Tesis: "Ephedrine"

1

Boyes, A. L. "Synthesis of the talaromycins A, B, C and E and synthetic studies towards ephedrine C". Thesis, University of Southampton, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233899.

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2

Link, Jeanne Meyers. "Mixed-mode chromatographic separation and whole column radiation detection to improve sensitivity in radiometabolite analysis : application to (Carbon-11)-meta-hydroxyephedrine in plasma /". Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/8578.

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3

Verner, Jennifer Joan. "Formulation and dissolution assessment of a novel repeat action tablet containing a decongestant and an antihistamine". Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1003276.

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Controlled and sustained release dosage forms are the focus of worldwide research. These dosage forms facilitate patient compliance by simplifying the dosage regimen, and decrease the risk of adverse effects by reducing large fluctuations in the plasma concentration of the drug. The objective of this study was to formulate a repeat-action tablet to provide a sustained release dose of pseudoephedrine sulfate (PSS), and an immediate release dose of both PSS and loratadine. The release profile was compared to that of a commercially available preparation, Clarityne-D®. This formulation developed presents a novel mechanism of sustaining the release of PSS. The prototype tablet consisted of a sustained release core coated with an ethylcellulose dispersion to introduce a lag phase into the release profile and a second outer film coat incorporating PSS and loratadine. The core comprised an ethylcellulose granulation of PSS compressed into a hydroxypropyl methylcellulose matrix. The release of PSS from prototypes was assessed using USP Apparatus 3, as this apparatus was more representative of in vivo conditions and discriminated more effectively between the different tablet compositions produced during development. All dissolution samples were analysed for PSS and loratadine using validated highperformance liquid chromatographic methods. The prototype sustained release cores were found to be more resistant than the reference product to elevated temperature and humidity (40°C/87% RH) with fewer observed changes to the release profiles following storage for up to six months. This study was a feasibility study to obtain proof of concept. The release profile obtained from the prototype tablets was similar (f₂ = 50.0) to that of the reference product. Further development and optimisation of this dosage form is necessary, including evaluation of the choice of hydrophobic polymer, the effect of compression force and tablet geometry and characterisation of the release mechanism from the coated matrix. Assessment of these factors is necessary in order to optimise the formulation with respect to the desired therapeutic objectives.

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4

Pasternak, Harley. "The effect of ingesting caffeine, ephedrine, and their combination on repeated strength performance". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/MQ53354.pdf.

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5

Hutchison, Panee. "The development of ephedrine-based chiral linkers for asymmetric reactions on solid phase". Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402748.

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6

Shah, Beena. "A study into the use of ephedrine, immobilised on a silica support and its use in asymmetric alkynylation reactions". Thesis, Kingston University, 2015. http://eprints.kingston.ac.uk/32206/.

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This work describes the preparation of an immobilised ephedrine silica supported catalyst and its application in asymmetric synthesis. (1R,2S)-(-)-Ephedrine is a controlled substance, whose use in synthesis is closely monitored by a licence regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). One way of reducing the demand for controlled substances as catalysts is to tether them onto a support medium so that afier use they may be recovered by filtration, washed and reactivated, if necessary, dried and then reused. In this project, (IR,ZS)-(-)-cphedrine was tethered onto a functionalised silica support and tested for its use in asymmetric alkynylation reactions involving a range of aromatic aldehydes and a terminal alkyne, phenylacetylene. The loading of the ephedrine on the supported catalyst was characterised by both elemental analysis and thermogravimetric analysis (TGA) due to the nature of the support material. The immobilised ephedrine catalyst was evaluated in asymmetric alkynylation reactions and was shown to provide good enantioselectivity (up to 92% for (R)-(+)- l ,3-diphenylprop-2-yn-l-ol) and high yields for the secondary propargylic alcohols (up to 97%). The use of the immobilised ephedrine catalyst in asymmetric alkynylation reactions was assumed to be novel. The results of the newly formed secondary propargylic alcohols proved to be comparable to those achieved by homogeneous systems. The secondary propargylic alcohols were analysed using a wide range of spectroscopic techniques such as nuclear magnetic resonance (NMR) spectroscopy, gas chromatography- mass spectrometry (GC-MS), optical rotation and high performance liquid chromatography (HPLC). Due to the restrictions placed on ephedrine, it was important to test the recyclability of the tethered catalyst to reduce the amount of the regulated drug in circulation. The catalyst demonstrated the ability to be recovered quantitatively from the reaction mixture using a simple filtration and then recycled in further asymmetric alkynylation reactions for three cycles before the yield was affected. In addition to the study, a novel tethering of ephedrine derivatives onto a silica support was investigation and its use in asymmetric alkynylation reactions explored. This was undertaken in an effort to optimise and improve upon the results obtained from N-methylcphedrine alone. Our initial results showed that it is possible to tether ephedrine derivatives onto a silica support and then employ them in asymmetric synthesis, thus opening up the possibility to use controlled ephedrine more efficiently.

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7

Fabre, Anne. "Ephédrine : utilisation thérapeutique et en pratique sportive ; contrôle antidopage". Bordeaux 2, 1996. http://www.theses.fr/1996BOR2P029.

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8

Erkinaro, T. (Tiina). "Fetal and placental haemodynamic responses to hypoxaemia, maternal hypotension and vasopressor therapy in a chronic sheep model". Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:9514281659.

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Abstract Knowledge of the effects of maternally administered vasopressors on human fetal and placental haemodynamics is sparse and limited to elective Caesarean deliveries in uncomplicated pregnancies. We hypothesized that, after short-term fetal hypoxaemia, which activates fetal cardiovascular compensatory mechanisms, treatment of maternal hypotension with ephedrine or phenylephrine results in divergent responses in fetal and placental haemodynamics. Chronically instrumented near-term sheep fetuses with either normal placental function or increased placental vascular resistance following placental embolization were exposed to two subsequent periods of decreased fetal oxygenation caused by maternal hypoxaemia and epidural-induced hypotension. The fetuses that underwent placental embolization were also chronically hypoxaemic. Fetal and placental haemodynamics were assessed by invasive techniques and by noninvasive Doppler ultrasonography. Our results show that umbilical artery blood flow velocity waveforms cannot be used to derive information of fetal cardiac function. Furthermore, the changes in placental volume blood flows and vascular resistances caused by maternal vasopressor treatment cannot be reliably recognized based on uterine and umbilical artery pulsatility index values. In response to acute hypoxaemia, a fetus with normal placental function redistributes its right ventricular cardiac output from the pulmonary to the systemic circulation and is able to increase its combined cardiac output, with a concomitant relative decrease in the net forward flow through the aortic isthmus. However, fetal haemodynamic responses to subsequent hypoxaemic insults may vary. Furthermore, the compensatory responses of fetuses with increased placental vascular resistance differ from those of normal fetuses. In these fetuses, repeated episodes of a further decrease in oxygenation lead to lactataemia. The effects of ephedrine on uteroplacental and umbilicoplacental circulations were more favourable than those of phenylephrine. Ephedrine restored the changes in fetal cardiovascular haemodynamics caused by maternal hypotension to the baseline conditions in both embolized and nonembolized fetuses. Phenylephrine did not reverse fetal pulmonary vasoconstriction or the relative decrease in the net forward flow through the aortic isthmus. Moreover, fetal left ventricular function was impaired by phenylephrine. Although no significant differences in fetal acid-base status were observed in fetuses with normal placental function, the lactate concentrations of the embolized fetuses increased further when maternal hypotension was treated with phenylephrine.

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9

Jonsson, Karin. "Flickors bruk av och attityd till illegala viktminskningspreparat. : En enkätundersökning riktad till flickor i årskurs tre på gymnasiet". Thesis, Karlstads universitet, Fakulteten för samhälls- och livsvetenskaper, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-7302.

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Newspaper articles and media have shown that the use of illegal weight loss compounds, such as ephedrine and Melanotan, is becoming more common among adolescent girls, who are at risk of becoming a new group of addicts. These girls are rarely aware of the risks that the use of these compounds entails and the consequences that could adversely affect their bodies, mentally and physically. The aim of this paper was to investigate the use of and attitudes towards illegal weight loss compounds amongst girls in year three, at Swedish upper secondary schools. In order to do that, a questionnaire was sent out to 120 girls in five different high schools, with varying college preparatory and vocational program directions. My research shows that the use of illegal weight loss compounds, particularly ephedrine, was found among girls in year three, at upper secondary schools. Seven percent of the girls claimed they use, primarily, ephedrine. This result exceeds earlier studies findings on boys' use of anabolic androgenic steroids (AAS). Throughout the survey a sense of how common the use of and attitudes towards illegal weight loss compounds were amongst these girls was formed. The girls' critical views of their bodies permeate my research, whereas almost half of all girls are experiencing dissatisfaction with their body weight and the majority of the girls want to lose body weight. Regarding the girls' attitudes towards the use of illegal weight loss compounds, one result accounted that almost half of all girls could think of using one if it guaranteed them to be thinner. My research also shows that more information needs to be targeted towards young girls; in order to make them conscious about the dangers of these illegal weight loss compounds.
Tidningsartiklar och media har belyst att bruk av illegala viktminskningspreparat såsom efedrin och Melanotan blir allt mer vanligt bland unga flickor och som riskerar att bli en ny grupp missbrukare. Dessa flickor är sällan medvetna om riskerna och följderna som negativt kan påverka deras kroppar både psykiskt och fysiskt vid bruk av dessa preparat. Syftet med detta examensarbete var att undersöka förekomsten av bruk och attityd till illegala viktminskningspreparat bland flickor i årskurs tre på gymnasiet. För att kunna ge svar på syftet utfördes en enkätundersökning på 120 flickor på fem olika gymnasieskolor, med varierande studieförberedande och yrkesförberedande programinriktning. Genom undersökningen skapades en uppfattning om hur förekommande bruket av och attityder till illegala viktminskningspreparat var bland flickorna. Min enkätundersökning visar att 7 % av respondenterna har använt ett illegalt viktminskningspreparat, främst efedrin. Detta resultat överstiger tidigare undersökningars och studiers resultat avseende pojkars bruk av anabola androgena steroider (AAS). Flickornas kritiska syn på sina kroppar genomsyrar min undersökning då nästan hälften upplever missnöje med sin kroppsvikt och majoriteten av flickorna önskar att gå ned i vikt. Avseende flickornas attityd gällande bruk av illegala viktminskningspreparat svarade nästan hälften att de inte är främmande till ett bruk ifall det garanterade dem att bli smala. Min undersökning visar också att mer information behöver riktas mot unga flickor för att medvetandegöra dem om farorna av dessa illegala viktminskningspreparat.

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10

Adams, Samantha. "A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and a non-reassuring fetal heart rate trace". Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29804.

