Enzon Pharmaceuticals (United States)

En 2009, tuve la alegría de celebrar, en Santa Catarina, la obra de Noé Jitrik, en vida y en presencia. Reconocía, en sus primeros escritos, la alternativa entre historia y genealogía, Hegel o Spinoza, que Pierre Macherey había pioneramente señalado (1977). Es decir, no tanto el aut... aut, disyuntivo que había marcado a los lectores de la revista italiana de 1968, sino los más cautos cuidados del vel. Hegel sive Spinoza. Esa alternativa es la fórmula de la identidad, pero es también la de la equivalencia entre dos términos cuyo sentido último se encuentra a medio camino, en la intersección de ambos dominios intelectuales, como una verdad suspendida, aunque captada entre la continuidad, la contestación y el conflicto, y cuya relevancia no dispone de la contundencia de una tesis, sino diseña el movimiento de una figura, de un argumento que estimule la diferencia y el debate. En los años de la redemocratización, como sabemos, fue fuerte el paradigma de Raymond Williams, la tensión campo versus ciudad. Pero creo que el pensamiento de Jitrik se pautaba más por la bipolaridad de un proceso histórico, según el cual la cultura argentina se capta en la dinámica ciudad vel campo, tradición sive ruptura, es decir, un esfuerzo por comprender el fenómeno cultural en toda su complejidad, aunque también en todo el dinamismo de su bipolaridad inmanente. 1

Montelukast sodium (MLS) is a leukotriene receptor antagonist that relieves asthma, bronchospasm, allergic rhinitis, and urticaria. A simple, robust, and stability-indicating normal phase high-performance liquid chromatography method was developed to separate and quantitatively estimate the S-enantiomer of MLS. The chiral separation was achieved using USP L51 packing material along with a mobile phase consisting of a solvent mixture (n-hexane, ethanol, and propionic acid), a flow rate of 1.0mL/min, a detection wavelength of 284 nm, a column temperature of 30°C and an injection volume of 20 μL. The enantiomers peaks were well separated from the peaks of the placebo, diluting solvent, MLS, and its known impurities with a resolution of more than 2.2 and with no interference. Accuracy and linearity were studied in a range of 0.36-3.597 μg/mL (0.03%-0.30%), with good recoveries between 92.5% and 96.8% and a linear regression coefficient above 0.996. The suggested chiral chromatography method is being considered as an alternative and equivalent method to the United States Pharmacopeia and European Pharmacopeia monographs. The developed method was effectively employed for the study of release and stability samples of MLS. This HPLC method is also capable of separating and estimating the stereo-selective isomers (R- and S-enantiomers) of sulfoxide impurity of MLS in pharmaceutical medicine.

Hibiscus rosasinensis and Butea monosperma have been traditionally claimed to be protective against liver injury. However, the hepatoprotective effect against iron overload is not yet validated scientifically. The present study was undertaken to evaluate the possible ameliorating effect of aqueous extract of Hibiscus rosasinensis (AQEHR) and Butea monosperma (AQEBM) against ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in rats. After extraction, total phenolics and flavonoids content of AQEHR and AQEBM were estimated. Further, antioxidant effect followed by hepatoprotective efficacy of AQEHR and AQEBM were evaluated against chronic iron overload by administering Fe-NTA for 8 successive days to rats in increasing order of doses from 6-15mg Fe/kg. Treatments with both the extracts were started 3 days before the administration of iron and together with iron administration for 8 days. Level of liver function tests, triglycerides, protein, and lipid were recorded. Oxidative biomarkers and histopathology were performed to find out the level of protection by extracts. AQEBM contains a high amount of total phenolic and flavonoids contents and exhibited potent antioxidant effects in all assays. Supplementation of both the extract showed hepatoprotective effect by amelioration of biochemical changes and oxidative biomarkers. AQEBM possesses a higher amount of phenolic components and exhibited better therapeutic potential than AQEHR.

The most common pharmaceutical dosage forms for topical delivery of drugs are creams, ointments, and gels, all of which are semisolid in consistency. Attributes that are critical to the effective performance of pharmaceutical semisolids include viscosity, API status, and bioavailability and shelf-life stability. Recent investigations have demonstrated that these critical attributes are driven by the microscale organization of matter (or microstructure) in the semisolid formulation. The microstructure is, in turn, affected by the selection of excipients, amount of excipients, quality of excipients, as well as the processing methods utilized to manufacture the semisolid product. This chapter explores the role of excipients in the microstructure of creams, ointments, and gels, as well as the impact of microstructure on their critical quality attributes and performance.

