CN100584352C - Fructus Schisandrae Chinensis and extract thereof the purposes in preparation treatment tumor multi-medicine drug-resistant medicine - Google Patents
Fructus Schisandrae Chinensis and extract thereof the purposes in preparation treatment tumor multi-medicine drug-resistant medicine Download PDFInfo
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Abstract
The present invention relates to five tastes of medicinal herb, Fructus Schisandrae Chinensis extrat new purposes, particularly share the tumor that treatment has multidrug resistance, improve sensitivity and the antineoplastic new purposes of tumor cell anticarcinogen with antitumor drug as multidrug-resistance reversal agent.
Description
Technical field
The present invention relates to Fructus Schisandrae Chinensis, Fructus Schisandrae Chinensis extrat new purposes, particularly share the tumor that treatment has multidrug resistance, improve the new purposes of tumor cell the sensitivity of anticarcinogen with antitumor drug as multidrug-resistance reversal agent.The invention still further relates to the new purposes of Fructus Schisandrae Chinensis antineoplastic.
Background technology
Tumor cell has one of major reason that inherent drug resistance remains the chemotherapy of tumors failure through the acquired drug-resistance that produces after the chemotherapy and some tumor cell itself.The mechanism that produces multidrug resistance is very complicated, the overexpression that is present in the multidrug resistance glycoprotein (P-gp) on the tumor cell membrane is main mechanism, many chemotherapeutics all are the substrates of P-gp, for example vinca, anthracene nucleus class, epipodophyllotoxin class, taxanes etc.Thereby the multidrug resistance of reversing tumor cell makes tumor cell recover that the sensitivity of chemotherapeutics is had very important clinical value.Have been found that so far many chemical compounds have very strong tumor multi-drug resistance reversal effect in external and interior animal experiment, as comprise calcium channel blocker, calmodulin, CaM antagonist, cyclosporine, quinolines, the anti-estrogens of verapamil, yet apply to clinically, except that the tumor drug resistance to some blood system has comparatively sure reverse effect, very undesirable to the drug-fast reverse effect of solid tumor.It is generally acknowledged, these chemical compounds can not reach effective reverse concentration in vivo under the human body tolerable dose, in case and escalated dose arrives its blood drug level to have in vitro tests when reversing active concentration, will produce serious toxic and side effects, can change the pharmacokinetic parameter of antitumor drug when perhaps inversion agent and antitumor drug share, thereby produce unpredictalbe toxicity.For example, as the verapamil of positive control,, be applied to and but find in the body when not reaching reversing drug resistance concentration, just to have produced Cardiovascular Toxicity, thereby limited its use clinically among the present invention though very strong tumor drug resistance reversal activity arranged external.So the multidrug-resistance reversal agent that developmental function is strong and toxic and side effects is little remains the main direction of research.
Fructus Schisandrae Chinensis is a Chinese medicine commonly used among the people, and Bearberry Extract is astringent or styptic treatment for spontaneous sweating, supplementing QI for promoting the production of body fluid, and the kidney calming effect, medical value is very high, is rare tonic, and its main chemical is schizandrin, volatile oil, benzene fruit acid etc.It can regulate cardiovascular system, improves blood circulation, promotes liver cell regeneration, strengthens the detoxification ability of liver, is the good medicine that cures mainly psychasthenia, dysentery, night sweat and hepatic disease.It also has excitation to the refreshing smart system of people's maincenter, and abnormal blood pressure is had Accommodation.In addition, the clothes Fructus Schisandrae Chinensis can also improve vision, and helps to treat ophthalmic.Discover; Fructus Schisandrae Chinensis multiple components energy the liver protecting is avoided the infringement of some chemical toxicants; and energy antagonism oxygen free radical injury; stimulate the anabolism of liver and the activity of enhancing Cytochrome P450, schisandrin B, third element, pure second, ester second, ester third, ester fourth etc. are the effective ingredient of transaminase lowering in 28 kinds of compositions in the Schizandra.Clinical liver-protecting tablet (two crane pharmacy) now commonly used, fall enzyme curing capsule (pharmacy of Asia-Pacific, Hunan), compound hepatitis B spirit (Double-Crane Pharmaceutical Co., Ltd) etc. and all have good enzyme and the liver-protecting activity of falling.
