Design, synthesis and evaluation of benzothiazole derivatives as multifunctional agents

Oxidative stress is the product or aetiology of various multifactorial diseases; on the other hand, the development of multifunctional compounds is a recognized strategy for the control of complex diseases. To this end, a series of benzothiazole derivatives was synthesized and evaluated for their multifunctional effectiveness as antioxidant, sunscreen (filter), antifungal and antiproliferative agents. Compounds were easily synthesized via condensation reaction between 2-aminothiophenols and different benzaldehydes. SAR study, particularly in position 2 and 6 of benzothiazoles, led to the identification of 4g and 4k as very interesting potential compounds for the design of multifunctional drugs. In particular, compound 4g is the best blocker of hERG potassium channels expressed in HEK 293 cells exhibiting 60.32% inhibition with IC50 = 4.79 μM

Фиксированная порошковая комбинация с антисептическими и барьерными свойствами для лечения ран: аспекты безопасности и эффективности

Лікування хронічних ран є величезною проблемою для охорони здоров’я всіх країн як в економічному аспекті (щорічні витрати сягають 9 млрд дол.), так і з точки зору часу, витраченого медичним персоналом на організацію адекватного тривалого моніторин­гу цієї категорії пацієнтів. У патогенезі хронічної рани можуть бути задіяні різноманітні етіологічні, системні та місцеві фактори. Ситуацію погіршує той факт, що з кожним роком резистентність мікроорганізмів до найширшого кола антибіотиків зростає. Прагнення скоротити витрати на охорону здоров’я при одночасному поліпшенні результатів лікування зумовлює пошук нових методів заміни традиційних антибіотиків. В останні десятиліття доведена значна ефективність використання адсорбентів різної природи, біо­полімерів, катіонних поверхнево-активних речовин і різних форм срібла для лікування ран. Мета цього огляду – узагальнити накопичені дані клінічних і доклінічних досліджень речовин, які широко використовуються в медичних засобах: срібла, хлоргексидину, гіалуронової кислоти та каоліну. Пошук альтернативних лікарських засобів для загоєння ран показав, що найбільш обнадійливі результати щодо різноспрямованої антимікробної активності та високої безпеки використання показали медичні засоби на основі іонів срібла, хлоргексидину, гіалуронової кислоти та каоліну. Поєднання цих сполук в одному медичному засобі дало можливість досягти оптимального ефекту, що було підтверджено клінічними випробуваннями Kadermin і Kadefort.Chronic wounds treatment is a huge problem for the health care of all countries both in the economic aspect (annual costs reach $ 9 billion) and in the time spent by medical personnel to organize adequate long-term monitoring of this category of patients. A variety of etiological, systemic, and local factors may be involved in the pathogenesis of a chronic wound. The situation is aggravated by the fact that with every year the resistance of microorganisms to the widest range of antibiotics is growing. The desire to reduce healthcare costs while improving outcomes drives search for new methods to replace traditional antibiotics. In recent decades, the effectiveness of the use of adsorbents of various nature, biopolymers, cationic surfactants, and various forms of silver for the treatment of wounds has been reassessed. The objective of this review is to summarize the accumulated data of clinical and preclinical studies of substances widely used in medical devices for wound healing: silver, chlorhexidine, hyaluronic acid, and kaolin. The search for alternative medicines for wound healing showed that the most encouraging results regarding multidirectional antimicrobial activity and high safety of use were shown by medicines based on silver, chlorhexidine, hyaluronic acid, and kaolin ions. Combinations of these compounds in one medical device allowed to achieve the optimal effect, which was confirmed by clinical trials of Kadermin (Kadefort).Лечение хронических ран является огромной проблемой для здравоохранения всех стран как в экономическом аспекте (ежегодные расходы достигают 9 млрд долл.), так и с точки зрения времени, затраченного медицинским персоналом на организацию адекватного длительного мониторинга этой категории пациентов. В патогенез хронической раны могут быть вовлечены различные этиологические, системные и местные факторы. Ситуацию усугубляет тот факт, что с каждым годом резистентность микроорганизмов к самому широкому кругу антибиотиков возрастает. Стремление сократить расходы на здравоохранение при одновременном улучшении результатов лечения обусловливает поиск новых методов замены традиционных антибиотиков. В последние десятилетия доказана значительная эффективность использования адсорбентов различной природы, биополимеров, катионных поверхностно-активных веществ и различных форм серебра для лечения ран. Цель этого обзора – обобщить накопленные данные клинических и доклинических исследований веществ, которые широко используются в медицинских средствах: серебра, хлоргексидина, гиалуроновой кислоты и каолина. Поиск альтернативных лекарственных средств для заживления ран показал, что наиболее обнадеживающие результаты относительно разнонаправленной антимикробной активности и высокой безопасности использования показали медицинские средства на основе ионов серебра, хлоргексидина, гиалуроновой кислоты и каолина. Сочетание этих соединений в одном медицинском средстве позволило достичь оптимального эффекта, что было подтверждено клиническими испытаниями Kadermin и Kadefort

PHARMACEUTICAL FORMULATIONS COMPRISING ACTIVE PHARMACEUTICAL PRINCIPLES ABSORBED ON TITANIUM DIOXIDE NANOPARTICLES.

