Title:  Controlled release drug delivery

United States Patent:  6,168,801

Assignee:  Cardiac Pacemakers, Inc. (St. Paul, MN)

Filed:  March 19, 1999

Biologically active materials are provided in a cylindrical carrier medium with better control over the rate of delivery and length of time of delivery by providing a carrier having dissolved or dispersed therein at least two compounds having a common biologically active nucleus, but with different solubility parameters. The combination of the two different variants of the same drug with different solubility parameters provides the material with control over the rate of release of the compounds (by varying the proportions of the variants) and most importantly, extending the useful life of the device by enabling release of effective levels of the compounds over a longer period of time. The cylindrical carrier medium, comprised of silicone, further includes a tail, a skirt, or a rate-limiting membrane.

SUMMARY OF THE INVENTION

A material is described for delivering a chemically active, biologically active or medically active compound. The material comprises a solid carrier having at least two active compounds dissolved and/or dispersed therein. Each of the at least two active compounds are medically or biologically active compounds. Each of the at least two active compounds have an active nucleus which is common to each of the active compounds. The at least two active compounds also have maximum solubility levels in a single solvent which differ from each other. In one embodiment, the maximum solubility level of a first active compound in the solvent exceeds the maximum solubility level of a second active compound in the same solvent by at least approximately 10% by weight. In another embodiment, the maximum solubility level of a first active compound in the solvent exceeds the maximum solubility level of a second active compound in the same solvent by at least a factor of approximately two when measured as percent by weight. In a further embodiment, a first active compound is generally hydrophilic and a second active compound is generally hydrophobic. In yet another embodiment, a first active compound is generally soluble in the solvent and a second active compound is generally insoluble in the same solvent. Generally insoluble will be defined as having a saturation level in a solvent at the trace or marginal (e.g., less than about 1% by weight) levels.

The solid carrier often comprises biocompatible polymeric material. The solvent is preferably an aqueous solvent at approximately 37 degrees Centigrade. The solvents may, for example, comprise distilled, deionized water at 37 (or 37.2) degrees Centigrade, a standard saline solution at room temperature of 37 degrees Centigrade, or a bodily fluid (e.g., blood) at approximately 37 degrees Centigrade. The at least two (e.g., biologically) active compounds preferably comprise compounds having a common (e.g., biologically) active nucleus with each of said at least two (e.g., biologically) active compounds having different substituents groups thereon. The different substituent groups provide, at least in part, different solubility characteristics to the at least two (e.g., biologically) active compounds.

For example, the at least two medically active compounds may comprise compounds having a common medically active nucleus with each of said at least two medically active compounds having different substituents groups thereon. The different substituent groups may provide, at least in part, different solubility characteristics to the at least two medically active compounds.

A process for delivery of a biologically active ingredient to a patient is also described which comprises the steps of:

a) providing a material for delivering an (e.g., medically) active compound comprising a solid carrier material having dissolved and/or dispersed therein at least two (e.g., medically) active compounds, each of said at least two (e.g., medically) active compounds having an (e.g., medically) active nucleus which is common to each of the (e.g., medically) active compounds, and the at least two (e.g., medically) active compounds having maximum solubility levels in a solvent which differ from each other, and

b) implanting said material into a patient.

Claim 1 of 43 Claims

What is claimed:

1. A material for delivering a biologically active compound comprising a solid carrier material having dissolved and/or dispersed therein at least two biologically active compounds, each of said at least two biologically active compounds having a biologically active nucleus which is common to each of the biologically active compounds, and the at least two biologically active compounds having maximum solubility levels in a single solvent which differ from each other by at least 10% by weight; wherein said solid carrier comprises a biocompatible polymeric material.

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