Chemotaxonomy is the classification of plants and microorganisms based on similarities and differences in their natural products and the biochemical pathways involved in their manufacture. The classification and identification of L rhinocerus, a medicinal fungus, for this research was based on secondary metabolites profiles by using chemical analysis that provides more objective and comparable results than traditional descriptions. Furthermore, chemical differentiation products could also be expected to be species-specific which is valuable for assessing the authenticity and quality of THMP containing this fungus. The aims of this research program were directed towards the characterization of key metabolites of the fungus by evaluating the identified metabolites structure that has significance pharmacological or toxicological impact and chemotaxonomic profiling. This research required to develop appropriate extraction techniques to fractionate biochemical compounds of L rhinocerus, to carry out qualitative and quantitative analyses (TLC, IR, UV, HPLC, LC-MS, GC-MS and NMR) of identified compounds and to establish robust quantitative techniques that may be applied in the routine quality assessment of samples of the fungal material. The best method of extraction was by using methanol-Et20 (1:1 v/v) in the presence of NaOH solution. Two identified compounds, ergosterol (0.39 mg/g) and ergone (0.03 mg/g) were isolated from flash chromatographic technique. The robustness of qualitative and quantitative analyses was demonstrated with good data of linearity (r, 0.9990) and %RSD value of precision and accuracy were less than 5.0%. Phenolic acid compounds were also detected and its total content (23.15~glg) was detennined by Folin-Ciocalteu method. Both classification of fungal sterols and PACs of L. rhinocerus were established using the optimum HPLC (chromatographic fingerprint) that may be applied in the routine quality assessment of samples of the fungal material. The main pharmacological effects of these compounds were anti-oxidant and anti-tumor effects. Consequently, overall aims and objectives of this research have been achieved.

Most methods used for the extraction of quaternary amines in biological fluids have been based on ion-pair extraction techniques. In this study, a sensitive and selective chromatographic procedure is described to measure the concentration of pyridostigmine, neostigmine and their major metabolites in the plasma and urine. The methods involve a preliminary selective ion-pair extraction of the unchanged drugs and their metabolites into dichloromethane and dichloromethane-acetone mixture respectively. Quantitation is possible down to 3 ng/ml for parent drugs and 50 ng/ml for the metabolites. The present work also described a modified procedure to measure neostigmine and pyridostigmine in plasma simultaneously, using a specially synthesized pyridostigmine analogue as a common internal marker. The plasma concentration of pyridostigmine was measured after three different doses of the quaternary amine (36.2 Ng/kg, 72.4 pg/kg and 144.8 )tg/kg) were given intravenously to twenty five surgical patients during anaesthesia. The relation between the plasma concentration of pyridostigmine and time was invariably expressed as a bi-exponential equation, and the data was interpreted in terms of a two compartment model. The slow disposition halflife of the drug was progressively prolonged as the dose of the drug was raised from 36.2 Ng/kg to 144.8 jig/kg. A similar increase in the half-life was observed in cross-over studies. The clearance of the quaternary amine was enhanced at intermediate dose (72.4 )xg/kg) but significantly reduced after high dose (144.8 pg/kg). It was suggested that these results may partially account for the observed differences in the duration of action of neostigmine and pyridostigmine in man. The dose of pyridostigmine used to reverse non-depolarizing neuromuscular block is 4-5 times greater than neostigmine. After intramuscular administration of neostigmine to five myasthenic patients, the plasma concentration of the drug declined monoexponentially from 21 ±2 no/ml to 9t1 ng/ml between 30 and 120 minutes and data was interpreted in terms of a one-compartment model. Estimates of the plasma half-life varied from 56.9 - 100.1 minutes. The oral administration of pyridostigmine alone and of both neostigmine and pyridostigmine in two different groups of myasthenic patients, were also studied. There was a direct linear relation between area, under the plasma concentration - time curve and total daily dose of pyridostigmine in the first group of patients (r = 0.95), but no such observation was noticed in either all patients (two groups; r=0.15) or in the second group who were treated with both drugs (r =-0.08). It was suggested that there might be a drug-drug interaction between pyridostigmine and neostigmine during oral absorption. The relation between plasma levels of pyridostigmine to clinical evaluation of muscle power was examined in nine myasthenic patients during treatment with pyridostigmine in doses of 60 to 1080 mg per day. Five of the nine subjects demonstrated a trend towards a positive correlation and in two of them was this significant at pt0.05. In addition, the presence or absence of a possible correlation between muscle power and plasma concentration was not related to the duration of disease, additional prednisolone therapy or thymectomy.

No description available.

No description available.

Oxidation of fluphenazine decanoate, a member of the neuroleptic phenothiazine drugs, is believed to occur in oily solution via the hydroperoxides formed as a result of autoxidation of the oil. Synthesis and characterisation of the expected oxidation products of the drug was undertaken so that the formation of these degradation products in oily solution, could be accurately determined. By this means the rate of oxidation of fluphenazine decanoate by various hydroperoxides was determined. Only in the case of the C-IB unsaturated fatty esters did the overall oxidation process obey simple kinetics (2nd order) enabling values for the respective rate-constants to be calculated. The presence of acid was clearly demonstrated to catalyse oxidation of the tertiary amine centres in the molecule, a finding contrary to reports in the literature. In addition, the catalytic effect was shown to be related to the pKa value of the acid. Benzyl alcohol is commonly added as a preservative to oily formulations and thus the effect of this material on the rate of fluphenazine decanoate oxidation was investigated. Evidence for the enhanced oxidation of the drug in the presence of benzyl alcohol in a naturally ageing formulation was obtained and a plausible mechanism for this phenomenon was sought. Autoxidation of the benzyl alcohol was deemed a likely explanation and since little information on this aspect of benzyl alcohol chemistry could be found in the literature an extensive study of benzyl alcohol autoxidation was conducted. It was finally concluded that autoxidation of benzyl alcohol leads directly to hydrogen peroxide offering one viable explanation of the enhanced degradation of the drug observed in the presence of the preservative.

