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WO2002017939A1 - Composition comprenant un agent pharmaceutique/nutriceutique et bio-activateur produit a partir de glycyrrhiza glabra - Google Patents

Composition comprenant un agent pharmaceutique/nutriceutique et bio-activateur produit a partir de glycyrrhiza glabra Download PDF

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Publication number
WO2002017939A1
WO2002017939A1 PCT/IN2000/000083 IN0000083W WO0217939A1 WO 2002017939 A1 WO2002017939 A1 WO 2002017939A1 IN 0000083 W IN0000083 W IN 0000083W WO 0217939 A1 WO0217939 A1 WO 0217939A1
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Prior art keywords
composition
compounds
agents
glycyrrhizin
group
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Ceased
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PCT/IN2000/000083
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English (en)
Inventor
Suman Preet Singh Khanuja
Sushil Kumar
Jai Shankar Arya
Ajit Kumar Shasany
Monika Singh
Soumya Awasthi
Subhas Chandra Gupta
Mahendra Pandurang Darokar
Laiq Ur Rahman
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Council of Scientific and Industrial Research CSIR
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Council of Scientific and Industrial Research CSIR
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Priority to PCT/IN2000/000083 priority Critical patent/WO2002017939A1/fr
Priority to AU2001228791A priority patent/AU2001228791A1/en
Publication of WO2002017939A1 publication Critical patent/WO2002017939A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016—Disaccharides, e.g. lactose, lactulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the invention provides novel compositions containing extracts and compounds obtained from the plant Glycyrrhiza glabra, useful as bio-enhancers and bioavailability facilitators for a variety of molecules including anti-infective, anti-cancer agents and nutritional compositions.
  • This invention also relates to a method for enhancing the biological availability, proficiency and effectivity of drugs, pharmaceuticals, nutraceuticals and other related compounds including amino acids, vitamins and other nutritional elements and ions.
  • the present invention has direct implication in drastically reducing the dosage of antibiotics, drugs and anti-cancer agents while increasing the efficiency of absorption of nutritional elements.
  • Antibiotics work either by killing bacteria (bacteriocidal) or by inhibiting growth (bacteriostatic) and their bioactivities have transformed human ability to treat many infectious diseases that previously were considered certain killers. It is estimated that globally humans consume above 250 million doses of antibiotics annually and 20%-50% of that use is unnecessary depending on the class of antibiotic. Further, widespread use of antibiotics promotes spread of antibiotic resistance many a times leading to multiple drug resistance. The total amount of antibiotic in the given dosage used for treatment of an infection generally is much higher than what is actually required to control a given population of parasite in the infected individual. This is so because all antibiotic given to the patient in a therapy does not reach the target site.
  • Such drug / molecule facilitators should have novel properties like non-toxic to humans, animals or plants, should be effective at a very low concentration in a combination, should be easy to formulate and most importantly enhance uptake/absorption and activity of the drug molecules. This can lead to development of judicious and strategic concentrations of antibiotics with specific bioenhancers to improve availability of the drug right up to the target for effectively controlling the infectious organisms.
  • the present invention was the result of planned experiments to provide a novel method for improving activity and bioavailability of antibiotics, drugs and other molecules using a plant glycoside "Glycyrrhizin" in different formulations.
  • the bioavailability of nutrients and enhancement of antibiotics/drugs effectivity is relevant to human, plant as well as animal health and thus the compositions and methods of the invention are also intended to be used in agriculture and veterinary practice.
  • trikatu dates back to the period-between the seventh century B.C. and the sixth century A.D., which is a Sanskrit word meaning three acrids. It refers to a combination of three elements namely, black pepper (Piper nigrum Linn.), long pepper (Piper longum Linn.) and ginger (Zingiber officinale Rose). It is believed that the use of "trikatu", and its constituents individually as well as collectively, enhances the bioavailability of a number of drugs.
  • Licorice (the extract from the root of the plant) is used to flavor foods, tobacco, drinks, medicines and sweets. It has expectorant action to treat bronchitis and can reduce inflammation, allergies, asthma, gastritis, peptic ulcers, rheumatism, and sore throat. It helps the liver to detoxify drugs and is used for treatment of liver disease. Licorice strengthens the immune system, stimulates the adrenal gland, and is diuretic and laxative. Licorice from roots of Glycyrrhiza glabra, contains glycyrrhizin, which is 50 times sweeter than sugar. Primary uses for licorice include treatment for peptic ulcers and stomach ailments, respiratory and intestinal passages. Licorice makes a wonderful expectorant expelling mucus from the chest area.
