Methods and kits for locally administering an active agent to an interstitial space of a host

• US 6,346,098 B1
• Filed: 03/07/2000
• Issued: 02/12/2002
• Est. Priority Date: 03/07/2000
• Status: Expired due to Fees

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Carter, Andrew, Fitzgerald, Peter J., Hassan, Ali H., Rezaee, Mehrdad, Yock, Paul G., Yeung, Alan Ching Yeun, Herity, Niall, Lo, Sidney
• Primary Examiner(s): Schwartzman, Robert A.
• Assistant Examiner(s): DAVIS, KATHARINE F
• Application Number:
  US09/519,950
• Time in Patent Office: 707 Days
• Field of Search: 514/2, 514/44, 514/54, 604/96.01, 604/508, 604/509, 604/510, 604/507, 607/1, 11/11
• US Class Current: 604/508
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04

Abstract

Methods are provided for locally administering an agent to a host. Specifically, the subject methods provide for the local administration of an agent to an interstitial space of a host. In the subject methods, an agent is retroinfused into a vessel of a host, typically a vein, under conditions sufficient for the agent to enter an interstitial space of the host proximal to the vessel location into which the agent is retroinfused. In practicing the subject methods, the agent is administered to the host in combination with the production of vascular stress at the site of administration, where the vascular tissue stress is sufficient to provide for transport of the agent from the vascular site of deposition into the target interstitial space. In a preferred embodiment, the agent is retroinfused at a pressure sufficient to provide for mechanical stress on the vessel proximal to the target interstitial space. Also provided are kits for use in practicing the subject methods. The subject invention finds use in the local administration of a variety of different agents for treatment of a variety of different disease or other conditions.

Claims

1. A method of locally administrating an active agent to a host, said method comprising:

retroinfusing said agent into a vascular vessel of said host under conditions sufficient to produce a disruption in said vessel and for said agent to enter an interstitial space of said host through said disruption so that said agent is locally administered to said host.

2. The method according to claim 1, wherein said vessel is a vein.

3. The method according to claim 1, wherein said retroinfusing comprises providing stress to said vascular vessel at a site at least proximal to said interstitial space.

4. The method according to claim 1, wherein said method further comprises using depot means.

5. The method according to claim 1, wherein said method further comprises administration of energy to said vessel.

6. The method according to claim 1, wherein said interstitial space is myocardial interstitial space.

7. The method according to claim 3, wherein said retroinfusing comprises administering said agent at a pressure sufficient to produce at least a mechanical stress on said vessel.

8. A method of locally administering an active agent to a host, said method comprising:

retroinfusing said agent into a vein of said host under conditions sufficient to produce a disruption in said vessel and for said agent to enter an interstitial space of said host through said disruption so that said agent is locally administered to said host.

9. The method according to claim 8, wherein said retroinfusing comprises administering said agent at a pressure sufficient to produce at least a mechanical stress on said vein.

10. The method according to claim 8, wherein said agent is a biological agent selected from the group consisting of peptides, proteins, nucleic acids, lipids, polysaccharides, and mimetics thereof.

11. The method according to claim 8, wherein said method further comprises producing inflamation in said vascular vessel.

12. The method according to claim 8, wherein said interstitial space is myocardial interstitial space.

13. The method according to claim 9, wherein said pressure is sufficient to at least distend said vein.

14. The method according to claim 9, wherein said pressure is sufficient to disrupt said vein.

15. A method of locally administering an active agent to a host, said method comprising:

retroinfusing said agent into a vein of said host with a catheter and at a pressure sufficient to produce a disruption on said vein such that said agent enters an interstitial space proximal to the vein through said disruption;

whereby said agent is locally administered to said host.

16. The method according to claim 15, wherein said pressure is sufficient to at least distend said vein.

17. The method according to claim 16, wherein said pressure is sufficient to disrupt said vein.

18. The method according to claim 16, wherein said agent is a biological agent selected from the group consisting of peptides, proteins, nucleic acids, lipids, polysaccharides, and mimetics thereof.

19. The method according to claim 16, wherein said method further comprises producing inflamation in said vascular vessel.