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Background: Studies in healthy patients undergoing elective caesarean delivery show that ephedrine used for spinal hypotension is associated with increased fetal acidosis compared with phenylephrine. This has not been investigated prospectively in severe preeclampsia. Methods: Patients with severe preeclampsia requiring caesarean delivery for a non- reassuring fetal heart tracing were randomised to receive bolus ephedrine (7.5-15 mg) or phenylephrine (50-100 μg) for spinal hypotension. The primary outcome was umbilical arterial base deficit. Secondary outcomes were umbilical arterial (UA) and venous (UV) pH and lactate level, venous base deficit, and Apgar scores. Results: A total of 133 women were included;; 64 required vasopressor treatment and were randomised to 2 groups of 32 with similar patient characteristics. Pre- delivery blood pressure changes were similar in the 2 groups. There was no difference in mean [SD] UA base deficit (-4.9 [3.7] vs -6.0 [4.6] mmol·L⁻¹ for ephedrine and phenylephrine respectively;; P = 0.29). Mean [SD] pH (UA and UV) and lactate levels were also similar between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol·L⁻¹ respectively). In addition, UV PO₂ was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P = 0.02). There was no difference in 1- or 5-minute Apgar scores, numbers of neonates with 1-minute Apgar scores < 7 (10/32 [31%] vs 12/32 [38%]), or with a pH < 7.2 (6/31 [19%] vs 8/29 [28%]). Conclusions: In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine vs phenylephrine to treat spinal hypotension.

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11

Leksawasdi, Noppol Biotechnology &amp Biomolecular Sciences (BABS) UNSW. "Kinetics and modelling of enzymatic process for R-phenylacetylcarbinol (PAC) production". Awarded by:University of New South Wales. Biotechnology and Biomolecular Sciences (BABS), 2004. http://handle.unsw.edu.au/1959.4/20846.

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R-phenylacetylcarbinol (PAC) is used as a precursor for production of ephedrine and pseudoephedrine, which are anti-asthmatics and nasal decongestants. PAC is produced from benzaldehyde and pyruvate mediated by pyruvate decarboxylase (PDC). A strain of Rhizopus javanicus was evaluated for its production of PDC. The morphology of R. javanicus was influenced by the degree of aeration/agitation. A relatively high specific PDC activity (328 U decarboxylase g-1 mycelium) was achieved when aeration/agitation were reduced significantly in the latter stages of cultivation. The stability of partially purified PDC and crude extract from R. javanicus were evaluated by examining the enzyme deactivation kinetic in various conditions. R. javanicus PDC was less stable than Candida utilis PDC currently used in our group. A kinetic model for the deactivation of partially purified PDC extracted from C. utilis by benzaldehyde (0?00 mM) in 2.5 M MOPS buffer has been developed. An initial lag period prior to deactivation was found to occur, with first order dependencies of PDC deactivation on exposure time and on benzaldehyde concentration. A mathematical model for the enzymatic biotransformation of PAC and its associated by-products has been developed using a schematic method devised by King and Altman (1956) for deriving the rate equations. The rate equations for substrates, product and by-products have been derived from the patterns for yeast PDC and combined with a deactivation model for PDC from C. utilis. Initial rate and biotransformation studies were applied to refine and validate a mathematical model for PAC production. The rate of PAC formation was directly proportional to the enzyme activity level up to 5.0 U carboligase ml-1. Michaelis-Menten kinetics were determined for the effect of pyruvate concentration on the reaction rate. The effect of benzaldehyde on the rate of PAC production followed the sigmoidal shape of the Monod-Wyman-Changeux (MWC) model. The biotransformation model, which also included a term for PDC inactivation by benzaldehyde, was used to determine the overall rate constants for the formation of PAC, acetaldehyde and acetoin. Implementation of digital pH control for PAC production in a well-stirred organic-aqueous two-phase biotransformation system with 20 mM MOPS and 2.5 M dipropylene glycol (DPG) in aqueous phase resulted in similar level of PAC production [1.01 M (151 g l-1) in an organic phase and 115 mM (17.2 g l-1) in an aqueous phase after 47 h] to the system with a more expensive 2.5 M MOPS buffer.

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12

Fagundes, Ana Cláudia. "Análise toxicológica de suplementos alimentares e compostos emagrecedores contendo efedrina, p-sinefrina e cafeína". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/166289.

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A busca por um padrão estético globalizado e o aumento da obesidade fazem crescer o uso de suplementos alimentares e compostos emagrecedores à base de extratos vegetais. Produtos contendo a associação de p-sinefrina, efedrina, salicina e cafeína são amplamente consumidos e não apresentam efetividade e segurança bem esclarecidas. Portanto, o objetivo deste trabalho foi avaliar a toxicidade subcrônica de p-sinefrina, efedrina, cafeína e salicina, isoladas e em associação, em ratos Wistar machos. Doses de salicina 6 mg/kg, efedrina 4 mg/kg, p-sinefrina 10 mg/kg, cafeína 80 mg/kg e a associação de salicina, efedrina, p-sinefrina e cafeína 100 mg/kg (6:4:10:80, respectivamente) foram testadas via oral por 28 dias consecutivos. A massa corporal foi verificada semanalmente e o teste da atividade locomotora foi realizado no 28º dia. O sangue foi coletado para análise bioquímica e órgãos vitais como fígado e rins foram utilizados para avaliação histológica. Os resultados mostraram uma redução significativa (p<0,05) na massa corporal nos dias 21 e 28 do grupo tratado com cafeína comparado ao grupo controle. Nos dias 14, 21 e 28 ocorreu um aumento significativo (p<0,05) da massa corporal no grupo tratado com p-sinefrina comparado com os grupos efedrina, salicina, cafeína e associação. No teste da atividade locomotora houve um aumento significativo (p<0,05) no grupo tratado com a associação comparado ao grupo controle. Não foram encontradas alterações nos marcadores bioquímicos de fígado, rim e coração, bem como nas avaliações macroscópicas dos órgãos vitais. Entretanto, na análise histológica do fígado, verificou-se em todos os grupos a presença de vacuolização e tumefação celular, congestão vascular e alargamento dos sinusóides, e apenas os grupos p-sinefrina, efedrina e salicina apresentaram degeneração hidrópica. Na histologia dos rins todos os grupos demonstraram vacuolização celular e aumento do espaço da cápsula de Bowman e o grupo p-sinefrina mostrou a presença de infiltrado inflamatório. Esses resultados sugerem que o uso dessas substâncias, tanto na forma isolada como em associação, apresenta um perfil toxicológico considerável.
The search for a globalized aesthetic standard and the increasing obesity are enhancing the use of food supplements and weight loss compounds from plant base extracts. Products containing the combination of p-synephrine, ephedrine, caffeine and salicin are widely consumed and the effectiveness and safety are not well understood. Therefore, the aim of this study was to evaluate the subchronic toxicity of p-synephrine, ephedrine, caffeine and salicin, isolated and in combination, in male Wistar rats. Doses of salicin 6 mg/kg, ephedrine 4 mg/kg, p-synephrine 10 mg/kg, caffeine 80 mg/kg and the association of salicin, ephedrine, p-synephrine and caffeine (100 mg/kg; 6:4:10:80, respectively) were administered orally for 28 consecutive days. Body weight was recorded weekly and a locomotor activity test was performed on the 28th day. Blood was collected for biochemical analysis and vital organs such as liver and kidneys were used for histologic evaluation. The results showed a significant reduction (p <0.05) in body mass on days 21 and 28 in the caffeine-treated group compared to control group. Besides that, on days 14, 21 and 28 a significant increase (p <0.05) in body weight was observed in the group treated with p-synephrine compared to the ephedrine, salicin, caffeine and association-treated groups. In the test of locomotor activity, a significant increase (p <0.05) was observed in the association-treated group treated compared to the control group. No changes were found in biochemical markers associated with liver, kidney and heart conditions or in macroscopic evaluations of vital organs. However, the histological analysis of the liver in all groups shown presence of cellular vacuolization and swelling, vascular congestion and enlargement of the sinusoids, whereas the p-synephrine, ephedrine and salicin groups exhibited hydropic degeneration. In the histology of kidneys, all groups showed cellular vacuolation and increased of the Bowman's capsule space and the p-synephrine group showed the presence of inflammatory infiltrate. These results suggest that the use of these substances either in isolation or in combination showed a considerable toxicological profile.

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13

Schmitt, Gabriela Cristina. "Análise química e toxicológica de suplementos alimentares e compostos emagrecedores contendo p-sinefrina associada a efedrina, salicina e cafeína". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/60372.

