doktorska disertacija
Jure Zekič (Author), Mitja Križman (Mentor), Drago Kočar (Thesis defence commission member), Iztok Jože Košir (Thesis defence commission member), Samo Kreft (Thesis defence commission member)

Abstract

Navadno konopljo (Cannabis sativa L.) so zaradi njene raznovrstne uporabnosti gojila že prazgodovinska ljudstva, še danes pa predvsem zaradi svojih zdravilnih, pa tudi psihoaktivnih lastnosti vzbuja veliko pozornosti. Prav zaradi slednjih je bila konoplja dolgo časa stigmatizirana, njena raba pa pogosto strogo omejena ali celo prepovedana. V zadnjem času ponovno prihajajo do izraza zdravilni učinki konoplje, tudi omejitve, povezane z njenim gojenjem in uporabo se v veliki meri rahljajo. Tako konopljine edinstvene zdravilne lastnosti kot tudi psihoaktivni učinki so posledica prisotnosti kanabinoidov, sekundarnih metabolitov, značilnih (skoraj) izključno za konopljo. V konoplji se nahajajo tudi druge skupine sekundarnih metabolitov, med katerimi so najbolj zastopani terpeni, nekoliko manj pa še različne fenolne spojine. Tudi ti dve skupini spojin imata dokazano bioaktivno delovanje, poleg tega pa je znano sinergistično delovanje terpenov s kanabinoidi. Doktorsko delo je osredotočeno predvsem na analitske vidike študija konoplje, poleg tega pa naslavlja tematiko povečevanja vodotopnosti poglavitnih kanabinoidov, kar je pomembno z vidika povečevanja njihove biorazpoložljivosti. Raziskovalno delo bi tako lahko razdelili v štiri glavne sklope. V prvem je bila razvita metoda plinske kromatografije, ki omogoča sočasno določevanje kanabinoidov in terpenov. Omeniti velja, da so za določevanje obeh skupin spojin v konoplji razvite že številne (zanesljive) kromatografske metode, naš pristop pa je inovativen predvsem zato, ker se lahko obe skupini metabolitov določi hkrati. Celoten postopek, od priprave vzorca do same kromatografske analize, je hiter in enostaven, po drugi strani pa še vedno dovolj robusten in točen, da ima široko praktično uporabnost. Drugi del je obravnaval izolacijo kislinskih oblik kanabinoidov iz rastline. Kislinske oblike so na splošno precej nestabilne in komercialno težje dostopne, kljub temu pa imajo že dokazane zdravilne lastnosti in so s tega vidika zanimive tako za nadaljnje študije kot uporabo. Optimizirana je bila izolacija kanabidiolne kisline. Za potrebe našega raziskovalnega dela se je kot praktična in še enostavnejša alternativa izkazala sinteza kanabidiolne ter kanabigerolne kisline iz kanabidiola oz. kanabigerola. Tretji del doktorskega dela se je nanašal na študije povečevanja vodotopnosti kanabinoidov, ki so sami po sebi v vodi zelo slabo topni (oz. skoraj netopni). Razvit je bil pristop tvorbe kompleksa z glukozaminom, ki znatno poveča vodotopnost tako kislinskih kot dekarboksiliranih oblik kanabinoidov. Nastanek kompleksa je bil dokazan z uporabo več komplementarnih analiznih tehnik, prav tako pa je bilo sistematično ovrednoteno povečanje vodotopnosti različnih kanabinoidov, tako izoliranih, kot prisotnih v ekstraktu. Izkazalo se je, da tvorba kompleksa z glukozaminom tudi stabilizira kislinske oblike kanabinoidov. Zadnji, četrti del doktorske naloge pa je bil osredotočen na fenolne spojine. Le-te veljajo za najbolj zastopano skupino sekundarnih metabolitov v naravi, prisotne pa so tudi v konoplji. Kljub temu so bile do sedaj konopljine fenolne spojine razmeroma malo preučevane, zaradi splošne osredotočnosti raziskav na kanabinoide in terpene. V okviru raziskovalnega dela sta bili razviti metodi tankoplastne in tekočinske kromatografije za določevanje fenolnih spojin, identifikacija pa je potekala tudi s pomočjo masne spektrometrije. Kot potencialni vir fenolnih spojin so bili ovrednoteni vodni preostanki po parni destilaciji konoplje, ki se sicer uporablja za pridobivanje eteričnega olja.

