We Claim:
I) Synthesis of curcumin conjugates with gycosminoglycans(GAGs) and PEGylated GAGs
which exhibit enhanced angiostatic activity of curcumin and also possibly the other
pharmacological activities of curcumin.
2) GAGs, as in claim I, include both sulfated and non-sulfated GAGS.
3) GAGs as in claim I include those having different molecular weights.
4) GAGs as in, claim I, include heparin and low and ultra low molecular weight heparins
prepared by various known methods.
5) PEGylated GAGs, as in claim I, include those derivatives having mPEG group attached to
some ofthe carboxyl groups of GAGS.
6) mPEG, as in claim 5, is mono methyl ether of polyethyleneglycol and includes those having
various molecular weights, preferably, that having an average mo]. weight of 5000 Daltons,
but not limited In it.
7) Methods for preparing conjugates, as in claim I, employing quaternary ammonium salts of
GAGs and PEGylated GAGs and functionalized curcumin.
8) Methods for preparing functionalized curcumin, as in claim 7, to facilitate the synthesis of
the conjugates, as in claim I, creating a suitable linker for covalently connecting curcumin to
GAGs and PEGylated GAGS.
9) Methods for preparing quaternary ammonium salts of GAGs and PEGylaled GAGS to
facilitate synthesis of‘conjugates, as in claim l.
10) Quaternary ammonium salts of GAGs and PEGylated GAGs, as in claim 9, are tetraalkyl
quaternary ammonium salts of carboxylic acid groups ofGAGs and PEGylated GAGS.
l l) Functionalized curcumin, as in claim 7, is halo alkanoyl esters of both the phenolic functions
of curcumin: wherein halogen atom may be chlorine, bromine, or iodine and may be present
on any ofthe carbon atoms ofthe alkyl group.
I
I2) Linker, as in claim 8, is an alkyl group with an ester function at both the phenolic groups of
curcumin molecule at one end and an ester function at the carboxylic group of GAGs or
PEGylated GAGs at the other end, connecting GAGs and PEGylated GAGs to curcumin.
13) A water soluble curcumin derivative, namely, PEGylated curcumin, wherein curcumin is
covalemly linked to mPEG.
I4) Method for preparing PEGylated curcumin as in claim 13.
15) Walcr soluble PEGylated curcumin, as in claim 14 and [5, synthesized by condensing
fumionalized curcumin with mPEG acid quat.salt (20), which is salt of carboxymethylated
mPEG.
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I6) Water soluble PEGylated curcumin, as in claim l4, exhibits enhanced angiostalic activity
and also anticipated to have other pharmacological activities of curcumin enhanced.
17) Water soluble PEGylated curcumin, as in claim 14, is expected to facilitate development of
sustained release pharmaceutical formulation ofcurcumin.
I8) Conjugates of curcumin, as in claim I, enhanced angiostatic activity of curcumin in
comparison with the activities of water soluble PEGylated curcumin and plain
microsuspension/solution of curcumin and are also anticipated to enhance other
pharmacological activities ofcurcumin
l9) Conjugates of curcumin with PEGylated GAGS, as in claim 1, also exhibited enhanced
angislatic activity of curcumin and are anticipated to exhibit similar enhancement of other
pharmacological activities ofcurcumin. Besides, these conjugates, by yinue of PEGylation,
apart from having improved water solubilities, are also expected to act like a depot,
exhibiting sustained release ofcurcumin in pharmaceutical formulations.
20) Use of all these conjugates in parenteral, ophthalmic, oral and tepical formulations to treat
deseases caused by uncontrolled angiogenesis, such as, age-related macular degeneration,
cancer, psoriasis, etc.
2]) Use of these conjugates as active ingredients in pharmaceutical formulations for imparting
other pharmacological activities attributed to natural curcumin.