Este trabalho apresenta um estudo dos processos de prensagem e sinterização do politetrafluoretileno (PTFE) com o objetivo principal de investigar a influência dos parâmetros desses processos na microestrutura e nas propriedades mecânicas do material após sinterização. O PTFE faz parte do grupo dos termoplásticos, mas assim como outros polímeros de alto peso molecular, apresenta elevada viscosidade no estado fundido que impede sua utilização em moldagem por injeção, e seu processamento é realizado por compactação a frio do pó polimérico seguida de sinterização. No processo de sinterização é aplicado um tratamento térmico acima da temperatura de fusão do material que é responsável por grandes deformações anisotrópicas que, por sua vez, são dependentes do histórico de carregamentos induzidos na fase de compactação. Com o objetivo de desenvolver modelos de comportamento termomecânicos para realizar simulações computacionais dessas etapas de fabricação, ensaios experimentais foram realizados para se investigar os diferentes mecanismos de evolução microestrutural e de deformações nas etapas de compactação e sinterização. O estudo experimental do processo de compactação compreendeu a realização de ensaios de compactação uniaxial (oedométrico), de compactação hidrostática em prensa isostática e ensaios triaxiais verdadeiros em um dispositivo original acoplado numa prensa triaxial com seis atuadores eletrohidráulicos. Através dos resultados obtidos dos ensaios de compactação foi possível identificar os parâmetros do modelo de Drucker-Prager/cap, disponível na biblioteca de leis de comportamento do programa de cálculo pelo método dos elementos finitos ABAQUSTM, que permitiu de simular numericamente alguns casos simples. O estudo experimental do processo de sinterização foi realizado com o auxílio de ensaios de termogravimetria (TGA), calorimetria exploratória diferencial (DSC) e ensaios de dilatometria em corpos-de-prova isótropos e anisótropos com diferentes índices de vazios. Através dos resultados obtidos destes ensaios foi possível identificar que a deformação global de sinterização é composta por uma deformação térmica reversível, uma deformação devido à mudança de fase cristalina em fase amorfa -ou vice-versa-, uma deformação devido ao fechamento dos vazios e uma deformação de recuperação. Este estudo foi realizado em dois tipos de materiais, sendo o PTFE puro e o PTFE reforçado com 5wt% de EkonolTM e 5wt% de fibras de carbono, respectivamente comercializados pelos nomes de TeflonTM 6407 e TeflonTM 6507. / The main objective of this work is to study the influence the process parameters on the microstructure and the mechanical properties of components manufactured by compaction at room temperature and sintering of polytetrafluorethylene (PTFE). Similary to other High Molecular Weight Polymers and although it belongs to the group of thermoplastic polymers, since it cannot be processed in the melt state because its very high viscosity, PTFE, is powder processed -that consists in sintering compacted powder-. Sintering corresponds to a heat treatment up to temperatures higher than the melting temprature, inducing finite deformations that are generally anistropic and dependent on the mechanical loading the material has been submitted to during the pre-compaction at room temperature. In order to develop thermo-mechanical constitutive equations that could be used during predictive numerical simulations of the whole process, different tests have been performed to study the different mechanisms that are responsible for microstructural evolutions and deformations during compaction and sintering. The experimental study of the compaction has been performed via uniaxial (oedometric) compaction tests, hydrostatic compaction tests that were made with an isostatic hydraulic press and triaxial tests that were made with and original device installed on an electrohydraulic testing machine six actuators. A \"Drucker-Prager/cap\" type elasto-plastic model -as available in the constitutiveequations library of ABAQUSTM industrial finite element software- has been identified from the results of these tests, so that a few simple cases have been numerically simulated. The experimental study of the sintering process has been performed via Thermo-Gravimetric Analyses (TGA), Differential Scanning Calorimetric analyses (DSC) and dilatometry tests that were performed on isotropic or anisotropic specimens with different values of the porosity From the results of these tests it has been possible to decompose the sintering deformation into different mechanisms, viz. a reversible thermal expansion, a strain that is linked to the transition from the crystalline phase to the amorphous phase -or vice versa-, a pore closure strain and a recovery strain. This study has been performed on a powder made of pure PTFE and a powder of PTFE filed with 5wt% EkonolTM and 5wt% of carbon fibres, respectively available as TeflonTM 6407 and TeflonTM 6507.

