CN101856393B - Application of compound Yiganling composition in aspect of auxiliary treatment of chemotherapy of tumors - Google Patents
Application of compound Yiganling composition in aspect of auxiliary treatment of chemotherapy of tumors Download PDFInfo
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Abstract
The invention discloses application of a compound Yiganling composition in the aspect of the auxiliary treatment of the chemotherapy of tumors. The functions are the function of synergy and toxicity reduction to the chemotherapy of the tumors, the function of relieving bone marrow suppression caused by chemotherapeutic medicines, the function of relieving leukopenia caused by the chemotherapeutic medicines, the function of alleviating the pathological injury of the tissues of the liver and the kidney, the function of promoting the regeneration of stem cells and the function of sensitivity enhancement to multi-medicine resistance caused by the chemotherapeutic medicines.
Description
Technical field
The present invention relates to a kind of purposes of medicine, be specifically related to the new purposes of compound liver-benepitino remedy compositions.
Background technology
Malignant tumor is the healthy major disease of serious threat human life.At present, the treatment of malignant tumor is that main Comprehensive Treatment is main means with the chemotherapy.And at perioperatively, chemotherapy also is widely used.Yet along with the application of chemotherapeutics, people are to the understanding of chemotherapy adverse effect and deepening continuously of consciousness of self-protection.Development and application to the chemotherapy ancillary drug have had intensive society need, thus because of its to improving chemotherapy effect, alleviating chemotherapy adverse effect and improve malignant tumor patient survival rate or life quality.But, often, limited its extensive utilization clinically because it costs an arm and a leg.Therefore seek in the Chinese medicine cheap and easy to get and have realistic meaning as the chemotherapy of tumors ancillary drug.
The compound liver-benepitino remedy compositions is meant silymarin 30g and schizandrol extractum 80g, can be made into tablet, capsule or soft capsule.Said composition is used for the hepatic and renal YIN deficiency at present, and the hypochondriac pain that humidity does not cause clearly, poor appetite, abdominal distention, the soreness of waist are weak, yellowish urine; Or the chronic hepatitis transaminase person of increasing.Silibinin can be stablized liver plasma membrane in the silymarin; Protect hepatocellular enzyme system, remove the reactive oxygen free radical in the hepatocyte, thereby improve the detoxification ability of liver; Avoid hepatocyte at long-term contact poison, take liver toxicity medicine, smoking, sustain damage under the situation such as drink.Silibinin capsule (the water woods is good) has splendid toleration, has direct reparation, stablizes liver plasma membrane, regulates liver lipid metabolism, alleviates the effect of the lipid peroxidation that noxious substance causes, is suitable for the long-term treatment of chronic hepatitis and fatty liver.
Summary of the invention
The multidrug resistance tumor is the major obstacle of chemotherapy of tumors, therefore needs to seek low toxic and side effects and definite multidrug-resistance reversal agent or the chemotherapeutic sensitizer of reversing effect, improves the success rate of chemotherapy of tumors.It is model with the human breast carcinoma drug-resistant cell strain MCF27/MDR1 of transfection people MDR1 that the scholar is arranged; Chemotherapeutics paclitaxel, vincristine, amycin and the homoharringtonine of having studied 4 kinds of anticancer mechanism of difference use separately or during with the schisandrin B Combined application to the effect of mdr cell relatively; The result finds; Schisandrin B all has sensitization to 4 kinds of medicines, and a kind of multidrug-resistance reversal agent of its schisandrin B is described.And it is think that its mechanism possibly be the BA that has suppressed P-glycoprotein pump, or relevant with the activation of GAP-associated protein GAP (caspase).
Along with people's is to Compositae Silybum plant Herba Silybi mariani and going deep into the magnoliaceae schisandra basic research; And the accumulation of the clinical use experience of chemotherapy ancillary drug, the compound liver-benepitino remedy compositions becomes possibility in the application that preparation has in the chemotherapy of tumors auxiliary treatment drugs with function.
The new purposes that the objective of the invention is to the pharmacy of open compound liver-benepitino remedy compositions.
Said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the chemotherapy to tumor has the effect of efficacy enhancing and toxicity reducing.
Said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has mitigation to the bone marrow depression that chemotherapeutics causes.
Said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has mitigation to the leukopenia that chemotherapeutics causes.
