WO2002080951A1 - Extrait d'herbes anticancereux - Google Patents

Extrait d'herbes anticancereux Download PDF

Info

Publication number
WO2002080951A1
WO2002080951A1 PCT/US2002/009937 US0209937W WO02080951A1 WO 2002080951 A1 WO2002080951 A1 WO 2002080951A1 US 0209937 W US0209937 W US 0209937W WO 02080951 A1 WO02080951 A1 WO 02080951A1
Authority
WO
WIPO (PCT)
Prior art keywords
extract
iaponica
chinensis
cell
cancer
Prior art date
Application number
PCT/US2002/009937
Other languages
English (en)
Inventor
Isaac Cohen
Original Assignee
Synergistix Biotech, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Synergistix Biotech, Inc. filed Critical Synergistix Biotech, Inc.
Publication of WO2002080951A1 publication Critical patent/WO2002080951A1/fr

Links

Classifications

    • 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

Definitions

  • This invention relates to extracts of herbs where the extracts, when placed in contact with solid tumor cancer cells, inhibits the activity, that is, the growth and/or proliferation, of the cells.
  • the extract may be an extract of one herb alone or it may be a combination of extracts of two or more herbs.
  • the herbs are selected from among the species Rhus chinensis, Acanthopanax gracilistylus, Panax ginseng, Epimedium grandiflorum, Lithospermum erythrorhizon, Boswellia carterii, Commiphora myrrha, Lobelia chinensis, Lonicer iaponica, Stella a dichotoma, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Carthamus tinctoris, Rhaponticum uniflorum, Taraxacum mongolica, Eupolyphaga sinensis (zoo.), Luffa cylindrica, Trichosanthes kirilowii, Dioscorea bulbifera, Imperata cylindrico, Prunella vugaris, Salvia chinensis, Scuttelaria barbata, Laminaha japonica, Caulis mutong, Gleditsia sinensis
  • the herbal extract or extracts are obtained from the species Panax ginseng, Lithospermum erythrorhizon, Boswellia ca erii, Commiphora myrrha, Lonicer iaponica, Stellaha dichotoma, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Carthamus tinctoris, Rhaponticum uniflorum, Taraxacum mongolica, Trichosanthes kirilowii, Dioscorea bulbifera, Salvia chinensis, Scuttelaria barbata, Caulis mutong,
  • the herbal extract or extracts are obtained are of the species Commiphora myrrha, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Salvia chinensis, Scuttelaria barbata, Gleditsia sinensis, Anemarrhena, Viscum coloratum, Ligustrum lucidum, Rheum palmatum, Duchesnea indica, Eriobotra iaponica, Rubia cordifola and Uncaria rhychophylla.
  • the solid tumor cancer cell the activity of which is inhibited by the herbal extract or extracts of this invention is an SKBR3 cell, an MCF7 cell, an MDA-MB231 cell, a BT474 cell or an MCNeuA cell.
  • a further aspect of this invention is a method for treating a solid tumor cancer, comprising administering to a patient a therapeutically effective amount of a composition comprising an extract of one or more of Rhus chinensis, Acanthopanax gracilistylus, Panax ginseng, Epimedium grandiflorum, Lithospermum erythrorhizon, Boswellia carterii, Commiphora myrrha, Lobelia chinensis, Lonicer iaponica, Stellaha dichotoma, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Carthamus tinctoris, Rhaponticum uniflorum, Taraxacum mongolica, Eupolyphaga sinensis (zoo.), Luffa cylindrica, Trichosanthes kirilowii, Dioscorea bulbifera, Imperata cylindhco, Prunella vugaris, Salvia chin
  • the composition used to treat a patient comprises an extract or extracts from the herb species Panax ginseng, Lithospermum erythrorhizon, Boswellia carterii, Commiphora myrrha, Lonicer iaponica, Stellaha dichotoma, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Carthamus tinctoris, Rhaponticum uniflorum, Taraxacum mongolica, Trichosanthes kirilowii, Dioscorea bulbifera, Salvia chinensis, Scuttelaria barbata, Caulis mutong, Gleditsia sinensis, Glycyrrhiza, uralensis,
  • Anemarrhena asphodeloides Viscum coloratum, Ligustrum lucidum, Rheum palmatum, Agrimonia pilosa, Duchesnea indica, Eriobotra iaponica, Rubia cordifola and Uncaria rhychophylla.
  • the extract or extracts used to treat a patient are obtained from the herb species Commiphora myrrha, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Salvia chinensis, Scuttelaria barbata, Gleditsia sinensis, Anemarrhena, Viscum coloratum, Ligustrum lucidum, Rheum palmatum, Duchesnea indica, Eriobotra iaponica, Rubia cordifola and Uncaria rhychophylla.
  • the solid tumor cancer being treated is an epithelial cell cancer in another aspect of this invention.
  • the epithelial cell cancer is breast or ovarian cancer in a still further aspect of this invention.
  • An aspect of this invention is a composition comprising a pharmaceutically acceptable carrier or excipient and an extract or extracts of one or more of Rhus chinensis, Acanthopanax gracilistylus, Panax ginseng, Epimedium grandiflorum, Lithospermum erythrorhizon, Boswellia carterii, Commiphora myrrha, Lobelia chinensis, Lonicer iaponica, Stellaha dichotoma, Vaccaria segetalis, Sarcandra glabra, Artemisia argyl, Carthamus tinctoris, Rhaponticum uniflorum, Taraxacum mongolica, Eupolyphaga sinensis (zoo.), Luffa cylindrica, Trichosanthes kirilowii, Dioscorea bulbifera, Imperata cylindhco, Prunella vugaris, Sal