Nach den Ergebnissen der zweiten Nationalen Verzehrsstudie sind in Deutschland bereits 66 % der Männer und 51 % der Frauen übergewichtig (BMI > 25) oder adipös (BMI > 30) [BMELV, 2008]. Bisher auf dem Markt befindliche „Light-Lebensmittel“ mit Fettaustausch- bzw. Fettersatzstoffen weisen jedoch häufig sensorische Mängel auf. Im Kooperationsprojekt „Pflanzliche Fettaustauschstoffe aus sphärischen Proteinmizellen“ (Universität Leipzig: Institut für Lebensmittelhygiene; Freising: Fraunhofer IVV) wurde ein Lupinenproteinisolat entwickelt, welches micellare Strukturen mit hydrophober Oberfläche ausbilden kann und sich aufgrund seiner fettähnlichen Eigenschaften als neuer proteinbasierter Fettaustauschstoff in Lebensmitteln eignet. Aufgrund der geringen mikrobiologischen Stabilität und einer hohen Belastung mit sporenbildenden Bakterien, z. T. Bacillus cereus, waren jedoch Maßnahmen zur Entkeimung der Rohstoffe sowie des Proteinisolats notwendig. Die Arbeit stellt diese Maßnahmen und deren Einfluss auf die mikrobiologische Beschaffenheit sowie sensorische, technofunktionelle und ausgewählte ernährungsphysiologische Eigenschaften dar. In der vorliegenden Arbeit wurde eine physikalische Methode der Saatgutentkeimung etabliert (130 °C/60 min), welche die mikrobielle Stabilisierung des lupinenproteinbasierten Fettaustauschstoffes sicherstellte, wobei die sensorische Qualität (Geschmack, Cremigkeit, Farbe) nur minimal, die ernährungsphysiologische (in-vitro-Verdaubarkeit, Maillard-Produkte, Polyphenolgehalt) jedoch nicht beeinflusst wurde. Starke Veränderungen der technofunktionellen Eigenschaften (z. B. Gelbildung, Wasserbindung, Emulgierbarkeit, Schaumbildung etc.) konnten sowohl im positiven als auch im negativen Sinne nicht beschrieben werden. Lichtmikroskopische Aufnahmen und Untersuchungen der Proteine mittels SDS-PAGE und DSC bestätigten eine nur geringfügige Beeinflussung der micellaren Struktur und Proteinzusammensetzung. Die Anwendung als Fettaustauschstoff in Lebensmitteln würde somit nicht beeinträchtigt. Der Einfluss der Saatgutbehandlung auf das Protein war wesentlich geringer als eine direkte thermische Behandlung des Proteinisolats. Im Hinblick auf den Gesamtprozess sollte eine Pasteurisierung der feuchten Proteinisolate im nichtproteinschädigenden Temperaturbereich (75 °C/5 min) dennoch durchgeführt werden, um während des Prozesses eingetragene Mikroorganismen zu inaktivieren.

This dissertation deals with quantitative perfusion analysis of MRI contrast-enhanced image time sequences. It focuses on two so far separately used methods -- Dynamic contrast-enhanced MRI (DCE-MRI) and Dynamic susceptibility contrast MRI (DSC-MRI). The common problem of such perfusion analyses is the unreliability of perfusion parameters estimation. This penalizes usage of these unique techniques on a regular basis. The presented methods are intended to improve these drawbacks, especially the problems with quantification in DSC in case of contrast agent extravasation and instability of the deconvolution process in DCE using advanced pharmacokinetic models. There are a few approaches in literature combining DCE and DSC to estimate new parameters of the examined tissue, namely the relaxivity of the vascular and of the interstitial space. Originally, in this scheme, the 2CXM DCE model was used. Here various models for DCE analysis are tested keeping in mind the DCE-DSC combination. The ATH model was found to perform better in this setting compared to 2CXM. Finally, the ATH model was used in alternating DCE-DSC optimization algorithm and then in a truly fully simultaneous DCE-DSC. The processing was tested using simulated and in-vivo data. According to the results, the proposed simultaneous algorithm performs better in comparison with sequential DCE-DSC, unleashing full potential of perfusion analysis using MRI.

