On the basis of our earlier studies in the group of 7,8-disubstituted derivatives of 1,3-dimetyl-3,7-dihydro-purine-2,6-dione, some new derivatives of theophylline were synthesized and tested for their electrocardiographic, antiarrhythmic and hypotensive activity as well as for α1-adrenoreceptor affinities. The performed preliminary tests indicated that new compounds did not significantly affect the normal ECG in vivo. As the result of present studies it may be concluded that all compounds did not possess hypotensive and arrhythmic activity. The results of the binding assays on α1-adrenergic receptors showed, that these derivatives display no affinity for α1-adrenergic receptors. Lack of antiarrhythmic and antihypertensive activity may result from the absence of affinity for the α1-adrenergic receptor. Performed chemical modifications lead to the loss of pharmacological activity previously observed among other derivatives in this group. Generally in comparison with the previously reported derivatives, replacing the phenoxyethylpiperazine by other moiety, changed the antiarrhythmic and hypotensive activity.
Chitosan is a cationic polymer capable of binding acidic drugs. In addition, it has haemostatic and antimicrobial activity. Chitosan derivatives withanti-fibrinolytic properties may present increased effectiveness, especially when the added substance forms an adduct with chitosan. The aim of this work was to study the haemostatic action of the chitosan–tranexamic acid complex. Two chitosan solutions (molecularweight of 250 and 625 kDa at pH 5.7 and 6.2, and after tranexamic acid had been added to chitosan solutions) werestudied. Haemostatic evaluation was performed on white outbred mice. The time to complete cessation of bleeding from the tail was determined. Chitosan 625 kDa at pH 6.2 had the best haemostatic properties. Adding tranexamic acid to the chitosan solution reduced the bleeding time. This phenomenon was more pronounced for chitosan 625 kDa. Compared with control animals, this chitosan reduced bleeding arrest time by 30% and the chitosan–tranexamic acid adduct reduced the bleeding arrest time by 75%.
The aim of this paper was to formulate the composition of a bioadhesive film obtained based on acyclovir incorporated into natural bioadhesive polymers (chitosan and guar gum) in different quantitative ratios. To this end, the author developed a technology for preparing films containing various quantitative ratios of chitosan to guar gum: 1:0.25; 1:0.50; 1:0.75; 1:1; and 1.2:0.50. The formulations were used to prepare mucoadhesive films containing 2% acyclovir. The dressings were tested with respect to their physicochemical properties and subjected to dissolution testing. A comparative analysis of Fourier-transform infrared (FT-IR) spectra of pure polymers, acyclovir, and films containing polymers in different quantitative ratios was conducted. The quantitative ratio of chitosan to guar gum significantly impacted the mechanical properties of films: texture, elasticity, tensile strength, swelling, and blur time of the testes carriers. The 1:1 formulation showed the highest mechanical strength and flexibility. The dressing containing 1.2% chitosan and 0.5% guar gum had the longest blur time. An increase in the chitosan content in the formulation significantly affected the drug dissolution parameters, which makes it possible to achieve the desired effect of extended-release time. The FT-IR spectra excluded the formation of drug-polymer interactions. Changes in the quantitative ratios of chitosan and guar game in the carrier’s composition may impact the mechanical properties of the drug formulation and changes in the parameters of active substance release.
The compounds activating adenosine system alleviated morphine withdrawal syndrome (the number of escape attempts and body shakes) in rats. Body shakes were decreased mostly by N-ethylcarboxamidoadenosine, cyclohexyladenosine, dipyridamole and 2-chloroadenosine, while R-phenylisopropyladenosine very strongly decreased the number of escape attempts. Adenosine receptor antagonists (caffeine and theophylline) increased the number of escape attempts in morphine-dependent rats. Caffeine (10 mg/kg), administered preventively, antagonized the ingibitory effects of adenosine analogs. These results suggest the existence of relation between opioid receptors and the adenosine system.
