WO2003047608A1 - A novel herbal chemical composition for the treatment of cancer - Google Patents

A novel herbal chemical composition for the treatment of cancer Download PDF

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WO2003047608A1
WO2003047608A1 PCT/IN2001/000214 IN0100214W WO03047608A1 WO 2003047608 A1 WO2003047608 A1 WO 2003047608A1 IN 0100214 W IN0100214 W IN 0100214W WO 03047608 A1 WO03047608 A1 WO 03047608A1
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composition
cells
growth
synergistic
inhibits
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French (fr)
Inventor
Janaswamy Madhusudana Rao
Pullela Venkata Srinivas
Jhillu Singh Yadav
Kondapuram Vijaya Raghavan
A. K. Saxena
M. Shanmugavel
Himani Kampasi
Gulam Nabi Qazi
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Council of Scientific and Industrial Research CSIR
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Priority to CA002469093A priority Critical patent/CA2469093A1/en
Priority to AU2002222501A priority patent/AU2002222501A1/en
Priority to KR10-2004-7008727A priority patent/KR20040072646A/ko
Priority to JP2003548863A priority patent/JP2005511659A/ja
Priority to CNB018239242A priority patent/CN100444837C/zh
Priority to EP01274887A priority patent/EP1465645A1/en
Priority to PCT/IN2001/000214 priority patent/WO2003047608A1/en
Publication of WO2003047608A1 publication Critical patent/WO2003047608A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13Coniferophyta (gymnosperms)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a novel herbal composition for the treatment of cancer.
  • the present invention particularly relates to an hert ⁇ al formulation comprising mixture of lignans isolated from the plant Cedrus Deodara.
  • Cancer or neoplasm is the malignant new growth anywhere and elsewhere in the body system. It is characterized by unregulated proliferation of cells and a growing public health problem whose estimated worldwide new incidence is about six million cases per year. In most of the countries, cancer is second only to heart disease as cause of death. It can arise in any organ of the body but some sites are prone to attack than others such as breast, throat, intestine, leukocytes etc. Each cancer is propagated from a single cell that cut at some stage, it becomes free from its territorial restraints, which form a family of cells that multiply without limits and appear in the form of tumors.
  • cancer cells have a) low pH b) greater free radical character c) tumor produced hormone peptides d) tumor associated antigens e) lower calcium ion and higher potassium ion concentration f) different potassium isotope ratios g) elevated amounts of methylated nucleotides h) higher concentrations of plasma microproteins and mucopolysacharides i) greater need of exogenous zinc and j) high biowater content.
  • Many of the gross causes of cancer such as dietary, environmental, occupational exposure to certain chemical substances or forms of electromagnetic radiation, have been elucidated through epidemiological studies.
  • Lignans have been isolated from a number of plants(Achenbach, H., Waibel, R. and Meusah, I. Phytochemistry, 22 (3), 749-753 (1983); Nishibe, S., Hisada, S. and Inagaki, I. Phytochemistry, 10, 2231-2232 (1971); Barrero, A. F., Haidour, A. and Dorado, M. M. J. Nat. Prod. 42,159-162(1979)).
  • Cedrus deodara is also a new source for these lignans.
  • (-)-Wikstromol was first reported from wikstroemia viridiflora (Nishibe, S., Hisada, S. and Inagaki, I. Phytochemistry, 10, 2231-2232 (1971)). Matairesinol was isolated from a number of sources before (Nishibe, S., Hisada, S. and Inagaki, I.
  • Main object of the invention relates to herbal compositions for the treatment of human cancer cells.
  • Another object of the invention relates to herbal compositions for the treatment of human cancer cells obtained from a plant source.
  • Another object of the invention relates to in- vitro cytotoxicity of lignan mixtures isolated from Cedrus deodara against various human cancer cell lines.
  • Still another object of the invention relates to cytotoxicity of individual lignans isolated from Cedrus deodara against various human cancer cell lines. Still another embodiment of the invention relates to a method of isolation of the active lignan mixture from the plant source namely Cedrus deodara.
  • Yet another object of the invention relates to a synergistic lignan composition obtained from plant cedrus deodara for inhibiting the growth of human cancer cells.
  • Yet another object of the invention relates to a composition comprising individual lignans isolated from plant cedrus deodara for inhibiting the growth of human cancer cells.
