CN105769888A - Application of chikusetsusaponin IVa to preparation of antitumor drugs - Google Patents
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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Abstract
The invention mainly relates to application of chikusetsusaponin IVa to preparation of antitumor drugs. Through studies on change experiments about the tumor size of a mouse injected with the chikusetsusaponin IVa, it is discovered that the rate that the chikusetsusaponin IVa inhibits growth of a tumor in the mouse in early period is basically unchanged, the tumor in the mouse injected with the chikusetsusaponin IVa increases in the same pace with that in animals of a model group, but after the tumor enters a logarithmic growth period, the chikusetsusaponin IVa has an increasingly inhibiting effect on enlarging of the tumor in the mouse and has the inhibition rate slightly higher than that in a slow growing period, and accordingly the chikusetsusaponin IVa has a good inhibiting effect on melanomas of the mouse. It is discovered that the chikusetsusaponin IVa has a good inhibiting effect on the melanomas of the mouse through studies on change experiments about tumor weight of the mouse injected with the chikusetsusaponin IVa and can be prepared into novel antitumor drugs.
Description
Technical field
The present invention relates to the application of panax japonicus saponin I Va, especially relate to panax japonicus saponin I Va application in preparing melanoma medicine.
Background technology
Malignant tumor, i.e. cancer, be the class serious threat caused by the infinite multiplication of endogenous cell a kind of commonly encountered diseases and the frequently-occurring disease of human health, is one of the three big diseases of human death.
At present, the Therapeutic Method of cancer mainly has surgical operation, X-ray therapy and chemotherapy etc..Chemotherapy be utilize chemicals block fissional mechanism thus anticancer growth and breeding and promote Carcinoma cell differentiation a kind of therapeutic modality, be also the Main Means for the treatment of malignant tumor.But, traditional chemotherapeutics a series of limitation when treatment cancer.Curative effect and prognosis such as common chemotherapeutics such as cisplatin, amycin, mitomycin and hydroxy camptothecin etc. are all poor.Therefore, find safely and effectively anti-tumor medicine and be possible not only to alleviate the slight illness of patient, family and the burden of society can be alleviated simultaneously.Therefore, people are always at the positive method finding new treatment cancer or medicine.
Along with modern medicine to cancer research progressively deeply, Chinese medicine anticancer with assist anticancer to achieve bigger progress.Find that some Chinese medicine monomer or effective ingredient can strengthen the chemotherapeutics inhibitory action to tumor cell proliferation in vitro, the laboratory animal sensitivity to chemotherapeutics can be improved in vivo, alleviate tumor weight experimentation and clinical observation all points out Chinese medicine that chemotherapeutics is had synergistic function.Chinese medicine suppressing tumor cell proliferation, stablize tumor bulk-growth, improve symptom and sign, attenuation synergistic, prevention of recurrence, raising life quality, extend life cycle etc. in there is unique advantage.By strengthening immunity, direct killing tumor cell, inducing apoptosis of tumour cell and regulating cell cycle！Reversing the various ways such as chemotherapy resistance and improve the curative effect of chemotherapeutics, effective site or the component for treating cancer of finding high-efficiency low-toxicity from Chinese medicine have become study hotspot.
Radix Ginseng is famous traditional tonic medicine, has strongly invigorating primordial QI, admittedly takes off, promotes the production of body fluid, calms the nerves and the effect such as Fructus Alpiniae Oxyphyllae.Saponin component is effective ingredient important in Radix Ginseng, separated from Chinese crude drug at present identifies tens kinds of ginsenoside's compounds, and great majority are all dammarane type (including diol type and three alcohol type) saponin.
Panax japonicus saponin I Va (chikusetsusaponinIVa) is distributed in the plants such as Radix Ginseng (Panaxginseng), Rhizoma Panacis Japonici (PanaxjaponicusC.A.Meyor), Rhizoma Panacis Majoris (PanaxjaponicusC.A.Meyor.var.major (Burk.) C.Y.WuetK.M.Feng).
