Water soluble tetrapyrollic photosensitizers for photodynamic therapy

• US 7,820,143 B2
• Filed: 02/19/2009
• Issued: 10/26/2010
• Est. Priority Date: 06/27/2002
• Status: Expired due to Fees

• Current Assignee: Health Research Incorporated
• Original Assignee: Health Research Incorporated
• Inventors: Pandey, Ravindra K., Goswami, Lalit, Gryshuk, Amy, Oseroff, Allan, Potter, William
• Primary Examiner(s): Sullivan; Daniel M
• Assistant Examiner(s): Nwaonicha; Chukwuma O
• Application Number:
  US12/378,751
• Publication Number:
  US 20090162289A1
• Time in Patent Office: 614 Days
• Field of Search: None
• US Class Current: 424/9.3
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 471/22 in which the condensed systems contains four or more hetero rings
• CPC Class Codes: C09B 47/00 Porphines; Azaporphines non-dyeing compounds C07D487/22
• CPC Class Codes: C09B 69/108 containing a phthalocyanine dye

Abstract

A tetrapyrollic photosensitizer compound having at least one pendant —CH₂CH₂CON(CH₂CON(CH₂COOH)₂)₂ or —N(CH₂COOH)₂ group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide. Desirably the compound has the formula:

or a pharmaceutically acceptable derivative thereof, wherein R₁-R₈ and R₁₀ are various substituents and R₉ is substituted or unsubstituted —CH₂CH₂CON(CH₂CON(CH₂COOH)₂)₂; or —N(CH₂COOH)₂. The invention also includes a method of treatment by photodynamic therapy by treatment with light after injecting the compound and a method of imaging by fluorescence after injection of the compound.

Claims

1. An article of manufacture, comprising packaging material and a compound contained within the packaging material or salt thereof wherein the compound or salt thereof is effective in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder;

and the packaging material includes a label that indicates that the compound or salt thereof is used in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder and the compound is a pharmaceutically acceptable tetrapyrollic photosensitizer compound having at least one pendant —

CH₂CH₂CON(CH₂CON(CH₂COOH)₂)₂ or —

N(CH₂COOH)₂ group or esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide wherein the compound has the formula;

2. A method for administering a therapy to a target comprising hyperproliferative tissue, comprising:

(i) administering to a subject by injecting a pharmaceutically acceptable compound that preferentially associates with the target, and

(ii) irradiating the subject with light of a wavelength and total fluence sufficient to produce a therapeutic effect;

wherein the compound is a tetrapyrollic photosensitizer compound having at least one pendant —

CH₂CH₂CON(CH₂CON(CH₂COOH)₂)₂ or —

N(CH₂COOH)₂ group or lower alkyl esters thereof said tetrapyrollic compound being a chlorin, bacteriochlorin, porphyrin, pyropheophorbide, purpurinimide, or bacteriopurpurinimide where the compound has the formula;

3. The method of claim 2, further comprising the step of allowing sufficient time for any of the compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject prior to the step of irradiating.

4. The method of claim 2 where the method is photodynamic therapy for treating hyperproliferative tissue in a subject and the subject is irradiated with light of a wavelength and fluence to sufficiently activate the compound to destroy or impair the hyperproliferative tissue.

5. The method of claim 4 wherein the compound has the formula: