Showing papers in "Bollettino chimico farmaceutico in 2004"

Assessment of quality control parameters and interchangeability of multisourced metformin HCl tablets marketed in Nigeria.

Abstract: A quality control assessment of five brands of metformin hydrochloride tablets marketed in Nigeria [Glucophage (R) (Merck, Quetta), Metformin BDC (Bangkok labs, Bangkok), Metformin (Medopharm, India), Glucophage (R) (Ilsan), Glucophage (Lipha)] was carried out in order to determine the brands that are interchangeable or switchable. The disintegration time, dissolution rate and absolute drug content were determined in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. The weight uniformity and hardness tests were also performed according to the official methods. A variation of the concept of dissolution efficiency (DE), known as predicted availability equivalent (PAE), was used to predict the likely in vivo bioavailability. Our results showed that all the five brands passed the uniformity of weight and disintegration tests. Dissolution efficiency was found to be higher in SGF than in SIF. In SGF, all the brands were bioequivalent. In SIF, all the brands, except Medopharm, were also bioequivalent. The study showed that four brands of metformin hydrochloride (Merck, BDC, Lipha and Ilsan) marketed in Nigeria are of acceptable standards and hence BDC, Lipha and Ilsan brands of glucophage are interchangeable with the innovator drug, glucophage R (Merck).

Tetrazolo[1,5-a] quinoline derivatives as anti-inflammatory and antimicrobial agents [1].

Abstract: Tetrazolo[1,5-a]quinoline derivatives bearing in the 4-position various thiazolidinone 3a-c, 5a-c and 7a-c, thiazinone 8a,b, thiazoline 9a-d and thiadiazoline 10a,b moieties have been synthesized and evaluated for anti-inflammatory activity and antimicrobial properties. The synthetic routes involved the reaction of tetrazolo[1,5-a]quinoline-4-carboxaldehyde 1 with amines and hydrazines to give the corresponding aniles 2a-c and hydrazones 4a-c respectively The latter compounds when treated with thioglycolic acid, furnished the corresponding thiazolidinone derivatives 3a-c and 5a-c. Moreover; thiosemicarbazone 6a-c derivatives were subsequently cyclized by various reagents giving rise the title compounds. Some of the products proved to possess potent anti-inflammatory and antimicrobial properties.

Analgesic and anti-inflammatory activities of (-)-o benzyl cubebin, a (-)-cubebin derivative, obtained by partial synthesis.

Abstract: The anti-inflammatory and antinociceptive effects of the benzylated cubebin derivative, obtained by reaction of (-)-cubebin with benzyl bromide, were investigated using different animal models. The (-)-o-benzyl cubebin showed a low anti-inflammatory effect (16.2%) in relation to cubebin (57%) and indomethacin (77%) in the carrageenin-induced paw edema in rats, but on the other hand it was more effective (80%) than (-)-cubebin (41%) in inhibiting acetic acid-induced writhing in mice, producing dose-response correlation with doses of 10, 20 and 40 mg/kg, respectively. Moreover, this derivative compound did not show activity in both the hot plate and the cell migration test in rats. Overall, the results showed that the benzylation of cubebin were efficient in enhancing only its analgesic activity.

Study of insolubility problems of dexamethasone and digoxin: cyclodextrin complexation.

Abstract: Cyclodextrins are able to form inclusion complexes with a number of drugs if their molecular dimensions correspond to those of the cyclodextrin cavity which leads to change of physicochemical and biopharmaceutical properties of drugs. 2-Hydroxypropyl beta cyclodextrin (HP beta CD) is suitable for parenteral application because of its considerable solubility in water and low hemolytic activity. Digoxin is insoluble in water, sensitive to light and is a subject of acidic hydrolysis, it is a challenge to the technologists of parenteral dosage forms. Dexamethasone (Dex) has a very small solubility in water (0.1 mg/ml), which caused troubles by preparing liquid medicine forms. The inclusion of hydroxy acids in CD-complexes in the necessary molar proportions leads to considerable increase in the solubility of a medicine and to several times decrease of the amount of CD used. Inclusion complexation was confirmed by the results from the studies of Differential Scanning Calorimetry. The present investigation demonstrated that Digoxin/CD complex shows stability in water medium and the optimum molar ratio Digoxin/HP beta CD is 1:6. The same results can be achieved through HP beta CD, by including Dex in a multicomponent composition containing HP beta CD and citric acid in a molar ratio of 1:4:1.