Panax japonicus saponin I Va, is the pentacyclic triterpene saponins being aglycon with oleanolic acid few in number in Radix Ginseng, and its structural formula is:
nullExperiment in vitro proves，Panax japonicus saponin I Va does not have hemolytic [Hase,J.,etal.,Thestructure-hemolysisrelationshipofoleanolicacidderivativesandinhibitionofthesaponin-inducedhemolysiswithsapogenins.JPharmacobiodyn,1981.4(11):833-837]，Kinds of tumor cells is substantially free of cytotoxicity [Baek,N.-I.,etal.,Cytotoxicitiesofginsengsaponinsandtheirdegradationproductsagainstsomecancercelllines.ArchivesofPharmacalResearch,1995.18(3):164-168.].nullCAMP phosphorglase inhibitor NikaidoT.etal.,InhibitorsofcyclicAMPphosphodiesteraseinPanaxginsengCAMeyerandPanaxjaponicusCAMeyer.Chemicalandpharmaceuticalbulletin,1984.32(4):1477-1483]，Anti-herpesvirus [Rattanathongkom,A.,etal.,EvaluationofchikusetsusaponinIVaisolatedfromAlternantheraphiloxeroidesforitspotencyagainstviralreplication.PlantaMed,2009.75(8):829-835]，Antithrombotic [Dahmer,T.,etal.,AntithromboticeffectofchikusetsusaponinIVaisolatedfromIlexparaguariensis(Mate).JMedFood,2012.15 (12): 1073-1080] biological activity such as.nullExcept Lee in 2015,K.M. report that HCT116 cell is had the outer [Lee of cytotoxic activity by its derivant panax japonicus saponin I Va methyl ester,K.M.,etal.,ChikusetsusaponinIVamethylesterinducescellcyclearrestbytheinhibitionofnucleartranslocationofbeta-catenininHCT116cells.BiochemBiophysResCommun,2015.459(4):591-596]，And have no with the report of the panax japonicus saponin I Va medicine being key component application aspect in preparing antitumor drug.
Summary of the invention
It is an object of the invention to be in that to avoid the deficiencies in the prior art part to provide a kind of application with the panax japonicus saponin I Va medicine being key component in preparing antitumor drug.
The present invention one side provide panax japonicus saponin I Va application in preparing antitumor drug.Panax japonicus saponin I Va of the present invention, is the triterpene saponin being aglycon with oleanolic acid few in number in Radix Ginseng, and its structural formula is:
Wherein, described panax japonicus saponin I Va is used alone in preparing antitumor drug or uses with chemotherapy drugs in combination.
Wherein, the dosage form of described antitumor drug is medicinal preparation for oral administration or injection medicament.
Preferably, described medicinal preparation for oral administration is capsule, microcapsule, liposome, granule, tablet, oral liquid, drop pill or freeze dried powder.
Preferably, injection medicament is injectable emulsion.
Preferably, injectable emulsion is Emulsion used for intravenous injection, intramuscular injection Emulsion, lumbar injection Emulsion or subcutaneous injection Emulsion.
The invention has the beneficial effects as follows: the present invention is by studying the change experiment of the mice Tumor size of injection panax japonicus saponin I Va, the suppression ratio of the tumor growth in Mice Body is basically unchanged by lump in early days that find in the Mice Body of panax japonicus saponin I Va, grow simultaneously with the lump volume of model group animal, but the inhibitory action rate that lump volume is increased by entrance logarithmic growth after date increases, suppression ratio is slightly above slow trophophase, it was demonstrated that murine melanoma is had good inhibiting effect by panax japonicus saponin I Va.Finding by studying the change experiment of the mouse tumor weight of injection panax japonicus saponin I Va, melanoma is had good inhibiting effect by panax japonicus saponin I Va.