  • the composition comprises aqueous extracts of the above herb species in an aspect of this invention.
  • the composition comprises alcohol extracts of the above species in a further aspect of this invention.
  • the alcohol used to extract the herbs is ethyl alcohol.
  • composition comprises a combination of aqueous and alcohol extracts of the above species of herbs in still another aspect of this invention.
  • Table 1 depicts herbs, from which extracts of this invention are obtained, listed by family, genus, species and traditional Chinese name, of this invention.
  • Table 1 shows the dry weight amount of material obtained from each herb by aqueous extraction.
  • Table 2 shows the degree of inhibition of the activity of several solid cancer tumor cell lines by the extracts of this invention.
  • Figures 1 A - 1 F are dose-response curves showing the response of several solid cancer tumor cells to aqueous extracts of herbs of this invention.
  • Figure 2 depicts a gel electrophoresis plate which demonstrates that nuclear DNA disintegration occurs during apoptosis of solid tumor cancer cells in contact with acqueous extracts of herbs of this invention. Definitions
  • the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by, practitioners of the chemical, pharmacological, biological, biochemical, medical and homeopathic arts.
  • inhibiting the activity refers to slowing, preferably stopping, the growth and/or proliferation of cancerous cells, both in-place, i.e., growth and proliferation at the initial site of tumor formation, and proliferation by metastasis. Inhibiting the activity also encompasses, in fact it is the most preferred embodiment of this invention, killing cancerous cells.
  • cancer refers to various types of malignant neoplasms, most of which can invade surrounding tissues, and may metastasize to different sites, as defined by Stedman's Medical Dictionary 25th edition (Hensyl ed. 1990).
  • Examples of cancers which may be treated by the present invention include, but are not limited to, brain, ovarian, colon, prostate, kidney, bladder, breast, lung, oral and skin cancers.
  • the cancer beign treated is breast or ovarian cancer.
  • contacting in the context of contacting a solid tumor cancer cell with an extract of this invention bringing an extract of this invention and a target cancer cell together in such a manner that the extract can affect the activity of the cell either directly or indirectly.
  • contacting refers to procedures conducted jn vitro, i.e. cancerous cells which are the object of this invention are studied, outside a patient. Cells existing outside the patient can be maintained or grown in cell culture dishes. For cells outside the organism, multiple methods exist, and are well-known to those skilled in the art, to contact extracts with cells including, but not limited to, simply placing cells in a broth containing an extract of this invention, with or without employment of various well- known transmembrane carrier techniques and direct cell microinjection.
  • an "extract” refers to the residue obtained after an herb, or selected part thereof is (1 ) for example, without limitation, chopped, crushed, pulverized, minced or otherwise treated to expose maximum surface area and (2) is placed in intimate contact with a liquid, usually, but not necessarily, under conditions of agitation and elevated temperature. Then, after a period of time under the foregoing conditions, the mixture is filtered to remove solids and the liquid removed by, for example but not limitation, evaporation or freeze drying.
  • the liquid used to obtain an extract may be water or an organic solvent, for example, without limitation, an alcohol such as methyl, ethyl or isopropy alcohol, a ketone such as acetone or methyl ethyl ketone (MEK), an ester such as ethyl acetate, an organochlorine compound such as methylene chloride, chloroform or carbon tetrachloride, a hydrocarbon such as pentane, hexane or benzene and the like.
  • An extract may also be obtained by using a combination of these solvents with or without water.
  • an "herb” refers to any plant that is reputed to have medicinal value in Traditional Chinese Medicine (TCM). That is, the use of extracts of various parts of these plants have been passed down from ancient to modern Chinese practitioners of homeopathy as a means for treating various ailments. In some instances, clinical evidence using standard Western medical research protocols have verified the utility of some of the extracts. While each of the herbs, and parts thereof, that make up the compositions of this invention have long been known in TCM, use of an extract or combination of extracts in a composition as disclosed herein for the treatment of solid tumor cancers, in particular breast and uterine cancer, has not been previously disclosed.
  • TCM Traditional Chinese Medicine