Influence of salt form and concentration on the absorption of magnesium in rat small intestine.

Abstract: The influence of magnesium concentration and salt form on the absorption of this element in the rat small intestine was investigated. The following magnesium salts were studied: gluconate, fumarate, and chloride. At 1 and 5 mM concentrations absorption was most efficient from gluconate whereas at 10 mM absorption from fumrate was more efficient. Mg2+ absorption half-life (t50%) varied with salt and concentration. The Mg2+ absorption half-life for magnesium gluconate at 10 mM concentration was 42 times as long as at 1 mM concentration. The biggest area under the curve, which characterizes substance bioavailability, was observed for each of the investigated salts at 5 mM. Therefore, we may conclude that magnesium administration at 5 mM concentration would be optimal.

Bioequivalence study of sildenafil citrate tablets in healthy human volunteers.

Abstract: Newly developed sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate (c-GMP) specific phosphodiesterase type 5 (PDE 5) in the corpus cavernosum is used for the oral treatment of erectile dysfunction. A convenient, sensitive and simple method for the determination of sildenafil in human plasma is presented. The analytical technique was based on reversed-phase high-performance liquid chromatography coupled with UV detector set at 295 nm. Rofecoxib was used as internal standard (I.S). Liquid-liquid extraction using diethyl ether was performed to recover sildenafil and rofecoxib. The retention time of I.S and sildenafil were 5.5 minutes and 7.2 minutes respectively. The method was validated over a linear range of 10 to 1000 ng/ml from plasma. Separate stability study showed that sildenafil is stable under conditions of analysis. The extraction efficiency from plasma varied from 79.69% to 81.13 %. The minimum quantifiable concentration was set at 10 ng/ml. (%o CV<12.5%). The method was used for Bioequivalence Study of Two Brands of Sildenafil citrate 50 mg tablets in healthy human volunteers. All pharmacokinetic parameter were calculated along with statistical evaluation.

Synthesis and biological evaluations of sulfa derivatives bearing heterocyclic moieties.

Abstract: Some new sulfa derivatives bearing a heterocyclic moieties fural, pyrimidinone, thiazolidinone, benzimidazole and 1,2,4-triazinone and the related compounds 2-19 have been synthesized from treatment of sulfa drugs with thioisocyanate, acid chlorides, 3-chloro-1,2,4-triazines, aldehydes, esters and/or 2-methylbenzoxazole followed by ring closure reactions. Structures of the products have been deduced from their elemental analysis and spectral data. Significant antimicrobial activities were observed in vitro for some members of the series. Compounds 9b, 16 are highly active, while compounds 4b, 6d, 7,9a, 10 and 14 showing a moderate active towards gramme positive bacterium (b.subtilis). gramme negative bacterium (E. coli) and two fungi namely (A.nidulans & A.terreus).

The influence of some aminoalkanolic xanthone derivatives on central nervous and cardiovascular systems in rodents.

Abstract: A series of appropriate aminoalkanolic derivatives 2- or 4-methylxanthone was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (scPtz) assays, and for neurotoxicity (TOX). The most interesting result was the anticonvulsant activity of (R,S)-2N-(6-chloro-2-xanthonemethyl-2N-methylamino-1-propanol hydrochloride (II, which displayed anti-MES and anti-scPtz activity. Some of the obtained compounds (I - IV and V - VII) were also tested for their effect on the circulatory system (the effect on normal electrocardiogram, protection against adrenaline-, barium-, calcium- and/or strophanthine-induced arrhythmias, the effect on the arterial blood pressure and respiratory movements) and acute toxicity.

Spectrophotometric determination of captopril with DTNB reagent in pharmaceutical formulation.