  • the compound when studied by the Applicants also showed enhancement in the activity of known azole class antifungal agents like clotrimazole against infectious fungal strain of Candida albicans. More important was the obvious enhancement in the cell division inhibitory activity against the breast cancer cell line MCF-7.
  • the Applicants have sought to increase the absorption of anti-infective, nutritional and anti-cancer compounds by the body and increase their utilization by the body by providing novel compositions containing extracts from the plant Glycyrrhiza glabra.
  • the main object of the invention is to provide novel compositions comprising extracts and compounds from the plant Glycyrrhiza glabra useful as a bioenhancer and capable of improving or enhancing the bio-availability of drugs such as antibiotics, anti-infective agents and of nutritional compounds.
  • Another object of the invention is to provide compositions comprising extracts and compounds from the plant Glycyrrhiza glabra usefiil as bio-enhancers and bioavailability facilitators, thus enabling effective transport of drugs and molecules across biological membranes to reach target sites.
  • Still another object is to provide methods for enhancing the bio-availability of drugs molecules and nutritional compounds to the target site in the body.
  • the invention provides novel compositions containing extracts and compounds from the plant Glycyrrhiza glabra useful as bio-enhancers and bio-availability facilitators for drugs and molecules such as antibiotics, anti-infective agents, anti-cancer agents and for nutritional compounds.
  • the invention also provides methods for enhancing the availability of drugs, molecules and nutritional compounds to effectively reach the target site in the body.
  • the invention provides 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.
  • glycyrrhizin and glycyrrhizic acid are obtained from the plant Glycyrrhiza glabra.
  • the anti-infective agents are selected from anti-bacterial, antifungal and anti-tuberculosis agents.
  • the extract from the roots of Glycyrrhiza glabra is licorice.
  • the compound as bioavailability enhancer facilitates the transport of the compound(s) across the biological membranes to reach the target site for better effectivity/activity.
  • the concentration of glycyrrhizin ranges from 0.05 to 50% of the weight of the anti-bacterial compounds.
  • the concentration of glycyrrhizin ranges from 0.10 to 10% of the weight of the nutraceutical compounds.
  • the concentration of glycyrrhizin ranges from 0.25 to 20% of the weight of the anti-fungal agents.
  • the anti-bacterial agent is selected from the group consisting of ⁇ - lactams, macrolides, quinolones, fluoro-quinolones, aminoglycosides, glycopeptides, rifamycins, folate inhibitors, tetracyclines, anti-tuberculosis agents and other similar microbicidal compounds.
  • the anti-fungal agent used is selected from . the group comprising of polyene, triazole, imidazole, clotrimazole and other fungicidal compounds.
  • bioenhancer improves the uptake of anti-infectives, anticancer agents and other molecules when glycyrrhizin is provided prior to the treatment with these molecules.
  • the anticancer agents include paclitxel (taxol) or other cell division inhibitors controlling the growth and multiplication of tumor/cancer cells.
  • living system used is selected from bacteria, fungi or any living cells.
  • bioenhancer element is used in pure form as glycyrrhizin or as precursor/derivatives like glycyrrhizic acid.
  • bioenhancer element is administered as licorice in form of aqueous/alcoholic extracts, decoction or direct root flakes/chips/sticks through wetting by any means.
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising of th ⁇ ' plant compound glycyrrhizin and a bio-active chemical compound selected from the group consisting of anti-bacterial, anti-fungal, anti-cancerous and other similar compounds including nutraceuticals wherein, the glycyrrhizin concentration ranges from 0.05 to 50% of the weight of the nutraceuticals compound used.
  • the anti-bacterial agent is selected from the group consisting of ⁇ -lactams, macrolides, quinolones, fluoro-quinolones, aminoglycosides, glycopeptides, rifamycins, folate inhibitors, tetracyclines, anti-tuberculosis agents and other similar microbicidal compounds wherein, the glycyrrhizin concentration ranges from 0.05 to 50% of the weight of the anti-bacterial compound used.
  • the macrolides comprise erythromycin, clarithromycin, azithromycin and other similar compounds.
