EP1214040A4 - Utilisation d'extraits de peau d'orange dans la prevention et le traitement du cancer - Google Patents

Utilisation d'extraits de peau d'orange dans la prevention et le traitement du cancer

Info

Publication number
EP1214040A4
EP1214040A4 EP00961973A EP00961973A EP1214040A4 EP 1214040 A4 EP1214040 A4 EP 1214040A4 EP 00961973 A EP00961973 A EP 00961973A EP 00961973 A EP00961973 A EP 00961973A EP 1214040 A4 EP1214040 A4 EP 1214040A4
Authority
EP
European Patent Office
Prior art keywords
extract
orange peel
methoxyflavone
resveratrol
cells
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP00961973A
Other languages
German (de)
English (en)
Other versions
EP1214040A1 (fr
Inventor
Geetha Ghai
Robert T Rosen
Chi-Tang Ho
Kuang Yu Chen
Nitin Telang
Martin Lipkin
Mou Tuan Huang
Charles Boyd
Katalin Csiszar
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rutgers State University of New Jersey
Original Assignee
Rutgers State University of New Jersey
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 Rutgers State University of New Jersey filed Critical Rutgers State University of New Jersey
Publication of EP1214040A1 publication Critical patent/EP1214040A1/fr
Publication of EP1214040A4 publication Critical patent/EP1214040A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • 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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704—Polygonum, e.g. knotweed
    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • Naturally occurring non-nutritive agents present in plants such as flavonoids, phenolic compounds, glucosinulates, terpenes and many others are believed to have disease preventive properties. Diets containing some of these substances have been shown to be protective against diseases such as colon and breast cancer in animals (Kuo, S.M. 1997. Clin . Rev. Oncogenesis 8:47-69; Verhoeven et al . 1996. Cancer Epid . Biomark . Prev. 5:733-748; Bradlow et al . 1991. Carcinogenesis 12:1571-1574; Lamartiniere et al . 1995. Proc . Soc . Exp . Biol . Med. 208:120-123). The clinical relevance of such natural phytochemicals is dependent on extrapolation from epidemiological data and from experiments in animal models of diseases of interest.
  • CN 1200277 describes use of a composition composed of 16 plant components, one of which is dried orange peel, for treatment of psychosis and nervous system disease.
  • CN 1116945 describes the use of orange peel along with several other natural products in a capsule form to sooth the liver, nourish the stomach, remove stasis, stop pain and cure various gastric diseases.
  • CN 1111134 discloses an oral liquid containing orange peel, among other things, for treatment of neurastenia, chronic bronchitis, asthma, coronary heart disease, high blood lipid levels, hepatitis, cytopenia, senility and immune dysfunction.
  • CN 1106673 is a patent for a disease-preventing nutrient tea that is produced from a variety of products, including soaked, crushed orange peel.
  • CN 1077124 describes a Chinese herb preparation for treatment of iron-deficiency anemia that is composed of a number of ingredients, including dried orange peel.
  • JP 57156761 discloses a heat-generating pad for orthopedic diseases that contains extracts and powders of many plants, including orange peel. It has now been found that an extract of orange peel has biological activity as a treatment and preventative agent for cancer .
  • An object of the present invention is an extract of orange peel which comprises 4 ', 5 , 6, 7, 8-pentamethoxyflavone and 3', 4', 5, 6, 7, 8-hexamethoxyflavone .
  • the composition may further comprise other polymethoxylated flavones.
  • Another object of the present invention is a composition which comprises an extract of orange peel and rosemary extract, a Mexican Bamboo extract, a Huzhang extract, resveratrol, a black tea extract, and/or a hydroxylated or methoxylated resveratrol analog.
  • Another object of the present invention is to provide a method for inhibiting tumor cell growth in an animal comprising administering to an animal an orange peel extract which is administered alone or in combination with rosemary extract, a Mexican Bamboo extract, a Huzhang extract, resveratrol, a black tea extract, and/or a hydroxylated or methoxylated resveratrol analog.
