Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Producción de astaxantina bajo factores de estrés utilizando un biorreactor a escala de laboratorio de 5 L / Astaxanthin production under stress factors using a 5L laboratory scale bioreactor / Astaxanthin production under stress factors using a 5L laboratory scale bioreactor

Resumen Introducción. Haematococcus pluvialis es una microalga que produce astaxantina, un beta-caroteno y antioxidante muy usado en la industria. Para obtener una mayor producción de astaxantina se planteó como objetivo utilizar diferentes factores de estrés, en un biorreactor a escala de laboratorio de 5 litros. Metodología. Se cultivó la microalga en el medio RM, pH 6,8, temperatura 20±2°C, aire filtrado, iluminación con lámparas blancas 20h luz/4h oscuridad, irradianza 70 μE m-2s-1, diferentes concentraciones de acetato de sodio y cloruro de sodio. Se determinó crecimiento celular, cambios morfológicos y cuantificación de astaxantina y clorofila por espectrofotometría. Se realizó un análisis estadístico utilizando ANOVA (95%). Resultados. Utilizando 0,299 mg/L de acetato de sodio se obtuvo un crecimiento celular de 2,0 x 104 Cel/mL y una concentración de astaxantina de 2,530 μg/mL, mientras que con 1,6 mg/L de acetato de sodio el crecimiento celular fue de 3,5 x 104 Cel/mL y una concentración de astaxantina de 1,9 μg/ml. El tratamiento al cual se le adicionó 1,6 g/L de acetato de sodio y 6,4 g/L de cloruro de sodio presentó la mayor producción astaxantina 7,3 μg/ml. El tratamiento con acetato de sodio 0,320 g/L + cloruro de sodio 1,28 g/L presentó el mayor crecimiento celular con 1,64x105 células/ml. Conclusión. Esta investigación destaca la importancia de cultivar inicialmente la microalga utilizando el biorreactor Tecferm de 5 litros y después de su fase exponencial someterla a factores de estrés con acetato de sodio y cloruro de sodio lográndose así la mayor producción de astaxantina 7,325 μg/ml.

Abstract Introduction. Haematococcuspluvialis is a microalgae that produces astaxanthin, a beta-carotene and antioxidant widely used in industry. In order to obtain a higher production of astaxanthin, the objective was to use different stress factors, in a 5-liter laboratory-scale bioreactor. Methodology. The microalgae was cultivated in the RM medium, pH 6.8, temperature 20 ± 2°C, filtered air, illumination with white lamps 20h light/4h darkness, irradiance 70 μE m-2s-1, different concentrations of sodium acetate and chloride of sodium. Cell growth, morphological changes and quantification of astaxanthin and chlorophyll were determined by spectrophotometry. Statistical analysis was performed using ANOVA (95%). Results. Using 0.299 mg/L of sodium acetate a cell growth of 2.0 x 104 Cel/mL and an astaxanthin concentration of 2.530 μg/mL were obtained, while with 1.6 mg/L of sodium acetate the cell growth It was 3.5 x 104 Cel/mL and an astaxanthin concentration of 1.9 μg/mL. The treatment to which 1.6 g L of sodium acetate and 6.4 g/L of sodium chloride were added showed the highest astaxanthin production, 7.3 μg/ml. Treatment with 0.320 g/L sodium acetate + 1.28 g/L sodium chloride showed the highest cell growth with 1.64x105 cells/ml. Conclusion. This research highlights the importance of initially cultivating the microalgae using the 5-liter Tecferm bioreactor and, after its exponential phase, subjecting it to stress factors with sodium acetate and sodium chloride, thus achieving the highest production of 7.325 μg/ml astaxanthin.

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy . However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors P-gp inhibition. Moreover, Western blot experiments revealed that inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying of multiple mechanisms to reverse MDR in lung cancer.

