CN102846868B - Tibetan medicine RENQINGMANGJUE is preparing the purposes in antitumor drug - Google Patents
Tibetan medicine RENQINGMANGJUE is preparing the purposes in antitumor drug Download PDFInfo
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Abstract
The invention discloses tibetan medicine RENQINGMANGJUE and prepare the novelty teabag in antitumor drug.The blue or green awns of core feels separately or applies with chemotherapy drugs in combination to have obvious antitumor action, and can improve immunologic function, and protection Thymus and spleen, has potentiation to chemotherapeutics.
Description
Technical field
The invention belongs to technical field of Chinese medicines, be specifically related to Chinese medicine and preparing the purposes in antitumor drug.
Background technology
The blue or green awns of core feels for traditional Tibetan proved recipe, records in Chinese Pharmacopoeia version in 2010 572 pages.Its major function with cure mainly as heat-clearing and toxic substances removing, the liver benefiting nourishing the stomach, more skin ulcer improving eyesight refreshment, nourishing and fit keeping function.Be used for the treatment of the various nosotoxicosis such as nature poison, preparation poison; The disease such as " Baconic ", " wooden cloth "; Acute and chronic gastritis ulcer, ascites, leprosy etc.
Summary of the invention
The object of the present invention is to provide the second medical usage of tibetan medicine RENQINGMANGJUE, namely prepare the novelty teabag in antitumor drug.
Another object of the present invention is to provide tibetan medicine RENQINGMANGJUE and the second drug combination preparing the purposes in antitumor drug
According to an aspect of the present invention, provide the blue or green awns of core to feel and preparing the novelty teabag in antitumor drug, the tumor of indication of the present invention can be entity tumor such as sarcoma and cancer (such as fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendothelial sarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon cancer, cancer of pancreas, breast carcinoma, ovarian cancer, carcinoma of prostate, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, syringocarcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, liver neoplasm, cancer of biliary duct, choriocarcinoma, spermocytoma, embryonal carcinoma, wilms' tumor, neck cancer, uterus carcinoma, carcinoma of testis, pulmonary carcinoma, small cell lung cancer, bladder cancer, epithelial cancer, glioma, astrocytoma, acoustic neuroma, Oligodendroglioma, schwannoma, meningioma, melanoma, neuroblastoma and retinoblastoma), also can be blood tumor such as leukemia (such as acute leukemia, acute lymphoblastic leukemia, acute myelocytic leukemia, acute pith mother cells leukemia, acute promyelocitic leukemia, acute myelomonocytic leukemia, Acute monocytic chronic myeloid leukemia, Di Guglielmo syndrome, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), polycythemia vera, lymphoma (Hokdkin disease, non Hodgkin's disaese), Walden Si Telunshi macroglobulinemia, heavy chain disease.Preferably, be sarcoma, hepatocarcinoma, pulmonary carcinoma, melanoma, leukemia, human esophagus cancer, adenocarcinoma of stomach.
In animal body, experimentation proves, the blue or green awns of core feels that independent application for the treatment of mice lung cancer, hepatocarcinoma, gastric cancer have significant anticancer effect, can extend mouse ascites tumor life span.
According to a further aspect in the invention, the blue or green awns feel of core is provided to prepare the purposes in antitumor drug with the second drug combination.Described the second medicament can be radiotherapy, chemotherapeutics, biopharmaceuticals or other medicaments for oncotherapy.Described the second medicament is preferably tumor chemotherapeutic drug, preferred tumor chemotherapeutic drug is selected from cyclophosphamide (cyclophosphamide, CTX), amycin (ADM), methotrexate (TMX), fluorouracil (5-Fu) and cisplatin (DDP).Described associating can be administration simultaneously, also can be Sequential administration, namely before or after giving the blue or green awns feel of patient's core, gives the second medicament.According to dosage and administering mode, blue or green for core awns feel can be mixed with test kit to facilitate administration with the second medicament.
In animal body, experimentation proves that the blue or green awns of core feels and chemotherapy drugs in combination applies the toxic reaction that can alleviate chemotherapeutics and bring, and can improve immune function of mice simultaneously, have protective effect to mouse thymus, spleen.Potentiation can be played to chemotherapeutics.
Blue or green for core awns can be felt be prepared into and anyly be suitable for oral pharmaceutical dosage form, include but not limited to pill, capsule, tablet, powder and granule etc.
Accompanying drawing explanation
Fig. 1 shows the blue or green awns of core and feels that capsule is to the in vivo antitumor effect of mice transplantation transplantable lung cancer Lewis ' L.C..
Fig. 2 shows the blue or green awns of core and feels that capsule is to mice transplantation lung cancer Lewis ' in vivo antitumor effect of L.C..
Fig. 3 shows the blue or green awns of core and feels that capsule is to mice transplantation tumor hepatocarcinoma H
22in vivo antitumor effect.
Fig. 4 shows the blue or green awns of core and feels that capsule is to mice transplantation tumor hepatocarcinoma H
22in vivo antitumor effect.
