The analgesic activity of new sulfur-containing di- and tetrahydropyridine derivatives in the hot plate test

Nowadays the search of new high-efficiency and safe drugs for the pharmacotherapy of diseases accompanied by pain syndrome is an active area of modern pharmacological research. 170 new derivatives of di- and tetrahydropyridines synthesized on the basis of the Chemex Research Laboratory, Vladimir Dahl Lugansk State University were exposed to the virtual bioscreening using the Swiss Target Prediction software. The paper describes screening studies in vivo of 5 samples of sulfur-containing di- and tetrahydropyridines (laboratory codes d02-138, as-262, f02-079, cv-074, cv-143) in the standard hot plate test in comparison with the reference drug — metamizole sodium. The compounds in the dose of 5 mg/kg were given intragastrically 1 hour and a half before placing the rats on the hot plate, the reference drug in the dose of 7 mg/kg also was given intragastrically 1 hour and a half before placing the rats on the hot plate. The compounds with laboratory codes as-262 (allyl 6-({2-[(4-acetylphenyl)amino]-2-oxoethyl}thio)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridine-3-carboxylate) and d02-138 (ethyl 4-[({[3-cyano-5-{[(2,4-dichlorophenyl)amino]carbonyl}-4-(2-furyl)-6-methyl-1,4-dihydropyridinе-2-yl]thio}acetyl)amino]benzoate) possess the most pronounced analgesic activity in the dose of 5 mg/kg, they demonstrated 2.03 and 1.9-fold efficiency in comparison to metamizole sodium respectively. The rest three specimens demonstrated metamizole sodium-like analgesic activity.

ANALYSIS OF SOCIAL AND MEDICAL PORTRAIT OF CHILDREN WITH PERTUSSIS, MENINGOCOCCAL INFECTIOUS, SCARLET FEVER AND ESTIMATION OF THEIR ASSIGNED PHARMACOTHERAPY

Introduction: The level of childhood bacterial diseases incidence does not have a downward trend. The aim: Conduction of a sociological analysis of medical cards for children with pertussis, meningococcal infection (MI), scarlet fever, and evaluation of consumed pharmacotherapy according to real clinical practice in Ukraine. Materials and methods: 1215 medical cards of inpatients; methods: sociological – document analysis, retrospective frequency. Results: Among the cards of children with pertussis: 50.2% – female, 49.8%– male; by age children up to 1 year (49.3%) were prevailed. In 79.6% incidence – medium-hard form pertussis, 42.2% with complications. Among patients with MI by sex there were: 50.5 % – boys and 49.5% – girls; by age – children aged 1-4 (40.2%); the structure of generalized forms of MI: 40.2% – meningococcemia, 11.4% – meningitis, 48.4% – combination. Scarlet fever was more frequently: boys (56.4%), children aged 5-9 (44.7%), urban residents (79.7%); it was 93.4% of a medium-hard form. Most of medicines were prescribed to children with MI – 15.8 trade names per 1 person, it was prescribed 191 INN, most often – Sodium chloride (90.0%), Ascorbic acid (68.5%), Ceftriaxone (65.8%); patients with pertussis – 11.2, 196 INN (Chlorpromazine (69.1%), Dexamethasone (53.2%), Butamirate (51.8%)); scarlet fever – 9.3 medicines, 114 INN (local action Comb drug for throat diseases treatment (94.4%), Ceftriaxone (48.7%), Metamizole sodium (38.1%)). Conclusions: Frequency analysis data of consumed pharmacotherapy in real pediatric practice in Ukraine shows the need for its further optimization in accordance with the principles of evidence-based medicine, the results of research on the socio-demographic characteristics of patients, forms and complications of course of the basic disease.

Influence of different excipients on the properties of hard gelatin capsules with metamizole sodium

Metamizole is an effective non-opioid analgesic drug used in the treatment of acute and chronic pain. Due to induced potentially life-threatening blood disorders, metamizole was withdrawn from market in many parts of the world, however, it is one of the most popular analgesics in Poland that is available as an over the counter drug. Patients tend to prefer capsules over tablets, as they are easier to swallow and taste better. The powder-filled capsules also have greater bioavailability and require less excipients, as compared to tablets. Polymic excipients are mainly used in capsule filling, and have influence upon the physico-chemical properties of the hard gelatin capsules and the powder formulation. The aim of the study was to determine whether various combinations of polymers impact the disintegration time and pharmaceutical availability of hard gelatin capsules with metamizole sodium. The results of our work demonstrated that the 80% of all active substance was released in all tested formulations within 15 minutes. Herein, the capsule containing lactose monohydrate had the longest release (4% after 2 min.), while capsules containing mannitol had the fastest release (81.2% after 2 min.). Moreover, the addition of HPMC to capsules with lactose brought about a slight increase in the metamizole release rate, while the addition of PVP 30 to capsules with microcrystalline cellulose slightly accelerated release. This data suggests that the use of different polymers in capsules formulation brings about changes in the physical properties of powders and modifies the release profile of metamizole. In our study, the most preferred formulation was one containing microcrystalline cellulose (good powder properties and fairly fast release).