Said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has mitigation to the leukopenia that chemotherapeutics causes.
Said have the hepatic and renal tissue damage that the effect of tumor chemoradiotherapy auxiliary treatment is meant that the compound liver-benepitino remedy compositions causes chemotherapeutics mitigation arranged, and alleviates liver, nephridial tissue pathology damage, promotes stem cell regenerating.
Said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has sensitization to the drug resistances of wanting that chemotherapeutics causes more.
Outstanding technical characterstic of the present invention:
In silymarin application of treatment field, people have confidence to its curative effect of treating hepatic fibrosis, alcoholic liver, and the conventional conduct of Fructus Schisandrae Chinensis protects the liver, cental system is excited, medicine for respiratory system uses; Like its function medicine card of Shennong's Herbal record be: " main QI invigorating, cough with dyspnea, impairment caused by overstrain weakness and emaciation; tonifying for the deficiency; reinforcing YIN-essence, beneficial man is smart ", be still the main reference foundation that instructs Chinese medicine to use Fructus Schisandrae Chinensis and preparation thereof so far.
And the compound liver-benepitino remedy compositions is used for the hepatic and renal YIN deficiency, and the hypochondriac pain that humidity does not cause clearly, poor appetite, abdominal distention, the soreness of waist are weak, yellowish urine; Or the chronic hepatitis transaminase person's of increasing function cures mainly, and the capsular legal function of former said composition preparation compound liver-benepitino remedy cures mainly the understanding that has limited the outstanding use value of said composition, and the present invention has overcome this technological prejudice.
Among the present invention, schizandrol extractum is collaborative mutually with the silymarin effect on the one hand, on the other hand, brings into play its reverse and wants drug-fast unique effect, thereby make the compound liver-benepitino remedy compositions become remarkably productive chemotherapy of tumors ancillary drug more.
Compound liver-benepitino remedy pharmaceutical composition of the present invention; Clinical acceptable forms be can be made into, compound liver-benepitino remedy capsule, compound liver-benepitino remedy tablet, compound liver-benepitino remedy granule, compound liver-benepitino remedy soft capsule, compound liver-benepitino remedy oral liquid, compound liver-benefiting dropping pill, compound liver-benepitino remedy dispersible tablet etc. included but not limited to.
Below with description of test but be not limited to the present invention:
Experimental example 1:
This experiment adopts cisplatin to set up the animal model of mouse kidney infringement, in order to probe into the influence of compound liver-benepitino remedy compositions to chemotherapy mice renal damage.
Materials and methods
The laboratory animal Male Kunming strain mice, in 5 ages in week, body weight (20.16 ± 0.54) g is provided by experimental animal feeding center, Guangdong Province, cleaning III level.The male s180 tumor-bearing mice of Kunming kind, in 5 ages in week, body weight (20.28 ± 0.43) g is provided by Traditional Chinese Medicine University Of Guangzhou new drug research development centre.
The experiment medicine
Compound liver-benepitino remedy compositions dry extract (moisture silibin 0.15g and the schizandrol extractum 0.40g of flying of every g) (Luofu Mountain, Guangdong traditional Chinese medicines limited company provides).Cisplatin for inj: 10mg/ bottle (the accurate word H37020524 of traditional Chinese medicines).
Experimental design
All adopt the table of random number random packet before all experiment mice experiments.All inoculate equivalent s180 tumor cell (10 in health same area (right oxter) simultaneously before the experiment of s180 tumor-bearing mice
6/ only), inoculation back 24h begins administration to be observed, and 7-10d is as a course of treatment.
Observe compound liver-benepitino remedy compositions dry extract to the serology of mice renal damage and the influence of pathology index:
Get 100 mices and be divided into 5 groups at random.Be respectively normal saline (blank) group, singly add compound liver-benepitino remedy compositions 60,120,240mgkg with cisplatin group, cisplatin
-1Group.
The blank group every every day gives the 0.3ml normal saline and irritates stomach, totally 7 days; List gave cisplatin 7mgkg on the 1st day with the cisplatin group
-1Lumbar injection 1 time respectively gave the 0.3ml normal saline and irritates stomach, qd on the 2nd～7 day; Cisplatin adds the compound liver-benepitino remedy compositions and respectively organizes the 1st day and give cisplatin 7mgkg
-1Lumbar injection 1 time, the 1st～7 day by group give 60,120 respectively, 240mgkg
-1The compound liver-benepitino remedy compositions is irritated stomach.
