Implantable therapy systems and methods

• US 5,487,739 A
• Filed: 06/02/1995
• Issued: 01/30/1996
• Est. Priority Date: 11/17/1987
• Status: Expired due to Fees

• Current Assignee: Neurotech S.A. (LivaNova Plc)
• Original Assignee: Brown University
• Inventors: Sanberg, Paul R., Aebischer, Patrick, Mulhauser, Paul J., Warner, Nicholas F., Vasconcellos, Alfred V., Goddard, Moses, Moldauer, John G., Rathbun, Anne M.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Bockelman, Mark
• Application Number:
  US08/459,815
• Time in Patent Office: 242 Days
• Field of Search: 604/93, 604/116, 604/117, 604/59, 604/60, 604/890.1, 604/892.1, 604/84, 604/285, 604/403, 604/164, 604/170, 604/264, 604/265, 604/53, 606/150, 424/424, 623/11, 623/12
• US Class Current: 604/890.1
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61K 2035/126 Immunoprotecting barriers, e.g. jackets, diffusion chambers
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/55 Glands not provided for in groups A61K35/22 - A61K35/545, e.g. thyroids, parathyroids or pineal glands
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0085 Brain, e.g. brain implants; Spinal cord
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61M 2210/0687 Skull, cranium
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 37/0069 Devices for implanting pellets, e.g. markers or solid medicaments for introducing of radioactive sources for interstitial radiation therapy, i.e. brachytherapy A61N5/1027
• CPC Class Codes: A61M 39/0208 Subcutaneous access sites for injecting or removing fluids transcutaneous access sites A61M39/0247; implantable infusion devices A61M5/14276
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0614 Adrenal gland
• CPC Class Codes: C12N 5/0619 Neurons
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Implantable therapy systems are disclosed for the local and controlled delivery of a biologically active factor to the brain, spinal cord and other target regions of a subject suffering from a debilitating condition. The method of the invention involves surgically exposing an insertion site, generally located above a predetermined treatment site (12), in a patient. A cannula (20), having an obturator (30) or dilator (104) positioned therein, is inserted at the insertion site, defining a pathway to the treatment site. In some instances, the cannula can be inserted along the path of a guidewire (102) previously positioned at the treatment site. The cannula (20) is preferably a low friction polymeric material such as polytetrafluoroethylene. The cannula (20) generally has an open proximal end for receiving the obturator (30) or dilator (104), and an open distal end, preferably a tapered end, for delivery of neurologically active factors to the treatment site (12). The obturator (30) is then removed from the cannula (20), and a biocompatible tethered vehicle (40) containing a biologically active material is inserted into the cannula along the passageway. A pusher can be inserted within the cannula, behind the vehicle (40), to position the proximal end of the vehicle at the distal end of the cannula (20b). Once the vehicle (40) is positioned near the distal end of the cannula (20), the cannula is removed from the passageway, followed by the pusher, leaving the vehicle (40) positioned at the treatment site (12).

Claims

1. A system for delivering a biologically active factor to a selected treatment site in a subject, comprising:

i) a single cannula adapted for penetration through tissue into a selected position in proximity with the treatment site, having a bore with a substantially smooth interior surface running axially therethrough through which a vehicle may slidably move, an open, proximal end into which the vehicle may be slidably inserted and a distal end having an opening through which the vehicle may slidably move wherein the external diameter and bore diameter are tapered toward the distal tip;

ii) an obturator disposable within the cannula to prevent tissue material from entering the distal end of the cannula when it is inserted into tissue;

iii) a vehicle which encapsulates the biologically active factor, the vehicle having an outer surface which comprises a biocompatible semipermeable outer membrane through which the biologically active factor may be released into the selected treatment site, and a shape which enables slidable insertion into the proximal end of the cannula, slidable movement along the bore of the cannula, slidable passage through the distal end of the cannula by removal of the cannula from the proximity of the treatment site; and

iv) a pusher disposable within the cannula to engage the outer surface of the vehicle, to slidably move the vehicle through the bore, and to hold the vehicle in place at the selected treatment site when the cannula is removed from the proximity of the treatment site, the pusher being removable after the vehicle is positioned at the treatment site.

2. The system of claim 1, further comprising:

i) a guidance needle having a lumen running axially therethrough and being insertable into proximity with the treatment site;

ii) a guidewire insertable into proximity with the treatment site and able to pass completely through the lumen of the guidance needle;

wherein the cannula is adapted to receive the guidewire and wherein the lumen of the guidance needle has a first open end for receiving the guidewire, and a second open end for passage of the guidewire to the treatment site, the guidance needle being fully removable after insertion of the guidewire to the treatment site without disturbing the proximity of the guidewire to the treatment site, and the guidewire being able to guide the insertion of the cannula to the treatment site.

3. The system of claim 2, further comprising at least one dilator disposable along the guidewire to enlarge a pathway through which the cannula is inserted, the dilator having a dilator bore running axially therethrough and able to pass the guidewire therein.