  • Another object of the present invention is to provide a method for preventing or treating cancer in an animal which comprises administering to an animal an effective amount of an orange peel extract which is administered alone or in combination with rosemary extract, a Mexican Bamboo extract, a Huzhang extract, resveratrol, a black tea extract, and/or a hydroxylated or methoxylated resveratrol analog.
  • orange peel extract is lipid soluble, a property which is desirable in many drug products because passage across biological membranes, and ultimately bioavailability, is enhanced.
  • Orange peel and its extracts have been used in a variety of herbal drug products in combination with many different plant components and extracts.
  • none of the previous research on orange peel or its extracts has examined or demonstrated activity against tumor cell growth or cancer. It has now been shown that orange peel extract inhibits tumor growth in vivo .
  • Orange peel extract is a mixture of highly bioactive and organic soluble, methylated flavonoids.
  • An extract was obtained from cold-pressed peel oil solids, a waste product from the orange juice industry. The peel oil solids were dissolved in warm ethanol and, after several repeated washes, became a standardized product, with a reproducible amount of flavonoids.
  • the extract comprises a mixture of various analogs and homologs of methylated flavonoids .
  • Atmospheric pressure chemical ionization mass spectrometry was used for molecular weight determinations.
  • HPLC-MS techniques such as particle beam (El) introduction was used to produce standard fragmentation patterns of the methylated flavonoids. Standards for many of the compounds were obtained from the Florida Department of Citrus.
  • the orange peel extract was then tested in an in vivo model for colon cancer.
  • Female CF-1 mice were injected with azoxymethane (AOM) once a week for four weeks at increasing doses (5, 10, 10 and 10 mg/kg) .
  • Orange peel extract was administered in the diet (0.2%) starting two weeks before the first AOM injection, during and continuing until the end of the experiment at 24 weeks.
  • the mice were given one last dose of AOM (10 mg/kg) .
  • the mice were then sacrificed and their colons removed (from anus to caecum) .
  • the colons were opened longitudinally, rinsed with normal saline, and stapled to a plastic sheet.
  • the colon samples were placed in a 10% neutral buffered formalin solution for 24 hours.
  • mice were injected with AOM (5, 10, 10 and 10 mg/kg) starting at 6 weeks of age, once each week and then once at 37 weeks after the first dose of AOM.
  • AOM 5, 10, 10 and 10 mg/kg
  • mice received either an AIN 76A diet or test compound in AIN 76A diet at 2 weeks before the first dose of AOM and continuing until the end of the experiment.
  • the test compounds were NDGA (0.2%) and orange peel extract (0.2%). Colon samples were again obtained at sacrifice, stored in 10% formalin phosphate buffer, and then colon tumor number was determined. The results are shown in Table 2.
  • tangeretin alone (0, 1, 5, 10, 20 or 50 ⁇ g/ml)
  • nobeletin alone (0, 1, 5, 10, 20 or 50 ⁇ g/ml)
  • a mixture of the two compounds at a total concentration of the two flavenoids of 0, 1, 5, 10, 20 or 50 ⁇ g/ml.
  • tangeretin and nobeletin produced only marginal effects to inhibit cell growth in transformed cells, even at the highest dose tested, and had no effect on normal cell growth.
  • tangeretin and nobeletin showed synergistic activity, with growth inhibition produced in transformed cells, in a dose dependent manner. There was no appreciable effect of the mixture on normal cell growth.
  • Orange peel extract at the maximum cytostatic dose of 100 ppm accumulated the cells in the G0/G1 phase and inhibited the S+G2/M phase of the cell cycle, leading to down-regulation of cell cycle progression. This alteration in the cell cycle progression resulted in a 5-fold increase in the G0/G1: S+G2/M ratio.
  • Treatment of 184-B5/HER cells with 100 ppm orange peel extract resulted in a 47.5% decrease in immunoreactivity to phosphotyrosine (marker for tyrosine kinase activity) and a 157.7% increase in immunoreactivity to the cyclin dependent kinase inhibitor pl6 INKA .
  • compositions comprising orange peel extract or a combination of components of the orange peel extract including but not limited to tangeretin and nobeletin, may be included in foods and dietary supplements or "nutraceuticals" for prevention or treatment of cancer.