  • the terms “treat”, “treating” and “treatment” refer to a method of alleviating or abrogating a solid tumor cancer and/or its attendant symptoms. In particular, the terms simply mean that the life expectancy of an individual affected with a cancer will be increased or that one or more of the symptoms of the disease will be reduced.
  • administer refers to the delivery of an extract or extracts of this invention or of a pharmaceutical composition containing an extract or extracts of this invention to a patient in a manner suitable for the treatment of particular cancer being addressed.
  • a “patient” refers to any higher organism that is susceptible to solid tumor cancers. Examples of such higher organisms include, without limitation, mice, rats, rabbits, dogs, cats, horses, cows, pigs, sheep, fish and reptiles. Preferably, "patient” refers to a human being.
  • the term "therapeutically effective amount” refers to that amount of an extract or combination of extracts of this invention which has the effect of (1 ) reducing the size of the tumor; (2) inhibiting (that is, slowing to some extent, preferably stopping) tumor metastasis; (3) inhibiting to some extent (that is slowing to some extent, preferably stopping) tumor growth; and/or, (4) relieving to some extent (or preferably eliminating) one or more symptoms associated with the cancer.
  • a "pharmaceutical composition” refers to a mixture of one or more of the extracts described herein with other chemical components, such as physiologically acceptable carriers and excipients. The purpose of a pharmacological composition is to facilitate administration of an extract or extracts of this invention to a patient.
  • a “physiologically acceptable carrier” refers to a carrier or diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered composition.
  • an “excipient” refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an extract or extracts of this invention.
  • excipients examples include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols. Discussion At one time, botanical agents were the most significant group of substances used by healers to treat patients. According to a WHO survey, 80% of the world's population still relies heavily on herbal medicine as their primary source of therapy. In Western culture one-quarter of the active components of currently prescribed drugs were first identified in plants and over half of the 50 most popular drugs today are derived form plant materials. In addition, over 60% of chemotherapeutic agents used in the treatment of cancer are derived from natural substances.
  • a useful strategy for the discovery of biologically active compounds from plants is the ethno-pharmacological approach which uses information about traditional medicinal uses of plants.
  • the long history of a plant's use in treating a disorder, regardless of whether the disorder is well-characterized, e.g., skin rash, or is rather more nebulous, e.g., hot blood, is a clear indicator that something in the plant has some manner of beneficial effect on a disorder, otherwise the use of the plant would have faded in time.
  • homeopathic practitioners have been administering the plant or an extract thereof to human patients for, often, centuries provides a compelling argument for the safety of the plant or its extract in human beings.
  • TCM Chinese medicine
  • the herbal extracts of this invention were prepared standard decoction procedures well-known in the art. For example, without limitation, a chopped, ground, minced or pulverized portion, e.g., likewise without limitation, root, fruit, stem, sclerotium, rhizome or leaves, of a herb plant is simmered in water for a period of time. At the end of that period, the liquid is decanted off, giving a "tea" containing substances that are soluble in hot water.
  • Table 1 shows the genus and species, as well as the Chinese name, of the herbs extracted and tested against a panel of solid tumor cancer cell lines. Table 1 also shows the dry weight of the water soluble component of the part of the herb extracted.
  • the effect of the above extracts on five cancer cell lines was evaluated.
  • the cell lines were four human breast cancer cell lines, SKBR3, MCF-7, MDA- MB231 and BT474, and one murine breast cancer cell line, MCNeuA.
  • Table 2 shows the inhibitory effect of the extracts.
  • a (-) indicates that the extract inhibited the activity of that cell line from 0 to 25%
  • a (+) indicates that the extract inhibited the cell line by 26 to 50%
  • a (++) indicates about 51 to 75% inhibition while a (+++) indicates 76 - 100% inhibition of the activity of that cell line.
  • an assay for DNA fragmentation when the cell lines were subjected to the extracts suggest that inducement of apoptosis may constitute one mechanism by which the components of the extracts inhibit the activity of the cancerous cells.
  • HMW DNA fragments are best resolved and analyzed using pulsed field gel electrophoresis. Although HMW DNA fragments are too large to be resolved by conventional gel electrophoresis, they are able to leave the wells and enter conventional agarose gels, forming a compression band of about 20 to 50 kb, the upper limit of fraction ation ability of these gels.