  • the quinolones and tluoroquinolones used are selected from the group consisting of nalidixic acid, norfloxacin, ciprofloxacin, sparfloxacin and similar other compounds.
  • aminoglycosides used are selected from the group consisting of streptomycin, gentamicin, -unikacin and other similar compounds.
  • glycopeptides used are vancomycin, teicoplanin and other similar compounds.
  • rifamycins used are rifampicin and other similar compounds.
  • the anti-tuberculosis agents used are isoniazid, pyrazinamide, ethambutol and other similar compounds.
  • the folate inhibitors are trimethoprim, sulphonamides and other similar compounds.
  • the ⁇ -Lactams comprise penicillin, flucloxacillin, cloxacukkub, methicillin, cephalosporins, carbapenenms and similar compounds.
  • other similar microbicidal compounds are streptogramins and oxazolidinones.
  • the anti-fii ⁇ gal agent is selected from the group consisting of polyene, triazole, imidazole, clotrimazole and other fungic lal compounds wherein, the glycyrrhizin concentration ranges from 0.25 to 20% of the weight of the anti-fungal compound used.
  • the poiyenes used are amphoterecin B, nystatin and other similar compounds.
  • the triazoles used are fluconazole, itraconazole and other sin ilar compounds.
  • the imidazoles used are ketoconazole and other similar compounds.
  • fungicidal compounds are griseofulvin and terbinafine.
  • the anti-cancer agent is selected from the group consisting of Paclitaxel (Taxol), Docetaxel (Taxotere), Vinblastine (Velban), Nincristine (Oncovin), Ninorelbine ( ⁇ avelbine) and other similar compounds used in cancer therapy.
  • the levels of glycyrrhizin ranges from 10 to 10,000 folds of the weight of the anti-cancer compound used.
  • the nutraceuticals used to increase the bio-activity and bioavailability are selected from the group consisting of vitamins, amino acids, hormones and other nutritional supplements.
  • compositions comprising of the plant compound glycyrrhizin in form of liquorice / dried root.; with the bioactive chemical compound(s) to increase their bioactivity and bioavailability wherein, the glycyrrhizin in form of liquorice preparation or dried root is given as one gram equivalent to 40 mg of glycyrrhizin.
  • the invention also provides a method for enhancing the bio-availability of herbal extracts, anti-infective agents, anti-cancer and nutraceutical compounds/compositions across biological membranes in living systems; said method comprising the steps of administering to a subject in need thereof, a composition comprising an effective amount of the bioenhancer obtained from the plant Glycyrrhiza glabra, and any one of anti-infective agents, anti-cancer agents and nutraceutical compounds.
  • the bio-enhancer is selected from the extract of Glycyrrhiza glabra, glycyrrhizin, glycyrrhizic acid obtained from Glycyrrhiza glabra or combinations thereof.
  • administration of the composition circumvents the side effects of chemotherapy by substantially reducing the dosages of therapeutic agents comprising of anti-bacterial, anti-fungal and anti-cancerous agents wherein the side effects of those agents can be bone marrow suppression, liver and kidney toxicity, pulmonary scarring, high fevers, skin reactions, Nausea and vomiting, hair loss, skin rash, mouth sores, , diarrhoea, loss of appetite and confusion, lethargy and ambulation problems (ataxia), anaphylactic reactions (consisting of fast heart rate, wheezing, lowered blood pressure and facial edema, cerebellar dysfunction (consists of slurring of speech, walking problems, as well as eye motion problems), loss of periods (menses), ovarian failure can occur, painful soft tissue ulcers, cardiotoxicity, hypersensitivity reactions, abnormal blood pressure, sweating, bleeding, shortness of breath and many related problems.
  • therapeutic agents comprising of anti-bacterial, anti-fungal and anti-cancerous agents wherein the side effects of those agents can be
  • the bioenhancer improves the uptake of anti-infectives, anticancer agents and other molecules when glycyrrhizin is-, provided prior to the treatment with these molecules.
  • the invention also provides use of the extract or the compound obtained from the plant Glycyrrhiza glabra, as a bioenhancer and bioavailability and facilitator of nutritional compounds and drugs and molecules selected from anti-infective and anti-cancer agents.