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Os suplementos alimentares e compostos emagrecedores a base de extratos vegetais têm uso muito difundido e indiscriminado, principalmente pela diversidade de produtos disponíveis e facilidade de acesso aos mesmos, aliada à falsa crença popular de que “o que é natural não faz mal”. Produtos contendo a associação de psinefrina, efedrina, salicina e cafeína são amplamente consumidos pela população. Entretanto, a efetividade e, sobretudo, a segurança da associação dessas substâncias ainda não é conhecida, visto que estudos sobre o sinergismo farmacológico e toxicológico dessa associação ainda são praticamente inexistentes. Logo, o objetivo deste trabalho foi elucidar o perfil toxicológico agudo e subcrônico, incluindo avaliação do estresse oxidativo e de alterações fisiológicas, bem como o desenvolvimento de metodologias que permitam analisar e quantificar o teor dessas substâncias nos produtos comerciais. Para avaliação da toxicidade aguda, doses de 300, 350 e 400 mg/kg da associação de p-sinefrina, efedrina, salicina e cafeína (10:4:6:80) foram testadas via oral em camundongos machos e fêmeas. Foi possível observar redução da atividade locomotora, ptose (em todas as doses em ambos os sexos), convulsões (350 mg/kg em fêmeas e 400 mg/kg em machos e fêmeas), além de salivação, agitação, piloereção em fêmeas, bem como mortes em machos (350 e 400 mg/kg) oriunda de hemorragia cardiopulmonar. Redução na atividade locomotora foi confirmada através do teste de atividade locomotora espontânea em machos que mostrou diminuição significativa (p<0,01) em todos os grupos tratados, sendo o mesmo resultado observado quando do teste de temperatura corporal, havendo decréscimo da mesma em todas as doses testadas. O teste de rota-rod mostrou ocorrência de neurotoxicidade em machos tratados com 400 mg/kg. A DL50 da mistura foi estimada entre 350 e 400 mg/kg. No teste de avaliação da toxicidade subcrônica, ratos machos e fêmeas foram tratados por via oral com a mesma mistura por 28 dias consecutivos nas doses de 50, 75, 100 e 150 mg/kg. Avaliações hematológicas, bioquímicas e de marcadores de estresse oxidativo foram realizadas, observando-se ocorrência de peroxidação lipídica e de dano hepático e renal em ratos machos (100 e 150 mg/kg), além de diminuição da GSH em todos os machos tratados. Nas fêmeas não houve indicação de estresse oxidativo, mas sim, ocorrência de alterações hepáticas não conclusivas. O diferente perfil de toxicidade apresentado por machos e fêmeas sugere influência hormonal sobre os efeitos fármaco-toxicológicos da mistura. Os resultados obtidos mostraram que a associação de p-sinefrina, efedrina, salicina e cafeína, nas doses testadas, apresenta considerável perfil de toxicidade, tanto agudo quanto subcrônico, indicando a necessidade de testes toxicológicos mais detalhados para total elucidação dos efeitos, incluindo avaliações relacionadas à influência da presença de estrogênio, avaliações que permitam períodos mais longos de exposição e avaliação de outros marcadores de estresse oxidativo, visto o grande número de acidentes toxicológicos relatados após utilização de suplementos alimentares e compostos emagrecedores cujas formulações frequentemente contém essa associação de substâncias. Com base no desenvolvimento da metodologia de análise, a extração em fase sólida com cartuchos de troca iônica SCX, seguida de extracção líquido-líquido com clorofórmio, subsequente reação de derivatização com anidrido trifluoroacético e posterior análise em CG/DIC (e GC/EM para confirmação) pode ser considerada uma alternativa promissora para analisar simultaneamente sinefrina, efedrina e cafeína em suplementos alimentares e compostos emagrecedores. O método por CG/DIC foi validado pela definição da faixa de linearidade para as substâncias (50, 100, 200, 500, 1000 e 2000 ug/mL para octopamina efedrina e p-sinefrina e 250, 500, 1000, 2500, 5000 e 10000 ug/mL para cafeína), limite de detecção, limite de quantificação, precisão, exatidão, seletividade, especificidade e robustez. O método de análise desenvolvida pode ser utilizado no controle de qualidade de produtos, para identificar e quantificar estas substâncias em uma ampla variedade de matrizes.
Dietary supplements and weight loss compounds plant-based are indiscriminate and widespread use, mainly for the diversity of products available and easy acess to them, coupled with the false popular belief that “what is natural does not hurt”. Products containing p-synephrine associated to ephedrine, salicin and caffeine are largely consumed. However, the effectiveness and safety of this mixture is still unknown, since studies about pharmacological and toxicological synergism are still nonexistent. Therefore, the aim of this study was evaluate the acute and subchronic toxicological profile, including assessment of oxidative stress physiological alterations, as well as the development of methodologies to analyze and quantify these substances in commercial products. To acute toxicological evaluation, 300, 350 and 400 mg/kg doses of association of p-synephrine, ephedrine, salicin and caffeine (10:4:6:80 w/w) were tested by oral gavage in male and female mice and was possible to observed a reduction in locomotor activity and ptose (in all treated groups for both male and female mice), seizures (350 mg/kg in female and 400 mg/kg in male and female), besides salivation, agitation and piloerection in female. Deaths occurred in male (350 and 400 mg/kg) and necropsy showed cardiopulmonary hemorrhage. The decrease in locomotor activity was confirmed throught the spontaneous locomotor activity, in which the number of crossings significantly decreased (p<0.01) in all treated groups, being the similar result obtained in body temperature evaluation, reducing in the all same doses. The rotarod test showed neurotoxicity in male treated with 400 mg/kg. The LD50 of the mixture was estimated between 350 and 400 mg/kg. In subchronic toxicity evaluation, male and female rats were treated by oral gavage with the mixture for 28 consecutive days at doses of 50, 75, 100 and 150 mg/kg. Hematological, biochemical and oxidative stress biomarkers were performed and showed lipid peroxidation, and hepatic and renal damages in male rats (100 and 150 mg/kg) and reduction in GSH levels and all treated male groups. In females, there were no indications of oxidative stress, but were observed not conclusive hepatic enzyme changes. The different toxicity profile displayed by male and female rats suggests hormonal influence in mixture effects. All the results obtained showed that the association of p-synephrine, ephedrine, salicin and caffeine in tested doses has considerable toxicity both acute and subchronic profiles, indicating the need of more detailed investigations for elucidate all the effects, including assessments related to protector role of estrogen, and more longterm studies of exposure, besides evaluations of more oxidative biomarkers, since the large number of toxicological report cases related to these products whose formulations usually contain these substances´s combination. On the basis of analytical methodology development, the SPE with SCX stationary phases followed by liquid-liquid extraction with chloroform and subsequent derivatization with anhydride trifluoroacetic and GC/FID (and GC/MS confirmation) analysis can be considered a promising alternative to analyze simultaneously synephrine, ephedrine and caffeine in supplements and weight loss products. The GC/FID method was validated by defining the linearity (50, 100, 200, 500, 1000 and 2000 μg/mL to ephedrine, octopamine and p-synephrine and 250, 500, 1000, 2500, 5000 and 10000 μg/mL to caffeine), limit of detection, limit of quantification, precision, accuracy, selectivity, specificity and robustness. The analysis method developed can be used in quality control to identify and quantificate these substances in a wide range of matrices.

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14

Sebben, Viviane Cristina. "Análise de efedrinas e anfetamina em urina empregando spe e spme por cg/em/em". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/12004.

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O Brasil ocupa posição de destaque no consumo mundial de anfetaminas, contrariamente à tendência mundial de retração. Devido aos efeitos colaterais e ao alto potencial de abuso, a produção e comercialização de anfetaminas vêm sendo controladas no mundo inteiro. Com a restrição de uso, houve um retorno a procura pelos equivalentes naturais, especialmente as efedrinas presentes em diversas especialidades farmacêuticas, utilizadas no tratamento de doenças respiratórias. São componentes de vários compostos emagrecedores, suplementos alimentares e dietéticos utilizados para perda de peso e ganho de massa muscular. Face ao uso indiscriminado e a grande incidência de resultados falso-positivos nos testes de triagem para anfetaminas por imunoensaio enzimático homogêneo, fazem-se necessários testes confirmatórios. Neste sentido, este trabalho se propôs a desenvolver um método confirmatório simples e rápido para detecção, identificação e quantificação de efedrinas (efedrina/pseudoefedrina) em amostras de urina por por cromatografia a gás / espectrometria de massas-massas (CG/EM/EM), passível de ser adotado na rotina de laboratórios de análises toxicológicas. Devido à complexidade da matriz e as peculiaridades do analito, inicialmente procedeu-se o estudo do tratamento da amostra, considerando as etapas de derivatização, extração, pré-concentração e purificação, de modo a fornecer um extrato límpido, livre de impurezas, interferentes e com melhor sensibilidade, linearidade e seletividade analítica. Os métodos de extração usados foram extração líquido-líquido (ELL), extração em fase sólida (SPE) e microextração em fase sólida (SPME). Os resultados indicaram que o reagente de derivatização ciclohexanona foi o que apresentou melhor desempenho, menor custo e promoveu maior seletividade dos diasterômeros EF/PEF em colunas normais de CG. Sendo que o método mais apropriado para a detecção e identificação de efedrinas/anfetamina por CG/EM é a SPME levando em consideração características como simplicidade, rapidez, custo, recuperação e ausência de interferentes. Entretanto, considera-se valido o uso de SPE para a quantificação, devido à possibilidade de pré-concentração do analito.
Brazil is one of the biggest amphetamine consumers in the world, going against the worldwide retraction tendency. Due to serious adverse effects and high abuse potential, the production and commercialization of amphetamines has been controlled around the world. With the restriction of its use, there was a return in the search of natural equivalents, especially the ephedrines found in many medicines utilized in the treatment of respiratory diseases. Furthermore, they are components of dietary supplements used to lose weight and muscular mass gain. Because of the indiscriminate use and the high incidence of false-positive results in the amphetamines screening tests by enzyme immunoassay technique, it is necessary confirmatory tests. In this way, the aim of this work is to develop a confirmatory simple and quickly method for the detection and quantification of ephedrines (ephedrine and pseudoephedrine) gas chromatography / mass-mass spectrometry (GC/MS/MS), with possibility to be adopted in toxicological analyses laboratorial routine. Due to the complexity of the matrix and analyte peculiarities, initially proceeds the study of sample treatment, considering the derivatization, extraction, pre-concentration and purification steps, obtaining a limpidous extract, free of impurities, interferents and with better sensitivity, linearity and analytical selectivity. The extraction method used were liquid-liquid extraction (LLE), solid-phase extraction (SPE) and solid-phase microextraction (SPME). The results indicate that cyclohexanone was the derivatization agent with the best performance, lower price and good selectivity in diasteromers EF/PEF separation in normal GC columns. The most appropriate method for detection and identification of ephedrines/amphetamine by GC/MS is SPME, considering characteristics as simplicity, speed, cost, recovery and absence of interferents. However, the use of SPE must be considered to quantification, since it allowed analyte pre-concentration.

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15

Russell, Michael Geoffrey Neil. "Studies towards the synthesis of ephedradine C". Thesis, University of Hertfordshire, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245352.

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16

Humphrey, G. R. "Approaches towards the total synthesis of the ephedradine alkaloids". Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378264.

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17

Karaminkov, Rosen. "Conformations and fragmentation of biologically relevant molecules and their binary complexes with water probed by high resolution UV and mass analyzed threshold ionization spectroscopy". kostenfrei, 2009. https://mediatum2.ub.tum.de/node?id=821610.

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18

Schmitt, Aline. "Reconnaissance de molécules d'intérêt biologique par les hémicryptophanes - stéréosélectivité, reconnaissance dans l'eau et fluorescence". Thesis, Lyon, École normale supérieure, 2014. http://www.theses.fr/2014ENSL0916.

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La reconnaissance moléculaire est un phénomène omniprésent dans les systèmes vivants et intervient dans de nombreux processus biologiques comme la reconnaissance cellulaire ou encore la transmission de signaux par les neurotransmetteurs. L’élaboration de molécules synthétiques capables de mimer l’action des récepteurs naturels en complexant sélectivement un substrat cible est, à l’heure actuelle, très recherchée pour la détection ou le diagnostic en biologie et médecine. Parmi l’ensemble des récepteurs synthétiques, les hémicryptophanes sont des molécules cages composées d’un cyclotribenzylène connecté à une autre unité moléculaire par trois bras espaceurs. Les travaux de cette thèse reposent sur l’élaboration de nouveaux hémicryptophanes et l’étude de leurs propriétés de complexation vis-à-vis de molécules d’intérêt biologique. Dans un premier temps, la chiralité de ces récepteurs a été utilisée pour étudier leurs propriétés de reconnaissance stéréosélective face à différents sucres et analogues de neurotransmetteurs. De bonnes diastéréosélectivités et énantiosélectivités ont ainsi pu être observées en milieu organique pour les substrats étudiés. En parallèle, plusieurs hémicryptophanes hydrosolubles ont été synthétisés et ont permis de reconnaitre sélectivement des neurotransmetteurs comme la choline dans l’eau. Enfin, une dernière partie de cette thèse à été consacrée à la mise en place d’une voie de synthèse pour rendre ces récepteurs fluorescents, dans le but d’élaborer par la suite des sondes moléculaires capables de détecter et de suivre spatio-temporellement des molécules d’intérêt biologique dans les systèmes vivants par fluorescence
Molecular recognition is a very important phenomenon for living systems as it occurs in many biological processes like cell-cell recognition or transmission of signals by neurotransmitters. Nowadays, the design of synthetic host molecules able to mimic natural receptors by complexing selectively a target substrate, is much sought-after for detection or diagnostic in biology and medicine. Among all the different synthetic receptors, hemicryptophanes are cage-shape molecules which are composed of a cyclotribenzylene moiety connected to another molecular unit by three spacer arms. This thesis is about the synthesis of new hemicryptophanes and the study of their complexation properties toward biologically important molecules. First, the stereoselective recognition of carbohydrates and neurotransmitter analogues by these chiral receptors was investigated in organic solvents and revealed good enantioselectivities and diastereoselectivities. In parallel, several water-soluble hemicryptophanes were synthesized and showed an aptitude for recognizing selectively ammonium substrates like choline in water. The last part was devoted to the development of a synthetic pathway to make hemicryptophanes fluorescent, in order to design molecular probes able to track biologically important molecules in living systems by fluorescence

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19

Geiger, Yannick. "Chiral complexes in catalysis and non-linear optics : study of non-linear effects in asymmetric catalysis and of sum-frequency generation". Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAE031.

