| 摘要 |
High purity pharmaceutical-grade water-soluble porphyrin derivatives having a general formula given by formula (1 or 2) and new methods to prepare and use such porphyrin derivatives: wherein B is a ring having the structure: (a) (b) (c) (d) (e) wherein : R1=-CH=CH2, -CH(Oalk)CH3, -CHO, -C(O)CH3, -CH2CH3, -CH(Alk)CH(COAlk)2, -CH2CH(COAlk)2, -CH(Alk)CH2COAlk, -CH(Alk)CH2CH(OH)CH3, and CH2CH2CH(OH)CH3 R2= -CH3, CHO, -CH(OH)Alk, CH=CHAlk, CH2OH, and CH2OAlk; R3= -OH, -Oalk, -NH-Alk, NH-X-COO-(HG)+, -NH-Y-NR8R9, -and NH-Y-OH; R4= -O-(HG)+, -Oalk, -NH-Alk, and NH-X-COO-(HG)+; R5= -O-(HG)+, -Oalk, -NH-Alk, and NH-X-COO-(HG)+; R6=H and COOAlk; R7=-O-(HG)+, -Oalk, -NH-Alk, and NH-X-COO-(HG)+; R8=H and Alk R9=H and Alk wherein: -NH-X-COO-= the residue of organic amino acid; X = alkylidene, peptides, oligopeptides and (CH2CH2O)nCH2CH2-, wherein n=1-30; Y = alklidene and (CH2CH2O)nCH2CH2 -, wherein n1-30; G = a hydrophilic organic amine(CHf.ex. N-methyl-D-glucamine and other amino-group containing carbohydrate derivatives, TRIS, amino acids, oligopeptides); and Alk = an alkyl substituent. An embodiment of the present invention consists of a method to prepare water-soluble porphyrin derivatives comprising the steps of one- or two-step direct acidic alcoholysis of biological raw material producing a crystalline alkyl pheophorbide, conversion of the obtained alkyl pheophorbide into an acidic porphyrin, and reaction of the acidic porphyrin in water or in an aqueous organic solution with a hydrophilic organic amine. Another embodiment of the present invention consists of a method to prepare water-soluble porphyrin derivatives, comprising reaction of acidic porphyrins prepared by any known method in water or in aqueous organic solution with a hydrophilic organic amine. Another embodiment of the present invention comprises the additional step of purification of the resurtant water-soluble porphyrin derivative by reversed phase chromatography using volatile solvents. The compound disclosed in the present invention can be used as photosensitizers for the photodynamic therapy of cancer, infectious and other diseases as well as for light irradiation treatment in other cases. |
