WO2009073918A2

WO2009073918A2 - Agent delivery device and method

Info

Publication number: WO2009073918A2
Application number: PCT/AU2008/001813
Authority: WO
Inventors: Ashish Diwan; Divya Diwan
Original assignee: Cellixe Pty Ltd
Priority date: 2007-12-10
Filing date: 2008-12-09
Publication date: 2009-06-18
Also published as: WO2009073918A3

Abstract

A device (10) for the delivery of an agent to a site in a patient's body at which tissue is to be treated comprises a delivery conduit (12) having a proximal end attachable to a source (14) of the agent. An emitter structure (16) is arranged at a distal end of the delivery conduit (12), the emitter structure (16) defining a plurality of spaced discharge apertures (18) through which the agent is delivered to the site. The emitter structure (16) is configured to promote diffuse distribution of the agent throughout the tissue at the site in the patient's body.

Description

"Agent delivery device and method"

Cross-Reference to Related Applications

The present application claims priority from United States of America Provisional Patent Application No 61/012,708 filed on 10 December 2007, the contents of which are incorporated herein by reference.

Field

This disclosure relates, generally, to the delivery of an agent to a site in a patient's body and, more particularly, to a device for the delivery of an agent and to a method of delivering an agent to a site in a patient's body.

Background

Back and/or neck pain (collectively referred to as axial pain) is a severe cause of personal and social disability and is the cause of the loss of a great deal of work days with a resultant reduction in productivity.

Axial pain is categorised as chronic if it persists for a period of more than three months. Further, persons who have suffered one episode of axial pain are likely to continue to suffer multiple episodes. Such pain can be categorised as moderate or severe, can present as multiple disabling episodes or can present as a background of low grade pain. In certain circumstances, although the causes are present no pain may be present and the causes manifest themselves in other ways.

The majority of axial pain can be attributed to disturbances within motion segment(s) of the spinal column and generally involves an intervertebral disc. These disturbances are, at least initially, biochemical in nature due to cellular dysfunction and then become a combination of biochemical and biomechanical disturbances that continue to cause ongoing pain.

An intervertebral disc consists of a central proteoglycan-rich gelatinous region called the nucleus pulposus, or nucleus, and an outer collagen fibre-rich annulus fibrosus, or annulus. Damage or injury to either or both of these structures leading to degenerative changes is a major source of axial pain. lntradiscal treatments in the past have consisted of injecting a proteolytic enzyme extracted from paw-paw (chymopapain) and intradiscal steroids. These have been injected using a standard needle concentrating the delivery of the agent in a small area. As far as the Applicant is aware, there is, to date, no remedy available to manage axial pain sufferers by slowing or inhibiting the degeneration of the nucleus or the annulus of the intervertebral disc. A therapeutic agent which the Applicant believes will address this issue is described in its co-pending International Patent Application No. PCT/AU2008/000243, dated 22 February 2008 and entitled "Composition and method for the treatment or prevention of spinal disorders" and US Provisional Patent Application No. 61/189,726, dated 22 August 2008 and entitled "Composition and method for the treatment or prevention of spinal disorders", the disclosures of both which are incorporated in this specification by reference in their entirety. This disclosure relates to a delivery device for delivering the therapeutic agent to a site in a patient's body at which tissue is to be treated.

Summary

In a first aspect, there is provided a device for the delivery of an agent to a site in a patient's body at which tissue is to be treated, the device comprising a delivery conduit having a proximal end attachable to a source of the agent; and an emitter structure at a distal region of the delivery conduit, the emitter structure defining a plurality of spaced discharge apertures through which the agent is delivered to the site and the emitter structure being configured to promote diffuse distribution of the agent throughout the tissue at the site in the patient's body.

Preferably, the apertures are dimensioned to achieve a substantially uniform flow rate of the agent through the apertures. The apertures may vary in size along the conduit to promote the substantially uniform discharge flow rate through the apertures. It will be appreciated that the apertures increase in size from a proximal aperture to a distal aperture to achieve the substantially uniform flow rate through the apertures. By "substantially uniform" is meant that the volume of agent discharged through each of the apertures per unit of time is substantially the same.