Accompanying drawing explanation
Fig. 1 is the variation tendency schematic diagram of mice subcutaneous mass size after inoculation melanoma cell；
Fig. 2 is from the big logotype of volume of the melanoma lump of the subcutaneous separation of mice after being administered 15 days；
Fig. 3 is from the melanoma lump weight size of the subcutaneous separation of mice after being administered the 15th day.
Detailed description of the invention
For making the object, technical solutions and advantages of the present invention clearly understand, below in conjunction with detailed description of the invention and with reference to accompanying drawing, the present invention is described in more detail.It should be understood that these descriptions are illustrative of, and it is not intended to limit the scope of the present invention.Additionally, in the following description, the description to known features and technology is eliminated, to avoid unnecessarily obscuring idea of the invention.
An aspect of of the present present invention provides panax japonicus saponin I Va application in preparing antitumor drug.
Panax japonicus saponin I Va of the present invention, is the triterpene saponin being aglycon with oleanolic acid few in number in Radix Ginseng, and its structural formula is:
The common tumor of six big classes includes:
One, tumor of head and neck: nasal cavity and nasal sinuses malignant tumor, nasopharyngeal carcinoma, oral cancer, laryngeal carcinoma, salivary tumor transformation, intracranial tumor, thyroid carcinoma, carcinoma of tongue；
Two, breast tumor: pulmonary carcinoma, esophagocardial carcinoma, breast carcinoma, mediastinum tumor；
Three, digestive system tumor: gastric cancer, colorectal cancer and sigmoid colon and rectal cancer, hepatocarcinoma, cancer of pancreas and peri-ampullar carcinoma, biliary tract, intestinal malignant tumor；
Four, genitourinary system tumor: renal carcinoma, carcinoma of prostate, bladder cancer, Testicular Malignant Tumors, carcinoma of penis, cervical cancer, carcinoma of endometrium, ovarian cancer；
Five, bone and soft tissue neoplasms: 1, soft tissue and cutaneous tumor: (1) malignant fibrohistiocytoma (2) rhabdomyosarcoma (3) synovial sarcoma (4) malignant melanoma of skin；2, bone tumor: (1) osteosarcoma (2) ewing's sarcoma；
Six, lymph and hematological system tumor: lymphoma, multiple myeloma, acute leukemia, chronic leukemia, erythrocytosis, thrombocytosis, myelodysplastic syndrome, myelofibrosis, malignant histocytosis.
Wherein, described panax japonicus saponin I Va is used alone in preparing antitumor drug or uses with chemotherapy drugs in combination.
Chemotherapeutics, be to pathogenic microorganism, parasite, some autoimmune disease, malignant tumor associated diseases medicine.Common chemotherapeutics type includes: alkylating agent, antimetabolite, plant, antitumor antibiotic, hormones, other classes.
Wherein, the dosage form of described antitumor drug is medicinal preparation for oral administration or injection medicament.
Preferably, described medicinal preparation for oral administration is capsule, microcapsule, liposome, granule, tablet, oral liquid, drop pill or freeze dried powder.
Preferably, injection medicament is injectable emulsion.
Preferably, injectable emulsion is Emulsion used for intravenous injection, intramuscular injection Emulsion, lumbar injection Emulsion or subcutaneous injection Emulsion.
Embodiment
1. test material
1.1 medicines and reagent
DMEM high glucose medium is purchased from Gibco company, and FBS hyclone is purchased from Clark company, and pancreatin is purchased from Suo Laibao bio tech ltd, Beijing.
1.2 cells and animal
Murine melanoma high-transfer cell B16F10, is purchased from Chinese Academy of Sciences's Shanghai cell bank.C57BL/6 mice, male, 20-22g, it is purchased from Beijing Vital River Experimental Animals Technology Co., Ltd..