The development and improvement of chitin applications have drawn special attention from the global scientific community due to their extraordinary features and abundance. In this study, β-chitin nanofibres were obtained using the ultrasonication treatment method. Then, hydroxyapatite/nanochitin (HAp/NCh) composites were prepared at different maturation times. In this case, mixtures of various amounts of β-chitin nanofibres (1%, 2%, and 5%) were added during the HAp precipitation approach. The prepared HAp/NCh materials were characterised with Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and energy-dispersive X-ray spectroscopy. The surface of prepared specimens was observed using scanning electron microscopy. The presence of nanofibres was confirmed by non-invasive backscattering with dynamic light scattering particle size analysis. Moreover, the synergic effect of chitin nanofibres on the mechanical resistance of HAp-based composite was investigated. The sample with 5% of chitin nanofibres exhibited about 10 times higher compression strength than the pure HAp. All these results essentially indicate that the prepared material can be a potential candidate for bone tissue engineering applications and further development.
These studies concerned the effect of composition on the substrate physicochemical parameters of hydrogels for use on skin. Hydrogels containing 1% of hydrocortisone and 1% of chitosan addition was made on the basis of methylcellulose, sodium carboxymethylcellulose and Carbopol 934 P. The release proceeds according to first-order kinetics. Depending on the type and composition of the polymer gels were obtained with various pharmaceutical availability of hydrocortisone. Addition of 1% chitosan affects the acceleration of the release in any given case.
Mania is a psychiatric disorder which may occur alternately with depression as a bipolar disorder, or much less often as an individual disease. It might be accompanied by other disorders, i.e. schizophrenia, dementia or withdrawal syndrome. Only a few effective drugs are used for the treatment of mania. Patients suffering from bipolar disorder are treated with mood-stabilizing drugs, administered during the course of the disease, and drugs that are implemented when mania or depression episodes occur. Some studies report effectiveness of anticonvulsant drugs in the cessation of mania, thus in our study we assessed the effectiveness of pregabalin in a mouse model of mania induced by administration of metylphenidate (5 mg/kg; s.c). Pregabalin was tested in the forced swim test (75 mg/kg, 100 mg/kg; i.p.) and the elevated plus maze test (75 mg/kg; i.p.) to assess its antidepressant-like and anxiolytic-like properties, respectively. In the elevated plus maze in MPH-treated mice pregabalin significantly reduced time spent in open arms (p<0.001 vs. MPH-treated control). In the forced swim test MPH compared to vehicle significantly (p<0.001) reduced duration of immobility. In MPH-treated mice pregabalin partially reversed this effect of MPH. This effect was significant only for the dose of 75 mg/ kg (p<0.05). In the rotarod test neither MPH, nor its combination with pregabalin (75 mg/kg; 100 mg/kg) influenced motor coordination of mice at any speed tested. To conclude our study revealed that pregabalin might reverse manic-like action of MPH related to hyperlocomotion, which may indicate for its possible effectiveness in mania episodes.
In clinical practice, in the treatment of obesity, a plurality of natural high-molecular compounds are used, the activity of which supports weight loss. During the use of dietary supplements containing chitosan, illness sometimes develops and other therapeutic agents are applied as antibiotics The aim of our study was to determine the binding capacity of the antibiotic erythromycin depending on variable physicochemical factors, in the model of the gastrointestinal tract, by chitosans found in slimming dietary supplements Erythromycin adsorption phenomenon was studied by static and dynamic pharmaceutical model (according to the modified method of the Polish Pharmacopoeia) simulating in vitro conditions. The amount of bound drug was used to calculate the average percentage of the adsorbed dose. The results obtained show that erythromycin is adsorbed by chitosans at various pH ranges, and the binding capacity of the environment depends on the pH, viscosity and concentration of the antibiotic, as well as the chitosan and type and additional substances present in the gastrointestinal tract. The average level of the adsorption of erythromycin in the chitosan-nutrients system depends on the pH of the medium. The highest amount of adsorption was noted above pH 7 (chitosan precipitated polymer forming the emulsion-gel system).
The aim of this work was to study the properties of methylcellulose hydrogels with supplements containing chitosan and 1% hydrocortisone. Depending on the composition of the substrate, gels are characterised by a variety of pharmaceutical availabilities. Increasing the concentration of chitosan has an influence on increasing the viscosity, hardness, and cohesiveness of the tested gels.
