WO2005099736A1 - Remède antitumoral - Google Patents

Remède antitumoral Download PDF

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Publication number
WO2005099736A1
WO2005099736A1 PCT/JP2005/000929 JP2005000929W WO2005099736A1 WO 2005099736 A1 WO2005099736 A1 WO 2005099736A1 JP 2005000929 W JP2005000929 W JP 2005000929W WO 2005099736 A1 WO2005099736 A1 WO 2005099736A1
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Prior art keywords
antitumor
cells
therapeutic agent
effect
etoposide
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PCT/JP2005/000929
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English (en)
Japanese (ja)
Inventor
Eibai Lee
Riyo Enomoto
Hiroyuki Hirano
Toshio Yokoi
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The New Industry Research Organization
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Priority to JP2006512263A priority Critical patent/JPWO2005099736A1/ja
Publication of WO2005099736A1 publication Critical patent/WO2005099736A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • 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
    • A61K36/539—Scutellaria (skullcap)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid

Definitions

  • the present invention relates to an antitumor therapeutic agent having an excellent combination effect, and more particularly to an antitumor therapeutic agent having few side effects when used in combination, and more effectively when used in combination.
  • the present invention relates to an antitumor therapeutic agent that can exert an effect.
  • Antitumor drugs include alkylating agents (cyclophosphamide, diphosphamide, carbone, etc.), antibiotics affecting nucleic acids (doxorubicin, bleomycin, etc.), platinum complexes (cisbratin, etc.), alkaloid antitumor drugs (vincristine, etc.) Vinblastine, etc.), antimetabolites (5-fluorouracil, etc.), topoisomerase inhibitors (etoposide, camptothecin, etc.), biological response regulators (interferon, etc.), hormone therapy agents (tamoxifen, etc.) are categorized.
  • Antitumor drugs have a mechanism of causing apoptosis in addition to the mechanism of action that damages DNA and causes necrosis of cancer cells and tumor cells. It induces apoptosis in cancer cells 'tumor cells and selectively kills cancer' tumor cells to provide an antitumor effect.
  • an antitumor drug is used in an amount sufficient to kill cancer 'tumor cells, normal cells also cause apoptosis, and there is a problem of side effects due to cell damage.
  • Non-Patent Document 1 Non-Patent Document 1
  • immunity As a biological reaction for a living body to identify non-self such as cancer or antibody-producing cells and protect itself.
  • cells produce heat shock proteins, a group of proteins that activate immunity, to protect themselves in the event of an invasion that is detrimental to cell survival.
  • This heat shock protein is involved in the cell cycle and cell differentiation even in normal cells, and plays an important role in maintaining the physiological functions of cells and tissues.
  • Non-Patent Document 1 YAKUKAGAKU ZASSHI, 122 (7), 471-480 (2002)
  • Patent Document 1 Japanese Unexamined Patent Publication No. 8-337535
  • Patent Document 2 Japanese Unexamined Patent Publication No. 5-25041
  • Patent Document 3 Japanese Patent Laid-Open Publication No. 2001-39875
  • the present inventors have conducted intensive studies to solve the above-mentioned problems.
  • a single agent of an antitumor agent having an apoptotic effect when administered, when an effective amount against a tumor is administered, normal cells also have side effects due to apoptosis.
  • the combination of a crude drug component, especially a component derived from yellow ginger reduces the apoptotic effect on normal cells and maintains or enhances the apoptotic effect on tumor cells. They discovered that they could be medicines and completed the present invention.
  • the present invention consists of the following.
  • An anti-tumor therapeutic agent characterized by using a combination of a component derived from yellow ginger and an anti-tumor agent having an apoptotic effect.
  • antitumor therapeutic agent according to the above item 1, wherein the antitumor agent having an apoptotic effect is a topoisomerase inhibitor, an alkaloid antitumor agent, a platinum complex, an antibiotic, or an alkylating agent.
