Abstract：
:The recombinant fusion proteins hybrid 1 [H1 (Ag85B-ESAT-6)] and hybrid 56 [H56 (Ag85B-ESAT-6-Rv2660c)] derived from Mycobacterium tuberculosis are promising antigens for subunit vaccines against tuberculosis. Both antigens are early batches of antigens to be enrolled in human clinical trials and it is therefore important to characterize their conformational stability in solution as well as upon interaction with adjuvants. In this study, the physical stability of the two antigens was characterized using a number of biophysical techniques. Dynamic light scattering and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses demonstrated that both antigens exist as a distribution of multimeric states under nonstressed conditions. Their conformational stability was monitored as a function of pH and temperature and visualized in three-index empirical phase diagrams. Both antigens showed a gradual loss of secondary as well as tertiary structure as a function of temperature, with no cooperative transitions observed. Preformulation studies with the Th1-inducing cationic adjuvant CAF01 showed that the antigens were almost completely surface adsorbed. Upon adsorption, the liposome size increased; however, the physical stabilities of the bound and the unbound antigens were comparable. This study provides important information about the biophysical properties of H1 and H56 and highlights the analytical challenges of characterizing complex vaccine formulations.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Hamborg M,Kramer R,Schanté CE,Agger EM,Christensen D,Jorgensen L,Foged C,Middaugh CRdoi
10.1002/jps.23669subject
Has Abstractpub_date
2013-10-01 00:00:00pages
3567-78issue
10eissn
0022-3549issn
1520-6017pii
S0022-3549(15)30876-5journal_volume
102pub_type
杂志文章abstract：:The fungal microorganism Cunninghamella echinulata was utilized to para-hydroxylate the synthetic substrate (+/-)-1-isopropylamino-3-phenoxy-propan-2-ol (1). The resulting product, (+/-)-1-(4-hydroxyphenoxy)-3-isopropylamino-propan-2-ol, or (+/-)-prenalterol, (2) was formed in greater than 85% yield. Extracts from inc...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600760220
更新日期：1987-02-01 00:00:00
abstract：:During stability studies at high temperature (70 degrees C) and low relative humidity ( approximately 0%), the recovery of an asparagine containing hexapeptide (VYPNGA) and its known deamidation products from solid polyvinylpyrrolidone (PVP) matrices was incomplete. To determine the causes of this mass loss, formulati...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.10316
更新日期：2003-03-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600671033
更新日期：1978-10-01 00:00:00
abstract：:The present work employs recent advances in high-resolution real-time magnetic resonance imaging (MRI) to investigate the disintegration process of tablets containing disintegrants. A temporal resolution of 75 ms and a spatial resolution of 80 × 80 µm with a section thickness of only 600 µm were achieved. The histogra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23789
更新日期：2014-01-01 00:00:00
abstract：:Spectrophotometric assay for cycloserine based on the interaction of the drug with 9-methoxyacridine as a chromogenic agent is described. The highly colored substituted acridine product was identified as 9-(d-4-imino-3-isoxazolidinone)acridine. Color development was affected by time and temperature of heating and by t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770519
更新日期：1988-05-01 00:00:00
abstract：:The organic anion-transporting polypeptide (OATP) 2B1 which is ubiquitously expressed in the human body is assumed to play an important role in the cellular uptake of many drugs. Although the expression and function of this solute carrier transporter is well characterized in the human liver and other tissues, little i...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2017.04.001
更新日期：2017-09-01 00:00:00
abstract：:Capillary gas chromatography using an open tubular fused silica column and NP-FID was applied to the simultaneous analysis of the antihistamine, carbinoxamine, and the antitussive, hydrocodone, in human serum. Carbinoxamine and hydrocodone were extracted into methylene chloride-2-propanol (9:1) under alkaline conditio...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600721126
更新日期：1983-11-01 00:00:00
abstract：:In this study, the adsorption of an IgG1 antibody to siliconized vials was investigated with focus on the formulation parameters pH, ionic strength, and nonionic surfactants. Electrophoretic mobility measurements were performed to investigate the charge characteristics of protein and siliconized glass particles at dif...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.24239
更新日期：2015-01-01 00:00:00
abstract：:The hepatic distribution, biliary excretion, and mass balance of liposomal amphotericin B (L-AmB) were investigated in recirculated isolated perfused rat liver. The results were compared with those from the conventional AmB formulation, amphotericin B deoxycholate (D-AmB). L-AmB was introduced as a bolus into the perf...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20239
更新日期：2005-01-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600681008
更新日期：1979-10-01 00:00:00
abstract：:Neural networks (NN) are computational systems implemented in software or hardware that attempt to simulate the neurological processing abilities of biological systems. A synopsis is presented of the operational characteristics, structures, and applications of NN. The NN technology has primarily been aimed at recognit...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820910
更新日期：1993-09-01 00:00:00
abstract：:The increased incidence of human immunodeficiency virus infection in women has identified an urgent need to develop a female-controlled method to prevent acquisition of human immunodeficiency virus and other sexually transmitted diseases. Women would apply the product intravaginally before intercourse. Development of ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20107
更新日期：2004-08-01 00:00:00