  • An extract of this invention can be administered to a patient either as such, that is, as a "tea” without combination with any other substances or further manipulation or it can be administered as a pharmaceutical composition where the extract is mixed with suitable carriers or excipient(s).
  • a therapeutically effective amount of the extract is administered.
  • a therapeutically effective amount refers to that amount of the extract that results in amelioration of symptoms or a prolongation of survival in a patient, and may include destruction of a malignant tumor of a microbial infection.
  • Toxicity and therapeutic efficacy of the extracts i.e., determining the LD 50 (the dose lethal to 50% of the population) and the ED 5 o (the dose therapeutically effective in 50% of the population) can be determined by standard pharmaceutical procedures in cell cultures or experimental animals,.
  • the dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD 50 /ED 5 o.
  • Extracts that exhibit large therapeutic indices are preferred.
  • the data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. In particular for internal use, the dosage of such extracts lies preferably within a range of circulating concentrations that include the ED 50 with little or no toxicity.
  • the dosage may vary within this range depending upon the dosage form employed and the route of administration utilized.
  • all the extracts of this invention have been used in TCM, they are known, at least singly, and many times in combination, to be relatively non-toxic to humans and therefore it is expected that they will exhibit large therapeutic indices.
  • the therapeutically effective dose can be estimated initially from cell culture assays.
  • a dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC 50 as determined in cell culture Such information can be used to more accurately determine useful doses in humans.
  • Levels in plasma may be measured, for example, by HPLC.
  • the exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition and based on knowledge of TCM. (See e.g. Fingl et al., in THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 1975, Ch. 1 p. 1). It should be noted that the attending physician would know how to and when to terminate, interrupt, or adjust administration due to toxicity, or organ dysfunction. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response is not adequate. The severity of the condition may, for example, be evaluated, in part, by standard prognostic evaluation methods. Further, the dose and perhaps dose frequency will also vary according to the age, body weight, and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine.
  • Suitable routes may include oral, rectal, transdermal, vaginal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections, to name just a few.
  • Oral administration is the procedure most often used in TCM and is the presently preferred method of this invention.
  • an extract of this invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer.
  • physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer.
  • penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
  • an extract of the present invention in particular those formulated as solutions, may be administered parenterally, such as by intravenous injection.
  • an extract can be formulated, using pharmaceutically acceptable carriers well known in the art, into dosages suitable for oral administration.
  • Such carriers enable extracts to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.
  • compositions suitable for use in the present invention are compositions wherein an extract is contained in an effective amount to achieve its intended purpose. Determination of the effective amounts is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.
  • a pharmaceutical compositions may contain suitable pharmaceutically acceptable carriers including excipients and auxiliaries that facilitate processing of the extracts into preparations that can be used pharmaceutically.
  • the preparations formulated for oral administration may be in the form of tablets, dragees, capsules, or solutions.
  • compositions of the present invention may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levitating, emulsifying, encapsulating, entrapping or lyophilizing processes.
  • compositions for parenteral administration include aqueous solutions of an extract in water-soluble form. Additionally, suspensions of an extract may be prepared as appropriate oily injection suspensions. Suitable lipophilic vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents that increase the solubility of an extract to allow for the preparation of highly concentrated solutions.
  • compositions for oral use can be obtained by combining an extract with solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores.
  • suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP).
  • fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol
  • cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-
  • disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.
  • Dragee cores are provided with suitable coatings.
  • suitable coatings may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures.
  • Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of extracts and/or doses.
  • compositions that can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol.
  • the push-fit capsules can contain the extract in admixture with fillers such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers.
  • the extract may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. Examples
  • Herbal extracts were prepared as "boiled teas," which is how most are prepared for use in traditional treatment regimes.
  • Aqueous extracts were prepared by adding 7.5 g of dry ground herb to 125 ml distilled water, bringing the mixture to a boil and then simmering for 45 minutes. The mixture was cooled, during which period most of the solids sank to the bottom of the vessel. The aqueous layer was carefully decanted off of the residual solids, centrifuged for 5 minutes at 1500 rpm, sterile filtered through a 0.45 ⁇ m fiilter and stored at 4° C until used. Generally, the extracts were tested within 1 - 2 weeks of preparation although most of the active extracts were found to retain activity after storage at 4° C for several additional weeks. An aliquot of each extract was dried under vacuum and the dry weight of the water soluble substances extracted from each herb determined.
  • the extracts were tested against four human breast cancer cell lines, SKBR3, MFC-7, MDA-MB231 and BT474, and one murine breast cancer cell line, MCNeuA. All lines were maintained in 90% DME supplemented with 2.0 mM L- glutamine, 100 lU/ml penicillin, 100 ⁇ g/ml streptomycin and 10% heat-inactivated fetal bovine serum. Cells at 70 - 80% confluence were used for plating for growth inhibition assays. In vitro inhibition of activity
  • Cells were plated in 96-well flat bottom plates at 5,000 to 10,000 cells/well. The difference in number of cells plated adjusts for differences in the gowth rates of these cell lines. Cells were allowed to adhere to the well walls overnight then the extracts were added to triplicate wells at a 1 :10 final dilution in culture medium for initial screening. For generating dose-response curves, serial 3-fold dilutions, starting at 1 :10 dilution over 6 rows of wells were used. Water was added to the control wells at 1 :10 dilution in culture medium. The plates were incubated at 37° C, 5% CO 2 , for 3 days and then assayed for growth inhibition using a crystal violet assay (Bemhardt, G., et al., Standardized Kinetic Microassay to Quantify
  • the percent inhibition was calculates as the average optical density of the control wells minus average optical density extract well divided by the average optical density of the control wells.
  • Dose-response curves on SKBR3, MCF7 and MCNeuA cells for several of the extracts are shown in Figure 1. As can be seen, the concentration at which the extracts inhibited the activity of the cells by 50% (the IC 50 ) ranged from over 1 mg/ml down to about 10 ⁇ g/ml. Induction of apoptosis
  • MCNeuA cells were plated at 5X10 5 cells/well in 6-well plates and allowed to adhere overnight. Aqueous herbal extracts were added to each well at a 1 :10 and a 1 :50 dilution. Sterile water, diluted 1 :10 in culture medium, was added to the control wells. After 24 hours, the cells were visually examined under a microscope and morphological changes noted. Attached and floating cells were harvested, washed with cold PBS and embedded in agarose droplets.
  • the agarose droplets containing the cells were incubated in lysis buffer (50 mM NaCI, 20 mM TrisHCI, pH 8.0, 20 mM EDTA, 0.5% sodium sarkosyl, 50 ⁇ g/ml RnaseA and 100 ⁇ g/ml proteinase K) for 1 hour at 37° C.
  • the cells were then washed with PBS and distilled water and placed in the wells of a conventional 1% agarose gel and electrophoresed overnight at approximately 1 V/cm.
  • the gels were then stained with ethidium bromide and photographed under UV transillumination to give inverse images.
  • the images obtained are shown in Figure 2.
  • Herbal extracts their uses for the inhibition of solid tumor cancer cells and the treatment of such cancers in patients are described herein. Although certain embodiments and examples have been used to describe the present invention, it will be apparent to those skilled in the art that changes to the embodiments and examples may be made without departing from the scope and spirit of this invention.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne des extraits d'herbes ainsi que leur utilisation comme inhibiteurs de lignées cellulaires cancéreuses in vitro et dans le traitement de tumeurs solides chez les humains.
PCT/US2002/009937 2001-04-06 2002-03-29 Extrait d'herbes anticancereux WO2002080951A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US28195801P 2001-04-06 2001-04-06
US60/281,958 2001-04-06

