A key trend in the PVC market is to replace or decrease the amount of phthalate plasticisers used due to increasing health concerns. Therefore, the demand for non-phthalate based plasticisers is growing rapidly. Mineral oils are used in a variety of rubber and polymer applications as plasticisers; however, due to the lower polarity their applicability in PVC compounds is limited. Therefore, these materials are typically used as secondary plasticiser along with a primary for the purpose of improved properties and cost reduction. Some of the non-phthalate based solutions are fast fusing plasticisers, which act like solvents and have too rapid and too high plasticizing effect. This makes the compounding difficult and could cause problems in production. These substances have good compatibility with mineral oils, and using them together in PVC compounds can help the compounding issue by reducing the solvent power and increasing the fusion time to a level where the production parameters are similar to compounding with phthalates.   The aim of this study was to evaluate the use of mineral oils as a secondary plasticiser in a non-phthalate system for PVC. Four different grades of mineral oil and three non-phthalate plasticisers were used in compounding and compression moulding of PVC sample films. Mechanical, physical and chemical testing were done to assess the properties in a comparative study with phthalate plasticized PVC.   Tensile testing and hardness measurements showed that the mineral oils did not contribute with any plasticizing effect for the non-phthalate plasticisers tested in the study. The hardness was instead slightly increased for all the sample films that contained mineral oil. This indicates that the mineral oil either is less efficient than the primary plasticiser or that it affects the primary plasticisers intramolecular shielding between the PVC chains.       The shrinkage test showed that the migration of mineral oil was acceptable, especially the thicker grades of mineral oils had low migration. Colour stability test showed that the thicker mineral oil grades had some problems with discolouration. The discolouration is probably related to content of polyaromatics and oxidation stability.

Six series of cunitic amphiphiles based on benzene sulfonates were synthesized. The molecular characterization was performed by IR and NMR spectroscopy and the purity was determined by elemental analysis and thin layer chromatography. The thermotropic properties of these cunitic sulfonate amphiphiles were subsequently investigated by means of a combination of DSC, polarized microscopy and X-ray scattering. Most of the synthesized sulfonates were found to exhibit hexagonal columnar mesophases, some of them exhibited a complex polymorphism. The polymorphism depended upon variation of the molecular structure. The Six series of cunitic amphiphiles based on benzene sulfonates were synthesized. The molecular characterization was performed by IR and NMR spectroscopy and the purity was determined by elemental analysis and thin layer chromatography. The thermotropic properties of these cunitic sulfonate amphiphiles were subsequently investigated by means of a combination of DSC, polarized microscopy and X-ray scattering. Most of the synthesized sulfonates were found to exhibit hexagonal columnar mesophases, some of them exhibited a complex polymorphism. The polymorphism depended upon variation of the molecular structure. The phase behavior was determined by the nature of headgroup cation Mn+ (n=1, 2), and for the same Mn+ by the carbon number at the hydrophobic tail and by temperature as well. The lyotropic properties of these cunitic sulfonate amphiphiles were also studied by investigating their gelation behavior and gelling capability. A number of the amphiphiles were found to be favorable organogelators that gel various organic solvents of either high or low polarity upon self-aggregation driven by the Coulomb interaction. The morphological results by means of SEM and TEM demonstrate that the organogelators are able to form fibrous network microstructures by self-organization and self-aggregation. The cylindrical aggregates with sulfonated headgroup in the center as well embody the potential to construct ion-selective transport membranes. The cunitic amphiphiles containing polar sulfonate units at their focal point and polymerizable olefin group on their periphery were exploited to prepare functional membranes that contain ion-active transport channels. The ion-selectivity of the formed membranes was investigated by means of ion transport experiments with LiCl, NaCl, KCl solutions of different concentration. By comparison of the ion transport rates across the membranes the ionic permselectivity was demonstrated.