Fig. 5 shows the blue or green awns of core and feels that capsule is to the effect of mice ehrlich carcinoma (EAC) life cycle.
Fig. 6 shows the blue or green awns of core and feels that capsule is to the in vivo antitumor effect of Human gastric cancer xenografts BGC823.
Fig. 7 shows the blue or green awns of core and feels that capsule is to the tumor variation diagram of Human gastric cancer xenografts BGC823.
Detailed description of the invention
Medicine source: core blue or green awns feel capsule, capsule 's content is drug, is chocolate brown powder, commercial, Gannan Foge Tibetan Medicine Co., Ltd; Specification: 0.25g/ grain, lot number: 100501, date of manufacture: on May 10th, 2010, authentication code: the accurate word Z20050177 of traditional Chinese medicines.
Animal origin: C57 mice is provided by Beijing HFK Bio-Technology Co., Ltd., Quality of Experimental Animals quality certification SCXK (capital) 2009-0007; Balb/c nude mice is provided by Nat'l Pharmaceutical & Biological Products Control Institute's Experimental Animal Center, Quality of Experimental Animals quality certification SCXK (capital) 2005-0004; Rat liver cancer H22 cell, builds strain, Beijing inspection center of Tumour Inst., Chinese Medical Academy routine preservation by branch of the Chinese Academy of Medical Sciences 1 Room tumor group etc.
Tumor cell is originated: mice lung cancer Lewis ' L.C. cell, builds strain, Beijing inspection center of Tumour Inst., Chinese Medical Academy routine preservation by Lewis etc.; People's poorly differentiated adenocarcinoma cancer BGC823 cell, builds strain by Cai Yuhui etc., Beijing inspection center of Tumour Inst., Chinese Medical Academy routine preservation; KM mice is provided by Nat'l Pharmaceutical & Biological Products Control Institute's Experimental Animal Center, Quality of Experimental Animals quality certification SCXK (capital) 2005-0004; Mice ehrlich carcinoma EAC cell, by Beijing inspection center of Tumour Inst., Chinese Medical Academy routine preservation.
Control drug is originated: Cyclophosphamide for injection, (Cyclophosphamideforinjection, CTX), specification 200mg: bottle, the accurate word H32020857 of traditional Chinese medicines, Hengrui Medicine Co., Ltd., Jiangsu Prov.'s product, lot number 08012721; Fluorouracil Injection (FluorouracilInjection), specification 10ml:0.25g, the accurate word H31020593 of traditional Chinese medicines, Shanghai Xudong Hipu Medicine Co., Ltd's product, lot number 081010; Hydrochloride for injection doxorubicin, amycin (Doxorubicin, ADM), specification 10mg: bottle, the accurate word H44024359 of traditional Chinese medicines, Wanle Pharmaceutical Co Ltd, Shenzhen's product, lot number 0811E2; Methotrexate for inj (methotrexateforinjection), Hengrui Medicine Co., Ltd., Jiangsu Prov.'s product, specification 1g/ bottle, lot number 09111011, the accurate word H32026197 of traditional Chinese medicines; Cisplatin injections, specification 50mg-50ml.)
The blue or green awns of [embodiment 1] core feels that capsule is independent or study Mice Bearing Lewis Lung Cancer tumor-inhibiting action with chemotherapy drugs in combination
1. experimental program
Healthy C57 mice 60,17 ~ 21g, gets subcutaneous well-grown Lewis ' L.C. tumor nodule that goes down to posterity in C57 Mice Body, oncocyte liquid is made by sterile working, be inoculated in C57 mouse armpit subcutaneous, 5x106cell/ Mus, animal is divided into 6 groups at random, often organize 10, after inoculated tumour the 2nd day starts administration, and the blue or green awns of core feels and CTX administration simultaneously, altogether administration 10 days, experimental drug group set time every day gastric infusion once, administration 10 days.Positive drug control group lumbar injection (ADM40mg/20ml/kg), every other day once, the administration time time limit is with experimental drug group (CTX is total to administration 5 times).Specifically be grouped as follows:
1) matched group;
2) positive drug CTX group (40mg/kg, ip, qod);
3) blue or green awns feel capsule in high dose group (1g/kg, po, qd) of core;
4) blue or green awns feel capsule in high dose+CTX group (1g/kg, po, qd+40mg/kg, ip, qod) of core;
5) dosage+CTX group (0.5g/kg, po, qd+40mg/kg, ip, qod) in core blue or green awns feel capsule;
6) blue or green awns feel capsule low dosage+CTX group (0.25g/kg, po, qd+40mg/kg, ip, qod) of core.
Last administration terminates rear 24h, and experimental mouse is got blood and made analysis of Hematology Changes, puts to death animal, completely takes tumor block and claims tumor heavy and body weight, thymus and spleen weight, gets each group of stomach, intestinal, hepatic tissue carry out light microscopic pathological study as paraffin section.Calculate tumour inhibiting rate, thymus and spleen index, drug combination Q-value, experimental result OfficeExcel software carries out statistical analysis.
