Pharmaceutical use and pharmaceutical composition of pyrroloquinoline quinine, its derivatives and/or its salts

Abstract

The present invention relates to the use of pyrroloquinoline quinine (PQQ), its derivatives and/or salts for the preparation of drugs for the treatment and/or prevention of endometriosis including adenomyosis, chocolate cyst of ovary, deeply infiltrating endometriosis and other type of endometriosis. In addition, the present invention relates to the use of PQQ in combination with one or more the following antioxidants: N-Acetyl-L-cysteine (NAC), resveratrol, epigallocatechin gallate, vitamin E or vitamin C for the preparation of drugs for inhibiting the proliferation, oxidative stress status, invasion and migration of endometrial stromal cell. The use of PQQ in combination with NAC shows a synergistic effect on inhibiting cell proliferation: significantly inhibiting the proliferation of endometrial stromal cell in vitro; significantly reducing the damaged size of tissue caused by endometriosis in vivo; significantly reducing the infiltration of endometrial stroma and glands; significantly reducing the dose of NAC as well. PQQ is beneficial for fertility, and increases the chances of getting pregnant. PQQ alone or PQQ in combination with NAC generally shows no side effects and will not interfere with pregnancy.

1 . A method of treating and/or preventing endometriosis, comprising: administering to a subject suffering therefrom a therapeutically effective amount of Pyrroloquinoline quinine (PQQ), its derivatives and/or salts. 
     
     
         2 . The method as described in  claim 1 , characterized in that said endometriosis is adenomyosis. 
     
     
         3 . The method as described in  claim 1 , characterized in that said endometriosis is chocolate cyst of ovary. 
     
     
         4 . The method as described in  claim 1 , characterized in that said endometriosis is deeply infiltrating endometriosis. 
     
     
         5 . A method of inhibiting the proliferation, oxidative stress status and invasion, and migration of endometrial stromal cell, comprising: administering to a subject suffering therefrom a pharmaceutically effective amount of Pyrroloquinoline quinine (PQQ), its derivatives and/or its salts. 
     
     
         6 . The method as described in  claim 5 , charictorized in that said Pyrroloquinoline quinine (PQQ), its derivatives and/or its salts are administered in combination with antioxidant. 
     
     
         7 . The method as described in  claim 6 , wherein the antioxidant is one or more members selected from the group consisting of: N-Acetyl-L-cysteine(NAC), resveratrol, epigallocatechin gallate, vitamin E and vitamin C. 
     
     
         8 . The method as described in  claim 6 , wherein the antioxidant is N-Acetyl-L-cysteine(NAC). 
     
     
         9 . The method as described in claim of  1 , characterized in that said pyrroloquinoline quinine (PQQ), its derivatives and/or its salts are the compounds of general structure (I) below, 
       
         
           
           
               
               
           
         
         wherein R1, R2 and R3 are same or not, and are each independently lower alkyl, lower alkenyl, lower alkynyl, alkaryl, aralkyl, phenyl, H, Na and K. 
       
     
     
         10 . The method as described in  claim 8 , characterized in that the ratio of pyrroloquinoline quinine (PQQ), its derivatives and/or salts to N-Acetyl-L-cysteine(NAC) is 1:5 to 1:50. 
     
     
         11 . The method as described in  claim 8 , characterized in that the daily dose of pyrroloquinoline quinine, its derivatives and/or salts is as low as 1 mg/kg/day, and the daily dose of N-Acetyl-L-cysteine is as low as 10 mg/kg/day. 
     
     
         12 . The method as described in  claim 8 , characterized in that the daily dose of Pyrroloquinoline quinine, its derivatives and/or salts is as low as 0.2 mg/kg/day and the daily dose of N-Acetyl-L-cysteine is as low as 5 mg/kg/day. 
     
     
         13 . The method as described in  claim 8 , characterized in that the daily dose of Pyrroloquinoline quinine, its derivatives and/or salts is within the range of 0.2 to 1 mg/kg/day and the daily dose of N-Acetyl-L-cysteine is in the range of 5 to 10 mg/kg/day. 
     
     
         14 . The method as claimed in  claim 5 , characterized in that the pyrroloquinoline quinine (PQQ), its derivatives and/or salts and N-Acetyl-L-cysteine(NAC) are administered in form of pharmaceutical preparations for sustained-release and/or stomach protection.