WO2007042902A2 - Composition pharmaceutique utilisee comme agent leishmanicide - Google Patents

Composition pharmaceutique utilisee comme agent leishmanicide Download PDF

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Publication number
WO2007042902A2
WO2007042902A2 PCT/IB2006/002805 IB2006002805W WO2007042902A2 WO 2007042902 A2 WO2007042902 A2 WO 2007042902A2 IB 2006002805 W IB2006002805 W IB 2006002805W WO 2007042902 A2 WO2007042902 A2 WO 2007042902A2
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Prior art keywords
body weight
composition
bioactive fraction
piperine
unit dose
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PCT/IB2006/002805
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WO2007042902A3 (fr
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Sharmila Chattopadhyay
Basudeb Achari
Avijit Poddar
Akhilesh Kumar
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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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Publication of WO2007042902A3 publication Critical patent/WO2007042902A3/fr
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    • 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)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a bioactive fraction obtained from the leaves of the plant night jasmine.
  • bioactive fraction in the treatment of visceral leshmaniasis.
  • the present invention also relates to the use of the compound calceolarioside A as a leishmanicidal agent.
  • compositions useful as a leishmanicidal agent comprising the therapeutically effective amount of said bioactive fraction obtained from the leaves of the plant night jasmine or selected from the combination comprising the bioactive fraction and sodium antimony gluconate or bioactive fraction and piperine or bioactive fraction and sodium antimony gluconate and piperine optionally along with one or more pharmaceutically acceptable carriers, additives, lubricant and diluents.
  • the present invention also relates to a method for the isolation of compound calceolarioside A from the bioactive fraction obtained from the leaves of the plant
  • Nyctanthes arbortristis is a traditionally used medicinal plant of India commonly used as an anthelmintic, antibilious, diaphoretic etc. and fpr the treatment of various diseases such as fever, rheumatism, intestinal worm disinfections etc. (The Wealth of India, Raw Materials, (1966) Vol. 7, pp 69-70). Tribal people of central India used various parts of this plant for relieving cough, dysentery, snakebite, sores etc. (S.KJain, Dictionary of Indian folk medicine and Ethnobotany, 1991). Most of the recent bioactivity studies on N.
  • arbortristis has been carried out from seed extract and iridoid glycosides (arbortristoside A, B, C, D, E) were isolated which showed antiviral (Anita Rathore, Vandita Srivastava, K.C.Srivastava and J.S. Tandon, Phytochemistry (1990) Vol.29 pp.1917-1920) or antileishmanial activity (J.S.Tandon, Vandita Srivastava and P.Y.Guru, Journal of Natural Products, (1991) Vol.54 pp.l 102-1104).
  • calceolarioside A a new class of compound to be reported from this plant, was isolated and purified from the methanolic extract of night jasmine leaf and showed significant antileishmanial activity both in vitro and in vivo test systems. This is the first isolation report of calceolarioside A from this plant as well as the first antileishmanial activity report of calceolarioside A.
  • the main object of the present invention is to provide a bioactive fraction obtained from the leaves of the plant night jasmine.
  • Another object of the present invention is to provide the use of said bioactive fraction in the treatment of visceral leishmaniasis. Further object of the present invention is to provide the use of the compound calceolarioside A as a leishmanicidal agent.
  • the present invention deals with a bioactive fraction obtained from the leaves of the plant night jasmine comprising a) calceolarioside A b) unidentified compounds c) kaempferol glycoside. It also provides the use of the said fraction and the compound calceolarioside A in the treatment of visceral leishmaniasis. Further, it also relates to a pharmaceutical composition and method of treating visceral leishmaniasis using said composition. The invention also relates to a method of isolation of said compound from the bioactive fraction obtained from the leaves of the plant Nyctanthes arbortristis.
