Improved hydrogen storage capacity through hydrolysis of solid NaBH4 catalyzed with cobalt boride

3 Delmas, J. Laversenne, L. Rougeaux, I. Capron, P. Garron, A. Bennici, S. Swierczynski, D. Auroux, A.In this article the feasibility of the reaction of liquid water with a solid NaBH4/catalyst mixture for improved hydrogen storage capacity and on-demand H-2 generation is reported. The synthesized low-cost nanosized catalyst consists of a Co2B core surrounded by an oxide layer, presenting a relatively large specific surface area (70 m(2) g(-1)). Calorimetric experiments coupled to simultaneous measurements of the evolved hydrogen volume have shown the positive effect of the locally heat release during reduction of the superficial oxidized layer. The synergetic effects of the exothermicity of both the oxidized layer reduction and the hydrolysis reaction coupled to the high efficiency of the cobalt boride catalyst led to an "enhanced regime" observed at room temperature. The "enhanced regime" corresponds to a global reaction stoichiometry of 1 mol of NaBH4 reacting with 3 mol of water, conducting to a hydrogen yield of 8.7 wt.%. Effects of temperature and catalyst content were studied. (C) 2010 Professor T. Nejat Veziroglu. Published by Elsevier Ltd. All rights reserved

How to Succeed in Marketing Marine Natural Products for Nutraceutical, Pharmaceutical and Cosmeceutical Markets

The marine ecosystem shelters a vast number of macro- and microorganisms that have developed unique metabolic skills to survive in diverse and hostile habitats. These survival strategies often result in the biosynthesis of an array of secondary metabolites with specific activities and functions in the cellular context. Several metabolites can give origin to high-value commercial products for nutraceutical, pharmaceutical and cosmeceutical markets, among others. This chapter outlines those industries’ paths for marketing marine natural products (MNPs), from discovery and development up to final product marketing. Focus is given on compounds that successfully reached the market and, particularly, the approaches employed by the nutraceutical, pharmaceutical and cosmeceutical companies that succeeded in marketing those products. Some key failures in each market segment are analysed, allowing lessons to be learned and key hurdles to be avoided in MNP development. The main challenges faced during MNP programs are assessed and mapped in the market funnel of common product development routes. Suggestions to surpass these challenges are provided, in order to improve market entry success rates of highly promising marine bioactives in current pipelines, highlighting what can be applied to novel and/or ongoing MNP development programs.info:eu-repo/semantics/publishedVersio

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change –4·0, 95 % CI –7·7 to −0·3; phase 2 OLE patisiran –4·7, –11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment −1·4, 95% CI –6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran. Funding: Alnylam Pharmaceuticals