Retardation of metalloproteinase incidental to HIV and/or AIDS

Abstract

The instant invention provides a product of manufacture for retarding the biochemical formation of metalloproteinase, including gelatinase, elastase, collaginase, and the like, within the tissues of the body of a patient who has been inflicted with the HIV virus and/or the HIV virus which has advance to the AIDS virus, through the administration of an effective amount of a non-antimicrobial/non-antibiotic/non-antibacterial, chemically modified tetracycline (CMT) analog, its salts, cojugates and/or derivatives, and combinations thereof.

I claim:  
     
       1. A method for healing HIV viral infections, or AIDS comprising administering to patients in need of such treatment an anti-retroviral amount of non-antimicrobial, non-antibiotic, non-antibacterial chemically modified tetracycline (CMT) analogs. 
     
     
       2. The method of  claim 1 , wherein the chemically modified tetracycline (CMT) is selected from the group consisting of: 
       4-dedimethylaliiinotetracycline,  
       4-dedimtntnhylamino-oxytetracycline,  
       4-dedimethylamino-7-chlortetracycline,  
       4-hydroxy-4-dedimethylaminotetracycline,  
       5a,6-anhydro-4-hydroxy-4-dedimethylaminotetracycline,  
       6-alpha-dcoxy-5-hydroxy-4-dedimethylaminotetracycline,  
       6-dernethyl-6-deoxy-4-dedimelhylaminotetracycline,  
       4-dedimethylamino-11-hydroxy-12a-deoxytetracyclins,  
       12a-deoxy-4-deoxy-4-dedimethylaminotetracycline,  
       6-alpha-deoxy-5-hydroxy-4-dedimethylaminodoxycycline,  
       12a,4a-anhydro-4-dedimethylaminotetracycline, minocycline-CMT,  
       7-dimethylamino-6-demethyl-6-deoxy-4-dedimethylaminotetracycline,  
       6a-benzylthiomethylenetetracycline,  
       the 2-nitrilo analogs of tetracycline (tetracyclinonitrile),  
       the mono-N-alkylated amide of tetracycline,  
       6-fluoro-6-demethyltetracycline,  
       11a-chlortetracycline,  
       tetracycline pyrazole,  
       12a-deoxytetracycline,  
       4-dedimethylamino-5-oxytetracycline,  
       5a,6-anhydro-4-hydroxy-4-dedimethylaminotetracycline,  
       12a,4a-anhydro-4-dedimethylaminotetracycline,  
       tetracyclonitrile,  
       7-chloro-4-dedimethylaminotetracycline,  
       12a-deoxy-4-deoxy-4-dedimethylaminotetracycline,  
       4-dedimethylamino-7-chlorotetracycline,  
       4-dedimethylamino-7-dedimethylaminotetracycline,  
       the 2-nitrilo analogs of tetracycline,  
       4-dedimethylamino 12a-deoyotetracycline,  
       tetracyclines altered at the 2-carbon position to produce a nitrile,  
       4-dedimethylamino-7-chlorotetracycline,  
       6-alpha-deoxy-5-hydroxy-4-dedimethylaminotetracycline,  
       tetracyclonitrile,  
       6-alpha-benzylthiomethyltetracycline,  
       the 2-nitrilo analog of tetracycline,  
       11-alpha-chlorotetracycline,  
       7-chlortetracycline,  
       5 hydroxytetracycline,  
       6-demethyl-7-chlortetracycline,  
       6-demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline,  
       6-alpha-benzylthiomethylenetetracycline,  
       a nitrile analog of tetracycline,  
       a mono-N-alkylated amide of tetracycline,  
       2-acetyl-8-hydroxy-1-tetracycline,  
       6-demethyl-6-deoxytetracycline,  
       6-demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline,  
       2-acetyl-8-hydroxyl-1-tetracycline,  
       4-hydroxy-4-dedimethylaminotetracycline,  
       5a,6-anhydro-4-hydroxy-4-dedimethylaminotetracycline,  
       6-demethyl-6-deoxy-4-dedimethylaminotetracycline,  
       6-deoxy-8-demethyl-4-dedimethylaminotetracycline,  
       6a-deoxy-5-hydroxy-4-dedimethylaminotetracycline,  
       tetracyclines altered at the 2-carbon position to produce a nitrile,  
       pyrazole derivative of tetracycline,  
       7-chloro-6-demethyl-4-dedimethylaminotetracycline,  
       11-apha-chlortetracycline,  
       4-dedimethylamino-7-chlortetracycline,  
       4-de(dimethylamino)-tetracycline,  
       4-de(dimethylamino)-5-oxytetracycline,  
       4-de(dimethylamino)-7-chlortetracycline,  
       7-chloro-6-demethyl-4-dedimethylaminotetracycline,  
       6-o-deoxy-5-hydroxy-4-dedimethylaminotetracycline,  
       6-alpha-obenzylthiomethylenetetracycline,  
       4-de(dimethylamino)-5-oxytetracycline,  
       4-de(dimethylamino)-7-chlortetracycline,  
       4-hydroxy-4-dedimethylaminotetracycline,  
       6-alpha-deoxy-5-hydroxy-4-dedimethylaminotetracycline,  
       4-de(dimethylamino)-tetracycline,  
       4-de(dimethylamino)-7-chlortetracycline,  
       7-chloro-6-demethyl-4-dedimethylaminotetracycline. dedimethylaminotetracycline  
       6-alpha-benzyl-thiomethylenetetracycline,  
       11-alpha-chlortetracycline,  
       6-demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline,  
       6-fluoro-demethyltetracycline,  
       and the salts, conjugates, derivatives and combinations thereof.  
     
