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New Chinese herbal drugs (rhizoma et radice) in the eleventh edition of the European pharmacopoeia
No full textFitoterapija predstavlja glavni oblik prevencije i liječenja bolesti u sustavu tradicionalne kineske medicine koja se primjenjuje u Kini već stotinama godina, a u novije vrijeme joj i zapadna medicina pridaje na važnosti. Sa ciljem proširenja znanja u području fitofarmacije, teorijski je istraženo pet biljnih droga dobivenih od korijenja i podanaka kineskih ljekovitih biljaka: Belamcandae chinensis rhizoma, Cyathulae radix, Rehmanniae radix, Sanguisorbae radix i Scrophulariae radix. Pregledom stručne i znanstvene literature, za navedene biljne droge u radu je dan pregled dosadašnjih spoznaja o biljnim izvorima, tradicionalnoj primjeni, fitokemijskom sastavu te pretklinički i klinički dokazanim učincima kao i hrvatski prijevod pripadajućih monografija u aktualnom, 11. izdanju Europske farmakopeje.Phytotherapy is the main form of prevention and treatment of diseases in the system of traditional Chinese medicine, which has been applied in China for hundreds of years, and in recent times Western medicine has also given importance to it. With the aim of expanding the knowledge in the field of phytopharmacy, five herbal drugs obtained from the roots and rhizomes of Chinese medicinal plants were theoretically investigated: Belamcandae chinensis rhizoma, Cyathulae radix, Rehmanniae radix, Sanguisorbae radix and Scrophulariae radix. Through a review of professional and scientific literature, an overview of current knowledge on plant sources, traditional use, phytochemical composition, and preclinical and clinically proven effects, together with the Croatian translation of the corresponding monographs in the actual, 11th edition of the European Pharmacopoeia, is given for the aforementioned herbal drug in this thesis
The use of medications with anticholinergic and sedative effects: a cross-sectional study in nursing homes
No full textS obzirom na rastući broj dokaza o rizicima povezanih s primjenom lijekova s antikolinergičkim i sedativnim učincima
kod osoba starije životne dobi, cilj ovog istraživanja bio je utvrditi, korištenjem DBI skale, prevalenciju izloženosti DBI
lijekovima te istražiti povezanost njihove primjene s karakteristikama ispitanika i neželjenim zdravstvenim ishodima
među korisnicima domova za starije i nemoćne u Republici Hrvatskoj.
Presječno istraživanje provedeno je u domovima za starije osobe u tri hrvatske regije između kolovoza i studenog 2022.
godine. U istraživanje je bilo uključeno 225 ispitanika u dobi od 65 i više godina. Podaci su prikupljeni pomoću
standardiziranog interRAI-LTCF upitnika za sveobuhvatnu gerijatrijsku procjenu. Mjere ishoda uključivale su
(ne)ovisnost u obavljanju svakodnevnih aktivnosti (ADLs), skalu kognitivnih sposobnosti (CPS), kliničku skalu krhkosti
(CFS), prisutnost simptoma depresije te broj padova i hospitalizacija. Izloženost lijekovima s antikolinergičkim i
sedativnim učincima izračunata je pomoću DBI (engl. Drug Burden Index) skale, internacionalno validirane mjere za
procjenu opterećenja antikolinergicima i sedativima.
Medijan dobi ispitanika iznosio je 83 (IQR 79-86) godine. Prevalencija izloženosti DBI lijekovima iznosila je 77% te je
bila značajno viša među ispitanicima koji su bili izloženi politerapiji (87%) i prekomjernoj politerapiji (95%) te
ispitanicima sa simptomima depresije (88%). Izloženost DBI lijekovima bila je značajno povezana s lošijim rezultatima
na ADL skali (p=0,036) te većom krhkosti ispitanika (p=0,009). Najupotrebljivaniji DBI lijekovi bili su diazepam (29%
ispitanika), tramadol (29%), zolpidem (18%) i alprazolam (16%).