  • Yet another embodiment relates to method of treating mammals, particularly human beings affected by cancer.
  • the present invention provides a novel synergistic composition of lignans exhibiting anticancer activities for breast, cervix, neuroblastoma, colon, liver, lung, mouth, ovary and prostate cancer obtained from the plant extract of Cedrus deodra, said composition comprising_of
  • synergistic composition of lignan may be used in combination with pharmaceutically acceptable carriers for inhibiting various human cancer cell lines.
  • the present invention provides a novel synergistic composition of lignans exhibiting anticancer activities for breast, cervix, neuroblastoma, colon, liver, lung, mouth, ovary and prostate cancer obtained from the plant extract of Cedrus deodra, said composition comprising_of
  • the synergistic lignans composition inhibits the growth of cancer cells of breast up to 80% at a concentration ranging from 30-100 ⁇ g/ml.
  • the breast cell line is selected from group consisting of MCF-7 and T-47-D.
  • the synergistic lignans composition inhibits the growth of cancer cells of cervix up to 89% at a concentration ranging from 30-100 ⁇ g/ml.
  • the cervix cell line is selected from the group consisting of Hela and SiHa.
  • synergistic lignans composition inhibits the growth of cancer cells of neuroblastoma up to 96% at a concentration ranging from 30-100 ⁇ g/ml.
  • cancer cell line of neuroblastoma is selected from the group consisting of SF-539, SKNMC, IMR-32, SKNSH and SNB-78.
  • synergistic lignan composition inhibits the growth of cancer cells of colon up to 97% at a concentration ranging from 30-100 ⁇ g/ml.
  • cancer cell line of colon is selected from the group consisting of Colo-205, HCT-15, HT-29 and SW-620.
  • the synergistic lignan composition inhibits the growth of cancer cells of liver up to 73% at a concentration ranging from 30-100 ⁇ g/ml.
  • the cancer cell line of liver is selected from the group consisting of Hep-2 and Hep-G-2.
  • synergistic lignan composition inhibits the growth of cancer cells of lung up to 83% at a concentration ranging from 30-100 ⁇ g/ml.
  • cancer cell line of lung is selected from the group consisting of A-549, NCI-H23 and HOP- 18.
  • synergistic lignan composition inhibits the growth of cancer cells of mouth up to 100% at a concentration ranging from 30-100 ⁇ g/ml.
  • cancer cell line of mouth is KB.
  • the synergistic lignan composition inhibits the growth of cancer cells of ovary up to 96% at a concentration ranging from 30-100 ⁇ g/ml.
  • the cancer cell line of ovary is selected from the group consisting of OVCAR-5, NIH-OVCAR-3 and SK-OV-3.
  • synergistic lignan composition inhibits the growth of cancer cells of prostrate up to 98% at a concentration of ranging from 30-100 ⁇ g/ml.
  • cancer cells line of prostrate tissue is selected from the group consisting of DU- 145 and PC-3.
  • synergistic composition of lignan is administered to the patient in combination with a pharmaceutically acceptable additive, carrier, diluent, solvent, filter, lubricant, excipient, binder, or stabilizer.
  • synergistic lignan composition can be administered systemically and/or orally or any other suitable method.
  • One more embodiment of the invention relates to a composition exhibiting anti cancer activities for cancer cell lines selected mainly from the group consisting breast, cervix, neuroblastoma, colon, liver and lung, said composition comprising pharmaceutically effective dosage of (-)-wikstromol or a formulation containing. (-)-wikstromol.
  • the cancer cell line used are selected from group consisting breast cells MCF-7 and ZR-75-1; cervix cell SiHa; neuroblastoma cells SKNMC and IMR-32; colon cells colo-205HT-29 and SW-620; liver cell Hep-2; and lung cell A-549.
  • Still another embodiment of the invention wherein above said composition inhibits the growth of cancer cells of breast up to 51% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of cervix up to 37% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of neuroblastoma up to 56% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of colon up to 67% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of liver up to 46% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of lung up to 56% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits is administered in combination with a pharmaceutically acceptable carriers, additives, diluents, solvents, filters, lubricants, excipients, binders and stabilizers.
  • composition can be administered systematically and/or orally or any other suitable method.
  • One more embodiment of the present invention provides a composition exhibiting anti cancer activities for cancer cell lines selected mainly from the group consisting breast, cervix, neuroblastoma, colon, liver and lung, said composition comprising a pharmaceutically effective dosage of (-)- Matairesinol or a formulation containing (-)- Matairesinol.
