Benzoporphyrin derivatives

Haimovici, R, Kramer, M, Miller, JW, Hasan, T, Flotte, TJ, Schomacker, KT, and Gragoudas, ES, 1997. Localization of lipoprotein-delivered benzoporphyrin derivative in the rabbit eye. Curr Eye Res 16, 83-90. 

The forms of phototherapy in common use include (i) the phototherapy of jaundice (neonatal hyperbilirubinemia) in the newborn, and especially in the prematurely born 5 (ii) the treatment of psoriasis using light in the UV-A range (320 100 nm) and an administered photosensitizer, such as 8-methoxypsoralen 6 (iii) the treatment of the wet form of age-related macular degeneration with a photosensitizer such as a benzoporphyrin derivative (VISUDYNE ), and a laser light source 7 and (iv) the treatment of certain cancers with a photosensitizer such as a porphyrin derivative, and red light.8... 

Benzoporphyrin derivative, monoacid, ring A adduct BPD, VERTEPORFIN, VISUDYNE... 

Chowdhary, R. K., Shariff, I., and Dolphin, D. (2003). Drug release characteristics of lipid based benzoporphyrin derivative.J. Pharm. Pharm. Sci., 6, 13-19. 

Fig. 2 Examples of photosensitizers presently approved for clinical applications or in clinical studies. mTHPC, tetra (meso-hydroxy) phenyl chlorin BPD-MA, benzoporphyrin derivative Photofrin is a mixture of several compounds where dimers or trimers of the indicated structure are assumed to be of major importance PpIX, protoporphyrin IX - accumulating upon treatment with 5-aminolevulinic acid or its ester derivatives, NPe6, HPPH, Hexyl pyropheophorbide TPPS2a, disulfonated (adjacent) tetraphenylporphin AlPcS2a, disulfonated (adjacent) aluminum phthalocyanine. Areas with ionic side groups are indicated in shadow...

A benzoporphyrin derivative mono ester (Figure 16) obtained by Diels-Alder addition of dimethylacetylenedicarboxylate to protoporphyrin dimethyl ester followed by rearrangement and partial hydrolysis has been studied by Richter et al. [53]. This material has a relatively strong absorption near 690 nm but appears to be rapidly cleared and/or metabolized in vivo, which may make proper dosimetry difficult as described above. 

Figure 16. Structure of a benzoporphyrin derivative-mono acid form.

Richter AM, Waterfield E, Jain AK, Sternberg ED, Dolphin D, Levy JG. In vitro evaluation of phototoxic properties of four structurally related benzoporphyrin derivatives. Photochem Photobiol 1990 52 495-500. 

Richter AM, Cerruti-Sola S, Sternberg ED, Dolphin D, Levy JG. Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice. J Photochem Photobiol B 1990 5 231-244. 

Richter AM, Waterfield E, Jain AK, et al. Photosensitising potency of structural analogues of benzoporphyrin derivative (BPD) in a mouse tumour model. Br J Cancer 1991 63 87-93. 

Richter AM, Yip S, Waterfield E, Logan PM, Slonecker CE, Levy JG. Mouse skin photosensitization with benzoporphyrin derivatives and Photofrin macroscopic and microscopic evaluation. Photochem Photobiol 1991 53 281-286. 

Moulton RS, Walsh AW, Miller JW. Response of retinal and choroidal vessels to photodynamic therapy using benzoporphyrin derivative monoacid. Invest Ophthalmol Vis Sci 1993 34 S1169. 

Kramer M, Miller JW, Michaud N, et al. Liposomal benzoporphyrin derivative verte-porfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys. Ophthalmology 1996 103 427-438. 

Husain D, Miller JW, Michaud N, Connolly E, Flotte TJ, Gragoudas ES. Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization. Arch Ophthalmol 1996 114 978-985. 

Busetti, A., Soncin, M., Jori, G., and Rodgers, M.A. (1999) High efficiency of benzoporphyrin derivative in the photodynamic therapy of pigmented malignant melanoma, Br. J. Cancer, 79 821-824. 

Benzoporphyrin derivative monoacid ring A (BPD-MA) Verteporfin Visudyne QLT Inc. Novartis Opthalmic 690... 

B.A. Allison, P.H. Pritchard, J.G. Levy (1994). Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative. Br. J. Cancer, 69, 833-839. 

B.A. Allison, M.T. Crespo, A.K. Jain, A.M. Richter, Y.N. Hsiang, J.G. Levy (1997). Delivery of benzoporphyrin derivative, a photosensitizer, into atherosclerotic plaque of Watanabe heritable hyperlipidemic rabbits and balloon-injured New Zealand rabbits. Photochem. PhotobioL, 65, 877-883. 

U. Schmidt-Erfurth, T. Hasan, K. Schomacker, T. Flotte, R. Birngruber (1995). In vivo uptake of liposomal benzoporphyrin derivative and photothrombosis in experimental corneal neovascularization. Lasers Surg. Med., 17, 178-188. 

L. Cincotta, D. Szeto, E. Lampros, T. Hasan, A.H. Cincotta (1996). Benzophenothiazine and benzoporphyrin derivative combination phototherapy effectively eradicates large murine sarcomas. Photochem. Photobiol, 63, 229-231. 

G. Simkin, M. Obochi, D.W.C. Hunt, A.H. Chan, J.G. Levy (1995). Effect of photodynamic therapy using benzoporphyrin derivative on the cutaneous immune response. In T.J. Dougherty (Ed.), Optical Methods for Tumor Treatment and Detection Mechanisms and Techniques in PDT IV (Proc. SPIE. Vol. 2392, pp. 23-33). 

D. Kessel (1989). In vitro photosensitization with a benzoporphyrin derivative. Photochem. Photobiol, 49, 579-582. 

Another porphyrin-based photosensitizer, benzoporphyrin derivative monoacid A (Verteporphin, Visudyne ), has received approval for treatment of age-related macular degeneration, and a form of pathologic myopia. 

H. Lui, L. Hruza, D. McLean, M. Grossman, G. Hruza, K. Gelmon, N. Kollias, J. Wimberly, M. Gagel, R.R. Anderson (1995). Photodynamic therapy of malignant skin tumors with BPD verteporfin (benzoporphyrin derivative). Laser Surg. Med., 7 (Suppl), 44. 

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