Nach den Ergebnissen der zweiten Nationalen Verzehrsstudie sind in Deutschland bereits 66 % der Männer und 51 % der Frauen übergewichtig (BMI > 25) oder adipös (BMI > 30) [BMELV, 2008]. Bisher auf dem Markt befindliche „Light-Lebensmittel“ mit Fettaustausch- bzw. Fettersatzstoffen weisen jedoch häufig sensorische Mängel auf. Im Kooperationsprojekt „Pflanzliche Fettaustauschstoffe aus sphärischen Proteinmizellen“ (Universität Leipzig: Institut für Lebensmittelhygiene; Freising: Fraunhofer IVV) wurde ein Lupinenproteinisolat entwickelt, welches micellare Strukturen mit hydrophober Oberfläche ausbilden kann und sich aufgrund seiner fettähnlichen Eigenschaften als neuer proteinbasierter Fettaustauschstoff in Lebensmitteln eignet. Aufgrund der geringen mikrobiologischen Stabilität und einer hohen Belastung mit sporenbildenden Bakterien, z. T. Bacillus cereus, waren jedoch Maßnahmen zur Entkeimung der Rohstoffe sowie des Proteinisolats notwendig. Die Arbeit stellt diese Maßnahmen und deren Einfluss auf die mikrobiologische Beschaffenheit sowie sensorische, technofunktionelle und ausgewählte ernährungsphysiologische Eigenschaften dar. In der vorliegenden Arbeit wurde eine physikalische Methode der Saatgutentkeimung etabliert (130 °C/60 min), welche die mikrobielle Stabilisierung des lupinenproteinbasierten Fettaustauschstoffes sicherstellte, wobei die sensorische Qualität (Geschmack, Cremigkeit, Farbe) nur minimal, die ernährungsphysiologische (in-vitro-Verdaubarkeit, Maillard-Produkte, Polyphenolgehalt) jedoch nicht beeinflusst wurde. Starke Veränderungen der technofunktionellen Eigenschaften (z. B. Gelbildung, Wasserbindung, Emulgierbarkeit, Schaumbildung etc.) konnten sowohl im positiven als auch im negativen Sinne nicht beschrieben werden. Lichtmikroskopische Aufnahmen und Untersuchungen der Proteine mittels SDS-PAGE und DSC bestätigten eine nur geringfügige Beeinflussung der micellaren Struktur und Proteinzusammensetzung. Die Anwendung als Fettaustauschstoff in Lebensmitteln würde somit nicht beeinträchtigt. Der Einfluss der Saatgutbehandlung auf das Protein war wesentlich geringer als eine direkte thermische Behandlung des Proteinisolats. Im Hinblick auf den Gesamtprozess sollte eine Pasteurisierung der feuchten Proteinisolate im nichtproteinschädigenden Temperaturbereich (75 °C/5 min) dennoch durchgeführt werden, um während des Prozesses eingetragene Mikroorganismen zu inaktivieren.:1 Einleitung und Zielstellung 1 2 Stand des Wissens 4 2.1 Die Lupine 4 2.1.1 Anbau und Verbreitung 4 2.1.2 Einsatz von Lupinenprodukten und -proteinen in der Humanernährung 5 2.1.3 Inhaltsstoffe und deren Verteilung 5 2.1.4 Lupinenproteine 10 2.1.4.1 Einteilung und Struktur der Lupinenproteine 10 2.1.4.2 Lupinenproteine und Allergenität 12 2.1.5 Eigenschaften der verschiedenen Lupinenproteinfraktionen 13 2.1.5.1 Ernährungsphysiologische Eigenschaften 13 2.1.5.2 Funktionelle Eigenschaften 15 2.1.5.3 Modifikation der Proteinstruktur 15 2.1.5.4 Herstellung verschiedener Lupinenproteinpräparate 16 2.1.5.5 Micellare Proteine 17 2.2 Möglichkeiten der Fettreduktion in Lebensmitteln 18 2.2.1 Fettaustauschstoffe 18 2.2.1.1 Fettaustauschstoffe auf Proteinbasis (Mikropartikulierte Proteine) 18 2.2.1.2 Fettaustauschstoffe auf Kohlenhydratbasis 19 2.2.1.3 Quellstoffe 19 2.2.2 Fettersatzstoffe 19 2.2.2.1 Spezielle Triglyceride 20 2.2.2.2 Kohlenhydratpolyester 20 2.2.2.3 Retrofette 20 2.3 Herstellung des lupinenproteinbasierten Fettaustauschstoffes 20 2.4 Saatgutbehandlung 21 2.4.1 Methoden der Lebensmittelkonservierung 22 2.5 