  • the antitumor therapeutic agent according to the above item 2 which is etoposide or camptothecin or a derivative thereof, which is a topoisomerase inhibitor.
  • a pharmaceutical composition comprising the antitumor therapeutic agent according to 1-11, 11 or 12 above.
  • FIG. 1 is a view showing the DNA fragmentation rate when YO-2 or etoposide and wogonin are used in combination with normal cells. (Example 1)
  • FIG. 2 is a view showing caspase-3-like activity when etoposide and wogonin are used in combination with normal cells. (Example 2)
  • FIG. 3 is a view showing the DNA fragmentation rate when etoposide or cisplatin and wogonin are used in combination in Jurkat cells. (Example 3)
  • FIG. 4 is a view showing a DNA fragmentation rate when etoposide or cisplatin and ogonin are used in combination in HL_60 cells. (Example 4)
  • FIG. 5 is a photograph showing the morphology of nuclei when etoposide and wogonin were used in combination in Jurkat cells.
  • FIG. 6 is a graph showing the effect on cell viability when doxorubicin and ogonin are used in combination in A549 cells. (Example 6)
  • FIG. 7 is a view showing the effect on cell viability when cisbratin and ogonin are used in combination in A549 cells. (Example 7)
  • FIG. 8 is a graph showing the effect on cell viability when a combination of carbocon and ogonin is used in A549 cells. (Example 8)
  • FIG. 9 is a view showing the effect on cell viability when vinblastine and ogonin are used in combination in A549 cells. (Example 9)
  • FIG. 10 is a graph showing the effect on cell viability when camptothecin and ogonin are used in combination in A549 cells. (Example 10)
  • FIG. 11 is a graph showing the effect on cell viability when etoposide and ogonin are used in combination in A549 cells. (Example 11)
  • FIG. 12 is a view showing the effect on cell viability when etoposide and wogonin are used in combination with NCI-H226 cells. (Example 12)
  • the antitumor therapeutic agent of the present invention is obtained by using a combination of a component derived from yellow ginger and an antitumor agent having an apoptotic effect.
  • an antitumor drug having an apoptotic effect may be simply referred to as an “antitumor drug” and is distinguished from an “antitumor therapeutic drug” according to the present invention.
  • the component used in the anti-inflammatory therapeutic agent according to the combination of the present invention is also a component derived from yellow ginger, contains flavonoids, and can specifically use wogonin, baicalin, baicalein, etc., and is preferably used. Ogonin can be used.
  • the components derived from yellow starch of the present invention are not limited to components extracted from natural products, but also include components containing flavonoids and having substantially the same effects as crude drugs as components of crude drugs. . If such a component is used, it may be a component obtained by synthesis.
  • Compounds containing the flavonoids and representing the above components include a basic skeleton represented by the following (Chemical Formula 1). The structure.
  • ⁇ gonin is an R
  • All of R are hydrogen atoms.
  • the anti-neoplastic agent having an apoptotic effect of the present invention can be selected from anti-neoplastic agents classified as topoisomerase inhibitors, alkaloid anti-neoplastic agents, platinum complexes, antibiotics, alkylating agents, etc., and is preferably used. Selected from platinum complexes and topoisomerase inhibitors You can choose S.
  • the topoisomerase inhibitor has a mechanism of action of indirect DNA chain cleavage via inhibition of topoisomerase II or inhibition of DNA synthesis by inhibition of topoisomerase I.
  • Examples of topoisomerase II inhibitors include etoposide, and examples of topoisomerase I inhibitors include camptothecin.
  • Topoisomerase II is a dimeric enzyme that forms a covalent bond at the five ends of DNA, binds to DNA in the nucleus in an ATP-dependent manner, causes transient DNA strand breaks, and alters the structure of the DNA strand. Recombining the cut DNA causes a change in its three-dimensional structure.
  • Etoposide is thought to exert an antitumor effect by forming a ternary complex of DNA and topoisomerase II and inhibiting the reconnection of transiently cut DNA strands.
