US 5,622,946 A · Radiation sensitization using texaphyrins

Abstract

Texaphyrins are provided for use as radiation sensitizers. Advantageous properties of texaphyrins for use as a radiation sensitizer include: i) a low redox potential which allows radiation-induced hydrated electrons to flow to texaphyrin rather than neutralizing hydroxyl radicals, allowing hydroxyl radicals to cause cellular damage, ii) a relatively stable texaphyrin radical that reacts readily to covalently modify neighboring molecules causing further cellular damage, iii) intrinsic biolocalization, and iv) indifference to the presence or absence of O.sub.2. These properties allow texaphyrins to be particularly effective for treating the hypoxic areas of solid neoplasms. Methods of treatment for an individual having a neoplasm or atheroma include the use of a texaphyrin as a radiation sensitizer and as an agent for photodynamic tumor therapy, or the use of a texaphyrin for internal and for external ionizing radiation. Novel texaphyrins are provided.

Claims46

Dependent claims

An improved method for radiation therapy of a patient with a neoplasm or atheroma employing a radiation sensitizer, wherein the improvement comprises treating said patient with an effective amount of a texaphyrin as the radiation sensitizer.

A method of radiation therapy for a host harboring a neoplasm or atheroma comprising:

administering to the host a texaphyrin, said texaphyrin having radiosensitization properties;
and
administering ionizing radiation to the host in proximity to the neoplasm or atheroma;
wherein the texaphyrin has the following structure A:
##STR7## where, M is H, a divalent metal cation or a trivalent metal cation;
R.sub.1 -R.sub.4 and R.sub.6 -R.sub.9 are independently hydrogen, halide other than iodide, hydroxyl, alkyl, aryl, haloalkyl other than iodoalkyl, nitro, formyl, acyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, aminoalkyl, oxyaminoalkyl, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule or a couple to a site-directing molecule;
R.sub.5 and R.sub.10 are independently hydrogen, alkyl, aryl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, aminoalkyl, oxyaminoalkyl, carboxyalkyl, carboxyamidealkyl or a couple to a site-directing molecule;
where R.sub.6 and R.sub.9 are other than hydrogen, then R.sub.5 and R.sub.10 are hydrogen or methyl;
where R.sub.5 and R.sub.10 are other than hydrogen, then R.sub.6 and R.sub.9 are hydrogen, hydroxyl, or halide other than iodide;
and
N is zero, 1 or 2.

8 more elements

Dependencies are inferred from the claim text.

Facts

Application

08/437,968Filed 10 May 1995 · continuation in part

Priority

12 Oct 1993

Granted

22 Apr 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification41 codes

A61K 51/0485
Complexes or complex-forming compounds, i.e. wherein a radioactive metal is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group:…
A61K 41/0038
Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations:…
A61K 41/0057
Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations: photodynamic…
A61K 41/0076
Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or…:…

Radiation sensitization using texaphyrins

Life of this patent

Radiation sensitization using texaphyrins

Life of this patent

Abstract

Claims46