Abstract: A simple and sensitive spectrophotoimetric method has been developed for the determination of captopril in its dosage form. The method is based on the reaction of the drug with DTNB reagent in pH 8 to produce a yellow coloured species measurable at 412 nm. The absorbance-concentration plot is linear over the range 1-10, * 10 - 5 M with correlation coefficient of 0.997. The molar absorptivity and minimum delectability were 13553 and 3.2 x 10 - 7 respectively. The proposed method was applied successfully for determination of captopril in its tablets form. The mean quantity and recovery were found to be 25.01 ′ 2% and 100.04 ′ 2% (each tablet contain 25 mg captopril). Quantification of the same tablets was determined, by a standard method such as HPLC. The Mean quantity of each tablet was found to be 25.07 ′ 1.22% by using HPLC method. It was not statistically significant difference between Eliman's and PtC method. This proposed method can be successfully applied to the determination of captopril in water and its dosage form and can use instead HPLC.

Hyperhomocysteinemia is a risk marker for development of maternal pre-eclampsia

Abstract: The objective of the current study was to determine whether homocysteine elevations precede the development of pre-eclampsia. and to examine the relationship between the occurrence of pre-eclampsia and the degree of hyperhomocysteinemia, so as to find a new prognostic parameter for women with liable to develop pre-eclampsia. The study comprised 203 pregnant females chosen of those attending the Antenatal Care Unit at Benha University Hospital and accepted to donate blood samples at the l6 t h week of gestation. Women, who delivered at Benha University Hospital, were retrospectively allocated into two groups: Control group (Group C): comprised 64 (71.1%) parturient, who completed their full term pregnancy without the development of pre-eclampsia. Pre-eclampsia group (Group PEc): comprised 26 (28.9%) parturient who developed pre-eclampsia throughout their course of pregnancy, but had, completed their full term pregnancy. Through the present study, estimated fasting plasma tHcys levels were higher than the 90 t h percentile of the control group (≥5.1 ng/dl) in 6(9.4%) women in group C and in 9 (34.6%) in group PEc. There was a significant (P<005) increase of fasting plasma tHeys levels in nullipara pre-eclamptic parturient as compared to multiparous control parturient. Also, a negative significant correlation was reported between parity and the fasting plasma tHcys level in pre-eclamptic parturient. The present results showed a significant increase of fasting plasma tHcys level in obese women with a positive significant correlation between fatting plasma tHcys level and BMI in PEc group. Thus, it can be concluded that hyperhomocysteinemia is an indirect risk factor for placental vasculopatky predating clinical pre-eclampsia, and can be used as a biomarker for identifying women at risk of complicalions and adverse Pregnancy outcomes.

Synthesis of some thiazolyl and thiadiazolyl derivatives of 4(3H)-quinazolinone as anti-inflammatory-antimicrobial agents.

Abstract: This paper describes the synthesis of four series of 4(3H)-quinazolinone derivatives. The first series was prepared by cyclization of the intermediate 3-aryl-2-substituted thiocarbamoylhydrazonomethyl-4(3H)-quinazolinones 2a,b with ethyl bromoacetate to afford the corresponding thiazolidinonyl derivatives 3a,b. The second series were prepared by the cyclization of the intermediate 2a,b with phenacyl bromide or 4-substituted phenacyl bromide giving rise to thiazolinyl derivatives 4a-f. Furthermore, the thiazolidinonyl derivatives 5a,b were obtained by reaction of the intermediate 2a,b with thioglycolic acid. On the other hand, heating the intermediate 2a,b with acetic anhydride afforded the corresponding thiadiazolinyl derivatives 6a,b. Some of the synthesized compounds showed promising anti-inflammatory-antimicrobial activities.

Effect of 5-substituted benzylideneaminosalicylic acid on carrageenan-induced ulcerative colitis.

Abstract: Mesalazine, a drug of choice in the management of ulcerative colitis, was chemically modified as 5-(E)-substituted benazylideneaminosalicylic acid by condensing 5-aminosalicylic acid with selected. aryl aldehydes with an intention to improve its pharmacological profile. The tests were performed to study their anti-inflanmatosy effect on carrageenan-induced ulcerative, colitis in albino rats. The histopathological findings, serum transaminase level and lipid peroxide content in the intestine and liver were taken as indices of pharmacological activity. The azomethine derivative formed from salicylaldehyde (5-ASASB3) was found to have maximum activity and it reversed the disease symptoms in experimental animals. The azomethine derivative markedly reduces the ulcerative colitis when compared with parent molecule, mesalazine.