The purpose of this research was to investigate the effect of ultra-high temperature process parameters on age gelation of milk concentrate. Skim milk was concentrated to 2X (volume reduction) using reverse osmosis. The milk concentrate was preheated at 75 or 90°C for 20 or 50 s and UHT-processed at 138 or 145°C for 4 or 16 s. Sterilizing methods used were direct steam injection and indirect plate heat exchanger. The samples were aseptically collected in presterilized plastic containers and stored at 15 or 35°C. At 15°C storage temperature, the steam-injected samples gelled in 5 months when 4 s UHT time was used. When UHT time was increased to 16 s, the samples gelled in 6 months. Of the samples that were UHT processed by indirect plate heat exchanger for 4 s and stored at 15°C, all gelled after 7 months. When UHT time was increased to 16 s, all the 138°C samples gelled after 7 months as did the samples that were preheated for 50 s and UHT-processed at 138°C. The samples preheated at 75°C for 50 sand UHT-processed at 145°C gelled after 8 months, whereas at 90°C preheat temperature the samples gelled after 9 months. The samples stored at 35°C did not gel but showed different sedimentation levels. The sediment depth in the container was always greater for the steam-injected samples. The samples that received higher heat treatments by the two processing methods had a higher sedimentation depth. The pH decreased during storage and the extent of reduction was higher at 35°C storage temperature . Maillard browning occurred at both storage temperatures. Browning was greater in samples stored at 35°C and processed by indirect plate heat exchanger.

The effect of ultra-high temperature processing by direct steam injection and room temperature storage of pH-adjusted and unadjusted 3X (volume reduction) skim milk retentate and the effect of storage at various temperatures of 3X skim milk retentate without pH adjustment on their ζ-potential, viscosity, and pH were determined. Pasteurized skim milk was concentrated to 3X by ultrafiltration. In the pH study portions of skim milk retentate were adjusted to pH 6.38 ± .02 with HCl and 6.85 ± .01 and 7.32 ± .02 with NaOH between ultrafiltration and ultra-high temperature processing. In the storage temperature study, storage temperatures used for pH-unadjusted retentate samples were 11°C, 23°C (room temperature), and 37°C. Although pH 6.38 samples had the lowest viscosity in the pH study before ultra-high temperature processing, these samples precipitated during ultra-high temperature processing. For non-acidified samples, increasing pH of retentate resulted in higher viscosities and quicker age gelation times. Destabilization occurred more rapidly at 37°C than at 23°C or 11°C. The pH drop tended to be greater for samples stored at a higher temperature or adjusted to a higher pH. During 28 weeks of 37°C storage the pH decreased from 6.54 to 6.06. During 32 weeks of 23°C storage pH of samples initially adjusted to pH 7.32 dropped to 7.06. ζ-Potentials of casein micelles were calculated from electrophoretic mobility obtained by measuring Doppler frequency shifts of scattered laser light in samples that had been diluted 300 fold with their own ultra.filtrate. Absolute values of ζ-potential of samples stored at 37°C decreased from -23.4 millivolts immediately after ultra-high temperature processing to -18.5 millivolts after 28 weeks of storage. For samples stored at 11°C and 23°C in the storage temperature study and control samples in the pH study, absolute values of ζ-potential decreased approximately 1.5 to 2.0 millivolts during 28 or 32 weeks of storage.

Indiana University-Purdue University Indianapolis (IUPUI) / A variety of polymers of synthetic origins (e.g., poly(ethylene glycol) or PEG) and naturally derived macromolecules (e.g., silk fibroin or gelatin) have been explored as the backbone materials for hydrogel crosslinking. Purely synthetic hydrogels are usually inert, covalently crosslinked, and have limited degradability unless degradable macromers are synthesized and incorporated into the hydrogel network. Conversely, naturally derived macromers often contain bioactive motifs that can provide biomimicry to the resulting hydrogels. However, hydrogels fabricated from a single macromer often have limitations inherent to the macromer itself. For example, to obtain high modulus PEG-based hydrogels requires an increase in macromer and crosslinker content. This is associated with an increase in radical concentration during polymerization which may cause death of encapsulated cells. Pure gelatin (G) hydrogels have weak mechanical properties and gelatin undergoes thermo-reversible physical gelation. Covalent crosslinking is usually necessary to produce stable gelatin hydrogels, particularly at physiological temperatures. The limitations of these hydrogels may be circumvented by combining them with another macromer (e.g., silk fibroin) to form hybrid hydrogels. Silk fibroin (SF) from Bombyx mori silkworms offers high mechanical strength, slow enzymatic degradability, and can easily form physical