Uočena je visoka prevalencija izloženosti lijekovima s antikolinergičkim i/ili sedativnim učinkom među korisnicima
domova za starije. Korisnici izloženi DBI lijekovima bili su značajno slabijih funkcionalnih sposobnosti. Ova saznanja
potvrđuju valjanost DBI skale kao jednog od alata za prepoznavanje osoba starije životne dobi pod povećanim rizikom
od funkcionalnog oštećenja te ukazuju na potrebu za unapređenjem upravljanja terapijom korisnika domova za starije
osobe. Visoka prevalencija upotrebe benzodiazepina, „Z lijekova“ i tramadola ukazuje na potrebu za depreskripcijom.Given the increasing evidence of risks of anticholinergic and sedative medications use in older people, the aim of this
study was to determine, using the DBI scale, prevalence of exposure to DBI medications and explore the association of
DBI medications use with participant's characteristics and adverse health outcomes among Croatian nursing homes
residents.
A cross-sectional study was conducted in nursing homes in three Croatian regions between August and November 2022.
The study included 225 participants aged 65 years and older. Data was collected using a standardized interRAI-LTCF
questionnaire for comprehensive geriatric assessment. Outcome measures included (in)dependence in activities of daily
living (ADLs), cognitive performance scale (CPS), clinical frailty scale (CFS), presence of depressive symptoms and
number of falls and hospitalizations. Exposure to anticholinergic and sedative medications was calculated using the
Drug Burden Index (DBI), internationally validated tool that measures the burden of anticholinergic and sedative
medications.
Median age of participants was 83 (IQR 79-86) years. Prevalence of exposure to DBI medications was 77% and it was
significantly higher among participants exposed to polypharmacy (87%) and hyperpolypharmacy (95%) and participants
with symptoms of depression. Exposure to DBI medications was significantly associated with poorer performance on
ADL scale (p=0,036) and higher frailty among participants (p=0,009). The most frequently used DBI medications were
diazepam (29% of participants), tramadol (29%), zolpidem (18%) and alprazolam (16%).
High prevalence of exposure to drugs with anticholinergic and/or sedative effects was observed among nursing home
residents in Croatia. Residents exposed to DBI drugs had significantly poorer functional performance. These findings
confirm the validity of DBI as the tool for identifying older adults at higher risk of functional impairment and indicate
the need for improving pharmacotherapy management of nursing home residents. High use of benzodiazepines, „Zdrugs“ and tramadol suggests there are opportunities for deprescribing
Determination of essential oil content and composition in cinnamon bark
No full textLjekarnička droga Cinnamomi cortex dobiva se od kore pravog, cejlonskog cimetovca (Cinnamomum verum J. Presl.) i
tradicionalni je biljni lijek za blage gastrointestinalne tegobe. S obzirom da je kora cimetovca jedan je od najstarijih i
često korištenih začina koji se zbog svog aromatičnog eteričnog ulja uvelike koristi u kulinarstvu i prehrambenoj
industriji, na tržištu nalazimo kore i nekoliko drugih vrsta cimetovaca. U okviru diplomskog rada provedena je
fitokemijska analiza u svrhu određivanja sadržaja i sastava eteričnog ulja u deset komercijalnih uzoraka kore cimetovca.
Metodom destilacije pomoću vodene pare utvrđeno je da uzorci cjelovite biljne droge sadrže od 16 do 30 mL eteričnog
ulja /kg, dok tržišni uzorci kore u prahu sadrže značajno manje eteričnog ulja (7 do 10 mL/kg). Metodom plinske
kromatografije spregnute s tandemskom spektrometrijom masa (GC-MS/MS) određen je kemijski profil izoliranog
eteričnog ulja kore cimetovca. Identificirane su 51 do 61 sastavnica koje su sačinjavale od 94,76 % do 99,90 % eteričnog
ulja. Glavna sastavnica je trans-cimetni aldehid (56,96-89,86 %), dok su ostale manje zastupljene eugenol (0,96-8,03
%), cinamil acetat (0,20-5,09 %) i p-metoksi-cimetni aldehid (0,25-2,59 %). Kumarin koji može biti štetan po ljudsko
zdravlje utvrđen je u previsokoj koncentraciji u samo jednom od 10 analiziranih eteričnih ulja. Dobiveni rezultati
ukazuju na važnost identifikacije izvorišne biljne vrste i kontrole kakvoće biljnih droga i pripravaka koji se primjenjuju
u suvremenoj fitoterapiji.Herbal drug Cinnamomi cortex consists of bark of the true Ceylon cinnamon tree (Cinnamomum verum J. Presl.) and is
a traditional herbal medicine for mild gastrointestinal complaints. Given that cinnamon bark is one of the oldest and
