A human 15-lipoxygenase (15-HLO) assay has been employed to discover new marine-sponge-derived bioactive compounds. Extracts from two different sponges, Jaspis splendens (order Choristida, family Jaspidae) and Suberea sp. (order Verongida, family Aplysinellidae), exhibited potent IC(50) values of 0.4 and 0.1 microg/mL, respectively. Both are sources of terpenoids, and the former is a known source of (+)-jasplakinolide (7), which is inactive as a 15-HLO inhibitor. The terpenoids included (+)-(5S,6S)-subersin (1, IC(50) > 100 microM), (-)-(5R,10R)-subersic acid (2, IC(50) = 15 microM), jaspaquinol (3, IC(50) = 0.3 microM), and (-)-jaspic acid (4, IC(50) = 1.4 microM). Structure elucidations and lipoxygenase activity studies of these compounds are reported.

Engineered particles comprised of lipid-coated microcrystals may provide an acceptable alternative formulation technology for metered dose inhalers in the new hydrofluoroalkane propellants.

Product performance test data are presented on Glycopyrrolate (GP), a LAMA, and Formoterol Fumarate (FF), a LABA, and their combination in Pearl's HFA MDI format (GP MDI, FF MDI, and GP/FF combination MDI). GP and FF MDIs consistently deliver 18 and 2.4 µg GP and FF per actuation, respectively, with over 50% of the delivered dose in a particle size range suitable for uniform deposition in human airways. Their aerodynamic particle size distributions show excellent long term stability when stored at refrigerated (2-8°C), room temperature (25°C/60% RH) or stressed (40°C/75% RH) conditions. The delivered doses and aerosol properties of GP MDIs remain unchanged upon repeat thermal excursions between-5°C and 40°C for several weeks, demonstrating the robustness of Pearl's novel HFA MDI suspensions. GP/FF MDIs also show excellent stability without any physical or chemical interaction between the two actives under a broad range of test conditions. The overall performance attributes for the two drugs in GP/FF MDI combination remain unchanged from the monotherapy GP and FF MDIs. Conclusions Pearl is well positioned to further develop its MDI products. Pearl's MDI products demonstrate the following characteristics:  Physical and chemical stability even under stressed conditions across a wide range of products  Ability to develop very low doses of potent molecules  High fine particle fraction (>50%) with low throat deposition for all products  Excellent dose content uniformity  No pharmaceutical effect observed when developing combination drug products  High speed of development; < 9 months from first formulation to dosing patients Pearl's porous particle platform is ideal for the development of robust MDI products in timelines not previously attainable.