CN1762450A - Application of magnolia vine fruit in preparation of anti-tumor medicine or multi-medicine tolerant reversal agent - Google Patents
Application of magnolia vine fruit in preparation of anti-tumor medicine or multi-medicine tolerant reversal agent Download PDFInfo
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Abstract
The invention provides the use of schisandra fruit in preparing medicament for treating tumors, wherein the schisandra is a plant of Schisandra chinesis(Turcz.)Baill. belonging to Magnoliales, it can effectively inverse the multi-drug tolerance of the tumors. The extracts of schisandra fruit can be acted on P-glucoprotein, MRP1 and MXR.
Description
(1) technical field
The present invention relates to the application of clearly application, the especially Fructus Schisandrae Chinensis of Chinese herbal medicine Fructus Schisandrae Chinensis in preparation medicine for treating tumor thing in preparation antitumor cell multidrug resistance inversion agent medicine.
(2) background technology
Tumor is to cause one of human main causes of death, and chemotherapy of tumors is a kind of main means of treatment tumor.Yet chemotherapy of tumors can be failed because of tumor cell obtains Drug resistance.
The reason of tumor cell generation multidrug resistance has multiple, the wherein most importantly bonded transport protein of tumor cells expression ATP [ATP binding cassette (ABC) transporters].P-glycoprotein (P-glycoprotein, P-gp), multidrug-associated protein 1 (multidrug resistant associatedprotein 1, MRP1) and breast carcinoma sorcin (breast cancer resistance protein BCRP, be also referred to as MXR or ABCG2), be several main protein that cause tumor multi-medicine drug-resistant of generally acknowledging at present.These protein are transmembrane protein, and their effect is equivalent to Teat pipette, the medicine that enters in the tumor cell can be discharged the extracellular, make intracellular drug level very low, and therefore tumor cell can escape the attack of antineoplastic agent.(Gottesman?MM，Fojo?T?&?Bates?SE.Nature?Review/cancer.2：48-58，2002)。
At present anticarcinogen that uses clinically such as amycin, mitomycin, epirubicin, daunorubicin, vincristine, high Folium et Ramulus Cephalotaxi ester, rice take off medicine such as anthraquinone and all do not escape the drug-fast destiny of tumor, because these medicines are the substrate of P-glycoprotein or MRP1 or BCRP.Therefore, behind P-glycoprotein or MRP1 in the tumor cell or BCRP high expressed, the Drug resistance that tumor cell obtains is not merely to a certain anticarcinogen, but to multiple anticarcinogen.Make the tumor cell of high expressed P-glycoprotein or MRP1 or BCRP regain sensitivity to anticarcinogen, effective method suppresses these proteinic functions exactly, makes it can not bring into play the function of ' Teat pipette '.Therefore, the medicine of these protein functions of development inhibition has important meaning to the chemotherapy of tumor.At present, a variety of anticarcinogens being arranged clinically, is medicine at P-glycoprotein or MRP1 or BCRP but do not have a kind of.Therefore, it is very urgent to develop a kind of like this medicine.
In recent years the interactional with Pgp of development is MDR reversal agents.Phenyl alkylamide derivant calcium antagonist verapamil is to find the earliest and have to reverse the active phenyl alkylamide derivant of MDR that the P-glycoprotein mediates more by force.Its calcium antagonistic activity and its MDR reverse effect to blood vessel, cardiac muscle is irrelevant, and relevant with the cardiovascular system side effect, its side effect seriously hinders clinical practice.
Fructus Schisandrae Chinensis, the dry mature fruit of magnoliaceae schisandra Schisandra chinensis (Turcz.) Baill. or Magnoliacea plant schisandra chinensis Schisandra sphenanthera Rehd.et Wils., Fructus Schisandrae Chinensis is listed in top grade in Shennong's Herbal, effect with convergence, astringent or styptic treatment for spontaneous sweating, supplementing QI for promoting the production of body fluid, kidney calming, it is traditional Chinese medical science strengthening by means of tonics medicine commonly used, has multiple pharmacological effect, but do not see that it has clear and definite antineoplastic report, does not especially see the report that it has artitumor multi-medicine-resistant.
(3) summary of the invention
The objective of the invention is for a kind of medicine that can be used as antitumor cell multidrug resistance inversion agent is provided.
For reaching goal of the invention the technical solution used in the present invention be:
Fructus Schisandrae Chinensis is applied to prepare tumor multidrug-resistance inversion agent medicine.Normally adopt the extract of Fructus Schisandrae Chinensis to prepare the reversal of multidrug resistance of tumor cells medicine.Fructus Schisandrae Chinensis extrat can adopt the acceptable organic solvent of medicine to extract with circumfluence method, percolation and obtain, or several different methods such as supercritical extraction obtains.
Usually extract with circumfluence method with non-proton polar organic solvent: be that extractant is an example with ethanol, fruit of Fructus Schisandrae Chinensis is ground into coarse powder, being soaked in 4 times of amount 50%～100% alcohol reflux temperature carries 2～3 times, each 2～12 hours, filter, collect and merging filtrate, decompression recycling ethanol, concentrated filtrate gets extractum.Equally also the method for available hot dipping requires the time of dipping longer relatively, each 6～24 hours.Various alcohol such as the above also available methanol of ethanol, propanol replace; Esters or ether solvent replacements such as also available other organic solvents such as ethyl acetate, ether.
Obtaining Fructus Schisandrae Chinensis extrat with percolation also is the method for using always: get Chinese Magnolivine Fruit with 6 times of amount 95% ethanol percolate extraction, percolation speed 3～4ml/min is percolation at a slow speed, reclaims the ethanol leachate, decompression recycling ethanol, concentrate thick paste.Same methanol, propanol, ethyl acetate, ether solvent or aprotic polar solvent etc. also can be used as the percolation extractant.
Available in addition super critical extraction: the careful coarse powder of the five tastes is used supercritical CO under 25MPa, 45 ℃
2Extract 2h, get the brown magma.
The application of Fructus Schisandrae Chinensis in preparation tumor multidrug-resistance inversion agent medicine, described inversion agent medicine reverses by P-glycoprotein (P-glycoprotein, the multidrug resistance of the tumor cell that P-gp) causes.Further, described inversion agent medicine reverses by multidrug-associated protein (multidrug resistantassociated protein, the multidrug resistance of the tumor cell that MRP1) causes.Further described inversion agent medicine reverses the multidrug resistance by the tumor cell of breast carcinoma sorcin (breast cancer resistant protein, BCRP is also referred to as MXR or ABCG2).
