Abstract:
:Alzheimer's disease (AD) is historically difficult to treat, in part because of the inaccessible nature of brain pathology. Amyloid beta and tau proteins drive pathology by forming toxic oligomers that eventually deposit as insoluble amyloid plaques and neurofibrillary tangles. Recent clinical studies suggest that effective drugs must specifically target oligomers, not native monomers or insoluble fibrils. Passive immunotherapy is a promising pharmaceutical strategy used to specifically target these oligomers in situ. Using the specificity of antibodies coupled with the natural power of the body's immune response, this treatment provides an opportunity for safe clearance of pathogenic protein species from the brain. Passive immunotherapies against amyloid beta and tau oligomers have progressed to clinical trials, with many currently in progress. Biochemical studies of antibody-oligomer complexes have helped identify previously unknown toxic epitopes, thus providing knowledge to the AD field as a whole. This mini-review focuses on the efforts to develop passive immunotherapy treatments for AD and discusses the knowledge gained from recent failures and clinical trials in progress.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Vander Zanden CM,Chi EYdoi
10.1016/j.xphs.2019.10.024subject
Has Abstractpub_date
2020-01-01 00:00:00pages
68-73issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(19)30661-6journal_volume
109pub_type
杂志文章abstract::A number of biopharmaceuticals are available as lyophilized formulations along with a prefilled syringe (PFS) containing water for injection (WFI). Submicron- and micron-size droplets of lubricating silicone oil (SO) applied to the inner surface of the PFS barrel might migrate into the WFI, to which protein pharmaceut...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2019.02.002
更新日期:2019-07-01 00:00:00
abstract::Midazolam (MDZ) is a benzodiazepine commonly administered in preanesthesia of children by oral or by sublingual routes. To mask its bitter taste and enhance its aqueous solubility, we already developed a 0.2% (w/v) MDZ oral solution containing γ-cyclodextrin (γ-CD), which proves to be better accepted by children in pe...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23558
更新日期:2013-07-01 00:00:00
abstract::The application of a stable isotope coadministration technique for estimating the fraction (fm) of imipramine (IP) that is converted to desipramine (DMI) is described. Four healthy male subjects received 25 mg of IP-d4 hydrochloride orally with 25 mg of DMI hydrochloride. The plasma concentrations of IP-d4, DMI-d4, an...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600790203
更新日期:1990-02-01 00:00:00
abstract::Methadyl acetate was metabolized by microsomal preparations of rat liver to yield nor-methadyl acetate and 6-(dimethylamino)-4,4-diphenyl-3-heptanol. The identification and separation of these three compounds was established by TLC, using iodoplatinate spray as a visualizing agent. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600650134
更新日期:1976-01-01 00:00:00
abstract::An important part of pharmacokinetic research is fitting models to observed data and estimating the parameters in the model. In general, parameter estimation in pharmacokinetics is a subset of the general problem of nonlinear regression or parameter estimation in nonlinear regression models. The same criteria, algorit...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760716
更新日期:1987-07-01 00:00:00
abstract::New dihydropyridine in equilibrium pyridinium salt-type redox carrier systems were developed in which the drug is linked via the ring nitrogen atom of nicotinamide. The rate of oxidation of the dihydropyridine forms, and thus the overall and brain-specific distribution of the corresponding 3-carbamoyl-1-carbamoylalkyl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740304
更新日期:1985-03-01 00:00:00
abstract::Amorphous dispersions provide an excellent way of increasing dissolution rates of poorly soluble drugs, but there may be concerns about stability. One way of assessing the stability of amorphous is the study of relaxation. In this study the relaxation at the surface of amorphous solid dispersions (SDs) was evaluated u...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21573
更新日期:2009-06-01 00:00:00
abstract::A method for the determination of sematilide levels in human plasma is described. After the addition of an internal standard, plasma samples are adjusted to pH 8.5 and extracted with a solution of 7.5% isopropanol in methylene chloride. Separation from co-extracted matrix constituents is performed by reversed-phase HP...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800214
更新日期:1991-02-01 00:00:00
abstract::A modified NF method for the quantitative determination of pentaerythritol tetranitrate is reported. A solution of powder is made directly from the dosage form in glacial acetic acid and is then reacted with phenoldisulfonic acid TS. The proposed method saves approximately 75% of the time required with the NF method. ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670543
更新日期:1978-05-01 00:00:00
abstract::Chlorthalidone was analyzed in the concentration range of 0.1-3.0 microgram/ml with a precision of +/- 0.05 microgram/ml. Chlorthalidone inhibition of the enzymatic hydrolysis rate of p-nitrophenyl acetate by bovine erythrocyte carbonic anhydrase was used as a basis for the determination. The amount of p-nitrophenol f...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600661220
更新日期:1977-12-01 00:00:00
abstract::Granules prepared by the high shear wet granulation (HSWG) process commonly exhibit the problem of overgranulation, a phenomenon characterized by a severe loss of the ability to form adequately strong tablet. We hypothesize that the incorporation of brittle excipients promotes brittle fracture of granules during compa...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24066
更新日期:2014-08-01 00:00:00
abstract::The plasma concentrations and urinary excretions of bisoprolol enantiomers in four Japanese male healthy volunteers after a single oral administration of 20 mg of racemic bisoprolol were evaluated. The AUC(infinity) and elimination half-life of (S)-(-)-bisoprolol were slightly larger than those of (R)-(+)-bisoprolol i...