2. statistical method
All data with
represent, compare between group and adopt t inspection, and SPSS11.5forwindows statistical software carries out one factor analysis of variance (One-WayANOVA), p value < 0.05 is significant difference, has statistical significance.
Drug effect criterion:
E in formula
afor A medicine tumour inhibiting rate, E
bfor B medicine tumour inhibiting rate, E
aBbe that two medicines share tumour inhibiting rate, q=0.85 ~ 1.15 are that the effect of share of two medicines is added, and q > 1.15 is that the effect of share of two medicines strengthens, and q < 0.85 is that two medicines share effect antagonism.
3. result
The blue or green awns of core feels that capsule has antitumor activity to mice lung cancer Lewis ' L.C..The blue or green awns of independent core feels that Capsules group (1g/kg, po, qd) tumour inhibiting rate is 38.59%, with model control group comparing difference remarkable (P < 0.05); The blue or green awns of core feels that capsule in high dose combined with CT X group (1g/kg, po, qd+40mg/kg, ip, qod) tumour inhibiting rate is 74.48%, with model control group comparing difference remarkable (P < 0.01); In core blue or green awns feel capsule, dosage combinations CTX group (0.5g/kg, po, qd+40mg/kg, ip, qod) tumour inhibiting rate is 72.08%, with model control group comparing difference remarkable (P < 0.01); The blue or green awns of core feels that capsule low dosage combined with CT X group (0.25g/kg, po, qd+40mg/kg, ip, qod) tumour inhibiting rate is 70.12%; The tumour inhibiting rate of positive control CTX group 40mg/kg is 70.41%.The blue or green awns of high dose core feels that combined with CT X group drug combination Q-value is 0.91, and the effect of prompting drug combination is added.
Table 1, Fig. 1 are group tumor weight each at the end of experiment, and table 2 is for respectively organizing thymus, spleen index at the end of experiment, and table 3 is for respectively organizing hemogram at the end of experiment.Histology pictures gets each group of stomach, intestinal, hepatic tissue at the end of being experiment, after 10% formalin is fixing, carry out light microscopic pathological study as paraffin section.
Microscopic observation paraffin section, model control group: hepatic tissue structural integrity, liver plate are clear, gastric mucosa is complete, without cell infiltration, intestinal structure is normal; Positive drug CTX group: hepatocellular apoptosis, stove shape cell infiltration, gastric mucosa is complete, normal, the slight cell infiltration of intestinal structure; The blue or green awns of core feels dosage combinations CTX group in capsule low dosage combined with CT X group and core blue or green awns feel capsule: slight hepatic cell apoptosis, gastric mucosa be complete, without cell infiltration, intestinal structure normally, without cell infiltration; The blue or green awns of core feels capsule in high dose combined with CT X group: hepatic tissue structural integrity, liver plate are clear, and gastric mucosa is complete, without cell infiltration, intestinal structure normally, without cell infiltration.
The blue or green awns of table 1 core feels that capsule is to mice lung cancer transplanted tumor Lewis ' L.C. inhibitory action
T compares with model group; T1 compares with high dose core blue or green awns feel group; T2 compares with positive controls
The dosage g (gram) of above Capsules group refers to crude drug content.
The blue or green awns of table 2 core feels the impact of capsule on Lewis ' L.C. mice with tumor thymus and spleen index
T compares with model group;
The blue or green awns of table 3 core feels that capsule is on the impact of Lewis ' L.C. mice with tumor hemogram
4. conclusion
Experimental result shows, the blue or green awns of core feels to have certain antitumor activity to mice lung cancer Lewis ' L.C., 1g/kg gastric infusion in capsule body, and tumour inhibiting rate is 38.59%.
The blue or green awns of core to feel in capsule Mice Body gastric infusion every day 1 time, totally 10 days, reacts without overt toxicity.
Lotus tumor model control group is due to the increase of band tumor splenomegaly weight, and the blue or green awns of core feels that Capsules group has restitution to splenomegaly, and the damage of the blue or green awns feel capsule of core to caused by cyclophosphamide mice with tumor thymus and spleen simultaneously has certain protective effect.
The blue or green awns of core feels that capsule combined chemotherapy Cytoxan (cyclophosphamide, CTX) is treated tumor Lewis ' L.C. and had efficacy enhancing and toxicity reducing effect.
Pathological examination shows, contrast medicine CTX group hepatocellular apoptosis, stove shape cell infiltration, and core blue or green awns feel capsule in high dose combined with CT X group hepatic tissue structural integrity, liver plate are clear, and gastric mucosa is complete, without cell infiltration.