1.3 animal models
1.3.1 the recovery of cell: cell frozen in liquid nitrogen is taken out, is immediately placed in 37 DEG C of water-baths, is melted into liquid, it is positioned over after sterilization in super-clean bench, it is transferred to 10ml centrifuge tube after Cell sap piping and druming uniformly, adds 2mlDMEM high glucose medium, 1000rpm, centrifugal 5min, supernatant discarded after taking-up, adds the DMEM high glucose medium containing 10%FBS (hyclone) in centrifuge tube, is transferred in Tissue Culture Flask after piping and druming uniformly, 37 DEG C, 5%CO2 incubator is cultivated.
1.3.2 the going down to posterity of cell: take the B16F10 cell of adherent growth, discard culture medium, PBS three times, with the trypsin digestion cell of 0.25%, add the DMEM high glucose medium containing 10%FBS and terminate digestion, Cell sap is transferred to centrifuge tube, centrifugal 1000rpm, 5min, abandoning supernatant, add the DMEM high glucose medium containing 10%FBS, piping and druming is uniformly, it is sub-packed in 3 Tissue Culture Flasks, completes once to go down to posterity.
1.3.3 prepared by cell suspension: B16F10 cell, through repeatedly stably going down to posterity, collects B16F10 cell before modeling, add normal saline, cell counting, adjust cell concentration so that it is cell density is 2 × 107Individual/ml.
1.3.4 cell inoculation: mice right shoulder arm place subcutaneous injection of tumor cells suspension 0.1ml, i.e. every mouse subcutaneous injection B16F10 tumor cell 2 × 106Individual.
1.4 administrations
Panax japonicus saponin I Va and positive drug cyclophosphamide are dissolved in normal saline (containing 2%DMSO and 2% tween 80).From the after mouse inoculation tumor the 2nd day, successive administration 15d, blank group and model control group administration normal saline (containing 2%DMSO and 2% tween 80), cyclophosphamide dosage is 20mg/kg, panax japonicus saponin I Va dosage is 25mg/kg, and administering mode is lumbar injection.
1.5 detections
Mouse Weight and gross tumor volume growth pattern is detected during administration.After being administered 15 days, water 12h is can't help in fasting, and next day dissects, and strips tumor, weighs.
1.6 data statisticss and analysis
Data statistics application EXCEL and GraphpadPrism software, data analysing method is the Dunnett'sMultipleComparisonTest in T-test and One-wayANOVA.Result mean ± SEM represents, p < 0.05 has significant difference, and p < 0.01 has pole significant difference.
2. result of the test
2.1 gross tumor volume variation tendencies
Fig. 1 is the variation tendency schematic diagram of mice subcutaneous mass size after inoculation melanoma cell.
In Fig. 1, N is the change of model group mice Tumor size, N=6；IVa is the change of the mice Tumor size of injection panax japonicus saponin I Va；P is the change of the mice Tumor size of injection cyclophosphamide；The dosage of panax japonicus saponin I Va and cyclophosphamide respectively 25mg/kg body weight and 20mg/kg body weight；Abscissa is the size of different time lump after inoculation lump.
It will be seen from figure 1 that be seeded to 13 days tumors to be in a slow rise period, after the 13rd day, enter exponential phase.Murine melanoma is had good inhibiting effect by positive drug cyclophosphamide, but is as tumor growth time lengthening, and lump increases basic Tong Bu with model group.The suppression ratio of the tumor growth in Mice Body is basically unchanged by lump in the Mice Body of injection panax japonicus saponin I Va in early days, grow simultaneously with the lump volume of model group animal, but the inhibitory action rate that lump volume is increased by entrance logarithmic growth after date increases, it is suppressed that rate is slightly above slow trophophase.
Fig. 2 is from the big logotype of volume of the melanoma lump of the subcutaneous separation of mice after being administered 15 days.
In Fig. 2, ModelControl is model group；PositiveControl is cyclophosphamide group；IVa is panax japonicus saponin I Va group；Photo amplification is 1:1.
Figure it is seen that from gross tumor volume, all experimental group individual variations are less, and group difference is notable；Tumor growth is had obvious inhibiting effect by panax japonicus saponin I Va.
