Methods for controlled depth injections into interior body cavities

• US 6,835,193 B2
• Filed: 10/23/2001
• Issued: 12/28/2004
• Est. Priority Date: 07/10/2001
• Status: Expired due to Fees

• Current Assignee: Myocardial Therapeutics Incorporated
• Original Assignee: Myocardial Therapeutics Incorporated
• Inventors: Kornowski, Ran, Epstein, Stephen, Fuchs, Shmuel
• Primary Examiner(s): Casler, Brian L.
• Assistant Examiner(s): WILLIAMS, CATHERINE SERKE
• Application Number:
  US10/000,851
• Publication Number:
  US 20030028172A1
• Time in Patent Office: 1,162 Days
• Field of Search: 604/22, 604/48, 604/200, 604/95.01, 604/73, 604/181, 604/187, 604/131, 604/141, 604/143, 604/148, 604/264, 604/507, 604/523, 604/533, 604/158, 604/164.01, 604/280, 606/167, 606/170, 600/434, 600/858
• US Class Current: 604/507
• CPC Class Codes: A61B 2090/062 penetration depth
• CPC Class Codes: A61M 2025/0089 Single injection needle protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip
• CPC Class Codes: A61M 2202/0021 removed from and reintroduced into the body, e.g. after treatment
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61M 2205/75 with filters
• CPC Class Codes: A61M 25/0084 being one or more injection needles

Abstract

A flexible tissue injection catheter is used to accomplish injections at a precisely controlled depth of precisely controlled volumes of a therapeutic or diagnostic agent into an interior body cavity, such as the epicardium or myocardium of the heart. In one embodiment, the invention method includes repeated injections at spaced intervals along the myocardium or epicardium of sterile fluid containing autologous bone marrow aspirate to promote angiogenesis. For myocardial injection, depth penetration is controlled by using a catheter that allows the operator to control depth penetration by means of an adjustable needle stop attached to the catheter handle. In another embodiment depth penetration during epicardial injections is controlled by use of an injection catheter having an operator-controlled adjustable needle stop that produces a sensible signal, such as a visible or audible signal, marking each increment of needle tip exposed by operation of the adjustable needle stop.

Claims

1. A method for injecting a therapeutic fluid a controlled distance into the surface of an interior body cavity in a subject in need thereof, said method comprising:

(a) introducing a catheter into the interior of a body cavity by advancing the catheter through the vascular system of the subject, said catheter comprising;

i) an elongate hollow catheter body having a proximal end and a distal end with a flexible portion at the distal end thereof, said catheter body being sized and constructed to be advanced intravascularly into an interior body cavity of a subject;

ii) a hollow needle housed throughout the catheter body, said needle having a distal portion with a sharp tip and a proximal portion in fluid communication with a fluid source, said needle further having a retracted needle position wherein the sharp tip of the needle is disposed within the catheter body, and an advanced needle position wherein the sharp tip of the needle extends a fixed distance beyond a distal end face of the catheter body,

iii) a needle stop attached to the needle that tethers the distal portion of the needle during flexure while the proximal portion of the needle remains freely slideable within the catheter body, and

iv) an advancement mechanism attached to the needle for advancing the needle distally a fixed distance to the advanced needle position;

wherein the needle stop prevents withdrawal of the distal portion of the needle into the catheter body upon flexure of the catheter prior to actuation of the advancement mechanism to advance the needle to the advanced needle position, thereby exposing a fixed length of the sharp tip of the needle;

(b) contacting the surface of the body cavity with the distal end face of the catheter body,

(c) advancing the sharp distal portion of the hollow needle the controlled distance into the surface of the body cavity; and

(d) introducing a therapeutic amount of a therapeutic fluid into the surface of the body cavity through the sharp tip of the hollow needle.