The invention provides methods for the adsorption of an active pharmaceutical ingredient on titianium dioxide nanoparticles which can be orally ingested allowing the drug release into the intestine without causing side effects to the upper gastrointestinal region

Risedronate pharmacokinetic studies after oral administration to rats of loaded TiO2 nanoparticles

Risedronate is indicated for the treatment and prevention of osteoporosis. The oral route is the most preferred for chronic drug therapy, even if it induces some disadvantages such as poor absorption (less than 1% of the dose) and dangerous adverse gastrointestinal effects. We propose a new formulation consisting in a colloidal suspension obtained by risedronate adsorption (up to 7%) on a slurry of colloidal TiO2 nanoparticles. The particles were prepared by hydrolysis of titanium isopropoxide. The drug adsorbed appeared no more water soluble in the pH range 0-5 and it was desorbed from TiO2 nanoparticles in the pH range 6-14, where it became water soluble. This behaviour should allow for protecting the gastric mucosa after oral administration. We have performed a comparison of the risedronate pharmacokinetic profile after its oral administration to rats as water solution or as TiO2 colloidal suspension form. After the water solution administration (60 mg of drug), risedronate was detected in the bloodstream with at tmax of about 30 min and became undetectable after 4 hours. On the other hand, the administration of the colloidal suspension allowed us to obtain a controlled release of the drug in the bloodstream up to 8 hours and a relative bioavailability up to 185%, calculated as ratio of AUC values obtained for the adsorbed and free drug. This behaviour could imply an improvement of the risedronate therapeutic effects and a reduction of its frequency of administration with a consequent amelioration of the beneficial/risk ratio

FUNCTIONAL NANOMATERIALS WITH ANTIBACTERIAL AND ANTIVIRAL ACTIVITY.

The present invention relates to nanomaterials comprised of metal oxides associated with cationic metals having antibacterial activity. In particular, the present invention relates to nanocrystalline compounds of formula (I) : AOx- (L-Men+) i, (I) where AOx represents the metal oxide or metalloid oxide, with x = 1 or 2; Me11'1' is a metal ion having antibacterial activity, with n = 1 or 2; L is a bifunctional molecule, either organic or organometallic, capable of binding simultaneously with the metal oxide or metalloid oxide and the metal ion Men+; and i represents the number of L-Men+ groups bound to a AOx nanoparticle

Particulate adducts based on sodium risedronate and titanium dioxide for the bioavailability enhancement of oral administered bisphosphonates

Adducts based on a bisphosphonate drug (sodium risedronate) and titanium dioxide (TiO2) particles have been developed and characterized in order to improve the bioavailability of orally administrated bisphosphonates. Nanocrystalline and colloidal TiO2, both characterized by powder X-ray diffraction, were used to obtain the adducts 1 and 2, respectively. Adducts 1 and 2 appeared constituted by nanoparticles of about 50 and 90 nm grouped in clusters of about 0,2 and 2,5 m, respectively. Higher amounts of drugs were adsorbed on adduct 2 (7,2 ± 0.3%) with respect to adduct 1 (4,0 ± 0.3%). In vitro studies demonstrate that the adducts were able to release the drug in the pH range 6-9, whereas they remained essentially stable in the pH range 0-5. In vivo studies indicate that after oral administration to male Wistar rats, the microparticles of adduct 2 were able to prolong the presence of risedronate in the bloodstream during an eight hours period, resulting in a relative bioavailability almost doubled with respect to the free drug. This behaviour allows envisioning an improvement of the risedronate therapeutic effects and/or a reduction of its frequency of administration with consequent reduction of gastrooesophageal injuries typically induced by oral administration of bisphosphonates

A new approach to UV protection by direct surface functionalization of TiO2 with the antioxidant polyphenol dihydroxyphenyl benzimidazole carboxylic acid

Skin cancer is the most common malignant cancer with an incidence of 1 million cases/year. It is well known that exposure to UV radiation from sunlight leads the most frequent risk factors for several skin disorders including skin cancer. Sunscreen filters represent a valid protection against dangerous effects derived from UV radiation, and they can be divided in organic and inorganic UV filters. Adding, at the product formulation, molecules with booster effect, or also substances that can increase the protecting effectiveness via synergic mechanisms, can further enhance their protection activity. Moreover, this approach leads to develop formulations with high SPF (Sun Protection Factor) with a reduced content of UV filters, this is in line with the recent decisions of yet a few countries (Palau, Thailand, Philippines, and Hawaii) to ban some sunscreen filters to preserve marine environments (i.e., reef). In this work, a new class of sunscreen UV filters has been synthesized, by means the combination of physical filter and Oxisol, an antioxidant molecule with booster effect. In this study, the synthesis of new physical multifunctional ingredients is reported, by means the direct surface functionalization of inorganic filters (in particular TiO2) with Oxisol. In this study, the full characterization of these multifunctional ingredients is also reported, in addition to the cytotoxicity tests, the photocatalytic activity and the rheological properties involved on skin application