Gastro-esophageal reflux is a term that defines the reverse flow of acid gastric contents into the esophagus. On the other hand, alkaline reflux occurs in the case when alkaline intestinal contents enter the esophagus. The aim of the study was to examine the pharmaceutical properties of gels for the treatment of gastro-esophageal reflux, covering the mucosa, allowing prolonged contact with the esophageal mucosa. Formulations containing the PVP K-30 showed the lowest pH, which is an important feature and can be used in the treatment of advanced alkaline reflux. Gels containing PVP K-90 and chitosan can be used in the treatment of acid reflux. The addition of chitosan significantly increased the dynamic viscosity of the tested gels. The study of the work of adhesion showed the effect of PVP K-30 and PVP K-90 and their concentration on the value of the work of adhesion. The presented studies have shown that it is possible to obtain gels with high adhesion to the esophageal mucous membrane.
The BCS class II includes drugs with low solubility and high permeability.. Fenofibrate is an example of this class drugs. The aim of the study was to investigate the effect of chitosan on the saturation solubility of fenofibrate incorporated into this polymer carrier. The study investigated fenofibrate in solid dispersions using a method of the solvent evaporation and physical mixtures at the drug to polymer ratio of 1:9,3:7,5:5.Solid dispersion of fenofibrate containing different ratio of medium and high molecular weight chitosan showed high saturation solubility compared to pure sample of drug. IR spectroscopy reveals that there was no chemical interaction between drug and the polymer. DSC studies showed that there is no change in the crystal structure of drug during the solid dispersion technique. Chitosan has been proposed as a useful excipient for enhancing the bioavailability of poorly water-soluble compounds.
The BCS class II includes drugs with low solubility and high permeability. Fenofibrate is an example of this class drugs. The aim of the study was to investigate the effect of chitosan about average molecular weight in various formulations on the dissolution of fenofibrate incorporated into this polymer carrier. The study investigated fenofibrate in solid dispersions using a method of the solvent evaporations at the drug to polymer ratio of 1:9;3:7;5:5. The highest dissolution of fenofibrate, amounting to 72.7%, was observed after 60 minutes from solid dispersions with drug-polymer weight ratio 1:9 in the presence chitosan A and was72 times higher in relation to the amount of added polymer in comparison to the solubility of pure drug. Investigations DSC showed that fenofibrate was remained in crystalline state in solid dispersion.
A series of alfa-sulfonyl-2-(-chloro)hetarylacetonitriles was prepared by the interaction of dichlorodiazines and R-sulfonylacetonitriles. Reaction of nucleophilic substitution of chlorine by different N-H-azoles has been studied. The compounds obtained showed 3 types of activity on cardiac papillary muscles: 1. a biphasic activity with increase in cardiac contractility at low concentration and inhibition in high concentration (1, 2, 4, 12-15), 2. a monophasic inhibitory activity (3, 5, 8-10), 3. non-active compounds (6, 7, 11). The preliminary SAR studies indicate the importance of chlorine atom at position 3 in diazine nucleus and of alkyl substituents in benzimidazole moiety for positive inotropic effects.
Hydrophilic powders passing gels containing lactic acid complexed with chitosan at a stoichiometric ratio of 1:1 and 8:1 revealed pH ranged from 3.92 to 4.44 and 2.36 to 2.84. Rheological studies demonstrated that the research gels obtained from powders possess the dynamic viscosity ranging from 53 to 398 mPa.s for the 1:1 stoichiometric ratio in the complex and from 19 to 242 mPa.s for the 8:1 ratio. As a result of the research, preparations with different pH values, including physiological range, were obtained. Powders show that the adhesion of the gel covering the surface of the apparatus simulates the conditions in the vagina. The gels obtained from the powders were characterised by the specific dynamic viscosity and possess the work of adhesion. The results obtained in the experimental studies proved that it is possible to produce a preparation with optimal pharmaceutical and application properties.
Alterations in membrane lipid composition, particularly fatty acids content is known to result in functional and structural changes. Dietary lipids and physical activity or stress play an important role in this change. It was of interest to study the influence of swimming in different temperatures on the content of fatty acids in the phospholipids of the erythrocyte membranes of rats. Our research demonstrated a significant influence of swimming on the content of fatty acids in the phospholipids of the erythrocyte membranes of rats. These changes of fatty acids, particularly the decrease of arachidonic acid and significant increase of saturated fatty acids in the phospholipids of the erythrocyte membranes in swimming rats may be induced by oxygen radicals generated in different kinds of stress.