The blue or green awns of [embodiment 2] core feels that ADM is to the research of the efficacy enhancing and toxicity reducing effect of rat liver cancer alone or in combination
1. experimental program
Healthy KM mice 60,18 ~ 22g, gets subcutaneous well-grown H that goes down to posterity in kunming mice body
22hepatic carcinoma tuberosity, oncocyte liquid is made by sterile working, be inoculated in KM mouse armpit subcutaneous, 5x106cell/ Mus, animal is divided into 6 groups at random, often organize 10, after inoculated tumour the 2nd day starts administration, and the blue or green awns of core feels and ADM administration simultaneously, altogether administration 10 days, experimental drug group set time every day gastric infusion once, administration 10 days.Positive drug control group lumbar injection ADM (3mg/kg, ip, qod), every other day once, the administration time time limit is with experimental drug group (ADM is total to administration 5 times).Specifically be grouped as follows:
1) matched group;
2) positive drug ADM group (3mg/kg, ip, qod);
3) blue or green awns feel Capsules group (1g/kg, po, qd) of core;
4) core blue or green awns feel capsule in high dose+amycin group (1g/kg, po, qd+3mg/kg, ip, qod);
5) dosage+amycin group (0.5g/kg, po, qd+3mg/kg, ip, qod) in core blue or green awns feel capsule;
6) core blue or green awns feel capsule low dosage+amycin group (0.25g/kg, po, qd+3mg/kg, ip, qod).
Last administration terminates rear 24h, and experimental mouse is got blood and made analysis of Hematology Changes, puts to death animal, completely takes tumor block and claims tumor heavy and body weight, thymus and spleen weight, gets each group of stomach, intestinal, hepatic tissue carry out light microscopic pathological study as paraffin section.Calculate tumour inhibiting rate, thymus and spleen index, drug combination Q-value, experimental result OfficeExcel software carries out statistical analysis.
2. statistical method
All data with
represent, compare between group and adopt t inspection, and SPSS11.5forwindows statistical software carries out one factor analysis of variance (One-WayANOVA), p value < 0.05 is significant difference, has statistical significance.
Drug effect criterion:
E in formula
afor A medicine tumour inhibiting rate, E
bfor B medicine tumour inhibiting rate, E
aBbe that two medicines share tumour inhibiting rate, q=0.85 ~ 1.15 are that the effect of share of two medicines is added, and q > 1.15 is that the effect of share of two medicines strengthens, and q < 0.85 is that two medicines share effect antagonism.
3. result
The blue or green awns of core feels that capsule is to rat liver cancer H
22there is antitumor activity.The blue or green awns of independent core feels that Capsules group (1g/kg, po, qd) tumour inhibiting rate is 30.95%, with model control group comparing difference remarkable (P < 0.05); The blue or green awns of core feels that capsule in high dose associating amycin group (1g/kg, po, qd+3mg/kg, ip, qod) tumour inhibiting rate is 46.45%, with model control group comparing difference remarkable (P < 0.01); In core blue or green awns feel capsule, dosage combinations amycin group (0.5g/kg, po, qd+3mg/kg, ip, qod) tumour inhibiting rate is 40.73%, with model control group comparing difference remarkable (P < 0.01); The blue or green awns of core feels that capsule low dosage associating amycin group (0.25g/kg, po, qd+3mg/kg, ip, qod) tumour inhibiting rate is 33.92%; The tumour inhibiting rate of positive control ADM group (3mg/kg) is 33.87%.The blue or green awns of core feels that capsule in high dose associating amycin group (1g/kg, po, qd+3mg/kg, ip, qod) drug combination Q-value is 0.86, and the effect of prompting drug combination is added.
Table 4, Fig. 3 are group tumor weight each at the end of experiment, and table 5 is for respectively organizing hemogram at the end of experiment, and Fig. 4 photo is the tumor tissue's photo at the end of experiment, and table 6 is for respectively organizing thymus, spleen index at the end of experiment.The blue or green awns of core feels that at the end of Capsules group experiment, the weight of animals increases, and compares, do not show toxic reaction with model control group.Histology pictures, gets each group of stomach, intestinal, hepatic tissue after 10% formalin is fixing, carries out light microscopic pathological study as paraffin section at the end of being experiment.
Microscopic observation paraffin section, model control group: hepatic tissue structural integrity, gastric mucosa is normally complete, and intestinal structure is normal; Positive drug ADM group: hepatocyte partial necrosis, stove shape cell infiltration, gastric mucosa is complete, normal, the slight cell infiltration of intestinal structure; Core blue or green awns feel capsule in high dose group: hepatocyte is normal, and gastric mucosa is normal, normal, the slight cell infiltration of intestinal structure; The blue or green awns of core feels that capsule low dosage combines dosage combinations ADM group in ADM group and core blue or green awns feel capsule: slight hepatic cell cell infiltration, and gastric mucosa is normally complete, intestinal tissue cell infiltration; The blue or green awns of core feels that capsule in high dose combines ADM group: normal, the slight cell infiltration of hepatocyte, gastric mucosa is normally complete, and intestinal tissue is normal.
The blue or green awns of table 4 core feels that capsule is to murine transplanted hepatocarcinoma H
22inhibitory action
T compares with model group; T1 compares with high dose core blue or green awns feel group; T2 compares with positive controls
The blue or green awns of table 5 core feels that capsule is to H
22the impact of mice with tumor hemogram
Table 6 respectively organizes thymus, spleen index
T compares with model group
4. conclusion
Experimental result shows, the blue or green awns of core feels that capsule body is interior to rat liver cancer H
22there is antitumor activity.
