Abstract:
:In vitro release behavior and cytotoxic activity, and in vivo plasma disposition of newly synthesized macromolecular derivatives of cisplatin (CDDP) were investigated and compared with CDDP. The derivatives included oxidized dextran conjugate of CDDP (OX-Dex/CDDP) and dicarboxymethylated dextran conjugate of CDDP (DCM-Dex/CDDP). In vitro release of platinum complex from dextran conjugated CDDP was determined by an equilibrium dialysis method. These dextran conjugates showed sustained release of the platinum complex. In vitro release half-life for DCM-Dex/CDDP was significantly longer (4.5 times) than that for OX-Dex/CDDP. In vitro cytotoxic activity of CDDP and dextran conjugated CDDP against colon 26, mouse colon cancer cell line, was measured using the MTT assay method. OX-Dex/CDDP showed a similar cytotoxic activity to CDDP. However, both cytotoxic activities were markedly decreased when preincubated with the medium containing serum. On the other hand, DCM-Dex/CDDP retained residual cytotoxic activity at a significantly higher level than OX-Dex/CDDP after preincubation with the medium containing serum, although it showed the lowest cytotoxic activity. This indicated longer maintenance of the in vitro antitumor activity of DCM-Dex/CDDP in serum compared with OX-Dex/CDDP. Plasma disposition of CDDP and dextran conjugated CDDP was determined by intravenous administration to rats. Although the total platinum plasma concentration-time profile for OX-Dex/CDDP was similar to that for CDDP, its markedly higher profile was achieved when DCM-Dex/CDDP was administered. The values of the total platinum AUC and MRT, where AUC is the area under the platinum concentration-time curve and MRT is the mean residence time, for DCM-Dex/CDDP were 11.2 times and 4.8 times significantly higher than with OX-Dex/CDDP in plasma, respectively. DCM-Dex/CDDP also showed a significantly lower total clearance compared with OX-Dex/CDDP. These results from the in vivo experiments revealed that retention of DCM-Dex/CDDP in blood circulation was much greater than that for OX-Dex/CDDP. DCM-Dex/CDDP thus has potential as a macromolecular derivative of CDDP for passive tumor targeting.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Nakashima M,Ichinose K,Kanematsu T,Masunaga T,Ohya Y,Ouchi T,Tomiyama N,Sasaki H,Ichikawa Mdoi
10.1248/bpb.22.756subject
Has Abstractpub_date
1999-07-01 00:00:00pages
756-61issue
7eissn
0918-6158issn
1347-5215journal_volume
22pub_type
杂志文章abstract::Rheumatoid arthritis (RA) is an inflammatory disease with joint dysfunction following cartilage degradation. The level of lysophosphatidic acid (LPA) has been reported to be augmented in human synovial fluid from patients with RA. However, it remains to be elucidated whether LPA participates in cartilage destruction. ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b20-00518
更新日期:2021-01-01 00:00:00
abstract::Liposomes were prepared from hydrogenated lecithin (H-PC) by sonication (S) or injection (I) of H-PC dissolved in ethanol containing dl-tocopherol acetate (VEA). The effects of liposomes on the dermal absorption of VEA were studied. The particle diameter of S-liposomes was smaller than that of I-liposomes. The penetra...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.19.758
更新日期:1996-05-01 00:00:00
abstract::Dihydropyrazines (DHPs), which are derived from sugars, inhibit the growth of Escherichia coli. Addition of copper(II) ion (Cu2+) accelerates the effect of DHPs, resulting in cell death. Investigation of the lethal effect in several DNA repair-deficient or detoxifying enzyme-deficient mutant strains and radical scaven...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.1161
更新日期:2005-07-01 00:00:00
abstract::The liver contrast effects of Sonazoid in two ultrasonographic imaging modes, gray-scale conventional and harmonic, were examined as a time-related study in normal rabbits, and evaluated quantitatively and visually with tumor-model rabbits to estimate the diagnostic potential. Peak enhancement of vessels and parenchym...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.26.1272
更新日期:2003-09-01 00:00:00
abstract::Biomacromolecules (>40 kDa) have been developed as drug delivery system (DDS) carriers of low-molecular weight drugs to promote these drugs' uptake by cancer tissues via enhanced permeability and retention (EPR) effects. Human serum albumin (HSA) has been found to accumulate in cancer tissues via this EPR effect. HSA ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b16-00867
更新日期:2017-01-01 00:00:00
abstract::Inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions. The aim of the current study is to investigate the anti-inflammatory effects of fasudil, a selective ROCK inhibitor, on high cholesterol diet-induced hypercholesterolemic rats and its possible mechanisms. In hypercholesterolemic rats, we fou...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.34.1684
更新日期:2011-01-01 00:00:00