Described inversion agent medicine also can contain the antitumor drug of Fructus Schisandrae Chinensis as tumor multidrug-resistance inversion agent sensitivity, and drug excipient or carrier.Be that the described inversion agent medicine that contains Fructus Schisandrae Chinensis adds simultaneously to antitumor drug and the drug excipient of Fructus Schisandrae Chinensis as tumor multidrug-resistance inversion agent sensitivity, when being equivalent to be used for the treatment of the multidrug resistance tumor patient, give the Fructus Schisandrae Chinensis extrat of a dosage when giving the antitumor drug of a dosage again.
Described antitumor drug is one of following or the mixing of its arbitrary proportion:
1. the 2. 3. substrate of BCRP of substrate of MRP1 of the substrate of P-glycoprotein.
Concrete, described antitumor drug be one of following or its two or more with the mixing of arbitrary proportion:
The Doxorubicin amycin; The Actinomycin D actinomycin D; Altreatamine; The Bleomycin bleomycin; The Busulphan busulfan; The Capecitabine capecitabine; The Carboplatin carboplatin; The Carmustine carmustine; The Chlorambucil chlorambucil; The Cisplatin cisplatin; The cyclophosphamide cyclophosphamide; The cytarbine cytosine arabinoside; Dacarabazine, the daunorubicin daunorubicin; The epirubicin epirubicin; The etoposide etoposide; Etoposide; Etoposide; The acid of fludarbine fluorine vidarabine; The fluorouracil fluorouracil; The gemcitabine gemcitabine; The herceptin Trastuzumab; The hydroxyurea hydroxyurea; The idarubicin idarubicin; The ifosfamide ifosfamide; The irinotecan Irinotecan; The lomustine lomustine; Lomustine; The melphalan melphalan; Alkeran; The mercaptopurine purinethol; The methotrexate methotrexate; The mitomycin mitomycin; The mitozantrone mitoxantrone; Dithranol; The oxaliplatin oxaliplatin; The procarbazine procarbazine; First (base) benzyl hydrazine; The rituxan Mabthera; The steroids steroid; The streptozocin streptozocin; Streptozotocin; The taxol paclitaxel, the taxotere taxotere; Tamozolomide, the thioguanine thioguanine; The thiotepa thio-tepa; Thiotef; Tespamin; Tomudex Raltitrexed (raltitrexed); The topotecan topotecan; The treosulfan treosulfan; The uracil-tegufur uracil; The vinblastine vinblastine; Vincaleucoblastine; The vindesine vindesine; The vinorelbine vinorelbine.
Described inversion agent medicine can be made into one of following dosage form: 1. 2. 3. 4. 5. decoction of granule of capsule of tablet of injection.
Described inversion agent medicine can also contain other inversion agent, or uses jointly with other inversion agent medicines, also can contain other Chinese medicine compositions.
The present invention also points out Fructus Schisandrae Chinensis to have clear and definite antitumor action, and Fructus Schisandrae Chinensis can be applicable to prepare the medicine for the treatment of tumor, or Fructus Schisandrae Chinensis extrat is applied to prepare the medicine for treating tumor thing.
The beneficial effect of the application of Fructus Schisandrae Chinensis of the present invention in preparation medicine for treating tumor thing is as follows: (1) has potential applicability in clinical practice, and Fructus Schisandrae Chinensis is the multidrug resistance of reversing tumor effectively, and Fructus Schisandrae Chinensis extrat acts on P-glycoprotein, MRP1 and MXR; (2) Fructus Schisandrae Chinensis has lower toxicity to the human normal cell, but toxic to tumor cell, and therefore, Fructus Schisandrae Chinensis also has the application prospect of good preparation medicine for treating tumor thing and clinical tumor chemotherapy.
(4) description of drawings
Fig. 1 is the expression percentage ratio of P-glycoprotein in multidrug resistance cell.
Fig. 2 is the expression of P-glycoprotein in multidrug resistance cell.
Fig. 3 is the expression percentage ratio of MRP1 in multidrug resistance cell.
Fig. 4 is the expression of MRP1 in multidrug resistance cell.
Fig. 5 gathers for the daunorubicin that schisandra chinensis ethyl hydrate extract increases in the P-gp high expressed multidrug resistance tumor cells.
Fig. 6 gathers for the daunorubicin that the Fructus Schisandrae Chinensis methanolic extract increases in the P-gp high expressed multidrug resistance tumor cells.
Fig. 7 gathers for the daunorubicin that schisandra chinensis ethyl hydrate extract increases in the MRP1 high expressed multidrug resistance tumor cells.
Fig. 8 is the dose-effect relationship that schisandra chinensis ethyl hydrate extract reverses the multidrug resistance tumor cells Drug resistance.
(5) specific embodiment
The present invention is described further below in conjunction with the specific embodiment:
Embodiment 1: the extraction of Fructus Schisandrae Chinensis
Circumfluence method:
(a) take by weighing Fructus Schisandrae Chinensis 15000g as raw material;
(b) fruit of Fructus Schisandrae Chinensis is ground into coarse powder, be soaked in 4 times the amount 90% ethanol in 12 hours.Here institute's concentration of ethanol that requires 50%～100% can, select 70%～90% ethanol as extractant usually, soak time can be at 6～24 hours.
(c) the Fructus Schisandrae Chinensis soak with ethanol liquid in the step (b) was extracted 3 hours at reflux temperature, filter, collect filtrate;
(d) filtering residue in the step (c) is added 3 times of amount 90% ethanol, extracted 2 hours, filter and collect filtrate at reflux temperature;
(e) filtering residue in the step (d) is added 3 times of amount 90% ethanol, reflux temperature extracted 2 hours, filtered and collect filtrate;
(f) merge (c) (d) (e) filtrate of collecting, decompression recycling ethanol concentrates to such an extent that proportion is the extractum of 1.23g/ml to there being the ethanol flavor, and is standby.
Various alcohol such as the above also available methanol of ethanol, propanol replace; Also available other organic solvents such as replacements such as ethyl acetate, ether solvent.
Embodiment 2: the extraction of Fructus Schisandrae Chinensis
Percolation: get the 5000g Chinese Magnolivine Fruit and measure 95% ethanol percolations, percolation speed 15ml/min with 6 times.Reclaim the ethanol leachate, decompression recycling ethanol concentrates to such an extent that proportion is the extractum of 1.15g/ml to there not being the ethanol flavor, and is standby.Various alcohol such as the above also available methanol of ethanol, propanol replace; Also available other organic solvents such as replacements such as ethyl acetate, ether solvent.