2. The method of claim 1, wherein a controlled amount of the fluid is administered.

3. The method of claim 1, wherein the controlled amount is in the range from about 0.1 ml to about 3 ml.

4. The method of claim 1, wherein the therapeutic fluid is introduced into the musculature of the heart.

5. The method of claim 4, wherein the catheter is attached to a source of substantially sterile fluid comprising cells autologous to the subject and the body cavity is the interior of the heart of the subject.

6. The method of claim 1, wherein the sharp distal portion of the needle is advanced into the surface a distance in the range from about 0.1 cm to about 2.0 cm.

7. The method of claim 5, wherein the surface is the myocardium of the heart of the subject.

8. The method of claim 7 wherein the method is repeated such that the fluid is administered at a plurality of spaced locations on the myocardium to promote transmyocardial revascularization.

9. The method of claim 8, wherein the amount of the fluid injected is controlled to be in the range from about 0.05 ml to about 5 ml at each of the spaced locations.

10. The method of claim 8, wherein the catheter is introduced into the interior of the heart during a cardiac surgical procedure.

11. The method of claim 10 wherein the catheter is introduced into the interior of the heart during beating heart surgery.

12. The method of claim 5, wherein the fluid further comprises one or more growth factors suitable for stimulating angiogenesis.

13. The method of claim 12, wherein the growth factor is selected from the group consisting of human vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and HIF-1.

14. The method of claim 5, wherein the fluid contains at least one polynucleotide encoding a growth factor suitable for stimulating angiogenesis.

15. The method of claim 14 wherein the polynucleotide encodes a growth factor selected from the group consisting of VEGF, bFGF, and HIF-1.

16. The method of claim 14 wherein the polynucleotide encodes a growth factor selected from the group consisting of PD-ECGF, EGF, TNFα

, and TGFα

.

17. The method of claim 1, wherein the fluid comprises autologous bone marrow aspirate or bone marrow cells in a substantially sterile condition.

18. The method of claim 1, wherein the fluid comprises autologous bone marrow cells in a substantially sterile condition.

19. The method of claim 18, wherein the bone marrow cells comprise angioblasts.

20. The method of claim 5, wherein the amount of the fluid introduced is precisely controlled by a pressure actuator in communication with the fluid source.

21. The method of claim 1, wherein the subject is a human.

22. The method of claim 1, wherein the catheter further comprises a deflection mechanism operable from the exterior of the catheter body via a tip deflector actuator for causing the distal flexible portion to deflect curvilinearly to address the surface.

23. The method of claim 1, wherein the advancement mechanism of the catheter comprises a needle actuator having a depressible plunger with plunger depth stop and spring-loaded return, wherein the plunger is depressed to advance the sharp distal portion of the injector needle the controlled distance into the surface of the body cavity.

24. The method of claim 5, wherein the catheter further comprises an electroconductive tip portion at the distal tip of the catheter body that is electrically connected to an electrical connector at the proximal portion of the catheter body and wherein the method further comprises using the electroconductive tip to determine when the distal end of the catheter contacts the surface of the myocardium.

25. A method for promoting angiogenesis of an area of a heart, said method comprising:

(a) introducing a catheter into the interior of the heart by advancing the catheter through the vascular system of the subject, said catheter comprising;

i) an elongate hollow catheter body having a proximal end and a distal end with a flexible portion at the distal end thereof, said catheter body being sized and constructed to be advanced intravascularly into an interior body cavity of a subject;

ii) a hollow needle housed throughout the catheter body, said needle having a distal portion with a sharp tip and a proximal portion in fluid communication with a fluid source, said needle further having a retracted needle position wherein the sharp tip of the needle is disposed within the catheter body, and an advanced needle position wherein the sharp tip of the needle extends a fixed distance beyond a distal end face of the catheter body,

iii) a needle stop attached to the needle that tethers the distal portion of needle during flexure while the proximal portion of the needle remains freely slideable within the catheter body, and

iv) an advancement mechanism attached to the needle for advancing the needle distally a fixed distance to the advanced needle position;

wherein the needle stop prevents withdrawal of the distal portion of the needle into the catheter body upon flexure of the catheter prior to actuation of the advancement mechanism to advance the needle to the advanced needle position, thereby exposing a fixed length of the sharp tip of the needle;

(b) contacting the myocardium of the heart with the distal end face of the catheter body;

(c) advancing the sharp distal portion of the hollow needle the controlled distance into the myocardium; and

(d) introducing a therapeutic amount of an angiogenesis-promoting fluid a precisely controlled depth into the myocardium at multiple spaced locations through the sharp tip of the hollow needle.