abstract::The therapeutic value of an antirheumatic alkaloid, sinomenine (SIN), was investigated in the acute experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). SIN is a bioactive alkaloid derived from the Chinese medicinal plant, Sinomenium acutum REHDER & E. H. WILSON (Family Menispermaceae). Ch...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.1438
更新日期:2007-08-01 00:00:00
abstract::In the present study, we designed and synthesized a novel 1,5-diarylpyrazole derivative, 2-amino-N-(2-methyl-5-(1-(4-sulfamoylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)phenyl) acetamide hydrochloride (CC06), which was intended to act as a prodrug and would exert potent anti-inflammatory activity after being converte...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.32.1032
更新日期:2009-06-01 00:00:00
abstract::The objective of this study was to study the effect of olmesartan medoxomil (OLM), an antihypertensive drug, on intra-articular inflammation induced by zymosan (Zy) in Wistar rats. Intra-articular inflammation was induced in the right knees of rats by 1 mg Zy dissolved in saline. The animals were divided into the foll...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b16-00296
更新日期:2016-01-01 00:00:00
abstract::Cry j 1 is one of the major allergens in Japanese cedar pollen. We attempt high throughput analysis and comprehensive identification of the linear IgE epitopes of Cry j 1. A series of overlapping synthetic Cry j 1 peptides chemically spotted on cellulose membrane was probed with sera from patients in Japan and United ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.28.1496
更新日期:2005-08-01 00:00:00
abstract::The present study investigated the effects of stable agonist for prostaglandin (PG) I2 receptor with PGI1 skeleton, SM-10906, on pro-inflammatory cytokine production by mouse peritoneal macrophages (PEMs) in comparison with PGE1 and PGI2. In mouse PEMs, SM-10906 and PGE1 slightly enhanced interleukin (IL)-6 secretion,...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.23.708
更新日期:2000-06-01 00:00:00
abstract::Polyethyleneglycol (PEG) compounds have a large hydrogen bonding capability and possess various functions that depend on the length of the chain and conformational diversity. Modification of a drug with PEG is a well-known technology for improving the physicochemical properties and biological responses of a drug. Ther...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b13-00087
更新日期:2013-01-01 00:00:00
abstract::We determined the in vivo and in vitro antitumor activities of gambogic acid (GA) and one of the possible mechanisms for its inhibitory activities. In vivo antitumor activity of GA was evaluated by the relative tumor growth ratio (T/C) in nude mice, and in vitro inhibition of SPC-A1 cells was measured by 3-(4,5-dimeth...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.27.1769
更新日期:2004-11-01 00:00:00
abstract::The extracellular matrix (ECM), which contributes to structural homeostasis as well as to the regulation of cellular function, is enzymatically cleaved by proteases, such as matrix metalloproteinases and cathepsins, in the normal and diseased heart. During the past two decades, matricryptins have been defined as fragm...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章,评审
doi:10.1248/bpb.b17-00308
更新日期:2017-01-01 00:00:00
abstract::Microanalytical methods were developed for measuring galactosyl-beta-cyclodextrin (Gal-betaCD) and mannosyl (Man)-betaCD in biological matrices of the rat by HPLC with pulsed amperometric detection. Then, using these methods, the absorption, distribution and excretion of intravenously and orally administered Gal-betaC...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.23.472
更新日期:2000-04-01 00:00:00
abstract::There exist limitations in the detection of exogenous oligosaccharides due to their polydisperse and diversiform nature, and particularly the interference of endogenous glycosaminoglycans (GAGs). Herein, a surface plasmon resonance (SPR) assay for detecting acidic oligosaccharide sugar chain (AOSC), an anti-Alzheimer'...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.60
更新日期:2006-01-01 00:00:00
abstract::We investigated the anti-allergic effect of tea-leaf saponin (TLS), which was a mixture of saponins separated from the leaves of Camellia sinensis var. sinensis, in guinea pigs and rats. TLS (20-100 mg/kg) dose-dependently inhibited experimentally-induced asthma, and ID50 was 61.7 mg/kg. TLS (20-100 mg/kg) dose-depend...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.20.565
更新日期:1997-05-01 00:00:00
abstract::A possible evaluation technique was devised for examing timely cholesterol synthetic activity in the rat liver. The principle of the technique is to measure the incorporation rate of 14C atoms into a few target metabolites excreted in bile with time after an intraportal injection of [1,2-14C] acetate to the conscious ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.1467
更新日期:1995-11-01 00:00:00