  • Figure 1 represents the effect of crude methanolic extract of Nyctanthes arbortristis leaf and PE on the growth of Leishmania donovani promastigotes in vitro in time and dose dependent manner. Viable cells, i.e., promastigotes (xlO 6 )/nil of culture. Data are shown for one representative experiment out of three with similar results. Solvent was DMSO+PBS.
  • Figure 2 represents the effect of Nyctanthes arbortristis crude methanolic leaf extract against established infection of visceral leishmaniasis in golden hamster model.
  • Two weeks infected golden hamsters were treated with crude extract at the dose of lOmg/kg, 20mg/kg, 40 mg/kg and 60mg/kg body weight for 21 days. Controls were infected untreated animals. Crude extract was administered through i.p route. Treated animals received total six shots of crude extract during three weeks of treatment schedule. Animals were sacrificed after six weeks of infection. Levels of parasite burden in spleen and liver are expressed in Leishman-Donovan units (LDU).
  • LDU Leishman-Donovan units
  • Figure 3 represents the effect of methanolic extract of Nyctanthes arhortritis leaf and SAG in established infection of Leishmania donovani.
  • Four weeks infected golden hamsters were treated intra-peritoneally with crude methanolic extract at the doses of 10mg/kg body weight, 20 mg/kg body weight and SAG 10mg/kg body weight for 7 days respectively.
  • Controls were infected untreated animals.
  • Treated animals received one shot in one week to complete the treatment.
  • Level of parasite burden in spleen is expressed in Leishman-Donovan units (LDU).
  • DMSO: PBS DMSO+PBS as solvent of crude extract
  • Figure 4 represents the effect of bioactive fraction and combined therapy of bioactive fraction + SAG in established infection of visceral leishmaniasis.
  • Viable cells i.e., promastigotes (xlO 6 )/ml of culture. Data are shown for one representative experiment out of three with similar results.
  • Figure 7 represents the effect of bioactive fraction and combined therapy of bioactive fraction, SAG and piperine against established infection of visceral leishmaniasis in golden hamster model. Effect of bioactive fraction, combined therapy of bioactive fraction + piperine, bioactive fraction + SAG and bioactive fraction + SAG + piperine against established infection of visceral leishmaniasis in golden hamster model.
  • Fig 8 HPLC chromatogram of bioactive fraction obtained from methanolic extract of night jasmine leaf.
  • Fig 9 HPLC chromatogram of calceolarioside A obtained from methanolic extract of night jasmine leaf. Detailed description of the invention:
  • the present invention provides a bioactive fraction obtained from the leaves of the plant night jasmine, wherein the said fraction comprising a) calceolarioside A 39.62% b) kaempferol glycoside 34.8%, c) two unidentified compound 5.2% & 5.8% and d) unidentified unresolved fraction 14.6%, wherein said weight percentages are percentages in the total weight of the fraction.
  • the said fraction is useful as a leishmanicidal agent.
  • the said fraction is non toxic to liver and kidney at the dose of 200mg/Kg body weight / day at least for three weeks.
  • the present invention also provides the use of the bioactive fraction in the treatment of visceral leshmaniasis.
  • the compound calceolarioside A as a leishmanicidal agent.
  • the said compound reduces the viability of
  • L. donovani promastigotes in vitro uptolOO % at the dose of 80 ⁇ g/ml of culture media for 24 hrs.
  • the present invention also provides a pharmaceutical composition useful as a leishmanicidal agent, wherein the said composition comprising the therapeutically effective amount of said bioactive fraction obtained from the leaves of the plant night jasmine or selected from the combination comprising the bioactive fraction and sodium antimony gluconate or bioactive fraction and piperine or bioactive fraction and sodium antimony gluconate and piperine optionally along with one or more pharmaceutically acceptable carriers, additives, lubricant and diluents.
  • the additives used are selected from the group comprising of proteins, carbohydrates, sugar, talc, magnesium state, cellulose, calcium, carbohydrate, starch-gelatin paste.