Recently there are some researches show also that Fructus Schisandrae Chinensis can strengthen cerebral cortex excitement and process of inhibition, make its mutual balance.Fructus Schisandrae Chinensis extrat has obvious sedation, with associations such as pentobarbital sodium, chlorpromazine with the convulsions that can the antagonism beta stimulant causes, the characteristics of tranquilizer are arranged.The main component of SHENGMAI ZHUSHEYE (Taihang pharmacy) also is a Fructus Schisandrae Chinensis, the clinical QIYINLIANGXU that is mainly used in, the cardiopalmus that deficient pulse is desired to take off, breathe hard, extremity are terribly cold, sweating, arteries and veins reach myocardial infarction, cardiogenic shock, septic shock etc. wild and have above-mentioned patient.
Summary of the invention
In order to overcome the deficiencies in the prior art part, main purpose of the present invention is to provide the new purposes of a kind of Fructus Schisandrae Chinensis extrat in the preparation multidrug resistance reversing agent.
Another object of the present invention is to provide a kind of Fructus Schisandrae Chinensis extrat to reach and the coupling of antitumor drug.
Described antitumor drug is included as the antitumor drug of P-gp substrate.The antitumor drug of described P-gp substrate comprises anthracene nucleus class, vinca, taxanes, Rhizoma Dysosmae Versipellis class, and mitoxantrone, actinomycin D, ametycin.Described tumor comprises inherent multidrug resistance with P-gp overexpression and entity tumor and the hematological system tumor that produces the acquisition multidrug resistance at chemotherapy process.
Therefore, the Fructus Schisandrae Chinensis extrat that the present invention relates to can be used to prevent and treat the multidrug resistance of reversing tumor.In other words, will contain patient's administration that the Pharmaceutical composition of Fructus Schisandrae Chinensis prevents and/or treats to needs.
The KBv200 cell multidrug resistance cell strain that to be human oral cavity epithelial cancer KB cell obtain through the vincristine screening is 230 times of responsive KB cell to the acquisition drug resistance of vincristine, and the cross resistance of amycin and paclitaxel is respectively 11 and 148 times.Fructus Schisandrae Chinensis extrat can reverse the KBv200 cell to the acquisition drug resistance of vincristine and to the cross resistance of amycin and paclitaxel, and presents tangible dose-dependence.The Fructus Schisandrae Chinensis extrat of 25 μ g/ml makes the half-inhibition concentration (IC of KBv200 cell vincristine
50) reduce to 4nmol/L by 2479nmol/L, reversing multiple is 637 times; Make the IC of amycin
50Reduce to 48nmol/L by 667nmol/L, reversing multiple is 14 times; Make the IC of paclitaxel
50Reducing to the reverse multiple by 1243ng/ml is 187.And at the KB of sensitivity cell, the Fructus Schisandrae Chinensis extrat under the same dose is to the IC of above-mentioned antineoplastic agent
50Influence very little.
MCF-7/Adr cell a kind of multidrug resistance cell strain that to be human breast carcinoma MCF-7 cell obtain through the amycin screening is 140 times of MCF-7 cell to the acquisition drug resistance of amycin.Fructus Schisandrae Chinensis extrat can reverse the drug resistance of MCF-7/Adr cell to amycin, and presents tangible dose-dependence.25 μ g/ml Fructus Schisandrae Chinensis extrats make the IC of MCF-7/Adr cell amycin
50Reduce to 401nmol/L by 45241nmol/L, reversing multiple is 27 times.Equally, for the MCF-7 cell of sensitivity, the Fructus Schisandrae Chinensis extrat of above-mentioned concentration is less to the sensitivity influence of amycin.
