Aryloxyphenylpiperazinylpropanols are a group of compounds exhibiting a wide range of biological activities, affecting the central nervous system and many cardiovascular mechanisms among them. As cardiovascular agents, aryloxyphenylpiperazinylpropanols work as antihypertensives, antiarrhythmics, cardiotonics or antiaggregants. The mechanism of action is almost always an α1-adrenolytic or combined α1- and β-adrenolytic effect, but sometimes other mechanisms (e.g., Ca2+ antagonism or phosphodiesterase inhibition) can positively participate. In some cases, compounds with a small modification of the connecting chain also exhibit the desired cardiovascular effects. Several studies dealt with chirality of aryloxyphenylpiperazinylpropanols and determined the differences between the particular activities of racemic and enantiomeric compounds.
- MeSH
- kardiovaskulární látky chemie farmakologie MeSH
- piperaziny chemie MeSH
- propanolaminy chemie farmakologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Autologous vein grafts used as aortocoronary bypasses are often prone to intimal hyperplasia, which results in stenosis and occlusion of the vein. The aim of this study was to prevent intimal hyperplasia using a newly developed perivascular system with sustained release of sirolimus. This system of controlled drug release consists of a polyester mesh coated with a copolymer of L-lactic acid and epsilon-caprolactone that releases sirolimus. The mesh is intended for wrapping around the vein graft during surgery. The mesh releasing sirolimus was implanted in periadventitial position onto arteria carotis communis of rabbits, and neointimal hyperplasia was then assessed. We found that implanted sirolimus-releasing meshes reduced intima thickness by 47+/-10 % compared to a vein graft after 3 weeks. The pure polyester mesh decreased vein intima thickness by 35+/-9 %. Thus, our periadventitial system for controlled release of sirolimus prevented the development of intimal hyperplasia in autologous vein grafts in vivo in rabbits. A perivascularly applied mesh releasing sirolimus is a promising device for preventing stenosis of autologous vein grafts.
- MeSH
- hyperplazie prevence a kontrola MeSH
- kardiovaskulární látky farmakologie chemie MeSH
- králíci MeSH
- nosiče léků MeSH
- okluze cévního štěpu patologie prevence a kontrola MeSH
- polyestery MeSH
- proliferace buněk účinky léků MeSH
- sirolimus farmakologie chemie MeSH
- tunica intima patologie účinky léků MeSH
- venae jugulares patologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
This paper presents a systematic study of the retention behavior of a model bisdioxopiperazine drug, dexrazoxane (DEX) and its three polar metabolites (two single open-ring intermediates-B and C and an EDTA-like active compound ADR-925) on different stationary phases intended for hydrophilic interaction liquid chromatography (HILIC). The main aim was to estimate advantages and limitations of HILIC in the simultaneous analysis of a moderately lipophilic parent drug and its highly polar metabolites, including positional isomers, under MS compatible conditions. The study involved two bare silica columns (Ascentic Express HILIC, Atlantis HILIC) and two stationary phases with distinct zwitterionic properties (Obelisc N and ZIC HILIC). The chromatographic conditions (mobile phase strength and pH, column temperature) were systematically modified to assess their impact on retention and separation of the studied compounds. It was found that the bare silica phases were unable to separate the positional isomers (intermediates B and C), whereas both columns with zwitterionic properties (Obelisc N and ZIC HILIC) were able to separate these structurally very similar compounds. However, only ZIC HILIC phase allowed appropriate separation of DEX and all its metabolites to a base line within a single run. A mobile phase composed of a mixture of ammonium formate (0.5 mM) and acetonitrile (25:75, v/v) was suggested as optimal for the simultaneous analysis of DEX and its metabolites on ZIC HILIC. Thereafter, HILIC-LC-MS analysis of DEX and all its metabolites was performed for the first time to obtain basic data about the applicability of the suggested chromatographic conditions. Hence, this study demonstrates that HILIC could be a viable solution for the challenging analysis of moderately polar parent drug along with its highly polar metabolites including the ability to separate structurally very similar compounds, such as positional isomers.