Publications (1)

Publication Number Publication Date
WO2002080951A1 true WO2002080951A1 (fr) 2002-10-17

Family

ID=23079491

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/009937 WO2002080951A1 (fr) 2001-04-06 2002-03-29 Extrait d'herbes anticancereux

Country Status (1)

Country Link
WO (1) WO2002080951A1 (fr)

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003075943A2 (fr) * 2002-03-06 2003-09-18 The Medical Research And Education Trust Compositions d'extrait botanique et procedes d'utilisation
WO2005049001A1 (fr) * 2003-11-13 2005-06-02 Compton Developments Ltd Composes terpeniques antitumoraux
WO2005099738A1 (fr) * 2004-04-14 2005-10-27 Universidad De Barcelona Extrait d'algue laminaria a titre d'agent therapeutique
EP1808172A2 (fr) * 2002-03-06 2007-07-18 The Medical Research and Education Trust Compostions à base d'extraits botaniques et procédés d'utilisation
WO2007099560A2 (fr) * 2006-03-02 2007-09-07 Promed Exports Pvt. Ltd. Procédé pour l'identification et la quantification des ingrédients d'une formulation comprenant plusieurs plantes
WO2008017280A1 (fr) * 2006-08-10 2008-02-14 Franz Udo Willerscheidt Soporus; sédatif comprenant de la myrrhe et de la réglisse
WO2009151762A2 (fr) * 2008-04-11 2009-12-17 Bionovo, Inc. Procédés anticancer utilisant des extraits d'anemarrhena asphodeloides bunge
CN102526313A (zh) * 2012-03-15 2012-07-04 荆兆峰 一种治疗跟痛症的药物组合物药包内芯的制备方法
CN102648956A (zh) * 2012-05-18 2012-08-29 漳州市中草药研究所 一种治疗乳腺癌的中草药制剂及其制备方法
CN102670793A (zh) * 2012-05-04 2012-09-19 山西华诚睿光生物科技有限公司 提高奶牛免疫力、降低牛奶体细胞数的中药制剂及制备方法
CN102670766A (zh) * 2011-03-09 2012-09-19 广州加原医药科技有限公司 一种治疗子宫肌瘤的中药组合物
CN102920810A (zh) * 2012-11-20 2013-02-13 汉仲月 一种用于白塞氏综合征的粘膜护理物
CN102973698A (zh) * 2012-12-18 2013-03-20 西安碑林药业股份有限公司 一种治疗乳腺增生的中药制剂
CN103083413A (zh) * 2012-12-06 2013-05-08 宁夏易欣回药科技有限公司 祛毒保肾中药组合物贴剂
CN103565985A (zh) * 2013-11-06 2014-02-12 陈兴日 一种治疗乳痛的中药组合物及其使用方法
CN103768167A (zh) * 2012-10-25 2014-05-07 奇复康药物研发(苏州)有限公司 一种猫爪草三萜成分提取方法
CN103773588A (zh) * 2012-10-25 2014-05-07 奇复康药物研发(苏州)有限公司 一种猫爪草精油提取工艺
CN103768168A (zh) * 2012-10-25 2014-05-07 奇复康药物研发(苏州)有限公司 一种猫爪草鞣质的提取方法
WO2014077433A1 (fr) * 2012-11-16 2014-05-22 주식회사 한국전통의학연구소 Composition contenant de l'extrait de semen gleditsiae utilisable pour traiter le cancer du rein et en tant qu'aliment fonctionnel
WO2014077434A1 (fr) * 2012-11-16 2014-05-22 주식회사 한국전통의학연구소 Composition contenant de l'extrait de semen gleditsiae utilisable pour traiter le cancer du pancréas et en tant qu'aliment fonctionnel
US8754052B2 (en) 2008-06-26 2014-06-17 Mayo Foundation For Medical Education And Research Treatment of nephrolithiasis and urolithiasis using 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG)
CN104127818A (zh) * 2014-07-24 2014-11-05 陈桂风 一种治疗乳腺癌的中药制剂
CN104688845A (zh) * 2015-03-25 2015-06-10 江苏永璋伟业健康科技有限公司 一种从猫爪草中分离制备吡咯丁酸自微乳的方法及用途
CN109303834A (zh) * 2018-08-28 2019-02-05 王庆国 一种抗肿瘤的药物及其制备方法
WO2021186456A1 (fr) * 2020-03-20 2021-09-23 Alkalay Rachel Compositions et méthodes de traitement de tumeurs solides et molles et de maladies prolifératives