All mices are got blood 0.5ml in the 4th day thorn eyeball, survey the plain ammonia (BUN) of hematuria, serum creatinine (Cr), N-acet-beta-amino glucosidase (NAG).In the 8th day whole mices are taken off cervical vertebra and put to death, dissect immediately and get kidney, 20% formalin is fixed, and is total to such an extent that the kidney BIAO and BEN is done the pathology inspection for 100 parts.
All experimental datas are carried out statistical analysis with SASS13 after standardization, calculate corresponding t value, and compare the P value.
The result:
To the cumulative order of injection cisplatin dosage, corresponding change also appears in the mouse kidney morphosis according to injecting normal saline.Injection cisplatin 7mgkg
-1The experimental group kidney between matter congested obviously renal tubules (especially proximal convoluted tubule) water degeneration is obvious, the necrosis of renal tubules point lamellar appears in severe patient.Cisplatin dosage is greater than 7mgkg
-1Experimental group presents cast in typical renal tubules lamellar necrosis, the renal tubules, manages all inflammatory cell infiltrations.
The blank group is normal kidney structure.Cisplatin adds 3 dose groups of compound liver-benepitino remedy, and no matter compound liver-benepitino remedy dosage is big or small, and the only slight water degeneration of renal tubules is at compound liver-benepitino remedy 10,30mgkg
-1Group has an example to have spotty necrosis respectively.And single serious relatively with cisplatin group mouse kidney pathological changes, significantly renal tubules water degeneration all appears, and kitchen range shape, lamellar renal tubules hemorrhagic necrosis appear in 14 examples.
Each is organized the biochemical indicator change and sees table:
| Group | N | BUN(mmol) | Cr(μmol) | NAG(U/L) |
| Blank control group | 20 | 7.32±1.94 | 72.5±14.28 | 62.44±14.28 |
| Compound liver-benepitino remedy (low) | 20 | 9.06±1.86 | 78.2±16.08 | 64.54±16.20 |
| Compound liver-benepitino remedy (in) | 20 | 8.12±2.02 | 76.6±15.74 | 61.42±15.04 |
| Compound liver-benepitino remedy (height) | 20 | 8.46±1.98 | 78.3±18.24 | 62.12±16.08 |
| The cisplatin matched group | 20 | 3532±2.06 | 372.2±24.18 | 128.48±21.42 |
Experimental example 2:
Compound liver-benepitino remedy is to the influence of chemotherapy mouse bone marrow cells CD34+ hematopoietic stem apoptosis.
Method: mice is adopted intraperitoneal injection of cyclophosphamide (CTX) modeling, and packet transaction was put to death after 9 days.Flow cytometer detects bone marrow CD34+ apoptosis; The RT-PCR method detects the expression of its Cyt-C, bcl-2mRNA.
Result: CTX group FITC+/PI-cell proportion is than saline group obviously raise (P＜0.05); And high, medium and low 3 dose groups and simple Chinese drug-treated group FITC^+/PI^-cell proportion obviously reduce, and compare with plain CT X group, and difference has significance (P＜0.01).
Plain CT X group Cyt-CmlLNA expresses than the saline group and raises (P＜0.05), and in, low 2 dose groups and simple Chinese drug-treated group express than plain CT X group and reduce (P＜0.05); Plain CT X group bCl-2mRNA expresses and reduces than the saline group; And high, medium and low 3 dose groups and simple Chinese drug-treated group bel-2mRNA express than the obviously rising of plain CT X group, and difference has significance (P＜0.01).
