Methods for the Treatment of Systemic Disorders Treatable with Mast Cell Stabilizers, including Mast Cell Related Disorders

Abstract

Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders, are provided.

Description

CROSS-REFERENCE[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 105,423, filed Jan. 20, 2015; and claims the benefit of U.S. Provisional Application No. 61 / 978,711, filed Apr. 11, 2014; and claims the benefit of U.S. Provisional Application No. 61 / 971,709, filed Mar. 28, 2014; and claims the benefit of U.S. Provisional Application No. 61 / 937,928, filed Feb. 10, 2014, all of which are incorporated herein by reference in their entireties.BACKGROUND OF THE INVENTION[0002]Mast cells play a key role in the inflammatory process. They are found in the perivascular spaces of most tissues and contain pro-inflammatory and vasoactive mediators, such as serine proteases, tryptase, histamine, serotonin, proteoglycans, thromboxane, prostaglandin D2, leukotriene C4, platelet-activating factor, and eosinophil chemotactic factor. When activated, mast cells rapidly release granules and various hormone mediators into the interstitium, a process referred to as degranulat...

AI Technical Summary

Benefits of technology

The patent text describes methods for treating various systemic mast cell related disorders by delivering a mast cell stabilizer to a patient. The methods involve administering the mast cell stabilizer through various routes such as inhalation, oral, or injection. The composition can be administered once a day, twice a day, or three times a day, depending on the patient's needs. The method can also involve using a high efficiency nebulizer to deliver the mast cell stabilizer to the patient. The technical effects of the patent text include providing a systemically effective amount of the mast cell stabilizer to treat the disorder and minimizing adverse events associated with the mast cell stabilizer.

Problems solved by technology

Systemic mast cell related disorders may result from excessive proliferation of mast cells or abnormal release of pro-inflammatory and vasoactive mediators.

The utility of mast cell stabilizers in the treatment of systemic mast cell related disorders, such as mastocytosis, has been limited.

For example, cromolyn sodium (also known as disodium cromoglycate or DSCG) was first approved in 1973 and is widely considered safe, but it has found limited utility because the amount of the compound that can be delivered systemically is inadequate.

However, the oral solution is only modestly effective for treating localized gastrointestinal symptoms, and it is not effective for the treatment of systemic symptoms because of the low oral bioavailability of cromolyn sodium (less than 1%).

Efforts have been made to increase the oral bioavailability of cromolyn sodium in order to provide systemically effective amounts for the treatment of systemic mast cell related disorders, but these efforts have not yielded products that achieve significantly higher oral bioavailability of cromolyn sodium in a practical, safe, and well-tolerated manner.