  • Alkaloid antitumor drugs bind to tubulin to prevent mitosis, act specifically in the M phase of the cell cycle, and are used for the treatment of positron sarcoma and malignant lymphoma.
  • An example of an alkaloid is vinblastine.
  • the platinum complex is a non-cell cycle specific anticancer drug that binds to guanine to distort the DNA structure.
  • Specific examples of the platinum complex include cisplatin (dsplatin).
  • Doxorubicin is an antitumor antibiotic extracted from anthracyclines, a product of Streptomyces. Doxorubicin has a mechanism of action that binds to DNA in tumor cells, prevents DNA cleavage during cell division, and causes inhibition of DNA replication and RNA synthesis. It also has the effect of inhibiting DNA-dependent RNA polymerase and deoxyribonuclease.
  • the alkylating agent inhibits DNA and RNA biosynthesis of tumor cells by alkylating DNA and RNA. In particular, it inhibits DNA biosynthesis. Specific examples of the alkylating agent include carboquone.
  • the amount of the anti-tumor agent having an apoptotic effect together with a component derived from yellow ginger used in combination can be determined based on the apoptotic effect on tumor cells and normal cells.
  • an antitumor drug having an apoptotic effect can be used alone or in an amount showing no apoptotic effect on tumor cells and normal cells when used alone.
  • the component derived from the yellow goblet used together has the ability of the antitumor agent to maintain the apoptotic effect on tumor cells. Or an amount that can reduce the apoptotic effect of the antitumor agent on normal cells.
  • the combined use of the yellow-waste-derived component enhances the apoptotic effect of the antitumor agent on tumor cells.
  • An amount that does not show an apoptotic effect on normal cells of the antitumor drug can be used.
  • the amount of the combination of the anti-cancer drug and the yellow-derived component in an amount capable of maximizing the apoptotic effect on tumor cells and reducing the side effects due to the apoptotic effect on normal cells as much as possible is as follows.
  • the ratio of the component derived from yellow ginger to the antitumor agent can be selected from a range of 10: 1 to 1:10 in terms of a molar ratio, preferably from a range of 2: 1 to 1: 2. You can choose.
  • the antitumor drug can be used in an amount of 0.01 to 100 ⁇ M, preferably 0.1 to 50 ⁇ M, more preferably 1 to 30 ⁇ m under cultured cell conditions.
  • the amount of the component derived from the yellow goat satisfies the above conditions, and can be selected from the range of 100 to 0.1 ⁇ m, preferably 50 0.1 ⁇ m, and more preferably 30-1.
  • the apoptotic effect can be confirmed biochemically and morphologically.
  • DNA Apoptosis can be confirmed by measuring the fragmentation of.
  • the measurement of DNA fragmentation can be performed according to a known method (McConkey, DJ, et al.,
  • lucocorticoids activate a suicide process m thymocytes through an elevation of cytosolic Ca 2+ concentration. Arch. Biochem. Biophys., 269: 365-370, 1989).
  • caspase-3-like activity when cells are destroyed by apoptosis, caspase-3-like activity is observed, so that apoptosis can be confirmed by measuring the activity.
  • Caspase-3-like activity can be measured by a known method (Takahashi, A., et al., Affinity labeling displays the stepwise activation of ICE-related proteases by Fas, staurosporine, and CrmA-sensitive caspase-8 Oncogene, 14: 2741-2752, 1997).
  • the antitumor therapeutic agent of the present invention shows an effective antitumor effect on a malignant tumor by an apoptotic effect.
  • the type of tumor is not particularly limited, and can be used for hematological cancer and solid cancer.
  • blood cancer can be used for leukemia, and solid cancer can be used for lung cancer.
  • the present invention relates to an antitumor therapeutic agent characterized by using a combination of a component derived from yellow ginger and an antitumor agent having an apoptotic effect. Further, the present invention extends to a pharmaceutical composition containing an antitumor therapeutic agent and exerting an effect on the above malignant tumor.
