Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-10-12
2003-01-28
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C540S122000, C540S136000, C540S137000, C540S139000, C540S140000, C514S184000, C514S185000
Reexamination Certificate
active
06511971
ABSTRACT:
BACKGROUND OF THE INVENTION
Phthalocyanines are a group of photoactive compounds that are somewhat structurally similar (i.e., have nitrogen containing ring structure) to the porphyrin family. Phthalocyanines are azaporphyrins consisting of four benzoindole nuclei connected by nitrogen bridges in a 16-membered ring of alternating carbon and nitrogen atoms around a central metal atom (i.e., C
32
H
16
N
8
M) which form stable chelates with metal cations. In these compounds, the ring center is occupied by a metal ion (such as a diamagnetic or a paramagnetic ion) that may, depending on the ion, carry one or more ligands. In addition, the ring periphery may be either unsubstituted or substituted.
Owing to their high stability and unique physicochemical properties, phthalocyanines and related macrocycles have found widespread applications in various disciplines (
Phthalocyanines-Properties and Applications
; Leznoff and Lever, Eds.; VCH: New York, 1989, Vol. 1; 1993, Vols. 2 and 3; 1996, Vol. 4.) Numerous studies have been carried out to modify these tetrapyrrole derivatives with the goal of modifying their properties and optimizing their performance as advanced materials. For some applications, such as photodynamic therapy, photoinactivation of viruses in stored blood products, and the photooxidation of mercaptans in petroleum distillates, it is desirable that the macrocycles are free of molecular aggregation (Bonnet,
Chem. Soc. Rev
. 1995, 19; Milgrom et al.
Chem. Br
. 1998 (May), 45; Rywiken, S. et al.
Photochem. Photobiol
. 1994, 60:165; Abe, H. et al.
Photochem. Photobiol
. 1995, 61:402; Allen, C. M. et al.
Photochem. Photobiol
. 1995, 62:184; Iliev, V. et al.
J. Chem. Soc. Catal. A. Chem
. 1995, 103:147; Kimura et al.
J. Porphyrins Phthalocyanines
, 1997, 1:309).
Molecular aggregation, a common phenomenon of this family of compounds, drastically decreases the compounds' luminescence quantum yield, which results in decreased photosensitizing efficiency (Tai, S. et al.
J. Chem. Soc. Perkin Trans
. 2 1991, 1275; Schutte, W. et al.
J. Phys. Chem
. 1993, 97:6069; Spikes, D. J.
Photochem. Photobiol
. 1986, 43:691; Vacus, J. et al
Adv. Mater
. 1995, 7:797; Dharni, S et al.
J. Photochem. Photobiol A: Chem
. 1996, 100:77; Howe, L. et al.
J Phys. Chem
. A, 1997, 101:3207). Increased water solubility of phthalocyanines has been shown to decrease their aggregation tendencies (Schelly, Z. A. et al.
J. Phys. Chem
. 1970, 74:3040; Yang, Y. C. et al.
Inorg. Chem
. 1985, 24:1765). Hydrophilic and non-aggregating phthalocyanines are potentially useful materials, but the study of these phthalocyanines is still in its infancy (Kimura, M. et al.
Chem. Commun
. 1997, 1215).
SUMMARY OF THE INVENTION
The invention pertains, at least in part, to phthalocyanine compounds of formula
wherein X
1-8
are each halogen and R
1-8
are each independently halogen or an anti-stacking moiety.
The invention also includes phthalocyanine compounds of formula II:
[M
x
L
y
S
z
]C
w
(II)
wherein M is a metal, L is an anion of a phthalocyanine compound of formula I as defined above, S is an organic or inorganic ligand, C is a counterion, x and y are numbers greater than zero, and z and w are numbers zero or greater. In preferred embodiments, M is a metal cation.
In one embodiment, R
1-8
are not all halogen. In another embodiment, each of X
1-8
is fluorine. In another embodiment, the anti-stacking moieties are inert to activated oxygen and may be selected such that the phthalocyanine compound is soluble in water. In yet another embodiment, the anti-stacking moieties are branched alkyl and are, advantageously, perhalogenated. In one embodiment, the anti-stacking moiety is perfluorinated branched alkyl. In another embodiment, M is diamagnetic.
The invention also pertains to a pharmaceutical composition, comprising a pharmaceutically acceptable carrier and an effective amount of a phthalocyanine compound of formula II, as described above, and pharmaceutically acceptable salts thereof. In one embodiment, the pharmaceutical composition is suitable for the treatment of a condition in a patient. In a preferred embodiment, the composition is suitable for treating cancer in a patient, e.g., by using photodynamic therapy.