     
       3. The method of  claim 1 , wherein said analog comprises a form suitable for oral administion. 
     
     
       4. The method of  claim 2 , wherein said analog comprises a form suitable for topical application. 
     
     
       5. The method of  claim 1 , wherein said analog comprises a form suitable for administion by way of an injection or intravenous perfusion. 
     
     
       6. The method of  claim 1 , wherein said analog comprises an amount suitable for providing a dosage of from about 0.1 mg/kg/day to about 100 mg/kg/day. 
     
     
       7. The method of  claim 6 , wherein said analog comprises an amount suitable for providing a dosage of from about 10 mg per kg per day to about 50 mg per kg per day. 
     
     
       8. The method of  claim 7 , wherein said analog comprises an amount suitable for providing a dosage of from about 20 mg per kg per day to about 25 mg per kg per day. 
     
     
       9. A method for treating the biochemical formation of materials incidental to HIV or AIDS or which promote the advancement of HIV or AIDS or which promote the advancement of AIDS and other opportunistic diseases to which a patient might become ill comprising administering to patients in need of such treatment an anti- retroviral amount of non - antimicrobial, non - antibiotic, non - antibacterial chemically modified tetracycline  ( CMT )  analogs.   
     
     
       10. The method of  claim 9  wherein the chemically modified tetracycline (CMT) is selected from the group consisting of: 
           4   - dedimethylaliinotetracycline,    
           4   - dedimethylamino - oxytetracycline,    
           4   - dedimethylamino -   7   - chlorotetracycline,    
           4   - hydroxy -   4   - dedimethylaminotetracycline,    
           5   - alpha -   6   - anhydro -   4   - hydroxy -   4   - dedimethylaminotetracycline,    
           6   - alpha - deoxy -   5   - hydroxy -   4   - dedimethylaminotetracycline,    
           6   - dimethyl -   6   - deoxy -   4   - dedimethylaminotetracycline,    
           4   - dedimethylamino -   11   - hydroxy -   12   - alpha - deoxytetracycline,    
           12   - alpha - deoxy -   4 deoxy -   4   - dedimethylaminotetracycline,    
           6   - alpha - deoxy -   5   - hydroxy -   4   - dedimethylaminotetracycline,    
           12   - alpha, 4 alpha - anhydro -   4   - dedimethylaminotetracycline,    
         minocycline - CMT,    
           7   - dimethylamino -   6   - dimethyl -   6   - deoxy -   4   - dedimethylaminotetracycline,    
           6   - alpha - benzylthiomethylenetetracycline,    
         the  2   - nitrilo analogs of tetracycline  ( tetracyclinonitrile ),  
         the mono - N - alkylated wide of tetracycline,    
           6   - fluoro -   6   - demethyltetracycline,    
           11 alpha - chlorotetracycline,    
       
         tetracycline pyrazole,  
       
           12   - alpha - deoxytetracycline,    
           4   - dedimethylamino -   5   - oxytetracycline,    
           5   - alpha,  6   - anhydro -   4   - hydroxy -   4   - dedimethylaminotetracycline,    
           12   - alpha,  4 alpha - anhydro -   4   - dedimethylaminotetracycline,    
       
