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 Sjrgren'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.

Powder formulations for inhalation which comprise microparticles containing an antibiotic and magnesium stearate are useful for the treatment of bacterial infections associated with certain pulmonary diseases.

The present disclosure features compounds such as those having the Formulae (I) and (II), which can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells. The present disclosure also features methods of treating a condition associated with decreased CFTR activity or a condition associated with a dysfunction of proteostasis comprising administering to a subject an effective amount of a disclosed compound, such as a compound of Formula (I) or (II).

The present disclosure features compounds such as those having the Formulae (I) and (II), which can increase cystic fibrosis transmembrane conductance regulator (CFTR) activity as measured in human bronchial epithelial (hBE) cells. The present disclosure also features methods of treating a condition associated with decreased CFTR activity or a condition associated with a dysfunction of proteostasis comprising administering to a subject an effective amount of a disclosed compound, such as a compound of Formula (I) or (II).

The present invention provides a method of reducing the quantity of mucus in the respiratory tract of a subject with elevated levels of mucus in said respiratory tract. The method includes administering to the subject a compound or composition containing a therapeutically effective amount of a fusion protein comprising a sialidase or an active portion thereof and an anchoring domain. The therapeutically effective amount comprises an amount of the fusion protein that results in a reduction of the quantity of mucus in the respiratory tract after administration of the compound or composition when compared to the quantity of mucus present prior to administration of the compound or composition.

Compounds of Formula I:

##STR00001##

pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.

The present disclosure relates to TGF-beta antibodies and binding fragments thereof, DNA encoding the same, host cells comprising said DNA and methods of expressing the antibody or binding fragment in a host cell. The disclosure also extends to pharmaceutical compositions comprising the antibody or a binding fragment thereof and use of the antibody, binding fragment and compositions comprising the same in treatment of various diseases including fibrosis.

The present disclosure relates to TGF-beta antibodies and binding fragments thereof, DNA encoding the same, host cells comprising said DNA and methods of expressing the antibody or binding fragment in a host cell. The disclosure also extends to pharmaceutical compositions comprising the antibody or a binding fragment thereof and use of the antibody, binding fragment and compositions comprising the same in treatment of various diseases including fibrosis.

This invention relates to compounds of Formula I: ##STR00001##
and pharmaceutically acceptable salts thereof, wherein each X and each R is defined within. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator.

The invention provides liquid formulation compositions and medicament delivery devices, and methods for preparing and using the same. For example, the liquid formulation composition is an emulsion including a solvent and liquid particles, which includes surfactants and are dispersed in the solvent. The volume average particle size of the liquid particles is less than about 100 m; the surface tension of the liquid formulation composition is less than about 60 mN/m; and the absolute value of zeta potential is greater than about 15 mV. The containment vessel may be a sprayer or a dropping device. The invention also provides methods for preparation of the liquid formulation compositions and medicament delivery devices as well as methods for using the same in treatment of various diseases and condition, for example, otitis media, otitis externa, rhinitis, sinusitis, lower respiratory tract inflammation, xerostomia (dry mouth), xerophthalmia (dry eyes) and xeromycteria (dry nose).