Use of UTP for the diagnosis of stenoses and other conditions of restricted blood flow

• US 20110085977A1
• Filed: 08/10/2010
• Published: 04/14/2011
• Est. Priority Date: 08/10/2009
• Status: Active Grant

• Current Assignee: P2 Science ApS
• Original Assignee: P2 Science ApS
• Inventors: Rosenmeier, Jaya Brigitte
• Granted Patent: US 8,394,355 B2
• Time in Patent Office: Days
• US Class Current: 424/9.1
• CPC Class Codes: A61B 5/026 Measuring blood flow A61B3/1233, A61B3/1241 take precedence
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/0478 complexes from non-cyclic ligands, e.g. EDTA, MAG3
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to methods for determining whether blood flow is restricted in a blood vessel of an individual suspected of compromised blood flow in the vessel, the method comprising the steps of delivering UTP, a derivative thereof, or a salt thereof to the vessel, assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel, comparing the obtained value with a reference value, and determining whether the individual has compromised blood flow based on the results of the comparison. The invention also provides for methods of diagnosing atherosclerotic and ischemic heart diseases using UTP, a derivative thereof, or a salt thereof, as well as methods for inducing maximal hyperemia for diagnostic purposes.

Claims

1. A method for determining whether blood flow is restricted in a blood vessel of an individual suspected of compromised blood flow in the vessel, the method comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to said vessel,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on the results of the comparison.

2. The method of claim 1, wherein the individual is suffering or suspected to be suffering from a disease or disorder selected from the group consisting of obesity, hypertension, vasculitis, increased thrombotic risk, hypercholesterolemia, atherosclerosis, diabetic complications, or vascular stenosis.

3. The method of claim 1 wherein said individual is suffering or is suspected to be suffering of Peripheral Artery Disease (PAD), coronary atherosclerosis, atherosclerosis, renal artery stenosis, or ischemic heart disease.

4. The method of claim 1, wherein the reference value is obtained by measuring blood flow in another similar vessel of said individual.

5. The method of claim 1, wherein blood flow is assessed by FFR, CFR, MAP, or APV measurement.

6. The method of claim 1, wherein UTP, a derivative thereof, or a salt thereof is delivered by in situ infusion.

7. The method of claim 1, wherein the UTP, a derivative thereof, or a salt thereof is selected from the group consisting of UTP, UTPγ

S, MRS2498, uridine 5′

-trisphosphate tris salt, uridine 5′

-trisphosphate salt dihydrate, uridine 5′

-trisphosphate salt solution, uridine 5′

-trisphosphate salt hydrate, uridine-¹³C₉, ¹⁵N₂ 5′

-trisphosphate sodium salt solution, uridine-¹⁵N₂ 5′

-trisphosphate sodium salt solution, uridine 5′

-triphosphate trisodium salt hydrate, uridine-¹³C₉, ¹⁵N₂ 5′

-triphosphate sodium salt solution, uridine-¹⁵N₂ 5′

-triphosphate sodium salt solution, 2-diuridine tetraphosphate, thioUTP tetrasodium salt, denufosol tetrasodium, and UTPγ

S trisodium salt.

8. The method of claim 1, wherein the UTP, a derivative thereof, or a salt thereof, is administered at a rate of infusion from about 50 to about 400 μ

g of the compound per minute.

9. The method of claim 1, wherein the UTP, a derivative thereof, or a salt thereof, is administered via continuous intravenous infusion, intracoronary infusion, drip infusion, intracoronary bolus injection, a guiding catheter, or an IC microcatheter.

10. The method of claim 9, wherein the UTP, a derivative thereof, or a salt thereof, is administered via a guiding catheter or an IC microcatheter.

11. The method of claim 9, wherein the UTP, a derivative thereof, or a salt thereof, is administered at a rate of infusion is about 80 to about 360 μ

g of the compound per minute.

33. The method of claim 1 wherein the amount of UTP, UTP salt or UTP derivative is effective to create maximal hyperemia in said vessel.

12. A method for determining whether blood flow is restricted in a blood vessel of an individual suspected of compromised blood flow in the vessel, the method comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to said vessel,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on whether there is a difference between the obtained value and the reference value indicative of a reduction in blood flow relative to a healthy vessel.

13. A method for determining whether blood flow in a blood vessel of an individual suspected of compromised blood flow in the vessel is restricted, the method comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to said vessel of an individual suspected of having an atherosclerotic or ischemic disease,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on the results of the comparison.

14. A method for determining blood flow in a blood vessel comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to an individual suspected of having a vessel with compromised blood flow,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on the results of the comparison.

15. The method of claim 14, wherein the compromised blood flow results from a blood clot or stenosis.

16. The method of claim 14, wherein the UTP, a derivative thereof, or a salt thereof, is administered via a guiding catheter or an IC microcatheter.

17. A method for diagnosing a disease selected from the group consisting of Peripheral Artery Disease (PAD), coronary atherosclerosis, and ischemic heart disease comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to an individual suspected of having said disease,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on the results of the comparison.

18. A method for the induction of maximal coronary hyperemia comprising delivering to an individual in need thereof UTP, a derivative thereof, or a salt thereof.

19. A kit for determining blood flow in a blood vessel comprising:

(a) UTP, a derivative thereof, or a salt thereof as an active diagnostic ingredient, and

(b) instructions for the use thereof in an individual with suspected compromised blood flow.

20. The kit of claim 19, wherein the kit further comprises a guiding catheter or microcatheter.

21. The kit of claim 19, wherein the kit further comprises a physiologically acceptable aqueous carrier.

22. The kit of claim 21, wherein the physiologically acceptable aqueous carrier is saline.

23. The kit of claim 21, wherein the physiologically acceptable aqueous carrier and active diagnostic ingredient are provided in separate containers.

24. A diagnostic composition comprising UTP, a derivative thereof, or a salt thereof in a pharmaceutically acceptable aqueous carrier suitable for administration into a human patient, wherein the composition contains from about 50 to about 400 μ

g/ml of UTP, a derivative thereof, or a salt thereof.

25. The diagnostic composition of claim 24, wherein the composition is delivered to an individual in need thereof in a total volume of about 2 ml to about 10 ml

26. A method for diagnosing renal artery stenosis comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to an individual suspected of having said disease,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on the results of the comparison.

27. A method for screening individuals at risk of developing an atherosclerotic or ischemic disease comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to the individual,

(b) assessing blood flow quantitatively in the vessel by obtaining a value that correlates to blood flow in said vessel,

(c) comparing the obtained value with a reference value, and

(d) determining whether the individual has compromised blood flow based on the results of the comparison.

28. A method for measuring fractional flow reserve (FFR) comprising:

(a) delivering UTP, a derivative thereof, or a salt thereof to a blood vessel in escalating stepwise doses,

(b) monitoring pressure across the blood vessel until distal pressure reaches a minimum value, wherein the minimum value corresponds to maximal blood flow.

29. The method of claim 28, wherein UTP, a derivative thereof, or a salt thereof is delivered by intracoronary infusion.

30. The method of claim 28, wherein FFR measures blood flow in a coronary artery.

31. The method of claim 28, wherein UTP, a derivative thereof, or a salt thereof is administered by a FFR thermodilution catheter, a microinfusion catheter or guiding catheter.

32. The method of claim 28, wherein the escalating stepwise doses are 20, 40, 80, 160, 240, 360, and 400 μ

g/min.