Barrier, Adsorptive, and Mechanical Properties of Containers Molded from PET/PP Blends for Use in Pharmaceutical Solutions

In this study, the adsorptive properties of L-menthol, moisture vapor transmission rate, and mechanical properties of poly (ethylene terephthalate) (PET), polypropylene (PP), and their blends were evaluated in containers fabricated by injection molding without a compatibilizing agent. These containers intended to hold pharmaceutical solutions containing lipophilic chemicals such as L-menthol. By the addition of a small amount of PP, the moisture barrier properties of PET were effectively improved, but its anti-adsorptive property was reduced. The strength of the PET/PP blends was reduced, but some PET/PP blends were still able to bear the experimental load required for application in eye-drop containers. PET/PP = 9/1 and PET/PP = 8/2 were found to be most applicable for using in the fabrication of containers for medicinal solutions.

Aqueous Leaf Extract of Moringa oleifera (Moringaceae) Effectively Treats Induced Hemolytic Anemia in Wistar Rats

Introduction: Moringa oleifera was a medicinal plant generally used by populations in the food and therapeutic fields. It’s used to treat anemia has been observed in the Djougou Zone in northern Benin. To our knowledge, there were no scientific data available that have evaluated its efficacy in the treatment of haemolytic anemia. This was what justifies this research work in which the phytochemical analysis, extraction and evaluation of the anti-anemic effect were carried out. Methods: Five groups of five Wistar rats each were formed. All the rats were rendered anemic by injection of phenylhydrazine hydrochloride on the first two days D0 and D1 except those in the negative control group. From the second day, the anemic groups were force-fed either with the aqueous extract of Moringa oleifera leaves at 200 or 300 mg/kg body weight/day, or with vitafer, the reference drug against anemia. The positive control group (anemia) was not treated. Blood samples were taken from all the rats on different days: D0, D2, D7, D10 and D15 to evaluate the data of the hemogram and the osmotic resistance of the red blood cells. Results: Phytochemical analysis revealed the presence of tannins, flavonoids, leucoanthocyanins, saponosides, triterpenes and mucilages. A good yield was obtained at the extraction. Both the extract and the reference drug vitafer completely corrected anemia within two weeks after stimulating hemoglobin synthesis and early release of immature red blood cells into the bloodstream. Its effect seemed dose-dependent and specific. Conclusion: Moringa oleifera leaves showed good therapeutic efficacy and can be considered and exploited for transformation into improved traditional medicines (ITM) in the treatment of anemia.

Glycyrrhizic Acid-Loaded Poly-ɛ-Caprolactone Nanoparticles Decrease PRRSV Infection in MARC-145 Cells

Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.

无溶剂条件下磷酸锆纳米粒子作为固体酸催化剂催化苯酚选择性烷基化(英文)

A facile synthesis of α-zirconium phosphate(ZP) nanoparticles as an effective, eco-friendly, and recyclable solid acid catalyst is reported. Polyvinylpyrrolidone(PVP) and polyvinyl alcohol(PVA) were used as organic matrix as dispersing agents and served as a template for the nanoparticles. Hydrogen bonds between ZP and PVA or PVP, along the polymer chains, appear to play an important role for improving the dispersion of in situ formed ZP. Following calcination of PVA/ZP or PVP/ZP, pure hexagonal ZP nanoparticles were obtained. The catalysts were characterized by nitrogen sorption, inductively coupled plasma optical emission spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy(FTIR), scanning electron microscopy, and transmission electron microscopy. Pyridine-FTIR and temperature-programmed desorption of NH3 suggest the presence of Brnsted acid sites. The acidic properties of the catalyst were studied in Friedel-Crafts alkylation of phenol by tert-butanol, producing 2-tert-butylphenol, 4-tert-butylphenol, and 2,4-ditert-butylphenol. The alkylation reaction was performed in the presence of catalysts P2O5/Al2O3, P2O5/SiO2, α-ZrP(prepared in the absence of the polymers), and various ionic liquids. The use of the hexagonal ZP nanoparticle catalyst afforded an excellent phenol conversion(86%) and selectivity towards 4-tert-butylphenol(83%) under optimized reaction conditions. The catalyst was easily recovered from the reaction mixture, regenerated, and reused at least four times without significant loss in the catalytic activity.

