Production Technologies of Pharmacologically Active Sesquiterpene Lactones

  • A.S. Kishkentayeva
Keywords: sesquiterpene lactone, α-santonin, alantolactone, isoalantolactone, tauremisin, arglabin, artemisinin, thapsigargin, trilobolide production technology

Abstract

Sesquiterpene lactones form a large group belonging to natural terpenoids series, generally found in plants of Asteraceae family and exhibiting anti-tumor, antiviral, immunostimulant, antifungal, antimicrobial, anti-inflammatory, antimutagenic, growth stimulating, antifeedant effects. Therefore, search for new compounds with a broad spectrum of pharmacological activity in this series provides the opportunities for effective and conceptually new drug design. The basis of the technology for the isolation of sesquiterpene lactones is the extraction of raw materials with various organic solvents, followed by chromatographic purification. Sesquiterpene lactones have no common properties that can be used in their isolation. Some of them are well soluble in non – polar solvents, others-only in polar, in this regard, the methods of isolation of sesquiterpene lactones are diverse. The greatest number of sesquiterpene lactones is isolated from leaves and flowers, slightly less –from roots and bark. Therefore, the development of methods for their isolation is associated with the selection of solvents and optimization of the extraction mode. Unfortunately, very few medicines based on sesquiterpene lactones are produced by the pharmaceutical companies today. Complexity of introduction of pharmacologically active sesquiterpene lactones technology into pharmaceutical production is in imperfection of their isolation methods from plant raw material, their purification and separation from obtained extracts. Production technologies of the patented medicines "Santonin", "Alanton" on the basis of sesquiterpene lactones are multiphase, labor-intensive, implying the use of many toxic organic solvents which is against the international GMP standards.

References

(1). S.A. Minina, I.E. Kaukhova Chemistry and technology of phytopreparations. Publishing house, Moscow, 559 p.

(2). USSR Patent No.202468 Production method of tauremisin. K.S. Rybalko, A.I. Bankovsky, R.I. Evstratova, V.A. Burnt. Application 13.05.1963, issued 23.11.1967. Bulletin No. 195.

(3). USSR Patent. No.577034. Production method of sesquiterpene lactones. P.P. Khvorost, D.G. Kolesnikov, N.F. Komisarenko, G.V. Oboleshcheva, A.I. Vidyukova, Ya.I. Khadzhai, M.M. Luchkova, V.P. Georgievsky, L.D. Degtyarov, V.V. Zinchenko. Application 15.04.1976, issued 25.10.1977. Bulletin No. 39.

(4). USSR Patent No.727646 Production method of alantolactone. N.V. Plekhanova, S.A. Lugovskaya, G.P. Fedorchenko. Application 02.02.1978, issued 15.04.1980. Bulletin No. 14.

(5). I.A. Milman, Chem. Nat. Compd. 3 (1990) 251–262. Crossref

(6). USSR Patent No.1710062 Production method of sesquiterpene lactones. N.F. Babayev, S.V. Serkerov. Application 09.01.1990, issued 07.02.1992. Bulletin No. 5.

(7). A. Trendafilova, Ch. Chanev, M. Todorova, Pharmacogn. Mag. 6 (2010) 234–237. Crossref

(8). K.V. Belyakov, D.M. Popov, Pharmacy 1 (2004) 37–38.

(9). V.P. Georgievsky. Technology and standardization of medicines. Kharkiv, Rireg, 1996, 749 p.

(10). I.A. Khabarov, Farmacevticheskij bjulleten' [Pharmaceutical Bulletin] 1-2 (2016) 89–101 (in Russian).

(11). Hugo A. Martinez-Correa, Raphaela G. Bitencourt, Anna Carolina A.V. Kayano, Pedro M. Magalhães, Fabio T.M. Costa, Fernando A. Cabral, Ind. Crop. Prod. 95 (2017) 535–542. Crossref

(12). Y.-L. Lin, C.-C.Yang, H.-K.Hsu, S.-L. Hsu, C.-M.J. Chang, J. Supercrit, Fluids 39 (2006) 48–53. Crossref

(13). S. Quispe-Condori, D. Sanchez, M.A. Foglio, P.T.V. Rosa, C. Zetzl, G. Brunner, M.A.A. Meireles, J. Supercrit. Fluids 36 (2005) 40–48. Crossref

(14). H. Misra, D. Mehta, B.K. Mehta, D.C. Jain, Organic Chemistry International (2013) Article ID 163028. Crossref

(15). T.C. Tzeng, Y.L. Lin, T.T. Jong, C.M.J. Chang, Sep. Purif. Technol. 56 (2007) 18–24. Crossref

(16). G. Della Porta, E. Reverchon, A. Benakis Extraction and fractionation of antimalaricdrugs by supercritical fluid, Ninth Meeting on Supercritical Fluids, 2004, p. 1-6.

(17). M. Kohler, W. Haerdi, P. Christen, J.L. Veuthey, J. Chromatogr. A 785 (1997) 353–360. Crossref

(18). R. Briars, L. Paniwnyk, Ind. Crop. Prod. 42 (2013) 595–600. Crossref

(19). H. Zhang, L. Zhang, X. Hu, Y. Zhou, C. Ding, R. Yang, X. Wang, D. Li, Sep. Sci. Technol. 49 (2014) 673–681. Crossref

(20). CN Pat. 101205232А. Technical new method for extracting artemisinin from sweet wormwood plants by ultrasonic assistance. Guojun Wang, Xiao Ruan, Qiang Wang. Application 19.12.2006, issued 25.06.2008.