Embodiment 3: the extraction of Fructus Schisandrae Chinensis
Supercritical extraction: Fructus Schisandrae Chinensis sample 1000g is ground into coarse powder (crossing 40 mesh sieves), puts the 1L supercritical CO
2In the extraction kettle, regulate pressure: 25MPa, temperature: 45 ℃, flow: 30kg/h, extraction time: 2h.Collection obtains the brown extract.
Embodiment 4: the preparation of Fructus Schisandrae Chinensis tablet
(1) takes by weighing embodiment 1 gained Fructus Schisandrae Chinensis extractum 110g, lactose 500g, starch 75g;
(2) with the Fructus Schisandrae Chinensis extractum in the step (1), lactose, starch mix homogeneously, spray adds 75% ethanol and makes wet grain, with 20 mesh sieve granulate, and the wet grain forced air drying under 50 ℃ of conditions that obtains;
(3) dried granule is through tablet machine compression moulding.
Embodiment 5: the capsular preparation of Fructus Schisandrae Chinensis
Take by weighing embodiment 2 gained Fructus Schisandrae Chinensis extractum 300g, add the Polyethylene Glycol of 0.5 times of amount, cross 25 mesh sieves and make granule, 50 ℃～60 ℃ forced air dryings, encapsulated with 40 mesh sieve granulate.Here the also available glycerin gelatine of Polyethylene Glycol replaces.
Embodiment 6: the preparation of Fructus Schisandrae Chinensis Granulae
(A) take by weighing 1000g Fructus Schisandrae Chinensis coarse powder, add 4 times of amount 75% ethanol, soaked overnight;
(B) ethanol of Fructus Schisandrae Chinensis coarse powder and immersion is put into reflux, back flow reaction 3 hours is filtered, and filtering residue is standby, and decompression filtrate recycling ethanol obtains the brown ethanol extraction to there not being the ethanol flavor;
(C) filtering residue in the step (B) is added 8 times of water gagings and decocted 3 hours, filter yellow decocting liquid, filtering residue is standby;
(D) step (C) gained filtering residue adds 6 times of water gagings and decocted 2 hours, filter yellow decocting liquid;
(E) merge (C) (D) yellow decocting liquid of step gained, be condensed into the extractum that proportion is 1.05g/ml;
(F) in the extractum of step (E), add an amount of dextrin mix homogeneously, granulate with spray drying method.
(G) ethanol extraction of step (B) is sprayed at equably in the granule that step (F) makes, drying, brown Fructus Schisandrae Chinensis Granulae.
Embodiment 7: the preparation of Fructus Schisandrae Chinensis decoction
(A) take by weighing 1000g Fructus Schisandrae Chinensis coarse powder, add 4 times of amount 95% ethanol, soaked overnight;
(B) (A) put into reflux, refluxed 3 hours, filter, filtering residue is standby, and decompression filtrate recycling ethanol obtains the brown ethanol extraction;
(C) with adding 8 times of water gagings in step (B) the gained filtering residue, decocted 3 hours, filter yellow decocting liquid, filtering residue is standby;
(D) step (C) gained filtering residue adds 6 times of water gagings, decocts 2 hours, filter yellow decocting liquid;
(E) merge (C) (D) step gained decocting liquid, be concentrated into 1000ml;
(F) with the ethanol extraction in step (E) the gained concentrated solution adding step (B), mixing is promptly made the Fructus Schisandrae Chinensis decoction.
Embodiment 8: the preparation of Fructus Schisandrae Chinensis injection
Take by weighing embodiment 1 gained 500g Fructus Schisandrae Chinensis extractum, add the fresh water for injection of 3 times of amounts, cold preservation 40 hours, draw supernatant, supernatant concentration adds the fresh water for injection of 500ml again to 500ml in filtrate, regulate pH value to 6.7 with 20%NaOH, cold preservation 40 hours, draw supernatant, supernatant adds 2% active carbon and boiled 15 minutes, filters, cold preservation 24 hours, regulate pH value to 6.7, boiling sterilization 30 minutes, cold preservation 24 hours with 10%NaOH, draw supernatant liquid filtering, regulate pH value to 6.7, add the water fresh water for injection to 6000ml, membrane filtration,, potting, sterilization, packing.
Embodiment 9: the P-glycoprotein (P-gp) of multidrug resistance cell and the detection of MRP1.
(1) experiment material:
Cell strain: K562/adr, MCF7/adr and KBV200 multidrug resistance cell strain are the cell of Pgp albumen high expressed.It is that MCF-7/adr and KBV200 multidrug resistance cell strain are available from Chinese Academy of Medical Sciences's Blood Research Institute that K562/adr is induced to build by the Zhejiang University institute of oncology.HL60/adr is the multidrug resistance tumor cells strain of MRP1 high expressed, available from Chinese Academy of Medical Sciences's Blood Research Institute.
The monoclonal fluorescent-labeled antibody of reagent: P-gp is U.S. company BD R-PE-17F9.MRP1 monoclonal fluorescent antibody is available from U.S. Santa Cruz company.
Instrument: culture bottle, culture plate, CO2 gas incubator, flow cytometer (FACS Calibur, U.S. Becton-Dickinson company).
(2) experimental technique:
Cell P-gp and MRP1 express and measure:
Each the strain cell of trophophase of taking the logarithm, collecting cell makes 1 * 10
6The suspension of/ml adds P-gp or MRP1 monoclonal antibody (1: 400), 4 ℃ of lucifuge reaction 45min, and PBS gives a baby a bath on the third day after its birth inferior, and after overhanging with PBS, flow cytometer detects cell fluorescence intensity.
(3) experimental result:
Fig. 1 is K562/ADR, MCF7/adr, the expression of the P-gp of KBV200 (P-glycoprotein) and its parent's susceptibility cell K562, the comparison of MCF-7 and KBV200.98% cellular expression P-gp is arranged in the K562/adr cell, and the K562 cell has only 1% cell that the expression of P-gp is arranged; 96% cellular expression P-gp is arranged in the MCF7/adr cell, and the MCF-7 cell has only 3% cell that the expression of P-gp is arranged; 92% cellular expression P-gp is arranged in the KBV200 cell, and the KB cell has only 1% cell that the expression of P-gp is arranged.Fig. 2 is K562/ADR, MCF7/adr, the expression of the P-gp of KBV200 (P-glycoprotein) and its parent's susceptibility cell K562, the comparison of MCF-7 and KBV200.The expression of K562/adr, MCF7/adr KBV200 cell P-gp is respectively its susceptibility parental cell K562, MCF-7 and KB cell 24.4,25.3 and 24.2 times.