The blue or green awns of core to feel in capsule Mice Body gastric infusion every day 1 time, totally 10 days, reacts without overt toxicity.
Lotus tumor model control group is due to the increase of band tumor splenomegaly weight, and the blue or green awns of core feels that Capsules group has restitution to mice spleen enlargement, and the capsule of the blue or green awns feel of core simultaneously has protective effect to the damage of amycin to mice with tumor thymus and spleen.
Amycin makes mice with tumor immunoglobulin reduce, and the blue or green awns of core feels that capsule has increasing action to mice with tumor immunoglobulin.
The blue or green awns of core feels that tumor H treated by capsule combined chemotherapy medicine amycin (Doxorubicin, ADM)
22there is efficacy enhancing and toxicity reducing effect.
Pathological examination shows, ADM group hepatocyte partial necrosis, stove shape cell infiltration, and the blue or green awns of core feels that capsule associating ADM group hepatocyte is normal, and gastric mucosa is normally complete, and intestinal tissue is normal.
The blue or green awns of [embodiment 3] core feel capsule alone or in combination MTX on the impact of mice ehrlich carcinoma life cycle
1. experimental program
Healthy KM mice 70,18 ~ 22g, be taken at the Ascitic Tumor Cells liquid that KM mouse peritoneal to go down to posterity after EAC the 9th day, aseptic 0.9% sodium chloride injection dilution, concentration is made to be 2 × 107/ml, every Mus intraperitoneal inoculation 4 × 106/0.2ml, animal is divided into 6 groups at random, often organizes 10, after inoculated tumour the 2nd day starts administration, the blue or green awns of core feels and ADM continues medication simultaneously, to the whole death ray of mice, the blue or green awns of core feels that set time every day gastric infusion once, positive drug lumbar injection (MTX10mg/20ml/kg), within every 3 days, once the administration time time limit is with experimental drug group.Specifically be grouped as follows:
1) Normal group
2) model control group;
3) positive drug MTX group (10mg/kg, ip, q3d);
4) blue or green awns feel Capsules group (1g/kg, po, qd) of core;
5) blue or green awns feel capsule in high dose+MTX group (1g/kg, po, qd+10mg/kg, ip, q3d) of core;
6) dosage+MTX group (0.5g/kg, po, qd+10mg/kg, ip, q3d) in core blue or green awns feel capsule;
7) blue or green awns feel capsule low dosage+MTX group (0.25g/kg, po, qd+10mg/kg, ip, q3d) of core.
2. statistical method
All data with
represent, compare between group and adopt t inspection, p value < 0.05 is significant difference, has statistical significance.Drug effect criterion:
E in formula
afor A medicine increase in life span, E
bfor B medicine increase in life span, E
aBbe that two medicines share increase in life span, q=0.85 ~ 1.15 are that the effect of share of two medicines is added, and q > 1.15 is that the effect of share of two medicines strengthens, and q < 0.85 is that two medicines share effect antagonism.
3. result
The blue or green awns of core feels that capsule is total to administration 21 days, extends have certain effect to mice ehrlich carcinoma EAC life.The blue or green awns of independent core feels that Capsules group (1g/kg, po, qd) increase in life span is 33.11%, with model control group comparing difference remarkable (P < 0.05); The blue or green awns of core feels that capsule in high dose joint injection is 78.14% with methotrexate group (1g/kg, po, qd+10mg/kg, ip, q3d) increase in life span, with model control group comparing difference remarkable (P < 0.01); In core blue or green awns feel capsule, dosage combinations injection methotrexate group (0.5g/kg, po, qd+10mg/kg, ip, q3d) increase in life span is 73.51%, with model control group comparing difference remarkable (P < 0.01); The blue or green awns of core feels that capsule low dosage joint injection is 66.89% with methotrexate group (0.25g/kg, po, qd+10mg/kg, ip, q3d) increase in life span; The increase in life span of positive control MTX group 10mg/kg is 68.87%.The blue or green awns of core feels that capsule in high dose joint injection is 0.99 with methotrexate group (1g/kg, po, qd+10mg/kg, ip, q3d) drug combination Q-value, and the effect of prompting drug combination is added.Table 7, Fig. 5 are for respectively organizing increase in life span at the end of experiment.
The blue or green awns of table 7 core feels that capsule acted on mice ehrlich carcinoma (EAC) life cycle
T compares with model group; T1 compares with high dose core blue or green awns feel group; T2 compares with positive controls
4. conclusion
Experimental result shows, the blue or green awns of core feels to have certain effect to the prolongation of mice ehrlich carcinoma EAC life in capsule body.
The blue or green awns of core feels that capsule joint injection methotrexate has synergism to the prolongation of mice ehrlich carcinoma EAC life.
