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Rational system design for nasal drug delivery to the central nervous system
No full textVeliki izazov u primjeni lijekova s djelovanjem na središnji živčani sustav (SŽS) predstavljaju odabir i priprema sustava koji ima mogućnost dostaviti lijek u dovoljnoj količini i odgovarajućem obliku. Upotreba racionalnog dizajniranja pri osmišljavanju rješenja doprinosi lakšem donošenju zaključaka i manjim troškovima u eksperimentalnim procesima. Iz tog razloga glavni cilj ovog rada je prikazati svojstva različitih sustava kao i svojstva nazalne primjene te prikazati mogućnost racionalnog dizajniranja u svrhu olakšavanja odabira najprikladnijeg dostavnog sustava. U radu je detaljno opisana nosna sluznica te su opisani sustavi i karakteristike koje utječu na efikasnost dostave lijeka. Kao pokusni lijek odabran je lijek hidrofilnog karaktera, dopamin. Predloženi sustav za dostavu dopamina je nanočestica sastavljena od polilakto-ko-glikolne kiseline koja se može stabilizirati pomoću Tween®80. Uklapanjem te čestice u hidrogel postiže se bolja kompatibilnost s nosnom sluznicom i pospješuje se intranazalna dostava.A major challenge in the use of drugs with action on the central nervous system (CNS) is the selection and preparation of a system that can deliver the drug in sufficient quantity and appropriate form. The use of rational design in designing solutions contributes to an easier drawing of conclusions and lower costs in experimental processes. For this reason, the main goal of this master's thesis is to present the properties of different systems and the properties of nasal application and to show the possibility of rational design to facilitate the selection of the most appropriate delivery system. The thesis describes in detail the nasal mucosa and describes the systems and characteristics that affect the efficiency of drug delivery. A hydrophilic drug, dopamine, was chosen as the experimental drug. The proposed dopamine delivery system is a nanoparticle composed of polylacto-co-glycolic acid that can be stabilized by Tween®80. Incorporating these particles into the hydrogel allows for better compatibility with the nasal mucosa, and intranasal delivery should improve
Regulatory, theoretical and practical aspects of the analytical method for determinig the composition of Cannabis Sativa L. oil
No full textCannabis Sativa L. je biljka iznimno bogatog kemijskog profila. Farmaceutska industrija koristi spojeve tetrahidrokanabinol (THC) i kanabidiol (CBD) iz kanabisa u lijekovima kao što su Dronabinol i Sativex kao terapiju za razne bolesti. Rekreacijsko korištenje kanabisa postalo je sve više popularno u zadnjih nekoliko godina, a posljedica toga je povećanje broja proizvoda na bazi kanabisa i povećanje tržišta takvih proizvoda u svijetu. Ovaj rad opisuje zakonsku problematiku vezanu za kategorizaciju i kontrolu proizvoda na bazi kanabisa, daje kratak prikaz analitičkih tehnika korištenih u analizi kanabisa i proizvoda na bazi kanabisa i na kraju koristi teoretske kalkulacije na osnovi Hansenovih parametara topljivosti u svrhu predviđanja retencijskog vremena molekula u kromatografskoj analizi. Rezultati kalkulacija pokazali su korelacije između različitih parametara izračunatih softwareom HSPiP.Cannabis Sativa L. is a plant with an extremely rich chemical profile. The pharmaceutical industry uses tetrahydrocannabinol (THC) and cannabidiol (CBD) compounds from cannabis in drugs such as Dronabinol and Sativex as a therapy for various diseases. Recreational cannabis use has become increasingly popular in recent years, resulting in an increase in the number of cannabis-based products and an increase in the market for such products worldwide. This thesis describes the legal issues related to the categorization and control of cannabis-based products, gives a brief overview of analytical techniques used in the analysis of cannabis and cannabis-based products and finally uses theoretical calculations based on Hansen solubility parameters to predict retention time of molecules in chromatographic analysis. The results of the calculations showed correlations between different parameters calculated by the HSPiP software
Measuring of surface tension and density of electroisolation liquids
