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11.
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Hollow microspheres for use as a floating controlled drug delivery system in the stomach. 总被引:6,自引:0,他引:6
Hollow microspheres (microballoons), loaded with drug in their outer polymer shells, were prepared by a novel emulsion-solvent diffusion method. The ethanol:dichloromethane solution of drug (tranilast or ibuprofen) and an enteric acrylic polymer were poured into an agitated aqueous solution of polyvinyl alcohol that was thermally controlled at 40 degrees C. The gas phase generated in the dispersed polymer droplet by the evaporation of dichloromethane formed an internal cavity in the microsphere of the polymer with the drug. The drugs incorporated in the solidified shell of the polymer were found to be partially or completely amorphous. The flowability and packability of the resultant microballoons were much improved compared with the raw crystals of drug. The microballoons floated continuously over the surface of acidic dissolution media containing surfactant for greater than 12 h in vitro. The drug release behavior of the microballoons was characterized as an enteric property, and drug release rates were drastically reduced depending on the polymer concentration at pH 6.8. 相似文献
13.
T Maeda M Niwa K Shigematsu M Kurihara Y Kataoka K Nakao H Imura H Matsuo H Tsuchiyama M Ozaki 《European journal of pharmacology》1990,176(3):341-350
Specific binding sites for porcine brain natriuretic peptide-26 (BNP-26), a member of the atrial natriuretic peptide family (ANPs), were investigated in the kidney by using receptor autoradiographic and membrane binding techniques with [125I]BNP-26. The binding sites were discretely localized in rat and porcine kidney areas corresponding anatomically to the glomeruli and inner medulla. There were no differences between the localization of [125I]BNP-26 and [125I]alpha-rat ANP binding sites in the kidney. [125I]BNP-26 binding to solubilized membranes from isolated glomeruli of the rat kidney was saturable, and a single class of high-affinity sites was labeled with a KD of 372 pM. The radioligand bound to two sites in solubilized inner medullary membranes of the rat, a low-affinity site with a KD of 30 nM, and a high-affinity site with a KD of 33 pM. The rank order of potency to inhibit binding was BNP-26 = alpha-rat ANP-(1-28) greater than atriopeptin III (ANP-(103-126)) much greater than atriopeptin I (ANP-(103-123)) greater than des-Cys105,Cys121- ANP-(104-126). Thus, [125I]BNP-26 presumably recognizes ANP receptors in the kidney. The possibility that BNP-26 regulates, as a circulating hormone, kidney functions by binding to ANP receptors would have to be considered. 相似文献
14.
Specificity of sulfated polysaccharides to accelerate the inhibition of activated protein C by protein C inhibitor 总被引:2,自引:0,他引:2
Y Kazama M Niwa R Yamagishi K Takahashi N Sakuragawa T Koide 《Thrombosis research》1987,48(2):179-185
The ability of various sulfated polysaccharides to activate protein C inhibitor (PCI) and the effect of molecular weight (Mr) and sulfur content of dextran sulfates were investigated. Besides dextran sulfate, highly sulfated polysaccharides such as chondroitin polysulfates 1 and 5, and pentosan polysulfate were more active than heparin in enhancing the activated protein C inhibition by PCI. The molecular weight and the sulfur content of dextran sulfate were critical for the second-order rate constant of the reaction and for the optimal concentration of the polysaccharide, respectively. These results suggest that the carboxyl groups of polysaccharides are not necessarily required, but some sulfate groups within polymers may play a critical role in the interaction with PCI. 相似文献
15.
Wakabayashi Y Watanabe H Inoue J Takeda N Sakata J Mishima Y Hitomi J Yamamoto T Utsuyama M Niwa O Aizawa S Kominami R 《Nature immunology》2003,4(6):533-539
The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development. 相似文献
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M Niwa M Ibaragi K Tsutsumi M Kurihara A Himeno K Mori M Ozaki 《Neuroscience letters》1988,91(1):89-94
We examined the specific rat 125I-alpha-rat atrial natriuretic peptide(1-28)[ANF-(99-126)] (125I-rANP) binding sites in the cerebral capillaries from the cerebral cortex of male adult Wistar rats. The binding of 125I-rANP at 37 degrees C was saturable and of high affinity with a Kd of approximately 100 pM and Bmax of 152 fmol/mg protein. Divalent cations, Mn2+ (2.2 mM) and Ca2+ (1.8 mM) potently inhibited the binding. The rank order for inhibition of the binding was rANP, alpha-human ANP and ANF-(101-126) greater than ANF-(103-126) and ANF-(103-125)"ANF-(103-123). These data on specific binding sites of ANP in cerebral capillaries suggest a possible role for ANP in the blood-brain permeability of water and electrolytes. 相似文献
19.
M Niwa K Shigematsu M Kurihara Y Kataoka T Maeda K Nakao H Imura H Matsuo H Tsuchiyama M Ozaki 《Neuroscience letters》1988,95(1-3):113-118
Specific binding sites of brain natriuretic peptide (BNP), a newly discovered peptide in the subfornical organ (SFO) of porcine brain were investigated, following incubation of related tissue sections with 125I-BNP, then using autoradiography and an image analysis coupled with computer-assisted microdensitometry. Specific 125I-BNP binding sites were found to be localized in the SFO, an area densely labeled by 125I-alpha-rat atrial natriuretic peptide and 125I-(Sar1,Ile8)-angiotensin II. Specific 125I-BNP binding to the SFO was displaced by unlabeled BNP, with a high affinity, and was calculated to be Ka = 0.385 x 10(-9) M and Bmax = 40.1 fmol/mg using a LIGAND computer program. Acquisition of these present findings enhances our knowledge of the physiology of BNP, atrial natriuretic peptides and angiotensin II system in the SFO. 相似文献
20.
The production of three kinds of oxygen radicals (superoxide, hydrogen peroxide, and hydroxyl radicals) by neutrophils from patients with bacterial infection or rheumatoid arthritis was measured. The stimulators used in this study were opsonized zymosan (1 mg/ml), phorbol myristate acetate (20 ng/ml), A23187 (1M, and platelet activating factor (1M). Oxygen radical production by neutrophils from patients with rheumatoid arthritis was not significantly different from that of the control group. Hydrogen peroxide production by the neutrophils from patients with bacterial infection was significantly enhanced by only opsonized zymosan, but the production of the other kinds of oxygen radicals was not. Cytochalasin B reduced the production of hydrogen peroxide induced by opsonized zymosan more markedly than that of any other kind of oxygen radical. The measurement of hydrogen peroxide is suggested to be the most accurate indicator of the enhancement of intracellular production of oxygen radicals by neutrophils during infection. 相似文献