# US 5,704,358 A · Method and apparatus for diagnosing capillary leak > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,704,358 A - Document ID: US5704358A - Status: Granted - Kind: A - Application number: 08/344,334 - Filed: 1994-11-22 - Granted: 1998-01-06 - Earliest claimed: 1994-11-22 - Assignees: The Trustees of Columbia University in the City of New York - Inventors: Bashir A. Zikria - Web page: https://patentgrep.com/patent/US5704358A ## CPC - A61K 49/0043: {Fluorescein, used in vivo} - A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers} - A61K 49/0056: {Peptides, proteins, polyamino acids} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract This invention provides a method for determining the presence of capillary leak in a subject which comprises (a) introducing into the subject's circulation a pharmaceutically-acceptable solution comprising biodegradable, nontoxic, macromolecules, which macromolecules are smaller than endothelial gaps in capillaries of a subject having capillary leak, and each of which macromolecules is labeled with a detectable marker; (b) obtaining a sample of blood from the subject; (c) quantitatively measuring the detectable marker in the sample; (d) repeating steps (b) and (c) at a plurality of suitably spaced points in time; and (e) comparing the quantities of detectable marker so measured so as to ascertain a change in the quantity of detectable marker in the subject's circulation over time, the change being indicative of the presence of capillary leak, thereby determining the presence of capillary leak in the subject. The subject invention also provides an apparatus for displaying the quantity of detectable marker in a subject's circulation over time after introducing into the subject's circulation a pharmaceutically-acceptable solution comprising biodegradable, nontoxic macromolecules, which macromolecules are smaller than endothelial gaps of capillaries in a subject having capillary leak, and each of which macromolecules is labeled with a detectable marker, which apparatus comprises (a) means for obtaining samples of blood from the subject at a plurality of points in time; (b) means for quantitatively measuring the detectable marker in the sample obtained at each time point; and (c) means for displaying the quantities so measured. The aforementioned apparatus of the subject invention is useful for diagnosing capillary leak. ## Claims ### Claim 1 A method for determining the presence of capillary leak in a subject which comprises: (a) introducing into the subject's circulation a pharmaceutically-acceptable solution comprising biodegradable, nontoxic, macromolecules, which macromolecules are smaller than endothelial gaps in capillaries of a subject having capillary leak, and each of which macromolecules is labeled with a detectable marker; (b) obtaining a sample of blood from the subject; (c) quantitatively measuring the detectable marker in the sample; (d) repeating steps (b) and (c) at a plurality of suitably spaced points in time; and (e) comparing the quantities of detectable marker so measured so as to ascertain a change in the quantity of detectable marker in the subject's circulation over time, the change being indicative of the presence of capillary leak, thereby determining the presence of capillary leak in the subject. ### Claim 2 (depends on 1) The method of claim 1, wherein the change indicative of the presence of capillary leak is a decrease in the quantity of detectable marker. ### Claim 3 (depends on 1) The method of claim 1, wherein the change indicative of the presence of capillary leak is an initial increase in the quantity of detectable marker followed by a decrease in the quantity of detectable marker. ### Claim 4 (depends on 1) The method of claim 1, wherein the subject is a mammal. ### Claim 5 (depends on 4) The method of claim 4, wherein the subject is a human. ### Claim 6 (depends on 1) The method of claim 1, wherein the subject is predisposed to capillary leak. ### Claim 7 (depends on 6) The method of claim 6, wherein the subject is suffering from trauma and/or anoxia. ### Claim 8 (depends on 7) The method of claim 7, wherein the trauma is associated with a burn, shock, ischemia, organ transplantation, a surgical technique, sepsis, poisoning, or anaphylaxis. ### Claim 9 (depends on 6) The method of claim 6, wherein the subject possesses a genetic condition predisposing the subject to capillary leak. ### Claim 10 (depends on 6) The method of claim 6, wherein the subject has undergone therapy predisposing the subject to capillary leak. ### Claim 11 (depends on 10) The method of claim 10, wherein the therapy comprises immune therapy. ### Claim 12 (depends on 10) The method of claim 10, wherein the therapy comprises chemotherapy. ### Claim 13 (depends on 1) The method of claim 1, wherein the solution is introduced into the subject's circulation by intravenous injection. ### Claim 14 (depends on 1) The method of claim 1, wherein the macromolecules are globular in shape. ### Claim 15 (depends on 14) The method of claim 14, wherein the macromolecules have an average molecular weight of from about 69,000 daltons to about 150,000 daltons. ### Claim 16 (depends on 15) The method of claim 15, wherein the macromolecules are derived from dextran. ### Claim 17 (depends on 16) The method of claim 16, wherein the macromolecules comprise FITC dextran 150. ### Claim 18 (depends on 15) The method of claim 15, wherein the macromolecules comprise albumin. ### Claim 19 (depends on 18) The method of claim 18, wherein the macromolecules comprise FITC labeled albumin. ### Claim 20 (depends on 1) The method of claim 1, wherein the detectable marker is a fluorophore, a chromophore, or a radioactive substance. ### Claim 21 An apparatus for displaying the quantity of detectable marker in a subject's circulation over time and determining the presence of capillary leak after introducing into the subject's circulation a pharmaceutically acceptable solution comprising biodegradable, nontoxic macromolecules, which are smaller than endothelial gaps of capillaries in a subject having capillary leak, and each of which macromolecules is labeled with a detectable marker, which apparatus comprises: (a) means for obtaining samples of blood from the subject at a plurality of points in time; (b) means for quantitively measuring the detectable marker in the sample obtained at each time point; (c) means for determining the presence of capillary leak using the quantities so measured; and (d) means for displaying the presence of capillary leak and quantities of detectable marker measured.