This shows the acquired multidrug resistance that Fructus Schisandrae Chinensis extrat can the reversing tumor cell.For the tumor cell of inherent multidrug resistance, Fructus Schisandrae Chinensis extrat also has very strong reverse effect, and also has tangible dose dependent.People's hepatocarcinoma Bel
7402Cell strain has inherent multidrug resistance, and Fructus Schisandrae Chinensis extrat makes Bel
7402Cell increases the sensitivity of vincristine and amycin, and wherein 25 μ g/ml Fructus Schisandrae Chinensis extrats make Bel
7402The IC of cell vincristine
50Reduce to 1.2nmol/L by 1776.8nmol/L, reversing multiple is 1563 times, makes the IC of amycin
50Reduce to 82nmol/L by 761nmol/L, reversing multiple is 9 times.
Conclude above result, Fructus Schisandrae Chinensis extrat reverses the drug-fast multiple of kinds of tumor cells medicine and sees the following form:
Annotate: drug resistance reversal fold=IC
50(antineoplastic agent)/IC
50(antineoplastic agent+be subjected to examination to reverse medicine)
The nude mice test shows that Fructus Schisandrae Chinensis extrat of the present invention shows good reverse multiple drug resistance of tumor activity in animal body equally.We have set up the drug-fast transplantability human tumor of vincristine model (KBv200 transplanted solid tumor) with nude mice, found that, independent lumbar injection vincristine 0.4mg/Kg, per two days once, totally 5 times, drug-fast KBv200 transplanted tumor only there is faint inhibitory action (compare tumour inhibiting rate is 12.7% with the blank group).Fructus Schisandrae Chinensis extrat is oral, once a day, totally 14 times, can significantly strengthen the inhibitory action of vincristine to the KBv200 transplanted tumor, wherein, 100,200 and 300mg/Kg Fructus Schisandrae Chinensis extrat and vincristine share, tumour inhibiting rate is respectively 27.6%, 25.2% and 41.9%, illustrate that Fructus Schisandrae Chinensis extrat and vincristine share, can significantly increase the sensitivity of drug-resistant tumor vincristine.It is existing that mensuration is respectively organized the nude mouse repeating transmission, respectively organizes body weight before and after the treatment all less than obvious decline, illustrates that it is safe and effective that Fructus Schisandrae Chinensis extrat and vincristine share the treatment drug-resistant tumor.
Fructus Schisandrae Chinensis extrat itself also has anti-tumor activity under higher dosage, 400 and the 600mg/Kg Fructus Schisandrae Chinensis extrat can significantly suppress the growth of H22 hepatocarcinoma, the 400mg/Kg Fructus Schisandrae Chinensis extrat can also significantly suppress the growth of S180 sarcoma.
The mechanism that further studies show that the Fructus Schisandrae Chinensis extrat reversal of multidrug resistance of tumor cells of the present invention is that activity and the expression with its inhibition multidrug resistance glycoprotein (P-gp) has substantial connection.
The activity that suppresses P-gp medicine efflux pump, and then increase the accumulation of anticarcinogen in the tumor cell is one of important mechanisms of the reversal agent of drug resistance chemosensitivity that increases anticarcinogen.Amycin is the anticarcinogen of anthracene nucleus class, can autofluorescence, and therefore use the fluorescence intensity that spectrofluorophotometer can detect amycin, thereby determine the content of amycin.When giving amycin, add Fructus Schisandrae Chinensis extrat 25 μ g/ml and Bel
7402Cell combined effect 3 hours can make the accumulation of amycin in the cell increase by 2～3 times, and is similar to 20 μ mol/L verapamil effects, and analyzing by statistics all has utmost point significant difference.Illustrate that thereby Fructus Schisandrae Chinensis extrat can increase antitumor drug and have the activity that reverses multidrug resistance intracellular the accumulating of drug-resistant tumor.
In sum, Fructus Schisandrae Chinensis extrat reverses the mechanism and the activity and the overexpression that suppress P-gp of multidrug resistance, accumulates relevant in the drug-resistant tumor cell and increased anticarcinogen.
