A number of patents are issued every month to many pharmaceutical companies. The purpose of this column is to highlight and summarize key patents issued from October to November 2014 by the US Patent Office (www.uspto.gov.)
Melampomagnolide B derivatives as antileukemic and cytotoxic agents.
P.A. Crooks, C.T. Jordan, S. Pel, and S. Nasim; U.S. Patent # 8,884,027. November 11, 2014.
Melampomagnolide B (MMB) is a new antileukemic sesquiterpene. A biotin-conjugated derivative of MMB was prepared to elucidate its mechanism of action. Acute myelogenous leukemia (AML) is a life-threatening disorder and there are very few drug options. The naturally occurring (plant derived) compound parthenolide (PTL) showed potential anti-leukemia properties. MMB was found, during the SAR studies of PTL, as a promising compound. MMB has low water solubility. More water-soluble prodrugs were prepared to improve the bioavailability of MMB.
Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery.
L.A. Dellamary, J. Reiss, E.G. Schutt, J.G. Weers, and T.E. Tarara; U.S. Patent # 8,877,162. November 4, 2014.
This invention is related to stable, dry metal ion-lipid microparticle compositions for drug delivery exhibiting improved stability and dispersability. Complexing lipids with metal cations substantially changes the structure of the lipid by increasing its ordering and reducing molecular mobility. This, in turn, reduces the instability problems of active compounds susceptible to humidity upon storage as typical of spray dried lipid and drug combinations. The stable dry pharmaceutical composition mentioned was preferably a dry powder comprised of microparticles exhibiting a glass transition temperature of at least 20°C above the recommended storage temperature.
Salts of physiologically active and psychoactive alkaloids and amines simultaneously exhibiting bioavailability and abuse resistance.
D.W. Bristol, C.R. King, J.P. Mitchener, Jr., and V.H. Audia; U.S. Patent # 8,859,622. October 14, 2014.
An organic salt of amine-containing pharmaceutically active compound was used to prepare a sustained release oral formulation. The formulation was bioavailable by oral administration, but bio-unavailable when illicit or abuseintended routes of administration were attempted. The drug formulation had two distinct dissolution pro les based on oral and other route of administration. The key objective was to minimize abuse potential. The API was resistant to direct extraction techniques either into an aqueous solution or into an organic solvent.
Stabilized compositions containing alkaline labile drugs.
M.M. Crowley, J.M. Keen, J.J. Koleng, and F. Zhang; U.S. Patent # 8,883,187. November 11, 2014.
An alkaline labile drug, such as fentanyl or testosterone, was incorporated in a non-alkaline thermoplastic bioadhesive matrix. An acidic excipient was mixed with an alkaline thermoplastic matrix-forming material (PEO) and the mixture was hot-melt extruded. The process neutralized the matrixforming material and to this the drug was added. It reduced the degradation of an alkaline-labile drug during hot-melt extrusion. The composition contained water-swellable, watersoluble or water-erodible polymers to produce a stabilized bioadhesive formulation.
Protein formulations and methods of making same.
W. Fraunhofer, A.Bartl, H.J. Krause, M.Tschoepe, and K. Kaleta; U.S. Patent # 8,883,146. November 11, 2014.
Instability can be a major problem while developing protein formulations. A way of improving stability is by including excipients that interact with the protein in solution to keep it stable, soluble and unaggregated. This patent claimed an aqueous formulation comprising an antibody at a concentration of at least 50 mg/mL, a nonionizable excipient, a buffer, and water, which gave the formulation characteristics such as low conductivity (less than about 2.5 mS/cm). The antibody had a molecular weight (Mw) greater than about 47 kDa. The protein of interest was dia ltered using water as a dia ltration medium. The present invention related to methods and compositions for an aqueous stable formulation without the need for additional agents.
Server for integrated pharmaceutical analysis and report generation service, method of integrated pharmaceutical manufacturing and research and development numerical analysis, and computer readable recording medium.
Y.J. Lee, C.F. Wang, H.L. Chen, and J.M. Chiu; U.S. Patent # 8,868,225. October 21, 2014.
A web-based tool (as a server) for integrated pharmaceutical analysis and report generation service was provided in this invention. It integrated the functions of heterogeneous software packages so as to analyze raw data and generate reports. The server could be used for numerical analysis and report generation of analytical method validation, stability testing, cleaning validation, BA/BE data, IVIVC data.
Calcium carbonate granulation.
K.W. Lang, J.W. Dibble, R. Levin, and G.B. Murphy; U.S. Patent # 8,883,223. November 11, 2014.
The recommended daily allowance of calcium for adults is 800 to 1400 mg. Calcium carbonate contains only 40% by weight of elemental calcium. Calcium carbonate, ~ 2.5 to 3.5 g, must be consumed daily to meet the recommendations. As a result, the calcium tablets are normally large in size. Inventors could reduce the tablet volume by selecting the median particle diameters of calcium carbonate between 1 to 15 µm. The granulation process involved (1) mixing powdered calcium carbonate, maltodextrin and excipients in a high shear mixer; (2) adding water to the composition and mixing; (3) adding oil to the composition and mixing; and (4) drying the resulting composition in a convection drying oven. Increased median particle size showed an increase in tap density. One would tend to select larger particle size. But smaller particles produced lower tablet volume upon compression.