Use of L-carnitine and derivatives for reducing ceramide levels and potentiating antiretroviral drugs

Abstract

The present invention provides a novel use of L-carnitine, the derivatives thereof and their pharmacologically acceptable salts in combination with antiretroviral drugs for reducing ceramide levels and enhance the activity of the aforesaid antiretroviral drugs for the therapeutic treatment of HIV-infection and AIDS.

1 . Use of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and their pharmacologically acceptable salts for producing a medicament suitable for reducing ceramide levels for the therapeutic treatment of HIV-infection and AIDS.  
     
     
         2 . The use of  claim 1  in combination with nucleoside-like inhibitors of reverse transcriptase, non-nucleoside inhibitors of reverse transcriptase and inhibitors of HIV protease, for producing a medicament suitable for reducing ceramide levels and enhancing the activity of the aforesaid antiretroviral drugs for the therapeutic treatment of HIV-infection and AIDS.  
     
     
         3 . The use of  claim 1  or  2 , wherein L-carnitine is used.  
     
     
         4 . The use of  claim 1  or  2 , wherein the acyl carnitine is isovaleryl L-carnitine.  
     
     
         5 . The use of  claim 1  or  2 , wherein a basic aminoacid, an acylated basic aminoacid or a pharmacologically acceptable salt thereof is used.  
     
     
         6 . An orally or parenterally administrable pharmaceutical composition for reducing ceramide levels for the therapeutic treatment of HIV-infection and AIDS which comprises as active ingredient an amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof, effective for reducing ceramide levels, and at least one pharmacologically acceptable excipient.  
     
     
         7 . An orally or parenterally administrable pharmaceutical composition for the therapeutic treatment of HIV infection and AIDS in combination with the administration of nucleoside-like inhibitors of reverse transcriptase, non-nucleoside inhibitors of reverse transcriptase or HIV-protease inhibitors, which comprises an amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof, effective for reducing ceramide levels and viral load and for enhancing the immunocompetence of HIV-infected patients, and at least a pharmacologically acceptable excipient.  
     
     
         8 . An orally or parenterally administrable pharmaceutical composition in unit dosage form for reducing ceramide levels and enhancing the efficacy of antiretroviral drugs for the therapeutic treatment of HIV-infection and AIDS, which comprises at least one antiretroviral drug selected from nucleoside-like inhibitors of reverse transcriptase, non-nucleoside inhibitors of reverse transcriptase or HIV-protease inhibitors and an amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof, effective for reducing ceramide levels and viral load and enhancing the immunocompetence of HIV-infected subjects, and at least a pharmacologically acceptable excipient.  
     
     
         9 . The pharmaceutical composition of  claim 6  or  7  wherein the amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof is such that the daily dose of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and antiretroviral drug is from 1 to 500 mg/kg and the ratio between L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and their pharmacologically acceptable salts thereof and the antiretroviral drug is from 1:40 to 40:1.  
     
     
         10 . The pharmaceutical composition of  claim 6  or  7  wherein the amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and their pharmacologically acceptable salts thereof is such that the daily dose of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and antiretroviral drug is from 20 to 100 mg/kg and the ratio between L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and the antiretroviral drug is from 1:10 to 10:1.  
     
     
         11 . The orally or parenterally administrable pharmaceutical composition of  claim 8 , in unit dosage form, wherein the amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof is such that the daily amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and antiretroviral drug is from 1 to 500 mg/kg and the ratio between L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and the antiretroviral drug is from 1:40 to 40:1.  
     
     
         12 . The orally or parenterally administrable pharmaceutical composition of  claim 8  in unit dosage form, wherein the amount of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof is such that the daily dose of L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and antiretroviral drug is from 20 to 100 mg/kg and the ratio between L-carnitine, acyl L-carnitines wherein the acyl group, straight or branched, has 2-6 carbon atoms and the pharmacologically acceptable salts thereof and the antiretroviral drug is from 1:10 to 10:1.  
     
     
         13 . The composition of any of the claims  1 - 12  which further comprises at least one component selected from dextran, alpha-TNF inhibitors, antioxidant drugs, immunomodulators, immunosuppressants, chemotherapeutic agents, vitamins and oligoelements.