Fig. 3 is the expression of MRP1 of HL60/adr and the comparison of its parent's susceptibility cell HL60.97% cellular expression MRP1 is arranged in the HL60 cell, and the HL60 cell has only 1% cell that the expression of MRP1 is arranged;
Fig. 4 is the expression of MRP1 of HL60/adr and the comparison of its parent's susceptibility cell HL60.The expression of HL60/adr cell MRP1 is 23.4 times of its susceptibility parental cell HL60 cell.
(4) conclusion:
K562/ADR, MCF7/adr, KBV200 are the multidrug resistance cell strain of P-gp high expressed.That is: P-gp is the main cause of these cell multidrug resistances.HL60/adr is the multidrug resistance cell strain of MRP1 high expressed, that is: MRP1 is the main cause of these cell multidrug resistances.
Embodiment 10: the antitumor action of Fructus Schisandrae Chinensis ethanol or methanolic extract
(1) experiment material:
Cell strain: human leukemia cell line K562, HL60, human liver cancer cell HepG2, human breast cancer cell MCF7, human large intestine cancer cell SW480 derives from U.S. ATCC company.Cultivation is in containing the RPMI1640 cell culture fluid of 10% calf serum.
Reagent: ethanol and methanolic extract by embodiment 2 method gained Fructus Schisandrae Chinensis are dissolved in DMSO respectively, are made into 100mg/ml as mother solution, are made into working solution with RPMI-1640 again.RPMI-1640 culture medium and calf serum are U.S. Gibco product; Tetramethyl azo azoles salt (MTT) is Sigma company product.
Instrument: culture bottle, culture plate, CO2 gas incubator, microplate reader, FCM.
(2) experimental technique:
Cell culture:
Cell strain: human leukemia cell line K562, HL60, human liver cancer cell HepG2, human breast cancer cell MCF7, human large intestine cancer cell SW480 cultivates in containing the RPMI1640 cell culture fluid of 10% calf serum.
The MTT check:
The trophophase cell of taking the logarithm, cell is inoculated in 96 well culture plates respectively, 10000 cell/100ul/ holes.At 37 ℃, 5%CO
2Under the condition after the overnight incubation, the schisandra chinensis ethyl hydrate extract 100ul that adds variable concentrations, zeroing hole and matched group add the culture fluid of respective volume, establish 4 parallel holes for every group, behind the cultivation 72h, every hole adds 5mg/ml MTT 20ul (except the zeroing group), cultivate 4h again, remove culture fluid, add DMSO 100ul/ hole, after Formazan to be crystallized dissolves fully, read absorbance (A) value after the zeroing of wavelength 570nm place zeroing group again with the enzyme linked immunological instrument.The mean of getting 4 hole A values by formula calculates cell inhibitory rate: cell inhibitory rate (IR)=[1-(experimental port A average/control wells A average)] * 100%.Calculating IR adopts Origin 7.0 data processing softwares to obtain half-inhibition concentration (IC with the match of Sigmodel function
50), every experiment triplicate.
Fructus Schisandrae Chinensis methanolic extract MTT testing sequence is the same.
(3) experimental result:
Experimental data such as table 1
Table 1. schisandra chinensis ethyl hydrate extract is to the killing activity of various human tumor cells
| Cell strain | IC 50(μg/ml) |
| K562 | 85 |
| HL60 | 56 |
| HepG2 | 87 |
| MCF7 | 67 |
| SW480 | 92 |
Conclusion: can find that from table 1 schisandra chinensis ethyl hydrate extract can effectively kill kinds of tumor cells.
Table 2. Fructus Schisandrae Chinensis methanolic extract is to the killing activity of various human tumor cells
| Cell strain | IC 50(μg/ml) |
| K562 | 78 |
| HL60 | 63 |
| HepG2 | 62 |
| MCF7 | 84 |
| SW480 | 75 |
Conclusion: can find that from table 2 the Fructus Schisandrae Chinensis methanolic extract also can effectively kill and wound kinds of tumor cells.Schisandra chinensis ethyl hydrate extract is similar to the lethal effect of tumor cell with methanolic extract.
Embodiment 11: schisandra chinensis ethyl hydrate extract is to people's Normocellular toxic action
(1) experiment material:
Material: people's normal peripheral blood mononuclear cells, human bone marrow mesenchymal cell, human liver cell, human fibroblasts are incubated in the RPMI1640 culture fluid that contains 15% calf serum.
Instrument: culture bottle, culture plate, CO2 gas incubator, microplate reader, FCM, high performance liquid chromatograph.
The ethanol extraction of reagent: embodiment 2 gained Fructus Schisandrae Chinensis is dissolved in DMSO, is made into 100mg/ml as mother solution, is made into working solution with RPMI-1640 again.RPMI-1640 culture medium and calf serum are U.S. Gibco product; Tetramethyl azo azoles salt (MTT) is Sigma company product.
Instrument: culture bottle, culture plate, CO2 gas incubator, microplate reader, FCM.
(2) experimental technique:
Cell strain: above cell culture is in containing the RPMI1640 cell culture fluid of 10% calf serum.Cell inoculation is in 96 porocyte culture plates, and 20000 cells in every hole divide into groups to add schisandra chinensis ethyl hydrate extract.Be positioned over CO
2Cultivate in the incubator, do the MTT experiment after 48 hours.
(3) experimental result:
Schisandra chinensis ethyl hydrate extract sees Table 3 to the toxicity data of 4 kinds of normal cells.Data show: schisandra chinensis ethyl hydrate extract is in the drug effect concentration range of energy kill tumor cell, to the normal cell avirulence.
Table 3 schisandra chinensis ethyl hydrate extract is to Normocellular killing activity
| Cell | IC 50(μg/ml) |
| The human peripheral blood mononuclear cell | ＞400 |
| Human liver cell | ＞400 |
| Human fibroblasts | ＞400 |
| The human bone marrow mesenchymal cell | ＞400 |
Embodiment 12: schisandra chinensis ethyl hydrate extract is to the toxic action of mice
Animal: the ICR mice is available from the Shanghai Experimental Animal Center.
Reagent: embodiment 2 gained schisandra chinensis ethyl hydrate extracts
Experimental technique: 7 mices, every mouse stomach schisandra chinensis ethyl hydrate extract (dosage: the 4g/kg body weight).
Observed for two weeks.
