Dendrimer conjugates

• US 8,889,635 B2
• Filed: 09/30/2009
• Issued: 11/18/2014
• Est. Priority Date: 09/30/2008
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Baker, James R. Jr., Cheng, Xue-min, Huang, Baohua Mark, Thomas, Thommey P., Van Der Spek, Abraham F. L.
• Primary Examiner(s): Singh, Anoop
• Assistant Examiner(s): FALKOWITZ, ANNA R
• Application Number:
  US12/570,977
• Publication Number:
  US 20100160299A1
• Time in Patent Office: 1,875 Days
• Field of Search: 514/221, 514/282, 514/237.2, 546/46
• US Class Current: 514/22
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.

Claims

1. A composition comprising pain relief complexes and pain relief antagonist complexes;

wherein said pain relief complexes consist of dendrimers separately conjugated with

     1) a pain relief agent via an ester linkage agent, wherein said pain relief agent is morphine,

     2) a locking agent, wherein said locking agent is trigonelline, and

     3) a targeting agent, wherein said targeting agent is transferrin;

wherein said pain relief antagonist complexes consist of dendrimers separately conjugated with

     1) a pain relief agent antagonist via an indolequinone trigger agent, wherein said pain relief agent antagonist is naloxone,

     2) a locking agent, wherein said locking agent is trigonelline, and

     3) a targeting agent, wherein said targeting agent is transferrin;

wherein said pain relief antagonist complexes are configured to prevent respiratory depression caused said pain relief complexes;

wherein said dendrimers within said pain relief complexes and pain relief antagonist complexes are separate within said composition.

2. The composition of claim 1, wherein said dendrimers are selected from the group consisting of a polyamideamine (PAMAM) dendrimer, a polypropylamine (POPAM) dendrimer, and a PAMAM-POPAM dendrimer.

3. The composition of claim 1, wherein the linkage agent comprises a spacer comprising between 1 and 8 straight or branched carbon chains, wherein said straight or branched chains are selected from the group consisting of i) unsubstituted, and ii) substituted with alkyls.

4. The composition of claim 1, wherein said dendrimers are acetylated.