  • Pharmaceutical compositions can include pharmacologically acceptable salts. “Pharmacologically acceptable salts” include conventional non-toxic salts, ie, acid addition salts and salts with various bases.
  • inorganic acid salts such as hydrochloric acid, nitric acid, and sulfuric acid
  • organic acid salts such as acetic acid, citric acid, fumaric acid, and tartaric acid
  • sulfonic acid salts such as methanesulfonic acid and ⁇ -toluenesulfonic acid
  • Amino acid salts such as syn and glutamic acid
  • inorganic base salts such as alkali metal salts (eg, sodium salt, potassium salt); alkaline earth metal salts (eg, magnesium salt, calcium salt); and triethylamine salts, pyridine salts; Picoline salt, ethanolanolamine salt, triethanolanolenamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, etc.
  • Organic amine salts such as hydrochloric acid, nitric acid, and sulfuric acid
  • organic acid salts such as acetic acid, citric acid, fuma
  • the pharmaceutical composition containing the antitumor therapeutic agent of the present invention can be prepared by selecting an optimal administration method such as oral administration, intravenous injection administration, or intramuscular injection administration according to the properties of various antitumor agents. Can administer S.
  • Thymocytes were collected from the thymus of young male rats (4-5 weeks of age) and adjusted to a cell density of 10 ⁇ 10 6 cells / ml in RPMI 1640 medium containing 10% fetal bovine serum. The cells were used for the experiment immediately after collection.
  • YO-2 As an antitumor agent, YO-2 (Lee, E., et al "Biochem. Pharmacol., 63: 1315-23, 2002; Okada, ⁇ ⁇ , et al" Bioorg. Med. Chem. Lett., 10: 2217 -21, 2000) (30 / i M), etoposide (10 ⁇ ), and cultured for 6 hours at 5% CO, 37 ° C, and 100 ⁇ g of ogonin for each. The apoptotic effect of the system was confirmed by measuring DNA fragmentation. The DNA fragmentation rate was measured by separating and quantifying fragmented DNA and non-fragmented DNA.
  • the DNA amount was determined according to the method described in McConkey, D.J., et al., Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca concentration.Arch.Biochem.Biophys., 269: 365-370, 1989.
  • the ratio of the amount of fragmented DNA to the total amount of DNA (fragmented DNA + non-fragmented DNA) was expressed in%.
  • Thymocytes (100 x 10 6 cells / ml) were cultured with etoposide (10 ⁇ l) in the presence or absence of ozonin (100 ⁇ l) for 14 hours, and then 50 ⁇ l of extraction buffer (50 mM
  • An enzyme preparation was prepared by suspending in chymostatin, 1 ⁇ g / ml leptin, 1 ⁇ g / ml pepstatin A, 2.83 ⁇ g / ml ( ⁇ -64-d) and repeating freeze-thawing.
  • Activity measurement buffer 100 mM HEPES_KOH, 10% sucrose, 0.1% 3-[(3_cholamidopropyl) dimethylammonio] propanesulfonic acid (CHAPS), 10 mM dithiothreitol, 0.1 mg / ml ovalbumin
  • Ac-DEVD-MCA acetyl-Asp_Glu-Va Asp-hy- (4-methyl-coumalyl-7-amide)
  • Jurkat cells acute lymphoblastic leukemia patient's peripheral blood-derived cells
  • 10% ⁇ also fetal serum using RPMI 1640 medium containing prepared so that cell density force IX 10 5 cells / ml of Was cultured under 5% CO, 37 ° C. and subcultured every 4 days.
  • An RPMI 1640 medium containing 10% fetal bovine serum was prepared to a cell density of 3 ⁇ 10 6 cells / ml.
  • FIG. 3 shows the results. According to FIG. 3, DNA fragmentation was not observed with wogonin alone, and no apoptotic effect on the cells was observed.
