A esquistossomose é uma doença parasitária aguda e crônica causada por vermes sanguíneos (vermes nematoides) do gênero Schistosoma. O homem contrai a esquistossomose através da penetração ativa da cercaria na pele. A importância do tratamento desta enfermidade consiste não só no fato de curar a doença ou diminuir a carga parasitária dos pacientes, bem como impedir sua evolução para formas mais graves. Para o tratamento da esquistossomose o fármaco de escolha é o praziquantel; isso se deve ao seu amplo espectro, sua eficácia, segurança e a relação custo/tratamento. A única forma farmacêutica disponível no Brasil é o comprimido, na dose de 600 mg, a qual pode ser subdividida em quatro partes de 150 mg, a fim de facilitar o ajuste de dose. No entanto, no momento da subdivisão dos comprimidos ocorre o rompimento do revestimento. Este fato acaba levando a uma exposição do fármaco e, consequentemente, de seu sabor amargo. Esta característica dificulta a administração do medicamento, principalmente na população infantil, prejudicando o tratamento e o controle da doença. Uma alternativa para este problema é o desenvolvimento de sistemas poliméricos microparticulados que associados ao fármaco impediriam o contato direto com as papilas gustativas e assim promoveriam uma melhoria na palatabilidade. Para isso utilizou-se a técnica modificada de deposição interfacial do polímero pré-formado seguido de secagem por aspersão. Três matrizes poliméricas, com diferentes características de liberação foram utilizadas, Eudragit RL 100 – liberação tempo dependente e Eudragit E100 e L30D-55 – liberação pH dependente. Além disso, dois tipos de sistemas carreadores do fármaco foram preparados, microcápsulas e microesferas poliméricas. Estes sistemas obtidos foram avaliados e caracterizados a fim de eleger a melhor proposta de formulação visando o mascaramento do sabor do fármaco. De acordo com os resultados obtidos selecionou-se um sistema composto por microcápsulas formadas a partir do polímero L30D-55. A partir de então inseriu-se este sistema na forma farmacêutica pó para suspensão oral, onde diferentes propostas de formulações, contendo dois edulcorantes auxiliares, aspartame e sacarina, separadamente, e seus respectivos placebos foram avaliadas através de um método in vitro para a determinação do sabor, a língua eletrônica ou sensor gustativo. As diferentes formulações avaliadas apresentaram capacidade em mascarar o sabor desagradável do fármaco e, assim resultam em uma promissora alternativa para o aumento da adesão por parte dos pacientes à terapêutica, principalmente para crianças, em virtude da facilidade de administração, do ajuste da dose em função da massa corpórea e ao sabor muito mais agradável ao paladar infantil. / Schistosomiasis is a parasitic disease acute and chronic caused by blood worms (nematodes worms) of the genus Schistosoma. Man acquires schistosomiasis through the active penetration of the worms in skin. The importance of treatment of this disease is not only the fact of curing the disease or decreases the parasite load of patients, well as prevent progression to more severe forms. For the treatment of schistosomiasis praziquantel is the drug of choice, this is due to its wide spectrum, its efficacy, safety and the relation cost / treatment. The single dosage form available in Brazil is tablet at a dose of 600 mg, which can be subdivided into four parts of 150 mg to facilitate dose adjustment. However when the subdivision of the tablets occurs the disruption of the coating. This fact provides a drug exposure and consequently of its bitter taste. This characteristic complicates the administration of the drug mainly in children, affecting the treatment and control of disease. An alternative for this problem is the development of microparticulate polymeric systems which associated with the drug would prevent direct contact with the taste buds and thus promote an improvement in palatability. For this was used a modified technique interfacial deposition of preformed polymer followed by spray drying. Three polymer matrices with different release characteristics have been used, Eudragit RL 100 – time dependent release, and Eudragit E100 and L30D-55 – pH dependent release. Furthermore, two