The emitter structure may be steerable. Thus the emitter structure may include a pull wire attached to the emitter structure, either within a lumen of the emitter structure or embedded in a wall of the emitter structure. Instead, the device may include a guide element for guiding the emitter structure into an operative position at the site in which diffuse distribution of the agent is promoted. The guide element may be a guide wire of a preformed shape extending through a lumen of the emitter structure. The guide wire may, for example, be of a shape memory alloy such as Nitinol^®. A wall of the emitter structure may be reinforced to maintain the integrity of the emitter structure in situ. More particularly, the emitter structure may be reinforced to inhibit collapsing of the lumen of the emitter structure as a result of pressure applied by the tissue at the site.

In an embodiment, the emitter structure may be shaped to form a loop at the site in the patient's body. In another embodiment, the emitter structure may be substantially annular. In still a further embodiment, the emitter structure may be forked into a plurality of branches. In this specification it is to be understood that "forked" may mean more than two branches.

The emitter structure may be formed integrally with the delivery conduit as a one-piece unit. The device may include a working cannula via which the unit is able to be delivered to the site in the patient's body percutaneously in a minimally invasive manner.

The emitter structure may carry at least one radio-opaque marker.

Each aperture may include a flow control device for inhibiting back flow of the agent into the emitter structure. The flow control device may be a one-way valve. The agent may be a therapeutic agent. Instead, the agent may be a diagnostic agent that may be: (a) a pain suppressor such as zylocaine; (b) a pain provocator such as saline or (c) an agent for imaging used as a disc visualiser being a radio opaque material such as BaSO₄ or iodine dye or MRI echo material like gadallonium or gamma scanner sensitive radio-isotopes tagged to diagnostic molecules. In a second aspect, there is provided a system for the delivery of an agent to a site in a patient's body, the system including a device as described above; and a source of the agent attached to the proximal end of the delivery conduit of the device. The source of the agent may be a fluid dispenser, such as a syringe.

In a third aspect, there is provided a device for the delivery of an agent to an intervertebral disc, the device including a delivery conduit having a proximal end attachable to a source of the agent; and an emitter structure at a distal region of the delivery conduit, the emitter structure being at least partially receivable within an interior of the disc and defining a plurality of spaced discharge apertures through which the agent is delivered to a part of the disc and the emitter structure further being configured to extend about the part of the disc to promote diffuse distribution of the agent throughout the part of the disc.

In a fourth aspect, there is provided a method of delivering an agent to a site in a patient's body, the method including accessing the site; inserting an emitter structure at least partially in the site, the emitter structure defining a plurality of spaced discharge apertures through which the agent is delivered to tissue at the site; manipulating the emitter structure so that the emitter structure at least partially surrounds the tissue to be treated; and discharging the agent through the apertures in such a manner so as to promote diffuse distribution of the therapeutic agent throughout the tissue at the site.

The method may include accessing the site percutaneously in a minimally invasive manner.

Further, the method may include guiding the emitter structure to the site in an inoperative configuration and, at the site, arranging the emitter structure in an operative configuration to at least partially surround the tissue. Thus, the method may include steering the emitter structure into its operative configuration. Instead, or in addition, the method may include guiding the emitter structure into its operative configuration.

The method may include discharging the agent through the apertures at a substantially uniform flow rate through all of the apertures. Preferably, the method includes discharging the agent through apertures that vary in size along the conduit to effect the substantially uniform flow rate through the apertures.

The method is intended particularly for delivering the agent to an intervertebral disc, and the method may include performing an annulotomy in an annulus of the disc and distributing the therapeutic agent substantially uniformly within the disc. The method may be used for implantation of the agent either post-nucleotomy or without the need for a nucleotomy depending on the state of degeneration of the disc.

The method may include deploying the emitter structure under one of endoscopic visualisation and fluoroscopic guidance. Hence, the emitter structure may carry at least one radio-opaque marker. Further, the method may include, once delivery of the agent has been completed, inhibiting back flow of the agent through the apertures into the emitter structure.

Brief Description of Drawings

Fig. 1 shows a schematic, three dimensional view of a first embodiment of a device for the delivery of an agent to a site in a patient's body at which tissue is to be treated;

Fig. 2 shows a schematic, plan view of the device of Fig. 1 ;

Fig. 3 shows, on an enlarged scale, a distal part of the device encircled by circle ¹A¹ in Fig. 2; Fig. 4 shows a schematic, sectional plan view of a second embodiment of a device for the delivery of an agent to a site in a patient's body at which tissue is to be treated;

Fig. 5 shows a schematic, three dimensional side view of a third embodiment of a device for the delivery of an agent to a site in a patient's body at which tissue is to be treated;

Fig. 6 shows a sectional side view of the device of Fig. 2;

Fig. 7 shows a schematic, sectional plan view of the device of Fig. 2;

Fig. 8 shows a schematic, plan view of a fourth embodiment of a device for the delivery of an agent to a site in a patient's body at which tissue is to be treated; and

Figs. 9-1 1 show various stages in the deployment of the device of Fig. 8, in use.

