Hematoporphyrin derivative and method of preparation and purification

• US 4,861,876 A
• Filed: 11/26/1986
• Issued: 08/29/1989
• Est. Priority Date: 11/26/1986
• Status: Expired due to Fees

• Current Assignee: Wayne State University
• Original Assignee: Wayne State University
• Inventors: Kessel, David
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US06/935,269
• Time in Patent Office: 1,007 Days
• Field of Search: 540/145
• US Class Current: 540/145
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

A substance effective for treatment of tumors having a fluorescent emission between 640 nm and 650 nm capable of preferentially localizing in and being retained in tumor cells, the substance being a product of esterification of hematorporphyrin with a chlorin and a process for destruction of tumor cells in a patient involving the steps of:

(a) injecting a solution containing the substance into a patient;

(b) allowing the substance to accumulate in the tumor cells; and

(c) irradiating the tumor site with light at a predetermined intensity and a wavelength between about 640 nm and about 650 nm.

Claims

1. A substance effective for treatment of tumor cells having a fluorescent emission between 640 and 650 nm and capable of preferentially localizing in and being retained in tumor cells over normal cells, the substance selected from the group consisting of:

##STR2## and its isomers;

##STR3## and its isomers;

II. the alkali metal salts thereof; and

mixtures thereof;

IV. the alkali metal salts thereof; and

mixtures thereof;

2. A process for the production and purification of the substance of claim 1 comprising the steps of:

(a) admixing a chlorin which is a reduced porphyrin selected from the group consisting of;

mesochlorin, bonellin and mixtures thereof, in an aqueous alkaline solution having a concentration of an alkali metal hydroxide between about 0.05 and about 0.5 M;

(b) adding an amount of hematoporphyrin diacetate to the solution formed in Step A, the hematoporphyrin being added over an interval of between two and twenty minutes;

(c) allowing the solution to react for a period sufficient to exhaust the chlorin available in solution;

(d) hydrolyzing any unreacted hematoporphyrin diacetates remaining in solution after the reaction period of Step C;

(e) adjusting the acidity of the solution to a pH of 5 after the reaction period of Step C;

(f) maintaining ambient temperatures throughout the process; and

(g) isolating the reaction product of esterification of hematoporphyrin with chlorin as a result of Steps a through f.

3. The process of claim 2 wherein the chlorin is admixed in an aqueous solution containing sodium hydroxide.

4. The process of claim 2 wherein the hydrolyzing step comprises adding a portion of aqueous sodium hydroxide to the reaction mixture.