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Un effet non-linéaire (NLE) hyperpositif a été observé dans l’addition énantiosélective de dialkylzincs sur du benzaldéhyde catalysée par un ligand chiral éphédrine N-benzylé. Ceci est la première preuve expérimentale d’un NLE hyperpositif, où le ee de produit maximal n’est pas obtenu avec un catalyseur énantiopur mais scalémique. L’origine de ce NLE hyperpositif a été identifiée comme venant d’un double système catalytique où des catalyseurs monomériques mais aussi dimériques homochiraux catalysent la réaction, avec des énantiosélectivités différentes. Avec un ligand scalémique, la précipitation d’un aggrégat hétérochiral diminue la quantité de catalyseur homochiral actif et en solution, déplaçant ainsi l’équilibre du catalyseur agrégé vers son homologue monomérique et plus énantiosélectif. Le système catalytique a été étudié en variant la concentration de catalyseur et la température, en déterminant l’état d’agrégation du catalyseur par RMN 1H DOSY, par des études cinétiques et des courbes de Hammett. Une version ditopique du ligand a également été étudiée pour ces effets non-linéaires en catalyse, qui se sont avérés être en partie hyperpositifs. De nouveaux métallopolymères constitués d’un ligand ditopique chiral et d’un métal ont été développé pour l’application en génération de somme de fréquence (SFG). Les ligands sont préparés par la double addition d’un aminoalcool ou d’une diamine chirale sur du terephtaldehyde pour obtenir des bis-imine-1,4-phenylènes absorbant vers 300 nm. Certains de ces complexes montrent une très forte activité en SFG mais s’avèrent être sensible à l’humidité et donc être difficile à manipuler. Une variante plus stable à base d’une 2-aminoaniline chirale a été développée par la suite et ces propriétés en spectroscopie UV-visible ont été étudiées
A hyperpositive non-linear effect (NLE) was observed in the enantioselective addition of dialkylzincs to benzaldehyde catalyzed by chiral N-benzyl ephedrine. This is the first experimental evidence of such phenomenon were the maximum product ee is not achieved with an enantiopure, but a scalemic catalyst. The origin for this hyperpositive NLE was traced back to a joint catalysis by monomeric as well as homochiral aggregated catalysts which bear different enantioselectivities. With scalemic ligands, the precipitation of heterochiral aggregates decreases the amount of active homochiral catalyst in solution, thus shifting the equilibrium from the aggregated to the more enantioselective monomeric catalysts. The catalytic system was studied by varying catalyst concentration and reaction temperature, by analysis of the catalyst aggregation state via 1H DOSY NMR, by kinetic studies and Hammett plots. A ditopic version of the ligand was also studied for NLEs, which in part turned out to be also hyperpositive. New metallopolymers consisting of a ditopic, chiral ligand and a metal were developed for the application in sum-frequency generation (SFG). The ligands are prepared by the double addition of a chiral aminoalcohol or diamine on terephtaldehyde to obtain bis-imine-1,4-phenylenes absorbing at 300 nm. Some complexes exhibited a very strong activity in SFG but proved to be sensitive to moisture and thus were difficult to handle. A more stable variant based on a 2-aminoaniline was developed and its UV-vis-characteristics were studied

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20

Flock, Angelika Marie [Verfasser]. "Studien zur Chiralitätsverstärkung und Anwendung von Ephedrin-basierten Thioharnstoffen in organokatalytischen Reaktionen / vorgelegt von Angelika Marie Flock (geb. Bruckmann)". Göttingen : Sierke, 2010. http://d-nb.info/1007465387/34.

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21

Mortezaei, Zanjani Gholam-Reza. "Photodeconjugaison asymetrique". Reims, 1987. http://www.theses.fr/1987REIMS011.

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Obtention d'alpha -vinyllactones par deconjugaison photochimique d'alpha -alkylidenelactomes. L'enantioselectivite de la reaction est obtenue grace a un catalyseur aminoalcool optiquement actif. Application de ce procede a la synthese d'esters beta ,gamma -insatures optiquement actifs

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22

Soares, Helena Cristina Mendes. ""The Chinese Phytotherapy: Oriental and Western Pathophysiological Aspects and Perpectives - The Example of Ephedrae Decotum"". Master's thesis, Instituto de Ciências Biomédicas Abel Salazar, 2009. http://hdl.handle.net/10216/26363.

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23

Soares, Helena Cristina Mendes. ""The Chinese Phytotherapy: Oriental and Western Pathophysiological Aspects and Perpectives - The Example of Ephedrae Decotum"". Dissertação, Instituto de Ciências Biomédicas Abel Salazar, 2009. http://hdl.handle.net/10216/26363.

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24

Shanati, Tarek [Verfasser] y Marion [Gutachter] Ansorge-Schumacher. "Enantiokomplementäre Dehydrogenasen aus Arthrobacter sp. TS-15 zur stereoselektiven Oxidation von Ephedrinen und Reduktion aromatischer Ketoverbindungen / Tarek Shanati ; Gutachter: Marion Ansorge-Schumacher". Dresden : Technische Universität Dresden, 2019. http://d-nb.info/1226901891/34.

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25

Chih-Jung, Chang y 張志榮. "Esymmetric Control By Use Of L-Ephedrine". Thesis, 1993. http://ndltd.ncl.edu.tw/handle/94234567579961840442.

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26

Leksawasdi, Noppol. "Kinetics and modelling of enzymatic process for R-phenylacetylcarbinol (PAC) production /". 2004. http://www.library.unsw.edu.au/~thesis/adt-NUN/public/adt-NUN20050426.141245/index.html.

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27

Malissar, Dean Graham Shane. "Asymmetric synthesis with an ephedrine based chiral auxilliary". Thesis, 1992. http://hdl.handle.net/10413/11384.

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28

Ranallo, Romolo Fausto. "The effects of an ephedrine/caffeine mixture on obese humans". Thesis, 1999. http://hdl.handle.net/2429/9055.

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Several studies have shown that a mixture consisting of ephedrine, a β-agonist, and caffeine, an adenosine antagonist, has the ability to stimulate thermogenesis in humans, and thus offer a treatment for obesity. However, most studies have also included a very low calorie diet and sometimes exercise in addition to the ephedrine/caffeine combination. The purpose of this study was to determine the amount of weight loss achievable using the ephedrine/caffeine mixture without controlling for diet and exercise. In a double-blind, placebo controlled, cross-over, repeated measures design, 20 obese subjects were administered a mixture containing ephedrine (20 mg), and caffeine (200 mg) or placebo, t.i.d. for 8 weeks. Body weight, resting metabolic rate (RMR), waist to hip ratio (WHR), body mass index (BMI), and sum of girths were measured. Fourteen subjects completed the study: 1 withdrew because of lack of interest; 1 encountered food poisoning; and 4 were dropped because of missed follow-up appointments. The treatment was well tolerated and side effects were transient. The most common side effects were insomnia and tremor. Withdrawal symptoms included headaches and tiredness. Change in body weight was -2.8 ± 2.4 kg (mean ± SD) after ephedrine/caffeine treatment and 0.5 ± 1.1 kg after placebo treatment (p<0.001). Body Mass Index (BMI) was 33.0 ± 5.4 kg/m² after treatment and 33.8 ± 5.9 kg/m² after placebo (p<0.001). There were no significant differences in RMR, WHR, and sum of girths. The results of this study show that an ephedrine/caffeine combination is able to promote weight loss without diet restriction and exercise.

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29

"Cardiovascular responses to ephedrine are directly mediated in the rodent". Tulane University, 2005.

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Ephedrine is sympathomimetic drug of abuse that causes serious cardiovascular toxicity. The mechanism of the pressor response to ephedrine is controversial. Due to the fact that both indirect and direct mechanisms of action have been reported for ephedrine, the hypothesis that ephedrine elicits cardiovascular responses through a direct mechanism in vivo and that the release of catecholamines from adrenergic nerve terminals does not play a significant role was investigated. In the present study iv injections of ephedrine increased systemic and pulmonary arterial pressure, and is injections decreased hindlimb blood flow in a dose-related manner in the rat. The systemic, pulmonary, and hindlimb responses to ephedrine were inhibited by alpha-receptor blocking agents, modulated by beta-receptor inhibition, and not attenuated by blockade of the norepinephrine reuptake transporter (NET). The magnitude of the pressor response to ephedrine was similar in anesthetized and conscious rats. Tachyphylaxis developed to pressor responses to ephedrine and amphetamine with sequential injections; however, ephedrine tachyphylaxis differed in that subsequent responses to alpha-receptor agonists were attenuated. In another series of experiments, reserpine or a combination of reserpine and alpha-methyl-p-tyrosine was administered to deplete tissue catecholamines. The responses to ephedrine were not inhibited following catecholamine depletion whereas responses to tyramine and amphetamine were inhibited by these treatments. These results suggest that the systemic and pulmonary pressor and hindlimb vasoconstrictor responses to ephedrine are mediated by direct action on alpha-adrenergic receptors and that the release of catecholamines from adrenergic terminals plays no significant role. In another series of experiments, injections of ephedrine increased systemic arterial pressure and heart rate in dopamine b-hydroxylase knockout mice (Dbh-/-) that do not synthesize norepinephrine and epinephrine. Responses to tyramine and amphetamine were abolished in Dbh-/- mice. These results provide support for the hypothesis that responses to ephedrine are directly mediated in vivo whereas responses to amphetamine are mediated in a large part by the release of norepinephrine from adrenergic terminals
acase@tulane.edu

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30

Kriel, Karina Nicole. "The use of ephedrine and camphor in asymmetric Diels-Alder reactions". Thesis, 1997. http://hdl.handle.net/10413/6001.

