DELIVERY OF AGENTS TO TISSUE

• US 20070106208A1
• Filed: 07/28/2006
• Published: 05/10/2007
• Est. Priority Date: 11/04/2005
• Status: Active Grant

• Current Assignee: Bayer Healthcare LLC (Bayer AG), Biomedical Enterprises Incorporated (Johnson & Johnson)
• Original Assignee: Medrad Incorporated (Bayer AG)
• Inventors: Trocki, Mark, Hirschman, Alan, Uber, Arthur, Cedarholm, Page, Trombley, Frederick, Rhinehart, Edward, Gelblum, Eugene, Reilly, David, Cowan, Kevin
• Granted Patent: US 7,713,232 B2
• Time in Patent Office: Days
• US Class Current: 604/65
• CPC Class Codes: A61J 1/1443 Containers with means for dispensing liquid medicaments in a filtered or sterile way, e.g. with bacterial filters
• CPC Class Codes: A61J 1/1456 using liquid filters
• CPC Class Codes: A61J 1/1475 Inlet or outlet ports
• CPC Class Codes: A61M 31/005 for contrast media
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61M 5/3145 Filters incorporated in syringes
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: G16H 20/17 delivered via infusion or injection

Abstract

A system for injecting an injectate into patient includes a first pressurizable container for holding the injectate; a patient interface in fluid connection with the first pressurizable container, the patient interface being adapted to pass the injectate into tissue of the patient; a powered injector in operative connection with the first pressurizable container to pressurize the injectate; a controller system in operative connection with powered injector; and a stereotactic localization frame adapted to be placed in operative connection with the patient interface to assist in controlling localization of the patient interface. A system for processing cells (and/or other injectate components) includes a container and a plunger adapted to be slidably positioned within the container. The system includes at least one inlet port through which a fluid can enter the system and at least one effluent port through which an effluent can exit the system. The plunger section forms a sealing engagement with the inner wall of the container such that rearward motion of the plunger is adapted to draw fluid into the system via the inlet and forward motion of the plunger is adapted to force effluent out of the system via the effluent port.

Claims

1. A system for injecting an injectate into patient, comprising:

a first pressurizable container for holding the injectate;

a patient interface in fluid connection with the first pressurizable container, the patient interface being adapted to pass the injectate into tissue of the patient;

a powered injector in operative connection with the first pressurizable container to pressurize the injectate;

a controller system in operative connection with powered injector; and

a stereotactic localization frame adapted to be placed in operative connection with the patient interface to assist in controlling localization of the patient interface.

2. The system of claim 1 further comprising a communication system in connection with the controller system to provide information to the controller system of at least one measured parameter, the controller system being adapted to transmit a control signal based at least in part on the measure parameter to control the powered injector.

3. The system of claim 2 further comprising at least one monitoring system adapted to measure at least one physiological property of the patient, the communication system being in connection with the monitoring system to provide information of the measured value of the at least one physiological property to the controller system, the controller system being adapted to transmit a control signal based at least in part on the measured value of the least one physiological property.

4. The system of claim 2 further comprising an imaging system adapted to image a region of the patient to which the injectate is delivered.

5. The system of claim 4 wherein the communication system is in connection with the imaging system to provide information of a measured property from the imaging system to the controller, the controller being adapted to transmit a control signal based at least in part on the measured property from the imaging system.

6. The system of claim 2 further comprising at least one sensor to measure at least one property of the injectate, the sensor being in connection with the communication system to provide information of the measured injection fluid property to the controller.

7. The system of claim 6 wherein the at least one property of the injectate provides a measurement of shear forces on the injectate.

9. The system of claim 1 wherein the first pressurizable container is a first syringe having a first plunger slidably disposed therein to pressurize the injectate, the injector being adapted to effect movement of the first plunger.

10. The system of claim 1 wherein the powered injector is in operative connection with a second pressurizable container, the second pressurizable container being in fluid connection with the first pressurizable container, pressurized fluid from the second pressurizable container being operable to pressurize the injectate within the first pressurizable container.

11. The system of claim 10 wherein the first pressurizable container is a first syringe having a first plunger slidably disposed therein to pressurize the injectate, pressurized fluid from second pressurizable container being operable to effect movement of the first plunger.