Biopharmaceutical and pharmacodynamic studies on topically applied diclofenac gel available in Indian market.

Abstract: In the present investigation, an attempt was made to study and compare, analgesic and anti-inflammatory activity produced by four marketed topical diclofenac formulations in order to justify their usefulness in the treatment of pain and inflammation. By using a diffusion cell, in vitro percutaneous permeation studies were carried out to correlate in vivo activity. The in vivo analgesic activity study was performed by tail flick method on Wistar albino rats. The anti-inflammatory activity was performed on rats by carrageenan induced inflammation. It was evident from the study that three among tested three gels; diclofenac permeated effectively through the skin and was able to elicit analgesic and anti-inflammatory responses. The study also indicated the presence of therapeutic inequivalence among the marketed topical formulation and the need of bio equivalency and therapeutic equivalency testing of marketed topical applications meant for therapeutic use.

Pharmacokinetics of selenium following oral administration selenium preparation in rabbits.

Abstract: The aim of study was to investigate the bioavailability of selenium after oral administration of selenium yeast. As a reference preparation was used sodium selenite. The preparations were investigated in rabbits, according to a randomized two way crossover design in the fasted state. Each animal was given selenium preparation in the form of the single oral dose 0.5 mg Se/kg body weight. A washout period of one week separated both treatment periods. The selenium concentration was determined in serum spectrofluorometry. The divalent equation of one-compartment model was the simplest formula describing the course of selenium changes in serum of rabbits and giving the pharmacokinetic parameters. Pharmacokinetic variables (mean maximum plasma concentration, mean time to reach maximum plasma concentration, and the mean area under the plasma concentration-time curve) were not statistically different for the two preparations. It can be concluded that the two selenium preparations are likely to be bioequivalent.

Photooxygenation of natural ã-terpinene.

Abstract: Photooxygenation reaction of a -terpinene (1) in the presence of tetraphenyl porphine (TPP) or Rose Bengal (RB) gave 2, 5-dihydroperoxy-1-isopropylene-4-methylene-cyclohexane (2), 3,6-dihydroperorxy-3-isopropyl-6-methyl-2,4-cyclohexadiene (3) and 1,2&4,5-diepoxy-1-isopropyl-4-methylcyclohexane (4). The epoxide 4 was also synthesised through the epoxidation reaction of a-terpinene (1) with m-chloroperbenzoic acid (mcpba).

Synthesis and biological evaluation of novel naphthoquinone derivatives as potential anticancer and antimicrobial agents.

Abstract: Four novel series of 1,4-naphthoquinone derivatives namely 2,3-disubstiuted 4-[(benzothiazol-2-yl)hydrazono]-1,4-dihydronaphthalen-1-one 4a-c, N1-(2,3-disubstituted-4-oxo-1,4-dihydronaphthalen-1-ylidene)-N2-(benzotriazol-1-yl)acetic acid hydrazide 5a-c, 2,3-disubstituted 4-[(5-aryl-2,3-dihyrothiazol-2-ylidene)hydrazono]-1,4-dihydronaphthalen-1-one 7a-c, and 3-methyl-2-substituted carbamoyl or thiocarbamoyl-hydrazinocarbonylmethylthio-1,4-dihydronaphthalene-1,4-dione 9a-c were synthesized. Three of the new compounds were chosen by NCI to be evaluated as anticancer agents and they showed promising activity. All the prepared compounds were tested as antimicrobial agents.

Novel nicotinate esters of vasodilatation activity.

