No abstract

The treatment and prevention of hair loss have been a serious aesthetic problem for the population for a long time due to the widespread occurrence of the condition and its undesirable medical and social consequences. The pharmacotherapeutic options for trichological practice are very limited, and the effectiveness of many of these drugs is small or questionable. The peripheral vasodilator minoxidil is one of the few medicinal substances that has been proven to stimulate hair growth. However, the number of minoxidil preparations allowed by the Ministry of Health for use in Ukraine is minimal and mainly represented by rare dosage forms for external use. Considering the above, the employees of the Department of Medicines Technology at Zaporizhzhia State Medical University have proposed rational formulations and technologies for two new soft dosage forms of minoxidil – a 2 % cream for external use based on an emulsion, and a shampoo in gel form – based on complex physical-chemical, pharmaco-technological, rheological, and biopharmaceutical research. These formulations are intended to stabilize hair growth and restore hair coverage in men and women suffering from androgenic alopecia. The aim of this research is to study the specific activity of the proposed topical dosage forms of minoxidil. Materials and methods. Experimental cream with 2 % minoxidil on an emulsion carrier and a gel-like shampoo containing 1 % minoxidil combined with phytoextracts of hops and burdock, as well as corresponding placebo compositions, were used as objects of preclinical studies. The compositions of the topical minoxidil pharmacotherapeutic agents are scientifically based, ensuring their optimal pharmacotechnological, biopharmaceutical, and consistent consumer properties. The study of the specific activity of soft medicinal forms of minoxidil for external use was carried out by evaluating their growth-stimulating and follicle-protective activity. “Pilfood Bosnalek” spray for external use (Bosnalijek, Bosnia and Herzegovina), containing 2 % minoxidil, was used as a reference drug when studying the growth-stimulating effect of 2 % cream for external use with minoxidil. The reference drug in the study of the similar activity of the gel-like shampoo “Trichlomine” was the shampoo against hair loss “Dove” (Unilever, Germany). Results. It has been found that a 2 % minoxidil cream for topical use, when used together with the reference drug “Pilfood Bosnalek” (Bosnalijek, Bosnia and Herzegovina), has a significant hair growth-stimulating effect, which statistically significantly increases hair growth in experimental animals from as early as 3–4 days of use. The shampoo “Trichlomine” also has a significant effect on hair growth in experimental animals, with results observed from 3–4 days of use. Furthermore, the strength of the hair growth-stimulating effect observed from the use of “Trichlomine” shampoo significantly exceeds that of the reference “Dove” shampoo (Unilever, Germany). These results demonstrate the presence of significant follicle-stimulating activity in the tested minoxidil preparations for treating experimental alopecia and their positive effects on the weight and structure of laboratory animal fur. The follicle-protective activity of experimental minoxidil dosage forms (2 % cream and gel-like shampoo) was also experimentally confirmed, due to the regulation of various metabolic pathways in the dermis. The use of 2 % minoxidil cream and comparison preparations (“Dove” shampoo and “Pilfood Bosnalek” spray) did not result in the normalization of the investigated indicators of dermal energy metabolism. However, a positive effect of “Trichlomine” shampoo was found, which is associated with the presence of a plant antioxidant complex in the pharmacotherapeutic agent and its potentiating effect with minoxidil. Conclusions. It was found that the application of soft dosage forms of minoxidil (2 % emulsion-based cream and 1 % gel-based shampoo) exhibited pronounced growth-stimulating and follicle-protective activity in the model of experimental alopecia in white rats. At the same time, it was established that the cream with minoxidil 2 % for external use and the reference spray for external use “Pilfood Bosnalek” (Bosnalijek, Bosnia and Herzegovina) have a significant statistically comparable growth-stimulating effect. The strength of the growth-stimulating effect recorded from the use of the “Trichlomine” shampoo significantly exceeded the effect of the reference shampoo “Dove” (Unilever, Germany). It was found that both experimental medicinal forms of minoxidil (2 % cream and gel-like shampoo) had a follicle-protective effect by normalizing various links of dermis metabolism. The most pronounced effect in this regard was recorded in the shampoo “Trichlomine”, which contained not only minoxidil but also plant-antioxidant complexes. Application of 2 % cream with minoxidil, as well as reference drugs (spray “Pilfood Bosnalek” and shampoo “Dove”), did not have a reliable effect on the indicators of energy exchange of the dermis studied.

