Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
• • 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

Definitions

• Dialysis solution is passed into the peritoneal cavity and allowed to dwell, typically for a period of hours, while it engages in dialysis across the membranes of the peritoneal cavity for removal of metabolic waste products.
• the dialysis solution is then removed from the peritoneal cavity, and, in the case of continuous ambulatory peritoneal dialysis, promptly replaced with another quantity of fresh dialysis solution.
• Keane et al pending Patent Application Serial No. 435,806, filed October 21, 1982 and entitled "Opsonins in Peritoneal Dialysis” teaches the use of opsonins such as immunoglobulin G in peritoneal dialysis solution to suppress peritonitis.
• Monophosphoryl lipid A (also called detoxified endotoxin) is a chemically modified component of bacterial endotoxin, a component of the outer cell wall of gram-negative bacteria.
• Bacterial endotoxin is an extremely toxic material to humans, comprising a ketodeoxyoctanate and diphosphoryl lipid A, which is a phosphorylated glucosamine disaccharide unit with ester-and amide-linked long-chain fatty acids.
• the ketodeoxyoctanate moiety can be selectively removed under mildly acidic conditions of pH 4.5.
• the resulting diphosphoryl lipid A fraction retains the full toxicity of the parent endotoxin, as determined by lethal ty in chick embryos.
• further treatment of the diphosphoryl lipid A with dilute hydrochloric acid results in selective removal of the phosphate group at the reducing end of the glucosamine disaccharide unit, to form monophosphoryl l pid A, which is substantially non toxic at effective doses in accordance with this invention.
• monophosphoryl lipid A may be administered to the peritoneal cavity of a patient in sufficient dose to suppress symptoms of peritonitis, and also, most preferably, in a dose which is less than that necessary to create any toxic reaction.
• the monophosphoryl lipid A is most desirably mixed with a peritoneal dialysis solution, preferably in a concentration of 0.3 - 100 micrograms of monophosphoryl lipid A per ml. of peritoneal dialysis solution.
• a conventional peritoneal dialysis procedure then may be performed, making use of such modified peritoneal dialysis solution, and making use of any desired mode of peritoneal dialysis, for example, continuous ambulatory peritoneal dialysis or continuous cycling peritoneal dialysis. It has been found that the presence of monophosphoryl lipid A in the peritoneal cavity results in strong suppression of peritonitis and, when used in the concentration range stated above, significant toxic symptoms are not expected..
• peritoneal dialysis solution Any desired, known peritoneal dialysis solution may be used in conjunction with this invention where solution is administered into the peritoneal cavity and thereafter withdrawn.
• the necessary parameters and ingredients for peritoneal dialysis solutions are well known, and those skilled in the art are capable of formulating without difficulty any of a large variety of peritoneal dialysis solutions. It is easily calculable what concentrations of solute may be used in peritoneal dialysis solutions. It is also well known and generally predictable which solutes may be used in peritoneal dialysis solutions and which may not.
• each peritoneal dialysis solution should contain physiological salts, for example, mixtures of salts such as sodium chloride, sodium lactate, calcium chloride, magnesium chloride, and perhaps a small amount of a potassium salt such as potassium chloride.
• An osmotic agent is also typically present in peritoneal dialysis solution, to cause ultrafiltration to take place through the patient's peritoneal cavity for removal of water from the patient. This is currently done by placing in a typical peritoneal dialysis solution from 1.5 - 4.25 grams of dextrose, although certain other osmotic agents have been suggested in the prior art, for example, ⁇ lycerol .
• a typical peritoneal dialysis solution which may be util zed in this invention may contain, per 100 ml., 1.5 to 4.25 grams of dextrose hydrous U.S.P., 500 mg. of sodium chloride U.S.P., 448 mg. of sodium lactate, 25.7 mg. of calcium chloride U.S.P., and 5.08 mg. of magnesium chloride U.S.P..
• the pH may preferably be about 5.5, as is conventional in current comrnercfally available peritoneal dialysis solutions. Broadly, the pH may range from about pH 5 to 7.
• peritoneal dialysis solution of this invention preferably from 0.5 to 50 micrograms of lyophilized monophosphoryl lipid A may be added per ml. of peritoneal dialysis solution, typically under aseptic conditions. Thereafter, the peritoneal dialysis procedure may take place in entirely conventional manner.
• the improved peritoneal dialysis solution of this invention exhibits a strong prophylactic or preventative effect against peritonitis in patients, who otherwise would exhibit susceptibility toward that disease.
• the improved peritoneal dialysis solution of this invention is also believed to exhibit a significant curative effect against peritonitis which already exists at the initial administration of the solution of this invention. However, it is preferred to make use of the solution of this invention to prevent peritonitis, rather than to attempt to cure it exclusively through the use of peritoneal dialysis solution as herein modified.
• Dianeal ® peritoneal dialysis solution containing ⁇ .5% dextrose sold by Travenol Laboratories, Inc.
• Dianeal ® peritoneal dialysis solution containing ⁇ .5% dextrose sold by Travenol Laboratories, Inc.
• CF-1 mice received 0.5 ml. of the unmodified peritoneal dialysis solution.
• mice were then monitored for three days and deaths noted.
• mice which had not received monophosphoryl lipid A, two out of twenty survived over three days. The two survivors were quite debilitated and inactive at the end of the three day period, although surviving.
• mice treated as above with monophosphoryl lipid A fifteen out of nineteen mice survived the three day period. Furthermore, most of the survivors exhibited far greater activity and other signs indicating significantly better health, when compared with the control animals.
• the improved peritoneal dialysis solution of this invention exhibits a strong capability to suppress peritonitis against a major bacterial challenge.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Emergency Medicine (AREA)
• Chemical & Material Sciences (AREA)
• Urology & Nephrology (AREA)
• Heart & Thoracic Surgery (AREA)
• Vascular Medicine (AREA)
• Engineering & Computer Science (AREA)
• Anesthesiology (AREA)
• Biomedical Technology (AREA)
• Hematology (AREA)
• External Artificial Organs (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Citations (2)

• 1985
  • 1985-05-09 WO PCT/US1985/000842 patent/WO1985005555A1/en not_active Application Discontinuation
  • 1985-05-09 JP JP60502363A patent/JPS61502234A/ja active Pending
  • 1985-05-09 EP EP19850902767 patent/EP0183773A4/de not_active Withdrawn
  • 1985-05-29 CA CA000482739A patent/CA1257203A/en not_active Expired

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