  • the cancer cell lines used are selected from the group comprising of breast cells MCF-7 and ZR-75-1; cervix cell SiHa; neuroblastoma cells SKNMC and EVIR-32; colon cells Colo-205, HT-29 and SW-620; liver cell Hep-2; and lung cell A-549.
  • composition containing (-)- Matairesinol inhibits the growth of cancer cells of breast up to 62% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of cervix up to 63% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of neuroblastoma up to 77% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of colon up to 93% at a concentration of about 100 ⁇ g/ml.
  • composition inhibits the growth of cancer cells of liver up to 64% at a concentration of about lOO ⁇ g/ml.
  • composition inhibits the growth of cancer cells of lung up to 65% at a concentration of about 100 ⁇ g/ml.
  • compositions wherein above said composition is administered to the patient in combination with a pharmaceutically acceptable carriers additives, diluents, solvents, filters, lubricants, excipients, binders and stabilizers.
  • composition may be administered systematically or orally.
  • step (a) wherein the plant part is wood and in step (b) the hydrocarbon solvent is selected from group of hexane and petroleum ether, preferably hexane.
  • the halogenated solvent is selected from carbon tetrachloride, methylene chloride or chloroform, preferably chloroform.
  • step (c) the extracts are concentrated under vacuum and the purification is carried out using silica gel as an adsorbent and eluting with different proportions of chloroform-methanol mixture to get pure compounds Qwikstromol, (-)-metairesinol, dibenzylbutyrolactol, an unidentified material and which together constitute as synergistic lignan composition.
  • One more embodiment of the invention provide a method of treating a patient with cancer mainly breast, cervix, neuroblastoma, colon, liver, lung, mouth, ovary and prostate, said method comprising administering a pharmaceutically effective dosage of synergistic composition of lignan composition to the patient.
  • synergistic lignan composition is used in combination with pharmaceutically acceptable carriers.
  • synergistic lignan composition may be administered systemically and/or orally or any other suitable method.
  • Still another embodiment of the invention wherein the subjects are selected from animals or mammals preferably humans. Yet another embodiment of the invention, wherein said synergistic lignan composition inhibits the growth of cancel cells of breast up to 80% at a concentration ranging from 30- 100 ⁇ g/ml.
  • breast cell lines inhibited are MCF-7 and T-47- D.
  • synergistic lignan composition inhibits the growth of cancel cells of cervix up to 81% at a concentration ranging from 30-100 ⁇ g/ml.
  • cervix cell lines inhibited are Hela and SiHa..
  • synergistic lignan composition inhibits the growth of cancel cells of neuroblastoma up to 92% at a concentration ranging from 30- 100 ⁇ g/ml.
  • neuroblastoma cell lines inhibited are SF-539, SKNMC, JMR-32, SKNSH and SNB-78.
  • synergistic lignan composition inhibits the growth of cancel cells of colon up to 95% at a concentration ranging from 30-100 ⁇ g/ml.
  • colon cell lines inhibited are Colo-205, HCT-15, HT-29 and SW-620.
  • synergistic lignan composition inhibits the growth of cancel cells of liver up to 73% at a concentration ranging from 30-100 ⁇ g/ml.
  • liver cell line inhibited is Hep-2.
  • synergistic lignan composition inhibits the growth of cancel cells of lung up to 92% at a concentration ranging from 30-100 ⁇ g/ml.
  • lung cell lines inhibited are A-549 and NCI-H23.
  • synergistic lignan composition inhibits the growth of cancel cells of mouth up to 99% at a concentration ranging from 30-100 ⁇ g/ml.
  • Yet another embodiment of the invention, wherein mouth cell line inhibited is KB.
  • synergistic lignan composition inhibits the growth of cancel cells of ovary up to 96% at a concentration ranging from 30-100 ⁇ g/ml.
  • Yet another embodiment of the invention, wherein ovary cell lines inhibited are OVCAR5 and SK-OV-3.
  • synergistic lignan composition inhibits the growth of cancel cells of prostrate up to 98% at a concentration ranging from 30-100 ⁇ g/ml
  • Still another embodiment of the invention, wherein prostrate cell lines inhibited are DU- 145 and PC-3.
