Intérêt du dosage de l interféron gamma par rapport à l IDR dans le diagnostic de tuberculose active

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

Détection de QTL associés à la résistance à la rouille courbeuse chez le Pin maritime

National audienc

Identification et modalités d'expression des gènes codant pour les PR-10 du pommier soumis à des stress biotiques et abiotiques

National audienc

Characterization in apple leaves of two subclasses of PR-10 transcripts inducible by acibenzolar-S-methyl, a functional analogue of salicylic acid

International audienc

Solid-State Overview of R-Baclofen: Relative Stability of Forms A, B and C and Characterization of a New Heterosolvate

International audienc

Relative stability of Arbaclofen polymorphs: selective pathways to isolate metastable phases via solvates formation

International audienceWhen considering polymorphism of a given API, the identification of the phase stability is a critical parameter [1]. In an industrial perspective, specific and robust pathways to isolate either one polymorph or another should be developed. Moreover, the solid-state landscape is often complicated by the presence of hydrates and solvates or non-reproducible chemical purity. Baclofen is a pharmaceutical active ingredient originally produced as a myorelaxant, which recently gain interests to prevent alcoholic addiction [2]. One pathway to limit the dosage without lowering the activity would result in a ‘chiral switch’ towards the main active enantiomer: R-Baclofen or Arbaclofen. The latter crystallizes in two already known polymorphs (A and B). A new polymorphic form (Form C) of enantiopure Baclofen was recently isolated and characterized by our team [3]. Crystal structures of R-Baclofen Form A and Form C were resolved from powder diffraction data, and a structural approach was established for Form B. In this work, we present the relative stability of these three forms based on structural data, thermal analyses and solvent-mediated conversions. The experiments highlight the energetical order A < C < B at 25 °C (A is the most stable form), whereas above 180°C it would likely be:C < A < B (C being the stable modification). Nevertheless, every polymorph displays a poor solubility in most of the usual solvents. Then, once R-Baclofen crystallizes, it would be difficult to convert, by slurrying, one form into another in a reasonable period of time (without redissolving a significant part of the material by salt formation). We present here a reproducible process to isolate metastable Form B. A new heterosolvate of the molecule was isolated with N,N-DMF and water. This heterosolvate offers a new pathway to isolate pure R-Baclofen Form B by simple desolvation in water, depending on the initial impurity level. Moreover, we discuss the impact of mechanical stress on Arbaclofen which could also lead to undesired polymorphic conversio

Anti-heparanase activity of ultra-low-molecular-weight heparin produced by physicochemical depolymerization

International audienceHeparanase is an endo-β-D-glucuronidase that plays an important role in cancer progression, in particular during tumor angiogenesis and metastasis. Inhibiting this enzyme is considered as one of the most promising approaches in cancer therapy. Heparin is a complex glycoaminoglycan known as a strong inhibitor of heparanase. It is primarily used in clinical practice for its anticoagulant activities, which may not be compatible with its use as anti-angiogenic agent. In this study, we described the production of ultra-low-molecular-weight heparins (ULMWH) by a physicochemical method that consists in a hydrogen peroxide-catalyzed radical hydrolysis assisted by ultrasonic waves. We assessed the structural characteristics, anticoagulant and anti-heparanase activities of the obtained heparin derivatives and compared them with three commercial low-molecular-weight heparins (LMWH), glycol-split non-anticoagulant heparins and heparins produced by enzymatic methods. ULMWH generated by the physicochemical method were characterized by high anti-heparanase and moderate anticoagulant activities. These heparin derivatives might be potential candidates for cancer therapy when a compromise is needed between anti-heparanase and anticoagulant activities

Production of heparin and λ-carrageenan anti-heparanase derivatives using a combination of physicochemical depolymerization and glycol splitting

International audienc