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Due to the ever increasing demand for the production of enantiopure drugs and biologically active compounds, the study of asymmetric synthesis and the production of more efficient and cost effective methods of obtaining chiral compounds suggests that there are expanding opportunities for Organic Chemists in this field. Of the broad range of chiral technologies available today for the synthesis of even the most complex multi-centre chiral molecules, the use of chiral auxiliaries continues to remain an important means of obtaining single enantiomer chiral compounds. In this investigation, the imidazolidinone chiral auxiliary (i) was synthesised in order to determine its efficiency and ability to transfer chiral information in Diels-Alder cycloaddition reactions. The products of such reactions are extensively used in the synthesis of natural compounds and pharmaceutical drugs. The synthesis of the imidazolidinone auxiliary is described and mention is made of the fact that the starting materials are cheap and readily available in both enantiomeric forms. The pathway involves only a single reaction that is easily carried out in moderate yields of 60-65%. An adaptation of this auxiliary is the cyclohexyl derivative (ii) which was obtained in a single hydrogenation step of (i) in very high yields (98%). This was compared to the synthesis of the bornane-1O,2-sultam auxiliary (ii). Although the starting materials are also cheap and readily available, there are more reaction steps involved. The synthesis of the imidazolidinone auxiliary proved to be much more simple as well as more time and cost effective. The huge advantage of these auxiliaries is the fact that they are both crystalline which facilitates their purification and that of their derivatives. A possible deficiency of the imidazolidinone auxiliary and the bornane-1O,2-sultam auxiliary was the fact that substitution reaction yields with various a,b-unsaturated acyl chlorides were consistently low (<50%). A major by-product of the acylation reaction was a 'double-adduct' compound that severely affected the reaction yields. This was overcome by employing a new method of acylation developed during the course of this research. It involves the use of DABCO as base with reaction yields between 60 and 98%. In addition to this, reaction conditions were mild and work up procedures simple. The N-acylimidazolidinone auxiliary proved to be extremely successful in Diels-Alder reactions with cyclopentadiene With results equalling those obtained with the well known and highly publicised bornane-10,2-sultam auxiliary. The scope of the N-acylimidazolidinone auxiliary in these reactions included the use of a- and b- substituted dienophiles. Although reactions with a-methyl and b-methyl substituted dienophiles were successful, the auxiliary proved to be unreactive with b-phenyl and b,b-dimethyl substituted dienophiles. The scope of dienes used was extended to include the relatively less reactive isoprene and 2,3-dimethyl-l,3-butadiene. Only the former reacted successfully in Diels-Alder reactions with the N-acylimidazolidinone auxiliary. Crystallinity was imparted to all the products except for the cyclohexyl derivative whose cycloaddition adducts only solidified on standing. The Diels-Alder adducts were successfully cleaved under standard reaction conditions to give products with ee's ranging from 95:5 to 99:1. This investigation also includes the use of the tertiary amine, DABCO, as a catalyst in the Diels-Alder reaction with, specifically, the N-acryloylimidazolidinone chiral auxiliary. Most examples of Diels-Alder reactions involve the use of Lewis acids as a means of improving the rate and selectivity of Diels-Alder reactions. DABCO not only increased the reactivity of the N-acryloylimidazolidinone auxiliary towards cyclopentadiene, but selectivity was also observed. An explanation was put forward as to the mechanism of the reaction as well as to the source of selectivity. Selectivity was much more pronounced in Diels-Alder reactions with the N-acryloylimidazolidinone auxiliary than with the N-acryloylbornane-10,2-sultam auxiliary. It was predicted that DABCO catalysed reactions are amenable to large scale procedures. Due to the fact that the diastereomeric cycloadducts are easily purified by recrystallization or chromatography, and together with the practical advantages and mild reaction conditions this could render the DABCO methodology with the N-acryloylimidazolidinone auxiliary industrially viable.
Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1997.

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31

Lin, Shih-Min y 林世明. "Development of an Analysis Method for Ephedrine Alkaloids from Chinese Medicine Preparations". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/42559382113163274097.

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碩士
國立成功大學
化學系專班
93
Abstract 　The use of Ephedra, known as Ma-huang, can be traced back to ancient times, since it has been used as a diaphoretic, diuretic and antiasthmatic, as well as agents for the treatment of bronchitis and acute nephritic edema. The main active components of Ephedra are three pairs of optically active diastereomeric ephedrine analogues: l-ephedrine, d-pseudoephedrine, l-norephedrine, d-norpseudoephedrine, l-methylephedrine and d-methylpseudoephedrine. Ephedra used in Chinese medicine showed quite variable quality because a number of species comprised its source in the market, which makes the identification of ephedrine essential. The methods for analysis of Ephedra alkaloids include TLC, GC, HPLC and CE; however, these methods required elaborate-clean-up and derivatization procedures in order to enhance sensitivity and to remove the compounds that interfere with the target compounds, which were not always satisfactory. The present study provides a qualitative and quantitative analysis of the ephedrine in Ephedra herbs in the market. The developed method not only eases the trouble of conventional analysis methods, but also increases the selectivity of ephedrine; in addition, it allows simultaneous determination of more than five ephedrine analogues without any calibration curves. 　A qualitative and quantitative analysis method for the determination of five ephedrine analogues from Ephedra herbs using 1H-NMR spectroscopy was described. It allows rapid and simultaneous determination of ephedrine analogues l-ephedrine, d-pesudoephedrine, l-norephedrine, d-norpesudoephedrine, and l-methylephedrine without any pre-cleaning steps. This method was applied for the analysis of Ephedra materials including E. sinica Stapf, E. equisetina Bge, and E. intermedia Schrenk for ephedrine analogues. In E. sinica Stapf, the quantity of ephedrine is two to three times more than that of pesudoephedrine. On the contrary, in E. intermedia Schrenk, the quantity of pesudoephedrine is two to three times more than that of ephedrine. In E. equisetina Bge, ephedrine is the major content. 　The method allows rapid detection of the exact kind of Ephedra used in scientific Chinese medicine formula containing Ephedra materials in the market and provides simultaneous quantitative analysis of the ephedrine in the formula; it has excellent concentration integral liner relationship. The study also focused on the quantitative analysis of ephedrine in 29 Chinese medicine preparations containing Ephedra provided by four domestic pharmaceutical companies. The quantity of ephedrine in these Ephedra preparations resulted in great variation, and the relative quantity of ephedrine in the preparation of each company was discussed. Moreover, some Chinese medicine preparations without ephedrine have been detected the existence of ephedrine, and the source of the ephedrine was identified by the 1H-NMR method. 　1H-NMR can serve as an analysis tool, providing a rapid, accurate, and convenient method for qualitative and quantitative analysis of ephedrine analogues from Ephedra species. This method can be applied to the analysis of commercial pharmaceutics or products of Ephedra and dietary supplements.

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32

ZHANG, ZHI-RONG y 張志榮. "Asymmetric reactions of ▫-amino alkenenitriles:use of 1-ephedrine as a chiral auxiliary". Thesis, 1989. http://ndltd.ncl.edu.tw/handle/59952903873879728846.

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33

Chen, Kuo-Hsiang y 陳國祥. "Synthesis of Pentavalent Phosphorus Ligands from l-Ephedrine and Application to Asymmetric Reactions". Thesis, 1998. http://ndltd.ncl.edu.tw/handle/63234111332010943747.

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博士
國立臺灣大學
化學系
86
Amines, alcohols or Grignard reagents reacted with (2R)-2-chloro-1, 3,2-oxazaphospholidin-2-one, which was derived from l- ephedrine and phosphoryl chloride, to give a series of HMPA-like chiral ligands in 47-97 % yields. These chiral ligands promoted asymmetric addition reactions of carbonyl compounds to yield optically active alcohols. These chiral ligands were stable in the air, and easily recovered from the reaction mixtures. The samarium-Barbier reactions using the HMPA-like ligand produced secondary and tertiary alcohols in moderate yields (62-88 %). However, these reactions showed no enantioseletivity. The HMPA-like chiral ligands promoted the asymmetric reduction reactions of prochiral ketones with borane to give optically active alcohols in high chemical yields (69-99 %) and moderate enantioseletivities (12-67 %ee). The asymmetric allylation reaction of benzaldehyde with trichloroallylsilane was promoted by the HMPA-like chiral ligands to give the corresponding alcoholin excellent yield (82 %) with low enantioseletivity (17 %ee). In the absence of the chiral ligands the allylation reaction do not occur.

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34

Kostraby, Margaret Mary. "The yeast mediated synthesis of the l-ephedrine precursor, l-phenylacetylcarbinol, in an organic solvent". Thesis, 1999. https://vuir.vu.edu.au/15623/.

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l-Ephedrine and d-pseudoephedrine are important pharmaceutical products commonly found in anti-asthmatic formulations, nasal decongestant mixtures and sinus preparations. d-Pseudoephedrine is the active ingredient in "Sudafed". l-Ephedrine is currently synthesised in a three step process. The first step utilises fermenting yeast in water to catalyse the acyloin condensation of benzaldehyde and acetaldehyde to form the l-ephedrine precursor, l-phenylacetylcarbinol (l-PAC). The second step involves the reaction of l-PAC with methylamine to form the corresponding N-methyl imine; the final step employs a metal catalyst to facilitate the reduction of the imine with hydrogen. This study is focused on the first step of the synthesis, which suffers from the drawback that two by-products, benzyl alcohol and l-phenylpropan-l,2-diol are always formed. The study aims to improve the efficiency of the l-PAC formation by performing the reaction with dried yeast in an organic solvent.

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35

Schmidt, Walter F. "Entropic and free energy considerations in the chromatographic resolution of the diastereoisomer and enantiomers of ephedrine". 1985. http://catalog.hathitrust.org/api/volumes/oclc/12803168.html.

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Thesis (M.S.)--University of Wisconsin--Madison, 1985.
Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 106-108).

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36

LIN, JUNG-CHIH y 林榮志. "Development of Microfluidic Platform for Real-time Analysis to Detect the Quantity of Ephedrine in Different Formula". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/x364dp.

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博士
逢甲大學
電機與通訊工程博士學位學程
106
In this study, based on the centrifugal microfluidic detection technology, a real-time detection centrifugal microfluidic platform has been developed for detecting the content of traditional Chinese medicine compound ephedrine, which can be applied to the rapid detection and analysis of the quality components of traditional Chinese medicine. The ion-sensing film was fabricated by electrospinning on the micro-channel structure, and the ion detection electrode reaction was used to detect the index content of ephedrine in the traditional Chinese medicine preparation, and the correlation of the ephedrine content of different samples was investigated. The experimental results of the ephedrine-related reaction change the concentration accordingly. The concentration of ephedrine increases due to the increase of the sample dose, and the voltage response also mutates. The experimental ephedrine concentration ranges from 2.69 mg/g to 16.64 mg/g. The real-time ion detection technology of this system had been proved to provide quantigtative analysis for concentrated Chinese medicine preparations, which is beneficial to the rapid and accurate analysis and application of Chinese medicine ephedrine preparations and index components.

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37

Lin, Chin-Hong y 林錦紅. "Qualitative and Quantitative Determination Street Drug of Amphetamine, Methamphetamine, Ephedrine, Pseudoephedrine, Methylenedioxymethamphetamine and Ketamine by Capillary Zone Electrophoresis". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/06998521327750495333.

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碩士
高雄醫學大學
藥學研究所碩士在職專班
92
In study, we tried to find a rapid, sensitive method to qualitative and quantitative of A, MA, EPH, PEPH, MDMA and K these six abuse drugs at the same time by using capillary zone electrophoresis The best result was achieved by used 500 mM Boric acid mix with 20 mM Borax（pH 6.88）then 40 mM Borax buffer（pH 7.23）and applied two steps voltage of 10 kV 13.5 mins and 8 kV 6.5 mins. And UV detection was at 214 nm absorbance. The analytical precision was characterized by relative standard deviation values （R. S. D）<10% for migration times intra-day and inter-day with peak area are producibility <1.60% linearity in the range 0.5 μg/ml~2 μg/ml was acceptable with amphetamine correltion coefficients >0.995；methamphetamine correlation coefficients >0.998 and ephedrine correlation coefficients >0.998；pseudoephedrine correlation coefficients >0.996；MDMA correlation coefficients >0.998；ketamine coreelation coefficients >0.996. The result of this study is suitable for separation of these compounds.