Experimental result: untoward reaction does not appear in 7 mices, illustrates that the toxicity of schisandra chinensis ethyl hydrate extract is very low.
Embodiment 13: Fructus Schisandrae Chinensis ethanol or methanolic extract gather daunorubicin in the multidrug resistance cell strain cell
(1) experiment material:
Cell strain: K562/adr, MCF7/adr, KBV200 multidrug resistance cell strain are main resistance mechanism with Pgp albumen high expressed.
Reagent: press embodiment 2 method gained Fructus Schisandrae Chinensis ethanol and methanolic extracts, be dissolved in DMSO respectively, be made into 100mg/ml, be made into working solution with RPMI-1640 again as mother solution; The RPMI-1640 culture medium; Daunorubicin.
Instrument: culture bottle, culture plate, FCM.
(2) experimental technique:
DNR gathers in the FACS method analysis of cells: K562/adr, MCF7/adr, KBV200 cell culture are in the fresh medium of no medicine.Experiment is divided into 2 groups, matched group and reverse group.Matched group adds fresh medium, and the reverse group adds the schisandra chinensis ethyl hydrate extract that concentration is respectively 50 μ g/ml, adds daunorubicin DNR after hatching 1h, and concentration is respectively 2 μ g/ml, and 37 ℃ of incubations are analyzed medicine with FCM after 90 minutes and gathered intracellular.
Fructus Schisandrae Chinensis methanolic extract experimental procedure as above.
(3) experimental result:
Fig. 5 illustrates that schisandra chinensis ethyl hydrate extract can increase daunorubicin gathering in MDR cell K562/Adr, MCF7/adr and KBV200 cell.
Fig. 6 illustrates that the Fructus Schisandrae Chinensis methanolic extract can increase daunorubicin gathering in MDR cell K562/adr, MCF7/adr and KBV200 cell.
Conclusion: Fructus Schisandrae Chinensis ethanol or methanolic extract can suppress the function of P-glycoprotein, and the drug accumulation in the recovery MDR tumor cell (Fig. 5, Fig. 6).
Embodiment 14: Fructus Schisandrae Chinensis ethanol or methanolic extract suppress MRP1
(1) experiment material:
Cell strain: the HL60/adr multidrug resistance cell strain is main resistance mechanism with MRP1 albumen high expressed.
Reagent: press embodiment 2 method gained Fructus Schisandrae Chinensis methanol or ethanol extractions, be dissolved in DMSO respectively, be made into 100mg/ml, be made into working solution with RPMI-1640 again as mother solution; The RPMI-1640 culture medium; Daunorubicin.
Instrument: culture bottle, culture plate, FCM.
(2) experimental technique:
Daunorubicin gathers in the FACS method analysis of cells: the HL60/adr cell culture is in the fresh medium of no medicine.Experiment is divided into 2 groups, matched group and reverse group.Matched group adds fresh medium, and the reverse group adds the schisandra chinensis ethyl hydrate extract that concentration is respectively 50 μ g/ml, adds daunorubicin DNR after hatching 1h, and concentration is respectively 2 μ g/ml, and 37 ℃ of incubations are analyzed medicine with FCM after 90 minutes and gathered intracellular.Fructus Schisandrae Chinensis methanolic extract test method as above.
(3) experimental result:
Fig. 7 illustrates that schisandra chinensis ethyl hydrate extract can increase daunorubicin gathering in MDR cell HL60/adr cell.
Does (correlogram of schisandra chinensis ethyl hydrate extract have? this is an extract, is an extractum.) conclusion: Fructus Schisandrae Chinensis ethanol or methanolic extract can suppress the function of MRP1, recover the drug accumulation (Fig. 7) in the MDR tumor cell.
Embodiment 15: schisandra chinensis ethyl hydrate extract is to the dose-effect relationship cell of the multi-drug resistance of the tumor of P-gp mediation: the K562/adr multidrug resistance cell strain is main resistance mechanism with Pgp albumen high expressed.
Reagent: embodiment 1 gained schisandra chinensis ethyl hydrate extract is dissolved in DMSO, is made into 100mg/ml as mother solution, is made into working solution with RPMI-1640 again; The RPMI-1640 culture medium; Daunorubicin.
Experimental technique:
Cell inoculation is to 96 porocyte culture plates, and 8000 cells in every hole after the overnight incubation, add the anticarcinogen (paclitaxel, amycin or vincristine etc.) of variable concentrations schisandra chinensis ethyl hydrate extract and variable concentrations, continue to cultivate after 72 hours, do the MTT experiment.Cell inhibitory rate (IR)=[1-(experimental port A average/control wells A average)] * 100%.Calculating IR adopts Origin 7.0 data processing softwares to obtain half-inhibition concentration (IC with the match of Sigmodel function
50), every experiment triplicate.Schisandra chinensis ethyl hydrate extract is that IC50 (adding schisandra chinensis ethyl hydrate extract) is divided by IC50 (not adding schisandra chinensis ethyl hydrate extract) to the drug resistance reverse multiple of MDR cell.
Experimental result:
Schisandra chinensis ethyl hydrate extract is dose dependent to the reverse of multidrug resistance in concentration is 12.5 μ g/ml to 50 μ g/ml scopes, increase schisandra chinensis ethyl hydrate extract concentration again, the unkehr effect of multidrug resistance is no longer increased, referring to Fig. 8.
Embodiment 16: Fructus Schisandrae Chinensis ethanol or methanolic extract are to the reverse of the multi-drug resistance of the tumor of P-gp mediation
Cell: K562/adr, MCF7/adr, KBV200 multidrug resistance cell strain are main resistance mechanism with Pgp albumen high expressed.
Reagent: press embodiment 1 method gained schisandra chinensis ethyl hydrate extract and methanolic extract, be dissolved in DMSO respectively, be made into 100mg/ml, be made into working solution with RPMI-1640 again as mother solution; The RPMI-1640 culture medium; Daunorubicin.
Instrument: culture bottle, culture plate, FCM.
Experimental technique:
Cell inoculation is to 96 porocyte culture plates, and 8000 cells in every hole after the overnight incubation, add schisandra chinensis ethyl hydrate extract and anticarcinogen (paclitaxel, amycin or vincristine etc.), continue to cultivate after 72 hours, do the MTT experiment.Cell inhibitory rate (IR)=[1-(experimental port A average/control wells A average)] * 100%.Calculating IR adopts Origin 7.0 data processing softwares to obtain half-inhibition concentration (IC with the match of Sigmodel function
50), every experiment triplicate.Schisandra chinensis ethyl hydrate extract is that IC50 (adding Fructus Schisandrae Chinensis ethanol or methanolic extract) is divided by IC50 (not adding Fructus Schisandrae Chinensis ethanol or methanolic extract) to the drug resistance reverse multiple of MDR cell.