(21). US Pat. 6685972А. Process for isolating artemisinin from Artemisia annua. Kumar Sushil, Gupta Shiv Kumar, Singh Digvijay, Gupta Madan Mohan, Jain Dharam Chand, Kahol Atul Prakash, Khanuja Suman Preet, Singh Ram Govind. Application Number: 10/112070, publ. 02.03.2004.

(22). CN Pat. 103694249A. Production technology for extracting artemisinin from Artemisia annua. Hu Canhua, Lei Yurong. Application 28.12.2013, issued 02.04.2014.

(23). CN Pat. 102617591А. Method for producing artemisinin from Artemisia annua serving as Chinese herbal medicine. Xiao Yuan, Dongbin Zhou, Junfei Gao, Chujin Shu. Application 07.03.2012, publ. 01.08.2012.

(24). CN Pat. 103664988А. Extraction and separation method for artemisinin. Li Zhipin. Application 25.12.2013, publ. 20.01.2016.

(25). CN Pat. 102219790А. Green extraction process for artemisinin. Shengqun Huang, Wugou Liu, Zongyan Huang, Huaxing Tan, Xueping Kong. Application 05.05.2011, issued 19.10.2011.

(26). CN Pat. 104628739А. Extraction technology of artemisinin. Tan Binfeng. Application 09.11.2013, publ. 20.05.2015.

(27). CN Pat. 1931860А. Process of extracting, separating and purifying artemisinin from sweet wormwood herb. Gang Xu, Liang Deng, Yaping Zhao. Application 28.09.2006, issued 19.08.2009.

(28). US Pat. 20100331553. Process for manufacturing artemisinin. Villanova Luciano, Villanova Azzurra, Cisale Felicia, Villanova Luigi. Application 25.09.2008, issued 30.12.2010.

(29). CN Pat. 104140433А. Artemisinin preparation method. Lan He. Application 10.05.2013, issued 12.11.2014.

(30). CN Pat. 103647480А. Method for extracting artemisinin and application of artemisinin. Nanjing Zelang Medical Technology Co. Ltd. Application 10.10.2013, issued 25.12.2013.

(31). DE Pat. 10336056 A l. Extracting pharmacological agent from Artemisia annua, useful for treating cancer and AIDS in addition to malaria, comprises using carbon dioxide at relatively low temperature and pressure. Doebel Katrin, Sandau Petra, Franke Horst, Pulz Otto. Application 01.08.2003, issued 24.02.2005.

(32). Pat. CN 103333178A. Method for preparing antimalarial active compound artemisinin through direct column chromatography. Chen Yegao, Ma Yanfang, Cui Guangxin. Application 29.07.2013, issued. 02.10.2013.

(33). Pat. US 2015328617. Method and device for the synthesis of artemisinin. Seeberger Peter, Kopetzki Daniel, Lirvesque Francois. Application 29.08.2011, issued 19.11.2013.

(34). Patent USA 6,242,617, B1, Jun.5.2001; Europian Patent № 0946565, 15.10.2003; Deutschen Patent № 697 2504.9-08, 23.10.03; Swiss Patent 97 947 981.3 (CH) EP 0946565; China. Patent ZL 2006 8 0055852.4, 26.12.12. S.M. Adekenov Method and device for production of lyophilized hydrochloride-1(10)β-epoxy-13-dimethylamino-5,7α,6,11β(H)-guaia-3(4)-en-6,12-olide.

(35). RK Patent No. 32482. Method of complex processing of raw wormwood smoothness. S.M. Adekenov, E.G. Tolokonnikov, Kh.I. Itzhanova, A.N. Zhabaeva, V.S. Korneev, I.A. Khabarov. Declared 03.12.2015, publ. 11.15.2017. Bul.No. 21.

(36). U. Rasmussen, B. Christensen, F. Sandberg, Acta Pharm Suec. 15 (1978) 133‒140. PMID: 79299

(37). V.P. Sulsen, V.S. Martino, Sesquiterpene Lactones. Advances in their Chemistry and Biological Aspects, Springer, Cham. Crossref

(38). G. Appendino, S. Prosperini, C. Valdivia, M. Ballero, G. Colombano, R.A. Billington, A.A. Genazzani, O. Sterner, J. Nat. Prod. 68 (2005)1213‒1217. Crossref

(39). A. Ollivier, R. Grougnet, X. Cachet, D. Meriane, J. Ardisson, S. Boutefnouchet, B. Deguin, J. Chromatogr. B 926 (2013) 16‒20. Crossref

(40). Pat. CZ 300806 Immunostimulation properties of trilobolide and a method of its preparation E. Kmoníčková, Z. Zídek, J. Harmatha, M. Buděšínský, K. Vokáč. Application 18.07.2007, issued 02. 07.2009. WO 2009/010021 A1.

(41). Z. Smítalová Sesquiterpene lactones from Laserpitieae, PhD Thesis, Czechoslov. Acad,.Sci. Prague 1987.

(42). J. Vyšohlíd Investigation of sesquiterpene derivatives, BSc. Thesis, UCT Prague 2016.

Published
2018-12-21
How to Cite
[1]
A. Kishkentayeva, “Production Technologies of Pharmacologically Active Sesquiterpene Lactones”, Eurasian Chem. Tech. J., vol. 20, no. 4, pp. 325-333, Dec. 2018.
Section
Articles