There are barriers to initiation, use or intensification of insulin therapy for patients with diabetes. A non-invasive therapeutic approach in insulin therapy should overcome these barriers. The development of alternative methods of insulin delivery is a complex task of fundamental medicine and pharmacy. The availability of oral / nasal insulin helps millions of people with diabetes avoid daily burden of subcutaneous insulin injections. The aim of the work was to study the current state of the latest developments in alternative routes of insulin delivery, their technology, and clinical trials. Materials and methods. The latest publications of scientific research on non-invasive insulin delivery systems were the study objects. Content analysis, bibliosemantic, analytical, summarizing analyzes were used. Results. The smart insulin delivery systems and pain-reducing technologies have been developed over the years. For this, research was conducted on numerous materials and technologies, including nanoparticles, hydrogels, liposomes, ionic liquids or special devices. Several alternative delivery technologies have been identified to reduce pain (pain-reducing technologies): oral, inhaled, intranasal, buccal, transdermal, and long-acting injectable insulins, but with low frequency of use. Various modern technological approaches are applying, namely, chemical modification of insulin; mucoadhesion system; protease inhibitors; increased absorption; particle delivery systems. Smart insulin delivery technologies are based on different strategies, materials, and glucose-responsive synthesis and conversion, but a common “diffuse-type” insulin release mechanism is used. Innovations in insulin chemistry and formulations have shown improved clinical outcomes when used. Conclusions. Innovations in alternative insulin delivery systems include algorithms for continuous glucose monitoring systems, glucose-sensitive polymer matrices and biological structures with insulin. The introduction of non-invasive systems would contribute to an earlier start of insulin therapy on medical advice, ensuring better glycemic control and reducing the risk of complications, which are the main burden on the health care system. The use of insulin in the form of alternative delivery systems may also be promising in the prevention of type 1 diabetes and other diseases.

In modern neurology, the main component of successful treatment of cerebrovascular pathology is pharmacotherapy. At the same time, the arsenal of effective medicines of evidence-based medicine in this area is quite limited. Vinpocetine (Cavinton) is one of the drugs that effectively selectively corrects cerebral perfusion. The use of alternative ways of absorption of vinpocetine (rectal and nasal) in certain soft application dosage forms will allow to significantly increase the bioavailability of the medicinal substance, reduce the level of adverse reactions from its use and expand the pharmacotherapeutic arsenal of domestic effective neuroprotective drugs. Taking into account the above, the employees of the Department of Medicines Technology of Zaporizhzhia State Medical University, on the basis of complex physical-chemical, pharmacotechnological, rheological and biopharmaceutical research, proposed rational formulations and technologies of two new soft application dosage forms of vinpocetine – rectal suppositories on a lipophilic basis and nasal cream on an emulsion basis for the therapy of arterial hypertension of II–III stages with cerebrovascular complications, reduction of the manifestation of neurological and/or mental symptoms in various forms of cerebral blood circulation insufficiency, consequences of a stroke, transient ischemic attack, etc. The aim of the work is to study the specific activity of the proposed innovative application dosage forms of vinpocetine. Materials and methods. Nasal ointment containing 0.5 % vinpocetine on an emulsion basis and rectal suppositories with vinpocetine 0.01 g on a lipophilic carrier were used as the object of preclinical studies, which ensure optimal release of the active pharmaceutical ingredient. The study of the specific activity of the developed medicinal forms of vinpocetine was carried out on a model of acute cerebrovascular accident of the type of ischemic stroke. Vinpocetin tablets (Astrapharm, Ukraine), which are used in neurological practice quite effectively and over a long period of time, were used as a comparison drug. Results. The comparative results showed that the appointment of all studied drugs led to an increase in motor activity. In addition, the administration of medicinal forms of