Title:  Prolonged release bioadhesive vaginal gel dosage form

United States Patent:  6,159,491

Assignee:  Biovector Technologies, Inc. (New York, NY)

Filed:  February 12, 1999

The present invention relates to a bioadhesive, prolonged release vaginal gel dosage form comprising a synergistic formulation of carrageenan, acrylic acid containing polymers, agarose and an effective amount of a therapeutic agent, whereby the therapeutic agent is released from this composition initially at a first relatively high rate, to provide a loading dose of the therapeutic agent, followed by a second, lower rate of release that provides a constant, maintenance dose of the therapeutic agent for up to 24 hours. More specifically, the present invention includes compositions within which the agarose is ultra low gelling temperature agarose and the acrylic acid containing polymer may be carbophil, a copolymer of acrylic acid and divinyl alcohol, a copolymer of acrylic acid and C₁₀ to C₃₀ alkyl acrylic acid or a polyacrylic acid homopolymer.

SUMMARY OF THE INVENTION

The present invention relates to a bioadhesive, prolonged release drug composition comprising a synergistic formulation of carrageenan, acrylic acid containing polymers, agarose and an effective amount of a therapeutic agent. The therapeutic agent is released initially at a first relatively high rate, to provide a loading dose of the therapeutic agent, followed by a second, lower rate of release that provides a constant, maintenance dose of the therapeutic agent for up to 24 hours.

In one embodiment of the present invention, the agarose is ultra low gelling temperature agarose (Fisher Scientific, Pittsburgh, PA.). In another embodiment of this invention, the acrylic acid containing polymer may be polycarbophil, a homopolymer of acrylic acid and divinyl glycol, a copolymer of acrylic acid and C₁₀ to C₃₀ alkyl acrylate copolymer Pemulen.TM. TR1, TR2, Carbopol.RTM. 1342 or 1382 resin.

In another embodiment, one or more of the therapeutic agents dispersed or dissolved within the bioadhesive, prolonged release drug composition of the present invention, are selected from the group consisting of a spermicide, antiviral, antibacterial, antifungal, antimycotic, antipruritic, emollient, humectant, anti-inflammatory, immunomodulator, hormonal, antineoplastic or an analgesic agent.

A further embodiment of this invention is directed toward a method of administering a therapeutic agent comprising providing a bioadhesive, prolonged release drug composition comprising carrageenan, an acrylic acid containing polymer, agarose and an effective amount of a therapeutic agent and applying this composition to the vaginal mucosa of the patient. This embodiment further contemplates that the therapeutic agent is, or the therapeutic agents are, released initially at a first relatively high rate, to provide a loading dose of the therapeutic agent, followed by a second, lower rate of release that provides a constant, maintenance dose of the therapeutic agent for up to 24 hours.

A still further embodiment of this invention is directed to a method for making a bioadhesive, prolonged release drug composition. This embodiment contemplates first dissolving soluble components, including, but not limited to sodium chloride, methylparaben, acetate buffer, and, optionally, a therapeutic agent in a suitable amount of purified water. The therapeutic agent is added either in the first step or the last step of this process depending upon whether or not heating would be required for dissolution of this material or upon the thermal stability of the specific therapeutic agent employed. The gelling agents, low melting temperature agarose and carrageenan, are gradually added, with stirring, to this first solution until a uniform dispersion is obtained. The acrylic acid containing polymer, selected from the group consisting of polycarbophil, a homopolymer of acrylic acid crosslinked with divinyl glycol, polyacrylic acid homopolymers (Carbopol 974P-NF and Carbopol 971P-NF and other carbomers), and other copolymers of acrylic acid, ETD (easy-to-disperse) resins and copolymers of acrylic acid and C₁₀ to C₃₀ alkyl acrylic acid, is added slowly, with stirring until dispersed. This mixture, while being stirred, is heated to 90^oC. for a short period of time and then cooled to 70^oC. for a second short period of time. The mixture is cooled until it reaches room temperature where stirring is continued until the mixture is uniform. If heating is not required for dissolution of the therapeutic agent, or if it is heat labile, it may be stirred into this mixture at room temperature.

In another embodiment of this process for making the bioadhesive, prolonged release drug composition of the present invention, the therapeutic agent is selected from the group consisting of a spermicide, antiviral, antibacterial, antifungal, antimycotic, antipruritic, emollient, humectant, anti-inflammatory, immunomodulator, hormonal, antineoplastic or an analgesic agent.

Claim 1 of 27 Claims

What is claimed is:

1. A prolonged-release bioadhesive drug composition comprising:

carrageenan;

at least one polymer comprising acrylic acid;

agarose; and

a therapeutically effective amount of at least one therapeutic agent.

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