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38

Liu, Yu-Min y 劉育閔. "Simultaneous determination of three β–carbolines alkaloids and Ephedrine in Pinellia Tuber by using LC/ESI(+)/MS/MS". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/78145565796511381099.

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碩士
中興大學
化學系所
99
Determination of four marker compounds ephedrine, harman, norharman and harmine were carried out in crude methanol extractions of Pinellia tubers derived from three different processing methods and of seven most popular Chinese medicinal preparations containing Pinellia tubers as the ingredient without any clean-up by using a HPLC / tandem Mass analysis. The best ionization characteristics were obtained using positive-ion electrospray ionization (ESI) and 0.05 % formic acid as additive. Good linearity over the range 10 - 250 ng/g for ephedrine and range 5 - 250 ng/g for harman, norharman and harmine were observed. The intra and inter precision within quantitation ranges varied between 4.4 - 18.7 % and 7.3 - 19.5 % respectively. The limit of detection was 4.5, 2.5, 1.5 and 4.2 ng/g for ephedrine , harman , norharman and harmine respectively. Recoveries from extract of the medicinal preparation sample Bann-Shiah-Shieh-Shin-Tang were 92, 96, 103 and 105 % respectively at concentration of 100 ng/mL spiking of harman , norharman , ephedrine and harmine. The amount of total alkloids vary in these Pinellia products in the following order: raw Pinellia > Pinellia dipped in ginger and alum juice > Pinellia dipped in Glycyrrhizae Radix plus sodium carbonate solution. The determination of the four markers in seven Chinese medicinal preparations was ranged between 5.8 – 31.3 ng/g for harman , 10.6 – 48.6 ng/g for norharman , 6.7 - 37.2 ng/g for ephedrine and N.D. – 6.5 ng/g for harmine.

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39

Webb, Adrian Arthur. "Re-evaluation of the role of intramuscular ephedrine as prophylaxis against hypotension associated with spinal anesthesia for Caesarean section". Thesis, 1997. http://hdl.handle.net/10539/21258.

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A research report submitted to the Faculty of Medicine, University of Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in the branch of Anaesthesia.
Spinal anaesthesia for Caesarean section is associated with an unacceptably high incidence of hypotension despite the administration of an intravenous fluid preload and the use of uterine displacement. The theoretical benefits of preventing hypotension as opposed to treating it as it occurs are the avoidance of considerable maternal discomfort, a reduced risk of serious cardiovascular or respiratory depression and the avoidance of transient foetal asphyxia. The use of prophylactic intramuscular ephedrine prior to spinal anaesthesia has been recommended but not well studied. The advantages of the intramuscular route for ephedrine administration are its simplicity and its favourable pharmacokinetic profile. Cardiovascular support is sustained throughout the surgery and into the post operative period. Opposition to the use of intramuscular ephedrine in the prevention of hypotension is based on two studies in which spinal anaesthesia was not used [1,2]. These studies showed an unacceptably high incidence of hypertension, a deleterious effect on foetal gas exchange and a lack of efficacy when intramuscular ephedrine was used in epidural and general anaesthesia respectively. This research report describes a randomised, double blind, interventional study designed to assess the safety (prevalence of hypertension, tachycardia or foetal compromise) and efficacy (prevalence of hypotension) of 37,5mg of ephedrine given prior to spinal anaesthesia for Caesarean section. Forty patients who had given informed consent were entered into the study. Blood pressures and pulse rates were recorded for 90 minutes after ephedrine administration, samples of umbilical venous blood were collected and Apgar scores assessed. This study found that giving 37,5mg of intramuscular ephedrine prior to spinal anaesthesia was safe from a maternal point of view in that it was not associated with reactive hypertension or tachycardia. When the ephedrine was given 10 minutes prior to induction of the spinal the technique proved to be effective in reducing the incidence and severity of hypotension. When used in the above manner the technique was not associated with foetal depression or acidosis.
WHSLYP2016

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40

Vallier, Ashley. "Chiral separation of the enantiomers of ephedrine, amphetamine, methamphetamine, MDA, MDMA, and phentermine in blood using LC-MS/MS". Thesis, 2018. https://hdl.handle.net/2144/31283.

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Amphetamine-type stimulants are widely abused due to their ability to stimulate the central nervous system and elicit feelings of confidence, wakefulness, mood elevation, and euphoria. After cannabis, amphetamines were the most abused group of illicit substances in 2016 according to the National Forensic Laboratory Information System Annual Report. Included in this group are ephedrine, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-metheylenedioxymethamphetamine (MDMA). Structurally, each of these compounds contain a chiral center, causing them to have an R-(-) and S-(+)- enantiomer (also called levo- and dextro-, respectively). Despite their similarity, the R- and S- enantiomers display differing pharmacological effects, with the S-enantiomer producing a stronger, longer-lasting effect than the R-enantiomer. Because of this, R-methamphetamine, for example, has therapeutic uses and is the active ingredient in some over-the-counter nasal decongestant products (e.g. Vicks® vapor inhaler). S-methamphetamine, on the other hand, is generally found in illicit sources. As a result of these chiral centers, these compounds have differing legal statuses. The aim of this research was to develop and validate a method for the separation and analysis of eleven amphetamine-class compounds in blood for forensic casework. This was accomplished using a liquid-liquid extraction and analysis on a liquid chromatography-tandem mass spectrometer (LC-MS/MS) (Agilent Technologies, Santa Clara, CA, USA). Chromatographic separation was achieved using a Phenomenex Lux® AMP chiral column (Phenomenex, Torrance, CA, USA), under gradient aqueous and organic mobile phase conditions, with a total run time of just over 17 minutes. The target analytes included 1S,2R-ephedrine, 1R,2S-ephedrine, R-amphetamine, S-amphetamine, R-methamphetamine, S-methamphetamine, phentermine, R-MDMA, S-MDMA, R-MDA, and S-MDA with 1S,2R-ephedrine-d3 and MDMA-d5 as the internal standards (Cerilliant, Round Rock, TX, USA). The analytical method was validated according to the Scientific Working Group for Forensic Toxicology guidelines (now a subcommittee of the Organization of Scientific Area Committees for Forensic Science), including the assessment of its linearity, limits of detection and quantitation, bias, precision, interferences, matrix effects, carryover, and processed sample stability [2]. The limit of detection (LOD) was 2 µg/L for all compounds except MDMA and MDA, which had LODs of 10 µg/L. The lower limit of quantitation (LLOQ) and upper limit of quantitation (ULOQ) was 10 µg/L and 1000 µg/L for all compounds, respectively. The precision was within 15% for all analytes, with the bias extending outside the ±20% range for at least one set of samples for all analytes except 1S,2R-ephedrine and both MDA enantiomers. Matrix effect studies showed average ion enhancement (140%-361%), extraction efficiencies (60%-123%), and process efficiencies (105%-432%) across all analytes. No interferences were detected from isotope internal standards, postmortem blood, antemortem blood, or 85 commonly seen drugs in forensic casework. No carryover was observed following injections of analytes at the ULOQ (1000 µg/L). To demonstrate applicability in authentic casework, the method was applied to 28 cases that had previously been analyzed using a non-chiral method. By selectively identifying R- and S- enantiomers, this method may be used in forensics laboratories where the question of the licit or illicit use of amphetamines is of importance.

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41

John, M. "An investigation of diet-induced thermogenesis during overfeeding, thermogenic responsiveness to ephedrine administration and diet-induced thermogenesis following propranolol administration". Thesis, 1985. https://eprints.utas.edu.au/20241/1/whole_JohnMichael1985_thesis.pdf.

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The current obesity literature places strong emphasis upon the influence that Diet-Induced Thermogenesis (DIT) has on weight regulation and the possible mediating role of Brown Adipose Tissue (BAT) in DIT. This focus arises from animal research which establishes the significance of DIT and BAT in the energy balance of rodents. Recent studies indicate differential postprandial DIT between lean and obese individuals. The contribution of resting state DIT to energy balance is equivocal, a situation in part due to disagreement regarding the extent of excess energy needed to trigger the response, and individual differences in responding. At present, only catechol-amine stimulation studies suggest the active presence of BAT in adults. This thesis addresses four research questions arising from the obesity literature: (i) Does the DIT response to overfeeding in either post-prandial or resting state conditions show any change over five days overfeeding? (ii) Is a subject's responsiveness to a standard test of thermogenic capacity (i.e. stimulation by the sympatheticomimetic drug ephedrine) predictive of their DIT response to overfeeding? (iii) Is BAT involved in mediating the DIT response during the postprandial period? and (iv) Can the DIT response to overfeeding be blocked by the beta-adrenergic antagonist propranolol? These questions were investigated in two studies. Experiment 1, testing seven subjects, examined questions (i) to (iii), Experiment 2 examined question (iv) with the three strongest responders from the first experiment. DIT and response to sympathetic stimulation were measured through metabolic rate (02 consumption and HR) increase. BAT activity was assessed via skin temperature change at sites of probable BAT deposits. The results suggest that in certain individuals resting state DIT can be achieved following a single day's overfeeding. The data also suggest that dietary history may underpin DIT response ability. As only a positive trend was found between MR stimulated by ephedrine and overfeeding respectively, the relationship between these responses remains equivocal. The BAT hypothesis was challenged by a failure to observe skin temperature increase following both ephedrine administration and overfeeding, and the failure of propanolol to inhibit DIT. The results are interpreted as clarifying the occurrence of resting state DIT in respect to short term overfeeding, and calling into question speculation regarding BAT's role in thermogenesis.

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42

Sun, Chin Lan y 孫嘉蘭. "Qualitative and Quantitative Determination of Amphetamine, Methamphetamine, Ephedrine, Pseudoephedrine, Morphine and Codeine by Capillary Zone Electrophoresis-Electrospray Ion-Trap Mass Spectrometry". Thesis, 2001. http://ndltd.ncl.edu.tw/handle/23823394733202575195.

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碩士
高雄醫學大學
職業安全衛生研究所
89
Because of the global overcast economy, domestic high unemployment, low work achievement, recession of life standard and illiteracy of teenagers, more and more people attempt to stupefy themselves by using drugs. Drug abuse impacts our society on direct and indirect cost to the medical and custodial care system. Additionally occupational accident and public danger will be occurred when people are working under the influence of drugs. Therefore screen for drug abuse is very important. Amphetamine (A), methamphetamine (MA), ephedrine (EPH), pseudoephedrine (PEPH), morphine (MO) and codeine (CO) are basic components of drugs. On the other hand those elements are also used on medical treatment. To confirm if it is truly drug abuse or not is especially important. The drug testing process is multifaceted. How to get rid of the interruption in analyzing and false positive in testing is very important. Many review papers only determination one kind of designer drug. In our study, we tried to find a rapid, sensitive method to qualitative and quantitative of A, MA, E, PEPH, MO and CO these six abuse drugs at the same time by using capillary zone electrophoresis coupled with electrospray interface (ESI) ion-trap tandem mass spectrometry (CE-ESI-MS2). The best result was achieved with a pH 2.44 2mM ammonium acetate-methanol (80:20,v/v) buffer and applied voltage of 20kV. The flow-rate of sheath liquid and sheath gas was optimized. Because the migration time in MS was different only few seconds, the ion-trap mass detector detected in one segment. All the analyses revealed the [M-H]+ ion mass spectra. Molecular ions of A (m/z 136), MA (m/z 150), EPH (m/z 166), PEPH (m/z 166), MO (m/z 286) and CO (m/z 300) were detected respectively, while product ions of MS2 for each compound were detected almost exactly at the same time.