Experimental result:
Schisandra chinensis ethyl hydrate extract can reverse the Drug resistance of multidrug resistance tumor cells.The results are shown in Table 4, table 5, table 6, table 7, table 8.
Table 4: schisandra chinensis ethyl hydrate extract (50 μ g/ml) is to the K562/ADR drug resistance inversion
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add schisandra chinensis ethyl hydrate extract | Add schisandra chinensis ethyl hydrate extract | ||
| Daunorubicin | 1.61 | 0.15 | 10.7 |
| Paclitaxel | 1.1 | 0.41 | 2.7 |
| Vincristine | 0.87 | 0.11 | 7.9 |
Table 5: Fructus Schisandrae Chinensis methanolic extract (50 μ g/ml) is to the K562/ADR drug resistance inversion
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add the Fructus Schisandrae Chinensis methanolic extract | Add the Fructus Schisandrae Chinensis methanolic extract | ||
| Daunorubicin | 1.61 | 0.20 | 8.1 |
| Paclitaxel | 1.1 | 0.35 | 3.1 |
| Vincristine | 0.87 | 0.14 | 5.0 |
Table 6: schisandra chinensis ethyl hydrate extract (50 μ g/ml) is to the drug resistance inversion of KBV200
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add schisandra chinensis ethyl hydrate extract | Add schisandra chinensis ethyl hydrate extract | ||
| Daunorubicin | 0.2 | 0.02 | 10 |
| Vincristine | 0.42 | 0.031 | 13.5 |
Table 7: schisandra chinensis ethyl hydrate extract (50 μ g/ml) is to the MCF7/adr drug resistance inversion
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add schisandra chinensis ethyl hydrate extract | Add schisandra chinensis ethyl hydrate extract | ||
| Daunorubicin | 0.32 | 0.031 | 10.3 |
| Paclitaxel | 0.73 | 0.25 | 2.9 |
| Vincristine | 0.49 | 0.21 | 2.3 |
Table 8: Fructus Schisandrae Chinensis methanolic extract (50 μ g/ml) is to the MCF7/adr drug resistance inversion
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add the Fructus Schisandrae Chinensis methanolic extract | Add the Fructus Schisandrae Chinensis methanolic extract | ||
| Daunorubicin | 0.32 | 0.027 | 11.9 |
| Paclitaxel | 0.73 | 0.19 | 3.8 |
| Vincristine | 0.49 | 0.23 | 1.8 |
Conclusion: Fructus Schisandrae Chinensis ethanol or methanolic extract can suppress the multi-drug resistance of the tumor of P-gp mediation.
Embodiment 17: schisandra chinensis ethyl hydrate extract or methanolic extract reverse the multi-drug resistance of the tumor of MRP1 mediation
Cell: the HL60/adr multidrug resistance cell strain is main resistance mechanism with MRP1 albumen high expressed.
Reagent: press embodiment 2 method gained Fructus Schisandrae Chinensis ethanol or methanolic extracts, be dissolved in DMSO respectively, be made into 100mg/ml, be made into working solution with RPMI-1640 again as mother solution; The RPMI-1640 culture medium.
Instrument: culture bottle, culture plate, FCM.
Experimental technique:
Cell inoculation is to 96 porocyte culture plates, and 8000 cells in every hole after the overnight incubation, add schisandra chinensis ethyl hydrate extract and anticarcinogen (paclitaxel, amycin or vincristine etc.), continue to cultivate after 72 hours, do the MTT experiment.Cell inhibitory rate (IR)=[1-(experimental port A average/control wells A average)] * 100%.Calculating IR adopts Origin 7.0 data processing softwares to obtain half-inhibition concentration (IC with the match of Sigmodel function
50), every experiment triplicate.Schisandra chinensis ethyl hydrate extract is that IC50 (adding Fructus Schisandrae Chinensis ethanol or methanolic extract) is divided by IC50 (not adding Fructus Schisandrae Chinensis ethanol or methanolic extract) to the drug resistance reverse multiple of MDR cell.
Fructus Schisandrae Chinensis methanolic extract experimental technique is the same.
Experimental result:
Schisandra chinensis ethyl hydrate extract or methanolic extract can reverse the Drug resistance of multidrug resistance tumor cells HL60/adr.The results are shown in Table 9 and table 10.
Table 9. schisandra chinensis ethyl hydrate extract (50 μ g/ml) is to the drug resistance inversion of HL60/adr
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add schisandra chinensis ethyl hydrate extract | Add schisandra chinensis ethyl hydrate extract | ||
| Daunorubicin | 0.50 | 0.01 | 50 |
| Paclitaxel | 0.001 | 0.0001 | 10 |
| Vincristine | 0.050 | 0.001 | 50 |
Table 10. Fructus Schisandrae Chinensis methanolic extract (50 μ g/ml) is to the drug resistance inversion of HL60/adr
| Medicine | IC 50 | Drug resistance is contrary |
| Do not add the Fructus Schisandrae Chinensis methanolic extract | Add the Fructus Schisandrae Chinensis methanolic extract | Change multiple | |
| Daunorubicin | 0.50 | 0.013 | 38 |
| Paclitaxel | 0.001 | 0.0001 | 10 |
| Vincristine | 0.050 | 0.0015 | 33 |
Conclusion: Fructus Schisandrae Chinensis ethanol or methanolic extract can suppress the MRP1 function, reverse the multi-drug resistance of the tumor of MRP1 mediation.
Embodiment 18: schisandra chinensis ethyl hydrate extract reverses the multi-drug resistance of the tumor of BCRP (MXR) mediation
Cell: melanoma cell strain 8226/MX20 multidrug resistance cell strain is main resistance mechanism with BCRP albumen high expressed.This cell strain by Minderman etc. set up (Minderman H, Brooks TA, O ' Loughlin KL, et al:Cancer Chemother Pharmacol, 53:363-3692004).
Reagent: embodiment 2 gained schisandra chinensis ethyl hydrate extracts are dissolved in DMSO, are made into 100mg/ml as mother solution, are made into working solution with RPMI-1640 again; The RPMI-1640 culture medium.
Instrument: culture bottle, culture plate, FCM.
