How to make hypericin water-soluble.

摘要: Received September 6, 2007, accepted October 2, 2007Andreas Kubin, PhD, Erlgasse 48, A-1120 Vienna, Austriaakubin@planta.at* Equally contributing and sharing first authorshipPharmazie 63: 263–269 (2008) doi: 10.1691/ph.2008.7292Hypericin, isolated from Hypericum perforatum, is an effective photodynamic substance as demon-strated by various studies. Practical forms of applications hypericin solutions for systemic use andintroduction into body cavities are, however, lacking. We developed aqueous solution hypericinnon-covalently bound to polyvinylpyrrolidone (PVP). PVP a poly-N-vinylamide degrees ofpolymerization intermolecular crosslinks suitable diagnostic therapeutic applica-tions. used (molecular weights between 10 kD 40 kD) complex formingagent prepare therapy diagnostics. In pure water, formsaggregates which are non-soluble non-fluorescent. The hypericin-PVP binds more than1000 mg in presence 100 g or less soluble 1 liter water. Aqueouscomplex display characteristic absorption spectrum fluorescenceemission band around 600 nm wavelength. Varying concentrations do not cause blue-or red-shift the maximum at 595 nm. Excitation 200 500 leads emission at590 nm; property conducive investigations both vitro vivo. Furthermore, hyper-icin-PVP exhibits high photostability oxygen broad light ensuresreproducible diagnosis. Conclusion: Hypericin liquid molecular chro-mophore complexes water when thus allowing biological media.1. IntroductionA new field medicine has arisen over last 25 years:the development selec-tive photosensitization treatment malignant types oftissues (Dougherty Marcus 1992; van Hillegersberget al. 1994; Henderson Dougherty Ochsner1997a; Manyak et 1988). Two promising methods are:1) induction photophysical effects (e.g. inducedfluorescence) within tissues perform di-agnosis (PPD) diagnosis (PDD) 2)induction photochemical processes underthe influence medicalphotodynamic (PDT). Since 1992 number ofmonthly presented scientific publications on PDD PDThas been increased factor 3 (Medline, Current con-tents Life sciences) indicating international interest inand increasing PDT successful form tumortherapy. Moreover, several research programs have recom-mended non-malignant diseases suchas vascular dysplasias virus infections (Ochsner 1997a).Wide clinical established mainly inthe ophthalmology maculardegeneration.PDD involve interactions sensitizersubstance administered delivered tissue substratesand must be introduced (Ochsner1997b; Freitas Baronzio 1991). Favorable sensitizersshould non-toxic after application shouldaccumulate specifically tumor tissue. Irradiation ofthe targeted using visible induces photo-chemical reactions type II I, whichcause destruction biomolecules, biomembranes sub-cellular organelles 1997b).Ideally, photosensitizer should sys-temic introduction cavities. Hy-pericin purified perforatum,is hasbeen demonstrated studies (Diwu 1995; Vander Werf 1996; Wynn Cotton Vandenbo-gaerde 1998; Falk 1999). Recent haveshown that inhibitstumor growth successfully mouse modelsvia apoptosis necrosis associated damage(Falk Mayr Kil D’Hallewin al.2000). However, in-vestigate phototherapeutic potentialof rare.Hypericin hydrophobic nearly insoluble water,oil, methylene chloride most other nonpolar solventsbut alkaline solutions, organic basessuch pyridine, polar substances includingacetone, ethanol, methanol, ethyl acetate, methyl ke-tone, solvents yielding red with fluor-