  • HL-60 cells peripheral blood-derived cells of patients with acute promyelocytic leukemia
  • RPMI 1640 medium containing 10% fetal serum to a cell density of 1.5 ⁇ 10 5 cells / ml.
  • the cells were prepared using RPMI 1640 medium at a cell density of 4 ⁇ 10 6 cells / ml and cultured for 6 hours with etoposide 5 ⁇ ⁇ ⁇ or cisbratin 30 in the presence or absence of each concentration of oligonin. Then, the DNA fragmentation rate of the HL-60 cells was examined. The measurement of DNA fragmentation followed the method described in Example 1.
  • FIG. 4 shows the results. According to FIG. 4, DNA fragmentation was not observed with wogonin alone.
  • the DNA fragmentation rate by etoposide was about 10% when ogonin was not added, whereas ogopenin at each concentration was added to etoposide and cultured.
  • increased DNA fragmentation was observed and increased apoptotic effect was observed depending on the concentration of added agonin.
  • Jurkat cells were cultured with 5 etoposide for 6 hours in the presence or absence of 10 ⁇ M phogonin and fixed in phosphate-buffered saline (PBS) containing 5% formaldehyde (4 ° C, 15 minutes) that's all). The cells were collected by centrifugation at 300 ⁇ g for 10 minutes and resuspended in PBS. The cell suspension was added with 12.3 ⁇ g / ml Hoechst 33342, reacted at room temperature for 10 minutes to stain the nucleus, washed with PBS, and confocal laser microscope (LSM GB200, Olympus Corporation) Was used to observe cell nuclei ( ⁇ 40).
  • PBS phosphate-buffered saline
  • Example 6 Effect of combined use of doxorubicin and wogonin on human lung cancer cells (A549 cells) (cell viability measurement) A549 cells (distributed by the Human Science Foundation) in the presence or absence of 25 ⁇ gongonin with 0, 1, 2, 5, 5, 10, 20, 50, 100, 200 and 500 / i / doxorubicin The cell viability after culturing was examined.
  • a MEM medium supplemented with 10% fetal calf serum (FCS) was used as a culture solution and used for culturing A549 cells.
  • A549 cells are suspended in the above culture solution at a density of 1.5 ⁇ 10 5 cells / ml, and 10 ml of the cell suspension is seeded on a culture dish having a diameter of 100 mm.
  • the culture medium was changed every 13 days, and the cells were grown to 80-90% (subconfluent).
  • the cells grown in the subconfluent are treated with a 0.25% trypsin solution to detach the cells from the culture dish, washed with the culture solution, and then a cell suspension of 5 ⁇ 10 4 cells / ml is prepared. did.
  • a cell suspension of 5 x 10 4 cells / ml was seeded in 200 ⁇ l aliquots into each well of a 96-well microplate. At this time, the number of cells in each well is 1 ⁇ 10 4 cells / well.
  • the amount of formazan produced is measured using a microplate reader for absorption of wavelength A.
  • a cell culture containing doxorubicin and ogonin and cultured in a culture medium was used as a control.
  • the absorbance of the control was set to 100%, and the cell viability when each concentration of the drug was added was calculated.
  • A549 cells (distributed by the Human Science Foundation) were cultured with 0, 1, 2, 5, 5, 10, 20, 50, 100, 200, and 500 ⁇ ⁇ ⁇ of cisplatin in the presence or absence of 25 ⁇ ⁇ ⁇ gonin Later cell viability was examined.
  • ⁇ 549 cells distributed by the Human Science Foundation
  • ⁇ 549 cells distributed by the Human Science Foundation
  • 50, 100, 200 and 500 / i ⁇ carbocon in the presence or absence of 25 ⁇ gonin Cell viability after feeding was examined.
