Claims for Patent: 5,261,876

Summary for Patent: 5,261,876

Title:	Enhanced peritoneal membrane plasmapheresis
Abstract:	The method of treatment called peritoneal membrane plasmapheresis for removal of plasma proteins is enhanced by specification of a sequence of two or three solutions for instilling into and draining from the peritoneal cavity. Solution 1 contains a vosodilator, solution 3 contains no vasoactive drug, and solution 2 contains a vasoconstrictor. Choice of the sequence of solutions to be instilled and drained according to the claimed methods results in sustained opening of peritoneal membrane pores and substantially elevated rates of plasma protein removal, avoiding the problem of declining rates due to local tissue compensatory mechanisms which are observed when only solution 1 is used. Resulting protein removal rates in an anticoagulated patient compare favorably with those attainable with extracorporeal phasmapheresis. An analogous process may be carried out to increase the pore size of any biological membrane accessible to the solutions.
Inventor(s):	Popovich; Robert P. (Austin, TX), Moncrief; Jack W. (South Austin, TX), He; Zhengzhi (Austin, TX)
Assignee:	Moncrief-Popovich Research Institute, Inc. (Austin, TX)
Application Number:	07/899,676
Patent Claims:	1. A method for removing plasma components from a patient, the method comprising serial instilling and draining of a first physiologic solution with added vasodilator drug, in the patient's peritoneal cavity followed by serial instilling and draining of a second physiologic solution with added vasoconstrictor drug in the patient's peritoneal cavity. 2. The method of claim 1 wherein instilling and draining of the first physiologic solution occur simultaneously, instilling occurring through a first peritoneal catheter and draining occurring through a second peritoneal catheter, said first and second catheters being implanted in the patient's peritoneal cavity. 3. The method of claim 1 wherein instilling and draining of the second physiologic solution occur simultaneously, instilling occurring through a first peritoneal catheter and draining occurring through a second peritoneal catheter, said first and second catheters being implanted in the patient's peritoneal cavity. 4. A method of removing plasma components from a patient's circulating blood using first and second physiologic solutions, the method comprising the steps: instilling a first physiologic solution with added vasodilator drug into a patient's peritoneal cavity, said vasodilator drug being in an amount effective to increase passage of plasma components into the solution; allowing the first solution to remain in the peritoneal cavity for a first dwell time sufficient to remove plasma components from the patient's circulating blood; draining the first solution from the peritoneal cavity; instilling a second physiologic solution with added vasoconstrictor drug into the patient's peritoneal cavity, said vasoconstrictor drug being in an amount effective to prevent material reduction in rate of removal of plasma components from the patient's circulating blood; allowing the second solution to remain in the peritoneal cavity for a second dwell time sufficient to effect removal of plasma components from the patient's circulating blood; and draining the second solution from the peritoneal cavity. 5. The method of claim 1 or 4 wherein the first physiologic solution with added vasodilator drug is employed for serial instilling and draining until an effective amount of plasma components is no longer removed during draining, after which the second physiologic solution with added vasoconstrictor drug is employed for serial instilling and draining until local peritoneal compensation effects induced by the first physiologic solution are effectively reduced, after which the first physiologic solution is employed again et seq. 6. The method of claim 1 or 4 wherein instilling and draining of the first physiologic solution is alternated with instilling and draining of the second physiologic solution. 7. The method of claim 1 or 4 wherein the first physiologic solution comprises plasma proteins. 8. The method of claim 1 or 4 wherein the second physiologic solution comprises plasma proteins. 9. The method of claim 1 or 4 wherein the first physiologic solution is hypertonic and the second physiologic solution is hypotonic. 10. The method of claim 1 or 4 wherein tonicity of the first and second physiologic solutions is hypotonic if the patient is hypovolemic prior to instilling of the solution; and hypertonic if the patient is hypervolemic prior to instilling of the solution. 11. The method of claim 1 or 4 wherein plasma expander is administered intravenously. 12. The method of claim 11 wherein plasma expander is administered while the patient is asleep. 13. The method of claim 1 or 4 wherein instilling and draining of the first physiologic solution is followed by instilling and draining of a third physiologic solution containing no added vasodilator or vasoconstrictor, followed by instilling and draining of the second physiologic solution. 14. The method of claim 13 wherein the third physiologic solution is hypotonic. 15. The method of claim 13 wherein the third physiologic solution is hypertonic. 16. The method of claim 13 wherein the third physiologic solution comprises plasma expander. 17. The method of claim 13 wherein tonicity of the third physiologic solution is hypotonic if the patient is hypovolemic prior to instilling of the solution; and hypertonic if the patient is hypervolemic prior to instilling of the solution. 18. The method of claim 13 wherein the third physiologic solution is employed for serial instilling and draining until an effective amount of plasma components is no longer removed during draining. 19. The method of claim 1 or 4 further comprising administering an anticoagulant to the patient in an amount and for a time effective to prevent clogging of a peritoneal dialysis catheter or of peritoneal membrane pores. 20. The method of claim 19 wherein the anticoagulant is administered intravenously by bolus. 21. The method of claim 19 wherein the anticoagulant is administered subcutaneously. 22. The method of claim 19 wherein the anticoagulant is heparin. 23. The method of claim 19 wherein the anticoagulant is administered orally. 24. The method of claim 1 or 4 wherein the plasma components comprise plasma proteins. 25. The method of claim 1 or 4 wherein the vasoconstrictor drug is norepinephrine. 26. The method of claim 1 or 4 wherein the vasodilator drug is dipyridamole. 27. The method of claim 1 or 4 wherein the vasodilator drug is sodium nitroprusside. 28. The method of claim 1 or 4 wherein the vasodilator drug is histamine phosphate. 29. The method of claim 1 or 4 wherein the vasodilator drug is dibenzyline. 30. The method of claim 1 or 4 further comprising the step of intermittently administering an anticoagulant intravenously. 31. The method of claim 1 or 4 further comprising the step of adding an anticoagulant drug to the physiologic solution for infusion into the peritoneal cavity. 32. The method of claims 1 or 4 wherein proteins are selectively removed from the drained solution, after which the drained solution is reused. 33. The method of claim 1 or 4 wherein proteins are selectively removed from the peritoneal cavity by adding absorbent to the first and second solutions. 34. The method of claim 1 or 4 wherein plasma proteins removed from the peritoneal cavity are concentrated, separated and selectively readministered to the patient. 35. The method of claim 4 wherein all of the steps are repeated. 36. The method of claim 4 further comprising the step of intermittently adding effective amounts of vasodilator drug at intervals during the first dwell time. 37. The method of claim 4 further comprising the step of intermittently adding effective amounts of vasoconstrictor drug at intervals during the second dwell time. 38. The method of claim 4 further comprising the step of continuously adding effective amounts of vasodilator drug at intervals during the first dwell time. 39. The method of claim 4 further comprising the step of continuously adding effective amounts of vasoconstrictor drug at intervals during the second dwell time. 40. The method of claim 4 wherein the first and second dwell times are about 30 minutes. 41. The method of claim 4 wherein the first and second dwell times are about 1.5 hours. 42. The method of claim 4 wherein the first and second dwell times are about 4 hours. 43. The method of claim 4 wherein the first and second dwell times are about 8 hours.

Details for Patent 5,261,876

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Alk-abello, Inc.	HISTATROL	positive skin test control-histamine	Injection	103754	09/29/1950		2040-01-29
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2040-01-29