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RMN Haut Champ Et Bas Champ Pour L'analyse De Produits De Santé RMN haut champ et bas champ pour l’analyse de produits de santé Gaëtan Assemat To cite this version: Gaëtan Assemat. RMN haut champ et bas champ pour l’analyse de produits de santé. Chimie thérapeutique. Université Paul Sabatier - Toulouse III, 2018. Français. NNT : 2018TOU30268. tel-02338817 HAL Id: tel-02338817 https://tel.archives-ouvertes.fr/tel-02338817 Submitted on 30 Oct 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE En vue de l’obtention du DOCTORAT DE L’UNIVERSITÉ DE TOULOUSE Délivré par l'Université Toulouse 3 - Paul Sabatier Présentée et soutenue par Gaëtan ASSEMAT Le 10 décembre 2018 RMN haut champ et bas champ pour l'analyse de produits de santé. Ecole doctorale : SDM - SCIENCES DE LA MATIERE - Toulouse Spécialité : Chimie-Biologie-Santé Unité de recherche : SPCMIB - Laboratoire de Synthèse et PhysicoChimie de Molécules d'Intérêt Biologique Thèse dirigée par Véronique GILARD-POTEAU et Myriam MALET-MARTINO Jury M. Stéphane VIEL, Rapporteur M. Pierre-Antoine BONNET, Rapporteur M. Patrick GIRAUDEAU, Examinateur Mme Françoise NEPVEU, Examinateur Mme Véronique GILARD-POTEAU, Directeur de thèse Remerciements Mes premiers mots se doivent d’aller à Messieurs Baltas et Génisson, Directeurs successifs du Laboratoire de Synthèse et PhysicoChimie de Molécules d’Intérêt Biologique (LSPCMIB) où j’ai réalisé ce doctorat; merci à vous de m’avoir permis d’intégrer votre laboratoire et d’effectuer ma thèse dans les meilleures conditions possibles. C’est ensuite naturellement que je voudrais remercier tous les membres du jury qui ont fait le déplacement pour juger mon travail. Chacun avec vos spécialités respectives, vous avez su conduire une conversation riche et exaltante, en faisant un moment d’échange scientifique riche et plein de bienveillance. Deux rapporteurs d’horizons bien distincts ont notamment permis de faire ressortir ce qui est à mon sens le point fort de cette thèse, à savoir une approche scientifique complexe au service de problématiques de santé publique. Monsieur Viel aura notamment grandement enrichi la discussion par ses connaissances manifestes sur la RMN diffusionnelle, mais également sur la RMN quantitative. Monsieur Bonnet aura quant à lui fait ressortir les complexités mais surtout les subtilités d’un monde où beaucoup de choses restent malheureusement encore à faire. Monsieur Giraudeau… Patrick, j’ai pris autant de plaisir à échanger avec toi en ce jour un peu spécial, qu’à travailler avec toi et toute ton équipe durant ces quelques semaines; c’est à chaque fois réellement enrichissant et j’espère que nos échanges perdureront ! Quant à Madame Nepveu, présidente hors pair, merci encore d’avoir accepté mon invitation et d’avoir enrichi la conversation d’une expérience forçant l’admiration. Dans ce Jury, il y avait également Mesdames Gilard et Malet-Martino, mais ici et vous m’en excuserez je l’espère, ce n’est pas en tant que juges que j’ai envie de vous remercier mais plutôt en tant qu’encadrantes. Madame Gilard, 3 années passées sous votre direction et à vrai dire je n’ai rien à redire, problèmes pratiques, théoriques, rédactionnels ou même humains, vous avez toujours été là, et avez toujours réagi extrêmement rapidement me permettant de travailler dans des conditions optimales sans jamais me décourager, et pour cela, merci beaucoup ! Madame Martino, je pourrais écrire une autre thèse sur tout ce que vous m’avez appris… mais je me contenterai de rappeler ici à quel point votre professionnalisme est exemplaire et je voudrais que vous sachiez qu’il a été et qu’il restera un exemple pour moi. Merci de m’avoir accueilli dans votre équipe et d’avoir fait de cette thèse un vrai plaisir. Dans cette équipe, on compte également Monsieur Balayssac Stéphane; précieux au quotidien tu m’as beaucoup appris et permis de devenir très vite autonome; tu n’étais certes ni dans le jury, ni dans la direction, mais tu as été pour moi tout aussi important ! La science nous a rapprochés mais ce sont surtout nos franches rigolades sans jamais aucun tabou que je retiendrai ! Encore merci d’avoir souvent agi « dans l’ombre ». Professeur émérite et on le serait pour moins, Robert Martino à également pris part à ce projet; nous n’avons pas pu nous côtoyer beaucoup et j’en suis le premier déçu, mais à chacune de vos visites qu’elles soient professionnelles ou non, j’ai adoré nos conversations. Votre présence à chacune de mes présentations locales m’a également grandement touché, et pour tout cela merci beaucoup. Rabab Hachem, tu as été