Detailed Description of Exemplary Embodiments

Referring initially to Figs. 1-3 of the drawings, reference numeral 10 generally designates a first embodiment of a device for the delivery of an agent to a site in a patient's body at which tissue is to be treated. The device has particular, but not necessarily exclusive, application in the treatment of a nucleus of an intervertebral disc and will be described with reference to that application below. The tissue to be treated is therefore the nuclear tissue of the intervertebral disc. Those skilled in the art will, however, readily appreciate that the device has numerous other applications.

The device 10 includes a delivery conduit 12 having a proximal end attachable to a source 14 of the agent, which may be a therapeutic agent or a diagnostic agent, the device 10 and the source 14 forming an embodiment of system for the delivery of the agent to a site in a patient's body. The source 14 is, typically, a syringe for dispensing the agent through the delivery conduit 12.

An emitter structure 16 is arranged at the distal end of the delivery conduit 12. The emitter structure 16 defines, as shown in greater detail in Fig. 2 of the drawings, a plurality of discharge apertures 18 arranged at longitudinally spaced intervals. The discharge apertures 18 are configured to effect uniform, diffuse distribution of the agent throughout an intervertebral disc nucleus 20 (Fig. 1) of an intervertebral disc 22. To effect the uniform, diffuse distribution of the agent, the diameter of the apertures increases from a proximal aperture 18, arranged closer to the distal end of the delivery conduit 12, to a distal aperture 18 distally of the emitter structure 16. In such a fashion, there is a substantially uniform flow rate of the agent through the apertures 18 of the emitter structure 16 to facilitate the diffuse distribution of the agent throughout the nucleus 20 of the intervertebral disc 22. The emitter structure 16 may have a diameter in a range from about 0.1mm to about 3.5mm.

In the embodiment shown in Figs. 1-3 of the drawings, the emitter structure 16 is formed of a suitable, reinforced plastics material. The reinforcing is, for example, in the form of bands (not shown in this embodiment) arranged at longitudinally spaced intervals to retain the emitter structure 16 in an open condition against pressure exerted by the tissue of the nucleus 20, in use.

The emitter structure 16 is steerable to adopt a loop shape in the nucleus 20 as shown in Figs. 1 and 2. To facilitate this, the emitter structure 16 has a steering wire or pull wire 24 embedded in its wall. Manipulation of the steering wire 24 is carried out by a clinician with the assistance of, for example, fluoroscopy, to ensure that the emitter structure 16 adopts a spread out configuration within the nucleus 20 of the intervertebral disc 22.

To introduce the emitter structure 16 into the nucleus 20 of the disc 22, an annulotomy is formed on an annulus 26 of the intervertebral disc 22. The annulotomy results in an access opening 28 being formed in the annulus 26 of the disc 22. A working cannula 30 is inserted percutaneously through the patient's skin in a minimally invasive manner. The working cannula 30 may also be used for performing the annulotomy on the annulus 26. Thus, a tip 32 (Fig. 2)of the working cannula 30 may be sharpened or bevelled for effecting perforation of the annulus 26.

Once the tip 32 of the working cannula 30 has been inserted into the nucleus 20 through the opening 28, the emitter structure 16 of the delivery device 10 is extended through the end 32 of the working cannula 30 to adopt the position shown, for example, in Fig. 2 of the drawings and enabling a diffuse, substantially uniform distribution of the agent throughout the nucleus 20 to be effected.

Once delivery of the agent has been completed a positive pressure is maintained in the emitter structure 16 to inhibit back flow of the agent through the apertures into the interior of the emitter structure 16. This is done in one of a number of ways such as (a) having a non-return valve in each aperture; (b) maintaining a continuous pressure, for example, by a motorised pneumatic device (not shown) while withdrawing the emitter structure 16 into the working cannula 30 or (c) pumping air into the emitter structure 16 behind the agent.