Compound liver-benepitino remedy is to the apoptotic influence of bone marrow CD34+
| Group | N | Dosage | FITC+/PI- | FITC-/PI- |
| Normal saline | 18 | -- | 3.20±2.18 | 16.34±5.74 |
| Simple Chinese drug-treated group | 18 | 240mg·kg -1 | 2.41±1.94 | 27.56±12.38 |
| The CTX group | 18 | 10mg | 7.15±2.52 | 11.10±6.22 |
| CTX group+compound liver-benepitino remedy (low) | 18 | 10mg+60mg | 3.12±3.20 | 15.38±6.46 |
| CTX group+compound liver-benepitino remedy (in) | 18 | 10mg+120mg | 2.73±1.68 | 19.94±7.74 |
| CTX group+compound liver-benepitino remedy (height) | 18 | 10mg+240mg | 2.96±1.84 | 21.42±6.18 |
Compound liver-benepitino remedy is to the influence of bone marrow CD34+ cell Cyt-CmRNA, bcl-2mRNA
| Group | N | Dosage | Cyt-CmRNA | bcl-2mRNA |
| Normal saline | 18 | - | 0.924±0.051 | 4.552±1.146 |
| Simple Chinese drug-treated group | 18 | 240mg·kg -1 | 1.020±0.122 | 8.942±1.784 |
| The CTX group | 18 | 10mg | 2.114±0.184 | 3.424±1.148 |
| CTX group+compound liver-benepitino remedy (low) | 18 | 10mg+60mg | 1.125±0.142 | 6.462±2.144 |
| CTX group+compound liver-benepitino remedy (in) | 18 | 10mg+120mg | 0.916±0.086 | 7.642±2.062 |
| CTX group+compound liver-benepitino remedy (height) | 18 | 10mg+240mg | 0.908±0.176 | 7.448±1.964 |
Conclusion: compound liver-benepitino remedy can effectively suppress chemotherapy mouse bone marrow cells CD34+ hematopoietic stem apoptosis, and raising the bcl-2mRNA expression possibly be one of its mechanism.
Experimental example 3:
The compound liver-benepitino remedy compositions suppresses the potentiation of S 180 growths to cyclophosphamide (Cy)
Method: 70 of 18-21g kunming mices are divided into 7 groups at random, and the 1st group as normal group, and 6 groups are inoculated in the subcutaneous preparation tumor-bearing mice of mice right fore axil animal model with the S180 tumor cell suspension in addition, are divided into the basic, normal, high dose groups (60mgkg of compound liver-benepitino remedy
-1, 120mgkg
-1, 240mgkg
-1) and cyclophosphamide (Cy) group, tumor matched group and compound liver-benepitino remedy associating Cy treatment group; Irritate stomach 7d inoculation S180 tumor; Measure malonaldehyde (MDA) content, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) vigor in the mouse liver even slurry behind the 19d; Estimate the effect of compound liver-benepitino remedy, observe treatment front and back body weight, heavy, the tumour inhibiting rate of tumor anti-oxidative ability of mice.
Adopt reverse transcription one polymerase chain reaction (RT-PCR) to detect the expression of IL-2, TNF-α, TGF-β 1mRNA, estimate compound liver-benepitino remedy effect of immunologic function.
The result: each dose groups of compound liver-benepitino remedy all can improve the active and SOD vigor of GSH-Px in the liver, but the compound liver-benepitino remedy high dose group significantly reduces MDA level (P＜0.01).TNF-α, IL-2mRNA relative expression quantity are reduced TGF-β 1 level simultaneously apparently higher than Cy group and tumor matched group (P＜0.01) in each dose groups tumor-bearing mice tumor tissues of compound liver-benepitino remedy.
The compound liver-benepitino remedy high dose has obvious inhibitory action to mice S180 tumor, and after share with Cy synergism is arranged, and has improved the TNF-α of mice, the expression of IL-2mRNA.
Compound liver-benepitino remedy to the influence of the tumor weight and the suppression ratio of S180 tumor-bearing mice (X ± s, n=10)
| Group | N | Dosage | Tumor weight (g) | Tumour inhibiting rate (%) |
| The normal control group | 10 | - | - | - |
| The tumor matched group | 10 | - | 1.48±0.32 | - |
| The Cy intervention group | 10 | 20mg.kg -1.d -1 | 0.54±0.18 | 63.5 |
| Compound liver-benepitino remedy (low) | 10 | 60mg·kg -1、 | 1.21±0.22 | 18.2 |
| Compound liver-benepitino remedy (in) | 10 | 120mg·kg -1 | 1.15±0.26 | 22.3 |
| Compound liver-benepitino remedy (height) | 10 | 240mg·kg -1 | 1.02±0.32 | 31.1 |
| Cy group+compound liver-benepitino remedy (in) | 10 | 20mg.kg -1.d -1 +120mg·kg -1 | 0.41±0.16 | 72.3 |
Conclusion: the tumor mechanism that presses down of compound liver-benepitino remedy possibly mainly be antioxidation and immunoregulation effect, and effect is relevant with dosage.
