Composition comprising pharmaceutical/nutraceutical agent and a bio-enhancer obtained from Glycyrrhiza glabra

Abstract

The invention relates to a new use of a non-alkaloid compound that is plant derived glycoside ‘glycyrrhizin’ as a highly potent bio-enhancer of activity and availability of antibiotics and other drugs including anti-infective and anticancer agents. The molecule of invention facilitates the absorption/uptake of antibiotics and other molecules across the cell membrane in plant and animal cells as well as Gram-positive and Gram-negative bacteria and therefore can be used as a drug facilitator or bioenhancer molecule to increase the affectivity of drugs and nutraceutical agents. The compound having no antimicrobial or cytotoxic activity of its own, is a safe candidate to reduce the drug dosage towards circumventing the problem of drug resistance and the other side effects in anti-infective and anti-cancer therapies.

1 . A composition comprising an effective amount of an extract or compound obtained from the plant  Glycyrrhiza glabra  and useful as a bio-enhancer and bioavailability facilitator together with a therapeutically effective amount of one or more nutraceuticals, antibiotics, anti-infective agents and anti-cancer agents.  
   
   
       2 - 4 . (canceled)  
   
   
       5 . A composition as claimed in  claim 1  wherein the anti-infective agents are selected from anti-bacterial, anti-fungal and anti-tuberculosis agents.  
   
   
       6 . (canceled)  
   
   
       7 . A composition as claimed in  claim 1  wherein the concentration of glycyrrhizin ranges from 0.10 to 10% of the weight of the nutraceutical compounds.  
   
   
       8 . A composition as claimed in  claim 1  wherein the concentration of glycyrrhizin ranges from 0.25 to 20% of the weight of the anti-infective agent.  
   
   
       9 . A composition as claimed in  claim 5  wherein the anti-bacterial agents are selected from the group comprising P-lactams, macrolides, quinolones, fluoro-quinolones, aminoglycosides, glycopeptides, rifamycins, folate inhibitors, tetracyclines, anti-tuberculosis agents and microbicidal compounds.  
   
   
       10 . A composition as claimed in  claim 9  wherein the quinolones and fluoro-quinolones are selected from the group consisting of nalidixic acid, norfloxacin, ciprofloxacin, sparfloxacin and similar other compounds.  
   
   
       11 . A composition as claimed in  claim 9  wherein the β-Lactams are selected from the group comprising penicillin, flucloxacillin, cloxacukkub, methicillin, cephalosporins and carbapenenms.  
   
   
       12 . A composition as claimed in  claim 9  wherein the macrolides are selected from erythromycin, clarithromycin, azithromycin and other similar compounds.  
   
   
       13 . A composition as claimed in  claim 9  wherein the aminoglycosides are selected from the group consisting of streptomycin, gentamicin, amikacin and similar compounds.  
   
   
       14 . A composition as claimed in  claim 9  wherein the glycopeptides are selected from vancomycin, teicoplanin and other similar compounds.  
   
   
       15 . A composition as claimed in  claim 9  wherein the rifamycins are rifunpicin and similar compounds.  
   
   
       16 . A composition as claimed in  claim 9  wherein the folate inhibitors are selected from trimethoprim, sulphonamides and other similar compounds.  
   
   
       17 . A composition as claimed in  claim 9  wherein the microbiocidal compounds are selected from streptogramins and oxazolidinones.  
   
   
       18 . A composition as claimed in  claim 5  wherein the anti-tuberculosis agents are selected from the group comprising isoniazid, pyrazinamide, ethambutol and other similar compounds.  
   
   
       19 . A composition as claimed in  claim 5  wherein the anti-fungal agents are selected from the group consisting of polyene, triazole, imidazole, clotrimazole and other fungicidal compounds.  
   
   
       20 . A composition as claimed in  claim 19  wherein the polyene is selected from amphoterecin B, nystatin and other similar compounds.  
   
   
       21 . A composition as claimed in  claim 19  wherein the triazole is selected from fluconazole, itraconazole and other similar compounds.  
   
   
       22 . A composition as claimed in  claim 19  wherein the imidazole is selected from ketoconazole and other similar compounds.  
   
   
       23 . A composition as claimed in  claim 19  wherein the fungicidal compound is selected from griseofulvin and terbinafine.  
   
   
       24 . A composition as claimed in  claim 1  wherein the anti-cancer agent is selected from the group consisting of paclitaxel, docetaxel, vinblastine, vincristine, and vinorelbine.  
   
   
       25 . A composition as claimed in  claim 1  wherein the concentration of giycyrrhizin ranges from 10 to 10,000 fold folds of the weight of the anti-cancer compound.  
   
