Pyropheophorbides and their use in photodynamic therapy

Abstract

Pyropheophorbide compounds are injected into a host and accumulate in tumor tissue to a higher degree than surrounding normal tissues. When the pyropheophorbide compounds are exposed to a particular wavelength of light the compounds become cytotoxic and destroy the tumor or diseased tissue without causing irreversible normal tissue damage. The pyropheophorbide compounds have shown improved results as compared to drugs currently used in photodynamic therapy. Further, they absorb light further in the red, optimizing tissue penetration mad are retained in the skin for short time periods relative to other drugs used in photodynamic therapy.

1. A compound of formula I: 
                 
 
       wherein R 1  is CH 2 OR 2  where R 2  is a primary or secondary alkyl containing 1 to 20 carbons; and R 3  is —CO 2 R 4  —CH 2   CH   2   CO   2   R   4  where R 4  is H or an alkyl containing 1 to 20 carbons. 
     
     
       2. The compound as claimed in  claim 1 , wherein R 1  is —CH 2 —O—hexyl. 
     
     
       3. The compound as claimed in  claim 1 , wherein R 2  is —CH 3 . 
     
     
       4. The compound as claimed in  claim 1 , wherein R 3  is —CO 2 CH 3 . 
     
     
       5. A method to effect the destruction of target virus, cells or tissue, comprising:
 contacting said target with an effective amount of compound of  claim 1 , and irradiating with light absorbed by said compound.  
 
     
     
       6. A pharmaceutical composition useful in treatment of a target virus, cells or tissue, comprising:
 an effective amount of the compound of  claim 1  in admixture with a pharmaceutically acceptable excipient.  
 
     
     
       7. A compound or formula II: 
                 
 
       wherein R 5  is —OR 6  wherein R 6  is a primary or secondary alkyl containing 1  5  to 20 carbons and R 7  is —CO 2 R 8  —CH 2   CH   2   CO   2   R   8  where R 8  is H or an alkyl containing 1 to 20 carbons. 
     
     
       8. The compound as claimed in  claim 7 , wherein R 5  is —O—hexyl. 
     
     
       9. The compound as claimed in  claim 7 , wherein R 7  is —CO 2 CH 3 . 
     
     
       10. The compound as claimed in  claim 7 , wherein R 5  is —O—(CH 3 ) 5 CH 3  and R 7  is selected from the group consisting of —CO 2 CH 3  and —CO 2 H. 
     
     
       11. A method to effect the destruction of target virus, cells or tissue, comprising:
 contacting said target with an effective amount of compound of  claim 7 ; and irradiating with light absorbed by said compound.  
 
     
     
       12. A pharmaceutical composition useful in treatment of a target virus, cells or tissue, comprising:
 an effective amount of the compound of  claim 7  in admixture with a pharmaceutically acceptable excipient.  
 
     
     
       13. A method of treating a human with abnormal cells which replicate at an abnormally high rate, comprising the steps of:
 administering to the human a therapeutically effective amount of a compound of formula II: 
                 
 
 
       wherein R 5  is OR 6  where R 6  is a primary or secondary alkyl containing 5 to 20 carbons and R 7  is —CO 2 R 8  —CH 2   CH   2   CO   7   R   8  where R 8  is H or —CH 3 ;
 allowing the compound of formula II to accumulate on the abnormal cells; and  
 irradiating the compound of formula II with a wavelength of light which is absorbed by the compound of formula I and thereby generating a cytotoxic effect with respect to the abnormal cells.  
 
     
     
       14. The method as claimed in  claim 13  wherein the compound is administered in an amount in the range of 0.01 mg/kg to 1.0 mg/kg of body weight. 
     
     
       15. The method as claimed in  claim 14  wherein the compound of formula II is administered at timed intervals in the range of from every 3 hours to every 72 hours for over a period of from 1 day to 30 days. 
     
     
       16. The method as claimed in  claim 15 , wherein R 5  is —O—hexyl and R 7  is —CO 2 H. 
     
     
       17. The method can claimed in  claim 16  wherein the wavelength of the light is in the range of 600 to 700 nm. 
     
     
       18. The method at claimed in  claim 17  wherein the wavelength or the light is about 600 nm.