  • the said composition further comprising the therapeutically effective amount of bioactive fraction obtained from the leaves of the plant night jasmine optionally along with one or more pharmaceutically acceptable carriers, additives and diluents.
  • the dosage of the said composition is administered at a unit dose of at least 100 to 200 mg/Kg body weight.
  • the said composition is preferably administered at a unit dose of 100 mg/Kg body weight at least for three weeks wherein the said composition reduces the parasitic load of spleen up to 81.6%.
  • the said composition is preferably administered at a unit dose of 100 mg/Kg body weight at least for three weeks wherein the said composition reduces the parasitic load of liver up to 85.42%.
  • the said composition further comprising the therapeutically effective amount of bioactive fraction and sodium antimony gluconate optionally along with one or more pharmaceutically acceptable carriers, additives and diluents wherein the ratio of bioactive fraction and sodium antimony gluconate is in the range of 200:1 to 20:1.
  • the dosage of the said composition is administered at a unit dose of at least 150mg/Kg body weight of bioactive fraction and 5 mg/Kg body weight of sodium antimony gluconate to 200mg/Kg body weight of bioactive fraction and 10 mg/Kg body weight of sodium antimony gluconate.
  • the dosage of the said composition is preferably administered at a unit dose of 150mg/Kg body weight of bioactive fraction and 5 mg/Kg body weight of sodium antimony gluconate at least for three weeks wherein the said composition reduces the parasitic load of spleen up to 95.1%.
  • the dosage of the said composition is preferably administered at a unit dose of 150mg/Kg body weight of bioactive fraction and 5 mg/Kg body weight of sodium antimony gluconate at least for three weeks wherein the said composition reduces the parasitic load of liver up to 99.85%.
  • the dosage of the said composition is preferably administered at a unit dose of 200mg/Kg body weight of bioactive fraction and 10 mg/Kg body weight of sodium antimony gluconate at least for three weeks wherein the said composition reduces the parasitic load of liver and spleen up to 100%.
  • the said composition further comprising the therapeutically effective amount of bioactive fraction and piperine optionally along with one or more pharmaceutically acceptable carriers, additives and diluents wherein the ratio of bioactive fraction and piperine is in the range of 200:1 to 20:1.
  • the dosage of the said composition is administered at a unit dose of lOOmg/Kg body weight of bioactive fraction and 0.5 mg/Kg body weight of piperine to 100 mg/Kg body weight of bioactive fraction and 5.0 mg/Kg body weight of piperine.
  • the dosage of the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 0.5 mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of spleen up to 98.8%.
  • the dosage of the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 0.5 mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of liver up to 79.8%.
  • the dosage of the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 5.0 mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of liver and spleen up to 100%.
  • the said composition further comprising the therapeutically effective amount of bioactive fraction and sodium antimony gluconate and piperine optionally along with one or more pharmaceutically acceptable carriers, additives and diluents wherein the ratio of bioactive fraction and sodium antimony gluconate and piperine is in the range of 40: 1 : 0.2 to 40: 1 : 2
  • the dosage of the said composition is administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 2.5 mg/Kg body weight of sodium antimony gluconate and 0.5 mg/Kg body weight of piperine to 100mg/Kg body weight of bioactive fraction and 2.5 mg/Kg body weight of sodium antimony gluconate and 5.0 mg/Kg body weight of piperine.
  • the dosage of the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 2.5 mg/Kg body weight of sodium antimony gluconate and 5.0mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of liver and spleen up to 100%.
  • the invention provides a method of treating visceral leishmaniasis in a subject, wherein the said method comprising the step of administering to the subject a pharmaceutical composition comprising the therapeutically effective amount of said bioactive fraction obtained from the leaves of the plant night jasmine or selected from the combination comprising the bioactive fraction and sodium antimony gluconate or bioactive fraction and piperine or bioactive fraction and sodium antimony gluconate , and piperine optionally along with one or more pharmaceutically acceptable carriers, additives, lubricant and diluents.
