bicarbonate. 
     
     
         40 . The dialysis liquid for use according to  claim 39 , wherein the dialysis liquid does not comprise a CO 2 -forming buffering agent. 
     
     
         41 . The dialysis liquid for use according to  claim 30 , wherein the dialysis liquid has a pH in the range from pH 8.0 to pH 9.0 and comprises (i) 10 to 40 mmol/l carbonate/bicarbonate and (ii) 10 to 60 g/l albumin. 
     
     
         42 . The dialysis liquid for use according to  claim 30 , wherein the dialysis liquid comprises one or more buffering agents selected from the group consisting of: Tris(hydroxymethyl)aminomethane (Tris, THAM), carbonate/bicarbonate and a water-soluble protein, preferably albumin. 
     
     
         43 . The dialysis liquid for use according to  claim 42 , wherein the dialysis liquid comprises 10 to 40 mmol/l carbonate/bicarbonate, 10 to 60 g/l albumin and wherein the dialysis liquid has a pH the range from pH 8.0 to pH 11.0, preferably pH 8.0 to pH 9.0. 
     
     
         44 . The dialysis liquid for use according to  claim 42 , wherein the dialysis liquid comprises 5 to 20 mmol/l Tris, 10 to 60 g/l albumin and wherein the dialysis liquid has a pH the range from pH 8.0 to pH 11.0. 
     
     
         45 . The dialysis liquid for use according to  claim 30 , wherein the dialysis liquid comprises more than 1.7 mmol/l calcium (Ca 2+ ) ions, preferably 2 to 4 mmol/l calcium (Ca 2+ ) ions, more preferably 2.4-2.6 mmol/l calcium ions. 
     
     
         46 . Method according to  claim 26  wherein the subject is selected from a subject suffering from respiratory acidosis, a subject suffering from metabolic acidosis, a subject suffering from lung failure, a subject suffering from liver failure, and a subject suffering from kidney failure, or a subject suffering from combinations of any of these. 
     
     
         47 . Method according to  claim 46 , wherein the subject suffers from respiratory acidosis, and wherein the dialysis liquid, when entering into the second chamber, is characterized by
 (a) presence of Tris and albumin as buffering agents, and   (b) a (combined) carbonate/bicarbonate concentration in the range from 0 to 10 mmol/l.   
     
     
         48 . Method according to  claim 46 , wherein the subject suffers from metabolic acidosis, and wherein the dialysis liquid, when entering into the second chamber, is characterized by presence of carbonate/bicarbonate and albumin as buffering agents, and preferably a (combined) carbonate/bicarbonate concentration in the range from 20 to 40 mmol/l. 
     
     
         49 . Method according to  claim 46 , wherein the subject suffers from lung failure, and wherein the dialysis liquid, when entering into the second chamber, is characterized by
 (a) presence of Tris and albumin as buffering agents, and   (b) absence of carbonate/bicarbonate, or a (combined) carbonate/bicarbonate concentration in the range from 0 to 10 mmol/l.   
     
     
         50 . Method according to  claim 46 , wherein at least one of bicarbonate, carbon dioxide or carbonic acid is removed from the dialysis liquid upon exiting the second chamber, and the dialysis liquid is subsequently recycled to the second chamber. 
     
     
         51 . Method according to  claim 46 , wherein the subject suffers from lung failure and kidney failure, and wherein the dialysis liquid is contacted with an adsorber upon exiting the second chamber, and the dialysis liquid is subsequently recycled to the second chamber. 
     
     
         52 . Method according to  claim 46 , wherein the subject suffers from lung failure and liver failure, and wherein
 (i) upon exiting the second chamber, the dialysis liquid is divided into two parallel flow paths, a first flow path and a second flow path;   (iia) the pH of the dialysis liquid in the first flow path is lowered by addition of acid;   (iib) the pH of the dialysis liquid in the second flow path is increased by addition of base;   (iii) the dialysis liquids of the first and the second flow path are merged, and the pH is adjusted to a pH in the range of 8.0 to 9.0;   and   (iv) the dialysis liquid of step (iii) is subsequently recycled to the second chamber.   
     
     
         53 . Process for regenerating a dialysis liquid as defined in  claim 30 , wherein the process comprises the following steps:
 (a) separating a flow of the dialysis liquid as defined in  claim 30  into a first flow and a second flow;   (b) adding an acidic fluid to the first flow of dialysis liquid;   (c) removing toxins by filtrating, dialysing, precipitating or diafiltrating the acidified first flow of the dialysis liquid;   (d) adding an alkaline fluid to the second flow of the dialysis liquid;   (e) removing toxins by filtrating, dialysing, precipitating or diafiltrating the alkalized second flow of the dialysis liquid; and   (f) merging the first and the second flow of the dialysis liquid.   
     
     
         54 . The process according to  claim 53 , wherein the process further comprises periodically switching a plurality of switching valves such that the flow of acidified dialysis liquid is alternatingly supplied to a first detoxification unit and to a second detoxification unit, whereas the flow of alkalized dialysis liquid is alternatingly supplied to the second detoxification unit and to the first detoxification unit. 
     
     
         55 . The process according to  claim 53 , wherein the process further comprises one or more of the following:
 regulating the temperature of the acidified dialysate;   removing toxins by precipitation due to the acidification;   regulating the temperature of the alkalized dialysate; and   removing toxins by precipitation due to the alkalization.   
     
     
         56 . The process according to  claim 53 , wherein the process further comprises a step of measuring at least one parameter of the blood and/or of the dialysis liquid, the parameter being selected from the group consisting of pH, carbon dioxide partial pressure, bicarbonate (HCO 3   − ) concentration, buffering capacity and deoxyhemoglobin (HHb) concentration or saturation. 
     
     
         57 . The process according to  claim 53 , wherein the process further comprises a step of adjusting the pH of said liquid to a pH in the range from pH 8.0 to pH 11.0, preferably pH 8.0 to pH 9.0, which preferably follows after step (f).