         tetracyclonitrile,  
       
           7   - chloro -   4   - dedimethylaminotetracycline,    
           12   - alpha -   4   - deoxy -   4   - dedimethylaminotetracycline,    
           4   - dedimethylamino -   7   - chlorotetracycline,    
           4   - dedimethylamino -   7   - dedimethylaminotetracycline,    
         the  2   - nitrilo analogs of tetracycline,    
           4   - dedimethylamino -   12 alpha - deoxyotetracycline,    
         tetracyclines altered at the  2   - carbon position to produce a nitrile,    
           4   - dedimethylamino -   7   - chlorotetracycline,    
           6   - alpha - deoxy -   5   - hydroxy -   4   - dedimethylaminotetracycline,    
       
         tetracyclonitrile,  
       
           6   - alpha - benzylthiomethyltetracycline,    
         the  2   - nitrilo analog of tetracycline,    
           11   - alpha - chlorotetracycline,    
           7   - chlortetracycline,    
           5   - hydroxytetracycline,    
           6   - demethyl -   7   - chlorotetracycline,    
           6   - demethyl -   6   - deoxy -   5   - hydroxy -   6   - methylenetetracycline,    
           6   - alpha - benzylthiomethylenetetracycline,    
       
         a nitrile analog of tetracycline,  
       
         a mono - N - alkylated amide of tetracycline,    
           2   - acetyl -   8   - hydroxy -   1   - tetracycline,    
           6   - demethyl -   6   - deoxytetracycline,    
           6   - demethyl -   6   - deoxy -   5   - hydroxy -   6   - methylenetetracycline,    
           2   - acetyl -   8   - hydroxyl -   1   - tetracycline,    
           4   - hydroxy -   4   - dedimethylaminotetracycline,    
           5   - alpha,  6   - anhydro -   4   - hydroxy -   4   - dedimethylaminotetracycline,    
           6   - demethyl -   6   - deoxy -   4   - dedimethylaminotetracycline,    
           6   - deoxy -   8   - demethyl -   4   - dedimethylaminotetracycline,    
           6   - alpha - deoxy -   5   - hydroxy -   4   - dedimethylaminotetracycline,    
         tetracyclines altered at the  2   - carbon position to produce a nitrile,    
       
         pyrazole derivative of tetracycline,  
       
           7   - chloro -   6   - demethyl -   4   - dedimethylaminotetracycline,    
           11   - alpha - chlorotetracycline,    
           4   - dedimethylamino -   7   - chlorotetracycline,    
           4   - de ( dimethylamino )- tetracycline,    
           4   - de ( dimethyl )-   5   - oxytetracycline,    
           4   - de ( dimethylamino )-   7   - chlorotetracycline,    
           7   - chloro -   6   - demethyl -   4   - dedimethylaminotetracycline,    
           6   - alpha - deoxy -   5   - hydroxy -   4   - dedimethylaminotetracycline,    
           6   - alpha - obenzylthiomethylenetetracycline,    
           4   - de ( dimethylamino )-   5   - oxytetracycline,    
           4   - de ( dimethylamino )-   7   - chlorotetracycline,    
           4   - hydroxy -   4   - dedimethylaminotetracycline,    
           6   - alpha - deoxy -   5   - hydroxy -   4   - dedimethylaminotetracycline,    
           4   - de ( dimethylamino )- tetracycline,    
           4   - de ( dimethylamino )-   7   - cholorotetracycline,    
           7   - chloro -   6   - demethyl -   4   - dedimethylaminotetracycline,    
       
         dedimethylaminotetracycline,  
       
           6   - alpha - benzyl - thiomethylenetetracycline,  11   - alpha - chlorotetracycline,    
           6   - demethyl -   6   - deoxy -   5   - hydroxy -   6   - methylenetetracycline,    
           6 -   fluoro - demethyltetracycline,    
       
         and the salts, conjugates, derivatives and combinations thereof. 
       
     
     
       11. The method of  claim 9  wherein said analog comprises a form suitable for oral administration. 
     
     
       12. The method of  claim 10  wherein said analog comprises a form suitable for topical application. 
     
     
       13. The method of  claim 9  wherein said analog comprises a form suitable for administration by way of an injection or intravenous perfusion. 
     
     
       14. The method of  claim 9  wherein said analog comprises an amount suitable for providing a dosage of from about  0 . 1  mg/kg/day to about  100  mg/kg/day. 
     
     
       15. The method of  claim 14  wherein said analog comprises an amount suitable for providing a dosage of from about  10  mg per kg per day to about  50  mg per kg per day. 
     
     
       16. The method of  claim 15  wherein said analog comprises an amount suitable for providing a dosage of from about  20  mg per kg per day to about  25  mg per kg per day.