  • the said subject is mammal including human.
  • the additives used are selected from the group comprising of proteins, carbohydrates, sugar, talc, magnesium state, cellulose, calcium, carbohydrate, starch-gelatin paste.
  • the said method further comprising the step of administering to the subject a pharmaceutical composition comprising therapeutically effective amount of bioactive fraction obtained from the leaves of the plant night jasmine optionally along with one or more pharmaceutically acceptable carriers, additives and diluents.
  • the said composition is administered at a unit dose of at least 100-to 200-mg/Kg-body weight.
  • the said composition is preferably administered at a unit dose of 100-mg/Kg body weight at least for three weeks wherein the said composition reduces the parasitic load of spleen up to 81.6%.
  • the said composition is preferably administered at a unit dose of 100-mg/Kg body weight at least for three weeks wherein the said composition reduces the parasitic load of liver up to 85.42%.
  • the said method further comprising the step of administering to the subject a pharmaceutical composition comprising the therapeutically effective amount of bioactive fraction and sodium antimony gluconate optionally along with one or more pharmaceutically acceptable carriers, additives and diluents wherein the ratio of bioactive fraction and sodium antimony gluconate is in the range of 200:1 to 20:1.
  • the said composition is administered at a unit dose of at least 150mg/Kg body weight of bioactive fraction and 5 mg/Kg body weight of sodium antimony gluconate to 200mg/Kg body weight of bioactive fraction and 10 mg/Kg body weight of sodium antimony gluconate.
  • the said composition is preferably administered at a unit dose of 150mg/Kg body weight of bioactive fraction and 5 mg/Kg body weight of sodium antimony gluconate at least for three weeks wherein the said composition reduces the parasitic load of spleen up to 95.1 %.
  • the said composition is preferably administered at a unit dose of 150mg/Kg body weight of bioactive fraction and 5 mg/Kg body weight of sodium antimony gluconate at least for three weeks wherein the said composition reduces the parasitic load of liver up to 99.85%.
  • the said composition is preferably administered at a unit dose of 200mg/Kg body weight of bioactive fraction and 10 mg/Kg body weight of sodium antimony gluconate at least for three weeks wherein the said composition reduces the parasitic load of liver and spleen up to 100%.
  • the said wherein the said method further comprising the step of administering to the subject .
  • a pharmaceutical composition comprising the therapeutically effective amount of bioactive fraction and piperine optionally along with one or more pharmaceutically acceptable carriers, additives and diluents wherein the ratio of bioactive fraction and piperine is in the range of200:l to 20:l.
  • the said composition is administered at a unit dose of lOOmg/Kg body weight of bioactive fraction and 0.5 mg/Kg body weight of piperine to 100 mg/Kg body weight of bioactive fraction and 5.0 mg/Kg body weight of piperine.
  • the said composition is preferably administered at a unit dose of lOOmg/Kg body weight of bioactive fraction and 0.5 mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of spleen up to 98.8%.
  • the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 0.5 mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of liver up to 79.8%.
  • the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 5.0 mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of liver and spleen up to 100%.
  • the said wherein the said method further comprising the step of administering to the subject a pharmaceutical composition comprising the therapeutically effective amount of bioactive fraction and sodium antimony gluconate and piperine optionally along with one or more pharmaceutically acceptable carriers, additives and diluents wherein the ratio of bioactive fraction and sodium antimony gluconate and piperine is in the range of 40: 1: 0.2 to 40: 1: 2.
  • the said composition is administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 2.5 mg/Kg body weight of sodium antimony gluconate and 0.5 mg/Kg body weight of piperine to 100mg/Kg body weight of bioactive fraction and 2.5 mg/Kg body weight of sodium antimony gluconate and 5.0 mg/Kg body weight of piperine.
