Lääkeaineiden ja terveysvaikutteisten aineiden puhdistaminen ali- ja ylikriittisellä uutolla ja kromatografialla

This thesis discusses the use of sub- and supercritical fluids as the medium in extraction and chromatography. Super- and subcritical extraction was used to separate essential oils from herbal plant Angelica archangelica. The effect of extraction parameters was studied and sensory analyses of the extracts were done by an expert panel. The results of the sensory analyses were compared to the analytically determined contents of the extracts. Sub- and supercritical fluid chromatography (SFC) was used to separate and purify high-value pharmaceuticals. Chiral SFC was used to separate the enantiomers of racemic mixtures of pharmaceutical compounds. Very low (cryogenic) temperatures were applied to substantially enhance the separation efficiency of chiral SFC. The thermodynamic aspects affecting the resolving ability of chiral stationary phases are briefly reviewed. The process production rate which is a key factor in industrial chromatography was optimized by empirical multivariate methods. General linear model was used to optimize the separation of omega-3 fatty acid ethyl esters from esterized fish oil by using reversed-phase SFC. Chiral separation of racemic mixtures of guaifenesin and ferulic acid dimer ethyl ester was optimized by using response surface method with three variables per time. It was found that by optimizing four variables (temperature, load, flowate and modifier content) the production rate of the chiral resolution of racemic guaifenesin by cryogenic SFC could be increased severalfold compared to published results of similar application. A novel pressure-compensated design of industrial high pressure chromatographic column was introduced, using the technology developed in building the deep-sea submersibles (Mir 1 and 2). A demonstration SFC plant was built and the immunosuppressant drug cyclosporine A was purified to meet the requirements of US Pharmacopoeia. A smaller semi-pilot size column with similar design was used for cryogenic chiral separation of aromatase inhibitor Finrozole for use in its development phase 2.Ylikriittinen teknologia mahdollistaa ympäristöystävällisten liuottimien, kuten hiilidioksidin käytön lääkeaineiden ja terveysvaikutteisten aineiden tuotannossa. Toisin kuin monet orgaaniset liuottimet, korkeapaineinen hiilidioksidi on hinnaltaan edullinen, myrkytön, palamaton ja ennen kaikkea helposti kierrätettävissä. Tämä väitöskirja keskittyy korkeapainehiilidioksidin käyttöön uutto- ja kromatografialiuottimena arvokomponenttien erotuksessa. Hiilidioksidia voidaan käyttää sellaisenaan lipofiilisten yhdisteiden kuten haihtuvaöljyjen, rasvahappomonoestereiden tai triglyseridien prosessoinnissa. Sen ominaisuuksia voidaan helposti muokata, lisäämällä siihen alkoholeja, mikä tekee hiilidioksidista liuotuskykyisen monille lääkeaineille. Korkeapainehiilidioksidi on hyvä liuotin, mm. Väinönputken (Angelica), katajanmarjan ja pomeranssinkuoriöljyjen uutossa. Sitä on käytetty myös kolesterolin poistoon mm. meijerituotteista ja munankeltuaisjauheesta. Tässä väitöskirjassa tarkastellaan uutto-olosuhteiden vaikutusta Väinönputkesta uutetun juuriesanssin laatuun. Vaitöskirjassa käsitellään myös yli- ja alikriittisen hiilidioksidin käyttöä korkeapainekromatografian liikkuvana faasina, joko sellaisenaan tai alkoholimodifioituna. Silika- ja C18-käänteisfaaseilla erotettiin syklosporiineja (hylkimisen estoaineita elinsiirroissa) ja omega-3 rasvahappojen monoestereitä, vastaavasti. Kiraalisia eli epäsymmetrisiä molekyylejä erotettiin peilikuvaisomeereistansa käyttäen kiraalisia stationäärifaaseja ja eluenttina nestemäistä hiilidioksidia hyvin kylmissä olossa. Prosessien ajo-olosuhteiden optimointiin kehitettiin empiirinen tilastollinen menetelmä, joilla laskennalliset tuotantonopeudet saatiin maksimoitua. Työssä kehitettiin myös rakenteeltaan täysin uusi painekompensoitu korkeapainekolonni, käyttäen hyväksi Suomessa kehitettyjen syvänmeren sukelluslaitteiden (Mir 1 ja 2) rakentamisessa saavutettua teknologiaa. Näiden kolonnien ympärille rakennettiin koetehdasmittainen kromatografiaprosessi bioteknisesti tuotettujen syklosporiinien erottamiseksi

Los sentidos de la manifestación: Prácticas, relatos e imágenes entorno de la "Masacre del 26 de Junio en Avellaneda"

The mobilization of the urban poor within the frame of piqueteros' organizations in the suburbs of Buenos Aires has been matter of two different approaches. On the one hand an ethnographic focus, that explores the associative networks interweaved by impoverished organizations and neighbors; and a sociological glance, that concentrates on the conditions and forms of collective construction of the organizations. Nevertheless, less attention has been paid to the public and interactive construction of the events of social protest that involve the piqueteros' organizations of this urban area. Building on this void, we seek to put forward a preliminary exploration of some dimensions of that public construction in the case of the socalled 'Massacre of June 26th in Avellaneda'. Understanding these events as a manifestation, that is to say: 'corporal and discursive interventions in the public sphere involving political content [in a broad sense of the term] and resorting to the tools of street mobilization', we seek both to reconstruct a narrative of those events and to develop a description and analysis of what several involved actors maintained that 'one had to think' about what had actually happenedLa movilización de los pobres urbanos en el marco de las organizaciones piqueteras del conurbano bonaerense ha sido materia de un doble enfoque. Una mirada de perfil etnográfico, que profundiza en las tramas asociativas que entretejen organizaciones y vecinos empobrecidos; y una mirada sociológica, que se concentra en las condiciones y las formas de construcción de las organizaciones. Sin embargo, menos atención se ha prestado ala construcción pública e interactiva de los eventos de protesta social que involucran a las organizaciones piqueteras de esta área urbana. Situándonos en este hueco nos proponemos avanzar en una exploración preliminar de algunas dimensiones de esa construcción pública en el caso de la denominada "Masacre del 26 de Junio en Avellaneda". Tomando estos eventos como manifestación, es decir : "intervenciones corporales y discursivas de contenido político [en el sentido amplio del término] en el espacio público recurriendo a los instrumentos de la movilización callejera', nos interesa tanto reconstruir un relato de lo que ocurrió en ese entonces como hacer una descripción y análisis de lo que diversos actores involucrados sostuvieron que "debía pensarse' de aquello que ocurri

Milk fat fractionation using supercritical carbon dioxide extraction

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Removal of cholesterol during milk fat fractionation by supercritical carbon dioxide

Milk fat contains compounds such as aroma substances which we may want to enrich, as well as compounds such as cholesterol which we may want to remove. The utilization of SC-CO2 extraction for enriching or removing such compounds has been studied on a pilot plant scale, with the most recent experiments focusing on the removal of cholesterol. It was found that more than 99% of milk fat cholesterol could be removed using an extraction system equipped with a silica gel column. The extraction was performed under a constant pressure of 320 bar and at a constant temperature of 52°C. The results show that the removal of cholesterol and milk fat fractionation based on the molecule size of triglycerides can be achieved simultaneously