journal_title:Journal of pharmaceutical sciences
pub_type: 临床试验,杂志文章
doi:10.1021/js970316d
更新日期:1998-03-01 00:00:00
abstract::A tetrazole ring is often used in drug discovery as a replacement for the carboxylic acid group. Previous work indicates that compounds containing a tetrazole moiety show asymmetric permeability in Caco-2 cells characteristic of an efflux transporter substrate. The aim of this study is to determine which transporters ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20526
更新日期:2006-04-01 00:00:00
abstract::Pretreatment with cyclosporine reportedly prolongs the effect of certain general anesthetics in humans and the sleeping time of mice after pentobarbital administration. This investigation was designed to determine the mechanism(s) of the cyclosporine-barbiturate interaction. Adult female Wistar rats received cyclospor...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600790106
更新日期:1990-01-01 00:00:00
abstract::Lipids were extracted from human stratum corneum and the remaining corneocytes were reaggregated with different lyotropic liquid crystals. Water transport through the reaggregated stratum corneum was determined using a diffusion chamber according to Smith and Blank. The permeability constant for the reaggregated strat...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800506
更新日期:1991-05-01 00:00:00
abstract::A stability-indicating reversed-phase high-performance liquid chromatographic method using a refractive index detector is described for the determination of propylene carbonate in pharmaceutical formulations. Good precision and accuracy of the method was demonstrated using an aqueous formulation. This method is also a...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740626
更新日期:1985-06-01 00:00:00
abstract::A previous report detailed the derivation and validation of an equation for calculating the Gibbs free energy of liquid-solid adsorption via high-performance liquid chromatography (HPLC). This study utilizes an improved form of that equation in conjunction with an in vitro model of solute adsorption to give an ordered...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600770609
更新日期:1988-06-01 00:00:00
abstract::The purpose of this study was to investigate corneal mucoadhesion, pharmacokinetics in lacrimal fluid and aqueous humor, the immune suppression induced by corneal transplantation of mycophenolate mofetil (MMF) nanosuspensions (NS), and the use of a chitosan-modified MMF nanosuspension (C-NS) as an ophthalmic delivery ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22356
更新日期:2011-04-01 00:00:00
abstract::An approach to analyzing and interpreting kinetic data from stability studies using factorial designs is presented. This may be useful for screening purposes or as an aid in identifying significant effects in complex systems. A typical 2n factorial experiment is discussed, and methods of variance estimation and statis...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600720410
更新日期:1983-04-01 00:00:00
abstract::The intense blue color formed in the official assay of menadione injection by treatment of the sample with 2,4-dinitrophenylhydrazine and ammonia is shown by data from visible light spectra and mass spectra and by comparison of the pKa value with that of the corresponding reaction product of acetone to be due to proto...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670235
更新日期:1978-02-01 00:00:00
abstract::Preliminary studies indicate that it may be possible to differentiate the effects of a nephrotoxic substance from those of diuretic agents by the measurement of both urine and plasma osmolarity. The nephrotoxic substance, mercuric chloride, decreases urinary osmolality and increases plasma or serum osmolality. The diu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600660411
更新日期:1977-04-01 00:00:00
abstract::A spectrodensitometric assay was developed for propranolol based on measurement of the absorbance of the drug on silica gel plates irradiated at 822 nm. Quantities as low as 0.10 microgram can be detected, and a linear relationship was obtained between 0.010 and 0.400 microgram. The percent recovery from plasma spiked...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600670931
更新日期:1978-09-01 00:00:00
abstract::A colorimetric determination of chlorhexidine is described. The method is based on the formation of a yellow complex between the drug and bromcresol green. The absorption peak of this complex, extracted by chloroform, is at 410 nm, and linear response is obtained from 2.5 to 30 micrograms of chlorhexidine/ml. The accu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600690229
更新日期:1980-02-01 00:00:00
abstract::To evaluate oral mucosal absorption of drugs in dogs, a newly designed in situ perfusion system with a circulating perfusion chamber was developed. The utility of the perfusion system was investigated by using three drugs: salicylic acid (SA), sulfadimethoxine (SM), and diltiazem (DIL). The oral mucosal absorption of ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600791103
更新日期:1990-11-01 00:00:00
abstract::Hydrogen triiodide adducts were prepared from N,N-dimethylacetamide, N-alkylpyrrolidone derivatives, and polyvinylpyrrolidone, and their structures were investigated by IR spectra and X-ray structure analyses and compared with the structure of povidone-iodine USP. The results suggest that the iodine in povidone-iodine...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600681211
更新日期:1979-12-01 00:00:00
abstract::Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21766
更新日期:2009-12-01 00:00:00
abstract::Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24544
更新日期:2015-10-01 00:00:00
abstract::This work establishes a predictive model that explicitly recognizes microstructural parameters in the description of the overall mass uptake and local gradients of moisture into tablets. Model equations were formulated based on local tablet geometry to describe the transient uptake of moisture. An analytical solution ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.05.030
更新日期:2016-08-01 00:00:00
abstract::The α-keto carboxylic acid, pyruvic acid (1) was found to be a very effective peroxide scavenger but is subject to an aldol-like self-condensation/polymerization reaction. The purpose of this study was to evaluate the hydrogen peroxide, H2O2, scavenging ability of 3-methyl-2-oxobutanoic acid (2), 4-methyl-2-oxopentano...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.03.041
更新日期:2016-09-01 00:00:00
abstract::The structural integrity and conformational stability of various IgG1-Fc proteins produced from the yeast Pichia pastoris with different glycosylation site occupancy (di-, mono-, and nonglycosylated) were determined. In addition, the physical stability profiles of three different forms of nonglycosylated Fc molecules ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23975
更新日期:2014-06-01 00:00:00