No full textTransformator je elektromagnetski uređaj koji radi na principu Faradeyevog zakona elektromagnetske indukcije. Transformatori služe za transformaciju razine napona kroz neku točku u elektroenergetskoj mreži. Transformatorsko ili elektroizolacijsko ulje je ulje posebnih karakteristika koje je stabilno na visokim temperaturama i ima dobra izolacijska svojstva. Uloga ulja u transformatorima je hlađenje, izolacija te zaustavljanje iskrenja i koronskog pražnjenja. Također transformatorsko ulje štiti celuloznu izolaciju tako što sprječava izravan kontakt između celuloze i atmosferskog kisika. Uz to štiti i namotaje koji su potpuno uronjeni u ulje. Dvije su glavne vrste transformatorskih ulja; mineralna ulja koja mogu biti inhibirana i neinhibirana te sintetička ulja. Kod elektroizolacijskih ulja promatramo električna, fizikalna i kemijska svojstva. U ovom će se radu posebno pratiti gustoća i granična površinska napetost ulja. Praćenje gustoće transfomatorskih ulja je osobito važno jer ulje nikako ne smije biti teže od vode, jer bi pri jako niskim temperaturama led mogao isplivati na površinu ulja. Pomoću mjerenja površinske napetosti ulja možemo otkriti prisutnost polarnih zagađivača i produkata oksidacije ulja. U ovom završnom radu ispitivani su uzorci transformatorskih ulja iz transformatora u eksploataciji i jedno novo ulje. Mjerene su karakteristike osam različitih uzoraka ulja različitih proizvođača.A transformer is an electromagnetic device which works on principle of Faraday´s Law of induction. Transformers are used to transform the voltage level through a point in the power grid. Transformer or electrical insulating oil is an oil with special characteristics that is stable at high temperatures and has good insulating properties. The role of oil in transformers is cooling, insulation and stopping sparking and corona discharge. Also transformer oil protects cellulose insulation by preventing direct contact between cellulose and atmospheric oxygen. It also protects coils that are completely immersed in oil. There are two main types of transformer oils; mineral oils that can be inhibited and uninhibited, and synthetic oils. In electrical insulation oils, we observe electrical, physical and chemical properties. In this paper, the density and ultimate surface tension of the oil will be particularily monitored. It is important to measure the density of transformer oils especially because the oil should never be havier than water, because at very low temperatures ice could float to the surface of the oil. By measuring the surface tension of the oil, we can detect the presence of polar pollutants and oil oxidation products. In this final work, samples of transformer oils from transformers in operation and one new oil were examined. The characteristics of eight different oil samples from different manufacturers were measured
Determination of supramolecular synthons in crystal structures of oxa-aza macrocyclic compounds
No full textMarkociklički spojevi najčešće su korišteni spojevi supramolekulske kemije. Primjenom koncepta supramolekulske kemije na čvrsto agregatno stanje govorimo o kristalnom inženjerstvu. Kristalno pakiranje povezano je s prirodom međumolekulskih interakcija. Klasična vodikova veza primjer je jake međumolekulske interakcije i ima značajnu ulogu u stvaranju supramolekulskih kristala. Snaga vodikovih veza ovisi o vrsti elektronegativnog atoma na koji je atom vodika pričvršćen i geometriji vodikovih veza. Supramolekulski sintoni su strukturne jedinice sastavljene od molekulskih i supramolekulskih elemenata, koje u kristalnoj strukturi čine mrežu motiva. Neki sintoni korisniji su od drugih sintona i kao takvi imaju puno veći utjecaj na pakiranje molekula u kristalnoj strukturi. Za jednostavno opisivanje sintona koristi se graf-set nomenklatura. Graf-set se prvo primjenjuje na motiv a zatim na mrežu. CSD baza podataka sadrži korisne informacije za ispitivanje sintona i međumolekulskih interakcija.Macrocyclic compounds are the most used compounds of supramolecular chemistry. By applying the concept of supramolecular chemistry to a solid-state, we are talking about crystal engineering. The crystal packing is related to the nature of intermolecular interactions. The classical hydrogen bond is an example of a strong intermolecular interactions and plays a significant role in the formation of supramolecular crystals. The strength can vary between different systems and depend on the type of electronegative atom to which the hydrogen atom is attached and the geometry that hydrogen bond forms in the structure. Supramolecular synthons are structural units composed of molecular and supramolecular elements, which in the crystal structure form a network of motifs. Some synthons are more useful than other synthons and as such have a much greater impact on the packing of crystal structures. A graph-set nomenclature is used to simplify the description of synthon. Usually the graph-set is applied first to the motive and then to the network. The CSD database contains useful information for examining synthons and intermolecular interactions