Abstract: A variety of 2-substituted-4, 6-diaryl-3-pyridinecarboxylates 4 were obtained through aromatic nucleophilic substitution. reaction of secondary amines with 2-bromo-3-pyridinecarboxylate derivatives 3. The latters were obtained through bromination of 3-aryl-4-benzoyl-2-cyanobutyrates 2 in glacial acetic acid. However; reaction of primary aromatic amines with 2-bromopyridines 3 afforded 2-arylamino-3-pyridinecarboxylates 5 beside the unexpected 2-amino analogues 6. On the other hand, 3-hydroxy-1H-pyrazolo[3,4-b]pyridines 7 were isolated via reaction of 3 with hydrazine hydrate. Good to complete muscle relaxation of rabbit's jejunium, rat's uterus and rabbits aorta was observed during screening representative examples (3a, 4c, Sd, 5f and 6b) of the newly synthesized 3-pyridinecarboxylates indicating the vasodilatation and antihypertension activity for the tested compounds.

Synthesis and antimicrobial properties of 3-sulfonyl-1,2,3,4-tetrahydropyrimido [4,5-d] pyrimidines.

Abstract: The paper presents the synthesis of sulfonyl tetrahydro-pyrimido[4,5-d]pyrimidine derivatives as well as the antimicrobial activily of the obtained compounds. The investigations showed that the obtained sulforyl derivatives of pyrimido[4,5-d]-pyrimidines and especially the compounds with free amino group reveal interesting antibacterial and antifungal activity.

Synthesis and pharmaceutical activity of new series of chromonyl derivatives.

Abstract: A new syythesis of chromonyl based on the reaction of formylfurochromone (4,9-dimethoxy -5-oxo- 5H-furo[3,2-g][1] benzopyran -6- carbaldehyde) 1 with semicarbazide hydrochloride and thiosemicarbazide afforded 4,9-dimethoxy -5-oxo- 5H-furo[3,2-g] ][1] benzopyran - 6- yl- (1-aminovinyl) hydrazone derivatives 2a,b Also 4,5-Diphenyl-2- (4,9-dimethoxy -5-oxo-5H-furo[3,2-g][1] benzopyran - 6- yl)- imidazole 3 was obtained by refluxing compound 1 with 1,2- diketone in presence of ammonium acetate Reaction of compound 1 with different amines afforded 3- (4,9-dimethoxy -5-oxo- 5H-furo[3,2-g][1] benzopyran-6-yl)- aryliminoethyl derivatives 4a-g Condensation reaction of compounds 4a-d to C-Hacid compounds were given 4-aminosubstituted -5- (6-hydroxy - 4,7 -dimethoxy -5-oxo-5H-benzofuranyl)- pyrano]2,3-b] cyclohexa2,3-diene 5a-d and 2- methyl -3-methoxy -4-(4-methoxyphenylamine)- 5- (6-hydroxy- 4,7- dimethoxy-5-oxo-5H-benzofuranyl) 6 Refluxing compound 4d with thiosemicarbazide formed 6-methanimine- (4,9-dimethoxy-5-oxo- 5H-furo[3,2-g][1] benzopyran-6-yl)-(1E)-1-phenylethan-1-one thiosemicarbazide 7 Also, the reaction of compound 4d with p-aminoacetophenone gave the aryliminehtyl compound 8 The reaction of compound 4d with different aldehydes were given 3-(4,9-dimethoxy -5-oxo- 5H-furo[3,2-g][1] benzopyran)- iminomethyl- (1-aryl-1-oxo-3-proponyl substituted) 9a-d Condensation of formyl fuorochromone 1 with phenolic compounds yielded 3-(4,9-dimethoxy -5-oxo- 5H-furo[3,2-g][1] benzopyran-6-yl)- derivatives 10a-dAll the tested compounds a significant increase in PT & APTT when compared with that of the control group Only the compound IIa treated rats induced significant increaseAst, alkaline phosphatase and urea during experimental period, while other tested compounds did not cause any significant changes in liver and kidney function Concomitantly, all the tested compound caused a significant decrease in serum cholesterol and triglyaside levels

Determination and correlation of the reversed-phase thin-layer chromatographic parameter (Rm) of a series of 3-(4-substituted-1-piperazinyl)-1-substituted-1-phenyl propanol derivatives with their LD50 values.