Where the agent is a therapeutic agent, it is in the form of a composition having the potential to augment production of the intervertebral disc nucleus extra-cellular matrix for inhibiting degeneration of the nucleus 20 and, consequently, effecting repair of a degenerate nucleus 20. An example of a suitable therapeutic agent is BMP-13 as described in the above referenced patent applications of the Applicant. In the case where the agent is a diagnostic agent, it is one of: (a) a pain suppressor such as zylocaine; (b) a pain provocator such as saline or (c) an agent for imaging used as a disc visualiser being a radio opaque material such as BaSO₄ or iodine dye or MRI echo material like gadallonium or gamma scanner sensitive radio-isotopes tagged to diagnostic molecules.

In Fig. 4 of the drawings, an embodiment of the device similar to that shown in Figs. 1-3 is illustrated. With reference to Figs. 1-3, like reference numerals refer to like parts, unless otherwise specified. In this embodiment, instead of the steering wire 24 arranged in the wall of the emitter structure 16, the device 10 includes a pre-formed guide wire 34 received in a lumen of the device 10. In use, once the annulotomy has been performed on the annulus 26 of the disc 22 and the working cannula 30 has been positioned relative to the disc 22, the guide wire 34 is ejected through the distal end of the emitter structure 16 to adopt a loop shape as illustrated in Fig. 4 of the drawings. The emitter structure 16 is then ejected through the opening 32 of the working cannula

30 along the guide wire 34 and follows the guide wire 34 to adopt a similar loop-shape.

Referring now to Figs. 5-7 of the drawings, a further embodiment of a device for the delivery of an agent to the nucleus 20 of the intervertebral disc 22 is illustrated.

Once again, with reference to the previous drawings, like reference numerals refer to like parts, unless otherwise specified.

In this embodiment, instead of a loop-shaped emitter structure 16, the emitter structure 16 is forked having a plurality of branches 36. Each of the branches 36 branches off the delivery conduit 12. Further, each branch 36 defines a set of spaced discharge apertures 18 for delivery of the therapeutic agent or diagnostic agent to the nucleus 20 of the intervertebral disc 22. It will be appreciated that, as in the previous embodiments, the apertures 18 in each branch 36 increase in size from a proximal aperture 18 to a distal aperture 18. As illustrated schematically in Fig. 5 of the drawings, when the nucleus 20 degenerates, it shrinks and the branches 36 of the emitter structure 16 are configured to surround the nucleus 20, both in a plane normal to, and in a plane parallel to, a medial plane of the nucleus 20 to effect the diffuse distribution of the agent through the nucleus 20 of the intervertebral disc 22.

Referring now to Figs. 8-11 of the drawings, yet a further embodiment of the device 10 is illustrated. As in the case of the previous embodiments, like reference numerals refer to like parts, unless otherwise specified. In this embodiment, the emitter structure 16, in its operative configuration, is substantially annular defining a closed loop in the nucleus 20 of the intervertebral disc 22 upon manipulation of the emitter structure 16 into its operative configuration in the nucleus 20 of the intervertebral disc 22.

In this embodiment, the emitter structure 16 is, prior to delivery into the intervertebral disc 22, arranged in a collapsed configuration in the working cannula 30. Once the distal end 32 of the working cannula has been inserted through the opening 28 in the annulus 26 of the intervertebral disc 22, the emitter structure 16 is extended from the working cannula 30 and expands to adopt the annular shape shown in Fig. 8 of the drawings. To assist in enabling the emitter structure 16 to expand as described, an outer perimeter of the device 10 carries a wire 38 of a shape memory alloy. More particularly, the wire 38 is of Nitinol^® which is preformed to have an annular distal part

40. Thus, when the emitter structure 16 is extended from the working cannula 30, the emitter structure 16 is formed into the annular shape illustrated.

In this embodiment, the bands which provide reinforcing for the device 10 are illustrated at 42 in Fig. 8 of the drawings. These bands 42 also provide strength in a longitudinal direction of the device 10.

Accordingly, it is an advantage of the described embodiments that a device 10 is provided which facilitates diffuse, substantially uniform distribution of an agent, be it a therapeutic agent or a diagnostic agent, in tissue at a site in a patient's body to be treated. In so doing, because the agent is more evenly distributed throughout the tissue, more effective treatment of the tissue can be effected. It is a further advantage of the described embodiments that they can be used for targeting a part of the tissue and concentrating the agent delivery in that targeted part of the tissue.

It is yet another advantage of the described embodiments that a device 10 is provided which can be positioned in a minimally invasive manner thus reducing trauma for the patient and reducing time for recovery.