  • synergistic lignan composition is administered to the patient in combination with a pharmaceutically acceptable additive, carrier, diluent, solvent, filter, lubricant, excipient, binder, or stabilizer.
  • amount of synergistic composition administered is ranging from 10 to 500 mg/kg body weight for at least one dose per day.
  • amount of synergistic composition administered is preferably ranging from 50 to 350 mg/kg body weight.
  • Another more embodiment of the invention relates to a method of treating a patient with cancer mainly breast, cervix, neuroblastoma, colon, liver, lung, mouth, ovary and prostate, said method comprising administering a pharmaceutically effective dosage of (-)- wikstromol or a composition containing (-)-woikstromol. to the patient.
  • the said composition inhibits the growth of cancer cells consisting of breast cells, cervix cells, neuroblastoma cells, colon cells, liver cell and lung cell up to 51%, 37 %, 56%, 67%,46% and 56% respectively.
  • the cancer cell lines are selected from the group comprising of breast cells MCF-7 and ZR-75-1; cervix cell SiHa; neuroblastoma cells SKNMC and IMR-32; colon cells Colo-205, HT-29 and SW-620; liver cell Hep-2; and lung cell A-549.
  • composition is used singly or in combination with pharmaceutically acceptable carriers.
  • composition can be administered systematically and/or orally or any other suitable method.
  • composition administered is ranging from 10 to 500 mg/kg body weight at least once in a day.
  • composition administered is preferably ranging from 75 to 300 mg/kg body weight at least once in a day.
  • One more embodiment relates to a method of treating a patient with cancer mainly breast, cervix, neuroblastoma, colon, liver and lung, said method comprising administering a pharmaceutically effective dosage of (-)-Matairesinol or a composition containing (-)- Matairesinol to the patient.
  • composition inhibits the growth of cancer cells consisting of breast cells, cervix cells, neuroblastoma cells, colon cells, liver cell and lung cell up to 62%, 63 %, 77%, 93%, 64% and 65% respectively.
  • cancer cell lines are selected from the group comprising of breast cells MCF-7 and ZR-75-1; cervix cell SiHa; neuroblastoma cells SKNMC and IMR-32; colon cells Colo-205, HT-29 and SW-620; liver cell Hep-2; and lung cell A-549.
  • the said composition is used singly or in combination with pharmaceutically acceptable carriers.
  • composition may be administered systematically or orally.
  • the amount of composition administered is ranging from 10 to 500 mg/kg body weight at least once in a day.
  • the amount of composition administered is preferably ranging from 75 to 300 mg/kg body weight at least once in a day.
  • the said composition is administered to the patient in combination with a pharmaceutically acceptable carriers additives, diluents, solvents, filters, lubricants, excipients, binders and stabilisers.
  • the present invention embodies isolation of new cytotoxic mixture from an entirely new source.
  • the lignan mixture in vitro, significantly inhibited the growth of number of human cancer cell lines (breast: MCF-7 & T-47-D, cervix: Hela & SiHa, neuroblastoma: SF-539, SKNMC, R-32, SKNSH & SNB-78; colon: Colo-205, HCT-15, HT-29 & SW- 620, liver: Hep-2, lung: A-549 & NCI-H23, mouth: KB, ovary: OVCAR5 & SK-OV-3 and prostate: DU-145 & PC-3) representing different organs.
  • the present invention relates to a synergistic composition
  • a synergistic composition comprising (-)-Matairesinol, (- )-Wikstromol, Dibenzylbutyrolactol and unidentified material providing a unexpected results of showing enhanced cytotoxicity against cancer cell lines, which is substantiated by remarkable cytotoxicity results against cancer cell lines selected from Breast, Cervix, Neuroblastoma, Colon, Liver, Lung, Oral, Ovary and Prostate tissues.
  • the compositions is synergistic because the activity is remarkable and such surprisingly enhanced activity of the composition cannot be expected from the mere aggregation of the properties of the individual ingredients.
  • the composition does not possess the mere addition of the properties of its ingredients, but an enhanced activity, which further substantiates the efficacy of the synergistic composition isolated. Further, the amounts of the ingredients also impart/contribute for the enhanced activity of the composition.
  • Figure 1 represents the structural formulae of (-)-Matairesinol [1]; (-)-wikstromol [2] and
  • the yield of Matairesinol is around 1-2%; the yield of (-)-wikstromol is around 10-14% The yield of Dibenzylbutyrolactol is around 1-2%.