The blue or green awns of [embodiment 4] core feels that 5-Fu (administration simultaneously) the efficacy enhancing and toxicity reducing effect to gastric cancer in nude mice combined by capsule
1. experimental program
Healthy nude mice 60,16 ~ 18g, get subcutaneous well-grown people's poorly differentiated adenocarcinoma cancer BGC823 cell tumour tuberosity that goes down to posterity in nude mouse, oncocyte liquid is made by sterile working, is inoculated in nude mice axillary fossa subcutaneous, 6x106cell/ Mus.Until tumor growth to when can touch (about 30 ~ 60mm3), animal is divided into 6 groups at random, often organizes 10, label of weighing, inoculated tumour starts administration on the 4th day, is specifically grouped as follows:
1) matched group;
2) positive drug 5-Fu group (25mg/kg, ip, qod);
3) blue or green awns feel Capsules group (1g/kg, po, qd) of core;
4) blue or green awns feel capsule in high dose+5-Fu group (1g/kg, po, qd+25mg/kg, ip, qod) of core;
5) dosage+5-Fu group (0.5g/kg, po, qd+25mg/kg, ip, qod) in core blue or green awns feel capsule;
6) blue or green awns feel capsule low dosage+5-Fu group (0.25g/kg, po, qd+25mg/kg, ip, qod) of core.
Experimental drug group set time every day gastric infusion once, is total to administration 12 days.Positive drug control group lumbar injection (5-Fu25mg/20ml/kg), every other day once, the administration time time limit is with experimental drug group (5-Fu is total to administration 6 times).
Last administration terminates rear 24h, and experimental mouse is got blood and made analysis of Hematology Changes, puts to death animal, completely takes tumor block and claims tumor heavy and body weight, spleen weight, gets each group of stomach, intestinal, hepatic tissue carry out light microscopic pathological study as paraffin section.Calculate tumour inhibiting rate, spleen index, drug combination Q-value, experimental result OfficeExcel software carries out statistical analysis.
2. statistical method
All data with
represent, compare between group and adopt t inspection, and SPSS11.5forwindows statistical software carries out one factor analysis of variance (One-WayANOVA), p value < 0.05 is significant difference, has statistical significance.
Drug effect criterion:
E in formula
afor A medicine tumour inhibiting rate, E
bfor B medicine tumour inhibiting rate, EAB is that two medicines share tumour inhibiting rate, and q=0.85 ~ 1.15 are that the effect of share of two medicines is added, and q > 1.15 is that the effect of share of two medicines strengthens, and q < 0.85 is that two medicines share effect antagonism.
3. experimental result
The blue or green awns of core feels that capsule is total to administration 12 days, has more obvious antitumor activity to Human gastric cancer xenografts BGC823.It is 46.44% that the blue or green awns of independent core feels that tumour inhibiting rate organized by capsule (1g/kg, po, qd), with model control group comparing difference remarkable (P < 0.01); The blue or green awns of core feels that capsule in high dose associating Fluorouracil Injection group (1g/kg, po, qd+25mg/kg, ip, qod) tumour inhibiting rate is 62.74%, with model control group comparing difference remarkable (P < 0.01); In core blue or green awns feel capsule, dosage combinations Fluorouracil Injection group (0.5g/kg, po, qd+25mg/kg, ip, qod) tumour inhibiting rate is 47.67%, with model control group comparing difference remarkable (P < 0.01); The blue or green awns of core feels that capsule low dosage associating Fluorouracil Injection group (0.25g/kg, po, qd+25mg/kg, ip, qod) tumour inhibiting rate is 43.41%; The tumour inhibiting rate of positive control 5-Fu group (25mg/kg) is 42.42%.The blue or green awns of core feels that capsule in high dose associating Fluorouracil Injection group (1g/kg, po, qd+25mg/kg, ip, qod) drug combination Q-value is 0.91, and the effect of prompting drug combination is added.Table 8, Fig. 6 are group tumor weight each at the end of experiment, and table 9 is for respectively organizing spleen index at the end of experiment, and table 10 is for respectively organizing hemogram at the end of experiment.
Microscopic observation paraffin section, model control group: hepatic tissue structural integrity, gastric mucosa is complete, without cell infiltration, intestinal structure is normal; Microscopic observation paraffin section positive drug 5-Fu group: pyknosis that liver cell nuclear is slight, the karyopycnosis of gastric mucosa part parietal cell, visible apoptosis, cell infiltration that intestinal is slight; Core blue or green awns feel capsule in high dose group: hepatocyte is normal, and gastric mucosa is normal, and enterocyte is normal; The blue or green awns of core feels dosage combinations 5-Fu group in capsule low dosage associating 5-Fu group and core blue or green awns feel capsule: normally, gastric mucosa is complete, without cell infiltration for hepatocyte, cell infiltration that intestinal tissue is slight; The blue or green awns of core feels capsule in high dose associating 5-Fu group: hepatocyte is normal, and gastric mucosa is complete, without cell infiltration, cell infiltration that intestinal tissue is slight.WBC result shows: positive drug 5-Fu group WBC is lower, and the blue or green awns of core feels that capsule associating 5-Fu group WBC counting is higher than positive drug 5-Fu group.
The blue or green awns of table 8 core feels that capsule is to Human gastric cancer xenografts BGC823 inhibitory action
T compares with model group; T1 compares T2 with high dose core blue or green awns feel group and compares with positive drug group.