hydrogels. The first objective of this thesis was to evaluate the effect of sonication and the presence of synthetic polymer (e.g., poly (ethylene glycol) diacrylate or PEGDA) or natural macromer (e.g., gelatin) on SF physical gelation kinetics. SF physical gelation was assessed qualitatively via tilt tests. Gelation of pure SF solutions was compared to mixtures of SF and PEGDA or G, both with or without sonication of SF prior to mixing. The effect of gelatin on SF gelation was also evaluated quantitatively via real time in situ rheometry. Sonication accelerated gelation of SF from days to hours or minutes depending on SF concentration and sonication intensity. Both PEGDA and G were shown to accelerate SF physical gelation when added to SF and sonicated SF (SSF) solutions. The second objective was to develop a simple strategy to modulate covalently crosslinked PEG-based hydrogel properties by physically entrapping silk fibroin. The physical entrapment of silk fibroin provides an alternative method to increase gel storage modulus (G’) without the cytotoxic effect of increasing macromer and crosslinker concentration, or altering degradation kinetics by increasing co-monomer concentration. The effect of SF entrapment on gel physical and mechanical properties, as well as hydrolytic degradation and chemical gelation kinetics were characterized. SF physical crosslinking within the PEG-based network was shown to increase gel storage moduli by two days after gel fabrication. There was no change hydrolytic degradation rate associated with the increased moduli. SF entrapment did not affect gelation efficiency, but did alter gel physical properties. The third objective of this thesis was to develop a silk-gelatin in situ forming hybrid hydrogel for affinity-based growth factor sequestration and release and in vitro cell culture. SF provides mechanical strength and stability, whereas G contains bioactive motifs that can provide biomimicry to the gel network. Hydrogel G’ and its dependency on temperature, SF processing conditions, and secondary in situ chemical crosslinking (i.e., genipin crosslinking) were studied. Gelatin can be conjugated with heparin, a glycosaminoglycan, to impart growth factor (GF) binding affinity. Growth factor sequestration and release were evaluated in a pair of designed experiments. The hybrid gels were evaluated as substrates for human mesenchymal stem cell proliferation.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20710号 / 工博第4407号 / 新制||工||1685(附属図書館) / 京都大学大学院工学研究科高分子化学専攻 / (主査)教授 古賀 毅, 教授 吉崎 武尚, 教授 竹中 幹人 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

Using various synthetic strategies, we designed several libraries of novel polysaccharide mixed ester derivatives for oral drug delivery applications. Cellulose and cellulose esters have been extensively studied and utilized for different applications such as separation membranes, sustainable plastics, and enteric coatings in oral drug delivery carriers. We sought to exploit the ring-opening of cyclic anhydrides, succinic and glutaric anhydride, to append ω-carboxyl groups to commercially available cellulose and cellulose ester substrates. We used scalable synthetic strategies and widely available and cheap reagents to show a proof-of-concept for the manufacturability of these different polymer derivatives. We incorporated different degrees of substitution of ω-carboxyl groups to impart a range of water solubility in these polymers. The derivatives displayed excellent <i>T</i>g values for ASD applications, adequate water solubility, and good amphiphilic properties. We designed very effective amorphous solid dispersion (ASD) oral drug delivery polymers that prevented recrystallization of felodipine for hours and had excellent congruent polymer-drug release from the formulation at 20% drug loading. During the ring-opening reactions of the cellulose derivatives with glutaric anhydride we discovered that crosslinking and gelation can occur, especially with cellulose and cellulose ester substrates with a high degree of substitution (DS) of hydroxy groups. We isolated and characterized these gelled products using rheology, and solid-state 1D and 2D NMR spectroscopy, to evaluate whether the gels are physical or chemical in nature and proposed a mechanism for gelation. We determined that the gels are mostly physical but can proceed to chemical crosslinking over time. We designed a library of cellulose ester derivatives, and we investigated their performance as amorphous solid dispersion (ASD) drug delivery vehicles for the lipophilic drug felodipine, through <i>in vitro</i> experiments. Aside from felodipine, many other active pharmaceutical ingredients (APIs) are also highly crystalline and poorly water-soluble. ASDs are used to disrupt the crystalline packing of these drugs through dispersing them in amorphous polymeric carriers, facilitating their water-solubility, and preventing their recrystallization. We showed that our polymers performed remarkably well in the <i>in vitro</i> studies and inhibited crystallization of model compound felodipine for several