  • Fig.1 represents the structural formula of Glycyrrhizic acid
  • Fig.2 represents the structural formula of Glycyrrhizin
  • n ⁇ num inhibitory concentration (MIC) of any antibiotic or drug molecule is determined against Escherichia coli (ATCC 10536), Bacillus subtilis (ATCC 6015 ) and Mycobacterium smegmatis (ATCC 14468) and Candida albicans (ATCC 10231 ) in broth and disc diffusion assays.
  • the antibiotics or antifungal agents at concentrations 1/10, 1/8, 1/6, 1/4, 1/3, 1/2 and equal to MIC are added alone and in combination with the test compound at varying concentrations in broth assays to evaluate the comparative level of inhibition and similarly at varying concentrations in disc diffusion assay.
  • the cells are treated with the bioenhancer/compound for 4 to 8 hours and then washed free of it by centrifugation and washing in sterile water. This is followed by treatment with antibiotic/drug as in steps (b) to (d) above.
  • f) The results of the bio-assays carried out are represented in the tables provided herein below wherein tables 1-6 represent the activity of glycyrrhizin. Tables 7-9 depict the activity of glycyrrhizic acid and tables 10-11 depict the activity of licorice.
  • MCF-7 Breast cancer cell line
  • MEM medium inoculated at a density of about 0.1 X 10 6 cells in MEM medium in the wells of 24 well plate.
  • the used up medium in these cultures is replaced with fresh medium after 18 hours in each well.
  • the test compound (s) is added at desired concentrations in different wells just after the medium replacement.
  • Observations are recorded on the cell count after 36 hours for which the following steps are required. i. The medium is removed from the wells. ii. The wells are rinsed with 1ml PBS (Phosphate buffer saline), iii. To each well 500 ⁇ l of freshly prepared trypsin solution (0.1% in PBS) is added, iv.
  • PBS Phosphate buffer saline
  • MEM Minimum Essential Medium
  • Example 3 Glycyrrhizin mediated enhancement in the killing action of antibiotics against bacterium Mycobacterium smegmatis
  • Example 4 Glycyrrhizin mediated enhancement observed in disc diffusion assays for the killing action of antifungal agent against Candida a ⁇ bicans.
  • the applicants observed glycyrrhizin-mediated enhancement in the cell division inhibitory action of anti-cancer agent taxol in the animal cell culture experiments using cancerous cell line MCF-7.
  • the anticancerous activity of 'Taxol' in terms of inhibiting the growth and multiplication of MCF-7 cancer cells was markedly enhanced by at least 5 folds.
  • the cancerous cells growth inhibition by Taxol (@ 0.01 ⁇ g ml) in presence of glycy ⁇ -hizin (@ 1 ⁇ g/ml) was higher than even the treatment with taxol (@ 0.05 ⁇ g/ml) alone.
  • Example 7 Glycyrrhizic acid mediated enhancement in the killing action of antibiotics against Escherichia coli in broth assay. Table 7
  • the Applicants used Glycyrrhizic acid to test the potency of this acid in enhancing the activity of antibiotics.
  • the Applicants observed that the killing action the antibiotics (such as Rifampicin) is enhanced when used with Glycyrrhizic acid.
  • Table 7 shows that when the cells were treated with Rifampicin alone, the survival fraction was about 0.57. However, the survival fraction of cells when treated with a combination of rifampicin and glycyrrhizic acid was much less i.e. about 0.281. This shows that the combination of glycyrrhizic acid with rifampicin enhances the availability of rifampicin to the cells.
  • the results of the disc diffusion assay also show that the combination of glycyrrhizic acid with rifampicin is more effective against Mycobacterium smegmatis than glycyrrhizic acid or rifampicin used singly.
  • Example 8 Licorice (25 ( ⁇ g/ml) mediated enhancement in the killing action of Rifampicin against Gram-negative bacterium Escherichia coli.
  • Table 11 Licorice (25 ⁇ g/ml) mediated enhancement in the killing action of antibiotics against Gram- positive bacterium Bacillus subtilus.
  • Tables 10 and 11 show the bio-enhancing effects observed in the use of licorice, the extract from the roots of Glycyrrhiza glabra. As can be seen from Tables 10, the survival rate of bacteria treated with the antibiotic Rifampicin is more than when treated with a combination of Rifampicin and licorice. Similarly, Table 11 shows that the survival rate of the bacteria treated with nalidixic acid is less than when treated with a combination of nalidixic acid and licorice. The results in Tables 10 and 11 demonstrate the use of licorice as an effective bioenhancer and bioavailability facilitator.