  • One of skill can use the results of experiments in cells and animals described herein to determine effective amounts to be administered to other animals, including humans.
  • effective amount it is meant a concentration that inhibits tumor growth either in vi tro in cells or in vivo in animals.
  • human test doses can be extrapolated from effective doses in cell studies, such as IC 50 values, or from effective doses in vivo by extrapolating on a body weight or surface area basis. Such extrapolations are routine in the art.
  • compositions comprising orange peel extracts can be formulated for administration as a food supplement using one or more fillers.
  • compositions comprising these extracts can be administered as conventional pharmaceuticals using one or more physiologically acceptable carriers or excipients.
  • Nutraceutical compositions can be formulated for administration by any route including, but not limited to, inhalation or insufflation (through mouth or nose), oral, buccal , parenteral, vaginal, or rectal administration.
  • oral administration the compositions are added directly to foods and ingested as part of a normal meal .
  • Various methods are known to those skilled in the art for addition or incorporation of nutraceuticals into foods.
  • compositions for use in the present invention can also be administered in the form or tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents, fillers, lubricants, disintegrants, or wetting agents. Examples of specific compounds for use in formulating tablets and capsules are described in detail in the U.S. Pharmacopeia. Tablets comprising the extract can also be coated by methods well known in the art.
  • Liquid preparations for oral administration can also be used. Liquid preparations can be in the form of solutions, syrups or suspensions, or a dry product for reconstitution with water or another suitable vehicle before use.
  • Such liquid preparations can be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents, emulsifying agents, non-aqueous vehicles, and preservatives. Again, specific additives are well known to those of skill and are listed in places such as the U.S. Pharmacopeia.
  • the oral preparation is formulated to provide controlled time release of the active nutraceutical components.
  • the extract can be formulated as a tablet or lozenge.
  • compositions for use in the present invention can be delivered in the form of an aerosol spray in a pressurized package or as a nebulizer, with use of suitable propellants.
  • the dosage unit can be determined by providing a valve to deliver a metered dose.
  • compositions are formulated to allow for injection, either as a bolus or as a continuous infusion.
  • Formulations for injection can be prepared in unit dosage forms, such as ampules, or in multi-dose units, with added preservatives.
  • the compositions for injection can be in the form of suspensions, solutions, or emulsions, in either oily or aqueous vehicles. They may also contain formulatory agents such as suspending agents, stabilizing agents, and/or dispersing agents.
  • the active ingredient may also be presented in powder form for reconstitution with a suitable vehicle before use. Specific examples of formulating agents for parenteral injection are found in the U.S. Pharmacopeia.
  • compositions for use in of the present invention can be formulated as suppositories, creams, gels, or retention enemas .
  • the extract can be added in concentrations up to 5% by weight and mixed according to methods routine in the art.
  • Dietary supplements for animals can be prepared in a variety of forms including, but not limited to, liquid, powder, or solid pill forms.
  • the orange peel extract can administered either alone or in combination with other phytochemicals known to affect tumor cell growth, where combining compounds or extracts would lead to synergistic effects .
  • phytochemicals which can be used in combination with orange peel extract include, but are not limited to, resveratrol and its hydroxylated and methoxylated analogs, rosemary extract, black tea extracts, Mexican Bamboo, and Huzhang extracts.
  • Resveratrol is a well known, biologically active phytochemical .
  • Resveratrol and its hydroxylated and methoxylated analogs have been shown to have activity both in vi tro and in vivo to affect cell proliferation and tumor cell growth.
