Pharmaceutical compositions

Abstract

An oral or injectable pharmaceutical composition is provided for treating diseases caused by retroviruses or hepatitis B viruses. The composition comprises a therapeutically effective amount of at least one anti-retroviral drug and a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof. Methods and kits are also provided.

What is claimed: 
     
         1 . An oral or injectable pharmaceutical composition comprising a therapeutically effective amount of at least one anti-retroviral drug and a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof. 
     
     
         2 . The oral or injectable pharmaceutical composition of  claim 1 , wherein (i) the at least one pharmacokinetic booster or enhancer or derivative thereof reduces a dosing frequency of the at least one anti-retroviral drug that is administered to a patient; and (ii) the at least one pharmacokinetic booster or enhancer or derivative thereof increases the bioavailability of the at least one anti-retroviral drug from about 10% to about 70%. 
     
     
         3 . The oral or injectable pharmaceutical composition of  claim 1 , wherein (i) the at least one anti-retroviral drug comprises a nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleotide analog reverse-transcriptase inhibitor, protease inhibitor (PI), integrase inhibitor, fusion inhibitor, CCR5 inhibitor, monoclonal antibody, glycoprotein inhibitor or combinations thereof; and (ii) the at least one pharmacokinetic booster comprises piperine, tetrahydropiperine, cis-piperine, trans-piperine, cis-trans piperine, trans,cis-piperine, cis,cis-piperine, trans,trans-piperine or a combination thereof. 
     
     
         4 . The oral or injectable pharmaceutical composition of  claim 3 , wherein the at least one anti-retroviral drug comprises a nucleoside reverse transcriptase inhibitor (NRTI) comprising lamivudine, abacavir, zidovudine, emtricitabine, didanosine, stavudine, entecavir, apricitabine, censavudine, zalcitabine, dexelvucitabine, amdoxovir, elvucitabine, festinavir, racivir, stampidine or a combination thereof; a non-nucleoside reverse transcriptase inhibitor (NNRTI) comprising lersivirine, rilpivirine, efavirenz, etravirine, doravirine, dapivirine or a combination thereof; a nucleotide analog reverse-transcriptase inhibitor comprising tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, adefovir or a combination thereof; a protease inhibitor (PI) comprising lopinavir, ritonavir, saquinavir, nelfinavir, amprenavir, indinavir, nelfinavir, atazanavir, lasinavir, palinavir, tirpranavir, fosamprenavir, darunavir, tipranavir or a combination thereof; an integrase inhibitor comprising dolutegravir, elvitegravir, raltegravir, bictegravir, cabotegravir or a combination thereof; a fusion inhibitor comprising maraviroc, enfuvirtide, griffithsin, aplaviroc, vicriviroc, plerixafor, fostemsavir, albuvirtide or a combination thereof; a CCR5 inhibitor comprising aplaviroc, vicriviroc, maraviroc, cenicriviroc or a combination thereof; a monoclonal antibody comprising ibalizumab; a glycoprotein inhibitor comprising sifuvirtide; or combinations thereof. 
     
     
         5 . The oral or injectable pharmaceutical composition of  claim 1 , wherein the ratio of the at least one anti-retroviral drug to the at least one pharmacokinetic booster or enhancer or derivative thereof is from about 100:1 to about 1:1 by weight. 
     
     
         6 . The oral or injectable pharmaceutical composition of  claim 4 , wherein the tenofovir disoproxil fumarate in the composition is from about 1 mg to about 300 mg. 
     
     
         7 . The oral or injectable pharmaceutical composition of  claim 4 , wherein the tenofovir alafenamide fumarate in the composition is from about 1 to about 25 mg. 
     
     
         8 . The oral or injectable pharmaceutical composition of  claim 4 , wherein the dolutegravir in the composition is from about 1 mg to about 50 mg. 
     
     
         9 . The oral or injectable pharmaceutical composition of  claim 4 , wherein the darunavir in the composition is from about 1 mg to about 800 mg. 
     
     
         10 . The oral or injectable pharmaceutical composition of  claim 4 , wherein (i) the elvitegravir in the composition is from about 1 mg to about 150 mg; and (ii) the raltegravir in the composition is from about 1 mg to about 400 mg. 
     
     
         11 . The oral or injectable pharmaceutical composition of  claim 3 , wherein the piperine is in the composition from about 0.5 mg to about 400 mg. 
     
     
         12 . An oral or injectable pharmaceutical composition comprising a therapeutically effective amount of at least one anti-retroviral drug; a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof; and one or more pharmaceutically acceptable excipients comprising carriers, diluents, fillers, binders, lubricants, glidants, disintegrants, bulking agents, flavorants or any combination thereof. 
     
