Methods for improving lung condition and airway

Abstract

The present invention provides methods for improving the lung condition of a cystic fibrosis patient, or for treating a clinical symptom in a patient's airway (e.g., nose, lung, and sinus), by administering a composition comprising an iodine-containing compound and a steroid to the patient.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application of U.S. application Ser. No. 14 / 127,846 filed on Dec. 19, 2013, which is the national phase application of PCT / US2011 / 041470 filed on Jun. 22, 2011, the contents of both of which are incorporated herein by reference in their entirety.BACKGROUND OF THE INVENTION[0002]Chronic rhinosinusitis (CRS) is a common clinical problem with significant morbidity and often-refractory symptoms that accounts for approximately 26.7 million office and emergency visits per year in the U.S. Originally part of the yogic and ayurvedic traditions, sinonasal irrigation is an adjunctive therapy for sinusitis and sinus symptoms that flushes the nasal cavity, facilitating a wash of the structures within. Several randomized controlled trials examining irrigation suggest that it is a safe, effective, and tolerable therapy for acute and chronic sinus symptoms. Previous studies have reported improvement of quality of life sc...

AI Technical Summary

Benefits of technology

[0015]Such surprisingly stable pharmaceutical compositions containing highly toxic iodine and anti-inflammatory steroids are capable of synergistically treating sinus symptoms and inhibiting or even eliminating biofilms without casing toxic inflammatory reactions of the sino-nasal tissues. Additionally, these compositions are able to limit the inflammatory cascade and eliminate microbial, fungal, and viral activators of inflammation because of their ability to safely deliver antiseptic iodine and minimally absorbed sinonasal steroids.

[0023]The compositions of this invention can be administered by employing an apparatus which includes a flexible bottle with an opening and conduit tube (such as that available commercially from NeilMed, Santa Rosa, Calif.). They are capable of providing iodophor in sufficient concentration to deliver molecular iodine at a low but sufficient level to adequately preserve the compositions or to adequately eliminate infectious organisms or to eliminate biofilms.

[0038]The pharmaceutical composition of this invention have great utility in the treatment of nasal and sinus inflammation where infection may also be present, in the treatment of non-infectious inflammation where there is a potential to form biofilms, in the treatment of inflammation where there are existing biofilms that may be destroyed by the iodine component, in the treatment of mixed infection and inflammation where irrigation with a mixed steroid-iodine containing solution could treat both infectious and inflammatory components, allergic inflammation of the sinuses and nasal passages and other cases of and inflammation such as that which occurs after surgery. Further, they are self-preserved and require no additional agents for prolonged sterile storage, thus eliminating the need of using benzalkonium, imidurea, and other toxic preservatives.

[0039]Surprisingly, irrigating the sinuses with a pharmaceutical composition of this invention (e.g., povidone-iodine / budesonide) improves the clinical symptoms in all parts of the airway (sinus, nose and lungs). The data from using PVP / I budesonide in patient with cystic fibrosis has shown clinically and statistically significant improved patient outcome scores (SNOT 22) and reduction in bacterial load.

Problems solved by technology

Diseases that compromise airway function, particularly cystic fibrosis, dramatically increase the risk and severity of sinusitis across all pathogen species with a greatly increased incidence of Pseudomonas.

Some of the mechanisms involved in biofilm resistance to antimicrobials may differ from the mechanisms responsible for antimicrobial resistance in planktonic bacteria, rendering traditional antibiotics less potent.

Mutations in the CFTR gene cause the production of abnormally functioning ion channels affecting certain glands in the mucus membranes, causing those glands to that produce thick, sticky mucus.

This condition occurs in the sino-nasal cavity and promotes recurrent sinus infections and polyp formation when the gene responsible for manufacturing an ion channel becomes mutated, causing the gene to work abnormally.

Most iodine preparations are toxic at useful concentrations, with the exception of iodophoric agents like povidone-iodine.

It has been widely known that iodine or iodine-releasing agents (e.g., iodophor) are incompatible with most steroid preparations due to the high potential for chemical reactivity between molecular iodine and steroid moieties.

Commonly used preservatives include benzalkonium can cause bronchoconstriction, impairment of ciliary beat frequency and other unwanted effects in patients using preservative-containing steroids.

However, studies have confirmed the possible harmful effects of conventional preservatives in solutions and suspensions.

Additional in vitro studies have demonstrated that benzalkonium preservatives can damage the ciliary epithelium of the nose and sinuses.