Presented here are the results of investigations into the preparation of three-component dressing materials from various biopolymers in the form of a single-layer film which is suitable as a carrier for pain-relieving (lidocaine) and bacteriostatic (sulphanilamid) therapeutic agents. Physical-chemical, biological and usable properties of the prepared materials were tested and assessed. The amount of added active substance was adopted based on the dose recommended by the Polish Pharmacopeia for external medicinal preparations. Antibacterial activity against gram (-) Escherichia coli and gram (+) Staphylococcus aureus was assessed in some of the biocomposites by quantitative methods. The cytotoxic action in direct contact with the mouse fibroblast NCTC clone 929 was also estimated. Thermal analysis (DSC), infrared spectrophotometry (FTIR) and nuclear magnetic resonance spectroscopy were employed to investigate the impact of the variable contents of chitosan, alginate, carboxymethyl cellulose (CMC), and the active substance upon the chemical- and phase-structure of the prepared three-component polymeric biocomposites. It was found that the quantitative composition of the biocomposites and the additive of active substances lidocaine and sulphanilamide exert a vital impact upon their physical-mechanical and usable properties (imbibition, absorption). Investigations into the release of the medicinal substance from the investigated biocomposites to an acceptor fluid led to the conclusion that the kinetics of the process may be described by a complex first order rate equation with two exponential functions.
In this study the authors have evaluated the effects of sommon antiepileptic drugs given alone or in combinations with baclofen on seizures evoked by intravenous flunarizine in rabbits. The abolition of clonic and clonic-tonic convulsion was taken as the end point. Baclofen was able to inhibit convulsions only in a relatively high dose (5mg/kg). Diazepam (1.5 mg/kg) and clonazepam (2mg/kg) completely abolished clonic seizures. Valproate (20 mg/kg) inhibited clonic seizures and remained without effect on tonic convulsions. Other antiepiloptics such as carbamazepine and acetazolamide were found inactive in this respect. Moreover, combinations of acetazolamide (100 mg/kg) and carbamazepine (50 mg/kg) with baclofen (2mg/kg) had no anticonvulsant effect. Thus, mainly GABA modulatory drugs reveal significant action against flunarizine-induced seizures.
In view of ongoing interest in biodegradable polymers, dibutyrylchitin was used as a matrix for controlled release of a model substance. Transdermal systems (films) are presently more commonly used as an alternative to standard forms of drug delivery. The presented results are concerned with the release of ibuprofen from dibutyrylchitin film. The obtained transdermal films were modified by applying a control layer to slow down the release process. The matrices were also modified by adding nanoclay (Nanofil 2). Dibutyrylchitin matrices were tested for swelling and release kinetics using UV-Vis spectrophotometer. The drug kinetics release was studied in phosphorus buffer of pH=5.5 at the temperature of 35˚C. Structural investigations of the obtained matrices were carried out by optical microscopy and FTIR spectrophotometry. An appropriate mathematical model was also fitted to the obtained experimental data
The aim of this research was to carry out a comparative study of lowering of uric acid by the use of dried powder of Colchicum luteum and allopathic drug (allopurinol) in rabbits, to determine whether herbal drugs can be used by patients instead of allopathic drugs. The herbal medicine, dried corm powder of Colchicum luteum 2.5 mg/kg/day and dried powder of allopurinol 2 mg/kg/day an allopathic medicine, was used in the study. The results of these medicines were observed in animal model, using 12 adult rabbits, which were divided into three groups A, B and C, respectively, where group C was taken as control. The SPSS version 17 was used for statistical analysis and analysis of variance (ANOVA) was used for comparing the data in different groups and the level of significance was 5%. It was resulted that dried corm of Colchicum luteum significantly reduced the uric acid in adult rabbits as reduced by allopathic medicine ñ allopurinol. In the light of present research we concluded that the herbal medicines can be used in lieu of allopathic drugs. Thus, the risk of side effects that are associated with the prolonged use of allopathic drugs can be minimized.
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