   
       26 . A composition as claimed in  claim 1  wherein the nutraceutical compounds are selected from the group consisting of vitamins, amino acids, hormones and other nutritional supplements.  
   
   
       27 . (canceled)  
   
   
       28 . A method for enhancing the bio-availability of a herbal extract, ant-infective agent, anti-cancer agent or nutraceutical compound across biological membranes in a patient in need thereof comprising administering to the patient composition comprising an effective amount of a bioenhancer obtained from the plant  Glycyrrhiza glabra,  and any one of an anti-infective agent, anti-cancer agent or nutraceutical compound.  
   
   
       29 . A method as claimed in  claim 28  wherein the bio-enhancer is selected from the extract of  Glycyrrhiza glabra,  glycyrrhizin, glycyrrhizic acid obtained from  Glycyrrhiza glabra  or combinations thereof.  
   
   
       30 . A method as claimed in  claim 28  wherein the bioenhancer is obtained from the roots, stem, stolon or leaves of the plant  Glycyrrhiza glabra.    
   
   
       31 . A method as claimed in  claim 28  wherein the anti-infective agent is an anti-bacterial agent anti-fungal agent or anti-cancer agent.  
   
   
       32 . A method as claimed in  claim 31  wherein the anti-bacterial agent is selected from the group consisting of β-lactams, macrolides, quinolones, fluoro-quinolones, aminoglycosides, glycopeptides, rifamycins, folate inhibitors, tetracyclines, anti-tuberculosis agents and microbicidal compounds.  
   
   
       33 . A method as claimed in  claim 31  wherein concentration of glycyrrhizin ranges from 0.05 to 50% the weight of the anti-bacterial agent.  
   
   
       34 . A method as claimed in  claim 32  wherein the quinolones and fluoroquinclones are selected from the group consisting of nalidixic acid, norfloxacin, ciprofloxacin, and sparfloxacin.  
   
   
       35 . A method as claimed in  claim 32  wherein the β-Lactams are selected from the group comprising penicillin, flucloxacillin, cloxacukkub, methicillin, cephalosporins and carbapenenms.  
   
   
       36 . A method as claimed in  claim 32  wherein the macrolides are selected from the group consisting of erythromycin, clarithromycin, and azithromycin.  
   
   
       37 . A method as claimed in  claim 32  wherein the aminoglycosides are selected from the group consisting of streptomycin, gentamicin, and amikacin.  
   
   
       38 . A method as claimed in  claim 32  wherein the glycopeptides are selected from vancomycin, and teicoplanin.  
   
   
       39 . A method as claimed in  claim 32  wherein the rifamycins are rifampicin.  
   
   
       40 . A method as claimed in  claim 32  wherein the anti-tuberculosis agents selected from the group consisting of comprising isoniazid, pyrazinamide, and ethambutol.  
   
   
       41 . A method as claimed in  claim 31  wherein concentration of glycyrrhizin ranges from 0.25 to 20% the weight of the anti-fimgal agent.  
   
   
       42 . A method as claimed in  claim 31  wherein the anti-fungal agent is selected from the group consisting of polyene, triazole, imidazole, and clotrimazole.  
   
   
       43 . A method as claimed in  claim 28  wherein the anti-cancer agent is selected from the group consisting of paclitaxel, docetaxel, vinblastine vincristine, and vinorelbine.  
   
   
       44 . A method as claimed in  claim 31  wherein the concentration of glycyrrhizin ranges from 10 to 10,000 fold of the weight of the anti-cancer agent.  
   
   
       45 . A method as claimed in  claim 28  wherein the nutraceutical compound is selected from the group consisting of vitamins, amino acids, hormones and other nutritional supplements.  
   
   
       46 . A method as claimed in  claim 28  wherein administration of the composition circumvents the side effects of chemotherapy by substantially reducing the dosage of the anti-infective or anti-cancer agent.  
   
   
       47 . A method as claimed in  claim 28  wherein the bioenhancer improves the uptake of anti-infectives, anticancer agents and other molecules when glycyrrhizin is provided prior to the treatment with these molecules.  
   
   
       48 . (canceled)  
   
   
       49 . A method as claimed in  claim 46 , wherein the side effect is bone marrow suppression, liver toxicity, kidney toxicity, pulmonary scarring, high fever, skin reaction, nausea, vomiting, hair loss, skin rash, mouth sores, diarrhea, loss of appetite, confusion, lethargy, ambulation difficulty, ataxia, an anaphylactic reaction, fast heart rate, wheezing, lowered blood pressure, facial edema, cerebellar dysfunction, slurring of speech, walking problems, eye motion problem, loss of periods, menses, ovarian failure, soft tissue ulcers, cardiotoxicity, a hypersensitivity reaction, abnormal blood pressure, sweating, bleeding, or shortness of breath.