The present invention relates to drug delivery apparatus and in particular to improved neurological drug delivery apparatus comprising a skull mountable percutaneous fluid delivery device.
The drug treatment of a number of neuro-degenerative disorders, hereditary neurological disorders, brain tumours and other diseases of the nervous system are compromised by the presence of the blood brain barrier which prevents the transfer of drugs from the vascular system or cerebrospinal fluid into the brain substance. Examples of drugs which do not adequately cross the blood brain barrier include protein molecules such as neurotrophins, monoclonal antibodies, viral particles for delivery of gene therapy, as well as a number of cytotoxic drugs for the treatment of tumours. It has been described previously how such drugs can be delivered to the brain by direct infusion into the parenchyma via one or more indwelling catheter. For example, a guide tube and catheter system is described in U.S. Pat. No. 6,609,020. A catheter with a small external diameter that can be precisely positioned in the brain is described in WO2003/077785. Percutaneous access ports have also been described in WO2008/062173 and WO2011/098769.
The percutaneous fluid delivery devices described in WO2011/098769 comprise a subcutaneous base portion that can be inserted into a recess formed in bone. One or more features on the base portion act to grip the bone and thereby secure the device to the subject. Although such a device performs well, it has been found that detachment of the device may occur when implanted in certain animal models. The present invention thus relates to an improvement to the percutaneous fluid delivery device of WO2011/098769.
According to a first aspect of the invention, an implantable percutaneous fluid delivery device is provided that comprises;
The present invention thus relates to an implantable percutaneous fluid delivery device or port unit for use in delivering fluid, such as therapeutic agents, to selected targets within the body. The implantable percutaneous fluid delivery device has one or more outlets or ports that are separately connectable to one or more implanted catheter devices. The implantable percutaneous fluid delivery device is particularly suited for use in delivering therapeutic agents to targets within the brain using one or more associated implanted intraparenchymal catheter devices.
The implantable percutaneous fluid delivery device comprises a subcutaneous base portion comprising one or more ports for supplying fluid to one or more implanted catheter devices. The term subcutaneous as used herein is intended to define a location below the outer surface of the skin. As described below, the subcutaneous base portion is preferably implantable below all of the skin. A percutaneous portion is also provided as part of the device that extends from the subcutaneous base portion and comprises an extracorporeal surface. As would be understood by those skilled in the art, when implanted a percutaneous device crosses the skin to provide a connection between the inside and outside of the body. The one or more ports of the subcutaneous base portion are accessible from the extracorporeal surface of the percutaneous portion; in other words, the extracorporeal surface (i.e. a surface accessible from outside of the body) provides fluidic access to the one or more outlet ports of the subcutaneous base portion of the device. It should be noted that the subcutaneous base portion and percutaneous portion may be formed together or may be formed as separate components that are attached together before use.
The subcutaneous base portion of the device of the first aspect of the present invention has one or more anchoring features for directly anchoring the subcutaneous base portion to the bone. In particular, the one or more anchoring features comprise at least one radially protruding wing. The provision of such a radially protruding wing has been found to stabilise the device and allow more secure attachment to bone. This is especially advantageous when implanting the device in thin skull bones that are covered in muscle. The device is thus preferably used for non-human subjects, such as primates.
Any number of radially protruding wings may be provided. Advantageously, the device comprises a plurality of radially protruding wings. Preferably, three or more radially protruding wings are provided. In a preferred embodiment, three radially protruding wings are provided; these may be spaced apart from one another by approximately 120 degrees. Alternatively, three radially protruding wings may be provided that are spaced apart by approximately 90 degrees.
The device may comprise a subcutaneous base portion having a central hub for press fit attachment to a hole formed in the skull. The central hub may include any of the features described in WO2011/098769. In addition, said at least one radially protruding wing preferably extends from the central hub. The central hub may be approximately cylindrical. The central hub may have a radius. Each wing preferably extends radially from the hub by a distance greater than half the radius of the hub. Each wing may radially extend from the hub by a distance that is greater than the radius of the hub. Each wing may radially extend from the hub by at least 0.5 mm, more preferably by at least 1 mm, more preferably by at least 2 mm, more preferably by at least 3 mm or more preferably by at least 4 mm.