  • ⁇ 549 cells distributed by the Human Science Foundation
  • 25 ⁇ gonin with 0, 1, 2, 5, 5, 10, 20, 50, 100, 200 and 500 ⁇ vinblastine
  • the cell viability after culturing was examined.
  • A549 cells (distributed by the Human Science Foundation) in the presence or absence of 25 ⁇ gongonin together with 0, 1, 2, 5, 10, 20, 50, 100, 200 and 500 ⁇ camptothecin The cell viability after culturing was examined.
  • Example 11 Effect of combined use of etoposide and ogonin on human lung cancer cells (A549 cells) (measurement of cell viability)
  • A549 cells (distributed by the Human Science Foundation) were cultured with 0, 1, 2, 5, 10, 20, 50, 100, 200 and 500 / ii etoposide in the presence or absence of 25 ⁇ gonin. Cell viability after feeding was examined.
  • Example 12 Combined effect of etoposide and oligonin on human lung cancer cells (NCI-H226 cells, ATCC No. CRL_5826) (measurement of cell viability)
  • NCI-H226 cells purchased from ATCC after culturing with 0, 1, 2, 5, 10, 20, 50, 100, 200 and 500 ⁇ ⁇ etoposide in the presence or absence of 25 ⁇ pggonin The survival rate was examined.
  • NCI-H226 cells were prepared by adding 10% fetal calf serum (FCS) to RPMI medium.
  • FCS fetal calf serum
  • the cell culture conditions temperature, time, etc.
  • drug concentration were calculated by the same method as in Example 11.
  • the antitumor therapeutic drug obtained by using the combination of the yellow ginger-derived component of the present invention and an antitumor drug can reduce apoptosis in normal cells and maintain or enhance apoptosis in tumor cells.
  • the side effects of the antitumor drug were reduced.
  • these antitumor therapeutic agents can be applied not only to hematological cancer but also to solid cancers such as lung cancer.

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Abstract

Il est prévu de fournir un remède antitumoral qui a un effet apoptotique régulé sur des cellules normales et un effet antitumoral amélioré. Un médicament antitumoral spécifique, en particulier un médicament ayant un effet apoptotique est combiné avec un composant issu de la racine de scutellaire. Lorsqu’il est utilisé seul, le médicament antitumoral ayant un effet apoptotique a un effet secondaire sur des cellules normales. Lorsque le médicament antitumoral est utilisé avec le composant issu de la racine de scutellaire, l’effet apoptotique sur les cellules normales est inversement diminué alors que l’effet apoptotique du médicament sur des cellules tumorales peut être maintenu ou amélioré, démontrant un excellent effet antitumoral.
PCT/JP2005/000929 2004-04-08 2005-01-25 Remède antitumoral WO2005099736A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100345537C (zh) * 2005-11-09 2007-10-31 中国药科大学 汉黄芩素在制备治疗白血病药物中的应用
CN103316119A (zh) * 2013-05-17 2013-09-25 胡庆华 一种治疗白血病的中药药物

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HORIBE S. ET AL.: "Kanpoyaku i yoru Koganzai Tazai Taisei Kokufuku (1): Paclitaxel no Gansaibo Zoshoku ni Oyobosu Kakushu Shoyaku no Eikyo.", NIPPON YAKUGAKUKAI NENKAI KOEN YOSHISHU, vol. 123, no. 4, 2003, pages 99, XP002992674 *
LEE W. ET AL.: "Wogonin and fisetin induce apoptosis in human promyloleukemic cells, accompanied by a decrease of reactive oxygen species, and activation of caspase 3 and Ca2+dependent endonuclease.", BIOCHEMICAL PHARMACOLOGY, vol. 63, no. 2, 2002, pages 225 - 236, XP001162761 *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100345537C (zh) * 2005-11-09 2007-10-31 中国药科大学 汉黄芩素在制备治疗白血病药物中的应用
CN103316119A (zh) * 2013-05-17 2013-09-25 胡庆华 一种治疗白血病的中药药物

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