According to embodiment of the present invention, described Fructus Schisandrae Chinensis extrat is acceptable on the pharmacodynamics, uses the Fructus Schisandrae Chinensis extrat that any method is extracted.
The invention still further relates to the pharmaceutical composition that contains Fructus Schisandrae Chinensis extrat and antitumor drug.For realizing purpose of the present invention, preferred antitumor drug is included as the antitumor drug of P-gp substrate; The antitumor drug of preferred P-gp substrate comprises anthracene nucleus class, vinca, taxanes, Rhizoma Dysosmae Versipellis class, and mitoxantrone, actinomycin D, ametycin; The antitumor drug of preferred P-gp substrate comprises vincristine, amycin, paclitaxel.
Therefore the present invention also relates to the pharmaceutical composition that contains Fructus Schisandrae Chinensis extrat and conventional medicine excipient or adjuvant.Usually pharmaceutical composition of the present invention contains the Fructus Schisandrae Chinensis extrat of 0.1-99% weight, or the Fructus Schisandrae Chinensis extrat of 0.1-99% weight and antitumor drug.
Pharmaceutical composition of the present invention can prepare according to methods known in the art.When being used for this purpose, if desired, effective ingredient and one or more solids or liquid medicine excipient and/or adjuvant can be combined, make and can be used as suitable administration form or the dosage form that people's medicine uses.
Pharmaceutical composition of the present invention can the unit dosage form administration, and route of administration can be intestinal or non-intestinal, as oral, muscle, subcutaneous, nasal cavity, oral mucosa, skin, peritoneum or rectum etc.
The route of administration of pharmaceutical composition of the present invention can be drug administration by injection.Injection comprises intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection and acupoint injection therapy etc.
Form of administration can be liquid dosage form, solid dosage forms.As liquid dosage form can be true solution class, colloidal type, particulate formulations, emulsion dosage form, mixed suspension form.Other dosage forms are tablet, capsule, drop pill, aerosol, pill, powder, solution, suspensoid, Emulsion, granule, suppository, lyophilized injectable powder etc. for example.
Pharmaceutical composition of the present invention can be made ordinary preparation, also can be slow releasing preparation, controlled release preparation, targeting preparation and various particulate delivery system.
For the unit form of administration is made tablet, can be extensive use of various carrier well known in the art.Example about carrier is, for example diluent and absorbent are as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, carbamide, calcium carbonate, kaolin, microcrystalline Cellulose, aluminium silicate etc.; Wetting agent and binding agent are as water, glycerol, Polyethylene Glycol, ethanol, propanol, starch slurry, dextrin, syrup, Mel, glucose solution, mucialga of arabic gummy, gelatine size, sodium carboxymethyl cellulose, lac, methylcellulose, potassium phosphate, polyvinylpyrrolidone etc.; Disintegrating agent, for example dry starch, alginate, agar powder, laminaran, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.; Disintegrate inhibitor, for example sucrose, glyceryl tristearate, cocoa butter, hydrogenation wet goods; Absorption enhancer, for example quaternary ammonium salt, sodium lauryl sulphate etc.; Lubricant, for example Pulvis Talci, silicon dioxide, corn starch, stearate, boric acid, liquid paraffin, Polyethylene Glycol etc.Tablet further can also be made coated tablet, for example sugar coated tablet, thin membrane coated tablet, ECT, or double-layer tablet and multilayer tablet.
For pill is made in the administration unit, can be extensive use of various carrier well known in the art.Example about carrier is, for example diluent and absorbent are as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, polyvinylpyrrolidone, Gelucire, Kaolin, Pulvis Talci etc.; Binding agent is as arabic gum, Tragacanth, gelatin, ethanol, Mel, liquid sugar, rice paste or batter etc.; Disintegrating agent is as agar powder, dry starch, alginate, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.
For suppository is made in the administration unit, can be extensive use of various carrier well known in the art.Example about carrier is, for example the ester of Polyethylene Glycol, lecithin, cocoa butter, higher alcohol, higher alcohol, gelatin, semi-synthetic glyceride etc.