frequently used spices, which is widely used in the culinary and food industry due to its aromatic essential oil, we also
find barks of several other types of cinnamon on the market. For this graduate thesis, a phytochemical analysis was
carried out in order to determine the content and composition of essential oil in ten commercial samples of cinnamon
bark. Using the method of steam distillation, it was determined that the samples of the herbal drugs in toto contain from
16 to 30 mL of essential oil/kg, while the market samples of powdered bark contain significantly less essential oil (7 to
10 mL/kg). The chemical profile of the isolated cinnamon bark essential oil was determined by the method of gas
chromatography coupled with tandem mass spectrometry (GC-MS/MS). Between 51 and 61 components were
identified, which constituted from 94.76% to 99.90% of the essential oil. The main component is trans-cinnamaldehyde
(56.96-89.86%), while the other less abundant are eugenol (0.96-8.03%), cinnamyl acetate (0.20-5.09%) and p-methoxy
cinnamaldehyde (0.25-2.59%). Coumarin, which can be harmful to human health, was found in too high a concentration
in only one of the 10 analyzed essential oils. The obtained results indicate the importance of identification of the source
plant species and quality control of herbal drugs and preparations used in modern phytotherapy
Influence of rice sample preparation on elemental composition - application of total reflection X-ray fluorescence spectroscopy
No full textRiža je namirnica koja se u velikim količinama konzumira svakodnevno diljem svijeta. Zbog zagađenosti okoliša, može biti kontaminirana teškim metalima te je stoga određivanje elementarnog sastava riže od iznimne važnosti za očuvanje ljudskog zdravlja.
Glavni cilj ovoga rada jest odrediti utjecaj različite predobrade uzoraka riže na elementarni sadržaj te usporediti učinkovitost korištenih tehnika u određivanju sadržaja metala (TXRF-Mo, ICP-MS). Prikupljeni uzorak riže prije postupka mikrovalne digestije korišten je i) bez prethodne obrade, ii) nakon što se tri puta isprao s ultra čistom vodom, iii) nakon što je usitnjen u mlinu. Svi uzorci su nakon predobrade podvrgnuti postupku mikrovalne digestije te analizirani primjenom TXRF-Mo i ICP-MS. U svim ispitanim uzorcima određeni su slijedeći elementi: željezo, bakar, mangan, cink, stroncij i nikal. Dobiveni rezultati za sadržaj elemenata u uzorcima samljevene riže i riže tri puta isprane s ultračistom vodom uspoređeni su sa sadržajem elemenata u uzorcima riže bez prethodne obrade.
Sadržaj analiziranih elemenata određenih s TXRF tehnikom usporediv je s rezultatima ICP-MS tehnike. U usporedbi s netretiranim uzorkom, rezultati analize su utvrdili da ispiranje zrna riže, za razliku od mljevenja, uzrokuje značajnije promjene sadržaja za sve određene elemente. Prethodna obrada uzorka je pokazala najveći utjecaj na sadržaj željeza, a najmanji na mangan. Unatoč tome, nije utvrđena statistički značajna razlika kod dodatne obrade uzorka te je stoga donesen zaključak kako predpriprema uzorka nije potrebna.
Analiza TXRF tehnikom iziskuje vrlo male količine uzoraka i reagensa, proizvodi malo kemijskog otpada, ne iziskuje rashladne sustave i plinove te uključuje jednostavnu kvantifikaciju dodatkom unutarnjeg standarada što ju čini bržom, jednostavnijom te ekološki i ekonomski prihvatljivijom tehnikom od ICP-MS-a.Rice is consumed daily in large quantities all over the world. Due to environmental pollution, rice can be contaminated with heavy metals, which is why controlling the elemental composition of rice grains is extremely important for the preservation of human health.
The main objective of this work is to determine the influence of different pretreatments of rice samples on elemental analysis and to compare the effectiveness of the techniques used to determine the metal content (TXRF-Mo, ICP-MS).
The rice sample collected before microwave digestion was used i) without pretreatment, ii) after washing three times with ultrapure water and iii) after milling in a mill. After processing, all samples were subjected to microwave digestion and analyzed by TXRF-Mo and ICP-MS. The following elements were determined in all analyzed samples: iron, copper, manganese, zinc, strontium and nickel. The results for the content of elements in samples of milled rice and rice washed three times with ultrapure water were compared with the content of elements in samples of rice without prior treatment.