     
         13 . The oral or injectable pharmaceutical composition of  claim 12 , wherein the oral composition is in the form of a tablet, mini-tablet, granules, sprinkles, capsules, sachets, powders, pellets, and the injectable composition is in the form of a solution, suspension, emulsion, lyophilized powder or in the form of a kit. 
     
     
         14 . The oral or injectable pharmaceutical composition of  claim 12 , wherein the oral or injectable pharmaceutical composition is for use in the treatment or prophylaxis of diseases caused by retroviruses. 
     
     
         15 . The oral or injectable pharmaceutical composition of  claim 12 , wherein the oral or injectable pharmaceutical composition is for use in the treatment of diseases caused by hepatitis B viruses. 
     
     
         16 . A method of treating diseases caused by retroviruses or hepatitis B viruses in a patient in need of such treatment, the method comprising: administering a pharmaceutical composition comprising (i) a therapeutically effective amount of at least one anti-retroviral drug or an antiviral drug; (ii) a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof; and (iii) one or more pharmaceutically acceptable excipients comprising carriers, diluents, fillers, binders, lubricants, glidants, disintegrants, bulking agents, flavourants or any combination thereof. 
     
     
         17 . The method according to  claim 16 , wherein the diseases caused by retroviruses comprises acquired immune deficiency syndrome or an HIV infection. 
     
     
         18 . A method of making a pharmaceutical composition that enhances the bioavailability of an anti-retroviral drug, the method comprising: mixing a therapeutically effective amount of at least one anti-retroviral drug and a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof with one or more pharmaceutically acceptable excipients to make the pharmaceutical composition. 
     
     
         19 . The method according to  claim 18 , wherein the at least one anti-retroviral drug comprises a nucleoside reverse transcriptase inhibitor (NRTI) comprising lamivudine, abacavir, zidovudine, emtricitabine, didanosine, stavudine, entecavir, apricitabine, censavudine, zalcitabine, dexelvucitabine, amdoxovir, elvucitabine, festinavir, racivir, stampidine or a combination thereof; a non-nucleoside reverse transcriptase inhibitor (NNRTI) comprising lersivirine, rilpivirine, efavirenz, etravirine, doravirine, dapivirine or a combination thereof; a nucleotide analog reverse-transcriptase inhibitor comprising tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, adefovir or a combination thereof; a protease inhibitor (PI) comprising lopinavir, ritonavir, saquinavir, nelfinavir, amprenavir, indinavir, nelfinavir, atazanavir, lasinavir, palinavir, tirpranavir, fosamprenavir, darunavir, tipranavir or a combination thereof; an integrase inhibitor comprising dolutegravir, elvitegravir, raltegravir, bictegravir, cabotegravir or a combination thereof; a fusion inhibitor comprising maraviroc, enfuvirtide, griffithsin, aplaviroc, vicriviroc, plerixafor, fostemsavir, albuvirtide or a combination thereof; a CCR5 inhibitor comprising aplaviroc, vicriviroc, maraviroc, cenicriviroc or a combination thereof; a monoclonal antibody comprising ibalizumab; a glycoprotein inhibitor comprising sifuvirtide; or combinations thereof. 
     
     
         20 . The method according to  claim 18 , wherein the at least one pharmacokinetic booster or enhancer or derivative thereof comprises piperine, tetrahydropiperine, cis-piperine, trans-piperine, cis-trans piperine, trans,cis-piperine, cis,cis-piperine, trans,trans-piperine or a combination thereof. 
     
     
         21 . A kit for treating disease caused by retroviruses or hepatitis B viruses, the kit comprising a therapeutically effective amount of at least one anti-retroviral drug and a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof, wherein the at least one anti-retroviral drug is in a separate composition from the at least one pharmacokinetic booster or enhancer or derivative thereof. 
     
     
         22 . A method of enhancing the bioavailability of an oral anti-retroviral drug, the method comprising: providing a therapeutically effective amount of at least one anti-retroviral drug and providing a therapeutically effective amount of at least one pharmacokinetic booster or enhancer or derivative thereof. 
     
     
         23 . The method of  claim 22 , wherein (i) the at least one anti-retroviral drug is in a first composition and the at least one pharmacokinetic booster or enhancer or derivative thereof is in a second composition; or (ii) the at least one anti-retroviral drug and the at least one pharmacokinetic booster or enhancer or derivative thereof is combined in one composition.