  • the compound glycyrrhizin enhances the transport of antibiotics e.g. Rifampicin, Tetracycline, Nalidixic acid, Ampicillin and vitamins like B-1 and B-12 across the gut as well as artificial membrane.
  • antibiotics e.g. Rifampicin, Tetracycline, Nalidixic acid, Ampicillin and vitamins like B-1 and B-12 across the gut as well as artificial membrane.
  • the enhancement in transport is approximately 2 to 6 folds.
  • Glycyrrhiza (Mulethi) has attracted sizable importance for compound(s) with hepatoprotective ability.
  • Glycyrrhiza glabra family, Leguminosae 12 different varieties (Biovars) are known. Among these only three namely typica, glandilifera and violacea are commonly used for the pharmaceutical and confectionary requirements. Glycyrrhiza glabra var.
  • Glycyrrhiza glabra var. glandilifera is the source of Russian liquorice, which is moderately sweet and some what bitter, also more or less acrid.
  • Glycyrrhiza glabra var. violacea is known as the Persian or Egyptian liquorice . of commerce and has thick roots.
  • the name Glycyrrhiza (popularly known as mulethi in India) is of Greek origin meaning sweet root. Cultivation of this species is mostly limited to US, Eastern Europe and several CIS of former USSR and scattered in western and northern India.
  • the roots of the plant Glycyrrhiza glabra are highly useful as these contain the important glycoside Glycyrrhizin for its hepatoprotective ability.
  • the root extracts also contain flavonoids, saponins, sterols, amino acids, gums essential oils, sugars and starches.
  • the plant takes at least 4-5 years to achieve substantial production of glycyrrhizin in the roots. Generating sufficient planting material for commercial cultivation is thus desirable for harvesting required quantity of Glycyrrhizin on sustainable basis.
  • This molecule (Glycyrrhizin) is a known sweetener and hepatoprotective drug. It helps the liver to detoxify drugs and is given for liver disease.
  • the molecule is known to be strengthening the immune system, stimulates the adrenal gland, and is diuretic and laxative. This is also used to treat peptic ulcers and stomach ailments, respiratory and intestinal passages. Considering the wide use of the molecule in traditional system of medicine and the level of toxicity well tested, this can be used along with the antibiotics and other molecule of importance to enhance the efficacy on the target.
  • This molecule in the Applicant's study facilitates the transport/uptake of various compounds including antibiotics, antifungal and anticancer agents, vitamins and amino acids etc. across the membrane thereby increasing the absorption or bioavailability various biological systems including bacteria, animal and plant cells. This thus has immense importance for absorption of the drugs, pharmaceuticals, nutraceutical and other related compounds and ions by the cells and hence huge potential of being used as drug/molecule facilitators.
  • the present invention enlarges the scope and use of the natural glycoside glycyrrhizin in therapeutical and nutraceutical. application.
  • These plants synthesizing multi-use molecules are Glycyrrhiza sps and Abarus sps.
  • the preferred plant is Glycyrrhiza glabra which is propagated through underground rhizome.
  • Plant material 250 gram was dipped in 900 ml of Butanol : glacial acetic acid : ethyl alcohol (1:1:1) for 48 hours.
  • the hydrolyzed reaction mixture was acidified (100 ml of glacial acetic acid and 5 ml of concentrated HC1) to pH 3.6 to form a ppt which was filtered and washed with ethanol. After isolation, the compound was checked for the purity compared to the standard glycyrrhizin obtained from Sigma chemical Inc.
  • test solution One gram of the isolated compound was extracted in 20 ml chloroform for 15 min. After filtration the filtrate was discarded. The marc was refluxed for 1 hour with 30 ml of 0.5 M H 2 SO 4 . The unfiltered mixture was then cooled and extracted with chloroform (2X20ml) and the combined CHC1 3 extract was concentrated. The residue was dissolved in 1.0 ml CHC1 3 : Methanol (1:1) mixture.
  • test and reference solutions were applied in two different tracks on a precoated silica gel GF 25 plate (5X15 cm) of uniform thickness (0.2 mm). The plate was developed in the solvent system to a distance of 12 cm.