Keywords

kanabinoidi;terpeni;fenolne spojine;plinska kromatografija;GC;tekočinska kromatografija visoke ločljivosti;HPLC;masna spektrometrija;izolacija kanabinoidov;vodotopnost kanabinoidov;doktorske disertacije;

Data

Language: Slovenian
Year of publishing:
Typology: 2.08 - Doctoral Dissertation
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
Publisher: [J. Zekič]
UDC: 543.544:547.9(043.3)
COBISS: 203285763 Link will open in a new window
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Downloads: 9
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Other data

Secondary language: English
Secondary title: Determination and isolation of cannabinoids, terpenes and phenolic compounds from industrial hemp (Cannabis sativa L.) with separation techniques
Secondary abstract: Hemp (Cannabis sativa L.) has been already cultivated by prehistoric societies due to its diverse usability. Today, it still attracts significant attention primarily for its medicinal effects and psychoactive properties. The latter have led to the long-standing stigmatization of hemp, with its use often strictly limited or even prohibited. However, in recent years, the medicinal effects of hemp are once again coming to attention, and restrictions related to its cultivation and use are largely loosening. The unique medicinal properties of hemp, as well as its psychoactive effects, are attributed to the presence of cannabinoids, secondary metabolites characteristic (almost exclusively) to hemp. Hemp also contains other groups of secondary metabolites, mainly terpenes, and various phenolic compounds. These two groups of compounds have proven bioactive effects, and there is also known synergistic action between terpenes and cannabinoids (»entourage effect«). The doctoral thesis primarily focuses on the analytical aspects of hemp study, furthermore it also addresses the theme of increasing the water solubility of key cannabinoids, which is important in terms of enhancing their bioavailability. The research work can be divided into four main sections. In the first part, a gas chromatography method for the simultaneous determination of cannabinoids and terpenes was developed. Event though numerous reliable chromatographic methods for determining both groups of compounds in hemp already exist, our approach is innovative mainly because both groups of metabolites can be determined simultaneously. The entire process, from sample preparation to chromatographic analysis, is fast and simple, but also robust and accurate enough to have broad practical usability. The second part addressed isolation of acidic forms of cannabinoids from the plant. Acidic forms are generally quite unstable and commercially less accessible. However, they posses proven medicinal properties, making them interesting for further studies and applications. During the research work, isolation of cannabidiolic acid was optimized. For the purposes of our research, the synthesis of cannabidiolic and cannabigerolic acids from cannabidiol and cannabigerol proved to be a practical and simpler alternative, compared to isolation. The third part of the doctoral thesis focused on studies with the purpose of increasing the water solubility of cannabinoids, which are inherently poorly soluble (or almost insoluble) in water. An approach involving the formation of a complex with glucosamine was developed, significantly increasing the water solubility of both acidic and decarboxylated forms of cannabinoids. The formation of the complex was demonstrated using multiple complementary analytical techniques, and the systematic increase in the water solubility of various cannabinoids, both isolated and present in the extract, was evaluated. It was found that the formation of the complex with glucosamine also stabilizes the acidic forms of cannabinoids. The final, fourth part of the doctoral thesis was focused on phenolic compounds. While these are the most prevalent group of secondary metabolites in nature, and they are present in hemp as well, hemp phenolics have been relatively understudied due to the general focus on cannabinoid and terpene research. Within the research, thin-layer and liquid chromatography methods were developed for the determination of phenolic compounds, and identification was performed using mass spectrometry. Water residues from hemp steam distillation, commonly used to obtain essential oil, were also evaluated as potential sources of phenolic compounds.
Secondary keywords: hemp;cannabinoids;terpenes;phenolic compounds;gas chromatography;high performance liquid chromatography;mass spectrometry;isolation of cannsbinoids;cannabinoid water solubility;Navadna konoplja;Kromatografija;Univerzitetna in visokošolska dela;
Type (COBISS): Doctoral dissertation
Study programme: 1001051
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. v Ljubljani, Fak. za kemijo in kemijsko tehnologijo
Pages: 125 f.
ID: 24530649