Abstract: The experimental Rm values of four series of 3-(4-substuted-1-piperazinyl)-1-substitued - 1-phenyl propanol derivatives, previously prepared for quantitative structure-activity relationship studies, were determined using reversed-phased thin-layer chromatography. The Rm values were determined for various concentrations of acetone in water (50 60, 70, 80 and 90%), and the obtained correlation lines of Rm against proportion of acetone were extrapolated to 100% water. The enxtrapolated Rm values of two of the four series of the 3- (4-benzyl-1-piperazinyl)-1-phenyl propanol derivatives were correlated with LD 3 0 values obtained from 24-hour acute toxicity studies in albino mice. The extrapolated Rm values correlated parabolically with the LD 5 0 s.

Synthesis and anticonvulsant activity of some piperazine derivatives.

Abstract: Various 1,4-substituted derivatives of piperazine (I-XII) were synthesized and evaluated for their anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (ScMet)--induced seizures and for neurotoxicity (TOX) in the rotorod test in mice and rats. The most promising compounds seem to be 1-[(2,4,6-trimethyl)-phenoxyethyl]-4-(2-hydroxyethyl)-piperazine dihydrochloride (II) and 1,4-bis-[(4-chloro-3-methyl)-phenoxyethyl]-piperazine dihydrochloride (X) which displayed anti-MES activity with their protective index (PI) higher than that for valproate II (rats), X(mice)).

Oral delivery system of insulin microspheres: effect on relative hypoglycemia of diabetic albino rats.

Abstract: The aim of the present work was to investigate the effectiveness of a dosage form approach for monitoring both the inactivation and the absorption process by targeting insulin delivery to the upper region of small intestine. The dosage form is based on the incorporation of insulin with protease inhibitor and absorption enhancer into polyacrylic polymer Eudragit L-100. Insulin microspheres were prepared by solvent evaporation technique. And also study the effect of these microspheres upon the relative hypoglycemia (RH) effect in white diabetic albino rats has been studied in comparison to that produced after subcutaneous injection of bovine insulin solution. The oral administration of formulation with aprotinin and bile salts gave significant (p< 0.01) hypoglycemia when compared with formulation with insulin alone and with insulin and bile salts. However, the duration, course and the intensity of effect were different for each formulation. It was interesting to observe that the co-administration of aprotinin and bile salts produce prolonged and significant reduction of blood glucose level. A reduction of 4.47-36.81% in plasma glucose levels and RH of about 11.7% relative to subcutaneous injection of soluble insulin solution can be achieved by encapsulation along with protease inhibitor and bile salts.

Evaluation of crosslinked chitosan hydrogel beads as a carrier for prolonged delivery of diclofenac sodium: in vitro and in vivo studies.

Abstract: Chitosan hydrogel beads containing diclofanac sodium were prepared using ionotropic gelation technique in which tripolyphosphate solution was used as a counterion. Chitosan molecular weight, tripolyphosphate concentration and crosslinking time were found to have an effect on the percentage of the drug loading. The loading efficiency of diclofenac sodium was very high (more than 90%). A longer-period of contact with the counterion ions decreased the efficiency of drug loading. The beads produced all had good spherical geometry. The beads showed a narrow size distribution in which 95% of the beads prepared were in the range of 2-3 mm. Comparison of release rate-time plots of dissolution data of marketed product with the newly developed dosage form indicated the ability of the later to sustain more diclofenac sodium release. The beads were evaluated for their bioavailability in six beagle dogs relative to the commercial enteric-coated Voltaren tablets. The in vivo availability study, reveled that the prepared beads filled in hard gelatin capsules had a 126.22% bioavailability relative to that of the commercial Voltaren tablets. The beads showed comparable pharmacokinetic parameters to that of the commercial tablets. The results suggested the possibility of producing a promising sustained drug delivery system for diclofenac sodium.

Melt extrusion bioadhesive delivery of diclofenac sodium granules using theobroma oil.