types of drug carrier systems have been prepared, polymeric microspheres and microcapsules. These systems obtained were evaluated and characterized in order to select the best proposal formulation aimed at masking the taste of the drug. According to the results we selected a system comprising microcapsules formed from L30D-55 polymer. From then was inserted into this system in the pharmaceutical form, powder for oral suspension, where different proposals formulations containing two auxiliary sweeteners, aspartame and saccharin, separately, and their respective placebos were evaluated in an in vitro method for determining the taste, the electronic tongue. The different formulations tested presented excellent ability to mask the unpleasant taste of the drug and thus present an excellent alternative for increasing adherence to therapy, especially for children, because of the ease of administration, according on dose adjustment of body mass and the much more palatable to children's taste.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22037号 / 医博第4522号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 湊谷 謙司, 教授 井上 治久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Idag är den största delen av textilierna antingen olje-(60 %) eller bomullsbaserade (30 %). Det är enbart en liten del som är baserade på träfibrer. Ett ökande behov av förnyelsebara textilier föreligger. Samtidigt är ett minskade pappersbehov en drivkraft till att använda de existerande pappersmaskinerna till att tillverka icke vävda textilliknande material. Till skillnad från vävda material kan materialet tillverkas direkt istället för att först tillverka trådar från fibrer. Möjligheter att ta fram textillika material av cellulosafibrer undersöktes. Dynamiska ark gjorda av en blandning av barrmassa och en blandning av barr- och lövmassa med 0, 55 och 70 vikt% polymjölksyra, PLA, tillverkades. Arken pressades ihop två och två med ett mellanlager av Expancel mikrosfärer och bindemedel. Mowilith DM 105 och Primal LT-2949 Emulsion användes som bindemedel. En jämförelse gjordes med ark med enbart bindemedel som mellanlager.   En subjektiv utvärdering av vilket förhållande mellan Expancel mikrosfärer och bindemedel som var bäst lämpad gjordes. För utvärderingen ytbehandlades ett standard papper med 70 vikt% PLA. Den sats med högst koncentration av Expancel mikrosfärer som band bra till bindemedelet valdes. Draghållfastheten testades genom dragprovning enligt ISO 1924-2:1994 men med endast 5 prover istället för 10.  Dragprovningen visade att tillsatsen av Expancel mikrosfärer ökade töjningen hos materialet. Materialen med högst koncentration av PLA gav den mjukaste känslan men också lägst styrka. / Today the main parts of textiles are either oil (60 %) or cotton based (30 %). It is only a small portion which is based on wood fibres. An increasing demand of renewable textiles is forthcoming. At the same time a decreasing demand of paper is one of the motivation of using the existing paper machines to produce nonwoven textile-like materials. Unlike woven fabrics the fabric can be manufactured directly rather than first producing yarn from fibres. Possibilities of developing a textile-like material of cellulose fibres were investigated. Dynamic lab sheets made of a mix of softwood pulp and a mix of softwood and birch pulp with 0, 55 and 70 weight % Poly(lactic acid), PLA, were manufactured. The sheets was pressed together two and two with a middle layer of Expancel microspheres and binder. Mowilith DM 105 and Primal LT-2949 emulsion were used as binders. A comparison was made between sheets with only binder as the middle layer.   A subjective evaluation of which ratio between Expancel microspheres and binder material was best suited was made. For the evaluation a paper containing 70 weight% PLA was coated. The batch with highest concentration of Expancel microspheres, which bonded well to the binder, was chosen. The tensile strength was measured according to ISO 1924-2:1994 but with only 5 test samples instead of 10. The tensile tests showed that with Expancel microspheres resulted in increase of elongation of the material. The materials with the highest concentration of PLA had softest feeling but also lowest strength.