The content of the elements analyzed with the TXRF technique corresponds to the ICP-MS element content. Compared to the untreated samples, the results showed that washing the rice grains, as opposed to milling, caused more significant changes in the content of all analyzed elements. The pre-treatment of the sample had the greatest influence on the iron content and the least on the manganese content. Regardless of this, no statistically significant difference was found with additional sample preparation, so it was concluded that pretreatment of the samples is not necessary.
Analysis using the TXRF technique requires very small amounts of samples and reagents, generates little chemical waste, does not require cooling systems or gasses and involves simple quantification with internal standards, making it a faster, simpler and more environmentally and economically acceptable technique than ICP-MS
Determination of iron and copper in encapsulated food supplements for the treatment of inflammatory bowel diseases
No full textU današnje vrijeme sve je veća primjena biljnih dodataka prehrani koje su važan izvor biološki aktivnih sastavnica, a čije djelovanje je pozitivno na zdravlje ljudi. S obzirom da se kurkuma, indijski tamjanovac i justicija koriste kao dodaci prehrani koji ublažavanju simptoma upalnih bolesti crijeva, cilj ovog rada bio je procijeniti kvalitetu dodataka prehrani s obzirom na sadržaj željeza i bakra. Koncentracije navedenih minerala u analiziranim dodacima prehrani određene su plamenom i grafitnom atomskom apsorpcijskom spektrometrijom, a prije analize u svrhu pripreme svi su uzorci spaljeni mikrovalnom digestijom. Rezultati istraživanja su pokazali da su koncentracije željeza i bakra u dodacima prehrani koji se koriste kod upalnih bolesti crijeva bile u dozvoljenim rasponima. Primjećuje se znatna razlika u ispitanim metalima kod uzoraka u tvrdim kapsulama u odnosu na one u mekim kapsulama, te se također može primijetiti značajnija koncentracija željeza u odnosu na koncentraciju bakra.Nowadays, there is an increasing use of herbal dietary supplements, which are an important source of biologically active components, and whose effects are positive for human health. Considering that turmeric, Indian frankincense and Justicia are used as dietary supplements to alleviate the symptoms of inflammatory bowel diseases, the aim of this work was to evaluate the quality of dietary supplements regarding iron and copper content. The concentrations of the mentioned minerals in the analyzed dietary supplements were determined by flame and graphite atomic absorption spectrometry, and before the analysis for the purpose of preparation, all samples were burned by microwave digestion. The results of the research showed that the concentrations of iron and copper in dietary supplements used for inflammatory bowel diseases were within the permissible ranges. A significant difference in the tested metals can be observed for samples in hard capsules compared to those in soft capsules, and a significant concentration of iron can also be observed in relation to the concentration of copper
New Chinese herbal drugs (fructus et semina) in the eleventh edition of the European pharmacopoeia
No full textTradicionalna kineska medicina drevni je medicinski sustav koji pridonosi ljudskom zdravlju već
tisućama godina na području Azije, a u novije vrijeme sve je više prihvaćaju i koriste pacijenti u
zapadnim zemljama. Sustavnim pretraživanjem i proučavanjem relevantne stručne i znanstvene
literature, ovime je radom dani sistematični pregled biljnih izvora, tradicionalne primjene, kao i
dosadašnjih znanstvenih spoznaje o fitokemijskom sastavu, pretkliničkom i kliničkom djelovanju za
četiri odabrane kineske biljne droge s dugom primjenom u sustavu tradicionalne kineske medicine:
Chaenomeles fructus, Forsythiae fructus, Armeniacae semen amarum i Persicae semen. Odabrane
su biljne droge dobivene od plodova i sjemenki kineskih biljaka za koje su utvrđene norme kakvoće
u obliku monografija u aktualnom 11. izdanju Europske farmakopeje te su sastavni dio rada i
hrvatski prijevodi tih monografija.Traditional Chinese medicine is an ancient medical system that has contributed to human health for
thousands of years in Asia, and in recent times it has been increasingly accepted and used by patients
in Western countries. Through a systematic search and study of the relevant professional and
scientific literature, this paper aims to provide a systematic overview of herbal sources, traditional
application, as well as current scientific knowledge about the phytochemical composition,
preclinical and clinical studies for four selected Chinese herbal drugs with a long history of use in
the system of traditional Chinese medicine: Chaenomeles fructus, Forsythiae fructus, Armeniacae
semen amarum and Persicae semen. Herbal drugs obtained from the fruits and seeds of Chinese
plants were selected, for which quality standards have been established in the form of monographs
in the current 11th edition of the European Pharmacopoeia, so the Croatian translations of these
monographs are an integral part of this thesis
Priprava i karakterizacija vezikularnog fosfolipidnog gela s timolom
No full textCilj istraživanja
Cilj ovog istraživanja bila je priprava i evaluacija vezikularnog fosfolipidnog gela (VFG) s
timolom, namijenjenog dermalnoj primjeni. Optimizirani su uvjeti priprave VFG-a, te je ispitan
utjecaj sastava VFG-a na fizikalna svojstava vezikula (liposoma) unutar VFG-a, oslobađanje
timola i reološke karakteristike formulacija.