Interpretation of result: research shows that compound liver-benepitino remedy does not have direct repression to tumor cell, is to play a role through the immunologic function that improves the host mostly.TNF-1 and IL-2 are that (biological responsemodifiers BRM) has the cytokine of antitumor action to host BRM in the system, have the effect of inducing apoptosis of tumour cell.TNF-1 is unusual important cytokine in the tumor body's immunity, is produced by monokaryon one macrophage, and it can the direct killing tumor cell, as through acting on after birth phospholipase, protease and nuclease approach killing tumor cell; Can also like the blood supply of blocking-up tumor cell, increase the blood coagulation activity of tumor vascular endothelial cell through indirect approach killing tumor cell, make vascular endothelial cell impaired, and suppress migration of vascular endothelial cells etc.IL-2 is T emiocytosis, is the signal of T cell proliferation, can promote the T cell to breed in a large number, can impel the activation and proliferation of NKT (NK) cell in addition, also can impel propagation, differentiation and the synthetic antibody of B cell.Therefore, TNF-1, IL-2 are two kinds of important antitumor action cytokines of generally acknowledging at present.This result of the test shows that also zymosan not only has obvious antitumor action, and in vivo under the antitumor effective dose, obviously strengthens the expression of TNF-1, IL-2mRNA in the tumor-bearing mice tumor tissues, and this possibly be one of mechanism of compound liver-benepitino remedy antitumor action.
Experimental example 4: the compound liver-benepitino remedy compositions suppresses the potentiation of U14 growth to cyclophosphamide (Cy)
Get 70 of mices, female, 19-24g, the 1st group as normal group, and all the other are divided into the basic, normal, high dose groups (60mgkg of compound liver-benepitino remedy
-1, 120mgkg
-1, 240mgkg
-1) and cyclophosphamide (Cy) group, tumor matched group and compound liver-benepitino remedy associating Cy treatment group, with experiment 3 inoculation U14 tumor pieces, put to death mice after treating 12d, peel off the tumor piece, remove surrounding tissue, observe body weight before and after the treatment, heavy, the tumour inhibiting rate of tumor.
Compound liver-benepitino remedy to the influence of the tumor weight and the suppression ratio of U14 tumor-bearing mice (X ± s, n=10)
| Group | N | Dosage | Tumor weight (g) | Tumour inhibiting rate (%) |
| The normal control group | 10 | - | - | - |
| The tumor matched group | 10 | - | 1.84±0.42 | - |
| The Cy intervention group | 10 | 20mg.kg -1.d -1 | 0.92±0.28 | 50.0 |
| Compound liver-benepitino remedy (in) | 10 | 120mg·kg -1 | 1.24±0.44 | 32.6 |
| Compound liver-benepitino remedy (height) | 10 | 240mg·kg -1 | 1.15±0.38 | 37.5 |
| Cy group+compound liver-benepitino remedy (in) | 10 | 20mg.kg -1.d -1 +120mg·kg -1 | 0.78±0.26 | 57.6 |
| Cy group+compound liver-benepitino remedy (height) | 10 | 20mg.kg -1.d -1 +120mg·kg -1 | 0.72±0.22 | 60.9 |
Experimental example 5: compound liver-benepitino remedy causes the influence of leukopenia to chemicotherapy
Gastric cancer 9 examples, the esophageal carcinoma 5 examples, mammary cancer 18 examples among the 55 routine patients, cervical cancer 4 examples, ovarian cancer 3 examples, colon cancer 7 examples, pulmonary carcinoma 3 examples, hepatocarcinoma 2 examples, cancer of pancreas 2 examples, bladder cancer 2 examples.Minimum 45 years old of age, maximum 71 years old.Postoperative chemicotherapy person 50 examples, non-postoperative chemicotherapy person 5 examples.All case is divided into treatment group 30 example and matched group 25 examples at random.
Therapeutic Method: treatment group: compound liver-benepitino remedy capsule (Luofu Mountain, Guangdong traditional Chinese medicines limited company) every day 3 times, each 4-6 grain.Matched group: Colla Corii Asini nourishing blood granule, each 10g, every day 2 times; The each 200mg of Ascorbyl c plate, every day 3 times; The each 20mg of vitamin B6 sheet, every day 3 times.All oral.Check routine blood test 1 time weekly.Treating for 2 weeks was 1 course of treatment.
