- Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance
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A series of polycationic gene delivery vectors were synthesized via Michael addition from low molecular weight PEI and linking compounds with various heteroatom compositions. Agarose gel electrophoresis results reveal that these polymers can well condense plasmid DNA and can protect DNA from degradation by nuclease. The formed polyplexes, which are stable toward serum, have uniform spherical nanoparticles with appropriate sizes around 200-350 nm and zeta-potentials about +40 mV. In vitro experiments show that these polymers have lower cytotoxicity and higher transfection efficiency than 25 KDa PEI. Furthermore, the title materials exhibit excellent serum tolerance. With the present of 10% serum, up to 19 times higher transfection efficiency than PEI was obtained, and no obvious decrease of TE was observed even the serum concentration was raised to >40%. Flow cytometry and confocal microscopy studies also demonstrate the good serum tolerance of the materials.
- Xun, Miao-Miao,Xiao, Ya-Ping,Zhang, Ji,Liu, Yan-Hong,Peng, Qi,Guo, Qian,Wu, Wan-Xia,Xu, Yong,Yu, Xiao-Qi
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- Synthetic transformations of higher terpenoids: XXXII.*synthesis of 16-alkenyl-substituted labdatrienes by oxidative coupling of methyl phlomisoate with alkenes
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Reactions of methyl phlomisoate with methyl acrylate, phenyl acrylate, methyl vinyl ketone, phenyl vinyl ketone, or N-substituted acrylamides catalyzed by Pd(OAc)2 in the presence of Cu(OAc)2, p-benzoquinone in the mixture of propionic acid and acetonitrile proceed regio- and stereoselectively with the formation of (E)- 16-vinyl labdatrienoates. The oxidative coupling under these conditions of the methyl phlomisoate with styrene results in a mixture of 15,16-distyryl-, 16-styryl-, and 16-(1-phenylvinyl)-derivatives of furanolabdanoid. Pleiades Publishing, Ltd., 2013.
- Kharitonov,Kremenko,Shults,Shakirov,Tolstikov
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p. 1690 - 1702
(2014/02/14)
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- NOVEL PROCESS FOR THE PREPARATION OF CISATRACURIUM BESYLATE
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The present invention is related to a novel process for the preparation of cisatracurium besylate, more particularly optically and geometrically pure cisatracurium besylate in large scale.
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Page/Page column 7; 10; 11
(2010/11/18)
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- Hydroxy functional acrylate and methacrylate monomers prepared via lipase-catalyzed transacylation reactions
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Candida antarctica lipase B (CAL-B, Novozyme 435) catalyzes the transacylation of methyl acrylate and methyl methacrylate with diols and triols in 2-methyl-2-butanol at 50 °C. Under the experimental conditions, up to 70 mol% of the acyl donor methyl acrylate was converted. Methyl methacrylate is the less efficient acyl donor (up to 60 mol%) due to the higher sterical hindrance in the enzymatic transacylation. Under the reaction conditions high yields of the mono-acylated products are obtained, which contain minor amounts of bis(meth)acrylates. In addition it was observed that Novozyme 435 catalyzes regioselectively the acylation of the primary hydroxyl groups. In comparison with the chemical catalyzed route no selectivity was observed for unsubstituted diols. For substituted diols more mono-acylated product was formed in the lipase-catalyzed reaction than in the chemical catalyzed reaction.
- Popescu, Dragos,Hoogenboom, Richard,Keul, Helmut,Moeller, Martin
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experimental part
p. 80 - 89
(2010/08/20)
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- The in vitro degradation of cisatracurium, the R, cis-R'-isomer of atracurium, in human and rat plasma
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Objective: To assess the mechanism and rate of in vitro degradation of cisatracurium in aqueous buffer and in human and rat plasma. Methods: Cisatracurium was incubated in aqueous buffer at various pH values or in human and rat plasma maintained at pH 7.4 with HEPES buffer. Cisatracurium and the degradation products, laudanosine and the monoquaternary alcohol, were quantitated by HPLC with use of fluorescence detection. Results: In Soerenson's phosphate buffer, cisatracurium degraded spontaneously by a chemical process commonly reffered to as "Hofmann elimination." The rate of degradation increased with increasing pH. From pH 6.4 to 7.8 there was a 6.5-fold increase in the rate of degradation of cisatracurium and, on a molar basis, the final decomposition product laudanosine accounted for all of the drug. At a pH of 7.4, cisatracurium degraded with a half-life of about 34.1 +/- 2.1 minutes. Cisatracurium incubated in human plasma degraded with a mean (+/- SD) half-life of 29.2 +/- 3.8 minutes, which is consistent with Hofmann elimination. Besides laudanosine, and unlike that observed in Soerenson's phosphate buffer, significant amounts of the monoquaternary alcohol were formed that slowly degraded to laudanosine. The micromoles of laudanosine formed eventually accounted for the total amount of cisatracurium incubated with human plasma. The monoquaternary alcohol appears to be a product of ester hydrolysis of a monoquaternary acrylate formed during the firts step in Hofmann elimination. Evidence for esterase involvement at this step in the degradation of cisatracurium was based on inhibition studies with O-cresyl benzodioxaphosphorin oxide (CBDP), a specific carboxylesterase inhibitor. The addition of CBDP to human plasma completely blocked the formation of monoquaternary alcohol and converted the degradation of cisatracurium to total Hofmann elimination. In rat plasma cisatracurium was hydrolyzed, with a half-life of only 3 1/2 minutes, by carboxylesterases. The addition of CBDP increased the half-life to 25 minutes, which is consistent with Hofmann elimination. Conclusion: In human plasma the rate-limiting step in the degradation of cisatracurium is Hofmann elimination, with the initial formation of a monoquaternary acrylate. The observation that the monoquaternary alcohol results from ester hydrolysis of the monoquaternary acrylate by plasma esterase(s) explains the presence of the monoquaternary alcohol metabolite in human plasma during clinical studies with cisatracurium. The rapid hydrolysis of cisatracurium by rat plasma relative to human indicates a major species difference in plasma esterase(s).
- Welch, Richard M.,Brown, Alan,Ravitch, Josh,Dahl, Ray
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p. 132 - 142
(2007/10/03)
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- Neuromuscular blocking agents
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1R-cis,1'R-cis isomer of a 2',2'-(3,11-dioxo-4,10-dioxatridecylene)-bis(1,2,3,4-tetrahydro-6, 7-dimethoxy-2-methyl-1-veratrylisoquinolium) said, substantially free from other geometrical and optical isomers thereof. The 1R-cis,1'R-cis isomer has been found to have an advantageous combination of pharmacological properties, notably greater neuromuscular blocking potency, weaker histamine-releasing potency, and at equivalent levels of neuromuscular blockade, fewer potential adverse effects on the autonomic nervous system (sympathetic and parasympathetic blockage), in comparison with the known mixture of geometrical and optical isomers.
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