Internet for Pharmaceutical and Biotech Communities
| Newsletter | Post Jobs | Advertising |
 
 
 

  

Pharm/Biotech
Resources

Outsourcing Guide

Cont. Education

Software/Reports

Training Courses

Web Seminars

Jobs

Buyer's Guide

Home Page

Pharm Patents /
Licensing

Pharm News

Federal Register

Pharm Stocks

FDA Links

FDA Warning Letters

FDA Doc/cGMP

Pharm/Biotech Events

Consultants

Advertiser Info

Newsletter Subscription

Web Links

Suggestions

Site Map
 

 
   



 

Title:  Biochemically balanced peritoneal dialysis solutions
United States Patent: 
7,011,855
Issued: 
March 14, 2006
Inventors:
 Martis; Leo (Long Grove, IL); Henderson; Lee W. (Lake Forest, IL)
Assignee: 
Baxter International Inc. (Deerfield, IL)
Appl. No.: 
955248
Filed: 
September 17, 2001


 

Pharm Bus Intell & Healthcare Studies


Abstract

A peritoneal dialysis solution that is biochemically balanced to correct metabolic acidosis associated with chronic renal failure in a more physiological manner. The peritoneal dialysis solution has a physiological pH, e.g., pH of 7.0 to 7.4, and contains bicarbonate at a concentration that is found in normal blood. Additionally, the solution contains carbon dioxide at a partial pressure that is similar to partial pressure of carbon dioxide found in normal blood. The peritoneal dialysis solution also contains a weak acid with a pKa of less than 5.0.

SUMMARY OF THE INVENTION

The present invention provides a peritoneal dialysis solution that is biochemically balanced to correct metabolic acidosis associated with chronic renal failure in a more physiological manner. The peritoneal dialysis solution has a physiological pH, e.g., pH of 7.0 to 7.4, and contains bicarbonate at a concentration that is found in blood involved in diffusive transport of solutes with dialysis fluid. This will block the loss of bicarbonate during peritoneal dialysis which is the case with present solutions. Additionally, the solution contains carbon dioxide at a partial pressure that is similar to partial pressure of carbon dioxide found in the blood capillaries. The peritoneal dialysis solution also contains a weak acid with a pKa of less than 5.0 at an amount needed to neutralize acid generated from endogenous metabolism. These weak acids are also the normal biochemical intermediates of glucose metabolism resulting in neutral end products.

To this end, the present invention provides a peritoneal dialysis solution including bicarbonate at a level of less than or equal to 30 mM/L, having a pCO2 that is less than 60 mmHg, and including at least one weak acid selected from the group consisting of: lactate; pyruvate; citrate; isocitrate; cis-aconitase; α-ketoglutarate; succinate; fumarate; malate; and oxaloacetate.

In an embodiment of the peritoneal dialysis solution, bicarbonate is present in the solution at 25 mM/L.

In an embodiment of the peritoneal dialysis solution, the weak acid is present in an amount comprising approximately 10 mEq/L to about 20 mEq/L.

In an embodiment of the peritoneal dialysis solution, the pCO2 of the solution is approximately the same as the pCO2 of blood.

In an embodiment of the peritoneal dialysis solution, the solution has a pH of approximately 7.4.

In an embodiment of the peritoneal dialysis solution, the weak acids have a pKa of <5.0.

In another embodiment, the present invention provides a peritoneal dialysis solution comprising:

   
  Dextrose (hydrous) (g/dl)  1.5-4.25
  Sodium (mEq/L) 100-140
  Chloride (mEq/L)  70-110
  Calcium (mEq/L) 0.0-4.0
  Magnesium (mEq/L) 0.0-4.0
  Bicarbonate (mEq/L) 20.0-30.0
  Weak acid (mEq/L) 10.0-20.0
   

wherein the weak acid is chosen from the group consisting of: lactate; pyruvate; citrate; isocitrate; cisaconitase; α-ketoglutarate; succinate; fumarate; malate; and oxaloacetate.

In an embodiment, the solution includes an osmotic agent other than dextrose.

In an embodiment, the present invention provides a method for correcting metabolic acidosis in a dialysis patient suffering or likely to suffer from same comprising the step of administering to a dialysis patient a peritoneal dialysis solution that has a bicarbonate level and carbon dioxide partial pressure that is substantially similar to that found in the normal person's blood.

An advantage of the present invention is that it provides an improved peritoneal dialysis solution.

Another advantage of the present invention is that it provides bicarbonate to the patient when blood bicarbonate is below normal.

Still an advantage of the present invention is that it removes bicarbonate when blood bicarbonate is above normal.

Another advantage of the present invention is that it provides a biochemically balanced peritoneal dialysis solution.

Furthermore, an advantage of the present invention is that it provides a peritoneal dialysis solution that corrects metabolic acidosis associated with end stage renal disease.

Moreover, an advantage of the present invention is that it provides a peritoneal dialysis solution that balances bicarbonate at a normal concentration with a pCO2 at normal partial pressure.

