Methods for delivering therapeutics across blood-barrier and for altering receptor binding affinity

• US 6,943,148 B1
• Filed: 10/29/1999
• Issued: 09/13/2005
• Est. Priority Date: 08/14/1998
• Status: Expired due to Fees

• Current Assignee: Nobex Corporation (Biocon Incorporated)
• Original Assignee: Nobex Corporation (Biocon Incorporated)
• Inventors: Rhadakrishnan, Balasingam, Ansari, Adam M., Ekwuribe, Nnochiri N., Price, Christopher H., Anderson, Wes Jr.
• Primary Examiner(s): CELSA, BENNETT M
• Application Number:
  US09/430,735
• Time in Patent Office: 2,146 Days
• Field of Search: 514/2, 514/8, 514/12, 514/17, 514/476, 514/506, 514/579, 514/2.1, 424/85.1, 424/85.2, 424/85.4
• US Class Current: 514/17.7
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 of the parathyroid hormones

Abstract

The present invention relates to amphiphilic drug-oligomer conjugates capable of traversing the blood-brain barrier (“BBB”) and to methods of making and using such conjugates. An amphiphilic drug-oligomer conjugates comprise a therapeutic compound conjugated to an oligomer, wherein the oligomer comprises a lipophilic moiety coupled to a hydrophilic moiety. The conjugates of the invention further comprise therapeutic agents such as proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, etc., and prodrugs, precursors, derivatives and intermediates thereof, chemically coupled to amphiphilic oligomers.

Claims

1. A method for inducing analgesia in a subject, the method comprising delivering across the blood brain barrier of the subject, into the subject'"'"'s central nervous system, a therapeutically effective amount of an amphiphilic drug-oligomer conjugate having a formula:

2. The method of claim 1 wherein the subject is a human.

3. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject orally.

4. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject intravenously.

5. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject by a route selected from the group consisting of pulmonary, intradermal, intramuscular, subcutaneous, and intranasal.

6. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject as a component of a pharmaceutical composition.

7. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject as a component of a pharmaceutical composition formulated for oral administration.

8. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject as a component of a pharmaceutical composition formulated for intravenous administration.

9. The method of claim 1 wherein the amphiphilic drug-oligomer conjugate is administered to the subject as a component of a pharmaceutical composition formulated for administration by a route selected from the group consisting of pulmonary, intradermal, intramuscular, subcutaneous, and intranasal.