Abstract: Carbopol 941 (C-941), a bioadhesive polymer and theobroma oil (TEO) were used in the formulation of melt extrusion bioadhesive tablets (MEBT) of diclofenac (DC). Different batches of the MEBT were formulated using different combinations of C-941 granules containing DC and TEO. The bioadhesive properties of the tablets were studied using a tensiometer by measuring the bioadhesive strength generated when the tablet interacts with the mucus of everted hog jejunum. Some physical properties of the tablets evaluated were weight uniformity, crushing strength, friability, tablet thickness and diameter, liquefaction time and absolute drug content. Release of DC from the MEBT was carried out in simulated intestinal fluid (SIF), pH 7.2. The tablets had low liquefaction times and were highly bioadhesive. Result of the study indicated that TEO could be used in the formulation of MEBT of DC granulated with C-941 for prolonged and controlled delivery of DC.

Isolation and properties of glycosylated pig prolactin (G-PRL).

Abstract: Isolation and properties of glycosylated pig prolactin (G-PRL) - Crude prolactin was received via extraction from lyophilized hypophyses with acidic 70% acetone, and then by protein precipitation via increasing acetone concentration in the extract to 92%. Received precipitate was dissolved in 0.1 M acetic acid and prolactin was precipitated in the isoelectric point at the pH=4.97. Prolactin precipitate was dissolved in phosphate buffer pH=7.50 and adsorbed on the DEAE-Sephadex column, and then eluated with linear gradient at NaCl concentration range 0.00-0.40 M. Prolactin with molecular mass 24.0 kD was eluated at NaCI concentration 0.09-0.16 M, and glycosylated prolactin at concentration 0,19-0,25 M. Using gel filtration method on Sephadex G-100 glycosylated prolactin was divided into 2 fractions with molecular mass equal - 55.8 and 17.4 kD. Both 24.0 kD - prolactin and its glycosylated form were characterized by high biological activity. Glycosylated prolactin contains among others mannose and fucose.

Synthesis of novel dihydropyridine, dihydropyrimidine, dithioacetal and chalcone derivatives from formylchromones.

Abstract: Condensation of 6-Formylfurochromone (4,9-dimethoxy- 5-oxo- 5H- furo [3,2-g][1] benzopyran- 6- carbaldehyde) 5a and malononitrile without solvent afforded (2E)- 2- cyano- 3 - (4,9 -dimethoxy-5-oxo-5H-furo[3,2-g]benzopyran-6-yl) acrylamide 8 at hydrolysis with dilute HCL. 2,6-diamino-4-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g] benzopyran- 6- yl)- 1, 4-dihydropyridine-3, 5- dicarbonitrile 9 and 6-(2,6-diacetyl-3,5-dimethylcyclohexa-2,5-dien-1-yl)-4,9-dimethoxy-5H-furo[3,2-g/[1] benzopyran-5 -one 10a,b were synthesized by one-pot cyclocondensation reaction of formyl 5a, malononitrile and ammonium acetate /or ammonium hydroxide/or aniline. The reaction of formyl 5a, malononitrile/acetylacetone (Thio) urea/guanidine HCL to give 6-amino-4-(4,9-dimethoxy-5-oxo-5H-furo[3,2-g][1] benzopyran- 6- yl)- 2-methylene-1,2,3,4-tetrahydropyrimidine- 5- carbonitrile compounds 11a,b, 6- (2-amino- 5,6- dimethyl- 1,4-dihydroipyrimidin- 4- yl)- 4,9dimethoxy- 5H-furo [3,2-g/[1] bezopyran- 5- one 12a,b. Condensation of formylfurochromone 5a with thiol compounds afforded 6-isopropyl-4-methoxy-9-(methoxy la or methyl Ib)-5H-furo[3,2-g][1] benzopyran-5-one 13a-f; 6-(1,3-dithiolan-2-yl)-4-methoxy-5H-furo[3,2-g]chromen-5-one 14a,b; 7-hydroxy-6-isopropyl-5-methoxy-2-methyl-4H-benzopyran- 4- one 15a-c; 6-hydroxy-7-[mercapto (methylthio) methyl]-8-methoxy-3-methyl-naphthalen-1(4H)-one 16. respectively. Formylfurochromones 5a-c were reacted with different substituted of acetyl compounds (khellinone, 2-acetyl pyrrol, 3-acetyl coumarin, methyl-2- thienyl ketone and p-aminoacetophenone respectively) to proceed 4-methoxy-9-(methoxy la or methyl Ib)- 6- [(1E)- 3- oxobut-1- enyl]- 5H-furo [3,2-g/[1] benzopyran-5-one 17. 5-methoxy-2-methyl-6-[(1E)-3-oxobut-1-enyl]- 4a, 5, 8, 8a- tetrahydro-4H-benzopyran- 4- one 18a-d, 4,9- dimethoxy- 6- [(1E)- 3- methoxyprop- 1- enyl]- 5H- furo [3,2-g/[1] benzopyran-5- one- N-methylene-N-phenylamine- 6- (iminomethyl)- 4,9-dimethoxy- 5H- furo [3,2-g/[1] benzopyran- 5- one 19.