Proteinfunktionalität 25 2.5.1 Definition und Zusammenhang zu Proteinen 25 2.5.2 Ausgewählte funktionelle Eigenschaften 26 2.5.2.1 Wasserbindevermögen 26 2.5.2.2 Ölbindevermögen 26 2.5.2.3 Löslichkeit 27 2.5.2.4 Emulgiervermögen 27 2.5.2.5 Schaumbildungsvermögen 28 2.5.2.6 Gelbildungsvermögen 29 2.5.2.7 Oberflächenhydrophobität 30 2.5.2.8 Bedeutung für die Lebensmittelentwicklung 30 3 Material und Methoden 32 3.1 Material 32 3.1.1 Saatgut 32 3.1.2 Geräte, Chemikalien, Verbrauchsmaterial, Software 32 3.1.3 Pufferlösungen 39 3.1.4 Herstellung Bradford-Reagenz, 5-fach 39 3.1.5 Auswahl der Vergleichssubstanzen 39 3.2 Methoden 40 3.2.1 Herstellung der Proteinisolate 40 3.2.2 Mikrobiologische Analysen 41 3.2.3 Bestimmung der Trockenmasse 41 3.2.4 Bestimmung des Proteingehalts 42 3.2.5 Thermische Behandlungsmethoden im Prozess 42 3.2.5.1 UHT-Erhitzung des Extraktes 42 3.2.5.2 Pasteurisierung des Isolats 44 3.2.6 Saatgutentkeimung 44 3.2.6.1 UVC-Bestrahlung 44 3.2.6.2 Trockene Erhitzung 45 3.2.6.3 Autoklavieren 46 3.2.7 Sensorische Untersuchungen 46 3.2.8 Proteinfunktionalität 47 3.2.8.1 Ölbindevermögen 47 3.2.8.2 Wasserbindevermögen 47 3.2.8.3 Gelbildungsvermögen 47 3.2.8.4 Emulgiereigenschaften 47 3.2.8.5 Schaumbildungsvermögen 48 3.2.8.6 Proteinlöslichkeit 48 3.2.8.7 Oberflächenhydrophobität 49 3.2.9 Ernährungsphysiologische Eigenschaften 50 3.2.9.1 in-vitro-Verdaubarkeit 50 3.2.9.2 Maillard-Produkte 50 3.2.9.3 Nachweis reduzierender Zucker .50 3.2.9.4 Nachweis von Glykoproteinen 50 3.2.9.5 Polyphenolgehalt der Lupinenflocken und Proteinisolate 51 3.2.10 Proteincharakterisierung 51 3.2.10.1 Lichtmikroskopie 51 3.2.10.2 Dynamische Differenzkalorimetrie 51 3.2.10.3 Natriumdodecylsulfat-Polyacrylamidgelelektrophorese 52 4 Ergebnisse und Diskussion 54 4.1 Thermische Behandlungsmethoden im Prozess 54 4.1.1 UHT-Erhitzung des Extraktes: Einfluss auf Mikrobiologie und Proteinausbeute 54 4.1.2 Pasteurisierungsversuche: Einfluss auf Mikrobiologie und Proteinqualität 55 4.2 Saatgutentkeimung - Mikrobiologie und Proteinausbeute 56 4.2.1 Versuchsreihe I 56 4.2.2 Versuchsreihe II 61 4.3 Sensorische Untersuchungen 63 4.3.1 Verkostungen 64 4.3.2 Farbmessung der Proteinisolate und Flocken 65 4.4 Proteinfunktionalität 69 4.4.1 Wasser- und Ölbindevermögen 69 4.4.2 Gelbildungsvermögen 72 4.4.3 Emulgiereigenschaften 74 4.4.4 Schaumbildungsvermögen 78 4.4.5 Proteinlöslichkeit 81 4.4.6 Oberflächenhydrophobität 83 4.5 Ernährungsphysiologische Eigenschaften 86 4.5.1 Maillard-Produkte 86 4.5.2 Nachweis reduzierender Zucker 87 4.5.3 Nachweis von Glykoproteinen 87 4.5.4 Verdaubarkeit 88 4.5.5 Polyphenolgehalte 89 4.6 Proteincharakterisierung 91 4.6.1 Lichtmikroskopie 91 4.6.2 Dynamische Differenzkalorimetrie 95 4.6.3 Natriumdodecylsulfat-Polyacrylamidgelelektrophorese 98 5 Zusammenfassung 105 Anhang 109

Biocomposites exhibit properties like many petrochemical-based polymers composites. They have the potentials be used in the automotive and decking industries and as biodegradable packaging. However, the high cost as well as, poor mechanical and thermal properties have restricted their widespread use. There are a number of technical issues that need to be addressed before bio-composites can be widely used. In this research Polylactic acid (PLA) composites, reinforced with natural fibres (wood, flax) and mineral fillers (talc) were investigated. The thermal and mechanical properties of the composites were studied by means of Differential Scanning Calorimetry (DSC), Tensile Testing and Dynamic Mechanical Analysis (DMA), while morphology and crystallization processes of the composites were studied by hot stage optical microscopy. The experimental results are also compared with different theoretical models of the response of the composites. PLA / wood composites were developed by mixing PLA with wood in different ratios using a melt compounding process. PLA/wood (90/10. 