  • the human cancer cell lines were obtained either from National center for cell science, Pune, India or National Cancer Institute, Frederick, MD, U. S. A. Cells were grown in tissue culture flasks in complete growth medium (RPMI-164Q medium with 2mM glutamine, 100 ⁇ g/ml streptomycin, pH 7.4, sterilized by filtration and supplemented with 10% sterilized fetal calf serum and 100 units/ml penicillin before use) at 37°C in an atmosphere of 5% CO2 and 90% relative humidity in a carbon dioxide incubator (WTB binder, Germany). The cells at subconfluent stage were harvested from the flask by treatment with trypsin (0.05% trypsin in PBS containing 0.02% EDTA) and suspended in complete growth medium. Cells with cell viability of more than 97%) by trypan blue exclusion technique were used for determination of cytotoxicity.
  • complete growth medium RPMI-164Q medium with 2mM glutamine, 100 ⁇ g/ml streptomycin, pH 7.4, sterilized by
  • (-)-Matairesinol was dissolved in DMSO (dimethyl sulphoxide) to obtain a stock solution of 20 mg/ml.
  • DMSO dimethyl sulphoxide
  • the stock solution was serially diluted with complete growth medium containing 50 ⁇ g/ml of gentamycin to obtain three working test solutions of 200, 60 and 20 ⁇ g/ml
  • the suspension of human cancer cell lines of required cell density in complete growth medium was prepared and cell suspension (lOO ⁇ l per wall) of each cell line) of 96-welI tissue culture plate. Three additional wells of each cell line were also prepared for control. Two blank wells for control and each experimental and each experimental set for every cell line were also included that contained equivalent amount of complete growth medium only.
  • the plates were incubated at 37°C in an atmosphere of 5% CO 2 and 90% relative humidity in a carbon dioxide incubator.
  • the working test solutions of (-)-Matairesinol of different concentrations (100 ⁇ l) were added after 24-hours incubation in all the wells including blanks of the experimental set. The equivalent amount of complete growth medium was added to control set.
  • the plates were further incubated for 48-hours (at 37°C in an atmosphere of 5% CO 2 and 90% relative humidity in a carbon dioxide incubator) after addition of test material etc. and then the ceil growth was stopped by gently layering of 50 ⁇ l of TCA (50% trichloroacetic acid) on top of the medium in all the wells.
  • TCA 50% trichloroacetic acid
  • the plates were incubated at 4°C for one hour to fix the cells attached to the bottom of the wells. Liquids of all the wells were gently pipetted out and discarded.
  • the plates were washed five times with distilled water to remove TCA, growth medium, low molecular weight metabolites, serum proteins etc. Plates were air-dried.
  • SRB sulforhodamine B dye
  • test material The cell growth in presence of test material was determined by subtracting mean OD value of respective blank from the mean OD value of experimental set. Like wise, cell growth in absence of test material (control set) and in presence of positive control was also determined. The per cent cell growth in presence of test material was determined considering the cell growth in absence of test material as 100% and in turn per cent inhibition was calculated.
  • Example-3 In vitro cytotoxicity of (-)-wikstromol against human cancer cell lines: The human cancer cell lines grown and harvested and cytotoxicity was determined exactly as per example 1 except that the test material used was (-)-wikstromol which was dissolved in DMSO and three working test solutions were prepared of the same concentrations as in example 1.
  • In vitro cytotoxicity of (-)-wikstromol was determined against human breast (MCF-7 & ZR-75-1), neuroblastoma (SK-N-MC & IMR-32), cervix (SiHa), colon (Colo-205, HT-29 & SW-620), liver (HEP-2) and lung (A-549) cancer cell lines. The results are summarized in Table- 1.
  • (-)-wikstromol showed dose dependent inhibition of cell growth of the human cancer cell lines studied. The inhibition varied from 32-67% at 100 ug/ml. It was most effective against human colon cancer cell line Colo-205 and least effective against colon cell line HT-29.
  • Example-4 A process for the isolation of novel chemical composition containing lignan mixture from Cedrus Deodara.
  • the dried wood powder of Cedus deodara was loaded (200 g.) in a soxhlet apparatus.
  • the powder was first extracted with hexane and followed by chloroform.
  • the chloroform extract concentrated under vacuum.