26. The method of claim 25, wherein the angiogenesis promoting fluid comprises cells autologous to the subject and the fluid is in a substantially sterile condition.

27. The method of claim 26, wherein the amount of the angiogenesis-promoting fluid is precisely controlled to be in the range from about 0.1 ml to about 3 ml.

28. The method of claim 27, wherein the controlled distance is in the range from about 0.1 cm to about 2.0 cm.

29. The method of claim 28, wherein the method is repeated such that the angiogenesis-promoting fluid is administered at a plurality of spaced locations on the myocardium to promote transmyocardial revascularization.

30. A method for promoting angiogenesis of an area of a heart, said method comprising:

(a) introducing a hollow needle housed throughout a catheter body a precisely controlled distance into the epicardium of the heart of the subject during a surgical procedure, the needle having a needle stop that tethers the distal portion of the needle during flexure while the proximal portion of the needle remains freely slidable within the catheter body, and

(b) injecting an angiogenesis promoting fluid comprising autologous bone marrow aspirate of the subject in a substantially sterile condition into the epicardium via the hollow needle at a plurality of spaced locations;

wherein therapeutic fluid is introduced at a controlled depth in the range from about 0.1 cm to about 2 cm and wherein the volume of the fluid introduced at each of the locations is controlled to be in the range from about 0.1 ml to about 2.0 ml.

31. The method of claim 30 wherein the hollow needle is contained in an injection catheter and wherein the depth of needle penetration is controlled by an operator-controlled adjustable needle stop fixedly attached to distal portion of the needle, and

wherein the method further comprises the operator exposing one or more precisely controlled increments of the distal tip of the needle by sliding the needle distally through one or more of a series of positions within the needle stop and wherein the needle stop provides a sensible signal to the operator that indicates how many of the precisely controlled increments of the distal tip have been extended from within the needle stop by the operator sliding the needle distally and wherein the depth of needle penetration is controlled by the length of the distal tip of the needle exposed by the operator.

32. The method of claim 30, wherein the adjustable needle stop comprises in co-axial arrangement:

a substantially cylindrical outer needle holder, and

a needle carriage having an interior shaped to receive the distal portion of the injection needle, said needle carriage being slideably mounted within the needle holder for movement between a recessed position, in which the distal tip of the needle does not protrude from the distal end of the needle holder, and a series of progressively advanced positions, in which the distal tip of the needle is advanced to expose the precisely controlled increments of the distal tip thereof; and

a locking mechanism for locking longitudinal movement of the needle carriage within the needle holder.

33. The method of claim 31, wherein each sensible signal corresponds to advancement of the needle tip an increment of 0.5 mm to about 2.0 mm.

34. The system of claim 31, wherein the sensible signal is a flash of light.

35. The system of claim 31, wherein the sensible signal is an audible and/or tactile signal.

36. The system of claim 32, wherein the needle holder comprises a flexible detent extending from the proximal end of the holder, and the exterior of the needle carriage comprises a longitudinal series of circumferential notches shaped to sequentially receive the flexible detent as the needle carriage slides within the needle holder, causing the detent to move from one notch to an adjoining notch along the series of circumferential notches so as to generate the audible and/or tactile signal.

37. The method of claim 32, wherein the amount of the angiogenesis-promoting fluid is precisely controlled to be in the range from about 0.1 ml to about 1 ml.

38. The method of claim 32, wherein the controlled distance is in the range from about 0.1 cm to about 2.0 cm.