Therapeutic outcome: treatment organize 16 routine total white blood cellses big/in 4*10
9/ L, 8 examples are greater than 3.5*10
9/ L; Total effective rate: 80%;
Matched group 13 routine total white blood cellses are big/in 4*10
9/ L, 4 examples are greater than 3.5*10
9/ L; Total effective rate: 68%.
Experimental example 6 compound liver-benepitino remedies reverse the drug-fast preliminary study of HCC
Method is used mtt assay and is measured the IC50 of application compound liver-benepitino remedy front and back 5-fluorouracil (5-Fu) to the Bel/Fu drug-resistant cell strain, calculates it and reverses multiple; Concentration relies on test and confirms that compound liver-benepitino remedy reverses concentration; Chemical sproof colony forms the preliminary effect of confirming compound liver-benepitino remedy reverse Bel/Fu of experiment.Compound liver-benepitino remedy is 2040 μ g/mL to Bel/Fu cell IC50 as a result, and pair cell did not have tangible lethal effect when its concentration was 490 μ g/mL, and 5-Fu has synergism with cancer therapy drug, and CDI is 0.89.Colony forms experiment and confirms the effect of compound liver-benepitino remedy reversion MDR from form, diminishes gradually with the increasing colony of compound liver-benepitino remedy concentration.The conclusion compound liver-benepitino remedy has reverse effect to hepatocarcinoma drug-resistant cell strain Bel/Fu cell multidrug resistance.
Experimental procedure:
1, hepatoma cell strain Bel/Fu recovers, cultivates, goes down to posterity and be frozen
From liquid nitrogen, take out freeze-stored cell, place 42 ℃ of aqueous solutions immediately, make the cell quick-thawing; The centrifugal 5min of room temperature 1000r/min abandons supernatant, adds the fresh RPMI1640 culture fluid that contains 10% hyclone; Move in the culture bottle; Cultivate in 37 ℃, 5%CO2 incubator, later per 2～3d changes culture fluid 1 time, treats to go down to posterity after cell covers with.After cell covers with, the culture fluid that inclines, add 0.25% trypsinization appropriate time after; Discard Digestive system, add the RPMI1640 culture fluid, blow and beat repeatedly with suction pipe; Make it become the individual cells suspension, can continue to go down to posterity to cultivate or cell added places liquid nitrogen frozen subsequent use in the frozen pipe.
2, compound liver-benepitino remedy IC50 measures
Be in the exponential phase cell with 0.25% trypsinization, be made into single cell suspension, 3 * 10 cells/mL with the RPMI1640 culture fluid that contains 10% hyclone; Be inoculated in 96 well culture plates, every pore volume 200, treat cell attachment after; Every hole adds 5uLBCDC, and the medicine final concentration is respectively 50,100,200,300,400,800 μ g/mL, 3 holes of each concentration; Establish not dosing control wells, culture fluid blank well, each 3 hole of control wells simultaneously, behind 37 ℃, the 5% ℃ cultivation 4d, every hole adds 50 μ 1MTT (5mg/mL); After continue cultivating 4h, remove supernatant and inhale in culture fluid with absorbent paper, every hole adds 150 μ LDMSO again; Vibrate dissolve fully to crystallization after, measure the A value of 490nm with ELIASA.
3, compound liver-benepitino remedy reverses the chemical sproof concentration of Bel/Fu and relies on experiment
Be in the exponential phase cell with 0.25% trypsinization, be made into single cell suspension with the RPMI1640 culture fluid that contains 10% hyclone, 3 * 10 cells/mE are inoculated in 96 well culture plates, every pore volume 200, treat cell attachment after, the dosing of every hole.Experiment is divided into groups as follows: the compound liver-benepitino remedy group adds 5 μ L compound liver-benepitino remedies, makes that its final concentration is 400,420,440,450,460,480,490,500g/mL, totally 8 groups; Compound liver-benepitino remedy+5-Fu group adds 5 μ l compound liver-benepitino remedies, and making its final concentration is 320,340,360,380,400,460,490,540 μ g/mL, totally 8 groups, and every group of every hole all adds 5 μ l5-Fu (final concentration is 0.02pg/mL); The cell matched group does not add medicine.5-Fu organizes only 75 μ l-Fu (final concentration is 0.02pg/mL) of every hole.Establish the culture fluid blank simultaneously.3 parallel holes are respectively established in all experiments, and after 37 ℃, 5%cOz were cultivated 4d, every hole added 50MTT (1mg/mL); After continuing to cultivate 4h, remove supernatant and blot culture fluid with absorbent paper, every hole adds 150gLDMSO again; Vibrate dissolve fully to crystallization after, measure the A value of 490nm with ELIASA.
