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31.
Poor aqueous solubility of drugs and the improvement thereof has always been a challenge for the pharmaceutical industry. With this, one of the focuses of the pharmaceutical research scientist involves investigating possible metastable forms of a given drug to be incorporated into solid dosage forms. The rationale being, the improved solubility offered by the metastable solid-state forms of drugs. Solubility remains a major challenge for formulation scientists, especially with antimicrobial agents where the emergence of resistance is directly dependent on the concentration and duration of the parasite exposed to the drug. Sulfadoxine-pyrimethamine combination therapies are still the recommended treatments for uncomplicated Plasmodium falciparum malaria. The aim of this study was to prepare an amorphous form of sulfadoxine and to investigate the stability and recrystallization behavior thereof. The amorphous form was prepared by the well-known quench cooling of the melt. The physico-chemical properties and stability of amorphous sulfadoxine were studied using hot-stage microscopy (HSM), scanning electron microscopy (SEM), x-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), as well as microcalorimetry. The recrystallization kinetics were studied isothermally by applying the Johnson-Mehl-Avrami model and non-isothermally by applying the Kissinger model. The physical stabilization of the amorphous form was investigated using physical mixtures of amorphous sulfadoxine with polyvinylpyrrolidone-25 (PVP-25). It was proved that sulfadoxine is a good glass former with relative high physical stability; however, water acts as a strong plasticizer for amorphous sulfadoxine, detrimentally affecting the stability during exposure to high moisture conditions. 相似文献
32.
33.
A "two-site" immunoradiometric assay (IRMA) was developed to specifically measure ANF (1-126), the precursor of ANF. This assay is based on the simultaneous use of antibodies against two different antigenic determinants: murine monoclonal antibody (2H2), which recognizes positions 101 through 103 of ANF, is linked to Immunobeads and employed to extract any ANF C-terminal; a second antibody, which is directed against positions 11 through 37, is radioiodinated and allows binding to any C-terminal-2H2-Immunobead material which bears the N-terminal antigenic site. A curvilinear relationship was obtained between radioactivity and the amount of proANF (1.5 to 400 fmol) added. Optimisation of IRMA was determined by the amount of 2H2-Immunobeads and labeled antibody used, incubation time as well as possible interference by both ANF (99-126) and ANF (1-98). Tissue extracts were used to validate the assay. proANF was detected in decreasing amounts in heart atria, heart ventricles, lungs, kidneys and adrenal glands. Its presence was further confirmed by reverse-phase HPLC followed by radioimmunoassay. IRMA is a simple and rapid method for the direct measurement of proANF in tissue extracts and chromatographic fractions. The presence of proANF in tissues strongly suggests local synthesis. 相似文献
34.
White rot fungi (WRF) are applicable to biodegradation of recalcitrant pollutants. However, excessive biomass growth typical for WRF cultivation can hinder their large scale applications. Therefore, immobilization of Irpex lacteus to liquid-core alginate beads restricting excessive mycelium growth and simultaneously keeping high degradation rate of pollutants was tested. Effective diffusivities of dyes to the beads varied from (2.98 ± 0.69) × 10?10 to (10.27 ± 2.60) × 10?10 m2/s. Remazol Brilliant Blue R (RBBR), Reactive Orange 16 (RO16), and Naphthol Blue Black (NBB) were used as model dyes. The immobilized fungus decolorized model dyes when applied both in microwell plates and in fluidized bed reactors. Using the microwell plates, the apparent reaction rate constants ranged from (2.06 ± 0.11) × 10?2 to (11.06 ± 0.27) × 10?2 1/h, depending on the dye used and its initial concentration. High initial concentrations negatively affected the dye decolorization rate. No fungal growth outside the beads was observed in fluidized bed reactors and thus no operational problems linked to an excessive biomass growth occurred. When RBBR was decolorized in subsequent batches in the fluidized bed reactor, the apparent reaction rate constant increased from (11.63 ± 0.35) × 10?2 to (29.26 ± 7.19) × 10?2 1/h. 相似文献
35.
De Savi C Pape A Sawyer Y Milne D Davies C Cumming JG Ting A Lamont S Smith PD Tart J Page K Moore P 《Bioorganic & medicinal chemistry letters》2011,21(11):3301-3306
A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. 相似文献
36.
Mapping of antigenic determinants of human apolipoprotein B using monoclonal antibodies against low density lipoproteins 总被引:16,自引:0,他引:16
Y L Marcel M Hogue R Theolis R W Milne 《The Journal of biological chemistry》1982,257(22):13165-13168
The reactivity of a series of monoclonal antibodies directed against human low density lipoproteins (LDL) has been tested with hepatic and intestinal apolipoprotein B (apo-B) termed B-100 and B-48, respectively (Kane, J. P., Hardman, D. A., and Paulus, H. E. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 2465-2469). Whereas those antibodies that have been previously shown to recognize determinants close to the LDL receptor recognition site reacted only with B-100, two antibodies specific for other regions of apo-B reacted with both B-100 and B-48. Therefore, it is probable that sequence homologies exist between the two proteins and it must be considered that all or parts of the B-48 sequence may be contained within that of B-100. The specificity of the reaction of these antibodies with proteins designated B-74 and B-26 supports the concept that they represent complementary fragments of B-100. The present results have been incorporated in a theoretical map of the antigenic determinants recognized by these antibodies on the LDL apo-B. 相似文献
37.