- MeSH
- chemické modely MeSH
- chromatografie kapalinová metody MeSH
- ethylendiaminy chemie izolace a purifikace MeSH
- glycin analogy a deriváty chemie izolace a purifikace MeSH
- hydrofobní a hydrofilní interakce MeSH
- kardiovaskulární látky chemie izolace a purifikace MeSH
- koncentrace vodíkových iontů MeSH
- razoxan chemie izolace a purifikace MeSH
- tandemová hmotnostní spektrometrie MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Autologous vein grafts are often used for treating damaged vessels, e.g. arteriovenous fistulas or arterial bypass conduits. Veins have a different histological structure from arteries, which often leads to intimal hyperplasia and graft restenosis. The aim of this study was to develop a perivascular sirolimus-delivery system that would release the antiproliferative drug sirolimus in a controlled manner. Polyester Mesh I was coated with purasorb, i.e. a copolymer of L-lactide and ɛ-caprolactone, with dissolved sirolimus; Mesh II was coated with two copolymer layers; the layer with dissolved sirolimus was overlaid with pure purasorb. This arrangement allowed sirolimus to be released for 6 and 4 weeks, for Mesh I and Mesh II, respectively. Mesh II released sirolimus more homogeneously, without the initial burst effect during the first week. However, the cumulative release curve was steeper at later time points than the curve for Mesh I. Both meshes inhibited proliferation of rat vascular smooth muscle cells during 14-day culture in vitro and preserved excellent cell viability. Newly developed sirolimus-releasing perivascular meshes are promising devices for preventing autologous graft restenosis.
- MeSH
- biokompatibilní potahované materiály MeSH
- chemie farmaceutická MeSH
- farmaceutická technologie metody MeSH
- kardiovaskulární látky aplikace a dávkování chemie farmakologie MeSH
- kinetika MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- léky s prodlouženým účinkem MeSH
- mikroskopie elektronová rastrovací MeSH
- molekulová hmotnost MeSH
- myocyty hladké svaloviny účinky léků MeSH
- nosiče léků MeSH
- okluze cévního štěpu prevence a kontrola MeSH
- polyestery chemie MeSH
- potkani Wistar MeSH
- povrchové vlastnosti MeSH
- příprava léků MeSH
- proliferace buněk účinky léků MeSH
- rozpustnost MeSH
- sirolimus aplikace a dávkování chemie farmakologie MeSH
- stabilita léku MeSH
- svaly hladké cévní účinky léků MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Práce se věnuje syntéze a studiu některých fyzikálně-chemických vlastností skupiny látek, potenciálníchantagonistů beta-adrenergních receptorů. Látky jsou hydrochloridy derivátů aryloxyaminopropanolu,kde bázickou část tvoří difenylmethylpiperazin a modifikována je aromatická částalkylestery (methyl až butyl) kyseliny karbamové v polohách 2-, 3-, 4-. Zastoupení prvků bylopotvrzeno elementární analýzou. Látky byly charakterizovány teplotou tání IČ a UV spektry. Bylastanovena jejich rozpustnost a povrchová aktivita. Pomocí TLC byla sledována čistota připravenýchlátek.
The paper is devoted to the synthesis and study of some physico-chemical properties of a group ofsubstances – potential antagonists of beta-adrenergic receptors. The substances are derivatives ofaryloxyaminopropanol, where the basic part consists of diphenylmethylpiperazine and the aromaticpart is modified with alkyl esters (methyl to butyl) of carbamic acid in positions 2-, 3-, 4-. Therepresentation of the elements was confirmed by elemental analysis. The substances were characterizedby melting point, IR and UV spectra. Their solubility and surface acitivity were determined.The purity of prepared substances was examined by means of TLC.
- MeSH
- beta blokátory farmakologie chemie MeSH
- chemie farmaceutická metody statistika a číselné údaje MeSH
- chromatografie na tenké vrstvě metody MeSH
- finanční podpora výzkumu jako téma MeSH
- kardiovaskulární látky chemická syntéza chemie MeSH
- propanolaminy farmakologie chemická syntéza chemie MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- kardiovaskulární látky farmakologie chemie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