ResumenLa investigadora inserta el fenómeno del acoso u hostigamiento escolar en un marco de debate filosófico-jurídico y psicosocial.A su vez, analiza la incidencia de la problemática familiar y de su violencia en los educandos, a través de diversas disciplinas y puntos de vista.Logra un marco de debate a través de variados apoyos documentales, vigentes y antiguos; por lo que logra un enfoque histórico-científico con el que realiza un análisis profundo de la problemática en estudio.En su labor aborda especialmente el tema sobre el trato y cuidado que deben darse, no sólo a los niños violentados, sino también a los niños bully que violentan a sus pares en las

Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

Irinotecan is cytotoxic in patients with advanced colorectal cancer (CRC). SN-38 (10-hydroxy-7-ethyl-camptothecin) is the active metabolite of irinotecan. Attachment of polyethylene glycol (PEG) polymer chains (pegylation) to SN-38 (EZN-2208) increases the solubility, exposure, and half-life of SN-38. Preclinical studies demonstrated superior in vitro efficacy of EZN-2208 when it was tested in irinotecan-refractory human CRC cell lines. Patients with metastatic or locally recurrent CRC who had previously received 5-flurouracil (5-FU), oxaliplatin, and irinotecan were assigned to receive EZN-2208 monotherapy (9 mg/m(2) on days 1, 8, and 15 every 28 days for patients with KRAS-mutant tumors only [arm A]), and patients with KRAS wild-type tumors were randomized (2:1) to receive either EZN-2208 plus cetuximab (400 mg/m(2) loading dose on day 1 followed by 250 mg/m(2) weekly starting on day 8 [arm B]) or irinotecan 125 mg/m(2) on days 1 and 8 every 21 days plus cetuximab at the same doses indicated above (arm C). The overall response rate and progression-free survival were 0% and 1.8 months, respectively, in arm A; 10.7% and 4.9 months (95% confidence interval [CI], 3.2-5.8 months), respectively, in arm B; and 14.3% and 3.7 months (95% CI, 2.1-5.8 months), respectively, in arm C. EZN-2208 was well tolerated in combination with cetuximab. No statistically significant difference in survival was observed between arm B (9.8 months; 95% CI, 7.2-11.2 months) and arm C (9.1 months; 95% CI, 6.0-13.0 months). EZN-2208, either as monotherapy or in combination with cetuximab, was well tolerated in patients with refractory CRC. Overall survival and progression-free survival were similar in the cetuximab plus irinotecan arm and the EZN-2208 arm.

EZN-2208 is a water-soluble, polyethylene glycol drug conjugate of SN38, which is the active moiety of irinotecan. In this study, the authors evaluated the tolerability, pharmacokinetics (PK), and activity of EZN-2208 in adult patients with advanced solid tumors. Patients in sequential cohorts (3 + 3 design) received intravenous EZN-2208 at doses between 1.25 mg/m(2) and 25 mg/m(2) once every 21 days. Thirty-nine patients received EZN-2208. The median number of prior therapies was 2 (range, 0-10 prior therapies). Seventeen patients received prior irinotecan. Two maximum tolerated doses (MTDs) were defined: EZN-2208 with (16.5 mg/m(2)) and without (10 mg/m(2)) granulocyte-colony-stimulating factor (G-CSF). The dose-limiting toxicity (DLT) was febrile neutropenia. Two of 19 patients who were heterozygous for a polymorphism in the uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene (UGT1A1*28) developed DLTs (dose, 25 mg/m(2) with G-CSF), and 2 patients who were homozygous for UGT1A1*28 were treated without DLTs (dose, 5 mg/m(2)). PK analysis indicated a mean terminal half-life of 19.4 ± 3.4 hours. Sixteen patients (41%) achieved stable disease, including 6 of 39 patients (15%) who had stable disease that lasted ≥ 4 months. One patient with cholangiocarcinoma (no prior irinotecan) achieved a short-lived 32% tumor regression. Among 6 patients who had stable disease that lasted for ≥ 4 months, 3 had received prior irinotecan, and 1 had KRAS-positive colorectal cancer. EZN-2208 was well tolerated and produced stable disease that lasted for ≥ 4 months/unconfirmed partial responses in 7 of 39 heavily pretreated patients (18%) with advanced solid tumors, including those who had failed prior irinotecan therapy.

Although the cure rate of newly diagnosed acute lymphoblastic leukemia (ALL) has improved over the past four decades, the outcome for patients who relapse remains poor. New therapies are needed for these patients. Our previous global gene expression analysis in a series of paired diagnosis-relapse pediatric patient samples revealed that the antiapoptotic gene survivin was consistently upregulated upon disease relapse. In this study, we demonstrate a link between survivin expression and drug resistance and test the efficacy of a novel antisense agent in promoting apoptosis when combined with chemotherapy. Gene-silencing experiments targeting survivin mRNA using either short-hairpin RNA (shRNA) or a locked antisense oligonucleotide (LNA-ON) specifically reduced gene expression and induced apoptosis in leukemia cell lines. When used in combination with chemotherapy, the survivin shRNA and LNA-ON potentiated the chemotherapeutic antileukemia effect. Moreover, in a mouse primary xenograft model of relapse ALL, the survivin LNA-ON decreased survivin expression in a subset of animals, and produced a statistically significant decrease in tumor progression. Taken together, these findings suggest that targeting endogenous levels of survivin mRNA by LNA-ON methods may augment the response to standard chemotherapy by sensitizing otherwise resistant tumor cells to chemotherapy.