For capsule is made in the administration unit, effective ingredient is mixed with above-mentioned various carriers, and the mixture that will obtain thus places hard gelatine capsule or soft capsule.Also effective ingredient can be made microcapsule, be suspended in and form suspensoid in the aqueous medium, in the hard capsule of also can packing into or make injection and use.
For example, compositions of the present invention is made injection preparation, as solution, suspensoid solution, Emulsion, lyophilized injectable powder, this preparation can be moisture or non-water, can contain acceptable carrier, diluent, binding agent, lubricant, antiseptic, surfactant or dispersant on a kind of and/or multiple pharmacodynamics.Can be selected from water, ethanol, Polyethylene Glycol, 1 as diluent, the isooctadecanol of ammediol, ethoxylation, the isooctadecanol of polyoxyization, Polyoxyethylene Sorbitol Fatty Acid Esters etc.In addition, ooze injection, can in injection preparation, add proper amount of sodium chloride, glucose or glycerol, in addition, can also add conventional cosolvent, buffer agent, pH regulator agent etc. in order to prepare etc.These adjuvants are that this area is commonly used
In addition, as needs, also can in pharmaceutical preparation, add coloring agent, antiseptic, spice, correctives, sweeting agent or other material.
Compositions of the present invention can be used for the treatment of inherent multidrug resistance with P-gp overexpression and entity tumor and the hematological system tumor that produces the acquisition multidrug resistance at chemotherapy process.
The dosage of the Pharmaceutical composition of Fructus Schisandrae Chinensis extrat of the present invention depends on many factors, for example to prevent or treat the character and the order of severity of disease, the sex of patient or animal, age, body weight, personality and individual reaction, route of administration, administration number of times etc., therefore therapeutic dose of the present invention can have large-scale variation.In general, the using dosage of Chinese materia medica composition of the present invention is well known to a person skilled in the art.The actual active drug quantity that can be according to the present invention be contained in the last preparation in the Pharmaceutical composition of Fructus Schisandrae Chinensis extrat, in addition suitable adjustment to reach the requirement of its treatment effective dose, is finished the purpose of reverse multiple drug resistance of tumor of the present invention.Usually to the about 75 kilograms of patients of body weight, the daily dose of the Fructus Schisandrae Chinensis extrat of giving is 0.001mg/kg body weight～1000mg/kg body weight, preferred 100mg/kg body weight～500mg/kg body weight.Above-mentioned dosage can the single dose form or be divided into several, for example two, three or four dosage form administrations, the dosage regimen that this is subject to administration doctor's clinical experience and comprises utilization chemotherapy, radiotherapy means.
Description of drawings
Fig. 1. Fructus Schisandrae Chinensis extrat is to Bel
7402The influence that amycin is accumulated in the cell.(* * *: p＜0.001) compared with the control
Fig. 2. Fructus Schisandrae Chinensis extrat to vincristine to the inhibiting influence of the drug-fast KBv200 transplanted tumor of nude mice.
The specific embodiment
The following examples are used for further specifying the present invention, but this and do not mean that the present invention is had any restriction.
Embodiment 1
KB, KBv200, MCF-7, MCF-7/Adr, the Bel of trophophase take the logarithm
7402Cell is inoculated in 96 well culture plates (Coster), cultivates after 24 hours, adds anticarcinogen, inversion agent and the control solvent of gradient concentration.Continue to cultivate 72 hours, discard culture fluid afterwards, every hole adds 0.5mg/ml Thiazolyl blue (MTT) 100 μ l (with the RPMI RPMI-1640 dilution that does not contain serum), continue to cultivate 4 hours, discard Thiazolyl blue, every hole adds dimethyl sulfoxide 150 μ l, and slight vibration makes resolution of precipitate, measures absorbance in microplate reader (Bio-Rad 450 types) 570nm place.Establish three to four multiple holes for every group and get its meansigma methods, calculate IC
50With 10 μ mol/L verapamils as positive control.Concrete outcome sees Table 1-10.