abstract::Effects of supplemented docosahexaenoic acid (DHA), given as diacylglycerol (DG) rich in DHA (DHA-DG), triacylglycerol (TG) rich in DHA (DHA-TG) or fish oil concentrate (DHA-70), on the serum concentration of TG and its bioavailability in the rats with diet-induced hyperlipidemia were studied. Hypertriglyceridemia was...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.2381
更新日期:2007-12-01 00:00:00
abstract::The ICR/f rat is a recessive-type hereditary cataractous strain, and opacity in the lens usually becomes evident at around 75 d of age. We previously found that the instillation of eye drops containing a disulfiram and hydroxypropyl-beta-cyclodextrin inclusion complex (DSF eye drops) delays lens opacification in ICR/f...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.31.981
更新日期:2008-05-01 00:00:00
abstract::Qingkailing injection is a well-known composite formula of traditional Chinese medicine and is commonly used in clinical practice, which could offer immunomodulatory effect from our clinical experience on uveitis treatment by Qingkailing. We did the experiment in order to investigate the curative effect and mechanism ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b12-00449
更新日期:2012-01-01 00:00:00
abstract::Cloning of polyketide synthase (PKS) gene for amphidinolide biosynthesis was attempted from a dinoflagellate Amphidinium sp. (strain Y-42). Fourteen beta-ketoacyl synthase gene fragments were obtained by Polymerase Chain Reaction (PCR) amplification from degenerated primer sets designed on the basis of the conserved a...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.29.1314
更新日期:2006-07-01 00:00:00
abstract::The current study reports several post-translational modifications of alphaB-crystallin in normal human lenses. The isoforms of post-translational modified alphaB-crystallin were isolated from the normal human lenses of >70-age group by ion exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrop...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.23.226
更新日期:2000-02-01 00:00:00
abstract::Rats stressed by specific alternation of rhythm in temperature (SART) show various symptoms of disautonomia, increased pulse rates, continuous hypotension, and severe orthostatic hypotension (OH) when they are subjected to postural change. The OH symptoms are improved by muscarinic M2-receptor blockers. In the present...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.30.303
更新日期:2007-02-01 00:00:00
abstract::Cannabinoids are the active ingredients in marijuana, which is among the most widely used addictive drugs despite the well-documented harmfulness related to its abuse. The mechanism underlying cannabinoid addiction remains unclear, which is attributed partially to the difficulty in behavioral testing of high-dose cann...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.b15-00834
更新日期:2016-05-01 00:00:00
abstract::Spontaneous transfer of protein from either influenza virus-infected or uninfected cells to dimyristoylphosphatidylcholine (DMPC) liposomes was examined. The amount of transferred protein of liposomes incubated with influenza virus-infected cells (I-lipo) was more than that of liposomes incubated with uninfected cells...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.1168
更新日期:1995-08-01 00:00:00
abstract::Chitooligosaccharides, the oligomers made up of beta-1,4-linked D-glucosamine, are obtained by partial hydrolysis of chitosan, a deacetylation product of chitin. The antioxidant activity of various chitooligosaccharides was tested in vitro with aminoguanidine, pyridoxamine, and Trolox as reference compounds. Hydroxyla...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.26.1326
更新日期:2003-09-01 00:00:00
abstract::Phospholipase (PL) A2 activity prepared from isolated rat fat pads incubated with sodium orthovanadate (vanadate) was increased in a time- and dose-dependent manner. The increasing effect of vanadate was reduced in the presence of tyrosine kinase inhibitors. Under the inhibition of protein synthesis by cycloheximide, ...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.18.347
更新日期:1995-02-01 00:00:00
abstract::The effects of alpha(1)-acid glycoprotein (AGP) on human erythrocyte membrane were examined in vitro. Bovine and dog AGP, in addition to human AGP or asialo human AGP were used, and the collected data were compared with that for human serum albumin (HSA). A new technique developed by Kikuchi was used to investigate er...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.26.123
更新日期:2003-01-01 00:00:00
abstract::We studied in vitro metabolites of 2,4,6,2',4',6'-hexachlorobiphenyl (HCB, IUPAC PCB No. 155) produced by liver microsomes of a phenobarbital (PB)-treated beagle dog. The major metabolites were 3-hydroxy-2,4,6,2',4',6'-HCB (M-1), 4-hydroxy-2,6,2',4',6'-pentachlorobiphenyl (PenCB, M-2) and 3,4-dihydroxy-2,6,2',4',6'-Pe...
journal_title:Biological & pharmaceutical bulletin
pub_type: 杂志文章
doi:10.1248/bpb.16.852
更新日期:1993-09-01 00:00:00