hours while providing optimal drug release, affording highly promising ASD polymers. If company formulators are unable to develop an effective oral-delivery carrier to prevent a drug from recrystallizing, then the drug cannot be tested in <i>in vivo</i> toxicology studies, and therefore cannot be brought to market because of its poor aqueous solubility and subsequent low bioavailability. To test the robustness of our polymers, we also performed <i>in vitro</i> ASD experiments at the pharmaceutical company AbbVie with their most rapidly crystallizing pipeline compounds, and several commercially available drugs (Compound A, axitinib, and ziprasidone). We demonstrated that our polymers could also prevent drug recrystallization with these rapid crystallizers, outperforming commercial polymers like FDA-approved hydroxypropyl methyl cellulose acetate succinate (HPMCAS (MF)), even at exceptionally high drug loading ratios of 40 times the concentration of polymer. α-1,3-Glucans are an emerging class of polysaccharides and are structurally different than cellulose due to their α (1→3) linkage versus the cellulose β (1→4) glycosidic linkage. We demonstrated that we could modify these derivatives using a variety of esterification strategies and TEMPO-mediated C6 selective oxidation, affording a myriad of different novel polymer products, some of which are structural analogs of the cellulose ester derivatives we previously created. The polymers had higher <i>T</i>g values than the cellulose ester polymers, which may be useful for applications where heat resistance is desired. In the future, we will screen some of these α-1,3-glucan derivatives with poorly water-soluble enzalutamide, posaconazole and celecoxib model drugs, to evaluate their crystallization inhibition properties and the influence of polymer morphology upon structure-property relationships. We expect that these synthetic polymer strategies will offer scalable routes to novel ASD polymers, which we demonstrated to be highly effective drug crystallization inhibitors against a variety of different hydrophobic pharmaceutical compounds. / Doctor of Philosophy / Polysaccharides are polymers comprised of many linked sugar molecules and are an incredibly abundant and renewable resource. They are found everywhere in nature such as the wood from trees, the shells of crabs, the exoskeletons of bugs, and the mushrooms that sprout in damp forests. The research in this dissertation focuses on the use and chemical modification of polysaccharides for designing new, polysaccharide-based oral drug delivery systems called amorphous solid dispersions (ASDs), which significantly aid in the solubility and bioavailability of important medications. We started with the chemical modification of cellulose, the most abundant plant polysaccharide on planet Earth, and previously modified commercial cellulose substrates (known as cellulose esters) to create novel polymers for ASDs. We successfully modified these polymers, characterized them, and evaluated their potential as oral drug delivery vehicles by formulating them with several different classes of potent drugs used to treat a variety of diseases such as hypertension and schizophrenia. We showed that our designed cellulose ester polymers kept these hydrophobic drugs water-soluble for long-enough so that they can be adequately absorbed in the human body through the gastrointestinal tract, significantly outperforming commercial polymers in many cases. During the chemical modification of the cellulose esters, we also observed that they were prone to form gels, and we investigated this gelation phenomena in more detail through rheometry, 1D and 2D solid-state nuclear magnetic resonance spectroscopy (similar in principle to the medical diagnostic method, magnetic resonance imaging or MRI). We discovered that these gels can be physically and/or chemically linked together, and that different gelation mechanisms can dominate depending on the polysaccharide substrate and the esterification reagent used. We extended our research to other polysaccharide derivatives called α-1,3-glucans, which can be sourced from fungi, and/or enzymatically synthesized in the lab. Using various synthetic esterification and oxidation chemical methods to functionalize this polysaccharide, we designed a library of entirely novel polymers with different physical structures relative to the cellulose ester polymers. The polymers displayed thermal properties that show promise in drug delivery vehicle applications and in applications where high heat resistance is required. Overall, we developed next-generation polymers for amorphous solid dispersion oral drug delivery applications. We displayed the versatility of using a select few chemistry strategies to create a variety of different polymers with very different physicochemical properties. We hope that this work will help researchers design sustainable, plant-based polymers for ASD applications and we hope to nurture future structure-function studies to improve ASD performance for the benefit of patients in need.

No description available.