  • the plant extract of Glycyrrhiza glabra and glycyrrhizin in the Applicant's study facilitates the transport/uptake of various compounds including antibiotics, antifungal and anticancer agents, vitamins and amino acids etc. across the membrane thereby increasing the absorption or bioavailability various biological systems including bacteria, animal and plant cells. This thus has immense importance for absorption of the drugs, pharmaceuticals, nutraceutical and other related compounds and ions by the cells and hence huge potential of being used as drug/molecule facilitators.
  • the present invention enlarges the scope and use of the natural glycoside glycyrrhizin in therapeutical and nutraceutical application. 3.
  • Glycyrrhizin is nontoxic to humans,animals or plants, is effective at very low concentrations in a combination,easy to formulate and enhances the uptake/absorption and activity of drug molecules.
  • the novel use of this compound as described in the present invention is safe and effective for bioenhancement of activity of drugs. Glycyrrhizin by its presence will not exert any selection pressure for the mutants to emerge resistant against them and reduce the dosage of antibiotics or drugs so that their ill effects are reduced.

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Abstract

L'invention concerne une nouvelle utilisation d'un composé non-alcaloïde, à savoir la glycyrrhizine, un glycoside d'origine végétale, en tant que bio-activateur puissant de l'action et de la disponibilité d'antibiotiques et d'autres médicaments, notamment d'agents anti-infectieux et d'agents anticancéreux. La molécule décrite favorise l'absorption/la résorption des antibiotiques et d'autres molécules à travers la membrane cellulaire des cellules végétales et animales, ainsi que des bactéries Gram positives et Gram négatives, et peut par conséquent être utilisée comme molécule stimulatrice ou de bioactivatrice, afin d'augmenter l'efficacité des médicaments et des agents nutriceutiques. Etant donné que ce composé ne présente aucune activité antimicrobienne ou cytotoxique propre, il constitue un candidat sûr permettant une réduction du dosage de médicaments en vue de surmonter les problèmes de résistance aux médicaments et d'autres effets secondaires dans les traitements anti-infectieux et anticancéreux.
PCT/IN2000/000083 2000-08-31 2000-08-31 Composition comprenant un agent pharmaceutique/nutriceutique et bio-activateur produit a partir de glycyrrhiza glabra Ceased WO2002017939A1 (fr)

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PCT/IN2000/000083 WO2002017939A1 (fr) 2000-08-31 2000-08-31 Composition comprenant un agent pharmaceutique/nutriceutique et bio-activateur produit a partir de glycyrrhiza glabra
AU2001228791A AU2001228791A1 (en) 2000-08-31 2000-08-31 A composition comprising pharmaceutical/nutraceutical agent and a bio-enhancer obtained from glycyrrhiza glabra

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004084641A1 (fr) * 2002-11-19 2004-10-07 Nutrinova Nutrition Specialties & Food Ingredients Gmbh Utilisation d'acides edulcorants pour la stabilisation microbiologique de produits alimentaires, cosmetiques, articles de premiere necessite et produits pharmaceutiques
EP1367999A4 (fr) * 2001-02-16 2007-04-18 Lavipharm Lab Inc Complexes hydrosolubles et palatables
WO2016203499A1 (fr) 2015-06-19 2016-12-22 Chigurupati Harsha Composition de boisson synergique
CN106491563A (zh) * 2016-09-20 2017-03-15 重庆希尔安药业有限公司 一种用于胃肠道疾病的磷霉素钙甲氧苄啶胶囊

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1367999A4 (fr) * 2001-02-16 2007-04-18 Lavipharm Lab Inc Complexes hydrosolubles et palatables
WO2004084641A1 (fr) * 2002-11-19 2004-10-07 Nutrinova Nutrition Specialties & Food Ingredients Gmbh Utilisation d'acides edulcorants pour la stabilisation microbiologique de produits alimentaires, cosmetiques, articles de premiere necessite et produits pharmaceutiques
WO2016203499A1 (fr) 2015-06-19 2016-12-22 Chigurupati Harsha Composition de boisson synergique
US10456359B2 (en) 2015-06-19 2019-10-29 Harsha Chigurupati Synergistic beverage composition
CN106491563A (zh) * 2016-09-20 2017-03-15 重庆希尔安药业有限公司 一种用于胃肠道疾病的磷霉素钙甲氧苄啶胶囊

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