Chelidonium majus L. a source of new pharmaceutical forms
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StatusThe thesis was presented on the 13 September, 2006Approved by NCAA on the 26 October, 2006 Abstract – 0.53 Mb / in romanianThesisCZU 615.322+615.4+615.244
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Keywords
greater celandine, alkaloids, HPLC coptisine, chelidonine, antimicrobial, antifungal, cytotoxic, acute toxicity, fresh juice, tincture, extract fluid, gel, capsules, tabletsSummary
In this thesis was made a complex study of species Chelidonium majus L, fam. Papaveraceae (Greater Celendine), was elaborated method of dosing of alkaloids in vegetal and extractive produces, was formulated and optimized technology of pharmaceutical drugs with standardized content of alkaloids, was elaborated analytical documentation.
HPLC method of dosing of alkaloids, whose content in plant is up to 30, gives us a possibility to emphasize two main alkaloids, coptisine and chelidonine. Quick and exact method of dosing of coptisine in aerial parts, roots and extractive produces, obtained from chelidonium majus L., was elaborated. Maximum content of coptisine and chelidonine was determined in tincture from chelidonii herba, prepared with 70% ethylic alcohol.
We propose a new method of high performance liquid chromatography to determine the quantity of coptisine in vegetal and extractive produces. Content of coptisine in vegetal produces is: 0,49%, in aerial parts and 0,58% in roots, which is higher by 2-3 times than results obtained by pharmacopoeia method (0,2%). The kinetics and fullness of extraction of coptisine from chelidonii herba was studied.
For extraction of coptisine from chelidonii herba is recommending Squibb method of repercolation, without preventive moistening of vegetal produce. This method is more efficient and gives an output of coptisine over 60%.
Dynamic of accumulation of coptisine and chelidonine was studied in aerial parts of Chelidonium majus L., collected in bud, first and second phases of blooming. Constant accumulation of coptisine in quantity higher than chelidonine was determined. Obtained results confirm data of past years, which shows that main alkaloid in chelidonium majus is coptisine and not chelidonine how it was considered before. Coptisine in fresh juice is prevelent in form of 8-oxocoptisine, which in process of drying of vegetal produce passes into coptisine. This date is confirmed in experiments.
First fructification phase was recommended as phase of collecting of vegetal produce used as primary substance for obtaining pharmaceutical products with content of coptisine.
To obtain fresh standardized juice from Chelidonium majus L. was proposed method with 96% ethylic alcohol added to fresh juice in equal parts which contributes to a higher content of coptisine in product.
Seven formulas of hydro gels, on basis of HPMC, Carbopol 940 with fresh juice of Chelidonium majus L., were obtained. Reological studies demonstrated that gels are tixotrop systems with Non-Newtonian plastically flow, which depends of time.
Plan method of experiences of the computerized program “Modde 7” was used to optimize composition of hard capsules with content of fresh juice of Chelidonii herba.
Researches of preformulation and formulation of matrix type tablets, with content of fresh juice of Chelidonii herba, were made to control coptisine release from tablet. As polymer was selected Carbopol 940.
DL50 for fresh juice from chelidonii herba, recalculated to coptisine, was determined on mouse and rats. DL50 is respectively – 24,82 mg/ml and 24,79 mg/ml.
Temporary Pharmacopeia’s monographs and Technological regulations of manufacture were elaborated at following pharmaceutical forms: tincture, fluid extract, capsules, tablets and fresh juice.
This products were implemented in “pilot phase” at: S.R.L. „NeoGalenaFarm”, „Farmaco” S.A. and Î.C.S. „Eurofarmaco” S.A.
Oficial Reviewers
- Vladimir Valica
doctor habilitat, professor, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova - Iuliana Popovici
doctor în farmacie, profesor universitar, UMF „Gr.T. Popa” Iaşi, România.
Theses