Vitamin E and neurodegenerative diseases
No full textVitamin E je biološki važna molekula koja, između ostalog, djeluje kao zaštita od štetnog djelovanja slobodnih radikala. Obzirom na strukturu, može se pojaviti kao tokoferol ili tokotrienol. Svaki od njih pojavljuje se u četiri varijante: α, β, γ i δ. Najaktivniji je α-tokoferol koji je zajedno s ß-tokoferolom izoliran iz ulja pšeničnih klica. Kao antioksidans, vitamin E štiti biomakromolekule (npr. polinezasićene masne kiseline) od oksidacijskog stresa i posljedičnih oštećenja. Neurodegenerativne bolesti su bolesti središnjeg živčanog sustava koje karakterizira oštećenje i smrt živčanih stanica mozga i leđne moždine. Neke od neurodegenerativnih bolesti su Alzheimerova bolest, Parkinsonova bolest te amiotrofična lateralna skleroza. Živčane stanice još nazivamo i neuroni, a njihova uloga je da stvaraju, primaju i prenose živčani impuls. Tako, živčane stanice imaju jednu od najvažnijih uloga pomoću koje možemo komunicirati, kretati se, hraniti i sl. Narušavanjem funkcije i građe membrana živčanih stanica gubimo sve prethodno navedene funkcije. Budući da vitamin E kao antioksidans štiti membrane živčanih stanica, on tako pomaže u sprječavanju nastanka neurodegenerativnih bolesti te kod oboljelih osoba usporava razvoj simptoma i napredovanja same bolesti.Vitamin E is a biologically important molecule that, among other activities, acts as protection against the harmful effects of free radicals. Based on its structure, it can appear as tocopherol or tocotrienol. Each of them appears in four variants: α, β, γ and δ. The most active is α-tocopherol which together with ß-tocopherol is isolated from wheat germ oil. As an antioxidant, vitamin E protects biomacromolecules (e.g., polyunsaturated fatty acids) from oxidative stress and consequent damage. Neurodegenerative diseases are diseases of the central nervous system characterized by the damage and death of the nerve cells of the brain and spinal cord. Some of the neurodegenerative diseases are Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Nerve cells are also called neurons, and their role is to generate, receive and transmit nerve impulses. Thus, nerve cells have one of the most important roles by which we can communicate, move, feed, etc. By disrupting the function and markup of membranes of nerve cells, we lose all the aforementioned functions. Because vitamin E as an antioxidant protects the membrane of nerve cells, it thus helps prevent the development of neurodegenerative diseases and slows the development of symptoms in patients and ultimately the disease
The toxicity of acrylamide
No full textAkrilamid ili 2-propenamid važan je kemijski spoj u industrijama koje ga ponajviše koriste za proizvodnju polimera i kopolimera. Prvi je put identificiran u hrani 2002. godine kada se otkrilo da nastaje termičkom obradom hrane koja u sebi sadrži visok udio ugljikohidrata, uz uvjet da je temperatura viša od 120℃. Glavnim mehanizmom nastanka akrilamida smatra se Maillardova reakcija u kojoj sudjeluju aminokiseline i reducirajući šećeri. S obzirom da akrilamid vrlo lako može dospjeti u organizam čovjeka, ali i životinja, nužno je razumjeti njegov toksični i mogući kancerogeni učinak. Mehanizam toksičnosti još uvijek nije u potpunosti razjašnjen, no smatra se da je oksidativni stres glavni čimbenik koji izaziva toksičnost akrilamida. Do sada je kod ljudi dokazano samo neurotoksično djelovanje akrilamida, dok su toksičnosti vezane za reproduktivni sustav i genetički materijal te kancerogenost dokazani samo na životinjama. Glicidamid, metabolički produkt akrilamida, toksičniji je od akrilamida te oba spoja mogu stvarati adukte s hemoglobinom i DNA. Adukti s hemoglobinom i DNA koriste se kao biomarkeri koji pokazuju izloženost akrilamidu. Budući da je akrilamid opasan spoj koji vrlo lako može dospjeti u organizam čovjeka, istražuju se načini smanjenja njegove količine u hrani