The blue or green awns of table 9 core feels that capsule is on the impact of Human gastric cancer xenografts BGC823 mice with tumor spleen index
T compares with model group
The blue or green awns of table 10 core feels that capsule is on the impact of people's transplantation cud cancer BGC823 mice with tumor hemogram
4. conclusion
Experimental result shows, the blue or green awns of core feels to have more obvious tumor-inhibiting action to Human gastric cancer xenografts BGC823 in capsule body.
The blue or green awns of core to feel in capsule Mice Body gastric infusion every day 1 time, totally 12 days, reacts without overt toxicity.
Lotus tumor model control group is due to the increase of band tumor splenomegaly weight, and the blue or green awns of core feels that Capsules group has restitution to Mus splenomegaly, and the capsule of the blue or green awns feel of core simultaneously has protective effect to Fluorouracil Injection to mice with tumor splenic trauma weight saving.
The blue or green awns of core feels that capsule combined chemotherapy medicine Fluorouracil Injection (FluorouracilInjection5-Fu) is treated tumor BGC823 and had efficacy enhancing and toxicity reducing effect.
Pathological observation positive drug 5-Fu group, pyknosis that liver cell nuclear is slight, the karyopycnosis of gastric mucosa part parietal cell, visible apoptosis, cell infiltration that intestinal is slight, the blue or green awns of core feels that capsule associating 5-Fu group hepatocyte is normal, and gastric mucosa is complete.
Peripheral blood cell counts, positive drug 5-Fu group WBC is lower, and the blue or green awns of core feels that capsule associating 5-Fu group WBC counting is higher than positive drug 5-Fu group.
The blue or green awns of [embodiment 5] core feel capsule alone or in combination 5-Fu, DDP (consecutive administration) to the efficacy enhancing and toxicity reducing effect of gastric cancer in nude mice
1. experimental program
Healthy nude mice 70, the nude mice axillary fossa subcutaneous vaccination BGC823 of experimental group, is then divided into above-mentioned 7 groups at random, starts administration (D1) after inoculation when tumor volume (30 ~ 80) mm3, tests 25 ~ 30 days.
Administration grouping scheme is as follows:
1) normal control nude mice 10 (PBS, QD, ig)
2) lotus tumor model comparison nude mice 10 (distilled water, QD, ig)
3) 10, lotus tumor model positive drug 5-Fu (5mg/kg, ip)+DDP (5mg/kg, ip), the 4th day starts to 5-Fu+DDP
4) blue or green awns feel capsule in high dose 10 (1g/kg, QD, ig) of core, the first gavage of core blue or green awns feel capsule 3 days.
5) the blue or green awns of core feels that capsule in high dose (1g/kg, QD, ig) only combines 5-Fu+DDP10, and the first gavage of core blue or green awns feel capsule 3 days, the 4th day starts associating 5-Fu+DDP again.
6) in core blue or green awns feel capsule, dosage (0.5g/kg, QD, ig) only combines 5-Fu+DDP10, and the first gavage of core blue or green awns feel capsule 3 days, the 4th day starts associating 5-Fu+DDP again
7) the blue or green awns of core feels that capsule low dosage (0.25g/kg, QD, ig) only combines 5-Fu+DDP10, and the first gavage of core blue or green awns feel capsule 3 days, the 4th day starts associating 5-Fu+DDP again
2. Testing index:
Weigh weekly once in experiment, measure weekly the length of tumor bodies and wide for 2 times.
Get blood at the end of experiment and do peripheral blood analysis;
Put to death animal after taking body weight, completely take tumor block, take pictures and claim tumor weight, calculate tumour inhibiting rate, potentiation index CDI or Q-value; Get spleen simultaneously, claim spleen weigh and calculate spleen index.
Get 1 ~ 7 group, intestinal, liver, nephridial tissue carry out light microscopic pathological study as paraffin section.
Finally statistical analysis is carried out to experimental result.
3. experimental result
The blue or green awns of core feels that capsule has more obvious antitumor activity to Human gastric cancer xenografts BGC823.Positive controls 5-Fu (5mg/kg, ip)+DDP (5mg/kg, ip) tumour inhibiting rate is 32.45%, core blue or green awns feel capsule in high dose group (1g/kg, po, qd) tumour inhibiting rate is 27.35%, with model control group comparing difference remarkable (P < 0.01); It is 33.45% that the blue or green awns of core feels that capsule in high dose (1g/kg, QD, ig) combines 5-Fu+DDP group tumour inhibiting rate, with model control group comparing difference remarkable (P < 0.01); In core blue or green awns feel capsule, dosage (0.5g/kg, QD, ig) combines 5-Fu+DDP group tumour inhibiting rate is 34.41%, with model control group comparing difference remarkable (P < 0.01); It is 39.82% that the blue or green awns of core feels that 5-Fu+DDP group tumour inhibiting rate combined by capsule low dosage (0.25g/kg, QD, ig).It is 0.93 that the blue or green awns of core feels that capsule in high dose (1g/kg, QD, ig) combines 5-Fu+DDP group drug combination Q-value, and the effect of prompting drug combination is added.Table 12 is group tumor weight each at the end of experiment, and table 11 is for respectively organizing hemogram at the end of experiment, and table 13 is for respectively organizing spleen index at the end of experiment.
