Abstract:
:A novel method for creating water soluble prodrugs of cisplatin analogues bearing chelating diamines is introduced. When 2-(amino-methyl)aniline is reacted with K2PtCl4 between a pH of 6 and 7, the neutral chelated complex [2-(aminomethyl)aniline)dichloroplatinum(II) (1) is isolated. On the other hand, when the complexation occurs under acidic conditions (i.e. pH 3), the zwitterionic, "open-ring" form [2-(ammonio-methyl)aniline-N1]trichloroplatinate(II) (2) is obtained, whereby only the aniline nitrogen is coordinated to platinum. Compound 2 has a solubility of 10 mM in acidic aqueous medium; that is ca. 20 times greater than that of 1. However, 2 rapidly converts to compound 1 at physiologic pH; thus 2 functions as a water soluble prodrug of 1. Both 1 and 2 are equally effective at halting the growth of three different human cancer cell lines in vitro, indicating that the prodrug is quantitatively converted to the parent drug in a complex, biologically relevant medium. In animal experiments, the prodrug form, when given at a dose of 25 mumol/kg three times a week for 6 weeks, significantly inhibits the growth of the MXT (M3.2) mammary tumor in BDF mice while the same dose of the parent drug has no antitumor activity.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Köckerbauer R,Bednarski PJdoi
10.1002/jps.2600840707subject
Has Abstractpub_date
1995-07-01 00:00:00pages
819-23issue
7eissn
0022-3549issn
1520-6017pii
S0022-3549(15)49848-Xjournal_volume
84pub_type
杂志文章abstract::Glassy states of nine acetaminophen-nifedipine compositions have been made by slowly supercooling their melts, and calorimetric T(g) and the nonexponential, nonlinear relaxation parameters beta and x that are used in modeling the mobility of a pharmaceutical determined. The T(g)-endotherm's shape varies with the alloy...
journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600831104
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journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/1520-6017(200008)89:8<1063::aid-jps11>3.0.
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abstract::Aqueous solubilities for some guanine derivatives were estimated by semiempirical equations developed by Yalkowsky and Valvani1 using the data for partition coefficient and melting temperature. It was shown that in the case of guanine derivatives examined in this study, the solubility values could not be estimated ade...
journal_title:Journal of pharmaceutical sciences
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abstract::Pharmacokinetic profiles of pentylenetetrazol in the dog were studied following rapid intravenous and oral administrations of a convulsant dose (15-20 mg/kg). Plasma level-time curves after a rapid intravenous injection showed biexponential decline, indicating that the disposition of this drug in the dog follows a two...
journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600740116
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abstract::Respirable crystals of cromoglycic acid (CA) were prepared by precipitation of CA with hydrochloric acid from aqueous solutions of cromolyn sodium and subsequent recrystallization from hot water or mixtures of dimethyl sulphoxide and water. The properties of the materials were established by melting point measurements...
journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600670212
更新日期:1978-02-01 00:00:00
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journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js960334f
更新日期:1997-04-01 00:00:00
abstract::The goal of this research was to evaluate the effectiveness of cationic liposomes for intranasal administration of proteins to the brain. Cationic liposomes were loaded with a model protein, ovalbumin (OVAL), and a 50 microg dose was administered intranasally to rats. In qualitative studies, liposomes were loaded with...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.21939
更新日期:2010-04-01 00:00:00
abstract::An Amended Solvation Energy Relationship (ASER) was recently reported to successfully predict the aqueous solubilities of a set of 664 organic compounds. The average absolute error and root mean square error are 0.43 and 0.62 log units, respectively. When the General Solubility Equation (GSE) is applied to the same se...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10022
更新日期:2002-02-01 00:00:00
abstract::Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admi...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.10223
更新日期:2002-11-01 00:00:00
abstract::Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing the phase transition properties of hydroxy propyl methyl cellulose K 15 M grade (HPMC) and carbopol 934. The sol-to-gel systems were sterilized by gamma radiation and/or filtration. The sol-to-gel systems were evaluated for rheological character...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.10290
更新日期:2003-02-01 00:00:00
abstract::Quantitative applications for pharmaceutical solid dosage forms using near-infrared (NIR) spectroscopy are central to process analytical technology (PAT) manufacturing designs. A series of studies were conducted to evaluate the use of NIR transmission mode under various pharmaceutical settings. The spectral variabilit...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21777
更新日期:2009-12-01 00:00:00
abstract::The anticonvulsant and CNS-depressant activities of 16 commercially available antiepileptics were subjected to regression analysis. For the maximal electroshock seizure test and pentylenetetrazol seizure threshold test, good correlations were obtained only after diazepam, clonazepam, and carbamazepam were deleted; for...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600680418
更新日期:1979-04-01 00:00:00
abstract::Antisense phosphorodiamidate Morpholino oligomers (PMO) are resistant to degradation by cellular hydrolases, DNases, RNases, and phosphodiesterases, but remain sensitive to prolonged exposure to low pH. The present studies evaluate the oral fractional bioavailability, stability, and efficacy of two distinct PMO sequen...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.10088
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journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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更新日期:2002-08-01 00:00:00
abstract::Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility...
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abstract::The aim of our study was to characterize and optimize a self-nanoemulsifying drug delivery system (SNEDDS) formulation by a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors were the amounts of Capryol PGMC (X(1)), Tween 20 (X(2)), and Transcutol HP (X(3)...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.23333
更新日期:2012-12-01 00:00:00
abstract::The geometry and structural features of the inclusion complexes of beta-cyclodextrin (beta-CD) with the chiral antiamnesic drugs (+/-)-1-benzyl-4-hydroxymethylpyrrolidin-2-one (WEB-1868). (+/-)-1-benzenesulfonyl-5-ethoxypyrrolidin-2-one (RU-35929), and (+/-)-1-(3-pyridinlysulfonyl)-5-ethoxypyrrolidin-2-one (RU-47010) ...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600811205
更新日期:1992-12-01 00:00:00
abstract::A wide variety of computational models covering statistical, mechanistic, and machine learning (locked and adaptive) methods are explored for use in biopharmaceutical manufacturing. Limited discussion exists on how to establish the credibility of a computational model for application in biopharmaceutical manufacturing...
journal_title:Journal of pharmaceutical sciences
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abstract::The pharmacokinetics of fluorouracil were examined after single 250-mg iv doses and 500-mg oral doses to female patients with breast cancer. In five patients who received intravenous fluorouracil, the mean peak plasma level of unchanged drug was 13.4 microgram/ml, the elimination half-life was 6.3 min, and the plasma ...
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更新日期:1980-12-01 00:00:00
abstract::Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.11.016
更新日期:2020-11-26 00:00:00
abstract::Acrylic acid-esterified starch was produced by reacting starch with acrylic acid chloride. This reaction was rapid and easy to control. Introduction of acrylic groups into starch reduced the enzymatic degradability of starch (e.g., with 12 acrylic groups/100 glucose residues, approximately 75% of the degradation produ...
journal_title:Journal of pharmaceutical sciences
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更新日期:1987-12-01 00:00:00