te se preporučuju vrijednosti dopuštene koncentracije akrilamida u hrani.Acrylamide or 2-propenamide is important chemical compound in the industry that is mostly used for production of polymers and copolymers. It was firstly identified in 2002 when it was discovered that it is formed by heat treatment of food rich in carbohydrates, provided when the temperature is higher than 120℃. The main mechanism of acrylamide formation is considered to be Maillard reaction involving amino acids and reducing sugars. Since acrylamide can very easily enter the human and animal body, it is necessary to understand its toxic and possible carcinogenic effect. The mechanism of toxicity has not yet been fully explained, but oxidative stress is thought to be a major factor causing acrylamide toxicity. So far only the neurotoxic effects of acrylamide have been demonstrated in humans, while reproductive toxicity, genotoxicity and carcinogenicity have only been demonstrated in animals. Glycidamide, a metabolic product of acrylamide, is more toxic than acrylamide and both compounds can form adducts with hemoglobin and DNA. Adducts with hemoglobin and DNA are used as biomarkers showing acrylamide exposure. Since acrylamide is dangerous compound that can very easily enter the human body, ways to reduce its amount in food are being investigated and the values of the permissible concentration of acrylamide in food are recommended
Estimation of biochemical parameters of the physiological state of mistletoe (Viscum Album)
No full textBijela imela (Viscum album L.) je poluparazitska biljka koja raste na različitim drvenastim vrstama. Zbog svojih protuupalnih, antibakterijskih i antitumorskih svojstava upotrebljava se u liječenju različitih bolesti i stanja. Posebno se ističu antioksidativna svojstva imele koja ovise o vrsti domaćina na kojem parazitira, regiji i vremenu uzorkovanja. U ovom je radu ispitivan utjecaj lokacije i vremena uzorkovanja na biokemijski sastav i antioksidativnu aktivnost svježe ubranih uzoraka imele te gotovih čajnih pripravaka imele. Veći sadržaj ukupnih topljivih polifenola, antioksidativna aktivnost i koncentracije karotenoida i ukupnog klorofila uočene su u uzorcima ubranima u listopadu u odnosu na one ubrane u veljači. Svježih uzorci i čaj nisu pokazali značajnu razliku u ispitivanim parametrima izuzev uzoraka u Istri, Petrijevcima i Aljmašu. Uočene su razlike između svježe ubranih uzoraka lista i grančica te sadržaja ukupnih topljivih polifenola i antioksidativne aktivnosti pojedinih čajnih pripravaka. Rezultati metode analize glavnih komponenata ukazao je na određena grupiranja među uzorcima sukladno rezultatima biokemijskih analiza. Dobiveni rezultati potvrđuju utjecaj lokacije i sezonskih varijacija na fitokemijski sastav imele.Common mistletoe (Viscum album L.) is a semi-parasitic plant that grows on various woody species. Due to its anti-inflammatory, antibacterial and antitumor properties, it is used in the treatment of various diseases and conditions. Particular emphasis is placed on the antioxidant properties of mistletoe, which depend on host type on which it parasitizes, the region and the sampling time. In this paper, the influence of location and sampling time on the biochemical composition and antioxidant activity of freshly harvested mistletoe samples and mistletoe tea preparations was investigated. Higher content of total soluble polyphenols, antioxidant activity, and concentrations of carotenoids and total chlorophyll were observed in samples harvested in October in comparison to those harvested in February. Fresh samples and tea did not show a significant difference in the examined parameters except for the samples in Istria, Petrijevci and Aljmaš. Differences were observed between freshly harvested samples of leaves and twigs and the content of total soluble polyphenols and antioxidant activity among individual tea preparations. The result of the principal components analysis method indicated certain groupings among the samples in accordance with the results of biochemical analyses. The obtained results confirm the influence of location and seasonal variations on the phytochemical composition of mistletoe
Electrochemical characterization of gallic acid