abstract：:The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstruc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23020
更新日期：2012-04-01 00:00:00
abstract：:There is a recognized need for new approaches to understand unit operations with pharmaceutical relevance. A method for analyzing complex interactions in experimental data is introduced. Higher-order interactions do exist between process parameters, which complicate the interpretation of experimental results. In this ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21565
更新日期：2009-05-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.01.020
更新日期：2018-06-01 00:00:00
abstract：:In previous studies (Yoneto et al., 1995. J Pharm Sci 84:312-317; Kim et al., 1992. Int J Pharm 80:17-31; and Warner et al., 2001. J Pharm Sci 90:1143-53), the transport enhancing effects of four homologous series of enhancers-the n-alkanols, 1-alkyl-2-pyrrolidones, 1,2-alkanediols, and N,N-dimethylalkanamides - on th...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10269
更新日期：2003-02-01 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：:Continuing work on the interaction of inorganic additives with nonionic surfactants in aqueous solution dealt with their effect on the CMC and surface tension. The surfactants were octoxynol and polyoxyethylated oleyl alcohol, containing an average of 9.5 and 10 ethylene oxide units, respectively. Their CMC values wer...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650706
更新日期：1976-07-01 00:00:00
abstract：:Acute experiments were performed on overnight fasted chloralose-urethan anesthetized dogs, cats, rabbits, and rats. Under these conditions, somatostatin practically abolished gastric contractions and decreased GI tonus in all species examined. The canine duodenum, jejunum, and ileum exhibited only a contractile respon...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680913
更新日期：1979-09-01 00:00:00
abstract：:The positively charged amino acids are commonly used excipients in biopharmaceutical formulations for stabilization of therapeutic proteins, yet the mechanisms for their modulation of protein stability are poorly understood. In this study, both lysine and histidine are shown to affect the thermal stability of myoglobi...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2016.09.013
更新日期：2016-12-01 00:00:00
abstract：:Contraceptive natural steroids, such as progesterone and estradiol, are ineffective when administered orally because of extensive metabolism in the gastrointestinal (GI) tract during absorption and first-pass metabolism. Consequently, highly potent and potentially harmful synthetic steroids are now being used in oral...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700435
更新日期：1981-04-01 00:00:00
abstract：:The cobalt 60 radiolytic degradation products have been identified in the following corticosteroids: cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, hydrocortisone sodium succinate, isoflupredone acetate, methylprednisolone, methylprednisolone acetate, prednisolone, prednisolone acetate, and pred...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720108
更新日期：1983-01-01 00:00:00
abstract：:The metabolic disposition of 14C-labeled carprofen [(+/-)-6-chloro-alpha-methylcarbazole-2-acetic acid] was investigated in rats, dogs, and humans. Carprofen is eliminated predominantly by biotransformation in these three species. In dogs and rats, the direct conjugation of carprofen to form an ester glucuronide and o...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600691104
更新日期：1980-11-01 00:00:00
abstract：:Poor dissolution performance is one of the challenges encountered in dosage form design of amorphous solid dispersions (ASDs). This study was aimed to investigate the effect of solid-liquid interactions of an encapsulated ASD on drug release. Drug release profiles of a molecularly interacting amorphous celecoxib solid...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22462
更新日期：2011-06-01 00:00:00
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：:Several amides of cyclic amines were prepared and tested as penetration enhancers in the diffusion of various drugs through hairless mouse skin in vitro. Hexamethylenelauramide (hexahydro-1-lauroyl-1H-azepine) was selected as a broad spectrum penetration enhancer worthy of further study. Later, the duration of the eff...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600751114
更新日期：1986-11-01 00:00:00
abstract：:The dielectric constant of a solid substance in the dissolved state may be found by using a solvent with a dielectric constant that remains invariable when the solid substance is dissolved. The slope values obtained from dielectric constant versus concentration plots of the solid substance in two solvents with differe...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680408
更新日期：1979-04-01 00:00:00
abstract：:A physiological flow model was developed for the distribution of sulfathiazole residues in various tissues in swine. The approach was compartmental, in which the compartments and equilibrium constants had physiological meaning. Differential equations were developed, and appropriate parameter values and initial conditi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600731107
更新日期：1984-11-01 00:00:00
abstract：:The integrated solutions (ABEC, area between baseline and effect curve) of four basic models of indirect pharmacodynamic responses are developed. These models assume that drug can inhibit or stimulate the production or loss of the response variable. For two models (I and III) with monoexponential drug disposition, exp...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970168r
更新日期：1998-01-01 00:00:00
abstract：:The placental and nonplacental clearances of metoclopramide were studied in nine chronically instrumented, near-term pregnant sheep using a two-compartment open model. Metoclopramide was administered to the ewe and fetus on separate occasions as an initial iv bolus loading dose followed by a constant-rate infusion, wi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600791204
更新日期：1990-12-01 00:00:00
