Treatment of esophagitis

Abstract

A method for treatment of esophagitis is disclosed in which a therapeutic composition is introduced into the esophagus to contact a mucosal surface within the esophagus. The pharmaceutical composition comprises a reverse-thermal gelation polyoxyalkylene block copolymer, a pharmaceutical substance and a pharmaceutical substance selected from the group consisting of glutathione and a precursor for glutathione biosynthesis.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of U.S. patent application Ser. No. 10 / 728,277, filed Dec. 4, 2003, which is a continuation of U.S. patent application Ser. No. 09 / 993,383 filed Nov. 21, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 721,516 filed Nov. 22, 2000, and the entire contents of each of said applications are incorporated herein by reference as if each and every part of said applications were set forth herein in full.FIELD OF THE INVENTION [0002] This invention relates to a therapeutic composition useful for treatment of mucositis and methods for using the therapeutic composition. BACKGROUND OF THE INVENTION [0003] Mucositis is a serious and often very painful disorder involving inflammation of the mucous membrane, with the inflammation often accompanied by infection and / or ulceration. Mucositis can occur at any of the different mucosal sites in the body. A nonlimiting list of examples of locations...

AI Technical Summary

Benefits of technology

[0011] In one aspect, the present invention provides a therapeutic composition for the treatment of mucositis. By treatment of mucositis, it is meant that the therapeutic composition is effective to prevent or reduce the incidence, severity and / or duration of the disease. The therapeutic composition comprises at least one pharmaceutical substance that, as formulated in the therapeutic composition, presents therapeutic effect in mammalian hosts, typically human hosts, for the treatment of mucositis, together with at least one biocompatible polymer that aids delivery of the pharmaceutical substance to the targeted mucosal site. One preferred embodiment of the therapeutic composition includes N-acetylcysteine as the pharmaceutical substance and a polyoxyalkylene block copolymer as the biocompatible polymer.

[0020] For enhanced performance of the therapeutic composition, it is important that one or more of the components of the therapeutic composition are sufficiently bioadhesive to promote ready adhesion to mucosal surfaces, thereby promoting retention of the pharmaceutical substance adjacent the mucosal surface for effective delivery to the targeted mucosal site. In one preferred embodiment, the biocompatible polymer is bioadhesive, so that when the therapeutic composition is contacted with a mucosal surface, at least a portion of the biocompatible polymer readily adheres to the surface. Preferably, the biocompatible polymer and the pharmaceutical substance are closely associated with each other in the therapeutic composition such that when the biocompatible polymer adheres to a surface inside the oral cavity, the pharmaceutical substance also adheres to the surface along with the biocompatible polymer. This will often be the case when the carrier liquid is water and the biocompatible polymer has surfactant properties. In a preferred embodiment the surfactant properties of the biocompatible polymer enhance solubility of the pharmaceutical substance in the carrier liquid. In one embodiment, the therapeutic composition includes, in addition to the biocompatible polymer, a separate bioadhesive agent that enhances the bioadhesive properties of the therapeutic composition. The bioadhesive agent is frequently a second polymer having even greater bioadhesive properties.

Problems solved by technology

Mucositis is a serious and often very painful disorder involving inflammation of the mucous membrane, with the inflammation often accompanied by infection and / or ulceration.

While cancerous cells are the primary targets of cancer therapies, other cell types can be damaged as well.

Exposure to radiation and / or chemotherapeutics often results in significant disruption of cellular integrity in mucosal epithelium, leading to inflammation, infection and / or ulceration at mucosal sites.

As one example, oral mucositis (OM) is a painful and costly complication of some cancer therapies.

The oral cavity is lined with mucosal epithelium, and exposure to radiation and / or chemotherapeutics results in the disruption of cellular integrity leading to the development of ulcerative lesions commonly referred to as oral mucositis.

The risk of developing mucositis is markedly exacerbated when chemotherapeutic agents that typically produce mucosal toxicity are given in high doses, in frequent repetitive schedules, or in combination with ionizing irradiation (e.g., conditioning regimens prior to bone marrow transplant).

These painful lesions often limit a patient's ability to eat and drink and in some cases require hospitalization.

The presence of these lesions can also interrupt scheduled chemotherapy and / or radiation treatments.

Although topical antifungal prophylaxis and treatment may clear superficial oropharyngeal infections, topical agents tend not to be well absorbed and have not been demonstrated to be effective against more deeply invasive fungal infections, which typically involve the esophagus and lower gastrointestinal tract.

Analgesics such as lidocaine mouthwashes are effective for short periods of time but within hours the pain and discomfort usually returns.

Also, studies utilizing nonsteroidal agents and coating agents, such as sucralfate (Carafate), have had conflicting results.

Finally, claims that chlorhexidine (Peridex) reduces mucositis in both irradiated patients and leukemia patients receiving bone marrow transplants have not been verified.

To date, none of these approaches has shown a significant impact.

Esophagitis in this patient population can impede the progress of cancer treatment.

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