12. The system of claim 11 wherein the second pressurizable container is a second syringe having a second plunger slidably disposed therein.

13. The system of claim 1 further comprising a sterile containment system adapted to encompass at least a portion of the first pressurizable container and a portion of the powered injector.

8. The system of claim 8 wherein the at least one property of the injectate is at least one of flow rate or pressure.

14. A container adapted to store and transport an injectate, the container being adapted to have a fluid introduced therein and effluent removed therefrom to effect processing of the injectate.

15. The container of claim 14 wherein the container is adapted to be subjected to freezing and thawing.

16. The container of claim 14 comprising a first port at a first axial position within the container and at least a second port at a second axial position within the container, the first axial position and the second axial position being different.

17. The container of claim 16 wherein the first port and the second port are formed monolithically with the container.

18. The container of claim 16 wherein the first port is on the distal end of a first tube extending through an end closure of the container and the second port is on the distal end of a second tube extending through the end closure the container.

19. The container of claim 18 wherein the end closure is a septum, the first tube is a first piercing member and the second tube is a second piercing member.

20. The container of claim 16 wherein the container encompasses viable cells within a first fluid, at least one of the first axial position and the second axial position being above an axial position of cells settled to a bottom of the container.

21. The container of claim 20 wherein the cells are retinal pigment epithelial cells supported on microspheres, mesenchymal stem cells, multipotent adult progenitor cells, embryonic stem cells, cardiac precursor cells, cardiac cells, beta-islet precursor cells, beta-islet cells, neural precursor cells, or neural cells.

22. The container of claim 14 comprising a divider within the container to create a first fluid path on a first side of the divider via which fluid can enter the container and a second fluid path on a second side of the divider via which fluid can exit the container, the second side fluid path including at least one filter through which fluid can pass but through which at least one component of the injectate cannot pass.

23. The container of claim 21 wherein the container encompasses viable cells within a first fluid and the filter prevents cells from passing therethrough.

24. The container of claim 23 wherein the cells are retinal pigment epithelial cells supported on microspheres, mesenchymal stem cells, multipotent adult progenitor cells, embryonic stem cells, cardiac precursor cells, cardiac cells, beta-islet precursor cells, beta-islet cells, neural precursor cells, or neural cells.

25. A method of processing cells prior to delivery thereof comprising the step of contacting the cells with at least one fluid to decrease the concentration of a hibernation solution in which the cells are transported wherein the occurrences of exposure of the cells to non-sterile air is minimized and the duration of any occurrence of exposure to non-sterile air is minimized.

26. The method of claim 25 wherein the cells are transported in container adapted to store and transport the cells, the container being adapted to have the at least one fluid introduced therein and effluent removed therefrom.

27. The method of claim 26 wherein the cells are retinal pigment epithelial cells supported on microspheres, mesenchymal stem cells, multipotent adult progenitor cells, embryonic stem cells, cardiac precursor cells, cardiac cells, beta-islet precursor cells, beta-islet cells, neural precursor cells, or neural cells.

28. The method of claim 25 wherein the at least one fluid comprises a buffer solution.

29. The method of claim 26 wherein a closed system is used in the processing.

30. The method of claim 29 wherein the closed system comprises a source of the first fluid adapted to be placed in fluid connection the container.

31. The method of 30 wherein the container comprises a first port for introduction of the at least one fluid and a second port for removal of effluent.

32. The method of claim 31 wherein the closed system comprises a pump system to effect flow of the at least on fluid into the container and effluent out of the container.

33. The method of claim 32 wherein the closed system further comprises a first one-way valve in fluid connection with the first port and a second one-way valve in fluid connection with the second port.

34. The method of claim 33 wherein the cells are retinal pigment epithelial cells supported on microspheres, mesenchymal stem cells, multipotent adult progenitor cells, embryonic stem cells, cardiac precursor cells, cardiac cells, beta-islet precursor cells, beta-islet cells, neural precursor cells, or neural cells.

35. The method of claim 31 wherein the container further comprises a third port adapted to provide air into the container and a sterile filter in fluid connection with the third port so that air can move in and out as fluid level changes in the container while maintaining sterility.