The radially protruding wings may be of any suitable shape. Advantageously, each radially protruding wing has a rounded distal end or tip. Some or all of the radially protruding wings may comprise an aperture for receiving a bone screw. The wing may then be secured to the skull by a screw. This may aid attachment to the subject prior to the osseointegration of the device. Each wing may curve upwards (i.e. away from the subject) as it extends radially. The distal end of each wing may sit on the surface of the bone. For example, the distal end of each wing may sit on the surface of the bone adjacent the aperture in the bone that is formed to receive the central hub.
Each radially protruding wing may comprise one or more apertures to promote osseintegration. Each radially protruding wing preferably comprises a plurality of apertures extending through the wing to promote osseintegration. For example, each radially protruding wing may comprise a substrate (e.g. a sheet of metal) with one or more holes formed therein. Alternatively, each radially protruding wing may be formed from a mesh (e.g. a “chicken wire” type structure) or from a porous material. Such structures allow bone to grow through the apertures to anchor the device to the bone.
Advantageously, at least part of the subcutaneous base portion comprises a coating or surface texture to promote osseintegration. The coating or surface texture may be applied to the at least one radially protruding wing and/or to any central hub.
When implanted, at least part (and preferably most) of the subcutaneous base portion is located below the outer surface of a bone. The device preferably includes a feature or features that allow the depth of insertion of the device into an appropriate recess formed in a bone to be predefined. Advantageously, the subcutaneous base portion comprises a protruding lip or step(s) for engaging the outer surface of a bone around the periphery of a recess formed in that bone. Such a lip thus sits on the outermost bone surface when inserted and, as well as setting the depth of insertion, also allows the device to be implanted in a hole that passes all the way through a bone.
The device may be made using any suitable manufacturing technique. For example, by machining, selective laser sintering or 3D printing.
The invention also extends to a device as described above in combination with at least one neurosurgical catheter.
The invention also extends to a device as described above in combination with a fluid connector for attachment to the extracorporeal surface to provide fluid access to said one or more ports.
The invention also extends to a method of neurosurgery. The method may include the steps of forming a recess in the skull of a subject and implanting a device as described above in said recess. The surgically formed recess may be shaped to receive the device. The implantation technique described in WO2011/098769 is preferably used.
As explained above, the present invention is an improvement to the device that is described in WO2011/098769. The whole contents of WO2011/098769 are thus incorporated herein by reference. The device of the present invention may thus further comprise any feature described in WO2011/098769.
The invention will now be described, by way of example only, with reference to the accompanying drawings in which:
Referring to
The device 2 comprises a percutaneous portion 4 and a subcutaneous base portion 6. The percutaneous portion 4 includes a transcutaneous region 8 that is roughened to promote skin adhesion and an extracorporeal surface 10. The side walls of the extracorporeal surface 10 are smooth to allow cleaning. A septum seal 12 is accessible via a top surface 14. The septum seal 12 provides fluidic access to ports provided in the subcutaneous base portion 6 that are also connected to a four-lumen supply tube 16. The supply tube 16 is further connected to four intracranial fluid delivery catheters 18 via a fluid hub 20. The device 2 may be formed as a single piece or from multiple parts and may include any of the internal or external configurations that are described in detail in WO2011/098769.
The present invention relates to the improved subcutaneous base portion 6. The base portion 6 comprises a central hub 22 that comprises broaching fins or ribs 23 for engaging and gripping a complementary hole formed in the bone of a subject. The central hub 22 also includes three radially protruding wings 24. In other words, the device has a longitudinal axis L that is typically arranged to be approximately perpendicular to the surface of the bone, when implanted. The wings 24 extend outwardly from the central hub 22 in directions perpendicular to the longitudinal axis L (i.e. they extend radially). The bone recess that is formed in the subject prior to implantation of the device will thus include a central aperture for receiving the central hub 22 and three radially extending slots corresponding to the size and spacing of the radially protruding wings 24. Each of the radially protruding wings 24 also comprises multiple apertures 26. These apertures 26 help promote osseointegration (i.e. bone can grow through the apertures thereby securing the device in place). Although three equidistantly spaced wings are shown, it should be note that a different number of wings could be provided and the radial spacing could be altered as required.
The implantable percutaneous fluid delivery device may be used as part of the drug delivery apparatus described in WO2011/098769. For example, the percutaneous fluid delivery device may be connected to one or more implantable intracranial catheters.
Referring to
The subcutaneous base portion 56 comprises a central hub 60 and three protruding wings 62 (noting that only two of the wings 62 are illustrated in the cross-sectional vie of
Although
Referring to
The device 102 includes a percutaneous portion 104 and a subcutaneous base portion 106. The percutaneous portion 104 is similar to those described above with reference to
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