Further, an advantage of the present invention is that the dialysis solution provides an additional contribution of bicarbonate by diffusion of bicarbonate to offset the end balance of the metabolic hydrogen load and vice versa for a supernormal concentration.

Another advantage of the present invention is that it provides a peritoneal dialysis solution at a physiological pH.

Additional features and advantages of the present invention are described in, and will be apparent from, the detailed description of the presently preferred embodiments.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

The present invention provides improved peritoneal dialysis solutions. The solutions are biochemically balanced to correct metabolic acidosis that is associated with chronic renal failure. Pursuant to the present invention, the solutions are biochemically balanced in a more physiological manner than prior peritoneal solutions.

To this end, the present invention provides peritoneal dialysis solutions that contain bicarbonate at a more physiological level, e.g., at a level substantially equivalent to that found in normal blood.

The peritoneal dialysis solution of the present invention, in an embodiment, includes bicarbonate present at a level of approximately 20 mM/L to about 30 mM/L. In a most preferred embodiment, bicarbonate is present at a level of 25 mM/L.

Additionally, the solution contains carbon dioxide at a partial pressure that is less than 60 mmHg. In a preferred embodiment the pCO2 of the solution is similar to the partial pressure of carbon dioxide found in blood capillaries.

Further, preferably, the dialysis solutions have a pH of 7.4. Therefore, the solution, although balanced biochemically, is a physiologically acceptable solution.

Additionally, the solutions include a weak acid with a pKa of less than 5. These weak acids are chosen so as to be normal biochemical intermediates of glucose metabolism. Preferably, the weak acids are chosen from the group consisting of: lactate; pyruvate; citrate; isocitrate; cis-aconitase; α-ketoglutarate; succinate; fumarate; malate; and oxaloacetate. These acids can be present either alone or in combination in the solution. Preferably, the weak acids are present at a level of approximately 10 to about 20 mEq/L. Preferably, the weak acid are present mainly as sodium salts. The weak acid is present in an amount that would offset the daily metabolic hydrogen production of approximately 1 mEq/kg/day.

In an embodiment, the peritoneal dialysis solution used in the method for correcting metabolic acidosis does not include lactate.

Pursuant to the present invention, any osmotic agent can be used in the solution. For example, dextrose, maltodextrin, glycerol, polyglucose, polypeptides and amino acids can be used as the osmotic agent.

Preferably, the peritoneal dialysis solution, if it contains dextrose as an osmotic agent, has a general composition such as that set forth below:

   
  Dextrose (hydrous) (g/dl)  1.5-4.25
  Sodium (mEq/L) 100-140
  Chloride (mEq/L)  70-110
  Calcium (mEq/L) 0.0-4.0
  Magnesium (mEq/L) 0.0-4.0
  Bicarbonate (mEq/L) 20.0-30.0
  Weak acid (mEq/L) 10.0-20.0
  pH 7.0-7.4
   

Preferably, solutions containing an osmotic agent other than dextrose composition have the general composition:

   
  Osmotic agent (miy/L)  1-200
  Sodium (mEq/L) 100-140
  Chloride (mEq/L)  70-110
  Calcium (mEq/L) 0.0-4.0
  Magnesium (mEq/L) 0.0-4.0
  Bicarbonate (mEq/L) 20.0-30.0
  Weak Acid (mEq/L)   10-20.00
  pH 7.0-7.4
   

The peritoneal dialysis solutions of the present invention balance bicarbonate at normal concentrations and have a pCO2 at normal partial pressure. The weak acid under usual circumstances will have an infinite gradient from dialysate to blood. Thus, the weak acid can be expected to perform in a relatively predictable manner in correcting the metabolic acidosis of chronic uremia.

Due to the composition of the present invention, should the patient's bicarbonate level drop below prescribed normal blood figure of 25 mM/L, then there will be an additional contribution by diffusion of bicarbonate to offset the unbalanced metabolic hydrogen load and vice versa for a supernormal concentration. Phrased in a different manner, the solution has a built in servo mechanism around the figure of 25 mM/L for bicarbonate. A pure bicarbonate solution at higher than normal concentrations does not offer this benefit.
 

Claim 1 of 15 Claims

1. A peritoneal dialysis solution including bicarbonate at a level of less than or equal to 30 mM/L, having a carbon dioxide partial pressure that is less than 60 mmHg and including a weak acid at a level of between approximately 15 mEq/L and approximately 20 mEq/L selected from the group consisting of: lactate; citrate; isocitrate; cis-aconitase; α-ketoglutarate; succinate; fumarate; malate; and oxaloacetate.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.

 

 

     
[ Outsourcing Guide ] [ Cont. Education ] [ Software/Reports ] [ Training Courses ]
[ Web Seminars ] [ Jobs ] [ Consultants ] [ Buyer's Guide ] [ Advertiser Info ]

[ Home ] [ Pharm Patents / Licensing ] [ Pharm News ] [ Federal Register ]
[ Pharm Stocks ] [ FDA Links ] [ FDA Warning Letters ] [ FDA Doc/cGMP ]
[ Pharm/Biotech Events ] [ Newsletter Subscription ] [ Web Links ] [ Suggestions ]
[ Site Map ]