OPSONINS IN PERITONEAL DIALYSIS

Abstract: Opsonins for microorganisms may be placed into the peritoneal cavity of a patient to suppress the symptoms of peritonitis and particularly to prevent its occurrence. The opsonin may be mixed with peritoneal dialysis solution.

Description: OPSONINS IN PERITONEAL DIALYSIS Technical Field and Prior Art Chronic peritoneal dialysis has been a highly successful means for the treatment of patients with end stage renal failure. Dialysis solution is passed into the peritoneal cavity and allowed to dwell 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. One significant drawback to the various forms of peritoneal dialysis is that patients who engage in it are subject to peritonitis. While it has been found that peritonitis can be handled with antibiotics, it is potentially among the most serious of infections, due to the sensitivity of the peritoneal cavity to infection. In accordance with this invention, a technique is proposed for the suppression of peritonitis and its symptoms, particularly that peritonitis which takes place in patients who undergo peritoneal dialysis. Description of Invention By this invention, an opsonin for microorganisms is administered to the peritoneal cavity of a patient in sufficient dose to suppress the symptoms of peritonitis. It is known that the peritoneal cavity contains white cells, particularly those known as peritoneal macrophages. By this invention, the addition of an opsonin, for example mixed with the peritoneal dialysis solution, potentiates the white cell activity in the peritoneal cavity, causing them to destroy greater numbers of bacteria and thus to suppress peritonitis symptoms. While opsonins may naturally be found in the peritoneal cavity, it has been noted that some patients appear to lack sufficient opsonin concentrations to effectively suppress peritonitis when exposed to it. The artificial addition of opsonins to the peritoneal cavity can be a valuable tool in suppressing the symptoms of peritonitis, and particularly to prevent its occurrence. It is believed that the types of opsonins which may be used in the method of this invention are unlimited, subject, of course, to the natural restrictions relating to toxicity, allergic reaction, and the like. Broadly, the word "opsonin" relates to any agent that modifies microorganisms to promote white cells to phagocytize the microorganisms, including bacteria, fungi, and the like. It is believed that a typical opsonin coats or otherwise- attaches itself to the microorganism, and facilitates the action of the white cell in phagocytizing and typically destroying it. For example, gamma globulin, a known therapeutic blood fraction, is a known opsonin, which is particularly effective against gram positive bacteria. Complement, which is also a therapeutic blood fraction, may also be used, being a known opsonin for gram negative bacteria. Separated components of gamma globulin and complement may also be used, i.e., specific IgG antibodies (e.g., peptidoglycan antibodies) or a C3B-containing component of complement. The opsonin may be administered to the peritoneal cavity in any desired way, for example by injection, but in the case of peritoneal dialysis patients it is preferable to make use of the peritoneal catheter, which provides communication between the peritoneal cavity and the exterior, to administer the opsonin. If desired, the opsonin may be added to the peritoneal dialysis solution prior to its administration to the peritoneal cavity by mixing with the solution just prior to such administration. In the alternative, the opsonin may be placed in the solution as it is manufactured so that it is unnecessary for the user to have to administer extra opsonin, above and beyond that which is provided by the peritoneal dialysis solution itself. The peritoneal dialysis solution which contains an opsonin such as gamma globulin or complement may have the opsonin present in any desired, safe and effective 10 concentration. For example, gamma globulin or components thereof may be present in the peritoneal dialysis solution in a concentration of 0.05 to 10 mg. of dialysis solution, preferably no more than 5 mg. per ml. The C3 portion of tne complement may be present in the solution in a - 5 concentration of 0.1 to 10 mg. per ml. of dialysis solution. It may also be desired for a mixture of the above concentrations of gamma globulin and complement to be present in the peritoneal dialysis solution for enhanced effectiveness against both gram positive and gram Q negative bacteria. Other possible opsonins may also be provided to the peritoneal dialysis solution or otherwise administered as may be desired, for example C-reactive protein or fibronectin. 2 The peritoneal dialysis solution into which the opsonins are added may be otherwise of conventional formulation, being of physiologically tolerable pH and having physiological salts and an osmotic agent, each in safe and effective concentrations to effect peritoneal 0 dialysis when placed in the peritoneal cavity of a patient. Typically, from 1 to 5 weight percent glucose may be pres'ent as the osmotic agent, while the ions of the physiological salts may include sodium, calcium, magnesium, chloride, acetate, and lactate, for example, in conventional concentrations. Potassium ion as well as other physiologically compatible ions may also be present if appropriate. Description of Drawings Figure 1 is a perspective view showing a container of peritoneal dialysis solution in communication with the peritoneal cavity of a patient, using conventional equipment. Description of Specific Embodiment Referring to the drawing, container 10 of peritoneal dialysis solution may be of a design which is commercially available from Travenol Laboratories, Inc. of Deerfield, Illinois. Container 10 communicates with a transfer set 12, which is also commercially available from the same company, and communicates with a conventional Tenckhoff catheter 14 which is permanently implanted in the peritoneal cavity of a patient 15. As previously stated, the solution contents of container 10 (typically 2 liters) can pass into the peritoneal cavity through set 12 and catheter 14, and the set is closed with clamp 16 so that the solution is retained therein. The patient can then fold or roll up the flexible container 10 into a small package and wear it under his clothes in compact form for a period of about four hours. Thereafter, in conventional manner, the patient unfolds container 10, opens catheter 14, and allows the spent dialysis solution to drain back into container 10. Thereafter he closes container 10 with a clamp, disconnects it from set 12, and replaces the connection with a new container of fresh dialysis solution. A typical peritoneal dialysis solution which may be utilized 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 ϋ.S.P, 448 mg. of sodium lactate, 25.7 gm. of calcium chloride ϋ.S.P., and 5.08 mg. of magnesium chloride U.S.P. The pH may preferably be about 5.5, broadly ranging from about pH 5 to 7. In accordance with this invention 100 mg. of gamma globulin per liter of dialysis solution present may be added to the container 10 by injection syringe 20 through auxiliary medication port 18, which may be of conventional design, to mix with the peritoneal dialysis solution present in container 10. Alternatively, 100 mg. per liter of dialysis solution of the C-3 component of complement may be added, either as part of whole complement or a purified fraction thereof. Alternatively, 100 mg. per liter of the same C-3 component may be added as a further additive to the solution along with the gamma globulin. Thereafter, administration of the dialysis solution to the peritoneal cavity causes peritoneal dialysis to proceed in ordinary manner, but with the symptoms of peritonitis being effectively suppressed, since the presence of opsonins causes greater white- cell phagocytosis and subsequent destruction of any bacteria or other microorganisms present. The above has been offered for illustrative purposes only and is not intended to limit the scope of the invention, which is as defined in the claims below. OMPI ^ξi τιo