In the case of the application of the device 10 in treating the nucleus 20 of an intervertebral disc 22, it is an advantage of the described embodiments that an agent can be delivered to the nucleus which, the applicant believes, will reduce the incidence of axial pain in patients thereby reducing patient's discomfort as well as reducing the work days lost due to occurrence of axial pain.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the specific embodiments without departing from the scope of the disclosure as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

CLAIMS:

1. A device for the delivery of an agent to a site in a patient's body at which tissue is to be treated, the device comprising a delivery conduit having a proximal end attachable to a source of the agent; and an emitter structure at a distal region of the delivery conduit, the emitter structure defining a plurality of spaced discharge apertures through which the agent is delivered to the site and the emitter structure being configured to promote diffuse distribution of the agent throughout the tissue at the site in the patient's body.

2. The device of claim 1 in which the apertures are dimensioned to achieve a substantially uniform flow rate of the agent through the apertures.

3. The device of claim 2 in which the apertures vary in size along the conduit to promote the substantially uniform discharge flow rate through the apertures.

4. The device of any one of the preceding claims in which the emitter structure is steerable.

5. The device of claim 4 which includes a guide element for guiding the emitter structure into an operative position at the site in which diffuse distribution of the agent is promoted.

6. The device of claim 5 in which the guide element is a guide wire of a preformed shape extending through a lumen of the emitter structure.

7. The device of any one of the preceding claims in which a wall of the emitter structure is reinforced to maintain the integrity of the emitter structure in situ.

8. The device of any one of the preceding claims in which the emitter structure is shaped to form a loop at the site in the patient's body.

9. The device of any one of claims 1 to 7 in which the emitter structure is substantially annular.

10. The device of any one of claims 1 to 7 in which the emitter structure is forked into a plurality of branches.

1 1. The device of any one of the preceding claims in which the emitter structure is formed integrally with the delivery conduit as a one-piece unit.

12. The device of claim 1 1 which includes a working cannula via which the unit is able to be delivered to the site in the patient's body percutaneously in a minimally invasive manner.

13. The device of any one of the preceding claims in which the emitter structure carries at least one radio-opaque marker.

14. The device of any one of the preceding claims in which each aperture includes a flow control device for inhibiting back flow of the agent into the emitter structure.

15. A system for the delivery of an agent to a site in a patient's body, the system including a device as claimed in any one of the preceding claims; and a source of the agent attached to the proximal end of the delivery conduit of the device.

16. The system of claim 15 in which the source of the therapeutic agent is a fluid dispenser.

17. A device for the delivery of an agent to an intervertebral disc, the device including a delivery conduit having a proximal end attachable to a source of the therapeutic agent; and an emitter structure at a distal region of the delivery conduit, the emitter structure being at least partially receivable within an interior of the disc and defining a plurality of spaced discharge apertures through which the therapeutic agent is delivered to a part of the disc and the emitter structure further being configured to extend about the part of the disc to promote diffuse distribution of the therapeutic agent throughout the part of the disc.

18. A method of delivering an agent to a site in a patient's body, the method including accessing the site; inserting an emitter structure at least partially in the site, the emitter structure defining a plurality of spaced discharge apertures through which the agent is delivered to tissue at the site; manipulating the emitter structure so that the emitter structure at least partially surrounds the tissue to be treated; and discharging the agent through the apertures in such a manner so as to promote diffuse distribution of the agent throughout the tissue at the site.

19. The method of claim 18 which includes accessing the site percutaneously in a minimally invasive manner.

20. The method of claim 19 which includes guiding the emitter structure to the site in an inoperative configuration and, at the site, arranging the emitter structure in an operative configuration to at least partially surround the tissue.

21. The method of claim 20 which includes steering the emitter structure into its operative configuration.

22. The method of claim 20 which includes guiding the emitter structure into its operative configuration.

23. The method of any one of claims 18 to 22 which includes discharging the agent through the apertures at a substantially uniform flow rate through all of the apertures.

24. The method of claim 23 which includes discharging the agent through apertures that vary in size along the conduit to effect the substantially uniform flow rate through the apertures.

25. The method of any one of claims 18 to 24 which is intended for delivering the agent to an intervertebral disc, the method including perforating an annulus of the disc and distributing the agent substantially uniformly within the disc.

26. The method of claim 25 which includes perforating the annulus by performing an annulotomy on the annulus of the disc.

27. The method of any one of claims 18 to 26 which includes deploying the emitter structure under one of endoscopic visualisation and fluoroscopic guidance.

28. The method of any one of claims 18 to 27 which includes, once delivery of the agent has been completed, inhibiting back flow of the agent through the apertures into the emitter structure.