20.500.12556/RUL-186702 Primerjalna analiza vsebnosti in profilov sproščanja resveratrola v izbranih prehranskih dopolnilih na slovenskem trgu Comparative analysis of the content and release profiles of resveratrol in selected dietary supplements on the Slovenian market Resveratrol (RSV) je naravni polifenol, ki je zaradi svojih številnih bioloških učinkov, vključno z antioksidativnim, protivnetnim, antidiabetičnim, protirakavim, kardioprotektivnim in nevroprotektivnim delovanjem v zadnjih desetletjih postal predmet intenzivnih raziskav. Kljub obetavnim rezultatom predkliničnih in kliničnih študij ostaja njegova klinična uporabnost omejena, predvsem zaradi njegove nizke biološke uporabnosti in hitre presnove po peroralni aplikaciji. Posledično RSV pogosteje uporabljamo v obliki prehranskih dopolnil (PD), katerih kakovost in učinkovitost nista vedno ustrezno nadzorovani. V okviru magistrske naloge smo se zato osredotočili na preverjanje kakovosti PD z RSV, s poudarkom na vsebnosti in lastnostih sproščanja v biorelevantnih medijih z namenom napovedi obnašanja PD v telesu. V prvi fazi magistrske naloge smo naredili literaturni pregled ključnih predkliničnih in kliničnih preskušanj, ki so raziskovale terapevtske učinke RSV na področju onkologije, antioksidativnega in protivnetnega delovanja, nevroloških, srčno-žilnih in presnovnih bolezni ter njegov vpliv na podaljšanje življenjske dobe. V eksperimentalnem delu smo izbrali 7 komercialno dostopnih PD z RSV. Z ustrezno ekstrakcijsko metodo in analizo s tekočinsko kromatografijo visoke ločljivosti smo izmerili dejansko vsebnost RSV, ki smo jo primerjali z deklariranimi vrednostmi proizvajalcev. Izdelkom, ki so bili v obliki kapsule, smo nato izmerili razpadni čas, ki neposredno vpliva na sproščanje učinkovine. Nadaljevali smo s testi sproščanja, za katere smo uporabili napravo z vesli po Evropski farmakopeji. Teste smo izvajali v medijih, ki posnemajo fiziološke pogoje, in sicer v mediju s pH vrednostjo 1,2, ki posnema pogoje v praznem želodcu in v mediju s pH vrednostjo 6,8, ki posnema pogoje v tankem črevesu. Zaradi slabe topnosti RSV smo raztapljanje izvajali tudi v »sink« pogojih, ki smo jih dosegli z dodatkom površinsko aktivne snovi. Za natančnejšo simulacijo prehoda farmacevtske oblike skozi prebavni trakt smo test sproščanja izvedli tudi z metodo z dolivanjem medija po Evropski farmakopeji. Rezultati so pokazali, da kakovost PD z RSV ni enotna, saj le štirje od sedmih analiziranih izdelkov ustrezajo deklarirani vsebnosti. Dodatno sta dva izdelka presegla dovoljeni razpadni čas (30 minut), kar lahko vpliva na sproščanje učinkovine. Sproščanje RSV je bilo v fizioloških pogojih omejeno (do 26 % v mediju s pH 1,2), medtem ko se je v prisotnosti PAS povečalo do 8-krat (s 4,3 % na 35,6 % v mediju s pH 6,8). Ugotovitve kažejo na pomembno variabilnost med izdelki in postavljajo pod vprašaj njihovo kakovost in učinkovitost. Predstavljajo pa tudi osnovo za nadaljnje raziskave na področju nadzora kakovosti in biofarmacevtskih lastnosti PD. Resveratrol (RSV) is a natural polyphenol that has attracted considerable scientific interest in recent decades due to its wide range of biological effects, including antioxidant, antiinflammatory, antidiabetic, anticancer,cardioprotective, and neuroprotective activities. Despite promising results from preclinical and clinical studies, its clinical application remains limited, primarily due to its low bioavailability and rapid metabolism following oral administration. Consequently, RSV is more commonly used in the form of dietary supplements (DS), whose quality and efficacy are not always adequately controlled. Therefore, the aim of this master’s thesis was to evaluate the quality of RSV-containing DS, with a particular focus on their content and release properties in biorelevant media for predicting the behaviour of DS in the body. Firstly, a review of key preclinical and clinical studies was conducted, focusing on the therapeutic effects of RSV in oncology, oxidative stress and inflammation, neurological, cardiovascular, and metabolic diseases, as well as its potential role in lifespan extension. In the experimental part, seven commercially available RSV-containing DS were selected. The actual RSV content was determined using an appropriate extraction method followed by high performance liquid chromatography analysis and compared with the declared values provided by the manufacturers. In addition, the disintegration time of capsules was determined, which directly effects the release of active substance. Dissolution testing was performed using a paddle apparatus in accordance with the European Pharmacopoeia. The tests were conducted in media simulating physiological conditions, namely at pH 1.2 (fasted stomach conditions) and pH 6.8 (intestinal conditions). Due to the poor solubility of RSV, dissolution was also evaluated under “sink” conditions using the addition of surfactants. To better simulate the transit of the dosage form through the gastrointestinal tract, a dissolution method with medium change was also employed. The results showed that the quality of RSV-containing DS is not consistent, as only 4 of the 7 analysed products complied with the declared content. Additionally, two products exceeded the permitted disintegration time (30 minutes), which may affect the release of active substance. RSV release under physiological conditions was limited (up to 26 % in pH 1.2 medium), whereas in the presence of surfactants it increased up to eightfold (from 4.3 % to 35.6 % in pH 6.8 medium). These findings highlight significant variability among products and raise concerns regarding their quality and effectiveness. Furthermore, they represent a basis for future research in the field of quality control and biopharmaceutical properties of DS. resveratrol raztapljanje vsebnost razpadni čas HPLC prehranska dopolnila resveratrol dissolution content disintegration time HPLC dietary supplements true false false [M. R. Brodnik] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2026-09-04 08:46:04 2026-09-04 08:46:17 2026-09-07 08:16:08 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 615.27(043.2) 128082 290138115 32954.pdf 32954.pdf 1 1BE46583B81197862A0C0300A48BF15B acb247e2fade66eb02833f9ec2865456908206b8fdaeaf30a0e192d90964d397 534d3707-a82c-11f1-8bc5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=246038 Fakulteta za farmacijo 0 0 0