Materijali i metode
Eksperimentalni dio rada obuhvaćao je izradu VFG-ova s timolom različitog (fosfo)lipidnog
sastava metodom visokotlačne homogenizacije. Provedeno je određivanje fizikalno-kemijskih
svojstava VFG-ova s timolom (srednji promjer, indeks polidisperznosti, zeta potencijal
liposoma unutar VFG-ova) te ispitivanje topljivosti timola u različitim otapalima kako bi se
odredio prikladan medij za provođenje ispitivanja in vitro oslobađanja. Ispitivanja in vitro
oslobađanja timola iz odabranih formulacija VFG-ova i kontrole (otopina timola) provedena
su metodom dijalize, a oslobođeni timol je određen spektrofometrijski. Reološka
karakterizacija formulacija uključivala je rotacijska (profil viskoznosti) i oscilatorna (test
promjene amplitude) mjerenja.
Rezultati
Visokotlačnom homogenizacijom uz primjenjeni tlak od 500 bara pripravljena su dva različita
tipa VFG-a srednjih promjera liposoma od 140 do 200 nm i blago negativnog zeta potencijala
(-5 do -8 mV). Postignuto je produljeno oslobađanje timola iz oba tipa VFG-a u odnosu na
kontrolu, pri čemu je (fosfo)lipidni sastav značajno utjecao na udio oslobođenog timola.
Prisustvo kolesterola u formulaciji je rezultiralo polaganijim oslobađanjem timola u odnosu na
formulaciju pripravljenu isključivo iz sojinog fosfadilkolina. (Fosfo)lipidni sastav VFG-a
utjecao je i na reološka svojstva formulacija. VFG pripravljen bez kolesterola bio je neznatno
viskozniji u odnosu na VFG s kolesterolom, dok temperatura na kojoj su provedena mjerenja
nije utjecala na viskoznost formulacija. Oba tipa VFG-a su pokazala viskoelastična svojstva
prikladna za dermalnu primjenu (G' > G“ u linearnom viskoelastičnom području).
Zaključak
Rezultati provedenih ispitivanja u sklopu ovog rada ukazuju na mogućnosti primjene VFG-a
kao inovativne polučvrste podloge za dermalnu dostavu timola. Reološkom karakterizacijom
potvrđena su pseudoplastična svojstva pripravaka, kojima se omogućuje produljeno
oslobađanje timola. Daljnjim ispitivanjima (permeabilnost kroz kožu, antimikrobni učinak,
biokomaptibilnost) procijenila bi se prikladnost formulacija VFG-ova s timolom za primjenu
na kožu.Objective
The aim of this research was to prepare and evaluate a vesicular phospholipid gel (VPG) for
dermal delivery of thymol. The preparation conditions of VPGs were optimized, and the impact
of the (phospho)lipid composition of the VPG on the release of thymol, physico-chemical
properties of the liposomes within the VPGs, and the rheological characteristics of the
formulations, was examined.
Material and Methods
Thymol-loaded VPGs of different (phospho)lipid composition were prepared using the highpressure homogenization method at applied pressure of 500 bar. The physicochemical
properties of liposomes within the thymol-loaded VPGs were determined (mean diameters,
polydispersity indexes, zeta potentials) and the solubility of thymol in different solvents was
tested in order to determine a suitable medium for conducting in vitro release studies. In vitro
release of thymol from the selected VPGs and the control (thymol solution) were performed
using the dialysis method, while the released thymol was determined spectrophotometrically.
