Multipart drug delivery system

• US 6,322,815 B1
• Filed: 07/22/1994
• Issued: 11/27/2001
• Est. Priority Date: 07/22/1994
• Status: Expired due to Fees

• Current Assignee: Colvin, O. Michael, Saltzman W. Mark, Susan Ludeman, Wenbin Dang
• Original Assignee: Colvin, O. Michael, Saltzman W. Mark, Susan Ludeman, Wenbin Dang
• Inventors: Colvin, O. Michael, Dang, Wenbin, Ludeman, Susan, Saltzman, W. Mark
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): TRAN, SUSAN T
• Application Number:
  US08/279,302
• Time in Patent Office: 2,685 Days
• Field of Search: 424/468, 424/486, 424/487, 424/488, 424/400, 424/423
• US Class Current: 424/486
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof

Abstract

Polymeric drug conjugates in controlled release matrices are provided which allow sustained concentrations of therapeutic agents within a treated area for a prolonged period. The polymeric drug conjugates hydrolytically degrade in the extracellular space in a controlled, pre-specified pattern, releasing active drug. The conjugates diffuse within the tissue reaching a greater distance from the matrix than free drug would, because of their reduced rate of clearance from the tissue via the capillary system.

Claims

1. A multipart drug delivery system for delivering free drug to the extracellular space of a tissue, said multipart drug delivery system providing a reduced rate of drug elimination from its target tissue and an enhanced drug penetration volume from its implantation site relative to free drug and relative to free drug incorporated in a controlled-release matrix, said multipart drug delivery system comprising:

a. a drug covalently attached via a first hydrolytically labile bond to

b. a water-soluble, high molecular weight first polymer, forming a first drug-polymer conjugate, said conjugate being incorporated in

c. a controlled-release matrix comprising a biocompatible second polymer.

2. The multipart drug delivery system of claim 1 wherein the first polymer is a polysaccharide.

3. The multipart drug delivery system of claim 2 wherein the polysaccharide is dextran.

4. The multipart drug delivery system of claim 1 wherein the hydrolytically labile bond is an ester bond.

9. The multipart drug delivery system of claim 1 wherein said drug is released from said conjugate at a rate providing a t_½

of at least 3 days in PBS at 37°

C.

10. The multipart drug delivery system of claim 1 wherein said drug is released from said conjugate at a rate providing a t_½

of at least 20 days in PBS at 37°

C.

5. A method of performing intrathecal therapy, comprising the step of:

administering directly to an intrathecal space a drug-polymer conjugate, said drug-polymer conjugate providing a reduced rate of drug elimination from its target tissue relative to free drug, said drug-polymer conjugate comprising;

a. a drug covalently attached via an hydrolytically labile bond to

b. a water-soluble, high molecular weight polymer

wherein said drug is released from said conjugate at a rate providing a t_½

of at least 20 days in PBS at 37°

C.

6. The method of claim 5 wherein the polymer is a polysaccharide.

7. The method of claim 6 wherein the polysaccharide is dextran.

8. The method of claim 5 wherein the hydrolytically labile bond is an ester bond.