No full textU ovom diplomskom radu ispitivana su elektrokemijska svojstva galne kiseline u različitim puferima i realnim uzorcima uporabom diferencijalne pulsne voltametrije. Vrijednosti pH pufera su varirale od pH = 3,0 do pH = 9,5. Cilj rada bio je ispitati utjecaj pH na potencijal oksidacijskog strujnog vrha galne kiseline, istražiti utjecaj koncentracije galne kiseline i brzinu promjene polarizacije elektrode na oksido-redukcijska svojstva galne kiseline, istražiti moguću adsorpciju oksidacijskog produkta galne kiseline na površinu radne elektrode te odrediti galnu kiselinu u realnim uzorcima. Elektrokemijska mjerenja provedena su u troelektrodnoj elektrokemijskoj ćeliji gdje su kao radne elektrode korištene zlatna, platinska i elektroda od staklastog ugljika, kao referentna elektroda korištena je Ag/AgCl elektroda, te kao protuelektroda korištena je platinska žica. Utvrđeno je da se galna kiselina oksidira pri navedenim eksperimentalnim uvjetima pri čemu su detektirana dva oksidacijska strujna vrha, te da dolazi do adsorpcije njenog oksidacijskog produkta na površinu elektrode. Visina oksidacijskog strujnog vrha galne kiseline je varirala s promjenom pH vrijednosti, dok je optimalna pH vrijednost za njenu oksidaciju bila oko pH = 6,0. Utvrđeno je da se oksidacijski strujni vrh galne kiseline povećava sa povećanjem koncentracije (linearna ovisnost u području od 0,1 μmol dm-3 do 66,6 μmol dm-3). Galna kiselina je detektirana u realnim uzorcima u kojima joj je koncentracija varirala od 0,4 μmol dm-3 do 35,6 μmol dm-3.In this thesis, the electrochemical properties of gallic acid in different buffers and real samples were investigated using differential pulse voltammetry. The pH values of the buffers ranged from pH = 3.0 to pH = 9.5. The aim of this study was to investigate the influence of pH value on the potential of oxidation current peak of gallic acid, to investigate the influence of gallic acid concentration and rate of electrode polarization change on oxido-reduction properties of gallic acid, to investigate possible adsorption of the oxidation product of gallic acid on the surface of the working electrode and determine the gallic acid in real samples. Electrochemical measurements were performed in a three-electrode electrochemical cell where gold, platinum and glassy carbon electrodes were used as working electrodes, Ag / AgCl electrode was used as a reference electrode, and platinum wire was used as a counter electrode. It was found that gallic acid is oxidized under these experimental conditions, where two oxidation current peaks were detected, and its oxidation product was adsorbed on the electrode surface. The height of the oxidation current peak of gallic acid varied with the change of pH value, while the optimal pH value for its oxidation was around pH = 6.0. It was found that the oxidation current peak of gallic acid increases with increasing concentration (linear dependence in the range from 0.1 μmol dm-3 to 66.6 μmol dm-3). Gallic acid was detected in real samples in which its concentration varied from 0.4 μmol dm-3 till 35.6 μmol dm-3
The application of gas chromatography (GC) for determination of residual solvent in melatonin
No full textU ovom radu provedeni su razvoj i validacija HSS-GC-FID metode za određivanje ostatnih otapala (metanola, 2-propanola, tert-butil-metil-etera i etil acetata) u sirovini melatonina. Melatonin je hormon epifize s brojnim biološkim učincima na organizam pa se sintetski melatonin često koristi kao aktivna tvar u pripremi farmaceutskih preparata. Ključni parametri validacije bili su specifičnost, linearnost, raspon, preciznost, točnost, stabilnost te limit (granica) detekcije i kvantifikacije. Metoda je validairana prema ICH smjernicama i određene su kvantifikacijske i detekcijske granice za svako otapalo. Rezultati su pokazali da je metoda visoko specifična (selektivna), linearna, točna i precizna unutar ispitivanog područja. Otopine standarda i uzorka stabilne su 2 dana na sobnoj temperaturi i u hladnjaku. S obzirom da su zadovoljeni kriteriji prihvatljivosti svih validacijskih parametara, može se zaključiti da je razvijena HSS-GC-FID metoda prikladna za određivanje ostatnih organskih otapala u sirovini melatonina.In this thesis HSS-GC-FID method for determination of residual solvents (methanol, 2-propanol, tert-butyl methyl ether and ethyl acetate) in melatonin was developed and validated. Melatonin is a hormone secreted by the human pineal gland and has many various effects on the body, hence synthetic melatonin is used as an active component in the preparation of pharmaceutical products. Key validation parameters were