  • the said composition is preferably administered at a unit dose of 100mg/Kg body weight of bioactive fraction and 2.5 mg/Kg body weight of sodium antimony gluconate and 5.0mg/Kg body weight of piperine at least for three weeks wherein the said composition reduces the parasitic load of liver and spleen up to 100%.
  • the administration route used is selected from the group consisting of oral, intraperitoneal, intravenous, intramuscular.
  • the said form for oral route is selected from the group consisting of capsule, syrup, concentrate, powder and granules.
  • the effective dose of the said composition is administered in such a manner that it does not interfere the other physiological activities.
  • the effective dose of the said composition is administered in such a manner that it does not create any clinical and pathological toxicity to the subject.
  • the present invention also provides a method for the isolation of compound calceolarioside A from the bioactive fraction, wherein the said method comprising the steps of: a) extracting the powdered dry mass of fresh leaves of Nyctanthes arbortristis with alcohol, b) concentrating the extract obtained from step (a) under reduced pressure at atleast 40 °C to obtain semi solid mass; c) performing repeatedly chromatography using organic solvent of the said mass as obtained from step (b) to get bioactive fraction; d) performing thin layer chromatography to get desired compound calceolarioside A.
  • the leaves of Nyctanthes arbortristis are collected from Jhargram, West Bengal and voucher specimen submitted to Botanical Survey of India, Shibpur, Howrah ( vide voucher specimen no. NAlOl, dated 28.06.2006).
  • the alcohol used is selected from the group comprising of methanol, ethanol, n-butanol.
  • the semi solid mass of step (b) is chromatographed over a silica gel column having mesh size 60nm-120nm.
  • the organic solvent used is chloroform.
  • the present invention is related to a method for novel drug development from natural sources without any clinical and pathological toxic effects, wherein the said method comprising preparing methanolic extract of night jasmine leaf, chromatographic purification of said extract, isolation bioactive fraction of containing a compound calceolarioside A , treatment of L.
  • a method for using night jasmine leaf extract as leishmanicidal agent comprising a) methanolic extraction of night jasmine leaf and chromatographic purification to isolate calceolarioside A containing bioactive fraction (PE). b) administering bioactive fraction at least 100-200mg/kg body weight/day through i.p for a period of at least three weeks to the L. donovani infected chronic golden hamster model. c) administering bioactive fraction at least 100-200mg/kg body weight/day and SAG at least 5 and 10mg/kg body weight/day through i .p for a period of at least three weeks to the L. donovani infected chronic golden hamster model. d) antileishmanial activity of calceolarioside A against axenic L. donovani promastigote culture.
  • a pharmaceutical composition of the present invention is useful as leishmanicidal agent against chronic visceral leishmaniasis.
  • SAG Sodium Antimony Gluconate
  • PE Calceolariside A containing bioactive fraction
  • the pure compound calceolarioside A was collected by preparative thin layer chromatography from this semi-pure bioactive fraction of example 2. Identification of the pure compound was done with 1 H, and 13 C Nuclear Magnetic Resonance (NMR). Spectra recorded with a Bruker DPX-300 machine. Both positive and negative ion- mode mass spectrometry were done with Micromass Q-Tof microTM to determine the molecular weight.
  • Leishmania donovani Ag83 was isolated from an Indian kala-azar patient and maintained in Golden hamster (Mesocrisetm auratus) model (A.K Ghosh, F. K. Bhattacharya and D.K Ghosh, Leishmania donovani: amastigote inhibition and mode of action of berberine (1985) Experimental Parasitology, Vol. 60 pp 404-413). Liquid parasite culture was done in Ml 99 media (Sigma, USA) supplemented with 10% Fetal Bovine Serum (Sigma, USA) at 22°C culture room. Stationary phase promastigotes of L .donovani were used for in- vitro assay.
  • the in-vitro activity of crude extract, bioactive fraction and pure compound calceolarioside A was determined on stationary phase promastigotes of L. donovani Ag83 strain.