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43

Yu, Wan-Nan y 余萬能. "Study on the Integration of the Policy Management and Regulations of the Controlled Drugs Use - Case Studies of Ephedrine Products and Iatrogenic Abuse". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/vu2ub2.

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博士
臺北醫學大學
藥學系(碩博士班)
106
Amendments to Pharmaceutical Affairs Law, Controlled Drugs Act and Narcotics Hazard Prevention Act were made to comply the legal system of Taiwan with the Single Convention on Narcotic Drugs (1961), Convention on Psychotropic Substances (1971) and United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (1988) of UN. Each law has different legislative purposes, subjects and constituent elements, which caused conflicts and difficulties in application and resulted in controlled drug abuse problems such as ephedrine preparations being used to produce amphetamines and iatrogenic addiction. Ephedrine products are often used to treat cold, cough or allergy and they are easy to obtain. Single compound or combinations of ephedrine products became material sources to produce amphetamines due to the similar chemical structures and simple chemical reactions. Measures such as limited packaging, limited supply, only sold behind the counter, and keeping record of purchases are commonly used to manage ephedrine products internationally. In Taiwan, we restrict the ephedrine products to pack into aluminum foil boxes and put a 7-day dose limit for adults. We also specified the responsibilities for the possible trafficking methods. Opiate analgesics and Benzodiazepines usually lead to iatrogenic abuse and would result in problems such as doctor shopping, forged prescriptions and drug thefts. Internationally controlled drugs guidances are provided for the doctors to follow and caring systems are built to reduce the drug abuse. In the U.S. , Prescription drug monitoring programs (PDMPs) are established to strengthen the management. To prevent the iatrogenic abuse of controlled drugs, the licenses for the use of controlled drugs are issued here in Taiwan like the U.S. and Japan. But the jurisdictions in Taiwan are not as distinguishable as they are in the U.S. and Japan. And how to apply legitimate medical purposes to Controlled Drugs Act or Narcotics Hazard Prevention Act is also a judicial practice issue. In this article we examine the differences in the purposes of Pharmaceutical Affairs Law, Controlled Drugs Act and Narcotics Hazard Prevention Act and the results of their application and we also explore the possible problems of the three regulations by reviewing the policies and organization structures to prevent iatrogenic abuse and develop a sound management system for controlled drugs and ephedrine products. We tried to improve the quality of regulations and policies through organization restructuring and regulation amendments. Systems including “management of medical use of Ephedrine products” and “medical use, monitor and integration of medical database of drug misuse and to conduct early warning system” were developed. And we suggested to set up Regulations of Manufacturer and Distributors Inspection of Ephedrine products combined with amendments of Controlled Drugs Act and Narcotics Hazard Prevention Act by introducing the electronic data intelligence processing function mechanism into the Health insurance card system and includes the restrictions for prescribing controlled drugs to oneself or ones direct relatives. We recommend that the Ministry of Health and Welfare should establish a traceability system for ephedrine products as article 6-1 of Pharmaceutical Affairs Act regulates. The Judicial system should to intervene in the management of drug hazards prevention and control business referring to the systems of U.S. and Japan. The reorganization should be accelerated and fully implemented to prevent controlled drug abuse thoroughly.

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44

Wang, Ju-Wen y 汪如文. "Determination the active compounds of Ma-Xing-Gan-Shi-Tang and its application of ephedrine and amygdalin pharmacokinetics in rats by UPLC-MS/MS". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/98894393558756673589.

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碩士
國立陽明大學
傳統醫藥研究所
103
The herbal preparation of Ma-Xing-Gan-Shi-Tang (MXGST) is one of the popular traditional Chinese formulations, which has been used for the treatment of cough and fever. The potential active components of MXGST are ephedrine, amygdalin, and glycyrrhizic acid. The aim of study is to develop a validated analytical method to measure these analytes with ultra pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) from the herbal preparation of MXGST. Multiple reaction monitoring (MRM) was used to monitor m/z 166.1148.1 for ephedrine ([M+H]+), 475.2163.0 for amygdalin ([M+NH4]+), and 840.6271.1 ([M+NH4]+) for glycyrrhizic acid. The analytes were separated by a reversed phase C18 column (100x2.1 mm, 2.6 μm). The mobile phase was consist of 5 mM ammonium acetate (0.1% formic acid) and 100% Methanol (0.1% formic acid) with a linear gradient elution. Five brands of commercial pharmaceutical industry products and laboratory extract of MXGST were analyzed. Moreover, the modified UPLC-MS/MS method was applied in the comparative pharmacokinetics of ephedrine in rat by the following three groups of (1) pure compound ephedrine, (2) single herbal extract of Ephedra, and (3) herbal preparation of MXGST. The plasma sample clean-up was prepared by protein precipitation with evaporation and reconstitution. The pharmacokinetic data showed that pure compound ephedrine was absorbed significantly faster than the Ephedra extract, and MXGST herbal preparation. But the elimination half life of ephedrine in the herbal Ephedra extract and MXGST groups was prolonged from 93.9 ± 8.07 min for pure compound of ephedrine, and Ephedra extract and MXGST groups were 133 ± 17 and 247 ± 57.6 min, respectively. The area-under concentration curves (AUC)were not significant difference for the three groups. These data suggest that the rest of herbal ingredients of Ephedra extract and MXGST may provide the compensation effect to reduce the peak concentration of ephedrine and prolong the elimination half-life. Also, we are curious about the comparative pharmacokinetics of amygdalin in rat by the following three groups of (1) pure compound amygdalin (intrathecal injection) (2) pure compound amygdalin (oral), (3) single herbal extract of Armeniacae semen extract (oral), and (4) herbal preparation of MXGST (oral). The result showed that amygdalin had low oral bioavailability and the bioavailability was located between 0.23~0.34%.

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45

Kirkman, Timothy. "Exploring signal transduction mechanisms in molecularly imprinted polymers for forensic applications". Thesis, 2014. http://hdl.handle.net/1959.13/1055291.

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Research Doctorate - Doctor of Philosophy (PhD)
This work explores the potential of two signal transduction mechanisms for molecularly imprinted polymers (MIPs) primarily for the detection of (-)-ephedrine (EPD). Firstly, gold nanoparticles were utilised resulting in a surface plasmon resonance based detection mechanism. Poly(acrylic acid-co-N’-isopropylacrylamide-co-N,N’-methylenebisacrylamide) (PAA-IPA-MBA), a conventional cross-linked MIP film, and poly(acrylic acid-co-acrylonitrile-co-methyl methacrylate) (PAA-AN-MMA), a phase-inversed 2D MIP film, were investigated. Gold nanoparticles were prepared and embedded into these polymers, with the resulting MIP systems demonstrating good selectivity and specificity for EPD. Spectroscopic detection studies based on hypsochromic shift in the wavelength of maximum absorbance in the surface plasmon resonance (SPR) of the embedded gold nanoparticles were performed. While SPR response was not observed for PAA-IPA-MBA, PAA-AN-MMA MIP films exhibited prominent shifts of up to 15nm after as little as 10 minutes of EPD sorption. Wavelengths shift observed in the non-imprinted PAA-AN-MMA after EPD sorption was minimal (≤8 nm) signifying MIP selectivity and significantly reduced (≤5 nm) in the presence of template analogues signifying MIP specificity. To the best of our knowledge, this is the first time SPR signal has been observed in 2D MIP films. Secondly, a composite of molecularly imprinted and poly(3,4 ethylenedioxythiophene): polystyrenesulfonic acid (PEDOT:PSS) conductive polymer (CP) was developed for the detection of EPD. 3-Methylthienyl methacrylate (MTMA) was successfully used as a dual purpose monomer to link between the CP (via its thiophene moiety) and MIP (via its vinylic group) components of the composite. Composite particles of PEDOT:PSS and cross-linked MIP of acrylic acid and methylenebisacrylamide afforded the highest level of MIP binding (0.91μmol/mg after 2 hours) and selectivity (imprinting factor of 27 obtained after 10 minutes stabilising to 11 after 2 hours). While this CP-MIP composite particles lost its selectivity when embedded into a PEDOT:PSS conductive matrix (to allow electrochemical detection) due to significant non-selective interaction between EPD and the PSS in excess, we have demonstrated, for the first time, the potential of a CP-MIP composite for electrochemical sensing given the right conditions and matrix. The design and formulation of all MIPs investigated in this study are supported by interaction studies between monomers and analytes (template and competing analogues) using semi-empirical molecular modelling and NMR spectroscopy.

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46

Shanati, Tarek. "Enantiokomplementäre Dehydrogenasen aus Arthrobacter sp. TS-15 zur stereoselektiven Oxidation von Ephedrinen und Reduktion aromatischer Ketoverbindungen". 2019. https://tud.qucosa.de/id/qucosa%3A34830.