Novel targeting approaches and signaling pathways of colorectal cancer: An insight

Colorectal cancer(CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog(SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a stepwise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virusdirected enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.

Extraction and RP-HPLC determination of taxol in rat plasma, cell culture and quality control samples

A rapid, sensitive, selective and validated reverse phase high-performance liquid chromatography （RP-HPLC） method for the estimation of paclitaxel in micro-sample of rat plasma and in culture of cancer cells was per- formed in this study. The mobile phase consisted of an （80： 20： 0.1, v/v/v）. Column elution at a flow rate of 1 optimized mixture of methanol：water： trifluroacetic acid mL/minute with UV detection at 225 nm at room tern- perature was used. The RP-HPLC method was successfully applied for the determination of paclitaxel in plasma samples and in culture of cancer cells with nano-quantity of estimation. The validation studies were performed in accordance with the International Conference on Harmonization （ICH） guidelines. The intra- and inter-day pre- cision showed that the coefficients of variation ranged from 1.07% to 4.27% at different levels of concentrations. To the best of our knowledge, this study also reported for the first time the optimization of different solvents for effective extraction of paclitaxel wherein tert.-butyl methyl ether （TBME）： diethyl ether （DEE） in 50：50 v/ v composition was found most efficient with extraction efficiency ranging between 77.99% and 91.74% and be- tween 76.14 and 93.66% in the plasma and cell culture, respectively. This proposed method was successfully ap- plied to study the pharmacokinetics of paclitaxel and the influence of verapamil and all-trans retinoic acid （atRA） on paclitaxel pharmacokinetics in rat models. This proposed method might emerge as a valuable aid in the labo- ratory monitoring of paclitaxel in a variety of in vitro as well as in vivo scenarios.

Insight to drug delivery aspects for colorectal cancer

Colorectal cancer(CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapiesare the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor(epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.

无溶剂条件下铜磷酸锆催化醇类和酚类化合物乙酰化(英文)

Copper zirconium phosphate nanoparticles have been used as an efficient catalyst for the acetyla-tion of a wide range of alcohols and phenols with acetic anhydride in good to excellent yields under solvent-free conditions. The steric and electronic properties of the different substrates had a signif-icant influence on the reaction conditions required to achieve the acetylation. The catalyst used in the current study was characterized by inductively-coupled plasma optical emission spectroscopy,energy dispersive spectroscopy, X-ray diffraction, N2 adsorption-desorption, scanning electron microscopy, and transmission electron microscopy. These analyses revealed that the interlayer distance in the catalyst increased from 7.5 to 8.0 when Cu2+ was intercalated between the layers, whereas the crystallinity of the material was reduced. This nanocatalyst could also be recovered and reused at least six times without any discernible decrease in its catalytic activity. This new method for the acetylation of alcohols and phenols has several key advantages, including mild and environmentally friendly reaction conditions, as well as good to excellent yields and a facile work-up.

Overview of milling techniques for improving the solubility of poorly water-soluble drugs

Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a“topedown”approach in the production of fine particles.Fine drug particulates are especially desired in formulations designed for parenteral,respiratory and transdermal use.Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents,often to enhance processability or solubility especially for drugs with limited aqueous solubility.The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size,specific surface area and shape of the drug particles as well as millinginduced amorphization and/or structural disordering of the drug crystal(mechanochemical activation).Technology advancements in milling now enable the production of drug micro-and nano-particles on a commercial scale with relative ease.This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs.Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.

