Porphycene compounds for photodynamic therapy

• US 5,409,900 A
• Filed: 08/06/1993
• Issued: 04/25/1995
• Est. Priority Date: 06/28/1991
• Status: Expired due to Term

• Current Assignee: Cytopharm, Inc.
• Original Assignee: Cytopharm, Inc.
• Inventors: Muller, Martin, Richert, Clemens, Benninghaus, Thomas, Vogel, Emanuel, Cross, Alexander D.
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): SRIPADA, PAVANARAM K
• Application Number:
  US08/102,772
• Time in Patent Office: 627 Days
• Field of Search: 540/472, 514/2, 514/32, 514/410, 514/17, 514/18, 424/9, 424/11
• US Class Current: 514/13.4
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings

Abstract

A porphycene having the structure ##STR1## wherein each R¹ is, independently, (a) --(CH₂)_n --X, where n=1-4, X is OR² and R² is C_1-6 alkyl, aralkyl or aryl; CN; OH; OSO₂ R² ; NH₂ ; NHR² ; NR₂² ; SH; SR² ; S(O)_1-2 R² ; COOH; CO₂ R² ; C(O)NH₂ ; C(O)NHR² ; C(O)NR₂² ; halogen; or CHO;

(b) --(CH₂)_m CH═CH₂ where m is 0-2; or

(c) --(CH₂)_n --O--G where G is a mono- or oligosaccharide;

(d) --(CH₂)_2n --X, where X is an amino acid, oligopeptide covalently bonded by an ether-, ester- or amine-bond or --Y-- (CH₂)_n -porphycene² (porphycene² being a compound of the same structure and Y is a direct bond; --O--; or --CH═CH₂); or

(e) where one, two or three of the substituents R¹ are C_1-6 alkyl or aryl and the remaining substituents are as above under (a)-(d), and salts and metal complexes thereof. The porphycene compounds and pharmaceutical compositions containing the compounds are useful in photodynamic therapy treatment of tumors and psoriasis.

Claims

1. A porphycene having the structure ##STR4## wherein each R¹ is, independently, (a) --(CH₂)_n -X where X is an amino acid, oligopeptide covalently bonded by an ether-, ester- or amine-bond or where X is --Y--(CH₂)_n -porphycene², where porphycene² is a compound of the same said structure, n=1-4 and Y is a direct bond;

--O--;

or --CH═

CH--;

or

(b) where one, two or three of the substituents R¹ are C_1-6 alkyl or C_6-20 carbocyclic aryl and the remaining substituents are as above under (a) and pharmaceutically acceptable salts and metal complexes thereof.

2. A pharmaceutical composition comprising the porphycene of claim 1 and a pharmaceutically acceptable carrier or diluent.

3. The pharmaceutical composition of claim 2, wherein said composition is a solution of said porphycene in water, water-alcohol or dimethyl sulfoxide.

4. A method of photodynamic therapy, comprising the steps of:

administering to a mammal in need thereof, an effective amount or,the porphycene of claim 1, and

irradiating said mammal with light at a wavelength in the absorption spectrum of said porphycene.

5. The method of claim 4, wherein said administering is topical administration.

6. The method of claim 4, wherein said administering is enteral, parenteral or intramuscular administration.

7. A method of purifying or decontaminating a fluid, comprising

contacting said fluid with the porphycene of claim 1, and

irradiating said fluid in contact with the porphycene with light at a wavelength in the absorption spectrum of said porphycene.

8. The method of claim 7, wherein said fluid is blood.

9. The method of claim 7, wherein said porphycene is covalently bonded to a stationary supports.

12. The porphycene of claim 1, wherein X is a naturally occurring amino acid.

13. The porphycene of claim 1, wherein X is an oligopeptide having 2-6 amino acid residues.

14. The porphycene of claim 13, wherein X is an oligopeptide having 2-3 amino acid residues.

10. The compound 9-acetoxy-2,7,12,17-tetrakis(methoxyethyl)porphycene.

11. A method of photodynamic therapy, comprising the steps of:

administering to a mammal in need thereof, an effective amount of the porphycene of claim 10, and

irradiating said mammal with light at a wavelength in the absorption spectrum of said porphycene.

15. A porphycene having the structure ##STR5## wherein each R¹ is, independently, (a) --(CH₂)_n -X where X is an amino acid, oligopeptide covalently bonded by an ether-, ester- or amine-bond or where X is --Y--(CH₂)_n -porphycene², where porphycene² is a compound of the same said structure, n=1-4 and Y is a direct bond;

--O--;

or --CH═

CH--;

or

(b) wherein 1, 2, or 3 of the substituents R¹ are C_1-6 alkyl and the remaining substituents are as above under (a).