Descripción histológica de los daños ocasionados por monoiodo acetato de sodio en articulación humeral de rata / Histologyc description of monosodium iodoacetate damage in rat humeral joint

La inyección con monoiodo acetato de sodio (MIA) es ampliamente utilizada para producir osteoartritis en diversas articulaciones. El objetivo fue describir los daños histológicos provocados por MIA en la articulación humeral de rata. Se inyectó 0,1 mL de mezcla de 0,5 mg de MIA disuelto en 10 mL de solución fisiológica en la articulación humeral izquierda de 21 ratas SpragueDawley. Como control se utilizó la articulación derecha de cada rata. Se realizó la eutanasia a las 4, 8 y 12 semanas post inyección en grupos de 7 ratas. Los miembros mantenidos en formalina tamponada al 10% fueron descalcificados con EDTA por tres meses. Para la evaluación histológica se realizó la inclusión en parafina y se realizaron cortes coronales de 5 µm de espesor, para posterior tinción con azul de toluidina. En el cartílago sano, se observó una superficie lisa sin fisuras, todas las células de las zonas del cartílago se observaron normales. Se observaron cambios en el cartílago articular a partir de las 4 semanas post inyección, los condrocitos de la zona radial hipertróficos con gran producción de proteoglicanos. A las 12 semanas post inyección, se observa un gran deterioro, el espacio articular se ve disminuido, La superficie del cartílago se observa con fisuras y grietas que llegan hasta la zona radial. Las células alrededor de estas fisuras han desaparecido. Se observa una pérdida prominente de proteoglicanos debido a la débil tinción con azul de toluidina. La inyección articular con MIA produce lesiones similares a la OA. La gran ventaja de la OA inducida por MIA, es la facilidad de su aplicación y la rapidez en la progresión de OA.

Injection with monoiode sodium acetate (MIA) is widely used to produce osteoarthritis in various joints. The aim of this work was to describe the histological damage caused by MIA in the rat humeral joint; 0.1 mL of 0.5 mg mixture of MIA dissolved in 10 mL of physiological solution was injected into the left humeral joint of 21 Sprague-Dawley rats. As a control, the right joint of each rat was used. Euthanasia was performed at 4, 8 and 12 weeks post injection in groups of 7 rats. The samples maintained in 10 % buffered formalin were descaled with EDTA for three months. For histological evaluation, paraffin inclusion was performed and 5 µm thick coronal cuts were made for subsequent staining with toluidine blue. In the healthy cartilage, a smooth surface was observed, all cells in the cartilage areas were normal. Changes in articular cartilage were observed after 4 weeks post injection, hypertrophic radial chondrocytes with high proteoglycan production. At 12 weeks post injection, a great deterioration was observed, the articular space was diminished. The surface of the cartilage was observed with fissures and cracks that reach the radial zone. The cells around these fissures have disappeared. A prominent loss of proteoglycans was observed due to weak toluidine blue staining. Joint injection with MIA produced lesions similar to OA. The great advantage of the OA induced by MIA, is the ease of its application and the rapidity in the progression of OA.

Effects of sodium acetate Ringer solution on electrolytes, blood glucose and lactate levels in pediatric neurosurgery / 中国中西医结合急救杂志