There has been growing interest in the utilization of plant-derived proteins as functional ingredients in many food and beverage applications because they are perceived as being more sustainable, healthy, and ethical than animal-derived proteins by many consumers. Traditionally, soy proteins have been the most widely employed plant protein in the food industry. However, a number of alternative plant-based protein sources have recently become available, with pulse proteins being one of the most popular. In this study, the physicochemical properties and functional attributes of various commercially available pulse protein isolates were compared with those of soy protein isolate to evaluate their potential application in foods and beverages. The water holding capacity, oil holding capacity, gelation properties, emulsifying properties, and color of faba bean (FPI), pea (PPI), lentil (LPI), and soy (SPI) protein isolates were therefore measured. SPI had a significantly higher water holding capacity (7.6 g/g) than the pulse protein isolates (2.2-5.1 g/g). Among the plant protein isolates, PPI had a significantly lower oil holding capacity and gelling property. LPI was more effective at producing small oil droplet sizes during homogenization than the other protein isolates. Nevertheless, all of the plant proteins were capable of forming relatively small oil droplets (D32 = 1-3 mm) at a protein-to-oil ratio of 1:10. As expected, droplet size decreased with increasing protein concentration for all plant protein isolates, which increased their resistance to creaming. These results suggest that pulse proteins may have similar or better techno-functional properties than soy proteins for certain applications. In particular, lentil proteins were more effective emulsifiers, whereas faba bean proteins were more effective gelling agents. These proteins may therefore be suitable for application in plant-based milks, eggs, cheese, or meats where emulsifying or gelling properties are required.

The phase diagrams for the thermoreversible gelation of poly(ether ether ketone) (PEEK) in dichloroacetic acid (DCA) and 4-chlorophenol (4CP) were constructed over broad temperature and concentration ranges, revealing that PEEK is capable of dissolving and forming gels in DCA and 4CP up to a weight fraction of 25 wt.%. Highly porous aerogels of PEEK were prepared through simple solvent exchange and solvent removal of the PEEK/DCA or PEEK/4CP gels. Solvent removal utilized freeze-drying (sublimation) methods or supercritical CO2 drying methods. Varying the weight fraction of PEEK dissolved in solution determined PEEK aerogel density. Mechanical properties (in compression) were shown to improve with increasing density, resulting in equivalent compressive moduli at comparable density regardless of preparation method (concentration variation, gelation solvent, solvent removal method, or annealing parameters). Additionally, density-matched aerogels from various MW PEEK showed a correlation between increasing MW and increasing compressive modulus. Contact angle and contact angle hysteresis revealed that PEEK aerogels have a high contact angle, exceeding the conditions necessary to be classified as superhydrophobic materials. PEEK aerogel contact angle decreases with increasing density and a very low contact angle hysteresis that increases with increasing density, regardless of gelation solvent or drying method. Small angle neutron scattering (SANS) contrast-matching experiments were used to elucidate the morphological origin of scattering features, wherein it was determined that the origin of the scattering feature present in the small angle scattering region was stacked crystalline lamella. Ultra-small angle X-ray scattering (USAXS)/SAXS/Wide angle X-ray scattering (WAXS) was then used to probe the hierarchical nanostructure of PEEK aerogels across a broad range of length scales. The Unified Fit Model was used to extract structural information, which was then used to determine the specific surface areas of PEEK aerogels. Regardless of gelation solvent, gel concentration, or solvent removal method, all PEEK aerogels display high surface areas as determined by SAXS and high surface areas as determined by nitrogen adsorption methods. Surface area values determined from SAXS data were consistently higher than that measured directly using nitrogen adsorption, suggesting that pore densification diminishes the accessible aerogel surface area. / Ph. D. / Poly(ether ether ketone) (PEEK) is a semicrystalline polymer with high temperature thermal transitions and excellent mechanical strength, making it an ideal candidate for many high-performance polymer applications. When PEEK is dissolved in particular solvents, it will form a 3-dimensional network where crystalline polymer is the cross-linking unit of the network. Careful solvent removal does not significantly perturb the gel network structure and produces a low-density aerogel. This work details the first reported instance of the monolithic gelation of PEEK and the first examples of PEEK aerogels. The nanostructure of these gels and aerogels is fully characterized to relate structural features to physical properties such as mechanical stiffness and wettability.