80/20, 60/40), PLA/wood/copolymers (85/10/05, 80/10/10, 75/20/05, 70/20/10, 55/40/05, 50/40/10) and PLA/wood/coupling agent (80/20/silane coating) were the three different composite systems that were developed. Adding increasing amount of wood into the PLA, the thermal properties remain unchanged but the mechanical properties increased significantly, bringing a stiffening effect to the composites. Tensile modulus increased from 4.1± 0.6 to 9.8 ± 1.2 (GPa) as the wood content increased from 0 to 40 (wt %), but the tensile strength at break reduced from 43.8 ± 3.1 to 31.8 ± 2.8 MPa. The experimental results of the PLA-wood composites were modelled according to the Halpin-Tsai equation. The addition of copolymer affected the thermal properties considerably by decreasing the glass transition temperature of the composite. The glass transition temperature dropped from 54 ± 0.7 (0C) to 48 ± 0.36 (0C) when the content of copolymer was increased from 0 to 10 (wt %). The cold crystallization temperature also decreased from 127 ± 1.41 (0C) to 103 ± 2.58 (0C) when the copolymer was incorporated into the PLA/wood composites. The significant aspect was the occurrence of a double peak in the melting endotherm. The degree of crystallinity also increased from 2 ± 0.83 (%) to 11 ± 1.23 (%) when the amount of copolymer was increased to 10 (wt %). PLA, flax and expoidizied natural rubber (ENR) composites were also developed using a melt compounding process. The mechanical properties were affected significantly when the flax fibres were mixed with PLA in the ratios of 10, 20 and 30 (wt %). Addition of flax fibres increased the elastic modulus significantly but reduced the tensile strength and strain at break. To improve the toughness of the PLA- Flax composites, ENR was incorporated into the PLA- Flax composites. In order to balance the modulus of the reinforcement and the matrix, the PLA- Flax and ENR composites were annealed above the glass transition temperature and the degree of crystallinity increased from 2 to 35 (%). The integral blending of PLA, Flax and ENR did not affect the brittle fracture but introducing a masterbatch of flax fibres and ENR into the PLA matrix during melt processing had a considerable effect on the fracture behaviour of the composites. The elastic modulus of the composites decreased due to the elastomeric content in the composites and there was an increase in elongation-to-break. The effect of talc on the crystallinity and mechanical properties of a series of polylactic acid (PLA) / talc composites was investigated. PLA talc composites were developed by incorporating different types of the talc into the PLA in the ratios of 10, 20 and 30 (wt %). The composites were prepared by melt blending followed by compression moulding. It was found that talc acted as a nucleating agent and increased the crystallinity of the PLA from 2% to 25%. There was significant improvement in Young s modulus of the composites with increasing talc addition and these results were found to fit the Halpin Tsai model. Thermo-mechanical tests confirmed that the combination of increased crystallinity and storage modulus leads to improvement in the heat distortion properties.