Objective To observe the effect of sodium acetate Ringer solution on serum levels of electrolytes, blood glucose (Glu) and lactic acid (Lac) in peri-operational stage of children undergoing neurosurgery. Methods Forty cases of children prepared to undergo neurosurgery admitted into Hunan Children's Hospital from December 2018 to April 2019 were enrolled, and according to the criteria of American Society of Anesthesiologists (ASA), they were classified into Ⅰ-Ⅱ grade. They were divided into a sodium acetate Ringer solution group and a sodium lactate Ringer solution group by random number table method, 20 cases in each group. Sodium acetate Ringer solution group was given the sodium acetate Ringer solution; sodium lactate Ringer solution group was given the sodium lactate Ringer solution, and both groups used intravenous infusion of their own respective solution at a rate of 10 mL·kg-1·h-1. Arterial blood gas detections were measured after anesthesia induction (T1), 1 hour after administration (T2), 2 hours after administration (T3) and at the end of surgery (T4); the changes in serum levels of electrolyte concentrations, blood Glu and Lac were observed in the patients of two groups. Results With the prolonged operation time, the levels of Glu and Lac in the two groups showed an increasing trend, compared with the levels at T1 and T2 , the levels were increased at T3 and T4 [the sodium lactate ringer solution group: Glu (mmol/L) were 5.85±1.02, 6.95±1.21 vs. 5.28±0.72, 5.20±0.62, and Lac (mmol/L) were 1.53±0.74, 1.91±1.41 vs. 1.23±0.71, 1.38±0.69; sodium acetate ringer solution group: Glu (mmol/L) was 5.44±0.86, 5.85±1.12 vs. 5.05±0.85, 5.14±0.74, Lac (mmol/L) were 1.58±1.31, 1.61±1.23 vs. 1.14±0.65, 1.28±0.95, all P < 0.05], the Lac and Glu levels at T4 in sodium acetate Ringer solution group were significantly lower than those in sodium lactate Ringer solution group (both P < 0.05). There were no statistically significant differences in pH value, Na+, K+ and residual base (BE) levels between the two groups at different time points (all P > 0.05). Conclusion Sodium acetate Ringer solution used in pediatric neurosurgery for more than 2 hours can reduce the blood lactic acid level without rising blood glucoselevel. Therefore, it is more suitable for infusion during pediatric neurosurgery.

Efficacy of acetate Ringer's solution for fluid therapy in patients with dangerous placenta previa un-dergoing cesarean section / 中华麻醉学杂志

Objective To evaluate the efficacy of acetate Ringer's solution for fluid therapy in the patients with dangerous placenta previa undergoing cesarean section. Methods One hundred fifty-two pa-tients, aged 22-41 yr, with body mass index of 20-30 kg/m2 , of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective cesarean section under general anesthesia, were allocated to 2 groups ( n=76 each) using a random number table method: acetate Ringer's solution group ( group AR) and lactated Ringer's solution group ( group LR) . Acetate Ringer's solution and lactated Ringer's so-lution 500 ml were intravenously infused at an initial rate of 15 ml·kg-1 ·h-1 followed by an infusion of 10 ml·kg-1·h-1 until patients leaved the operating room in two groups. Blood samples were collected from the left radial artery immediately before fluid replacement, at the end of fluid replacement and at 6 h after sur-gery for blood gas analysis. The development of arrhythmia was recorded during fluid replacement. The postpartum hemorrhage at 2 h after surgery was calculated. Results Compared with group LR, the Mg2+level was significantly increased and blood glucose was decreased at the end of fluid replacement, the inci-dence of arrhythmia was decreased ( P ＜ 0. 05) , and no significant change was found in each parameter of blood gas analysis at 6 h after surgery, postpartum hemorrhage at 2 h after surgery or consumption of ephed-rine in group AR ( P＞0. 05) . Conclusion Acetate Ringer's solution can be effectively used for fluid ther-apy, maintain the internal environment stable and prevent the occurrence of arrhythmia effectively during cesarean section in the patients with dangerous placenta previa.

Inactivation of Listeria monocytogenes ATCC 7644 on fresh-cut tomato using nisin in combinations with organic salts

ABSTRACT The inhibition of Listeria monocytogenes ATCC 7644 on fresh-cut tomato was investigated using nisin alone, and in combinations with organic salts. Nisin at a concentration of 5000 UI/mL was introduced alone or in combination with an organic salt (sodium citrate or sodium acetate each at 3 and 5 g/100 mL each) on fresh-cut tomato previously inoculated with 108 CFU/mL of L. monocytogenes ATCC 7644. Chlorine at 200 ppm was used as a control. The inoculated samples were incubated at different temperatures (4, 10 and 25 °C) and examined at 0, 24, 48 and 72 h. The effects of the antimicrobial treatments on quality parameters of tomato (pH, soluble solids, titratable acidity and vitamin C) were also evaluated, and colour parameters were observed at the lowest storage temperature for 10 days. Both nisin and the organic salts inhibited growth of L. monocytogenes, but the combinations of two compounds were more effective. The nisin-sodium citrate (5%) combination was significantly (p ≤ 0.05) effective, while chlorine was least effective against L. monocytogenes. The quality parameters were substantially retained, especially at 4 °C, suggesting good shelf stability at a low temperature. These results substantiate the use of the cheap and eco-friendly approach to reducing this pathogen of health concern in common fresh produce.