Table 1. Fructus Schisandrae Chinensis extrat is to the influence of KBv200 cell to vincristine sensitivity
Table 2. Fructus Schisandrae Chinensis extrat is to the influence of KB cell to vincristine sensitivity
Table 3. Fructus Schisandrae Chinensis extrat is to Bel
7402Cell is to the influence of vincristine sensitivity
Table 4. Fructus Schisandrae Chinensis extrat is to the influence of KBv200 cell to amycin sensitivity
Table 5. Fructus Schisandrae Chinensis extrat is to the influence of KB cell to amycin sensitivity
Table 6. Fructus Schisandrae Chinensis extrat is to the influence of KBv200 cell to paclitaxel sensitivity
Table 7. Fructus Schisandrae Chinensis extrat is to the influence of KB cell to paclitaxel sensitivity
Table 8. Fructus Schisandrae Chinensis extrat is to the influence of MCF-7/Adr cell to amycin sensitivity
Table 9. Fructus Schisandrae Chinensis extrat is to the influence of MCF-7 cell to amycin sensitivity
Table 10. Fructus Schisandrae Chinensis extrat is to Bel
7402Cell is to the influence of amycin sensitivity
Embodiment 2
Trophophase Bel takes the logarithm
7402Cell when treating the 70-80% at the bottom of cell is paved with bottle, is changed the RPMI RPMI-1640 that contains amycin 10 μ mol/L, and the adding final concentration is 25 μ g/ml Fructus Schisandrae Chinensis extrats, with the positive contrast of 10 μ mol/L verapamils, establish three parallel sample for every group, 37 ℃, 5%CO
2Continue to cultivate 3 hours, give a baby a bath on the third day after its birth all over the back collecting cell with ice-cold PBS (pH 7.4), get some cells, with 1.2ml hydrochloric acid (0.3N)-ethanol (50%) suspension cell, and after smashing cell on the ultrasonoscope, 10, centrifugal 15 minutes of 000rpm gets supernatant 1.0ml and adds the above-mentioned hydrochloric acid-alcoholic solution of 2.0ml, fluorescent value with the fluorescent spectrophotometer assay amycin, excitation wavelength is 470nm, and emission wavelength is 580nm, calculates 10 with amycin content-fluorescence standard curve
6The content of amycin in the individual cell.The results are shown in Figure 1.
Embodiment 3
Select good ascitic type S180 sarcoma of growth conditions and H22 hepatocarcinoma kunming mice, draw neck to put to death, behind skin of abdomen iodine tincture, the alcohol disinfecting, aseptic condition is suction ascites down, injects in the aseptic conical flask (ice bath), adds normal saline and be diluted to suitable concn.Behind kunming mice right fore iodine tincture, the ethanol skin degerming, the armpit subcutaneous vaccination, 0.2ml tumor liquid/only, and next day, the administration of dividing into groups immediately, every group of 8-10 only after 10 days, puts to death, and the stripping tumor is weighed.Administering mode is as follows: for the S180 sarcoma, and Fructus Schisandrae Chinensis extrat, 200 and 400mg/Kg, for H22 hepatocarcinoma, Fructus Schisandrae Chinensis extrat 400 and 600mg/Kg, oral, once a day, totally 10 times, oral volume: 10ml/Kg, solvent control, Tween 80, oral, once a day, totally 10 times, oral volume: 10ml/Kg; The positive control cyclophosphamide, 60mg/Kg, lumbar injection, once, volume: 10mg/Kg.