The result: cell matched group and the no significant difference of 5-Fu group ratio prove the 5-Fu drug-resistant cell strain; 400～490 μ g/mL compound liver-benepitino remedies and cell matched group do not show tumor-inhibiting action than zero difference, but 500 μ g/mL and cell matched group show tumor-inhibiting action than variant; There were significant differences with 5-Fu group ratio for 5-Fu+ compound liver-benepitino remedy 490,500 μ g/mL.
The specific embodiment:
Embodiment 1: the compound liver-benepitino remedy capsule, every moisture silibin that flies of every dress 0.2g is counted the 90%-110% that indicates content 21mg with silibinin, contains schizandrol extractum and is no less than 0.6mg in schisandrin B.Be used for: the auxiliary treatment of tumor chemotherapeutic drug, each 4.3 times on the one, one after each meal.
Embodiment 2: the compound liver-benepitino remedy capsule, every moisture silibin that flies of every dress 0.2g is counted the 90%-110% that indicates content 21mg with silibinin, contains schizandrol extractum and is no less than 0.6mg in schisandrin B.Be used for: the leukopenia that chemotherapy of tumors causes, each 4.3 times on the one, one after each meal.
Embodiment 3: the compound liver-benepitino remedy capsule, every moisture silibin that flies of every dress 0.2g is counted the 90%-110% that indicates content 21mg with silibinin, contains schizandrol extractum and is no less than 0.6mg in schisandrin B.Be used for: the hepatic and renal tissue damage that chemotherapy of tumors causes, each 4.3 times on the one, one after each meal.
Embodiment 4: the compound liver-benepitino remedy capsule, every moisture silibin that flies of every dress 0.2g is counted the 90%-110% that indicates content 21mg with silibinin, contains schizandrol extractum and is no less than 0.6mg in schisandrin B.Be used for: the bone marrow depression that chemotherapy of tumors causes, each 4.3 times on the one, one after each meal.
Embodiment 5: the compound liver-benepitino remedy capsule, every moisture silibin that flies of every dress 0.2g is counted the 90%-110% that indicates content 21mg with silibinin, contains schizandrol extractum and is no less than 0.6mg in schisandrin B.Be used for: the reverse of hepatocarcinoma, breast carcinoma chemotherapy resistance, medicine enhanced sensitivity, each 4-6 grain.3 times on the one, one after each meal.
Claims (6)
1. the compound liver-benepitino remedy compositions has the application in the tumor chemoradiotherapy auxiliary treatment drugs with function in preparation.
2. application according to claim 1, wherein said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the chemotherapy to tumor has the effect of efficacy enhancing and toxicity reducing.
3. application according to claim 1, wherein said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has mitigation to the bone marrow depression that chemotherapeutics causes.
4. application according to claim 1, wherein said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has mitigation to the leukopenia that chemotherapeutics causes.
5. application according to claim 1; Wherein said have liver, the nephridial tissue damage that the effect of tumor chemoradiotherapy auxiliary treatment is meant that the compound liver-benepitino remedy compositions causes chemotherapeutics mitigation arranged; Alleviate liver, nephridial tissue pathology damage, promote stem cell regenerating.
6. application according to claim 1, wherein said have the effect of tumor chemoradiotherapy auxiliary treatment and be meant that the compound liver-benepitino remedy compositions has sensitization to the multidrug resistance that chemotherapeutics causes.
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Effective date of registration: 20190220 Address after: 516133 Bianling Pai Industrial Zone of Guangshan Highway, Changning Town, Boluo County, Huizhou City, Guangdong Province (Luofushan Pharmaceutical City) Patentee after: Guangdong Luofushan Sinopharm Co., Ltd. Address before: 516100 No. 36 Qiaodong three road, Luoyang Town, Boluo County, Huizhou, Guangdong Patentee before: Lin Xiulian |
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