Rheological characterization of the formulations included rotational (viscosity profile) and
oscillatory (amplitude test) measurements.
Results
Two different types of VPGs, with liposomes exhibiting mean diameters of 140 - 200 nm and
a slightly negative zeta potentials (-5 to -8 mV), were prepared by high-pressure
homogenization method. Prolonged release of thymol from the both types of VPGs was
achieved compared to the control, whereby the (phospho)lipid composition had a significant
effect on the release of thymol. The presence of cholesterol in the VPG resulted in a slower
release of thymol compared to the VPG prepared exclusively from soy phosphadylcholine. The
(phospho)lipid composition of VPGs also affected the rheological properties of the
formulations. VPG prepared without cholesterol was slightly more viscous compared to VPG
with cholesterol, while the temperature at which the measurements were carried out did not
affect the viscosity of the formulations. Both types of VPGs showed viscoelastic properties
suitable for dermal application (G' > G“, in linear viscoelastic region).
Conclusion
The results of all conducted studies indicate the suitability of VPG as an innovative semisolid
vehicle for dermal delivery of thymol. The rheological characterization confirmed the
pseudoplastic properties of VPGs, which enabled the prolonged release of thymol. However,
further investigations are required, such as skin permeability studies, antimicrobial testing, and
biocompatibility assessment, to evaluate the suitability of thymol-loaded VPGs for skin
application
Comparison of ICP-MS and TXRF techniques for elemental analysis of whey protein
No full textProteini sirutke jedni su od često upotrebljavanih dodataka prehrani te stoga određivanje njihovog mineralnog sastava može biti od velikog interesa za potrošače te od koristi za proizvođače. U mineralnom je sastavu proteina sirutke dokazana prisutnost teških metala. S obzirom na moguće štetne utjecaje na ljudsko zdravlje, korisno je odrediti sadržaj prisutnih teških metala u proteinima sirutke. Glavni cilj ovog eksperimentalnog diplomskog rada bio je odrediti elementarni sastav proteina sirutke dostupnih na tržištu pomoću TXRF i ICP-MS tehnike te usporediti rezultate dobivene dvjema različitim tehnikama. Prikupljeni uzorci pripremljeni su postupkom mikrovalne digestije. U svim uzorcima primjenom obje tehnike određeni elementi su: željezo, bakar, cink, stroncij, rubidij. U svim uzorcima primjenom TXRF tehnike određen je i brom. Drugim spektroskopskim tehnikama brom nije jednostavno odrediti što čini još jednu prednost ove tehnike u usporedbi s ostalim spektroskopskim tehnikama za elementarnu analizu. Analizom rezultata uočene su značajne razlike u sadržaju elemenata u različitim uzorcima proteina sirutke. U svim uzorcima najzastupljeniji element je željezo, a nakon njega većinom slijedi cink zatim bakar ili stroncij. Dobiveni rezultati s obje tehnike u većini slučajeva nisu pokazali statističku značajnu razliku, što potvrđuje da se umjesto standardizirane ICP-MS tehnike kao alternativa u određivanju sadržaja proteina sirutke može koristiti i TXRF. Primjena TXRF tehnike prvenstveno zbog uporabe vrlo male količine uzorka i reagensa, nekorištenja rashladnih sustava i plinova, kvantifikacije pomoću unutarnjeg standarda je jednostavnija, brža te ekonomski i ekološki održivija tehnika u usporedbi s ICP-MS tehnikom. Obećavajući rezultati dobiveni primjenom ove tehnike za određivanje sadržaja teških metala u proteinima sirutke otkrivaju veliki potencijal ovog uređaja za brzu i jednostavnu analizu različitih tipova uzoraka.Whey proteins are among the most commonly used dietary supplements, so determining their mineral composition can be of great interest to consumers and benefit to manufacturers. The presence of heavy metals has been detected in the mineral composition of whey proteins. Considering the possible harmful effects on human health, it is useful to determine the concentration of heavy metals present. The main objective of this experimental work was to determine the elemental composition of whey proteins available on the market using the TXRF and ICP-MS techniques and to compare the results obtained with the two different techniques. The following elements were determined in all samples using both techniques: Iron, Copper, Zinc, Strontium, Rubidium. Bromine was also determined in all samples using the TXRF technique. Bromine is difficult to determine using other spectroscopic