Claims: THAT WHICH IS CLAIMED IS: 1. The method of administering an opsonin for microorganisms into the peritoneal cavity of a patient in sufficient dose to suppress symptoms of peritonitis. 2. The method of Claim 1 in which said opsonin comprises gamma globulin. 3. The method of Claim 1 in which said opsonin comprises complement. 4. The method of performing peritoneal dialysis on a patient by administering peritoneal dialysis solution to the peritoneal cavity of a patient, and thereafter withdrawing said solution from the peritoneal cavity, the improvement comprising: adding an opsonin for microorganisms to said peritoneal dialysis solution in sufficient concentration to suppress symptoms of peritonitis. 5. The method of Claim 4 in which said opsonin comprises gamma globulin. 6. The method of Claim 3 in which said opsonin comprises complement. 7. The method of Claim 4 in which said opsonin comprises a mixture of gamma globulin and complement. 8. A peritoneal dialysis solution which comprises a water solution of physiologically tolerable pH having physiological salts and an osmotic agent, each in safe and effective concentrations to effect peritoneal dialysis when placed in the peritoneal cavity of a patient, the improvement comprising, in combination: an opsonin for microorganisms dispersed in said peritoneal dialysis solution in sufficient concentration to suppress symptoms of peritonitis when inserted into the peritoneal cavity in a peritoneal dialysis procedure. 9. The peritoneal dialysis solution of Claim 8 in which said opsonin comprises gamma globulin. 10. The peritoneal dialysis solution of Claim 9 in which said gamma globulin is present in a concentration of 0.05 to 10 g. per ml. of dialysis solution. 11. The peritoneal dialysis solution of Claim 8 in which said opsonin comprises complement. 12. The peritoneal dialysis solution of Claim 11 in which said complement is present in a concentration of 0.1 to 10 mg. per ml. of dialysis solution. 13. The peritoneal dialysis solution of Claim 8 in which said opsonin comprises a mixture of from 0.1 to 10 mg. of gamma globulin and from 0.1 to 10 mg. of complement, per ml. of dialysis solution. 14. A peritoneal dialysis solution which comprises a water solution of physiologically tolerable pH having physiological salts and an osmotic agent, each in safe and effective concentrations, to effect peritoneal dialysis when placed in the peritoneal cavity of a patient, the improvement comprising, in combination: an opsonin for microorganisms comprising at least one peptidoglycan antibody dispersed in said peritoneal dialysis solution in a concentration of 0.05 to 10 mg./ml. of dialysis solution. 15. The peritoneal dialysis solution of Claim 14 in whic:hh nnco more than 5 mg./ml. of said dispersed antibody is present.

Inventors: KEANE WILLIAM F, PETERSON PHILLIP K, KEANE, WILLIAM, F., PETERSON, PHILLIP, K.
Applicants: MINNEAPOLIS MED RES, MINNEAPOLIS MEDICAL RESEARCH FOUNDATION INC.
Application year: 1983
Main classification: A61K39
IPC codes: A61K35, A61M1, C07K16