Experimental technique:
Cell inoculation is to 96 porocyte culture plates, and 8000 cells in every hole after the overnight incubation, add schisandra chinensis ethyl hydrate extract and anticarcinogen (rice takes off anthraquinone, daunorubicin), continue to cultivate after 72 hours, do the MTT experiment.Cell inhibitory rate (IR)=[1-(experimental port A average/control wells A average)] * 100%.Calculating IR adopts Origin 7.0 data processing softwares to obtain half-inhibition concentration (IC with the match of Sigmodel function
50), every experiment triplicate.Schisandra chinensis ethyl hydrate extract is that IC50 (adding schisandra chinensis ethyl hydrate extract) is divided by IC50 (not adding schisandra chinensis ethyl hydrate extract) to the drug resistance reverse multiple of MDR cell.
Experimental result: schisandra chinensis ethyl hydrate extract can reverse the Drug resistance of multidrug resistance tumor cells HL60/adr.The results are shown in Table 11.
Table 11: schisandra chinensis ethyl hydrate extract (50 μ g/ml) is to the drug resistance inversion of 8226/MX20
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add schisandra chinensis ethyl hydrate extract | Add schisandra chinensis ethyl hydrate extract | ||
| Daunorubicin | 0.42 | 0.041 | 10 |
| Rice takes off anthraquinone | 0.23 | 0.035 | 6.7 |
Conclusion: schisandra chinensis ethyl hydrate extract (50 μ g/ml) can reverse the multidrug resistance of BCRP (MXR) mediation.
The extract of embodiment 13 to 18 explanation Fructus Schisandrae Chinensis can effectively suppress P-gp, MRP1 and BCRP, the resistance that this three ' Teat pipette ' can make tumor cell produce multiple anticarcinogen (sees Gottesman MM etal:Nature Medicine for details, 2:48-58,2001; Krishna R etal:European Journal ofPharmaceutical Science 11:265-283,2000).In the research of MDR reversing drug, generally acknowledge as long as determine the target spot of MDR reversing drug effect, and energy reversion MDR cell is to the Drug resistance of typical anticarcinogen, but just can think Drug resistance (Teodori Eetal:Il Parmaco 57:385-415,2002 of this medicine reversion MDR tumor to other drug; Seelig A et al:European Journal ofPharmaceutical Sceinces 12:31-40,2000; United States Patent Serial No003215; United States Patent Serial No 714506; United States Patent Serial No354443).We have confirmed the action target spot (P-gp of Fructus Schisandrae Chinensis extrat in an embodiment, MRP1 and BCRP), and clear and definite Fructus Schisandrae Chinensis extrat effectively the Drug resistance of the right typical medicaments of reversion MDR tumor cell reverse, but so the inference Fructus Schisandrae Chinensis extrat also the reversion MDR tumor to the Drug resistance of other antitumor drug.
In sum: Fructus Schisandrae Chinensis extrat can efficiently kill kinds of tumor cells, therefore can be made into antitumor drug; Fructus Schisandrae Chinensis extrat also can effectively reverse the multi-drug resistance of the tumor by mediations such as P-gp, MRP1, BCRP, and therefore, Fructus Schisandrae Chinensis extrat can be made into the medicine of reverse multiple drug resistance of tumor, and has clear and definite target spot.
Embodiment 19: the Fructus Schisandrae Chinensis supercritical extract reverses the multi-drug resistance of the tumor of BCRP (MXR) mediation
Cell: K562/adr, MCF7/adr, HL60/adr, 8226/MX20
Reagent: embodiment 3 gained Fructus Schisandrae Chinensis supercritical extract are dissolved in DMSO, are made into 100mg/ml as mother solution, are made into working solution with RPMI-1640 again; The RPMI-1640 culture medium.
Instrument: culture bottle, culture plate, FCM.
Experimental technique:
Cell inoculation is to 96 porocyte culture plates, and 8000 cells in every hole after the overnight incubation, add Fructus Schisandrae Chinensis supercritical extract and anticarcinogen, continue to cultivate after 72 hours, do the MTT experiment.Cell inhibitory rate (IR)=[1-(experimental port A average/control wells A average)] * 100%.Calculating IR adopts Origin 7.0 data processing softwares to obtain half-inhibition concentration (IC with the match of Sigmodel function
50), every experiment triplicate.The Fructus Schisandrae Chinensis supercritical extract is that IC50 (Fructus Schisandrae Chinensis supercritical extract) is divided by IC50 (Fructus Schisandrae Chinensis supercritical extract) to the drug resistance reverse multiple of MDR cell.
Experimental result: the Fructus Schisandrae Chinensis supercritical extract can reverse the multi-drug resistance of the tumor by Pgp, MRP1 and MXR mediation.
Table 12: Fructus Schisandrae Chinensis supercritical extract (50 μ g/ml) is to the K562/ADR drug resistance inversion
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add the Fructus Schisandrae Chinensis supercritical extract | Add the Fructus Schisandrae Chinensis supercritical extract | ||
| Daunorubicin | 1.61 | 0.11 | 14.6 |
| Paclitaxel | 1.1 | 0.32 | 3.4 |
| Vincristine | 0.87 | 0.15 | 5.8 |
Conclusion: the Fructus Schisandrae Chinensis supercritical extract can reverse the multi-drug resistance of the tumor by the Pgp mediation
Table 13: Fructus Schisandrae Chinensis supercritical extract (50 μ g/ml) is to the MCF7/ADR drug resistance inversion
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add the Fructus Schisandrae Chinensis supercritical extract | Add the Fructus Schisandrae Chinensis supercritical extract | ||
| Daunorubicin | 0.32 | 0.021 | 15.2 |
| Paclitaxel | 0.73 | 0.13 | 5.6 |
| Vincristine | 0.49 | 0.15 | 3.3 |
Conclusion: the Fructus Schisandrae Chinensis supercritical extract can suppress the multi-drug resistance of the tumor of P-gp mediation.
Table 14. Fructus Schisandrae Chinensis supercritical extract (50 μ g/ml) is to the drug resistance inversion of HL60/adr
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add the Fructus Schisandrae Chinensis supercritical extract | Add the Fructus Schisandrae Chinensis supercritical extract | ||
| Daunorubicin | 0.50 | 0.021 | 24 |
| Paclitaxel | 0.001 | ＜0.0001 | ＞10 |
| Vincristine | 0.050 | 0.0022 | 23 |
Conclusion: Fructus Schisandrae Chinensis supercritical extract extract can suppress the MRP1 function, reverses the multi-drug resistance of the tumor of MRP1 mediation.