  • the thick syrupy residue was dissolved in ethylacetate (for about 50g. of residue around 60 ml. of ethyl acetate).
  • the solution of residue in ethyl acetate was added drop wise to hexane (around 5L.).
  • the solid separated was filtered off. Yield of lignan mixture is around 20g.
  • the composition of lignan mixture was assayed by HPLC for three batches and the results are summarized in Table-2. Column used for HPLC is ODS, 1 .5ml flow rate at 225nm wavelength.
  • Example-5 In vitro cytotoxicity of lignan mixtures isolated from Cedrus deodara against human cancer cell lines:
  • the human cancer cell lines grown and harvested and cytotoxicity was determined exactly as per example 1 except that the test material used was three lignan mixtures isolated from Cedrus deodara, which were dissolved in separately in DMSO and three working test solutions were prepared of the same concentrations as in example 1.
  • Lignan mixture showed dose dependent inhibition of cell growth of the human cancer cell lines studied. All the three mixtures showed more or less the similar pattern of activity. The inhibition varied from 37 to 100% at 100 ⁇ g/ml. All the three mixtures were most effective against human oral cancer cell line KB and showed considerably high inhibition towards cervix (SiHa), neuroblastoma (SK- ⁇ -MC), colon (Colo-205, HCT-15, HT-29 & SW-620), ovary (ONCAR-5) and prostate (PC-3) cell lines. All the colon cell lines used were found to be highly sensitive to lignan mixtures and there may be tissue specificity for colon. The maximum effect towards liver Hep-G-2, lung HOP-18 and ovary ⁇ IH-ONCAR-3 cell lines was observed.
  • the lignan mixture obtained from cedrus deodra is showing anti cancer activity against quite number of cell lines.
  • Table 1 In vitro cytotoxicity of (-)-Matairesional and Wikstromol against human cancer cell lines.
  • Table 3 In-vitro cytotoxicity of lignan mixtures isolated from Cedrus deodara against human cancer cell lines.

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PCT/IN2001/000214 2001-12-05 2001-12-05 A novel herbal chemical composition for the treatment of cancer Ceased WO2003047608A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CA002469093A CA2469093A1 (en) 2001-12-05 2001-12-05 A novel herbal chemical composition for the treatment of cancer
AU2002222501A AU2002222501A1 (en) 2001-12-05 2001-12-05 A novel herbal chemical composition for the treatment of cancer
KR10-2004-7008727A KR20040072646A (ko) 2001-12-05 2001-12-05 암치료용 약초 화학 조성물
JP2003548863A JP2005511659A (ja) 2001-12-05 2001-12-05 癌の処置のための新規な草本化学組成物
CNB018239242A CN100444837C (zh) 2001-12-05 2001-12-05 用于治疗癌的新草本化学组合物
EP01274887A EP1465645A1 (en) 2001-12-05 2001-12-05 A novel herbal chemical composition for the treatment of cancer
PCT/IN2001/000214 WO2003047608A1 (en) 2001-12-05 2001-12-05 A novel herbal chemical composition for the treatment of cancer

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CN109206394A (zh) * 2018-08-16 2019-01-15 广西壮族自治区中国科学院广西植物研究所 一种倍半木脂素化合物、其制备方法及应用

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KR101416505B1 (ko) * 2012-03-15 2014-07-09 연세대학교 산학협력단 마타이레시놀을 포함하는 혈관신생 억제용 약제학적 조성물
CN104523721A (zh) * 2014-11-11 2015-04-22 济南星懿医药技术有限公司 一种抗肿瘤的药物组合物
CN113633704B (zh) * 2021-08-23 2022-06-07 中山大学 一种细轴荛花叶提取物的制备方法及其应用

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
US9168243B2 (en) 2010-12-06 2015-10-27 Emilia Peuhu Pharmaceutical compositions comprising 8-substituted dibenzylbutyrolactone lignans
CN109206394A (zh) * 2018-08-16 2019-01-15 广西壮族自治区中国科学院广西植物研究所 一种倍半木脂素化合物、其制备方法及应用

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JP2005511659A (ja) 2005-04-28
CA2469093A1 (en) 2003-06-12
EP1465645A1 (en) 2004-10-13
CN100444837C (zh) 2008-12-24
AU2002222501A1 (en) 2003-06-17
KR20040072646A (ko) 2004-08-18

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