Bleaching of browned water yam (Dioscorea alata) with African oil bean seed lipoxygenase (Part 2).

Abstract: Purified African oil bean seed lipoxygenase was used to bleach water yam tubers that were browned by exposing their cut surfaces to air. The enzyme solution destroyed the polyphenols extracted from the browned water yams and the polyphenols at the brouned yam tubers which resulted in the bleaching of the browned yam tubers to their original white colour. The destruction of the polyphenol extract and the bleaching of the brouned yam tubers were found to be dependent on the enzyme concentration of the enzyme.

Studies on the development of taste-masked suspension of chloroquine.

Abstract: A non-bitter chloroquine suspension formulation for pediatric use was prepared in the form of an ion-pair of chloroquine with pamoic acid. Various parameters involved in the formulation of a stable and palatable suspension have been optimized. The suspension was characterized for particle size analysis, viscosity, physical and chemical stability and taste. Release of chloroquine from the ion-pair conducted as dissolution rate studies in simulated gastric media showed near to 100% release instantaneously. In-vivo bioavailability study conducted in albino rats indicated comparable bioavailability of chloroquine from the suspension with that of chloroquine phosphate syrup taken as standard. Stability study conducted over a period of 3 months showed the intactness of the ion-pair and the tasteless behavior of the suspension throughout the period of storage.

Assessment of pharmacy patients' compliance in Bulgaria (2001--2002).

Abstract: The goal of this issue is to assess the Jevel of compliance, respectively of non-compliance among pharmacy patients between the years 20001 and 2002 in Sofia, Bulgaria. The authors study and emphasize on the factors that influence the non-compliance of the patients and also try to find different ways to increase the rate of compliance in Bulgaria. Two types of standard individual questionnaires are applied for assessment of the state of complianee and non-compliance among the pharmacy patients. The obtained results show that the main reasons, influencing the non-adherenec of the patients are: the high average price of the drugs, the overload daily regimen, inattention,, distust to the treatment and others. The drug form appears to be one of the main factors that cause non-compliance, especially when the patients receive more than one drug in different drug forms few times a day and especially if elderly patients are addressed. Despite the presented comparatively high level of compliance among the patients (from 53% for 2001, to 82% for 2002), there are strategies to enhance compliance that have to be initiated. They incorporate communication tactics, patient's education, and proper dosage of the drugs and scheduling of the drug application. The results of the analysis of the received data show an increase in the level of compliance for the pharmacy patients in Bulgaria. For 2001 it was 53%, while for 2002 it has increased to 82%. This fact shows the influence of strategeis for improvement of compliance.

Immobilization and release of etophylin from hydrogels, based on polyacrylic acid and macrodiisocyanates.

Abstract: Hydrogels, based on polyacrylic acid and various macrodiisocyanates that contain polyethylene glycol, polypropylene glycol or polytetramethylene glycol in the main chain are synthesized. The obtained hydrogels are studied as possible polymer carriers of drug substances. Etophylin was applied as a model drug. It is exposed that the etophylin release rate from the hydrogel depends on the way of drug comprise in the polymer net, from its density from the chemical nature of the crosslinking agent and from the pH of the environment. The carried out studies let us to conclude that the obtained hydrogels are possible materials as drug carriers.