36. The method of claim 31 wherein the first port has a first tube extending therethrough to a first length within the container and the second port has a second tube extending therethrough to a second length within the container, the first length being greater than the second length, such that when the container is in a generally upright position and cells are settled to the bottom thereof, the end of the first tube is within the cells and the end of the second tube is above the level of the cells.

37. A system for use in the processing of cells encompassed in a container, the system comprising at least a first fluid path adapted to introduce at least one fluid into the container and at least a second fluid path adapted to remove effluent from the container.

38. The system of claim 37 further comprising a pump system to effect flow of the fluid into the container and flow of effluent from the container.

39. The system of claim 38 further comprising a valve system to control at least flow of the fluid into the container and flow of effluent from the container.

40. The system of claim 39 wherein the valve system comprises at least a first one way valve in fluid connection with the first fluid path and at least a second one way valve in fluid connection with the second fluid path.

41. The system of claim 39 further comprising a controller in operative connection with at least one of the pump system or the valve system.

42. The system of claim 41 wherein the controller comprises a computer processor.

43. The system of claim 37 further comprising a third fluid path adapted to be placed in fluid connection with the container and be placed in connection with a fluid delivery system in which the cells can be loaded for delivery to a patient.

44. The system of claim 37 further comprising at least a fourth fluid path adapted to be placed in fluid connection with the container to remove a sample from the container for analysis.

45. The system of claim 37 further comprising at least a fifth fluid path adapted to introduce air into the container.

46. The system of claim 45 wherein a filter is placed in fluid connection with the fifth fluid path to assist in maintaining sterility.

47. The system of claim 37 further comprising a source of the fluid in fluid connection with the first fluid path.

48. A system for processing cells comprising a container and a plunger adapted to be slidably positioned within the container, the system including at least one inlet port through which a fluid can enter the system and at least one effluent port through which an effluent can exit the system, the plunger section forming a sealing engagement with the inner wall of the container such that rearward motion of the plunger is adapted to draw fluid into the system via the inlet and forward motion of the plunger is adapted to force effluent out of the system via the effluent port.

49. The system of claim 48 wherein the effluent port is adapted to effect delivery of cells therethrough to a patient.

50. The system of claim 48 further comprising an outlet port adapted to effect delivery of cells therethrough to a patient.

51. The system of claim 48 comprising a filter in fluid connection with the effluent port to prevent cells from exiting via the effluent port.

52. The system of claim 48 further comprising a first check valve in fluid connection with the inlet port and a second check valve in fluid connection with the effluent port.

53. The system of claim 48 wherein the plunger comprises a filter disposed therein that allows fluid to pass therethrough but prevents cells from passing therethrough.

54. The system of claim 53 wherein the filter separates the cells from the effluent port.

55. The system of claim 53 wherein the filter also separates the cells from the inlet port.

56. The system of claim 55 further comprising an outlet port in fluid connection with the cells adapted to effect delivery of cells therethrough to a patient.

57. The system of claim 55 wherein the outlet port is adapted to be closed during processing of the cells during which fluid enters the system via the inlet port and effluent exits the system via the effluent port.

58. The system of claim 57 wherein the effluent port is adapted to be closed when the outlet port is opened to deliver cells therethrough.

59. The system of claim 56 wherein the inlet port is in fluid connection with a passage through the plunger so that the fluid can enter the plunger and pass through the filter.

60. The system of claim 56 wherein the effluent port is in fluid connection with a passage through the plunger so that the effluent can pass through the filter and exit the efluent port.

61. The system of claim 48 wherein the plunger includes a sealing member adapted for form a sealing engagement with an interior wall of the container.

62. A plunger for use in connection with a container encompassing cells to effect processing of the cells, the plunger comprising a filter through which fluid can pass but cells cannot pass and a sealing member adapted for form a sealing engagement with an interior wall of the container.

63. The plunger of claim 62 further comprising an inlet port to introduce fluid into the plunger to pass through the filter to enter the container and an effluent port through which effluent can flow through the filter to exit the container.

64. The plunger of claim 63 further comprising a one way valve in fluid connection with the inlet port.

65. The plunger of claim 64 further comprising a one way valve in fluid connection with the effluent port.