ABSTRACT
The mechanochemical preparation of solid compositions of praziquantel with plant saponin (glycyrrhizic acid disodium salt) is described. The study of a number of physicochemical parameters showed that dissolving solid compositions in water is accompanied by the inclusion of praziquantel molecules into micelles, which are formed in the solution of the glycyrrhizic acid disodium salt. Using the opisthorchiasis model caused by Opisthorchis felineus, we found a 4- to 11-fold increase in the anthelmintic activity of praziquantel in the composition as compared to the official praziquantel. According to the pharmacokinetic data, the use of the composition increased the bioavailability of praziquantel 3 times.
Subject(s)
Antiplatyhelmintic Agents/chemical synthesis , Antiplatyhelmintic Agents/pharmacology , Glycyrrhizic Acid/chemistry , Mechanical Phenomena , Opisthorchiasis/drug therapy , Praziquantel/chemical synthesis , Praziquantel/pharmacology , Animals , Antiplatyhelmintic Agents/pharmacokinetics , Antiplatyhelmintic Agents/therapeutic use , Biological Availability , Chemical Phenomena , Chemistry Techniques, Synthetic , Cricetinae , Praziquantel/pharmacokinetics , Praziquantel/therapeutic useABSTRACT
In this study, bornyl- and cytisine-based cyanopyrrolidines as potent dipeptidyl peptidase-IV (DPP-IV) inhibitors were synthesised. The in vitro inhibiting activities of bornyl- and cytisine derivatives towards DPP-IV were evaluated. Bornyl-based cyanopyrrolidines were shown to have moderate inhibitory activity with regard to DPP-IV (1.27-15.78⯵M). A docking study was performed to elucidate the structure-activity relationship of the obtained compounds. The in vivo hypoglycemic activities of the same compounds were evaluated with the oral glucose tolerance test (OGTT) in mice. Bornyl-based cyanopyrrolidines were shown to have good hypoglycemic activity.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Hypoglycemic Agents/therapeutic use , Pyrrolidines/chemistry , Alkaloids/chemistry , Animals , Azocines/chemistry , Binding Sites , Camphor/chemistry , Catalytic Domain , Dipeptidyl Peptidase 4/chemistry , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucose Tolerance Test , Humans , Hypoglycemic Agents/chemical synthesis , Male , Mice , Molecular Docking Simulation , Pyrrolidines/therapeutic use , Quinolizines/chemistry , Structure-Activity RelationshipSubject(s)
Galactans/chemistry , Larix , Nitrogen Oxides/pharmacokinetics , Animals , Capillary Permeability/drug effects , Electron Spin Resonance Spectroscopy , Free Radicals/pharmacokinetics , Galactans/pharmacokinetics , Gastrointestinal Absorption/drug effects , Male , Molecular Structure , Nitrogen Oxides/chemistry , Permeability , Rats, Wistar , Solubility , Solutions , Spin LabelsSubject(s)
Aspirin/administration & dosage , Drug Compounding/methods , Galactans/chemistry , Larix/chemistry , Platelet Aggregation/physiology , Ulcer/chemically induced , Animals , Aspirin/adverse effects , Aspirin/chemistry , Dose-Response Relationship, Drug , Galactans/adverse effects , Macromolecular Substances/adverse effects , Macromolecular Substances/chemical synthesis , Male , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/chemical synthesis , Rats , Rats, Wistar , Solubility , Stress, Mechanical , Ulcer/prevention & controlABSTRACT
Toxicological pharmacological study of the molecular complex of nifedipine and glycyrrhizic acid 1:10 (glycidipine) obtained using mechanochemical technique was carried out. High hypotensive and cardioprotective effects of the agent were demonstrated. Chronic administration (45 days) produced no toxic effects in vital organs and systems of Wistar rats and ISIAH rats.
Subject(s)
Antihypertensive Agents/administration & dosage , Cardiotonic Agents/administration & dosage , Glycyrrhizic Acid/administration & dosage , Nifedipine/administration & dosage , Animals , Anti-Arrhythmia Agents/pharmacology , Antihypertensive Agents/chemistry , Antihypertensive Agents/toxicity , Cardiotonic Agents/chemistry , Cardiotonic Agents/toxicity , Drug Combinations , Drug Evaluation, Preclinical , Energy Metabolism/drug effects , Female , Glycyrrhizic Acid/chemistry , Glycyrrhizic Acid/toxicity , Hypertension/drug therapy , Male , Myocardial Ischemia/chemically induced , Myocardial Ischemia/drug therapy , Nifedipine/chemistry , Nifedipine/toxicity , Oxidative Stress/drug effects , Rats , Rats, Wistar , Solubility , Verapamil/pharmacologySubject(s)
Chelating Agents/pharmacology , Galactans/pharmacology , Animals , Anti-Arrhythmia Agents/administration & dosage , Antihypertensive Agents/administration & dosage , Chelating Agents/administration & dosage , Chelating Agents/isolation & purification , Galactans/administration & dosage , Galactans/isolation & purification , Larix/chemistry , Male , Nifedipine/administration & dosage , Rats , Rats, WistarABSTRACT
A new water-soluble form of the calcium blocker nifedipine (NF) with glycyrrhizic acid (GA) (with molecular ratio 1:4) has been obtained by mechanochemical synthesis. Its pharmacological advantages in comparison with nifedipine were determined. An effective dose of nifedipine in complex reduced to 10 times as compared to its therapeutic dose while high antihypertensive activity preservation and pleiotropic antiarhythmic activity enhancement. This new antihypertensive and antiarhythmic agent (complex of NF:GA = 1:4) is chemically stable and safe for parenteral administration.
Subject(s)
Antihypertensive Agents/pharmacology , Glycyrrhizic Acid/pharmacology , Nifedipine/pharmacology , Animals , Antihypertensive Agents/chemistry , Antihypertensive Agents/toxicity , Female , Glycyrrhizic Acid/chemistry , Glycyrrhizic Acid/toxicity , Male , Mechanical Phenomena , Nifedipine/chemistry , Rats , Rats, WistarABSTRACT
Complexation of known drugs with carbohydrate-containing plant metabolites is a promising way to synthesize new drugs that does not only save pharmacological properties of initial agent but also acquire a number of advantageous features such as increased water solubility, bioavailability and decreased toxicity. This review reports on the development and pharmacological evaluation of novel complexes of various well-known drugs with vegetable coplexation agents: glycyrrhizic acid, Stevia glycosides, gypsogenin tetraoside, pectin, xyloglucan, arabinogalactan. The aim of this review is to describe advantages of the new approach, suggested by authors, in the development of low toxic and high-performance drugs.