  • Resveratrol and several of its analogs (3,5- dihydroxystilbene : R-l; 3, 3', 4, 5 ' -tetrahydroxystilbene : R- 2; 3, 4, 4', 5-tetrahydroxystilbene : R-3; 3, 3', 5, 5'- tetrahydroxystilbene (R-4), 3, 3', 4, 5, 5'- pentahydroxystilbene : R-5; 3, 5-dimethoxystilbene : MR-1; 3, 4', 5-trimethoxystilbene: MR-0; 3, 3', 4, 5'- tetramethoxystilbene : MR-2; 3, 4, 4', 5-tetramethoxystilbene : MR-3; 3, 3', 5' 5 ' -tetramethoxystilbene : MR-4 ; and 3, 3', 4, 5, 5 ' -pentamethoxystilbene : MR-5) were evaluated in cell culture studies using standard methodologies.
  • W138 human diploid fibroblasts and cancerous SV40- transformed W138 cells were used in a cell proliferation assay. Growth rate and viability of these cells was determined following addition of resveratrol or one of its analogs. Doses tested ranged from 50 ng to 300 ⁇ g per ml or 1 ⁇ M to 100 ⁇ M concentrations in culture media. Resveratrol inhibited cell growth at concentrations less than 10 ⁇ M. The resveratrol analogs R3 and MR-0 also inhibited cell growth. At a concentration of 1 ⁇ M, MR-3 completely blocked proliferation of W138VA cells, although it had no effect on growth of W138 cells. MR-4 inhibited growth of W138 cells but not W138VA cells at doses of 100 ⁇ M. MR-1 was not active as an inhibitor of cell growth even at doses as high as 100 ⁇ M.
  • Resveratrol and its analogs were also tested in preneoplastic 184-B5/HER human mammary epithelial cells. Results showed that there was a dose-dependent inhibition of growth in response to treatment with resveratrol as well as the methoxy derivatives MR-0, MR-2 and MR-3. The concentration that inhibited growth by 50% (IC 50 ) for the tested compounds were: resveratrol, 10.5 ⁇ M; MR-0, 10.5 ⁇ M; MR-2 120 ⁇ M; MR-3, 1.0 ⁇ M . A cell cycle analysis revealed that treatment with MR-0, MR-2 and MR-3 resulted in progressive arrest of cells in the G2/M phase relative to solvent -treated control cultures and that MR-3 was the most effective compound.
  • mice were transplanted with oncogene-expressing, preneoplastic breast epithelial cells. Mice were then divided into groups with the control group fed AIN-76A diet alone. Another group of mice was fed AIN-76A diet supplemented with MR-3 (400 ppm) . After 12 weeks of continuous feeding, all mice in the control group exhibited palpable tumor formation at the transplant sites (100% tumor incidence) . In contrast, the group fed diet supplemented with the analog MR-3 had a 20% tumor incidence, with only one mouse of the five tested exhibiting tumor growth. Weight gains in the groups were comparable indicating that the analog had little toxicity.
  • Extracts of rosemary have also been shown to have anti- tumor activity and chemopreventive properties (Huang et al . 1994. Cancer Res .54 :701-708; Tokuda et al . 1986. Cancer Lett . 33:279-285; Singletary et al . 1996. Cancer Lett . 104:43-48; Singletary, K.W. and J.M. Nelshoppen. 1991. Cancer Lett . 60:169-175).
  • a diet containing 1% of rosemary extract significantly inhibited the initiation of mammary tumorigenesis in rats (Singletary, K.W. and J.M. Nelshoppen. 1991. Cancer Lett . 60:169-175) .
  • Palpable tumor incidence in rats fed the rosemary extract was 47% less than that of rats fed a control diet. Therefore, rosemary extracts were cancer preventive .
  • Black tea and its extracts have also been well-studied as potential pharmacological agents. Epidemiological studies have suggested that tea consumption has a protective effect against certain forms of human cancer (Stoner, G.D. and H. Mukhtar. 1995. J. Cell Biochem . Suppl . 22:169-180; Fuj iki et al . 1996. Nutr. .Rev. 54:S67-S70).
  • extracts of black tea in particular have been shown to be potent inhibitors of tumorigenesis in several animal model systems (Javed et al . Biomed . Environ . Sci . 11:307-313; Yang et al . 1997.
  • a combination diet of dietary supplement comprising orange peel extract and at least one other phytochemical will also be useful to treat or prevent cancer in animals, including humans.
  • Orange peel extract may be used in combination with rosemary extract, resveratrol and its analogs, Mexican Bamboo or Huzhang extracts, and black tea extracts. Doses of each extract used in the combination product are selected based on known activity of the extract in animals or cells.