No description available.

No description available.

No description available.

Sulphathiazole is a highly polymorphic model system exhibiting at least five polymorphic forms: I, II, III, IV, and V. Polymorph stability is known to be susceptible to solvent environment, and it is established that 1-propanol stabilizes the most metastable form I. This study examines the effect of a range of alcohols on polymorph selection and attempts to elucidate the mechanism. The role of the alcohol functional group in the polymorph selection process is thus investigated and evaluated. Crystals were characterized using optical microscopy, SEM, PXRD, DSC, IR, and single-crystal X-ray diffraction for their polymorphic identity. The role of solvent in the stabilization of polymorphs was investigated by visualizing and calculating energy requirements for the interaction of each solvent molecule with α- and β-dimers of sulphathiazole, using Cerius2 modeling software and GRID based systematic search simulation. These studies showed that solvent had a significant impact on polymorph selection. In common with 1-propanol, 1-butanol was found to stabilize form I by inhibiting the formation of the β-dimer, which is necessary for nucleation of and transformation to forms II-IV. Shorter chain alcohols and branched chain alcohols such as methanol, 2-propanol, and ethanol did not stabilize form I but stabilized forms II, III, and IV, respectively, showing that it is not only the alcohol functionality but also the steric effects of the alkyl chain that contributed to the effect. Sulphathiazole form I normally has a needlelike morphology. Form I with a modified rodlike morphology was produced by crystallization from 1-propanol with the addition of methanol in low concentration, showing that it is possible to control the morphology and selectively isolate polymorphs. Indomethacin is known to exhibit at least five polymorphs but only the stable γ Form and metastable α Form are reported to be reliably produced by standard methods. The metastable α Form has an undesirable fibrous needle-like morphology. The current study focused on producing crystals of α Indomethacin with a well-defined morphology using additives. Adipic acid, myristic acid, oleic acid and structurally related 3-indoleacetic acid were selected as additives and their impact on the morphology and polymorphism of indomethacin were investigated in this study. Additives did not change the needle-like morphology of α-indomethacin but less fibrous and less aggregated well defined needles were observed in presence of adipic acid, oleic acid and 3-indole-3-acetic acid.

Background & Aim: Osteoarthritis (OA) sufferers frequently turn to complementary and alternative medicine (CAM), of which the most common are acupuncture and homeopathy, to improve manageability of their condition. However, there is little extant evidence of effectiveness for these treatments for OA, particularly for homeopathy. One criticism of homeopathic studies is that treatment protocols do not reflect true homeopathy. The nature of true homeopathy is not documented in extant literature. In the current study a mixed methods approach was used to investigate the use of homeopathy for osteoarthritis using a survey, conducted with a parallel acupuncture survey for comparison, follow up interviews with homeopaths and a patient-centred study in a homeopathic department offering treatment on the NHS, in order to inform future studies. Method: The current study involved three phases; (1) A descriptive survey conducted on n=362 medical and non-medical homeopaths and acupuncturists, was used to , investigate practice of the therapies (2) Follow up interview of n=28 of the homeopathic practitioners. (3) A patient-centred study of n=11 patients with OA receiving homeopathy in the primary care setting. Results: (1) Most commonly encountered conditions were chronic diseases. Medical and non-medical acupuncturists practised very different forms of acupuncture particularly in terms of diagnostic techniques used and theoretical underpinning. Homeopathic practitioners used individualised treatments, abiding by classical homeopathy. Differences between medical and non-medical homeopaths included time spent in the consultation (p= 0.01), strength of confidence in homeopathy for asthma (p=0.01), musculo-skeletal (p=0.046) and acute conditions (p=0.01)., and confidence in conventional medicine (p=0.01). There was a belief amongst acupuncturists and homeopaths that the treatments may work on electrodynamic fields in the body. (2) A similar approach was taken by participants during a detailed initial consultation. However, irrespective of medical status, varied approaches were used to identify the remedy, potency, and remedy f6mi, and the source of remedy also varied. Main themes regarding the modus operandi of homeopathy included stimulation of self healing mechanisms and identifying in detail events at the point where the initial health imbalance occurred. Identification of this point together with the patient was considered a potential trigger for the healing process to begin, adding a particular importance to the role of the consultation. (3) OA patients in the primary care setting identified pain or stiffness as the most common primary complaint., with an emotional factor such as anxiety and limitations caused by their condition as a secondary complaint. A desire to reduce their medication or to improve the manageability of their condition was a common theme for interest in receiving homeopathy, with access to NHS homeopathic treatment and perceived safety of receiving treatment from medical doctors being important factors. Following 6 months of' homeopathic treatment, most participants reported an improvement in the manageability of their condition. This, however was not supported by results from VAS pain, VAS stiffness, MYCAW scores or SF36 subscore, or salivary concentration of substance P results which were not found to be significant. Few correlations were found between outcome measures. Substance P level was strongly correlated with the functional limitations sub-score of the SF36 (p=0.01), indicating a potential role for this biochemical measure in future studies. Conclusion: Findings from the current study can inform future studies on how to enhance the evidence base for homeopathic and acupuncture treatment, and inform the integration debate. Future advances in the understanding of subtle processes in the body, the placebo response, and the nature of cure may add to our understanding of' CAM treatments. However, it is likely that in order to advance the evidence base on the effectiveness of homeopathy for OA, more effective tools that are sensitive to changes in biopsychosocial dimensions of health will be necessary. Future research on combination therapies is also warranted.