Compatible Stability of Carbohydrate-Electrolyte Injection and Commonly Used Vitamin-Electrolyte Injections / 医药导报

Objective To study the compatible stability of the carbohydrate-electrolyte injection and commonly used vitamin-electrolyte injections. Methods By simulating clinical use of medicines,the carbohydrate-electrolyte injection and various vitamin-electrolyte injections were mixed respectively.The content of sodium acetate was measured by HPLC,and changes in appearance,pH value and insoluble particles of the injections were observed. Results At room temperature,the compatibility solutions showed no significant changes in appearance,pH value,the number of insoluble particles and the content of sodium acetate within 8 h. Conclusion The carbohydrate-electrolyte injection is compatible with commonly used vitamin-electrolyte injections,and the admixtures are stable within 8 h at room temperature.

Determination of Compound Sodium Acetate Injection / 中国药师

Objective:To improve the determination method for compound sodium acetate injection. Methods:Atomic absorption spectrophotometry ( AAS) was used to determine sodium chloride, calcium chloride and potassium chloride in compound sodium acetate injection. Results:The linear range of calcium ion, potassium ion and sodium ion was 9.124 ×10 -7-1.369 ×10 -5 g·ml-1(r =0.999 5),1.501 ×10 -7 ~4.504 ×10 -6 g·ml-1(r=0.999 2) and 7.500 ×10 -8-2.251 ×10 -6 g·ml-1(r=0.999 5), and the av-erage recovery was 100. 4%(RSD=1. 4%,n=9),102. 4%(RSD=1. 6%,n=9) and 100. 3% (RSD=1. 1%,n=9), respectively. Conclusion:The method is simple, accurate and reproducible, and can be used to control the quality of compound sodium acetate in-jection.

Therapeutic effect of hypertonic sodium acetate dextran combined with dopamine on hemorrhagic shock with pulmonary edema in rats first entering high altitude / 中华创伤杂志

Objective To study the therapeutic effects of hypertonic sodium acetate dextran (HAD) in combination with dopamine (DA) on hemorrhagic shock complicated by pulmonary edema in the rats first entering high altitude. Methods Forty-two SD rats, first transported to Lhasa, Tibet (3 760 meters above the sea level), were anesthetized with sodium pentobarbital (30 mg/kg, ip). Hemorrhagic shock model with pulmonary edema was induced by hemorrhage (blood pressure at 50 mm Hg) plus intravenous injection of oleic acid (5 _l/100 g) for 1 hour. All the rats were equally divided into 6 groups, ie, normal control (no hemorrhage or oleic acid), hemorrhagic shock with pulmonary edema (HSPE), HSPE plus lactated Ringer's solution (LR, 4 ml/kg), HAD (4 ml/kg) alone, DA (2 mg/kg) alone and the combined use of HAD and DA groups. After drug administration, the hemodynamic parameters including mean arterial blood pressure (MAP), left intraventricular systolic pressure (LVSP) and the changes of intraventricular pressure (?dp/dt max) were observed at the 15th, 30th, 60th and 120th minutes respectively, blood gases at the 30th and 120th minutes respectively and the water content of the lung and the brain at the 120th minutes. Results As compared with LR control group, HAD (4 ml/kg) or DA (2 mg/kg) used alone significantly increased MAP, LVSP and ?dp/dt max ( P