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne des compositions et des méthodes permettant d'empêcher le développement des cellules tumorales, de traiter et de prévenir le cancer. Ces méthodes consistent à administrer un extrait de peau d'orange seul ou associé à d'autres produits phytochimiques.
EP00961973A 1999-09-21 2000-09-20 Utilisation d'extraits de peau d'orange dans la prevention et le traitement du cancer Withdrawn EP1214040A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US15501899P 1999-09-21 1999-09-21
US155018P 1999-09-21
PCT/US2000/025733 WO2001021137A1 (fr) 1999-09-21 2000-09-20 Utilisation d'extraits de peau d'orange dans la prevention et le traitement du cancer

Publications (2)

Publication Number Publication Date
EP1214040A1 EP1214040A1 (fr) 2002-06-19
EP1214040A4 true EP1214040A4 (fr) 2004-06-23

Family

ID=22553801

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00961973A Withdrawn EP1214040A4 (fr) 1999-09-21 2000-09-20 Utilisation d'extraits de peau d'orange dans la prevention et le traitement du cancer

Country Status (5)

Country Link
EP (1) EP1214040A4 (fr)
JP (1) JP2003509447A (fr)
AU (1) AU7384900A (fr)
CA (1) CA2383224C (fr)
WO (1) WO2001021137A1 (fr)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1147764A3 (fr) * 2000-04-19 2002-03-20 Nof Corporation Composition cosmetique
WO2002039956A2 (fr) 2000-11-15 2002-05-23 Rutgers, The State University Of New Jersey Extrait de the noir pour prevention de pathologies
US7087790B2 (en) 2003-08-29 2006-08-08 Rutgers, The State University Of New Jersey Benzotropolone derivatives and modulation of inflammatory response
US7351739B2 (en) 2004-04-30 2008-04-01 Wellgen, Inc. Bioactive compounds and methods of uses thereof
US20070042972A1 (en) * 2005-05-24 2007-02-22 Mckeever Kenneth H Compositions and methods for optimizing exercise recovery
US20070184132A1 (en) * 2006-02-09 2007-08-09 Kgk Synergize Inc Methods of treating canine osteosarcoma
WO2008035208A2 (fr) * 2006-05-19 2008-03-27 Kgk Synergize Inc Utilisation de flavonoïdes pour inhiber la croissance cellulaire
CN100422168C (zh) * 2006-06-15 2008-10-01 中国科学技术大学 橙皮素衍生物及其制备方法
DE102007037772A1 (de) * 2007-08-10 2009-02-12 Csabai, Zsolt, Dr. Ph. Antioxidantenkomplex auf Grape Vital Basis (Citrus- und/oder Traubenkern und/oder Flavonoidbasis)
JP5742050B2 (ja) * 2011-03-01 2015-07-01 国立研究開発法人農業・食品産業技術総合研究機構 Ｎｋ細胞活性化剤、及びｎｋ細胞活性化方法
WO2013172682A1 (fr) 2012-05-16 2013-11-21 연세대학교 산학협력단 Utilisation d'un composé de flavone pour la prévention ou le traitement de l'obésité
US9132117B2 (en) 2013-06-17 2015-09-15 Kgk Synergize, Inc Compositions and methods for glycemic control of subjects with impaired fasting glucose
KR20180093990A (ko) * 2015-12-07 2018-08-22 고쿠리츠 다이가쿠 호진 교토 다이가쿠 Pd-1 시그널 저해제의 병용 요법
CN115772145A (zh) * 2022-11-29 2023-03-10 三峡大学 一种柑橘属果实提取物及其制备方法与应用

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2220223C (fr) * 1995-05-05 2008-07-29 Hauser Inc. Isolement d'acide carnosique pur dans des extraits de romarin et de sauge par precipitation regie par le ph
JPH09176009A (ja) * 1995-12-27 1997-07-08 Inahata Koryo Kk 新規な抗変異原剤及び抗変異原性作用物質
US5830738A (en) * 1996-06-04 1998-11-03 Clemson University Extraction of pigment from plant material
US6251400B1 (en) * 1997-09-26 2001-06-26 Kgk Synergize Inc Compositions and methods of treatment of neoplastic diseases and hypercholesterolemia with citrus limonoids and flavonoids and tocotrienols
JP3571899B2 (ja) * 1997-12-18 2004-09-29 小川香料株式会社 香味劣化抑制剤

