Targeted therapeutic delivery of vitamin D compounds

• US 6,929,797 B2
• Filed: 02/13/1998
• Issued: 08/16/2005
• Est. Priority Date: 02/13/1997
• Status: Expired due to Term

• Current Assignee: Bone Care International LLC
• Original Assignee: Bone Care International LLC
• Inventors: Bishop, Charles W., Mazess, Richard B.
• Primary Examiner(s): Chan, Christina
• Assistant Examiner(s): HUYNH, PHUONG N
• Application Number:
  US09/402,636
• Publication Number:
  US 20020136731A1
• Time in Patent Office: 2,741 Days
• Field of Search: 424/195.11, 424/457, 514/167, 530/307, 530/351
• US Class Current: 424/195.11
• CPC Class Codes: A61K 47/548 Phosphates or phosphonates, e.g. bone-seeking phospholipids A61K47/544
• CPC Class Codes: A61K 47/554 the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
• CPC Class Codes: A61K 47/6898 using avidin- or biotin-conjugated antibodies
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention is directed to a conjugate which includes at least one vitamin D moiety thereof and at least one targeting molecule moiety to pharmaceutical compositions of the conjugate, and to methods for using the conjugate for target-specific delivery of vitamin D or analogs thereof to tissues in need thereof. When a particularly preferred form is administered to a patient, the targeting molecule component of the conjugate of this invention seeks out and binds to a tissue of interest, such as bone or tumor tissue, where the vitamin D has a therapeutic effect.

Claims

1. A conjugate comprising 1α

-(OH)-24-aminoalkyl-1,1-bisphosphonate-D₂, 1-aniinoalkyl-1,1-bisphosphonate-24-(OH)-D₂, 1α

,24-(OH)₂-3-aminoalkyl-1,1-bisphosphonate-D₂, 1α

-aminoalkyl-1,1-bisphosphonate-25-(OH)-D₃, 1α

,25-(OH)₂-3-aminoalkyl-1,1-bisphosphonate-D₃, 1α

-(OH)-25-aminoalkyl-1,1-bisphosphonate-D₃, or a combination thereof.

2. A pharmaceutical composition comprising:

a conjugate comprising 1α

-(OH)-24-aminoalkyl-1,1-bisphosphonate-D₂, 1-aminoalkyl-1,1-bisphosphonate-24-(OH)-D₂, 1α

,24-(OH)₂-3-aminoalkyl-1,1-bisphosphonate-D₂, 1α

-aminoalkyl-1,1-bisphosphonate-25-(OH)-D₃, 1α

,25-(OH)₂-3-aminoalkyl-1,1-bisphosphonate-D₃, 1α

-(OH)-25-aminoalkyl-1,1-bisphosphonate-D₃, or a combination thereof, and

a suitable pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2, further comprising an additional therapeutic agent.

4. The pharmaceutical composition of claim 3, wherein the therapeutic agent comprises at least one of conjugated estrogens or their equivalents, antiestrogens, calcitonin, bisphosphonates, calcium supplements, cobalamin, pertussis toxin, boron, dehydroepiandrosterone, transforming bone growth factor beta, activin, bone morphogenic protein and a combination thereof.

5. The pharmaceutical composition of claim 2, further comprising a differentially degradable coating encapsulating the conjugate for time release delivery of the conjugate.

6. The pharmaceutical composition of claim 5, wherein said coating is an enteric coating.