磷酸铜锆催化剂上醇选择性氧化（英文）

The catalytic activity of copper zirconium phosphate(ZPCu) in the selective oxidation of alcohols to their corresponding ketones or aldehydes, using H2O2 as an oxidizing agent, was studied. The oxida‐tion reaction was performed without any organic solvent, phase‐transfer catalyst, or additive. Steric factors associated with the substrates influenced the reaction. The catalyst was characterized using X‐ray diffraction, inductively coupled plasma atomic emission spectroscopy, energy‐dispersive X‐ray spectroscopy, and scanning electron microscopy. It was shown that the interlayer distance increased from 0.74 to 0.80 nm and the crystallinity was reduced after Cu2+ intercalation into the layers. This catalyst can be recovered and reused three times without significant loss of activity and selectivity.

Synthesis and antibacterial evaluation of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives

Objective:To synthesis 2-substituted-4,5-diphenyl-N- alkyl imidazole derivatives,and evaluate their antibacterial activity.Methods:A mixture of benzil（10 mmol） and ammonium acetate（0.1 mol）（immediately fused） in glacial acetic acid（25 mL） was stirred at 80-100℃for 1 h under nitrogen atmosphere（to prevent incorporation of any atmospheric impurities and moisture）. Substituted aldehydes（10 mmol） in glacial acetic acid（5 mL） was added drop-wise over a period of 15-20 min at the same temperature and stirred for another 4 h,the progress of the reaction was monitored by TLC test using ethyl acetate as eluent.The newly synthesized compounds were characterized by IR,1HNMR,13CNMR and by mass spectroscopy.Results:All the synthesized compounds were confirmed by spectroscopical techniques and evaluated for antimicrobial activity against Staphylococcus aureus（S.aurius）,Bacilus subtilus（B.subtilus）,and Escheria coli （E.coli）.These compounds showed antibacterial activity（zone of inhibition） against S.aurius ranged from 3 mm to 9 mmin diameter,B.subtilus,4 -8 mm,and E.coli 5 -12 mm.Out of 2a-2e, only 2a and 2b showed some sort of activity but none of them had considerable activity compared with that of the standard.Conclusions:All the synthesized compounds show moderate activity against the tested bacteria S.aurius,B.subtilus,and E.coli.So,further structural modification is necessary to improve the antibacterial action of 2-substituted-4,5-diphenyl-N-alkyl imidazole derivatives.

Compaction of coated multi-particulates

There has been a strong interest for controlled release solid dosage forms,and to achieve controlled release,coating of particulates is often attempted to modify drug release.Due to the disadvantages of coated single-unit dosage forms,such as occurrences of dose dumping and local irritation,coated multiparticulates are often preferred.However,coated multiparticulates are often filled into capsules.Compressed tablet dosage form is more desirable than capsules as the unit production costs of tablets are lower and tablet presses are more common.

磷酸锆镍上的醇选择性氧化（英文）

Nickel zirconium phosphate nanoparticles were found to function as efficient catalysts for the selective oxidation of a wide range of alcohols to their corresponding ketones and aldehydes using H2O2 as an oxidizing agent and without any organic solvents, phase transfer catalysts, or additives. The steric and electronic properties of various substrates had significant influence on the reaction conditions required to achieve acetylation. The results showed that this method can be applied for the chemoselective oxidation of benzyl alcohols in the presence of aliphatic alcohols. The catalyst used in the current study was characterized by ICP-OES, XRD, NH3-TPD, Py-FTIR, N2 adsorption-desorption, SEM and TEM. These analyses revealed that the interlayer distance in the catalyst increased from 0.75 to 0.98 nm when Ni2+ was intercalated between the layers, whereas the crystallinity of the material was reduced. The nanocatalyst could also be recovered and reused at least seven times without any discernible decrease in its catalytic activity. This new method for the oxidation of alcohols has several key advantages, including mild and environmentally friendly reaction conditions, short reaction time, excellent yields and a facile work-up.