la première personne à qui j’ai eu à faire, formatrice, amie, protectrice, pendant ces quelques mois tu as eu pour moi une importance plus grande que tu ne l’estimes. Merci pour tout, sans ta bonne humeur communicative, cette thèse aurait pu être bien différente. Une thèse en chimie analytique ne serait rien sans une instrumentation fonctionnelle et un personnel compétent, et pour avoir rendu mon quotidien plus tranquille, je voudrais sincèrement remercier tous les services communs : Isabelle Fabing en chromatographie avec qui j’ai passé plusieurs journées… souvent de galère mais toujours avec le moral ! Nathalie Martins et Catherine Claparols en spectrométrie de masse, ceux qui ont lu ou qui liront cette thèse comprendront à quel point elles ont été indispensable à ce projet ! Et enfin et surtout le service commun de RMN, je vous ai dérangé environ…tous les jours (vacances comprises) et vous avez toujours répondu présents ! Masochisme ou professionnalisme ? Mon choix est fait, merci à vous Marc Vedrenne, Pierre Lavedan, Caroline Topan, Stéphane Massou et Claude Andreu. Je voudrais appuyer mes remerciements envers toi Stéphane, réel passionné aux compétences indénombrables, tu as été pour moi une source de motivation intarissable. Merci également à tous mes amis doctorants rencontrés pendant ces 3 années, Lori Gonnet et Thomas Levy, vous êtes les suivants alors bonne chance à vous, même si je ne m’inquiète pas vraiment ! Un énorme merci également à deux personnes qui sont devenus de vrais amis après avoir été de vrais soutiens, je pense ici à vous Romain et Aritz, pas de formalisme entre nous, mais je suis persuadé que vos carrières seront aussi belles que l’amitié que l’on a liée. Une pensée aussi pour Jin Hui Wang, aujourd’hui rentré en Chine, un ami plein de sagesse et toujours de bon conseil. Quelques mots enfin pour Baptiste Amouroux, ami de longue date, qui aurait imaginé qu’on en serait là ? Bon courage pour la finalisation de ta belle thèse et bon courage pour la carrière académique à laquelle tu aspires. Enfin, je voudrais remercier ma famille, mes parents et mon frère dans un premier temps, soutien infaillible du premier au dernier jour, cela fait 26 ans que je me considère chanceux de vous avoir à mes côtés et cela n’est pas près de changer. Un merci tout particulier également à toi Poema pendant ces 3 ans la vie n’a pas forcément été évidente pour nous, mais tu as su la rendre bien plus facile et surtout bien plus agréable pour moi; on a malgré tout passé des moments magnifiques et j’en suis persuadé, les plus beaux restent à venir. Finalement je voudrais dédier ce mémoire à mes grands-parents, source sans fin de respect, de bonne humeur et d’humilité, vous qui ne vous êtes jamais soucié d’autres choses que de mon bonheur, aujourd’hui, même si la santé vous fait défaut, et que comme vous aimiez le dire vous ne compreniez rien à ce que je faisais, j’espère que vous êtes aussi fiers que moi je peux l’être. Sommaire Abréviations Introduction générale .......................................................................................................................... 1 Partie 1 ................................................................................................................................................... 5 1 Les compléments alimentaires, leurs possibles adultérations et leurs méthodes d'analyse ......... 7 1.1 Les compléments alimentaires .............................................................................................. 7 1.1.1 Définitions et premières tentatives d'harmonisations européennes ............................. 7 1.1.2 Compléments alimentaires et régulation ........................................................................ 8 1.1.2.1 Un contrôle de la composition encore très disparate au sein de l’UE .................. 10 1.1.2.2 Une règlementation française plus stricte ............................................................ 11 1.1.3 Marché Européen .......................................................................................................... 12 1.1.3.1 Données commerciales ......................................................................................... 12 1.1.3.2 Consommation : Impacts et tendances ................................................................. 13 1.1.3.3 Le marché en France ............................................................................................. 15 1.1.3.4 La nécessite de contrôle des canaux de distributions ........................................... 16 1.2 Adultération
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