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No further relevant documents disclosed *
See also references of WO0121137A1 *

Also Published As

Publication number Publication date
AU7384900A (en) 2001-04-24
CA2383224C (fr) 2010-12-07
JP2003509447A (ja) 2003-03-11
WO2001021137A1 (fr) 2001-03-29
CA2383224A1 (fr) 2001-03-29
WO2001021137A8 (fr) 2001-07-26
EP1214040A1 (fr) 2002-06-19

Similar Documents

Publication Publication Date Title
FI119100B (fi) Flavanolignaanien käyttö valmistettaessa lääkkeitä, joilla on antiproliferatiivista vaikutusta kohdussa, munasarjoissa ja rintarauhasessa
ES2224337T3 (es) Procedimiento de preparacion y uso de productos fitoquimicos.
Nyamai et al. Medicinally important phytochemicals: an untapped research avenue
CA2383224C (fr) Utilisation d'extraits de peau d'orange dans la prevention et le traitement du cancer
Rios et al. An update review of saffron and its active constituents
Tamayo et al. The chemistry and biological activity of herbs used in Flor‐Essence™ herbal tonic and Essiac
Kumara et al. Extraction, isolation and characterisation of antitumor principle, α-hederin, from the seeds of Nigella sativa
US20020028852A1 (en) Resveratrol analogs for prevention of disease
US6391310B1 (en) Method of preparing and using isoflavones for the treatment of neurological symptoms
Salehi et al. Astragalus species: Insights on its chemical composition toward pharmacological applications
US20060035981A1 (en) Inhibition of anaerobic glucose metabolism and corresponding composition as a natural non-toxic approach to cancer treatment
US7201928B1 (en) Extracts of orange peel for prevention and treatment of cancer
Sun et al. The phenolic profiles of Radix Tetrastigma after solid phase extraction (SPE) and their antitumor effects and antioxidant activities in H22 tumor-bearing mice
US20050214394A1 (en) Hippophae rhamnoides compositions for cancer therapy
Minamiyama et al. Fermented grain products, production, properties and benefits to health
Tang et al. Protection of seven dibenzocyclooctadiene lignans from Schisandra chinensis against serum and glucose deprivation injury in SH-SY5Y cells.
US20210315960A1 (en) Compositions of azadirachta indica and methods of treating cancer
Chu et al. Antiproliferative effect of sweet orange peel and its bioactive compounds against human hepatoma cells, in vitro and in vivo
Shehab et al. Preparation and antihepatotoxicity activity of Fagonia indica extract and its solid dispersion formulation.
Samee et al. Effectiveness of milk thistle on human body against diseases: A comprehensive review
KR20140049218A (ko) 갈근 추출물을 함유하는 약학 조성물
Birla et al. Phytochemical and anticarcinogenic evaluation of Triphala powder extract, against melanoma cell line induced skin cancer in rats
Bawa et al. Clinical Uses of Piperine: A Review
JPH06340542A (ja) 薬用植物由来の骨疾患の予防・治療剤
Shafique et al. Anti-Carcinogenic Possessions of Citrus Peel Extracts and Flavonoids: A Review

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20020328

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY

A4 Supplementary search report drawn up and despatched

Effective date: 20040512

RIC1 Information provided on ipc code assigned before grant

Ipc: 7A 61K 6/00 A

Ipc: 7A 61K 7/44 B

Ipc: 7A 61K 7/42 B

Ipc: 7A 61K 7/00 B

Ipc: 7A 61K 35/78 B

17Q First examination report despatched

Effective date: 20060704

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RIC1 Information provided on ipc code assigned before grant

Ipc: C07D 311/40 20060101ALI20130226BHEP

Ipc: A61K 31/352 20060101ALI20130226BHEP

Ipc: A61P 35/00 20060101ALI20130226BHEP

Ipc: C07D 311/30 20060101AFI20130226BHEP

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20130716