磷酸锆铁催化无溶剂条件下醇和苯酚乙酰化(英文)

Iron zirconium phosphate(ZPFe) nanoparticles were found to function as an efficient catalyst for the acetylation of a wide range of alcohols and phenols using acetic anhydride, generating good to excellent yields under solvent-free conditions. The steric and electronic properties of various sub-strates had a significant influence on the reaction conditions required to achieve the acetylation. The catalyst used in the current study was characterized by inductively coupled plasma-optical emission spectrometry, X-ray diffraction, N2 adsorption-desorption, scanning electron microscopy, and transmission electron microscopy. These analyses revealed that the interlayer distance in the catalyst increased from 7.5 to 9.3 when Fe3+ was intercalated between the layers, whereas the crystallinity of the material was reduced. This nanocatalyst could also be recovered and reused at least six times without any discernible decrease in its catalytic activity. This new method for the acetylation of alcohols and phenols has several important advantages, including mild and environ-mentally friendly reaction conditions, as well as good to excellent yields and a facile work-up.

Sodium alginate ameliorates indomethacin-induced gastrointestinal mucosal injury via inhibiting translocation in rats

AIM:To investigate the effects of sodium alginate(ALNa)on indomethacin-induced small intestinal lesions in rats.METHODS:Gastric injury was assessed by measuring ulcerated legions 4 h after indomethacin(25 mg/kg)administration.Small intestinal injury was assessed by measuring ulcerated legions 24 h after indomethacin(10mg/kg)administration.AL-Na and rebamipide were orally administered.Myeloperoxidase activity in the stomach and intestine were measured.Microvascular permeability,superoxide dismutase content,glutathione peroxidase activity,catalase activity,red blood cell count,white blood cell count,mucin content and enterobacterial count in the small intestine were measured.RESULTS:AL-Na significantly reduced indomethacininduced ulcer size and myeloperoxidase activity in the stomach and small intestine.AL-Na prevented increases in microvascular permeability,superoxide dismutase content,glutathione peroxidase activity and catalase activity in small intestinal injury induced by indomethacin.AL-Na also prevented decreases in red blood cells and white blood cells in small intestinal injury induced by indomethacin.Moreover,AL-Na suppressed mucin depletion by indomethacin and inhibited infiltration of enterobacteria into the small intestine.CONCLUSION:These results indicate that AL-Na ameliorates non-steroidal anti-inflammatory drug-induced small intestinal enteritis via bacterial translocation.

Determination of metronidazole in a rat stomach by HPLC for obtaining basic data of the eradication therapy of Helicobacter pylori

In the eradication therapy of Helicobacter pylori changes of antibiotics as these concentrations or amount in the stomach after oral administration were not clear. A simple and accurate method for determining the concentration of metronidazole （MTZ） in homogenate of rat stomach was developed in order to obtain basic data to design a pharmaceutical preparation having targeting ability to the surface of gastric-mucosa. This method included a deproteinization process by methanol, separation with reversed-phase high-performance liquid chromatography, and detection with an ultraviolet wavelength of 370 nm. Regression analysis showed that the method was linear over a standard curve nmge from 5 ug/mL to 2000 g/mL. The inter-day precision and accuracy values between thc ranges were 5.0% or better and -7.5 to 5.2%, respectively. The newly developed method was applied to an analysis of gastric samples after oral administration of MTZ at a dose of 5 mg/kg. It was found that the residual MTZ in the stomach was determined within 5 h after dosing. This method is useful for monitoring MTZ in stomach after its oral administration to rats.

Preparation of slab-shaped lactose carrier particles for dry powder inhalers by air jet milling

Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.

QSAR analysis on benzodithiazine derivatives as HIV-1 integrase inhibitors

Objective:Inhibition of HIV-1 integrase is an important strategy for the treatment of HIV and AIDS.There-fore, HIV-1 integrase inhibitory activity of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines has been analyzed with different physicochemical parameters.Methods:In the present work,quantitative structure activity relationship studies were performed on a series of benzodithiazines as HIV-1 integrase inhibitors using the modeling software Win CAChe version 6.1.Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated for statistical significance and predictive power by internal and external validation.Results:The best QSAR models were having good correlation coefficient (r) with low standard error of estimation(SEE) and cross validated square of correlation coefficient (q^2 ).The robustness of the models was checked by Y-randomization test and they were identified as good predictive models.The model for HIV integrase(wt) inhibitory activity of benzodithiazines suggest that the increase of dipole moment(Z) of molecules leads to reduce 3’processing and strand transfer inhibitory activity, substitution with high electro positive groups is conducive for the 3’processing inhibitory activity,and the increase in heat of formation is favorable for 3 -processing and strand transfer inhibitory activity.Conclusion: The model for HIV integrase(C65s) inhibitory activity of benzodithiazines suggest that the increase of dipole moment(X) of molecules leads to reduce 3’processing and strand transfer inhibitory activity,and the substitution with high hydrophobic groups is conducive for the 3’processing and strand transfer inhibitory.