The aim of this work was to assess the suitability of vibrational spectroscopic techniques (Raman, FT-IR and FT-NIR spectroscopy) as a means for the solid-state structural analysis of pharmaceuticals. Budesonide, fluticasone propionate, salbutamol hemisulfate, terbutaline hemisulfate, ipratropium bromide, polymorphic forms of salmeterol xinafoate and two polymorphic forms of sulfathiazole were selected since they are used in the management of certain respiratory disorders and from different chemical and pharmacological entities along with some pharmaceutical excipients. Conventional visual examination is not sufficient to identify and differentiate spectra between different pharmaceuticals. To confirm the assignment of key molecular vibrational band signatures, quantum chemical calculations of the vibrational spectra were employed for better understanding of the first five selected drugs. The nondestructive nature of the vibrational spectroscopic techniques and the success of quantum chemical calculations demonstrated in this work have indeed offered a new dimension for the rapid identification and characterisation of pharmaceuticals and essentially warrant further research. The application of simultaneous in situ Raman spectroscopy and differential scanning calorimetry for the preliminary investigation of the polymorphic transformation of salmeterol xinafoate polymorphs and two polymorphic forms of sulfathiazole has also been explored in this work leading to the development of a new method for the solid-state estimation of the transition temperature of entantiotropically related pharmaceutical polymorphs which represents the first analytical record of the use of this approach for pharmaceutical polymorphs.

Analysis of the molecular speciation of organic compounds in solution is essential for the understanding of ionic complexation. The Raman spectroscopic technique was chosen for this purpose because it allows the identification of compounds in different states and it can give information about the molecular geometry from the analysis of the vibrational spectra. In this research the ionisation steps of relevant pharmaceutical material have been studied by means of potentiometry coupled with Raman spectroscopy; the protonation and deprotonation behaviour of the molecules were studied in different pH regions. The abundance of the different species in the Raman spectra of aqueous salicylic acid, paracetamol, citric acid and salicylaldoxime have been identified, characterised and confirmed by numerical treatment of the observed spectral data using a multiwavelength curve-fitting program. The non-destructive nature of the Raman spectroscopic technique and the success of the application of the multiwavelength curve-fitting program demonstrated in this work have offered a new dimension for the rapid identification and characterisation of pharmaceuticals in solution and have indicated the direction of further research. The work also covers the formation of novel cocrystal systems with pharmaceutically relevant materials. The existence of new cocrystals of salicylic acid-nicotinic acid, DLphenylalanine , 6-hydroxynicotinic acid, and 3,4-dihydroxybenzoic acid with oxalic acid have been identified from stoichiometric mixtures using combined techniques of Raman spectroscopy (dispersive and transmission TRS), X-ray powder diffraction and thermal analysis. Raman spectroscopy has been used to demonstrate a number of important aspects regarding the nature of the molecular interactions in the cocrystal. Cocrystals of salicylic acid - benzamide, citric acid-paracetamol and citric acid -benzamide have been identified with similar analytical approaches and structurally characterised in detail with single crystal X-ray diffraction. From these studies the high selectivity and direct micro sampling of Raman spectroscopy make it possible to identify spectral contributions from each chemical constituent by a peak wavenumber comparison of single-component spectra (API and guest individually) and the two- component sample material (API/guest), thus allowing a direct assessment of cocrystal formation to be made. Correlation of information from Raman spectra have been made to the X-ray diffraction and thermal analysis results. Transmission Raman Spectroscopy has been applied to the study cocrystals for the first time. Identification of new phases of analysis of the low wavenumber Raman bands is demonstrated to be a key advantage of the TRS technique.

Les fibres d'acide polylactique (PLA), issues de ressources agricoles renouvelables, ont suscité à leur apparition un grand intérêt car il s'agit de fibres ayant les avantages des fibres synthétiques. Or très vite des inconvénients sont apparus en particulier lors de leur teinture : elles se saturent très facilement conduisant a des nuances pastel et les solidités aux lavages des teintures sont médiocres. Nous avons vérifié que la cristallinité des fibres de PLA est du même ordre de grandeur que celle du polyester classique (55- au pire 60%). Par contre les traitements aqueux type teinture font croître cette cristallinité, peut-être par hydrolyse des zones amorphes. Mais la teinture est très rapide, ce qui signifierait que les zones amorphes sont à peine orientées ce qui est confirmé par RX (un fond continu vraiment plat) et de ce fait elles ne retiennent pas le colorant. Les isothermes d'adsorption montrent également qu'il n'y a pas d'adsorption mais " solution " puisqu'elles sont de type Nernst et que la fixation de colorant décroît avec la croissance de la température. En plus, à chaque traitement aqueux de la fibre est hydrolysée ce qui entraîne une perte de colorant et une réduction lente des propriétés mécaniques de la fibre. Ce dernier phénomène étant relativement long d'où nous avons formulé une hypothèse que l'hydrolyse des bouts de chaine serait plus rapide que celle des milieux de chaine.

