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排序方式: 共有388条查询结果,搜索用时 31 毫秒
1.
Timothy Pas Bjorn Vergauwen Guy Van den Mooter 《International journal of pharmaceutics》2018,535(1-2):47-58
Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions. 相似文献
2.
Carsten Goebel John Troutman Jenny Hennen Helga Rothe Harald Schlatter G. Frank Gerberick Brunhilde Blömeke 《Toxicology and applied pharmacology》2014
The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their sensitizing properties, it may also impair their color performance. With introduction of a methoxymethyl side chain we found the primary intermediate 2-methoxymethyl-p-phenylenediamine (ME-PPD) with excellent hair coloring performance but significantly reduced sensitizing properties compared to PPD and PTD: In vitro, ME-PPD showed an attenuated innate immune response when analyzed for its protein reactivity and dendritic cell activation potential. In vivo, the effective concentration of ME-PPD necessary to induce an immune response 3-fold above vehicle control (EC3 value) in the local lymph node assay (LLNA) was 4.3%, indicating a moderate skin sensitizing potency compared to values of 0.1 and 0.17% for PPD and PTD, respectively. Finally, assessing the skin sensitizing potency of ME-PPD under consumer hair dye usage conditions through a quantitative risk assessment (QRA) indicated an allergy induction risk negligible compared to PPD or PTD. 相似文献
3.
Tetrandrine, a constituent of Chinese herb Stephania tetrandra, causes cell death in prostate cancer, but the molecular mechanisms leading to apoptosis is not known. Here we demonstrated that tetrandrine selectively inhibits the growth of prostate cancer PC3 and DU145 cells compared to normal prostate epithelial PWR-1E cells. Tetrandrine-induced cell death in prostate cancer cells is caused by reactive oxygen species (ROS)-mediated activation of c-Jun NH2-terminal kinase (JNK1/2). JNK1/2-mediated proteasomal degradation of c-FLIPL/S and Bcl2 proteins are key events in the sensitization of prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Tetrandrine-induced JNK1/2 activation caused the translocation of Bax to mitochondria by disrupting its association with Bcl2 which was accompanied by collapse of mitochondrial membrane potential (MMP), cytosolic release of cytochrome c and Smac, and apoptotic cell death. Additionally, tetrandrine-induced JNK1/2 activation increased the phosphorylation of Bcl2 at Ser70 and facilitated its degradation via the ubiquitin-mediated proteasomal pathway. In parallel, tetrandrine-mediated ROS generation also caused the induction of ligand-independent Fas-mediated apoptosis by activating procaspase-8 and Bid cleavage. Inhibition of procaspase-8 activation attenuated the cleavage of Bid, loss of MMP and caspase-3 activation suggest that tetrandrine-induced Fas-mediated apoptosis is associated with the mitochondrial pathway. Furthermore, most of the signaling effects of tetrandrine on apoptosis were significantly attenuated in the presence of antioxidant N-acetyl-l-cysteine, thereby confirming the involvement of ROS in these events. In conclusion, the results of the present study indicate that tetrandrine-induced apoptosis in prostate cancer cells is initiated by ROS generation and that both intrinsic and extrinsic pathway contributes to cell death. 相似文献
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不同组织膜蛋白及二甲基亚砜对小脑颗粒细胞突起生长的影响 总被引:2,自引:0,他引:2
目的探讨不同组织膜蛋白提取物和二甲基亚砜对大鼠小脑颗粒细胞(CGC)突起生长的影响。方法提取成年大鼠肝、坐骨神经和脑白质的组织膜蛋白包被盖片,接种CGC于盖片上,同时将二甲基亚砜(DMSO)作为添加剂加入培养液,观察CGC突起的生长。结果①脑白质膜蛋白能明显抑制CGC突起的生长,随浓度增加抑制效应更加明显;坐骨神经膜蛋白对CGC突起生长抑制不明显,肝组织膜蛋白则能促进突起生长;②随DMSO浓度升高CGC突起生长逐渐受到抑制,当DMSO浓度小于1%时,CGC突起长度与对照对照差别不大。结论脑白质膜蛋白对CGC突起生长有明显抑制作用,而DMSO添加到培养液中在低浓度时不会显著影响神经元突起生长,可用于检测药物及疏水性分子对体外培养的神经细胞突起生长的作用。 相似文献
7.
The participation of metal ions between C8 and C9 during the final stages of immune hemolysis could not be verified. EA, EAC1-7, and EAC1-8 all lyse completely when tested with 40 mM or higher concentrations of phenanthroline derivatives, only some of which are metal chelators. Only those phenanthrolines that carry a nitrogen in the No. 1 position and are also uncharged are lytic. 1.7-phenanthroline, not a chelator, lyses EAC1-8 more readily than EA and EAC1-7, suggesting an influence of the C5b-8 complex on this type of lysis. Unlike C9 lysis of EAC 1-8, phenanthroline induced lysis of EAC 1-8 cannot be inhibited by incubation with anti-C8, indicating different binding sites for C9 and phenanthrolines.The phenanthrolines neither protect nor promote hypotonic lysis, as do local anesthetics which are known to perturb primarily the membrane lipid phase. Likewise, sublytic drug concentrations do not modify immune hemolysis. 相似文献
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利用5%、10%、15%、20%、25%、30%浓度的二甲基亚砜和甘油肝浸汤培养液对临床分离的阴道毛滴虫进行4℃保存观察。二甲基亚砜和甘油两实验组最适保种浓度分别为15%和10%,50%虫体存活率天数分别为29和27 d,最长保存天数分别为31和29 d;而空白对照组仅为5和7 d。结果表明,15%二甲基亚砜或10%甘油肝浸汤培养液4℃冷藏保存阴道毛滴虫可显著延长其保存期。 相似文献
10.
Harry LeVine III Qunxing Ding John A. Walker Randal S. Voss Corinne E. Augelli-Szafran 《Neuroscience letters》2009
Soluble oligomeric amyloid-β (Aβ) species are toxic to many cell types and are a putative etiological factor in Alzheimer's disease. The NINDS-Custom Collection of 1040 drugs and biologically active compounds was robotically screened for inhibitors of Aβ oligomer formation with a single-site biotinylated Aβ(1–42) oligomer assembly assay. Several quinoline-like compounds were identified with IC50's <10 μM, including the antiprotozoal clioquinol that has been reported to have effects on metal ion metabolism. The 2-OH, 4-OH, and 6-OH quinolines do not block Aβ oligomer formation up to a concentration of 100 μM. Analogs of clioquinol have shown activity in reducing Aβ levels and improving behavioral deficits in mouse models of Aβ pathology. The inhibitory effects of clioquinol and other 8-OH quinoline derivatives on oligomer formation in vitro are unrelated to their chelating activity. Crosslinking studies suggest that clioquinol acts at the stage of trimer formation. These preliminary data may suggest that 8-OH quinolines have the potential for suppressing Aβ oligomer formation which should be considered when assessing the effects of these compounds in animal models and clinical trials. 相似文献