Compounds of general formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions.

##STR00001##

The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

The invention provides a compound for use in treating or preventing a disease or condition selected from cystic fibrosis, chronic obstructive pulmonary disease (COPD), asthma, mild pulmonary disease, bronchitis, bronchiectasis, idiopathic bronchiectasis, allergic bronchopulmonary aspergillosis, sinusitis, rhinosinusitis, CFTR-related metabolic syndrome (CRMS), pancreatitis, idiopathic chronic pancreatitis and Sjörgren's syndrome, or for use in preventing male infertility caused by congenital absence of the vas deferens, in a patient by modulating CFTR activity, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a composition comprising (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (ii) a leukotriene receptor antagonist. The invention also provides a composition comprising (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (ii) a CFTR potentiator or a CFTR corrector.

Provided are mucolytic agents represented by formula (Ia)-(Id): ##STR00001##
where the structural variables R.sub.1, R.sub.2, R.sub.5 and R.sub.6 are as defined herein. Also provided are a variety of methods of treatment which take advantage of the mucolytic properties of the compounds represented by formula (Ia)-(Id).

A method of treating a pulmonary disease in a subject in need thereof includes administering to the subject a therapeutically effective amount of an agent that inhibits the renin-angiotensin signaling pathway.

A method of treating a pulmonary disease in a subject in need thereof includes administering to the subject a therapeutically effective amount of an agent that inhibits the renin-angiotensin signaling pathway.

Compound I of the formula (formula) A pharmaceutically acceptable salt of Compound I. Pharmaceutical compositions containing at least Compound I and methods of treating cystic fibrosis comprising administering at least Compound I. Pharmaceutical compositions containing a pharmaceutically acceptable salt of at least Compound I and methods of treating cystic fibrosis comprising administering a pharmaceutically acceptable salt of at least Compound I.

##STR00001##

A method of reducing or treating parainfluenza or influenza virus infection in an immunocompromised patient by administering to the respiratory tract of the patient a composition comprising a therapeutically effective amount of protein having sialidase activity.

Disclosed is a method of treating in a subject of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator. The method comprises administering to the subject Compound (I):

##STR00001##

or pharmaceutically acceptable salts thereof, together with food. Also disclosed are products comprising Compound (I) and the use of such products.