Claims for Patent: 5,283,255

Summary for Patent: 5,283,255

Title:	Wavelength-specific cytotoxic agents
Abstract:	A group of hydro-monobenzoporphyrins "green porphyrins" (Gp) having absorption maxima in the range of 670-780 nanometers is useful in treating disorders or conditions which are subject to hematoporphyrin derivative (HPD) treatment in the presence of light, or in treating virus, cells and tissues generally to destroy unwanted targets. The use of the Gp of the invention permits the irradiation for therapy to use wavelengths other than those absorbed by blood. The Gp of the invention may also be conjugated to ligands specific for receptor or to specific immunoglobulins or fragments thereof to target specific tissues or cells for the radiation treatment. Use of these materials permits lower levels of drug to be used, thus preventing side reactions which might destroy normal tissues.
Inventor(s):	Julia G. Levy, David Dolphin, Jack J. Chow, Ethan Sternberg
Assignee:	University of British Columbia
Application Number:	US07/943,895
Patent Claims:	1. A method to detect, photosensitize, destroy or impair the functioning of target biological material which comprises contacting said target with an effective amount of a hydro-monobenzoporphyrin (Gp) having a light absorption maximum between 670-780 nm;wherein the Gp is selected from the group consisting of ##STR17## and mixtures thereof and the metalated and labeled forms thereof, wherein each R1 and R2 independently selected from the group consisting of carbalkoxy (2-6C), alkyl (1-6C) sulfonyl, Aryl (6-10C) sulfonyl, aryl (6-10C); cyano; and --CONR5 CO-- wherein R5 is aryl (6-10C) or alkyl (1-6C) each R3 is independently carboxyalkyl (2-6C) or a salt, amide, ester or acylhydrazone thereof, or is alkyl (1-6C); and R4 is CHCH2, CH2 OR4', --CHO, --COOR4 CH(OR4')CH3, CH(OR4')CH2 OR4', --CH(SR4')CH3, --CH(NR2)CH3, --CH(CN)CH3, --CH(COOR4')CH3, --CH((OOCR4')CH3, --CH(halo)CH or --CH(halo)CH2 (halo), wherein R4' is H, alkyl (1-6C) optionally substituted with a hydrophilic substituent, or wherein R4 is an organic noninterfering group of <12C resulting from direct or indirect derivatization of vinyl, or wherein R4 consists of 1-3 tetrapyrrole-type nuclei of the formula --L--P wherein --L-- is selected from the group consisting of ##STR18## and P is selected from the group consisting of Gp which is of the formula 1-6 but lacking R4 and conjugated through the position shown as occupied by R4 to L, and a porphyrin of the formula: ##STR19## wherein each R is independently H or lower alkyl (1-4C); wherein two of the bonds shown as unoccupied on adjacent rings are joined to R3 and one of the remaining bonds shown as unoccupied is joined to R4 and the other to L; with the proviso that if R4 is CHCH2, both R3 cannot be carbalkoxyethyl; and irradiating said target with light absorbed by said Gp. 2. The method of claim I wherein each R3 is --CH2 CH2 COOH or a salt, amide, ester or acylhydrazone thereof. 3. The method of claim 1 wherein each of R1 and R2 is carbalkoxy (2-6C). 4. The method of claim 2 wherein each of R1 and R2 is carbalkoxy (2-6C). 5. The method of claim 1 wherein the Gp has formula 3 or 4. 6. The method of claim 4 wherein the Gp has formula 3 or 4. 7. The method of claim 1 whereinthe Gp has formula 3 or 4 and mixtures thereof, and wherein each R1 and R2 independently selected from the group consisting of carbalkoxy (2-6C), alkyl (1-6C) sulfonyl, aryl (6-10C) sulfonyl, aryl (6-10C) cyano; and --CONR5 CO-- wherein R5 is aryl (6-10C) or alkyl (1-6C); each R3 is independently carboxyalkyl (2-6C) or a salt, amide, ester or acylhydrazone thereof, or is alkyl (1-6C); R4 is CHCH2 CH2 OR4', --CHO, --COOR4', CH(OR4')CH3, CH(OR4')CH2 OR4', --CH(SR4')CH3, --CH(NR4' 2)CH3, --CH(CN)CH3, --CH(COOR4')CH3, --CH((OOCR4')CH3, --CH(halo)CH3, or --CH(halo)CH2 (halo), wherein R4' is H, alkyl (1-6C) optionally substituted with a hydrophilic substituent. 8. The method of claim 1 whereinthe Gp has formula 3 or 4 and mixtures thereof, and wherein each R1 and R2 is independently selected from the group consisting of carbalkoxy, alkyl (1-6C) sulfonyl, aryl (6-10C) sulfonyl, aryl (6-10C) cyano; and --CONR5 CO-- wherein R5 is aryl (6-10C) or alkyl (1-6C); each R3 is independently carboxyalkyl (2-6C) or a salt, amide, ester or acylhydrazone thereof, or is alkyl (1-6C); and wherein R4 is a substituent containing 1-3 tetrapyrrole-type nuclei, of the formula --L--P as herein defined. 9. The method of claim 1 wherein the target materials are cells or tissue harbored in a subject and said contacting comprises administering the Gp in vivo to said subject harboring said cells or tissue. 10. The method of claim 9 wherein the administering is by an oral route. 11. The method of claim 9 wherein the administering is topical. 12. The method of claim 9 wherein the administering is by injection. 13. The method of claim 9 wherein the Gp further contains a label. 14. The method of claim 13 wherein the label is selected from the group consisting of technetium, gallium and indium. 15. The method of claim 1 wherein the target is contained in a biological fluid. 16. The method of claim 15 wherein the biological fluid is blood or blood plasma. 17. The method of claim 16 wherein the fluid is treated ex vivo. 18. The method of claim 1 wherein said method is to photosensitize, destroy or impair the functioning of target biological material, and where said irradiating is conducted with light of wavelength between 670-780 nm. 19. The method of claim 18 wherein said irradiation is supplied by a laser. 20. The method of claim 18 wherein said irradiation is supplied by a light-emitting diode. 21. The method of claim 1 wherein the target material is the lesions of psoriasis. 22. The method of claim 1 wherein the target material is atherosclerotic plaque. 23. The method of claim 1 wherein the target material is a virus. 24. The method of claim 1 which is to detect the target biological material and wherein said irradiating excites said Gp to emit fluorescence. 25. A method to detect or impair the metabolism of or to effect the destruction of target virus, cells, or tissues which comprises contacting said target with an effective amount of the Gp compound as defined in claim 1, or a pharmaceutical composition thereof, and irradiating the contacted virus, cells, or tissues with light absorbed by the Gp. 26. The method of claim 25 wherein the target comprises cells selected from tumor cells, T-suppressor cells and infective cells.