  • the stationary phase promastigotes were collected from parasite culture by centrifugation and re-suspended with 10% FBS supplemented Ml 99 medium.
  • For drug sensitivity assay 50mg/ml stock solution for each test material were prepared with minimum amount of DMSO and PBS and serially diluted with sterile PBS to achieve the desired dose. Assay was performed in sterile tubes with 450 ⁇ l of parasite suspension. Then 50 ⁇ l of test solutions were added to each tube and one control only with solvent (DMSO and PBS) was maintained. Tubes were incubated at 22 0 C for 72hrs and data was collected after each 24hrs .Mortality rate of the parasite was determined microscopically on Neubauer Counter Chamber (HBG, Germany).
  • HPLC Shiadzu, Japan chromatogram of bioactive fraction containing calceolarioside A is obtained from methanolic crude extract of night jasmine leaf. The analysis was performed with C 18 column (250x4 mm I. D; SGE International PTY, Australia) attached with a Guard column (Supelco) a Rheodyne injection valve with a 100- ⁇ l loop and PDA detector (SPD-M 10 Avp).
  • a linear gradient elution was carried out with methanol: water mixtures from 0:100,(v/v) to 100:0,(v/v) within 0 to 60 min at a flow rate of 0.5 ml/min.
  • the column was maintained at room temperature and the detection was performed at UV 210 nm and 254 nm.

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Abstract

L'invention porte sur l'activité leishmanicide d'un extrait des feuilles du jasmin nocturne, lequel procédé consiste: à préparer un extrait méthanolique des feuilles du jasmin nocturne; à procéder à la purification chromatographique dudit extrait afin d'obtenir un fragment bioactif contenant du calcéolarioside A (PE); à isoler et caractériser le calcéolarioside A et l'activité leishmanicide du calcéolarioside A sur une culture axénique de promastigotes de Leishmania donovan; à traiter un hamster doré atteint d'une infection chronique par L. donovani avec un fragment actif pendant une période de 21 jours afin de détecter l'activité leishmanicide in vivo; à administrer un PE à un hamster normal afin d'obtenir une thérapie de combinaison naturelle non toxique d'un fragment bioactif + SAG par rapport au modèle, afin d'arriver à une synergie de l'activité antileishmaniale et à une clairance complète de la parasitémie du foie et de la rate tel qu'illustré par les LDU, l'invention constituant un médicament potentiel contre le kala-azar.
PCT/IB2006/002805 2005-10-10 2006-10-09 Composition pharmaceutique utilisee comme agent leishmanicide Ceased WO2007042902A2 (fr)

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CN101816665A (zh) * 2010-03-18 2010-09-01 长春理工大学 一种免疫抑制药物
EP2805722A4 (fr) * 2012-01-19 2015-09-02 Suntory Holdings Ltd Extrait d'olive contenant du dé(rhamnosyl)-actéoside
US20160158302A1 (en) * 2014-12-06 2016-06-09 B. Arvind Shah Regulation of Brain Biogenic Amines Associated with Depression by a Formulation from Botanical Source

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101816665A (zh) * 2010-03-18 2010-09-01 长春理工大学 一种免疫抑制药物
EP2805722A4 (fr) * 2012-01-19 2015-09-02 Suntory Holdings Ltd Extrait d'olive contenant du dé(rhamnosyl)-actéoside
AU2013210416B2 (en) * 2012-01-19 2017-03-23 Suntory Holdings Limited Desrhamnosyl acteoside-containing olive extract
US20160158302A1 (en) * 2014-12-06 2016-06-09 B. Arvind Shah Regulation of Brain Biogenic Amines Associated with Depression by a Formulation from Botanical Source
US10111921B2 (en) 2014-12-06 2018-10-30 Govind Prasad Dubey Regulation of brain biogenic amines associated with depression by a formulation from botanical source

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