M Prescott N M Thorne A D Milne A G McLennan 《The International journal of biochemistry》1992,24(4):565-571
1. A P1,P3-bis(5'-nucleosidyl)triphosphate pyrophosphohydrolase (Np3 Nase) has been partially purified from Artemia embryos. 2. The Np3 Nase has a native Mr of 115,000 and preferentially hydrolyses substrates of the form Np3 N. Relative rates of hydrolysis are Ap3A (Vrel = 1.0), Gp3G (Vrel = 0.71), Ap4A (Vrel = 0.08), Ap5A (Vrel = 0.09), Gp4G (Vrel = 0.3) and Gp5G (Vrel = 0.33). An NMP is always one of the products. 3. The Km values for Ap3A and Gp3G are 15 and 10 microM respectively. 4. Mg2+, Mn2+ and Ca2+ ions all stimulate the activity, while Zn2+, Co2+ and Ni2+ ions are inhibitory. 5. The activity of the Np3 Nase remains constant during pre-emergence development of encysted embryos but decreases slightly after hatching. 相似文献
38.
Modulation of apolipoprotein B antigenic determinants in human low density lipoprotein subclasses 总被引:4,自引:0,他引:4
B Teng A Sniderman R M Krauss P O Kwiterovich R W Milne Y L Marcel 《The Journal of biological chemistry》1985,260(8):5067-5072
To investigate the effect of low density lipoprotein (LDL) heterogeneity on the conformation of LDL apolipoprotein B (apo-B), the immunoreactivities of 6 monoclonal antibodies against LDL apo-B were measured in 3 LDL subfractions isolated by equilibrium density gradient ultracentrifugation. To ensure a broad range of LDL particles, the LDL subfractions were prepared from normal subjects and patients with hyperapobetalipoproteinemia. With 3 of the antibodies, 1D1, 5E11, and 3A10, LDL fractions 1 (the most buoyant), 2 (the intermediate), and 3 (the densest) were equally immunoreactive and competed similarly with reference whole LDL. In contrast, with 3 other antibodies, 2D8, 3F5, and 4G3, fraction 1 was significantly more reactive than fraction 3; that is for each in turn, 290, 250, and 150% more of the densest LDL protein was required to achieve the same displacement as with fraction 1. Further, the immunoreactivities of the 3 LDL fractions with antibodies 2D8, 3F5, and 4G3 were negatively correlated with their LDL cholesterol to LDL protein ratio with r values of 0.727, 0.898, and 0.870, respectively, suggesting that as LDL particle size decreases, the conformation of the LDL apo-B changes progressively. It is of interest that the antigenic determinants recognized by 3F5 and 4G3 are close to the LDL receptor recognition site on LDL apo-B. Therefore, it is possible that the reduced immunoreactivity of these determinants in dense LDL may be the in vitro correlate of the reduced fractional catabolics rate of dense LDL compared to buoyant LDL previously observed in vivo. 相似文献
39.
Hybrids between the acid-loving species Rhododendron ferrugineum and the basic soil species Rhododendron hirsutum occur on soils of intermediate pH in the European Alps. Material from two hybrid zones ~500 m apart, and also nearby populations of each parent species, was surveyed for presence/absence of 31 random amplified polymorphic DNA markers that distinguish parents. Based on morphological assessment, the material comprised 51 putative hybrids, 18 putative R. ferrugineum individuals and 26 putative R. hirsutum plants. RAPD data were analysed using a Bayesian approach implemented by the program newhybrids , and also by principal coordinates analysis. The identity of all R. ferrugineum plants examined was confirmed; however, of the putative R. hirsutum individuals examined, two were certainly and 11 possibly hybrid derivatives. Among all hybrid derivatives examined, about half were designated as F1 s or a similar class, otherwise backcrosses to R. hirsutum appeared to be common whereas other hybrid classes were rare and backcrosses to R. ferrugineum possibly absent. Despite this, artificially generated seed of F2 class and backcrosses in each direction showed greater viability than one parent ( R. hirsutum ). Introgression from R. ferrugineum was also detected in a population that from morphology appeared to contain only R. hirsutum . Hence, the direction of backcrossing might be highly asymmetric within hybrid zones, causing unidirectional gene flow from R. ferrugineum into R. hirsutum . Conversely, the rarity of backcrosses to R. ferrugineum , F2 s and later hybrid generations, which might be due to phenology effects and habitat-mediated selection, could play a part in restricting gene flow towards R. ferrugineum . 相似文献
40.
Prashant G. Bhat Ajay M. V. Kumar Balaji Naik Srinath Satyanarayana Deepak KG Sreenivas A. Nair Suryakanth MD Einar Heldal Donald A. Enarson Anthony J. Reid 《PloS one》2013,8(12)