Table 15: Fructus Schisandrae Chinensis supercritical extract (50 μ g/ml) is to the drug resistance inversion of 8226/MX20
| Medicine | IC 50 | Drug resistance reverses multiple | |
| Do not add the Fructus Schisandrae Chinensis supercritical extract | Add the Fructus Schisandrae Chinensis supercritical extract | ||
| Daunorubicin | 0.42 | 0.032 | 13.1 |
| Rice takes off anthraquinone | 0.23 | 0.042 | 5.5 |
Conclusion: the Fructus Schisandrae Chinensis supercritical extract can reverse the multidrug resistance of BCRP (MXR) mediation.
In sum, Fructus Schisandrae Chinensis extrat is the multidrug resistance of reversing tumor effectively, and its safety is good, therefore has bigger potential applicability in clinical practice.
Claims (14)
1. the application of Fructus Schisandrae Chinensis in preparation tumor multidrug-resistance inversion agent medicine.
2. the application of Fructus Schisandrae Chinensis as claimed in claim 1 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that: the application of the extract of described Fructus Schisandrae Chinensis in preparation tumor multidrug-resistance inversion agent medicine.
3. the application of Fructus Schisandrae Chinensis as claimed in claim 2 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that: the extract of described Fructus Schisandrae Chinensis is the extract of organic solvent of Fructus Schisandrae Chinensis or the extract that obtains with supercritical process.
4. the application of Fructus Schisandrae Chinensis as claimed in claim 1 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that described inversion agent medicine reverses the multidrug resistance of the tumor cell that is caused by the P-glycoprotein.
5. the application of Fructus Schisandrae Chinensis as claimed in claim 1 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that described inversion agent medicine reverses the multidrug resistance of the tumor cell that is caused by multidrug-associated protein.
6. the application of Fructus Schisandrae Chinensis as claimed in claim 1 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that described inversion agent medicine reverses the multidrug resistance by the tumor cell of breast carcinoma sorcin.
7. the application of Fructus Schisandrae Chinensis as claimed in claim 1 in preparation tumor multidrug-resistance inversion agent medicine, it is characterized in that: described inversion agent medicine also contains the antitumor drug of Fructus Schisandrae Chinensis as tumor multidrug-resistance inversion agent sensitivity, and drug excipient or carrier.
8. the application of Fructus Schisandrae Chinensis as claimed in claim 3 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that: described antitumor drug is one of following or the mixing of its arbitrary proportion:
1. the 2. 3. substrate of BCRP of substrate of MRP1 of the substrate of P-glycoprotein.
9. the application of Fructus Schisandrae Chinensis as claimed in claim 8 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that: described antitumor drug is one of following or two or more mixing with arbitrary proportion:
The Doxorubicin amycin; The Actinomycin D actinomycin D; Altreatamine;
The Bleomycin bleomycin; The Busulphan busulfan; The Capecitabine capecitabine;
The Carboplatin carboplatin; The Carmustine carmustine; The Chlorambucil chlorambucil;
The Cisplatin cisplatin; The cyclophosphamide cyclophosphamide; The cytarbine cytosine arabinoside;
Dacarabazine, the daunorubicin daunorubicin; The epirubicin epirubicin; The etoposide etoposide; Etoposide; Etoposide; The acid of fludarbine fluorine vidarabine;
The fluorouracil fluorouracil; The gemcitabine gemcitabine; The herceptin Trastuzumab;
The hydroxyurea hydroxyurea; The idarubicin idarubicin; The ifosfamide ifosfamide;
The irinotecan Irinotecan; The lomustine lomustine; Lomustine; The melphalan melphalan; Alkeran; The mercaptopurine purinethol; The methotrexate methotrexate; The mitomycin mitomycin; The mitozantrone mitoxantrone; Dithranol;
The oxaliplatin oxaliplatin; The procarbazine procarbazine; First (base) benzyl hydrazine; The rituxan Mabthera; The steroids steroid; The streptozocin streptozocin; Streptozotocin; The taxol paclitaxel, the taxotere taxotere; Tamozolomide, the thioguanine thioguanine; The thiotepa thio-tepa; Thiotef; Tespamin; Tomudex Raltitrexed (raltitrexed); The topotecan topotecan; The treosulfan treosulfan; The uracil-tegufur uracil; The vinblastine vinblastine; Vincaleucoblastine; The vindesine vindesine; The vinorelbine vinorelbine.
10. the application of Fructus Schisandrae Chinensis as claimed in claim 1 in preparation tumor multidrug-resistance inversion agent medicine is characterized in that described inversion agent medicine can be made into one of following dosage form:
1. 2. 3. 4. 5. decoction of granule of capsule of tablet of injection.
11., it is characterized in that described inversion agent medicine can also contain other inversion agent as the application of the described Fructus Schisandrae Chinensis of one of claim 1～6 in preparation tumor multidrug-resistance inversion agent medicine.
12., it is characterized in that described inversion agent medicine can also contain other Chinese medicine extract as the application of the described Fructus Schisandrae Chinensis of one of claim 1～6 in preparation tumor multidrug-resistance inversion agent medicine.
13. the application of Fructus Schisandrae Chinensis in preparation medicine for treating tumor thing.
14. want the application of 13 described Fructus Schisandrae Chinensis in preparation medicine for treating tumor thing as right, it is characterized in that the application of described Fructus Schisandrae Chinensis extrat in preparation medicine for treating tumor thing.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102908405A (en) * | 2012-09-29 | 2013-02-06 | 暨南大学 | Traditional Chinese medicine composition of reversing tumor multi-drug resistance (MDR) and preparation method thereof |
| CN103721189A (en) * | 2013-12-27 | 2014-04-16 | 刘玉含 | Meningeoma nursing medicine and preparation method thereof |
| CN115044411A (en) * | 2022-05-25 | 2022-09-13 | 湖南诺泽生物科技有限公司 | Schisandra chinensis essential oil and preparation method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102908405A (en) * | 2012-09-29 | 2013-02-06 | 暨南大学 | Traditional Chinese medicine composition of reversing tumor multi-drug resistance (MDR) and preparation method thereof |
| CN102908405B (en) * | 2012-09-29 | 2014-12-31 | 暨南大学 | Traditional Chinese medicine composition of reversing tumor multi-drug resistance (MDR) and preparation method thereof |
| CN103721189A (en) * | 2013-12-27 | 2014-04-16 | 刘玉含 | Meningeoma nursing medicine and preparation method thereof |
| CN115044411A (en) * | 2022-05-25 | 2022-09-13 | 湖南诺泽生物科技有限公司 | Schisandra chinensis essential oil and preparation method and application thereof |
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