Table 11. Fructus Schisandrae Chinensis extrat is to the inhibitory action of kunming mice H22 liver cancer growth
*: compare P＜0.05 with 2% tween 80
Table 12. Fructus Schisandrae Chinensis extrat is to the inhibitory action of kunming mice S180 sarcoma growth
Compared with the control, * *: P＜0.01; * *: P＜0.001
Embodiment 4
Under the aseptic condition, collect the KBv200 cell, be diluted in the normal saline every nude mice subcutaneous vaccination 1 * 10
8Individual in the oxter, when treating that tumor is grown to the about 1cm of diameter, under aseptic condition, select well-grown tumor piece to be cut into about 30～40mm
3Fritter, the oxter that is inoculated into nude mice with the trocar is to carry out going down to posterity of KBv200 transplantability entity tumor.
When carrying out in the Fructus Schisandrae Chinensis extrat body experiment of reversing tumor drug resistance, get well-grown KBv200 and be cut into small pieces, be inoculated into the right oxter of nude mice.KBv200 tumor proliferation to be inoculated (about two weeks) random packet administration when diameter is 7～15mm, be the 1st day this moment, 7～8 every group.Be divided into 6 groups, blank group: be left intact; Vincristine (VCR) group: vincristine 0.4mg/Kg, second day beginning lumbar injection (i.p.), per two days are once, totally 5 days; The solvent control group: 3% tween 80, oral, once a day, continuous 14 days; Vincristine (VCR)+Fructus Schisandrae Chinensis extrat 100mg/Kg, vincristine (VCR)+Fructus Schisandrae Chinensis extrat 200mg/Kg and vincristine (VCR)+Fructus Schisandrae Chinensis extrat 300mg/Kg, oral, once a day, continuous 14 days, vincristine gives method single together to the vincristine group, the oral volume of the Fructus Schisandrae Chinensis extrat of 3% Tween 80 and each dosage is 10ml/Kg, and with the interval of vincristine lumbar injection be 3 hours.Vincristine is dissolved in physiological saline solution, and Fructus Schisandrae Chinensis extrat arrives desired concn with distilled water diluting then earlier with Tween 80 (volume is 3%) hydrotropy.Body weight of per two days mensuration nude mices and the length of tumor and wide are used formula V=a
2(wherein a is wide to * b/2, and b is length, unit: mm) calculate tumor size, use formula RTV=V
X/ V
1Will be not tumor size criteriaization on the same group, wherein RTV is a relative tumour volume, V
XThe gross tumor volume of measuring when being X days, V
1For treating the gross tumor volume of measuring in first day.Estimate the effect of Fructus Schisandrae Chinensis extrat, meansigma methods * 100% of RIR=(meansigma methods of the meansigma methods of blank group RTV-treatment group RTV)/matched group RTV with relative tumour inhibiting rate (RIR).Concrete outcome sees Table 13 and Fig. 2.
The 15th day Fructus Schisandrae Chinensis extrat of table 13. administration to vincristine to the inhibiting influence of KBv200 transplanted tumor
With only compare to VCR,
*: P＜0.05.
Claims (9)
1. the application of five tastes of medicinal herb in the medicine of preparation reverse multiple drug resistance of tumor.
2. the application of five tastes of medicinal herb seed extract in the medicine of preparation reverse multiple drug resistance of tumor.
3. according to arbitrary described application in the claim 1,2, it is characterized in that described tumor comprises the tumor of inherent multidrug resistance, acquired multidrug resistance.
4. according to claim 1,2 arbitrary described application, it is characterized in that described tumor comprises the tumor of P-glycoprotein overexpression.
5. according to claim 1,2 arbitrary described application, it is characterized in that described tumor comprises entity tumor, hematological system tumor.
6. the application of pharmaceutical composition in preparation treatment tumor multi-medicine drug-resistant medicine of forming by Fructus Schisandrae Chinensis extrat and antitumor drug.
7. according to the application of claim 6, antitumor drug is to be the antitumor drug of substrate with the P-glycoprotein.
8. according to the application of claim 7, the antitumor drug of P-glycoprotein substrate is selected from anthracene nucleus class, vinca, taxanes, Rhizoma Dysosmae Versipellis class, mitoxantrone, actinomycin D, ametycin.
9. application according to Claim 8, the antitumor drug of P-glycoprotein substrate is selected from vincristine, amycin, paclitaxel.
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