selectivity, linearity, range, precision, accuracy, stability, and limits of detection and quantification. Method has been validated in accordance with ICH guidelines and quantification and detection limit for all studied solvents was determined. Results of validation experiments confirmed that this method is highly selective, linear in working range, accurate and precise. Standard and sample solutions were stable for two days at room temperature and in the fridge. Considering all conditions for validation were met, it can be concluded that developed HSS-GC-FID method for the determination of residual organic solvents in melatonin raw material is suitable for its intended purpose
Determination and comparison of the vitamin C content in selected fruit and fruit products
No full textVitamin C, (5R)-[(1S)-1,2-dihidroksietil]-3,4-dihidroksifuran-2(5H)-on, je vrlo snažan antioksidans prisutan u voću i povrću te sastojak brojnih suplemenata. Bitan je za rad imunološkog sustava koji stimulira aktivnost leukocita te povećava koncentraciju interferona. Povećana koncentracija interferona rezultira lučenjem hormona prsne žlijezde i stvaranjem antitijela. Sudjeluje u metabolizmu masnih kiselina te sintezi karnitina i kolagena. TakoĎer, pomaže u oblikovanju eritrocita, sudjeluje u apsorpciji željeza i transformaciji folne kiseline u njezin aktivni oblik, 5-metiltetrahidrofolnu kiselinu. U svježem voću i povrću nalazi se najveća koncentracija vitamina C, a obradom namirnica dolazi do smanjenja njegove koncentracije jer je lako topljiv u vodi, fotosenzibilan i podložan oksidaciji. Iznimno je nestabilan te gubi svoje karakteristike i smanjuje mu se koncentracija pri visokim temperaturama (termički raspad vitamina C) i dugotrajnim skladištenjem. U ovom radu, jodometrijska titracija je upotrijebljena za ispitivanje efekta skladištenja i vrste obrade na koncentraciju askorbinske kiseline u voću i voćnim preraĎevinama. Metoda je jednostavna i praktična za brzo odreĎivanje vitamina C. Dobivene vrijednosti usporeĎene su s USDA bazom podataka kako bi utvrdili koliko je korištena metoda primjenjiva u tu svrhu. Metoda je dobra u našem slučaju ako su otopine uzorka svijetlijih boja te je onda lako uočljiva promjena boje otopine u tamno plavu. Kod uzoraka tamnijih boja je teže odrediti završnu točku titracije. Rezultati ovog istraživanja ukazuju da je sadržaj vitamina C mnogo manji u voćnim preraĎevinama nego u svježem voću. Smanjenje sadržaja vitamina C u biljnim materijalima uzrokuje priprema, termička obrada i dugotrajno skladištenje hrane.Vitamin C, (5R)-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one, is a very powerful antioxidant present in fruits and vegetables and an ingredient in many supplements. It is important for the work of the immune system, which stimulates the activity of leukocytes and increases the concentration of interferon. Increased interferon concentrations result in the secretion of thymus hormones and the production of antibodies. It participates in the metabolism of fatty acids and the synthesis of carnitine and collagen. It also helps in the formation of erythrocytes, participates in the absorption of iron and the transformation of folic acid into its active form, 5-methyltetrahydrofolic acid. Fresh fruits and vegetables have the highest concentration of vitamin C, and food processing reduces its concentration because it is easily soluble in water, photosensitive and susceptible to oxidation. It is extremely unstable and loses its characteristics and its concentration decreases at high temperatures (thermal decomposition of vitamin C) and long-term storage. In this paper, iodometric titrations were used to determine the effect of storage and type of processing on the concentration of ascorbic acid in fruits and fruit products. The method is simple and practical for the rapid determination of vitamin C. The values collected were compared with the USDA database to determine how applicable used method was for that purpose. The method is good in our case if the sample solutions are lighter in colour so the colour change to dark blue is easily noticeable. For darker coloured samples, it is more difficult to determine the end point of the titration. The results of this study indicate that the content of vitamin C is much lower in fruit products than in fresh fruit. Reduction of vitamin C content in plant materials is caused by preparation, heat treatment and long-term storage of food