In yet another embodiment, the invention features a method for treating a condition in a patient, by administering to the patient an effective amount of a phthalocyanine compound of formula II, as described above. In one embodiment, the method comprises exposing the patient to light to achieve photodynamic therapy. Preferably, the condition is cancer and the effective amount is effective to treat cancer.
The invention also includes a method of photoinactivating viruses in blood, by contacting the blood with an effective amount of a phthalocyanine compound of formula II, as described above. The invention also pertains to a dye and a composition for organometallic catalysis each comprising at least one phthalocyanine compound of formula II.
REFERENCES:
patent: 4576173 (1986-03-01), Parker et al.
patent: 4592361 (1986-06-01), Parker et al.
patent: 4649151 (1987-03-01), Dougherty et al.
patent: 4656186 (1987-04-01), Bommer et al.
patent: 4693885 (1987-09-01), Bommer et al.
patent: 4814256 (1989-03-01), Aldag et al.
patent: 4827938 (1989-05-01), Parker
patent: 4861876 (1989-08-01), Kessel
patent: 4866168 (1989-09-01), Dougherty et al.
patent: 4889129 (1989-12-01), Dougherty et al.
patent: 4913907 (1990-04-01), Jori et al.
patent: 4932934 (1990-06-01), Dougherty et al.
patent: 5484778 (1996-01-01), Kenney et al.
patent: 5945439 (1999-08-01), Richter et al.
patent: 0 134 518 (1988-07-01), None
patent: 0 155 780 (1990-03-01), None
patent: 0 337 209 (1993-08-01), None
patent: 2229190 (1990-09-01), None
patent: 63141982 (1988-06-01), None
patent: 02049785 (1990-02-01), None
patent: 05222046 (1993-08-01), None
patent: 06072873 (1994-03-01), None
Howe et al J. Phys. Chem. A 101 (1997) 3207-3213.*
Nishisaka et al Chemical Abstract accession No. 1994:290090 for JP-06072873.*
Ito et al Chemical Abstract accession No. 1994:314462 for JP-05222046.*
Yamada et al Chemical Abstract accession No. 1990:508094 for JP-02049785.*
Okidaka et al Chemical Abstract accession No. 1989:77513 for JP-63141982.*
Abe, H. et al., “Analysis of Viral DNA, Protein and Envelope Damage After Methylene Blue, Phthalocyanine Derivative or Merocyanine 540 Photosensitiation,”Photochem. Photobiol.61(4):402-409 (1995).
Abernathy, C.D. et al., “Activity of Phthalocyanine Photosensitizers against Human Glioblastoma in Vitro,”Neurosurgery, 21(4):468-473 (1987).
Allémann, E. et al., “Photodyanamic Activities and Biodistribution of Fluorinated Zinc Phthalocyanine Derivatives in the Murine EMT-6 Tumour Model,”Int. J. Cancer, 72:289-294 (1997).
Allémann, E. et al., “Photodynamic Therapy of Tumours with Hexadecafluoro Zinc Phthalocyanine Formulated in Peg-Coated Poly(Lactic Acid) Nanoparticles,”Int. J. Canc.66:821-824 (1996).
Allen C.M. et al., “Sulfophthalocyanines for Photodynamic Inactivation of Viruses in Blood Products: Effect of Structural Modifications,”Photochem. Photobiol.62(1):184-189 (1995).
Ben-Hur, E. et al., “The phthalocyanines: a new class of mammalian cells photosensitizers with a potential for cancer phototherapy,”Int. J. Radiat. Biol.47(2):145-147 (1985).
Berg, K. et al., “Evaluation of sulfonated aluminum phthalocyanines for use in phtochemotherapy. Cellular uptake studies,”Cancer Letters44:7-15 (1989).
Berge, S. M. et al., “Pharmaceutical Salts”,J. Pharm. Sci.66(1):1-19 (1977).
Bonnet, Raymond, “Photosensitizers of the Porphyrin and Phthalocyanine Series for Photodynamic Therapy,”Chem. Soc. Rev.19:19-33 (1995).
Brasseur, N. et al., “Synthesis and Photodynamic Activities of Silicon 2,3-Naphthalocyanine Derivatives,”J. Med. Chem.37:415-420 (1994).
Brédas, J. L. et al., “Third-Order Nonlinear Optical Response in Organic Materials: Theoretical and Experimental Aspects,”Chem. Rev.94:243-278 (1994).
Britton, Doyle, “Tetrafluorophthalonitrile,”Acta Crystallogr., Sect C(CrStr. Comm.) 44:1020-1022 (1988).
Ch
Brown University Research Foundation
Habte Kahsay
Lahive & Cockfield LLP
Lauro, Esq. Peter C.
Raymond Richard L.
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