RESUMEN

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

Asunto(s)

RESUMEN

In pursuing the study on pyridodiazepinone derivatives, in order to verify the variation of biological activity induced by replacement of the heteroaromatic with an aromatic nucleus and by the introduction of chlorine on the benzene ring, a series of 1-[(dialkylamino)alkyl]-4-phenyl-1,3-dihydro-2H-1,4-benzodiazepin- 2-ones and of 7-chloro-analogues were prepared. Some benzodiazepinones and their 7-chloro-analagous were subjected to pharmacological experimentation in order to evaluate and compare their effect upon mice with regard to exploratory activity, motor coordination and spontaneous motility. In addition their anti-strychnine, anti-cardiazole, anti-amphetamine and anti-reserpine activities were also evaluated.

Asunto(s)

RESUMEN

Five 1-lupinyl-3R'-6R"-quinoxalin-2(1H)-ones were tested in mice for acute toxicity, explorative activity inhibition, analgesic activity and for antagonism against physostigmine, strychnine and pentylentetrazol (cardiazol). As reference compounds were used chloropromazine, morphine, atropine and diazepam respectively. All tested compounds inhibit the explorative activity and exhibit high analgesic activity. Compound (I) protects completely the animals from physostigmine toxicity, while compound (IV) antagonizes, although only slightly, all the toxicants tested.

Asunto(s)

RESUMEN

Eight tert-aminoalkyl derivatives of 3-methyl-6R-quinoxalin-2-one, 3-methyl-6/8-azaquinoxalin-2-ones and 3-methyl-6,8-diazaquinoxalin-2-one, previously selected for their deconditioning activity in rats were now tested in mice for analgesic, explorative and incoordinating (muscle relaxant) activities; acute toxicity was also determined. Several compounds show a good degree of activity in the tests used.

Asunto(s)

RESUMEN

By condensating ethyl pyruvate with 4-dialkylaminoalkyl-5-aminopyrimidine, obtained by hydrogenolysis of the corresponding 6-chloroderivatives, were prepared 3-methyl-6,8-diazaquinoxalinee-2(1H)-ones which carry on position 1 a tert-aminoalkyl chain (dimethylaminoethyl-, morpholinylethyl-, dimethylaminopropyl- and N-methylpiperazinylpropyl-). The synthetized compounds were tested to verify the effects on acquisition and modification of a conditioned avoidance response (C.A.R.) in rats. In these tests 1-dimethylaminoethyl-3-methyl-6,8-diazaquinoxalin-2(1H)-one, shows activity comparable with that of the cloropromazine.

Asunto(s)

RESUMEN

Eight derivatives of 3-methyl-6-azaquinoxalin-2(1H)-one and of 3-methyl-8-azaquinoxalin-2(1H)-one were prepared. They bear on position 1 an aminoalkyl chain (dimethylaminoethyl, morpholinylethyl, dimethylaminopropyl and N-methylpiperazinylpropyl). Three of these compounds exhibit a high degree of deconditioning activity on rats; compound (I) is particularly active on the acquisition of a conditioned avoidance response, while compound (II) is more active than chloropromazine on the modification of a C.A.R. Compound (II) is characterized also by low toxicity.

Asunto(s)

RESUMEN

Sixteen derivatives of 3-methylquinoxalin-2(1H)-one were prepared; they are variously substituted on position 6 (R = H, COCH3, OCH3, CF3) and bear on position 1 an aminoalkyl chain (dimethylaminoethyl, dimethylaminopropyl, N-methylpiperazinylpropyl and morpholinylethyl). Most of these compounds exhibit a high degree of deconditioning activity on rats; compound (X) is significantly more active than chlorpromazine in the tests used.

Asunto(s)

Asunto(s)