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63201130A (ja) * 1987-02-17 1988-08-19 Ikeda Yakusou Kk 抗腫瘍剤
US5919821A (en) * 1994-12-21 1999-07-06 Thomas Simmet Use of boswellic acid for treating brain tumors
CN1240147A (zh) * 1997-09-29 2000-01-05 李宗贤 坤元919口服液
US6039949A (en) * 1997-02-27 2000-03-21 Campamed, Inc. Method of preparation and composition of a water soluble extract of the plant species uncaria

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63201130A (ja) * 1987-02-17 1988-08-19 Ikeda Yakusou Kk 抗腫瘍剤
US5919821A (en) * 1994-12-21 1999-07-06 Thomas Simmet Use of boswellic acid for treating brain tumors
US6039949A (en) * 1997-02-27 2000-03-21 Campamed, Inc. Method of preparation and composition of a water soluble extract of the plant species uncaria
CN1240147A (zh) * 1997-09-29 2000-01-05 李宗贤 坤元919口服液

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE JPAB [online] XP002951646, accession no. WEST *
DATABASE WPI Week 200036, Derwent World Patents Index; AN 2000-413081 *

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003075943A3 (fr) * 2002-03-06 2004-04-22 Sophie Chen Ph D Compositions d'extrait botanique et procedes d'utilisation
EP1808172A2 (fr) * 2002-03-06 2007-07-18 The Medical Research and Education Trust Compostions à base d'extraits botaniques et procédés d'utilisation
WO2003075943A2 (fr) * 2002-03-06 2003-09-18 The Medical Research And Education Trust Compositions d'extrait botanique et procedes d'utilisation
EP1808172A3 (fr) * 2002-03-06 2010-05-26 Activephyto Technologies Limited Compostions à base d'extraits botaniques et procédés d'utilisation
AU2004290946B2 (en) * 2003-11-13 2010-04-22 Compton Developments Ltd Anti-tumour terpene compounds
WO2005049001A1 (fr) * 2003-11-13 2005-06-02 Compton Developments Ltd Composes terpeniques antitumoraux
WO2005099738A1 (fr) * 2004-04-14 2005-10-27 Universidad De Barcelona Extrait d'algue laminaria a titre d'agent therapeutique
WO2007099560A2 (fr) * 2006-03-02 2007-09-07 Promed Exports Pvt. Ltd. Procédé pour l'identification et la quantification des ingrédients d'une formulation comprenant plusieurs plantes
WO2007099560A3 (fr) * 2006-03-02 2007-12-27 Promed Exports Pvt Ltd Procédé pour l'identification et la quantification des ingrédients d'une formulation comprenant plusieurs plantes
WO2008017280A1 (fr) * 2006-08-10 2008-02-14 Franz Udo Willerscheidt Soporus; sédatif comprenant de la myrrhe et de la réglisse
WO2009151762A2 (fr) * 2008-04-11 2009-12-17 Bionovo, Inc. Procédés anticancer utilisant des extraits d'anemarrhena asphodeloides bunge
WO2009151762A3 (fr) * 2008-04-11 2010-04-01 Bionovo, Inc. Procédés anticancer utilisant des extraits d'anemarrhena asphodeloides bunge
US8754052B2 (en) 2008-06-26 2014-06-17 Mayo Foundation For Medical Education And Research Treatment of nephrolithiasis and urolithiasis using 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG)
CN102670766A (zh) * 2011-03-09 2012-09-19 广州加原医药科技有限公司 一种治疗子宫肌瘤的中药组合物
CN102526313A (zh) * 2012-03-15 2012-07-04 荆兆峰 一种治疗跟痛症的药物组合物药包内芯的制备方法
CN102526313B (zh) * 2012-03-15 2013-11-27 徐金林 一种治疗跟痛症的药物组合物药包内芯的制备方法
CN102670793A (zh) * 2012-05-04 2012-09-19 山西华诚睿光生物科技有限公司 提高奶牛免疫力、降低牛奶体细胞数的中药制剂及制备方法
CN102648956A (zh) * 2012-05-18 2012-08-29 漳州市中草药研究所 一种治疗乳腺癌的中草药制剂及其制备方法
CN103768168A (zh) * 2012-10-25 2014-05-07 奇复康药物研发(苏州)有限公司 一种猫爪草鞣质的提取方法
CN103768167A (zh) * 2012-10-25 2014-05-07 奇复康药物研发(苏州)有限公司 一种猫爪草三萜成分提取方法
CN103773588A (zh) * 2012-10-25 2014-05-07 奇复康药物研发(苏州)有限公司 一种猫爪草精油提取工艺
WO2014077433A1 (fr) * 2012-11-16 2014-05-22 주식회사 한국전통의학연구소 Composition contenant de l'extrait de semen gleditsiae utilisable pour traiter le cancer du rein et en tant qu'aliment fonctionnel
WO2014077434A1 (fr) * 2012-11-16 2014-05-22 주식회사 한국전통의학연구소 Composition contenant de l'extrait de semen gleditsiae utilisable pour traiter le cancer du pancréas et en tant qu'aliment fonctionnel
CN102920810B (zh) * 2012-11-20 2013-10-02 汉仲月 一种用于白塞氏综合征的粘膜护理物
CN102920810A (zh) * 2012-11-20 2013-02-13 汉仲月 一种用于白塞氏综合征的粘膜护理物
CN103083413A (zh) * 2012-12-06 2013-05-08 宁夏易欣回药科技有限公司 祛毒保肾中药组合物贴剂
CN102973698A (zh) * 2012-12-18 2013-03-20 西安碑林药业股份有限公司 一种治疗乳腺增生的中药制剂
CN103565985A (zh) * 2013-11-06 2014-02-12 陈兴日 一种治疗乳痛的中药组合物及其使用方法
CN104127818A (zh) * 2014-07-24 2014-11-05 陈桂风 一种治疗乳腺癌的中药制剂
CN104688845A (zh) * 2015-03-25 2015-06-10 江苏永璋伟业健康科技有限公司 一种从猫爪草中分离制备吡咯丁酸自微乳的方法及用途
CN109303834A (zh) * 2018-08-28 2019-02-05 王庆国 一种抗肿瘤的药物及其制备方法
WO2021186456A1 (fr) * 2020-03-20 2021-09-23 Alkalay Rachel Compositions et méthodes de traitement de tumeurs solides et molles et de maladies prolifératives