4. The system of claim 3, wherein the guidance needle has a beveled, curved tip.

5. The system of claim 2, further comprising at least one obturator for insertion within and along the lumen of the guidance needle to prevent backfill of materials into the guidance needle during insertion of the guidance needle, the obturator being fully removable after insertion of the guidance needle into proximity with the treatment site.

6. The system of claim 1, wherein at least a portion of the proximal end of the cannula is transparent to permit monitoring the progress of the vehicle during insertion into the cannula and during passage through the transparent portion of the cannula.

7. The system of claim 1, wherein the distal end of the cannula is rounded to reduce ancillary tissue damage, and wherein the active factor comprises at least one neuroactive factor selected from the group consisting of peptide neurotransmitters, growth factors, trophic factors, catecholamines, opioid peptides and hormones.

8. The system of claim 1, wherein the system is adapted for delivering the vehicle into a human spinal region, and wherein the vehicle releases at least one antinociceptive agent useful in a treatment for pain relief.

9. The system of claim 1, wherein the vehicle encapsulates cells that secrete the biologically active factor.

10. The system of claim 9, wherein the encapsulated cells comprise adrenal medullary chromaffin cells.

11. The system of claim 9, wherein the distal end of the cannula is rounded to reduce ancillary tissue damage, and wherein the active factor comprises a neuroactive factor selected from the group consisting of peptide neurotransmitters, growth factors, trophic factors, catecholamines, opioid peptides and hormones.

12. The system of claim 1, wherein the vehicle further comprises an impermeable protective barrier material which coats a portion of the outer membrane.

13. The system of claim 1, wherein the cannula is constructed from material comprising a low friction polymer.

14. The system of claim 13, wherein the polymer comprises polytetrafluoroethylene.

15. The system of claim 1, wherein the active factor comprises at least one antinociceptive agent useful in a treatment for pain relief.

16. The system of claim 1, wherein the cannula is flexible for the delivery of the vehicle through a curved pathway.

17. A method for delivering a biologically active factor to a selected treatment site in a subject, comprising:

i) surgically opening an insertion site located near the selected treatment site;

ii) inserting a single cannula adapted for penetration through tissue and an obturator disposed therein into the insertion site and placing the distal end of the cannula at a selected position in proximity with the treatment site, the cannula having a bore with a substantially smooth surface running axially therethrough through which a vehicle may slidably move, an open, proximal end into which the vehicle may be slidably inserted and a distal end having an opening through which the vehicle may slidably move wherein the external diameter an bore diameter are tapered toward the distal tip;

iii) removing the obturator from the cannula;

iv) introducing within the bore of the cannula a vehicle which encapsulates the biologically active factor, the vehicle having an outer surface which comprises a biocompatible semipermeable outer membrane through which the biologically active factor may be released into the selected treatment site, and a shape which enables slidable insertion into the proximal end of the cannula, slidable movement along the bore of the cannula, slidable passage through the distal end of the cannula by removal of the cannula from the proximity of the treatment site;

v) delivering the vehicle to the distal end of the cannula with a pusher disposable within the cannula to engage the outer surface of the vehicle, to slidably move the vehicle through the bore, and to hold the vehicle in place at the selected treatment site when the cannula is removed from the proximity of the treatment site;

vi) removing the cannula from the tissue, while leaving the vehicle inserted at the treatment site; and

vii) removing the pusher from the tissue.

18. The method of claim 17, further comprising before a step of inserting the cannula,

i) inserting a guidance needle having a lumen running axially therethrough into proximity with the treatment site;

ii) inserting a guidewire through the lumen of the inserted needle and into proximity with the treatment site, the guidewire able to pass completely through the lumen of the guidance needle; and

iii) removing the guidance needle from the treatment site without disturbing the proximity of the guidewire to the treatment site;

wherein the cannula is adapted to receive the guidewire and wherein the lumen of the guidance needle has a first open end for receiving the guidewire, and a second open end for passage of the guidewire to the treatment site, the guidance needle being fully removable after insertion of the guidewire to the treatment site without disturbing the proximity of the guidewire to the treatment site, and the guidewire being able to guide the insertion of the cannula to the treatment site.

19. The method of claim 18, further comprising disposing, after removing the guidance needle, at least one dilator along the guidewire and towards the treatment site to enlarge a pathway through which the cannula is inserted, the dilator having a dilator bore running axially therethrough and able to pass the guidewire therein, the dilator being removed before the cannula is removed.

20. The method of claim 18, further comprising, before a step of inserting the guidewire, disposing at least one obturator in the lumen of the guidance needle, the obturator of the type designed for insertion within and along the lumen of the guidance needle to prevent backfill of materials into the guidance needle during insertion of the guidance needle into proximity with the treatment site, the obturator being removed before the guidewire is inserted.