techniques, which represents a further advantage of this technique over other spectroscopic techniques for elemental analysis. The analysis of the results showed considerable differences in the element content of the different whey protein samples. Iron was the most abundant element in all samples, followed by zinc, copper and strontium. The results obtained with both techniques showed no statistically significant difference in most cases, confirming that the TXRF technique can be used as an alternative to the standardised ICP-MS technique for the determination of whey protein content Compared to the ICP-MS technique, the TXRF technique is simpler, faster, more economical and more environmentally friendly, as only a very small amount of samples and reagents are required, no cooling systems or gases are used and quantification is performed with an internal standard. The promising results obtained with this technique in the determination of heavy metal content in whey proteins show the great potential of this device for fast and easy analysis of different types of samples
Elemental impurities in formulated dietary supplements for the treatment of inflammatory bowel diseases
No full textU 21. stoljeću primijećen je porast oboljelih od upalnih bolesti crijeva zbog industrijalizacije i
modernog načina života. Liječenje se fokusira na indukciju i održavanje remisije pomoću lijekova
iz različitih farmakoterapijskih skupina. Nerijetko se, zbog neučinkovitosti ili sigurnosnog profila
terapije, pacijenti okreću dodacima prehrani o kojima se provodi i sve veći broj znanstvenih
istraživanja. Budući da se primjenjuju dugotrajno, iznimno je važna kvaliteta proizvoda. Kurkuma,
indijski tamjanovac i justicija biljke su čiji se ekstrakti nalaze u brojnim dodacima prehrani za
liječenje upalnih bolesti crijeva na tržištu. Stoga je cilj ovog rada bio odrediti sadržaj kroma, nikla i
selena, elementarnih onečišćenja i potencijalno toksičnih tvari, u analiziranim dodacima prehrani.
Sadržaj navedenih kemijskih elemenata određen je metodom grafitne atomske apsorpcijske
spektrometrije. Dobiveni rezultati upućuju na povezanost sadržaja elementarnih onečišćenja i vrste
kapsule. Količine elementarnih onečišćenja u analiziranim dodacima prehrani zadovoljavaju
zahtjeve važećih ICH Q3D smjernica o najvećem dozvoljenom dnevnom unosu elementarnog
onečišćenja farmaceutskim proizvodom.In the 21st century, there has been an observed increase in cases of inflammatory bowel disease due
to industrialization and modern lifestyles. Treatment focuses on inducing and maintaining remission
through medications from various pharmacotherapeutic groups. Due to the inefficacy or safety
profile of the therapy, patients often turn to dietary supplements, which are also the subject of
increasing scientific research. Since these supplements are used long-term, the quality of the
products is extremely important. Turmeric, Indian frankincense, and King of Bitters are plants whose
extracts are found in numerous dietary supplements for the treatment of inflammatory bowel
diseases on the market. Therefore, the aim of this study was to determine the content of chromium,
nickel, and selenium as elemental impurities and potentially toxic substances in the analyzed dietary
supplements. The content of these chemical elements was determined using the graphite furnace
atomic absorption spectrometry method. The obtained results showed a correlation between the
content of elemental impurities and the type of capsule. The amounts of elemental impurities in the
analyzed dietary supplements meet the requirements of the current ICH Q3D guidelines on the
maximum daily intake of elemental impurities by a pharmaceutical product
Synthesis and characterization of a proteolysis-targeting chimera (PROTAC) for the targeted degradation of glycogen synthase kinase 3Beta (GSK3Beta) And dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A)
No full textAlzheimerova bolest (AB) jedna je od najčešćih neurodegenerativnih bolesti današnjice. Terapija ove bolesti ograničena je na nekoliko lijekova koji djeluju simptomatski te ne dovode do izlječenja, zbog čega je potrebno kontinuirano istraživati i razvijati nove lijekove koji ciljaju nove mete s potencijalom za modificiranje tijeka bolesti. Posljednjih godina istražuje se mogućnost ciljanja različitih signalnih molekula uključenih u patofiziologiju AB, uključujući kinazu glikogen sintaze 3 (GSK3) i dvospe-cifične tirozinskom fosforilacijom regulirane kinaze 1A (DYRK1A).