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Zur stereoselektiven Herstellung von α-Hydroxyketonen aus prochiralen Ketonen stellen die Alkoholdehydrogenasen eine ökologische als auch ökonomische Alternative zu den verfügbaren industriellen Syntheserouten dar. Zurzeit stoßen sowohl die Biokatalyse als auch die organische Katalyse bei der Herstellung von sterisch anspruchsvollen α-Hydroxyketonen an ihre Grenzen. Die Synthese von enantiomerenreinem (R)-Phenylacetylcarbinol [(R)-PAC] und S- Phenylacetylcarbinol [(S)-PAC] aus dem prochiralen α-Diketon Phenylpropan-1,2-dion (PPD) stellt eine anspruchsvolle Synthese sowohl für akademische als auch für industrielle Zwecke dar. Diese chiralen Bausteine dienen als Vorgänger bei der Synthese von (‒)-Ephedrin und (+)-Pseudoephedrin. (‒)-Ephedrin und (+)-Pseudoephedrin werden jährlich in großen Mengen hergestellt, was zunehmend ein ernsthaftes ökologisches Problem darstellt. Aufgrund ihrer Toxizität als auch ihre Persistenz in der Umwelt, beispielsweise in Abwasserkläranlagen, wurden sie kürzlich als neu auftauchende Kontaminanten eingestuft. In dieser Arbeit wurde die Biodegradierung der Isomere von Ephedrin untersucht. Dabei wurde der neue Stamm Arthrobacter sp. TS-15 isoliert, welcher mit Ephedrin als einzige Kohlenstoffquelle wachsen kann. Dieser Stamm wurde bei der DSMZ unter der Nummer (DSM 32400) hinterlegt. Das Genom dieses Stammes wurde sequenziert und unter der Zugangsnummer (SDXQ00000000) in der Genbank verwahrt. Anhand verschiedener phylogenetischer Untersuchungen wurde TS-15 als eine Subspezies von Arthrobacter aurescens eingeordnet. Des Weiteren wurde der Einfluss der Isomerie von Ephedrin auf dessen Biodegradierung sowie auf die Wachstumsrate von TS-15 untersucht. Es wurde festgestellt, dass das Isomer (‒)-Pseudoephedrin am langsamsten abgebaut wird und dementsprechend einen negativen Einfluss auf das Kulturwachstum hat. Hingegen zeigte sein Enantiomer (+)-Pseudoephedrin die schnellste Biodegradierung mit einem positiven Effekt auf das Wachstum von TS-15. Anhand der Analyse der Metabolite im Kultivierungsmedium als auch aus den Zellextrakten von TS-15 wurde ein neuer katabolischer einleitender Schritt detektiert, in dem das Ephedrin zu Methcathinon VII oxidiert wird. Zur Bestimmung der oxidierenden Enzyme wurden Proteinanreicherungsverfahren eingesetzt. Mittels Peptidmassenfingerprints wurden 51 Proteinhits ermittelt. Nach einer kombinierten Analyse mittels der Proteinhits und des rationalen Genomminings wurde ein neues Gencluster zum Abbau von Ephedrin identifiziert. Zwei postulierte Dehydrogenasen wurden aus dem Genom isoliert, kloniert und in dem E. coli T7 SHuffle Stamm heterolog exprimiert. Dadurch wurden neue enantiokomplementäre Enzyme entdeckt. Die Pseudoephedrin Dehydrogenase (PseDH) ist enantiospezifisch für (+)-S,(N)-(Pseudo-)-Ephedrin, während die Ephedrin Dehydrogenase (EDH) nur die enantiospezifische Oxidation von (‒)-R,(N)-(Pseudo-)-Ephedrin katalysieren kann. Beide Dehydrogenasen sind NADH-abhängig und der Superfamilie der kurzkettigen Dehydrogenasen untergeordnet. Bei der Charakterisierung dieser Dehydrogenasen konnte gezeigt werden, dass das Substratspektrum wertvolle chirale Produkte umfasst. Beide Dehydrogenasen zeigen strikte Regio- und Enantioselektivität gegenüber dem α-Diketon Phenylpropan-1,2-Dion (PPD). Somit wurde PPD zu (S)-PAC (ee >99%) und (R)-PAC (ee >99%) mittels PseDH bzw. EDH mit vollem Umsatz reduziert. Darüber hinaus wurde die Kristallstruktur der PseDH im Rahmen einer Zusammenarbeit mit der Universität von York mit einer Auflösung von 1,8 Å aufgeklärt. Die Kristallstruktur wurde in PDB unter der Zugangsnummer (6QHE) hinterlegt. Mittels der Kristallstruktur der PseDH und des Homologiemodells der EDH wurden Strukturanalysen durchgeführt und die ersten Hypothesen zur Funktionsweise dieser Enzyme aufgestellt. Des Weiteren wurden über Peptidsequenzanalysen zu diesen Enzymen Rückschlüsse auf ihren evolutionären Ursprung gezogen. Die Stabilität der Dehydrogenasen wurde mit unterschiedlichen Lösungsmitteln bestimmt. CPME wurde als geeignetstes organisches Lösungsmittel für die Biokatalyse mit diesen Enzymen ermittelt. Beide Enzyme wurden mittels eines organisch-wässrigen Zweiphasensystems unter enzymgekoppelter Cofaktorregenerierung getestet. Dadurch wurde der Zugang zur Produktion von (S)-PAC und (R)-PAC aus PPD mittels PseDH bzw. EDH geschaffen.

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47

Nováková, Lucie. "Analýza historických léčivých přípravků naloxonu, adrenalinu a efedrinu". Master's thesis, 2015. http://www.nusl.cz/ntk/nusl-331784.

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The aim of the thesis was to analyze the historical pharmaceutical preparations, including the determination of the active substance and identify theirs possible degradation products. A historical pharmaceutical preparation of naloxone was analyzed by mass spectrometry. Historical pharmaceutical preparations of adrenaline and ephedrine were analyzed by UHPLC-MS and were quantified using a calibration curve. In the historical injection solution of naloxone, "NARCAN", dated around 1980, there were no significant degradation products and the measured mass and UV spectrum was consistent with the spectrum of naloxone. The analyzed sample of naloxone was stable even after 35 years of storage. In the analyzed historical injection solution of adrenaline, "Adrenalin Hydrochlor., Dr. Heisler" (dated between 1917 and 1938) was determined 5.26 ± 0.11 % of the declared amount of adrenaline. In the measured spectras were noticeable degradation products, which have not been described in the literature yet and their identification was beyond the scope of this paper. The analyzed sample of adrenaline was almost completely degraded during about ninety years. The stability test carried out with four standard solutions of adrenaline proved influence of oxygen, light, temperature and time on the degradation of adrenaline. In...

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48

Chuang, Mei-Ling y 莊美玲. "A survey of ephedrines and caffeine in replacement meal". Thesis, 2008. http://ndltd.ncl.edu.tw/handle/10334901698248516672.

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碩士
國立臺灣體育大學(桃園)
運動科學研究所
96
A survey of ephedrines and caffeine in replacement meal Abstract 　　Replacement meal products have become a popular food for weight loss. Ephedrines and caffeine may be added into replacement meal products in order to get weight loss or appetite inhibition. According to the World Anti-doping Code, ephedrines are in the list of prohibited substances and caffeine is in the list of the monitoring program substance. The purposes of this study were to establish a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to analyze the ephedrines and caffeine in replacement meal products and to examine labels on the packages of replacement meal products according to the “Act Governing Food Sanitation”. The results showed the LC-MS-MS method can be used to detect caffeine, norephedrine, cathine, ephedrine, pseudoephedrine, and methylephedrine in a single chromatographic run. The LOD were 0.2μg/mL for norephedrine、ephedrine、pseudoephedrine and methylephedrine. The LOD were 0.4μg/mL for cathine and caffeine. Linearity was observed for norephedrine、ephedrine、pseudoephedrine and methylephedrine, concentrations ranging from 0.2 to 6.4μg/ml with a correlation coefficient of 0.9992 to 1.0000. Linearity was observed for cathine and caffeine, concentrations ranging from 0.4 to 6.4μg/ml with a correlation coefficient of 0.9996 to 0.9998. Thirty-two replacement meal products were purchased from the internet and drugstores. Ephedrines were not detected in any product. Four products were detected caffeine positive, however, no labeling was found on the packages of these products. Three products were not provided the information of food labeling in Chinese and common symbols on the package. Seven products were not marked nutrition labeling.

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49

Hu, Szu-Yun y 胡斯雲. "Traditional Chinese medicine preparations containing the doping substances - ephedrines". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/06675518838583962401.

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碩士
國立體育大學
運動科學研究所
99
Ephedrae Herba is one of the prescriptions in Traditional Chinese Medicine (TCM) preparations for releasing symptoms due to cold. The major ingredients of Ephedrae Herba, ephedrines, including ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, and methylephedrine are banned/monitoring substances by the World Anti-Doping Agency (WADA). In previous study, the amount of ephedrine per therapeutic single-dose of Sho-seiryu-to was 2.98 mg and the mean of maximum urinary concentration (Cmax) of ephedrine was 4.67 μg/mL following individuals took single dose of the preparation. Based on this result, it is speculated that an individual who takes a single-dose of TCM preparation that contains 6.38 mg of ephedrine may lead to anti-doping rule violation. The purpose of this study was to determine the amounts of ephedrines per therapeutic single-dose in TCM preparations for colds by HPLC. We collected the TCM preparations from three GMP pharmaceuticals companies in Taiwan, and determinted the content of ephedrines n these preparations. The results show that 34% of those TCM preparations had more than 6.38 mg ephedrine in a therapeutic single-dose, such as Ma-hsing-kan-shih-to (10.269 mg), Mahwang-to (9.018 mg) and Ma-huang-fu-tzu-hsi-hsin-to (6.578 mg) from A company, Dah-ching-long-to (10.008 mg), Ma-hsing-kan-shih-to (7.215 mg), Mahwang-to (7.614 mg), Ma-huang-fu-tzu-hsi-hsin-to (15.818 mg) and Kakkon-to (10.518 mg) from B company, Sho-seiryu-to (9.514 mg), Chinfeitsao-san (20.792 mg), Ma-hsing-kan-shih-to (8.663 mg), Mahwang-to (34.970 mg) and Ma-huang-fu-tzu-hsi-hsin-to (31.262 mg) from C company. Therefore, the excretion of ephedrine in urine might exceed 10 μg/mL after taking only a single dose of these TCM preparations. In conclusion, it is estimate that all the TCM preparations for cold that contain E over 6.38 mg may cause a positive ephedrine test result, which violates the WADA rules. We suggest that athletes should avoid take these TCM preparations for cold.

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50

Huang, Guan-Qian y 黃冠蒨. "Investigation of commercial Traditional Chinese Medicine Preparations Containing the Doping Substances - Ephedrines". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/70326100008665788760.

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碩士
國立體育大學
運動科學研究所
102
Anti-rheumatic and anti-moisture herbal preparation is one of the Traditional Chinese Medicines (TCM) to treat muscle pain, arthritis, stroke, water retention, and blood shortage. The main ingredient in these TCM preparations contains ephedrines. Ephedrines are prohibited In-Competition in the World Anti-Doping Agency (WADA) doping list in the S6 - stimulants. The thresholds in urine for ephedrine, methylephedrine, norpseudoephedrine, pseudoephedrine are 10, 10, 5, 150 μg/mL, respectively. Research indicated that if one ingested the ephedrine more than 6.38 mg, the ephedrine concentration in urine may exceed the WADA’s threshold. The purpose of this study was to analyze the amount of ephedrines in anti-rheumatic and anti-moisture commercial preparations by high performance liquid chromatography. Three GMP manufactures supplied the anti-rheumatic TCM preparations. Six kinds of TCM preparations (Shiau-Shiu-Ming-Tang, Wu-Yau-Shuen-Chi-San, Ma-Shin-Yi-Gan-Tang, Guei-Jr-Shau-Yan-Jr-Mu-Tang, Yi-Yi-Ren-Tang, Yue-Pi-Jia-Shu-Tang) were obtained from each GMP manufacture. The highest amount of ephedrines in these anti-rheumatic commercial preparations was ephedrine. The results show that 22% (4 out of 18) of these TCM preparations had the amount of ephedrine over 6.38 mg in each one gram. These included Yue-Pi-Jia-Shu-Tang (16.893 mg) from A company, Wu-Yau-Shuen-Chi-San (7.294 mg) and Ma-Shin-Yi-Gan-Tang (7.144 mg) from B company, and Yue-Pi-Jia-Shu-Tang (8.446 mg) from C company. Furthermore, 72% (13 out of 18) of these TCM preparations had the amount of ephedrine over 6.38 mg in therapeutic single-dose. Thus, the excretion of ephedrine in urine might exceed 10 μg/mL after taking most of the single-dose of these TCM preparations. We suggest that athletes should avoid taking these TCM preparations in order to reduce the misuse occurs.

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