Microscopic observation paraffin section, model control group: hepatic tissue structural integrity, gastric mucosa is complete, without cell infiltration, intestinal structure is normal; Positive drug 5-Fu (5mg/kg, ip)+DDP (5mg/kg, ip) group: pyknosis that liver cell nuclear is slight, the karyopycnosis of gastric mucosa part parietal cell, visible apoptosis, cell infiltration that intestinal is slight; Core blue or green awns feel capsule in high dose group: hepatocyte is normal, and gastric mucosa is normal, and enterocyte is normal; The blue or green awns of core feels that capsule in high dose combines 5-Fu+DDP group: hepatocyte is normal, gastric mucosa is complete, without cell infiltration, in cell infiltration core that intestinal tissue is slight blue or green awns feel capsule, dosage combinations 5-Fu+DDP group and the blue or green awns of core feel that capsule low dosage combines 5-Fu group: hepatocyte is normal, gastric mucosa is complete, without cell infiltration, cell infiltration that intestinal tissue is slight.
Hemogram result shows: positive drug 5-Fu group WBC, RBC are lower, and the blue or green awns of core feels that capsule associating 5-Fu+DDP group WBC, RBC counting are higher than positive drug 5-Fu group.
The blue or green awns of table 11 core feels that capsule is on the impact of people's transplantation cud cancer BGC823 mice with tumor hemogram
In table: 5-represents 5-Fu, mould is p-represents lotus tumor model comparison, and D-represents DDP, and core is high-represent the blue or green awns of core and feel high dose, and core is low-represent the blue or green awns of core and feel low dosage, in core-represent the blue or green awns of core feel in dosage.
The blue or green awns of table 12 core feels that capsule is on the impact of people's transplantation cud cancer BGC823 mice with tumor gross tumor volume
In table: 5-represents 5-Fu, mould is p-represents lotus tumor model comparison, and D-represents DDP, and core is high-represent the blue or green awns of core and feel high dose, and core is low-represent the blue or green awns of core and feel low dosage, in core-represent the blue or green awns of core feel in dosage.
The blue or green awns of table 13 core feels the impact of capsule on people's transplantation cud cancer BGC823 mice with tumor body weight and spleen
In table: 5-represents 5-Fu, mould is p-represents lotus tumor model comparison, and D-represents DDP, and core is high-represent the blue or green awns of core and feel high dose, and core is low-represent the blue or green awns of core and feel low dosage, in core-represent the blue or green awns of core feel in dosage.
4. conclusion
Experimental result shows, the blue or green awns of core feels to have more obvious tumor-inhibiting action to Human gastric cancer xenografts BGC823 in capsule body.Lotus tumor model control group is due to the increase of band tumor splenomegaly weight, and the blue or green awns of core feels that Capsules group has restitution to Mus splenomegaly, and the capsule of the blue or green awns feel of core simultaneously has protective effect to 5-Fu+DDP to mice with tumor splenic trauma weight saving.The blue or green awns of core feels that capsule combined chemotherapy medicine 5-Fu+DDP treats tumor BGC823 and has efficacy enhancing and toxicity reducing effect.Pathological observation positive drug 5-Fu+DDP group, pyknosis that liver cell nuclear is slight, the karyopycnosis of gastric mucosa part parietal cell, visible apoptosis, cell infiltration that intestinal is slight, the blue or green awns of core feels that capsule associating 5-Fu+DDP group hepatocyte is normal, and gastric mucosa is complete.Peripheral blood cell counts, positive drug 5-Fu+DDP group WBC is lower, and the blue or green awns of core feels that capsule associating 5-Fu+DDP group WBC counting is higher than positive drug 5-Fu+DDP group.
Claims (5)
1. tibetan medicine RENQINGMANGJUE is preparing the purposes in antitumor drug, and wherein said tumor is pulmonary carcinoma, hepatocarcinoma or gastric cancer.
2. purposes according to claim 1, the blue or green awns of wherein said core feels the arbitrary oral formulations be prepared in the pharmaceutical formulations being selected from pill, capsule, tablet, powder and granule.
3. tibetan medicine RENQINGMANGJUE and the second drug combination are preparing the purposes in antitumor drug, and wherein said tumor is pulmonary carcinoma, hepatocarcinoma or gastric cancer, and described the second medicament is chemotherapeutics.
4. purposes according to claim 3, wherein said chemotherapeutics is selected from cyclophosphamide, amycin, methotrexate, fluorouracil and cisplatin.
5. purposes according to claim 3, the blue or green awns of wherein said core feels the arbitrary oral formulations be prepared in the pharmaceutical formulations being selected from pill, capsule, tablet, powder and granule.
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| 藏医药与现代医学对肿瘤的研究比较;扎西东主等;《中国民族民间医药杂志》;20061231(第79期);第74页"3 治疗学"项下 * |
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