Cilj ovog rada je sinteza i karakterizacije nove kimere koja usmjerava ciljanu proteolizu (PROTAC) GSK3β i DYRK1A. Ciljni PROTAC sastoji se od tri dijela: liganda za ciljne proteine (harmin) i liganda za E3 ligazu (talidomid) koji su povezani alkil-triazolskom poveznicom. U svrhu priprave PROTAC-a potrebno je sintetizirati odgovarajuće prekursore: azid 3 i alkin harmina 6 te karboksilnu kiselinu talidomida 5. Sinteza alkina 6 odvija se u jednom reakcijskom koraku, alkiliranjem harmina propargil-bromidom u bazičnim uvjetima. Azid 3, prekursor alkiltriazolske poveznice, sintetiziran je u tri koraka iz etanolamina. Derivat talidomida 5 sintetiziran je 4-hidroksitalidomida i tert-butil-2-bromoacetata pri čemu nastaje eter kojem se u drugom koraku skida tert-butiloksikarbonilna zaštitna skupina (Boc) trifluoroctenom kiselinom. Alkin 6 i azid 3 povezani su preko 1,2,3-tria-zolskog prstena u jednom reakcijskom koraku Huisgenovom 1,3-dipolarnom cikloadicijom. Spoju 7 je uklonjen Boc s amino skupine u kiselim uvjetima pri čemu nastaje amin 8. PROTAC 9 dobiven je coupling reakcijom između karboksilne kiseline talidomida 5 i amina 8 uz pomoć coupling reagensa HATU.
Novosintetizirani spoj karakteriziran je analitičkim i spektroskopskim metodama (1H i 13C NMR, MS i FT-IR) te su mu web alatom SwissADME predviđeni fizičko-kemijski parametri koji procjenjuju ograničenu oralnu bioraspoloživost i nemogućnost prolaska krvno-moždane barijere. Također se predviđa da je PROTAC 9 inhibitor CYP enzima i supstrat P-glikoproteina. Spo-sobnost razgradnje ciljnih kinaza bit će ispitana u daljnjim istraživanjima.Alzheimer's disease (AD) is one of the most common neurodegenerative diseases today. The therapy for this disease is limited to only a few drugs that only alleviate symptoms but do not cure nor significantly modify disease progression. Therefore, continuous research to develop new disease-modifying drugs for new targets is necessary. In recent years, the possibility of targeting various signal molecules involved in the pathophysiology of AD, including glycogen synthase kinase 3 (GSK3) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), has been investigated.
The aim of this study is to synthesize and characterize a novel proteolysis-targeting chimera (PROTAC) for the targeted degradation of GSK3β and DYRK1A. The target PROTAC consists of three parts: a ligand for proteins of interest (harmine) and a ligand for E3 ligase (thalidomide) linked by an alkyltriazole linker. To prepare PROTAC, it is necessary to synthesize the appropriate precursors: azide 3, harmine alkyne 6, and the carboxylic acid of thalidomide 5. The synthesis of alkyne 6 is carried out in a single reaction step by alkylation of harmine with propargyl bromide in the presence of a base. Azide 3, a precursor of the alkyltriazole linker, is synthesized in three steps from ethanolamine. The thalidomide derivative 5 is synthesized from 4-hydroxythalidomide and tert-butyl-2-bromoacetate to form an ether 4, from which, in the second step, tert-butyloxycarbonyl protecting group (Boc) is removed with trifluoroacetic acid. Alkyne 6 and azide 3 are connected via a 1,2,3-triazole ring in a single reaction step by Huisgen 1,3-dipolar cycloaddition. The removal of Boc from the amino group of compound 7 gives an amine 8. PROTAC 9 was obtained in the coupling reaction between the carboxylic acid of thalidomide 5 and amine 8 using the coupling reagent HATU.
The novel compound is characterized by analytical and spectroscopic methods (1H and 13C NMR, MS, and FT-IR). The SwissADME web tool predicted limited oral bioavailability and blood-brain barrier penetration, based on the physicochemical properties. PROTAC 9 is also predicted to be a CYP inhibitor and a P-glycoprotein substrate. The potential for the degradation of target kinases will be investigated in further studies