2.2 mouse tumor weight
Fig. 3 is from the melanoma lump weight size of the subcutaneous separation of mice after being administered the 15th day.
In Fig. 3,1 is positive drug cyclophosphamide；2 is panax japonicus saponin I Va；3 is animal pattern；N=6.
Figure it is seen that it is shown that melanoma is had good inhibiting effect by panax japonicus saponin I Va.
As mentioned above, describe the panax japonicus saponin I Va of the present invention application in preparing antitumor drug in detail, the present invention is by studying the change experiment of the mice Tumor size of injection panax japonicus saponin I Va, the suppression ratio of the tumor growth in Mice Body is basically unchanged by lump in early days that find in the Mice Body of panax japonicus saponin I Va, grow simultaneously with the lump volume of model group animal, but the inhibitory action rate that lump volume is increased by entrance logarithmic growth after date increases, suppression ratio is slightly above slow trophophase, prove that murine melanoma is had good inhibiting effect by panax japonicus saponin I Va.The present invention finds by studying the change experiment of the mouse tumor weight of injection panax japonicus saponin I Va, and melanoma is had good inhibiting effect by panax japonicus saponin I Va, can prepare into new antitumor drug.
It should be appreciated that the above-mentioned detailed description of the invention of the present invention is used only for exemplary illustration or explains principles of the invention, and it is not construed as limiting the invention.Therefore, any amendment of making when without departing from the spirit and scope of the present invention, equivalent replacement, improvement etc., should be included within protection scope of the present invention.Additionally, claims of the present invention be intended to fall in the equivalents on scope and border or this scope and border whole change and modifications example.
Claims (6)
1. panax japonicus saponin I Va application in preparing antitumor drug.
2. apply as claimed in claim 1, it is characterised in that described panax japonicus saponin I Va is used alone in preparing antitumor drug or uses with chemotherapy drugs in combination.
3. the application as described in any one of claim 1-2, it is characterised in that the dosage form of described antitumor drug is medicinal preparation for oral administration or injection medicament.
4. apply as claimed in claim 3, it is characterised in that described medicinal preparation for oral administration is capsule, microcapsule, liposome, granule, tablet, oral liquid, drop pill or freeze dried powder.
5. the application as described in any one of claim 3-4, it is characterised in that described injection medicament is injectable emulsion.
6. apply as claimed in claim 5, it is characterised in that described injectable emulsion is Emulsion used for intravenous injection, intramuscular injection Emulsion, lumbar injection Emulsion or subcutaneous injection Emulsion.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020526594A (en) * | 2017-07-13 | 2020-08-31 | イースト チャイナ ユニバーシティ オブ サイエンス アンド テクノロジー | Saponin compounds targeting PD-1 and their applications |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55122721A (en) * | 1979-03-13 | 1980-09-20 | Res Inst For Prod Dev | Antidiabetic agent |
| CN104434940A (en) * | 2014-12-02 | 2015-03-25 | 中国人民解放军第四军医大学 | Application of panax japonicus IV a in prevention and treatment of cardiovascular disease and complication of cardiovascular disease |
-
2016
- 2016-03-16 CN CN201610150469.2A patent/CN105769888A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55122721A (en) * | 1979-03-13 | 1980-09-20 | Res Inst For Prod Dev | Antidiabetic agent |
| CN104434940A (en) * | 2014-12-02 | 2015-03-25 | 中国人民解放军第四军医大学 | Application of panax japonicus IV a in prevention and treatment of cardiovascular disease and complication of cardiovascular disease |
Non-Patent Citations (2)
| Title |
|---|
| CHUN LIANG等: "Oleanane-type triterpenoids from Panax stipuleanatus and their anticancer activities", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| 文德鉴等: "竹节人参总皂苷抗炎作用的实验研究", 《时珍国医国药 》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020526594A (en) * | 2017-07-13 | 2020-08-31 | イースト チャイナ ユニバーシティ オブ サイエンス アンド テクノロジー | Saponin compounds targeting PD-1 and their applications |
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