vinpocetine reduced the development of cognitive and cognitive disorders after acute disorders of cerebral blood circulation. It was found that the highest result was shown by the group of animals that received a course of vinpocetine intranasally. In the groups of animals that received vinpocetine for 4 days, markers of oxidative stress – aldehyde phenylhydrazones and ketone phenylhydrazones – were significantly reduced. The highest activity was demonstrated by the pharmaceutical form of vinpocetin, which was used intranasally for 4 days. The introduction of dosage forms of vinpocetine exerted an energizing effect, which was expressed in an increase in the level of macroergic phosphates. Evidently, vinpocetine has a direct positive effect on the three-carbon sections of the Krebs cycle and increases the production of adenosine triphosphate (ATP). At the same time, the vinpocetine nasal cream applied intranasally for 4 days demonstrated the greatest energizing activity. Conclusions. Preclinical studies of the developed application soft medicines with vinpocetine on the model of acute cerebrovascular accident type ischemic stroke experimentally confirmed the expressed neuroprotective activity of rectal suppositories and nasal cream with vinpocetine and it was found that the effectiveness of therapy with these application medicinal forms is demonstrably higher than that in comparison with oral tablet means.

The external treatment of seborrheic dermatitis of the scalp depends on the withdrawal of clinical symptoms and the complaints the patient made to the doctor. At present Ukrainian dermatology has several dozen pharmacotherapeutic products in this direction, with dominating medicines of ketoconazole, zinc pyrition, and their combinations. They are characterized by the short-term or weak effect, associated with the pathogenic microorganisms’ resistance against the background of long-term use of biologically active substances which are their active parts. One way to solve the problem is using the drugs with new highly active pharmaceutical ingredients. Employees of the Department of Technology of Medications of the Zaporizhzhia State Medical University proposed the composition of a new applicate semisolid dosage form of pirocton olamine based on complex physical-chemical, pharmacotechnological, biopharmaceutical, and rheological investigations – topical ointment on the hydrophilic base in combination with resin-free naphthalene for external use in the complex etiotropic treatment of seborrheic dermatitis of the scalp. The aim of this work is to study the specific activity of the combined ointment with pirocton olamine and resin-free naphthalene on a hydrophilic vehicle. Materials and methods. As the object of preclinical studies used experimental ointment containing 1 % piroctone olamine and 5 % resin-free naphthalene on the base of sodium carboxymethylcellulose glycerogel, providing optimum release of active pharmaceutical ingredients from the vehicle, and appropriate placebo semisolid dosage form. The study of the specific activity of the developed ointment under the conditional name “Oktonaf” was carried out by evaluating its antimicrobial, anti-inflammatory, and antioxidant effects given the foreseeable therapeutic focus and the literature on the spectrum of biological activity of active substances. The anti-inflammatory and antioxidant action of the proposed composition was evaluated by the allergic contact dermatitis model. As a reference drug cream “Psoricap” (KMP, Ukraine), which has long been applied in dermatological practice was used. Results of comparative microbiological studies proved that composite anti-seborrheic ointment with piroctone olamine and resin-free naphthalene by the antibacterial effect in relation to the size of the growth delay zones for Staphylococcus aureus and Escherichia coli (gram-positive and gram-negative microorganisms) slightly exceeds the effective dermatological medication reference cream “Psoricap”. At the same time, the antimycotic activity of experimental ointment in relation to Candida albicans practically does not differ from the same reference drug. A study of antioxidant and anti-inflammatory activity of the developed piroctone olamine ointment on a hydrophilic basis using the model of allergic contact dermatitis revealed that its level reliably was exceed the efficacy of topical reference medication “Psoricap”. Conclusions. Obtained data of a spectrum of specific activity of a combined ointment with piroctone olamine and resin-free naphthalene can predict the high clinical value of the proposed drug for practical domestic dermatology.