La résistance multi-drogue (MDR) est un facteur majeur de l'échec partiel de nombreuses chimiothérapies anticancéreuses, antiparasitaires ou antibactériennes. Dans le but d’inhiber ce phénomène, de nouvelles molécules au pouvoir reversant ont été découvertes. Ainsi une série de molécules, basée sur un squelette pyrido[3,2-g]quinoléine, portant différentes chaînes alkylamines et diversement substituées sur le motif hétérocyclique, a été synthétisée et montré in vitro une activité reversante de la résistance multiple aux médicaments. Afin de démontré le processus suivi par une molécule biologiquement active de sa synthèse à sa mise en forme galénique, le 4,6-Bis[2’(diéthylamino)éthoxy]2,8,10-triméthylpyrido[3,2-g]quinoléine (BG 637) a été choisi. Nous avons procédé dans un premier temps à la caractérisation physicochimique du BG 637 par des techniques telles que l’analyse calorimétrique différentielle (DSC), la spectroscopie UV-VIS, la spectrométrie de masse (CG/SM) couplée à la chromatographie de gaz, la spectroscopie Infra Rouge à Transformée de Fourrier (IRTF), la résonance magnétique nucléaire (RMN), la diffraction aux rayons X et la cristallographie. Des études stabilité ont également été menées sous différentes conditions de stockage. Des études d’interactions entre différents excipients et le BG 637 ont été réalisées et analysées par DSC, IRTF et UV. Les résultats ont montré que le BG 637 est un composé stable et compatible avec les excipients choisis. Enfin, la mise en forme galénique orale, le comprimé, a été réalisée. / Multi-drug resistance represent a major problem for chemotherapy unsuccessful in oncology, parasitoly and bacteriology. The new molecules which reverse this phenomenon were discovered.The pyrido[3,2-g]quinolines family which are substituted by various alkylamine side chains and various substituents on the heterocyclic moiety was prepared and the in vitro activity against the multi-drug resistance was showed.With the aim to show the processes of the new biological compound from his synthesis to the galenic form, the 4,6-Bis[2’(diéthylamino)éthoxy]2,8,10-triméthylpyrido[3,2-g]quinoline (BG 637) was chosen. To characterize BG 637, techniques such as Differentiel Scanning Calorimetry (DSC), Fourier Transform Infrared spectrometry (FT-IR), Ultra Violet spectrometry (UV), Mass spectrometry (GC/MS) coupled with Gas Chromatography, Nuclear Magnetic Resonance (NMR) and X-Ray Powder Diffraction (XRPD) were used. Several of them were also used to show the stability of the drug during various storage conditions.DSC supported by FT-IR and UV were used as the screening techniques for assessing the compatibility of BG 637 with several commonly used pharmaceutical excipients. These results showed that BG 637 is a very stable compound and compatible with several pharmaceutical excipients. Finally, the appropriate formulation for direct compression was determined.

Thermal stability of theG37 tRNA methyltransferase proteins from Thermotoga maritima and Aquifex aeolicus have been compared using Differential Scanning Calorimetry. It was shown that the Thermotoga protein is remarkably stable and is denatured at temperatures in excess of 100 degrees Centigrade. The Aquifex aeolicus protein was less stable, denaturing broadly at temperatures between 55oC and 100oC. In contrast, the mesophilic E. coli protein was completely denatured at 55oC. Enzymatic activity of the proteins was measured at various temperatures. Both the Thermotoga and Aquifex enzymes are active at ambient temperatures, and display a significant decrease in activity when the temperature is raised above 50oC. This may relate to subtle changes in protein structure causing an effect on the tRNA based assay. Both enzymes contain inter subunit disulfide bonds which might contribute to thermal stability. Assays of the enzymes in the presence of high concentrations of Dithiothreitol (DTT) did not significantly reduce activity at higher temperatures, but did stimulate activity at lower temperatures. Site directed mutagenesis of non -conserved protein sequences within Thermotoga maritima were initiated in order to determine what structures might confer heat stability on the protein. Alanine mutagenesis of lysine residues 103,104 led to reduced catalytic activity, but did increased activity at higher temperatures. Aspartate is the most common residue at the relative position 166 in the variable loop of most TrmD genes. It has been shown that in E. coli this is essential for catalytic activity and possibly the residue which carries out N1 deprotonation on residue G37 in tRNA. In Thermotoga glutamate is present at this position. Alanine mutagenesis of this residue did not eliminate activity suggesting another nearby residue may function in this capacity in the Thermotoga TrmD protein.