Evaluation of in vitro antioxidant, antiglycation and antimicrobial potential of indigenous Myanmar medicinal plants

Objective： Myanmar has a long history of using medicinal plants for treatment of various diseases. To the best of our knowledge there are no previous reports on antiglycation activities of medicinal plants from Myanmar. Therefore, this study was aimed to evaluate the antioxidant, antiglycation and antimicrobial properties of 20 ethanolic extracts from 17 medicinal plants indigenous to Myanmar. Methods： In vitro scavenging assays of 2,2-diphenyl-l-picrylhydrazyl （DPPH）, nitric oxide （NO）, superoxide （SO） radicals were used to determine the antioxidant activities. Folin-Ciocalteu＇s method was performed to determine the total phenolic content. Antiglycation and antimicrobial activities were detected by bovine serum albumin-fluorescent assay and agar well diffusion method. Results： Terminalia cbebula Retz. （Fruit）, containing the highest total phenolic content, showed high antioxidant activities with inhibition of 77.98% ± 0.92% 88.95% ± 2.42%, 88.56% ±1.87% and 70.74% ±2.57% for DPPH, NO, SO assays and antiglycation activity respectively. It also showed the antimicrobial activities against Staphylococcus aureus, Bacillus cereus, Escherichia coil, Pseudomonas aeruginosa and Candida albicans with inhibition zone of 19, 18, 17, 25 and 15 ram, respectively. Garcinia mangostana Linn. showed the strongest activities for SO and antiglycation assays with inhibition of 93.68% ± 2.63% and 82.37%± 1.78%. Bark of Melia sp. was the best NO radical scavenger with inhibition rate of 89.39%± 0.60%. Conclusion： The results suggest that these plants are potential sources of antioxidants with free radical-scavenging and antiglycation activities and could be useful for decreasing the oxidative stress and glycation end-product formation in glycation-related diseases.

SYNTHESIS AND CHARACTERIZATION OF NOVEL OPTICALLY ACTIVE POLY(AMIDE-IMIDE)S AND POLY(ESTER-IMIDE)S CONTAINING CALIX[4]ARENE AND AMINO ACID UNITS WITH BINDING ABILITY TOWARDS ALKALI METAL AND TOXIC HEAVY METAL CATIONS

A novel calix[4]arene derivative 2 with amino functional groups at the lower rim was first prepared via introduction of nitro functional groups and amination of the dinitro derivative of calix[4]arene. The optically active monomers were synthesized by dehydration of L-leucine （and L-isoleucine） and 3,3＇,4,4＇-benzophenonetetracarboxylic- 3,3＇,4,4＇-dianhydride （3） followed by reaction with thionyl chloride to form 5a and 5b. Two methods, polymerization under microwave irradiation and solution polymerization in CH2Cl2/TEA, were then employed to carry out the condensation polymerization of 2 with the optically active monomers 5a and 5b, respectively. The polymerization conditions affected the kind of resulting polymers, poly（amide-imide）s （PAIs） 6a and 6b and poly（ester-imide）s （PEIs） 6a＇ and 6b＇ were obtained selectively in good yields and moderate inherent viscosities. Sorption-extraction experiments were carried out using cram picrate extraction method and verified good binding ability of the resulting calixarene-based polymers towards silver, alkali metal and toxic heavy metal cations. Also thermogravimetric analysis indicated that the resulting PAIs and PEIs were thermally stable.