Absorbable brachytherapy and chemotherapy delivery devices and methods

• US 6,248,057 B1
• Filed: 07/27/1999
• Issued: 06/19/2001
• Est. Priority Date: 07/28/1998
• Status: Expired due to Term

• Current Assignee: Biosurface Engineering Technologies, Inc. (Ferring Holding SA)
• Original Assignee: InnerDyne, Inc. (Medtronic Plc)
• Inventors: Stern, Robert A., Mavity, William G., Zamora, Paul O., Osaki, Shigemasa
• Primary Examiner(s): Lacyk, John P.
• Application Number:
  US09/361,553
• Time in Patent Office: 693 Days
• Field of Search: 600/1-8
• US Class Current: 600/3
• CPC Class Codes: A61N 2005/1019 Sources therefor
• CPC Class Codes: A61N 5/1027 Interstitial radiation therapy

Abstract

Combination radiation delivery and chemotherapy devices comprise bioabsorbable structures with radionuclides and chemotherapeutic agents immobilized on said structures. The bioabsorbable structures have a predefined persistence period which is usually substantially greater than the half-life of the radionuclides, thus assuring that the radionuclides remain localized and sequestered at a desired target site while significant radioactivity remains. The radiation delivery and chemotherapy devices are suitable for a wide variety of medical purposes, being particularly suitable for the treatment of solid tumors by injection or open surgical introduction of the devices at a target site. Kits comprising the devices together with instructions for use are also provided.

Claims

1. A radiation delivery device, said device comprising:

a bioabsorbable structure having a predefined persistence period when implanted in a patient wherein the bioabsorbable structure is formed as an implantable macrostructure comprising a continuous core structure with a minimum width of at least 1 mm; and

a radionuclide having a known half-life immobilized on said structure, where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide so that loss of radioactivity from the target site is minimized.

2. A radiation delivery device as in claim 1, wherein the bioabsorbable structure has a persistence period in the range from 2 days to 90 days.

3. A radiation delivery device as in claim 1 or 2, wherein the radionuclide has a half-life of 60 days or less.

4. A radiation device as in claims 1 or 2, wherein the bioabsorbable structure is composed of a biological polymer.

5. A radiation device as in claims 1 or 2, wherein the bioabsorbable structure has a drug incorporated into said structure.

6. A radiation device as in claim 5, wherein the drug incorporated into the biodegradable structure is substantially released within two half-lives of the radionuclide.

7. A radiation device as in claim 5, wherein the drug incorporated into the biodegradable structure is a chemotherapeutic agent.

8. A radiation delivery device as in claim 1, wherein the radionuclide is selected from the group consisting of Cu-162, Cu-64, Cu-67, Ru-97, Rh-105, Pd-109, Sm-153, Ho-166, Re-186, Re-188, Au-198, Au-199, Pb-203, Pb-211, Bi-212, I-125, I-131, Y-90, Pd-103, Ir-192 and P-32.

9. A radiation delivery device as in claim 1, wherein the radionuclide is covalently bound to a preformed surface on the bioabsorbable structure.

10. A radiation delivery device as in claim 9, wherein the radionuclide is covalently bound through a linker which is bound to the surface.

11. A radiation delivery device as in claim 1, wherein the radionuclide is chelated, adsorbed, precipitated, or complexed to a preformed surface on the bioabsorbable structure.

12. A method for localized delivery of radioactivity to a target site in tissue, said method comprising implanting a radiation delivery device, wherein said device comprises:

a radiation delivery device said device comprising;

a bioabsorbable structure having a predefined persistence period when implanted in a patient;

wherein the bioabsorbable structure is formed as an implantable macrostructure comprising a continuous core structure with a minimum width of at least 1 mm; and

a radionuclide having a known half-life immobilized on said structure where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide so that loss of radioactivity from the target site is minimized.

14. A method as in claim 12 or 13, wherein implanting comprises surgically exposing the target site and placing the device at the surgically exposed site.

13. A method for localized delivery of radioactivity and drugs to a target site in tissue, said method comprising implanting a radiation delivery device at said target site, wherein said device comprises:

a bioabsorbable structure having a predefined persistence period when implanted in a patient;

a radionuclide having a know half-life immobilized on said structure where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide so that loss of radioactivity from the target site is minimized; and

a drug incorporated into said structure.

15. A method for preparing a treatment delivery device, said method comprising:

providing a bioabsorbable structure having a predefined persistence period and a surface wherein at least a portion of the surface has been coated with a substrate material;

providing a radioactive material including a bonding constituent which is capable of bonding to the substrate material and a radioactive isotope, where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide;

determining the specific activity of the radioactive material; and

bonding an amount of the radioactive material to the substrate material on the structure selected to provide a predetermined radioactive dosage.

16. A method as in claim 15, wherein the predetermined dosage is in the range from 20 gray to 200 gray.

17. A method as in claim 15, wherein the bioabsorbable structure has a persistence period in the range from 2 days to 90 days.

18. A method as in claim 15 or 17, wherein the radionuclide has a half-life of 60 days or less.

19. A method as in claim 15, wherein the bonding step comprises covalently bonding the radioactive material to the substrate material.

20. A method as in claim 15, wherein the biodegradable structure is composed of a biological polymer.

21. A method as in claim 15 or 20, wherein the biodegradable structure is formed as an implantable macrostructure comprising a continuous core structure with a minimum width of at least 1 mm.

22. A method as in claim 15 or 20, wherein the biodegradable structure is formed as an implantable microstructure comprising core particles having an average width below 1 mm.

23. A method as in claim 15, wherein the substrate material is selected from the group consisting of siloxanes and bifunctional chelating agents.

24. A method as in claim 15, wherein the radioactive material comprises a radionuclide and a bonding component.

25. A method as in claim 15, wherein the bioabsorbable structure has dispersed therein a drug.

26. A method as in claim 15, further comprising the steps of:

providing a sustained release drug material which is capable of bonding to the substrate material, where the persistence period of the bioabsorbable structure is substantially longer than the period required to release substantially release the drug; and

bonding an effective amount of the sustained release drug material to the substrate material on the device.

27. A method as in claims 25 or 26, wherein the drug is a chemotherapeutic drug.

28. A kit comprising:

a radiation delivery device, said device comprising;

a bioabsorbable structure having a predefined persistence period when implanted in a patient;

wherein the bioabsorbable structure is formed as an implantable macrostructure comprising a continuous core structure with a minimum width of at least 1 mm;

a radionuclide having a known half-life immobilized on said structure, where the persistence period of the bioabsorbable structure is substantially longer than a half-life of the radionuclide so that loss of radioactivity from the target site is minimized; and

instructions describing a method for implanting the device in tissue.

29. A kit as in claim 28, further comprising a package which contains the device and the instructions.

30. A kit as in claim 29, wherein the instructions further set forth a method for coating the radiation delivery device with a radioactive material prior to implantation.