Injectable drug delivery formulation
AssigneeSurModics, Inc.
InventorJoram Slager
Life of this patent
Estimating the term…
Abstract
The invention provides an injectable formulation that includes an active agent; a biocompatible solvent system, crosslinkable polymers such as polysaccharides; and crosslinking agents; wherein the formulation is substantially free of water. The invention also provides a drug delivery depot formed from the injectable formulation wherein the polymers crosslink in the presence of water in the body of a patient, or in the air, prior to implantation in the patient. Also provided are methods of treatment using such formulations and drug delivery systems.
Claims25
An injectable formulation comprising:
- an active agent;
- a non-aqueous, aprotic, biocompatible solvent system, wherein the solvent system comprises one or more solvents, and at least one of the solvents is non-miscible with water;
- a plurality of polymers that each include a plurality of hydroxyl groups;
- and
- a plurality of crosslinking agents, wherein the crosslinking agent comprises X—(C1-C16)alkyl-X or X—(CH2CH2—O)n—CH2CH2—X where n is 0 to about 20, and each X is independently a chlorosilane group, a trialkoxysilane group, or —NCO;
- wherein the solvent system is chemically inert with respect to the crosslinking agents, and the formulation is substantially free of water.
An in vivo biodegradable crosslinked matrix comprising:
- a non-aqueous aprotic biocompatible solvent system wherein the solvent system comprises one or more solvents and at least one of the solvents is non-miscible with water;
- a plurality of polymers that each include a plurality of hydroxyl groups, where a plurality of the polymers are crosslinked by:
- —(Y)2Si—(C1-C16)alkyl-Si(Y)2— groups;
- —(Y)2Si—(CH2CH2—O)n—CH2CH2—Si(Y)2— groups where n is 0 to about 20;
- —C(═O)NH—(C1-C16)alkyl-Si(Y)2— groups;
- —C(═O)NH—(CH2CH2—O)n—CH2CH2—Si(Y)2— groups where n is 0 to about 20;
- —C(═O)NH—(C1-C16)alkyl-NH—C(═O)— groups;
- —C(═O)NH—(CH2CH2—O)n—CH2CH2—NH—C(═O)— groups where n is 0 to about 20;
- or a combination thereof;
- where each Y is independently —OH, —O-alkyl, or alkyl;
- and
- an active agent that is dissolved or dispersed throughout the crosslinked matrix.
A method of delivering an active agent to a subject comprising:
- injecting a formulation comprising:
- an active agent;
- a non-aqueous, aprotic, biocompatible solvent system, wherein the solvent system comprises one or more solvents and at least one of the solvents is non-miscible with water;
- a plurality of polymers that each include a plurality of hydroxyl groups;
- and
- a plurality of crosslinking agents, wherein the crosslinking agent comprises X—(C1-C16)alkyl-X or X—(CH2CH2—O)n—CH2CH2—X where n is 0 to about 20, and each X is independently a chlorosilane group, a tri(C1-C3)alkoxysilane group, or —NCO;
- wherein the solvent system is chemically inert with respect to the crosslinking agents and the formulation is substantially free of water;
- and
- the formulation forms a gel matrix within the subject and the gel matrix becomes crosslinked when the polysaccharides and crosslinking agents are contacted by fluids in the body of the subject;
- and
- the matrix releases the active agent, over a period of weeks, to the body of the subject;
- thereby delivering the active agent to the subject.
Dependencies are inferred from the claim text.