Microencapsulation of 5-fluorouracil was successfully accomplished with poly(ortho esters) polymer by emulsification-solvent evaporation method. While actual drug loading increased with increasing drug load (5 to 15% w/w), the entrapment efficiency remained essentially unaffected under a given set of experimental conditions. Incorporation of sorbitan sesquioleate enhanced entrapment efficiency, decreased the volume-surface mean diameter of the poly(ortho esters) microspheres and provided controlled release of 5-fluorouracil. The volume of aqueous phase was more important than the concentration of polyvinyl alcohol in it. The entrapment efficiency improved from 13 to 33% (w/w) when the volume of the aqueous phase was increased from 20 to 80 ml. The volume of organic phase (methylene chloride) and the concentration of polymer in it played an important role. The use of smaller volumes of more concentrated polymer solution enhanced actual drug loading and entrapment efficiency, and produced larger microspheres. The release of 5-FU from the microspheres prepared with sorbitan sequioleate was found to be nearly independent of the initial drug load with a mean zero-order rate constant of 0.0063 % per hr. The data suggested that drug release was largely a diffusional process with contributions from dissolution and polymer degradation.

The curing characteristics of photopolymer resin determine the relationship between the vat polymerization (VP) process parameters and the layer thickness, geometric accuracy, and surface quality of the 3D printed specimen. Dispersing filler material into the photopolymer resin changes its curing characteristics because the filler scatters and absorbs light, which modifies the curing reaction. However, the ability to cure photopolymer resin with high filler volume fraction is important to 3D print material specimens for specific engineering applications, e.g. structural polymer composite materials, electrical and thermal conductive materials, and ceramic materials for biological and high-temperature environments. We methodically measure the curing characteristics of diacrylate/epoxy photopolymer resin with dispersed glass microspheres. The experiments show that the curing depth, degree-of-cure, and surface roughness depend on both the light exposure dose and the filler fraction. We determine that the degree-of-cure increases with increasing filler fraction for constant exposure dose, and approaches 90% with increasing exposure dose, independent of the filler fraction. The geometric accuracy of the 3D printed specimens decreases with increasing exposure dose and with increasing filler volume fraction due to so-called profile broadening. Finally, we show that the average surface roughness of the 3D printed specimens decreases with increasing exposure dose and filler fraction. This work has implications for VP of photopolymer resins with high filler fraction. / Master of Science / Photopolymer resin is a gel-like liquid material that hardens (cures) into solid after absorbing light energy, and such a material is often used in the field of additive manufacturing (3D printing) to create complex geometry. Certain types of filler materials, such as metal powder or carbon fiber, can be added into the photopolymer resin to tailor the material properties, and thus, affects the curing behavior of photopolymer resin mixed with these filler materials. We conducted an experiment to understand how adding glass microspheres to a consumer grade photopolymer resin affects the process of creating 3D objects. This is important in the context of 3D printing engineered composite materials that derive their function from the organization and orientation of filler material in a matrix. To do this, we created many samples in the shape of a "VT" logo using the composite resin we made and measured their thickness (curing depth), degree-of-cure, surface roughness, and geometric accuracy, as a function of the amount of light energy being exposed to the resin (exposure dose) and the amount of the glass filler being added into the resin (filler fraction). We observed that when we increased the amount of light exposure, it resulted specimens that are thicker and more in degree of cure. Adding the glass filler to the liquid had mixed effects on the hardening process, because glass can scatter light and change how light travels within the resin. As a result, the printed objects became less accurate in shape and have smoother surface with increasing exposure dose and filler fraction, because more light is scattered off the designed curing profile and unintentionally cured the surrounding resin.

The effects of taste masking are determined by interactions between drug and excipients as well as the microstructures of the particulate drug delivery systems (DDS). Cyclodextrin (CD) is a widely used taste masking agent, to which the relationship between kinetic parameters (Ka and Kd) of a drug and taste masking remains unexplored, which is investigated for the first time in this study. A data base of the kinetic parameters for drug-CD was established by Surface Plasmon Resonance Imaging (SPRi) and High Performance Affinity Chromatography (HPAC). Combined with the electronic tongue, Ka and Kd based models for the taste masking effect of HP-β-CD were successfully established and applied to the prediction of taste masking effects. Paracetamol was used as a model drug for taste masking formulation optimization. As well as drug release the microstructure of solid DDS has considerable influence on drug taste. The microstructure of lipid microspheres and the molecular distribution of drug and excipients in lipid microspheres were investigated by Synchrotron radiation-based micro-computed tomography (SR-μCT) and Synchrotron radiation-based Fourier-transform infrared spectromicroscopy (SR-FTIR), respectively. The results demonstrated that the polymeric formulation components as well as shape and particle size of the drug were the key factors to taste masking of paracetamol by inhibiting bust release thereby reducing the interaction intensity of the bitterness. The FTIR absorption spectra confirmed the deposition and formation of chitosan and gelatin films on the drug microsphere surface by layer-by-layer coating. In conclusion, this research demonstrates the molecular kinetic basis of CD taste-masking as well as microstructural basis of particle systems for bitter taste masking.

This research is directed towards understanding the mechanisms associated with the manufacture of solid microspheres less than 100 [micrometers], from liquid droplets with nanosuspensions in a microfluidic T-junction, which are heated downstream of the channel. Preliminary material characterization tests on colloidal suspensions of alumina and copper oxide demonstrate promising temperature dependent viscosity results indicating solidification in the temperature range of 40°C-50°C. The solidification mechanism is referred to as Temperature Induced Forming and is described by polymeric bridges formed between nanoparticles in suspension at elevated temperatures, resulting in a solid structure. The polymer network results from the ionization of alumina at elevated temperatures whereby polymeric binders adhere to newly formed charged sites on the alumina particle. This study aims to investigate the aspects of manufacturing microstructures in microfluidic Tjunctions, droplet morphology, size and frequency of production. Preliminary low solid concentration experiments (1%-10% volume concentration of alumina in H2O) have indicated solidification and a regression in droplet diameter when heated near the saturation temperature of the water used to disperse the particles. The microstructures from this solidification process are uniform and are estimated to be 30 [micrometers] in size.

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