Similar Documents

Publication Publication Date Title
WO2002080951A1 (fr) Extrait d'herbes anticancereux
US7700136B2 (en) Scutellaria barbata extract for the treatment of cancer
US6911221B2 (en) Anti-neoplastic drug
WO2014139282A1 (fr) Compositions pharmaceutiques pour le traitement du cancer de l'appareil génital et leur procédé de préparation
CA2706326A1 (fr) Extrait de scutellaria barbata et combinaisons le contenant pour le traitement du cancer
JP2011503237A (ja) Ｓｃｕｔｅｌｌａｒｉａｂａｒｂａｔａｄ．ｄｏｎの精製抽出物を作製するためのプロセス
CN103479963A (zh) 一种治疗类风湿关节炎的中药胶囊及其制备方法
CA3219768A1 (fr) Composition pharmaceutique pour le traitement de la polyarthrite rhumatoide et son procede de preparation
Iljazović et al. Efficacy in treatment of cervical HRHPV infection by combination of beta interferon, and herbal therapy in woman with different cervical lesions
KR100310979B1 (ko) 간질환 예방 및 치료용 생약조성물
CN101342249B (zh) 一种治疗乙肝的中药制剂及其制备方法
CN104547902A (zh) 中药制剂用于制备治疗慢性肠炎、阑尾炎药物中的用途
CN104491459A (zh) 一种治疗肿瘤的中药组合物
CN105012793A (zh) 一种治疗外阴细胞增生外洗液的制备方法
CN110179893B (zh) 十味参归灌肠液及其制备工艺
CN101167915B (zh) 治疗慢性浅表性胃炎的中药组合物及其制备方法
CN103585275B (zh) 用于治疗风湿骨病的中药组合物及中成药的制备方法和应用
CN112402565B (zh) 一种治疗膝关节滑膜炎的中药组合物及其制备方法
TW201827064A (zh) 中草藥萃取物用於製備治療乳癌藥物的用途
Zhou et al. Chinese medicinal herbs in treating model rats with hepatic fibrosis
CN105106271B (zh) 一种中药组合物及其制备方法、用途和制剂
Luo Research progress of traditional Chinese medicine and its monomer compounds and extracts on alcoholic gastric injury
TW202011981A (zh) 一種治療乳癌的中草藥組成物
CN116270949A (zh) 一种降低高尿酸的中药组合物及其制备方法
CN110801491A (zh) 一种治疗肿瘤的中药组合物

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP