CN1264580A - Application of tanshinone in preparing medicine for treating tumor - Google Patents
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Abstract
An application of tanshinone in preparing medicine for treating tumor is disclosed, which is based on the fact that said tanshin one has high effect on killing tumor cells and induce the tumor cells to differentiate or die. Its advantages are rich raw material, simple preparing process and low toxic by-effect.
Description
The present invention relates to the purposes of salviamiltiorrhizabung extract TANSHINONES in the preparation pharmaceutical product, the particularly application of TANSHINONES in the medicine of preparation treatment tumor.
Radix Salviae Miltiorrhizae is the root of Labiatae salvia (Salvia miltiorrhiza Bunge), is blood-activating and stasis-removing commonly used
[1]Its cold nature, bitter in the mouth, nontoxic.The function that has promoting blood circulation to restore menstrual flow, removing heat from blood detumescence, relieving restlessness to clear away heart-fire.Compendium of Material Medica
[2]On records such as " superfluous toxic swelling erysipelas of Treated with Radix Salviae Miltiorrhizae malignant boil scabies, wart and evacuation of pus pain relieving, growth muscle " is arranged.(Tanshinone Tan) is the ether or the ethanol extraction of Radix Salviae Miltiorrhizae root to TANSHINONES.For seeking the effective ingredient in the Radix Salviae Miltiorrhizae, study the relation between its pharmacological action and chemical constitution, lot of domestic and foreign scholar has carried out extensive work, successively separate 15 kinds of compositions that obtain Radix Salviae Miltiorrhizae, measured their structural formula (see figure 1) simultaneously, and with these compositions called after Tanshinone I successively (I), tanshinone (II), Tanshinone II B (III), cryptotanshinone (IV), iso tanshinone I (V), iso tanshinone IIA (VI), different cryptotanshinone (VII), hydroxyl tanshinone (VIII), Methyl tanshinoate (IX), Miltirone (X), Salviol (XI), dihydrotanshinone I (XII), neotanshinone A (XIII), neotanshinone B (XIV) and neotanshinone C (XV)
[3]Studies show that by these 15 kinds of constituent structure tanshinone all contains o-quinone or para-quinoid structure as the effective ingredient of Radix Salviae Miltiorrhizae to Radix Salviae Miltiorrhizae.Because the quinones composition is reduced easily and changes the diphenols derivant into, the oxidized again quinone that changes into easily again of the latter plays the electronics transfer function in transition process.Simultaneously, their metabolites in vivo participate in the multiple biochemical reaction of body, and as the coenzyme of biological respinse some biochemical reaction are risen and to promote or interference effect, thereby show multiple pharmacological effect, as antibiotic, antiviral etc.
Discover, TANSHINONES has the natural anti-oxidation effect, Chinese Academy of Medical Sciences's tanshinone that biophysics has been studied is to hepatocyte lipid peroxidation product and the interactional influence of DNA, and reach a conclusion, think that tanshinone is a kind of new effective lipid within endothelial cells peroxidating product and interactional inhibitor of DNA.It may be to block the chain reaction of lipid peroxidation by eliminating the lipid free radical to the protective effect of DNA, suppresses the generation of DNA addition product, thereby has reduced the latter's cytotoxicity
[4]
TANSHINONES mainly has the cardiovascular pharmacological effect clinically, but its atherosclerosis
[5], have the myocardial infarction area of dwindling, reduce myocardial oxygen consumption, thrombosis and platelet aggregation all had inhibitory action
[6,7]Simultaneously, Tanshinone II B (III), cryptotanshinone (IV), Methyl tanshinoate (IX), hydroxyl tanshinone (VIII), dihydrotanshinone I (XII) have stronger inhibitory action to staphylococcus aureus and Resistant strain thereof.Tanshinone I (I), tanshinone (II), cryptotanshinone (IV), hydroxyl tanshinone (VIII) are to Bacillus tuberculosis (H
37RV) bacterial strain has stronger inhibitory action
[3]
TANSHINONES is mainly used in treatment coronary heart disease, acne, dysmenorrhea, insomnia and anti-inflammation clinically, and the golden Portugal bacterium in amygdala inflammation, furuncle of ear, suppurative osteomyelitis, the burn infects, and effect is remarkable
[8]
At present, malignant tumor constitutes threat greatly to human health, and the treatment of malignant tumor mainly contains approach such as operation, chemotherapy, radiotherapy.For most of solid tumors, common treatment means is for performing the operation in conjunction with radiotherapy (radiotherapy) and chemotherapy (chemotherapy), chemotherapeutics is by the cytotoxic effect kill tumor cell to tumor cell, the defective that but most of chemotherapeutics are toxic greatly, side effect is big, many patients are because of being difficult to bear the toxicity therapy discontinued of chemotherapeutics; And on the other hand, some tumor cell is because of undesirable to chemotherapeutics or the insensitive therapeutic effect that makes of radiotherapy ray.Therefore, need to seek, develop the antitumor drug that new toxic and side effects is little, therapeutic effect is good clinically.
The induction-differential therapy malignant tumor is the new way of cancerous protuberance treatment, the fundamental difference of induction-differential therapy and traditional chemical treatment is not killing tumor cell, but transform to normal cell by drug-induced tumor cell, simultaneously normal cell there is not lethal effect, and side effect such as rare bone marrow depression.So induction-differential therapy is compared with other treatment approach bigger superiority is arranged, and causes the extensive attention of medical circle thus
[9]1986, the success of all-trans-retinoic acid (ATRA) induction-differential therapy acute promyelocytic leukemic (APL) promoted the basis of induction-differential therapy malignant tumor and the progress of clinical research greatly
[10]But retinoic acid related syndromes and the drug resistance that takes place have fast limited the clinical practice of this medicine, therefore, press for the new differentiation agent of inducing efficient, low toxicity of searching and improve the induction-differential therapy of tumor
[11-13]
At the defective of prior art, the object of the present invention is to provide the new purposes of TANSHINONES in preparation medicine for treating tumor thing; Described treatment tumor includes but not limited to killing tumor cell, inducing tumor cell differentiation and inducing apoptosis of tumour cell.
According to an aspect of the present invention, the present invention relates to the application of TANSHINONES as preparation medicine for treating tumor thing, described tumor includes but not limited to leukemia, hepatocarcinoma, pulmonary carcinoma, cerebral glioma, osteosarcoma, cervical cancer, ovarian cancer, colorectal cancer, gastric cancer, cancer of pancreas, renal carcinoma, bladder cancer, laryngeal carcinoma, nasopharyngeal carcinoma.
According to a further aspect in the invention, the present invention relates to the application of TANSHINONES as the medicine of induction-differential therapy tumor, described tumor includes but not limited to leukemia, pulmonary carcinoma, hepatocarcinoma, cerebral glioma, osteosarcoma, gastric cancer, colorectal cancer, renal carcinoma, bladder cancer.
According to another aspect of the invention, the present invention relates to the application of TANSHINONES as the medicine of apoptosis-induced treatment tumor, described tumor includes but not limited to leukemia, pulmonary carcinoma, hepatocarcinoma, cerebral glioma, osteosarcoma, straight colon cancer, gastric cancer, renal carcinoma, bladder cancer.
In order to understand essence of the present invention better, below by to TANSHINONES lethal effect, the introduction of inducing differentiation and apoptosis-induced experimental study of effect result, describe the present invention in detail:
One. the effect of TANSHINONES killing tumor cells
Experiment in vitro shows that TANSHINONES has lethal effect to kinds of tumor cells, and the tanshinone of 1 μ g/ml is to human promyelocytic leukemia cell strain HL-60, the NB of In vitro culture
4, the slow grain of people erythroleukemia cell strain K562, human hepatoma cell strain SMMC-7721, human lung carcinoma cell line SPC-A-1, human stomach cancer cell line SGC7901, human nasopharyngeal carcinoma cell line CNE1 etc. all have lethal effect.
Two. differentiation of TANSHINONES inducing tumor cell and effect of apoptosis
Find that after deliberation the TANSHINONES of non-toxic can be induced kinds of tumor cells differentiation and apoptosis.The tanshinone of employing 0.25～0.5 μ g/ml acts on the human promyelocytic leukemia cell strain (HL-60 and the NB that are in exponential phase of In vitro culture respectively
4), the erythroleukemia cell strain (K562) of the slow grain of people, human hepatoma cell strain (SMMC-7721), human lung carcinoma cell line (SPC-A-1), human stomach cancer cell line (SGC7901) and human nasopharyngeal carcinoma cell line CNE1, with 0.01%DMSO (solvent of TanIIA) is blank, with the clinical positive contrast of differentiation medicament all-trans-retinoic acid (ATRA) of inducing commonly used at present, behind the drug effect 5 days, collecting cell, carry out light microscopic, electron microscopic observation cellular morphology, calculate tumor cell induction differentiation rate, apoptosis rate and growth inhibition ratio; Flow cytometer (Flow cytometry) carries out cell cycle analysis and gene expression detects, and the results are shown in Table 1
The external evoked differentiation of table 1 TANSHINONES
*Compare with blank group (DMSO), there were significant differences in P＜0.01
*Compare P＞0.05, no significant difference with positive controls (ATRA)
The result shows, but the TANSHINONES inducing tumor cell to optimum or normal cell differentiation, its induction of differentiation does not have significant difference with the differentiation agent ATRA that induces that uses at present clinically.In addition, TANSHINONES also has the effect (heavy dose of TANSHINONES has the cell toxicant lethal effect) of inducing apoptosis of tumour cell in the inducing tumor cell differentiation, illustrates that the non-toxic TANSHINONES has the effect of treatment tumor equally.
Three. the mechanism of TANSHINONES treatment tumor
Experiment in vitro shows that TANSHINONES has differentiation of inducing and antitumaous effect, and its anticancer mechanism that presses down cancer is: 1. it is synthetic to suppress cell proliferation and DNA
The flow cytometer testing result shows that TANSHINONES can stop cell in G
0/ G
1Phase makes it can not enter the S phase, thereby suppresses the synthetic and cell proliferation of DNA.TANSHINONES can be expressed by suppressing PCNA (PCNA), influences DNA polymerase δ activity, and it is synthetic to suppress DNA, thereby suppresses cell proliferation, the inducing cell differentiation.2. inducing cell breaks up and apoptosis
Studies show that the curative effect of cancer therapy drug not only depends on the interaction of itself and specific target cell, also depend on the ability of its cell death inducing, tumor cell is the key factor of decision chemotherapy effect to the sensitivity of apoptosis.TANSHINONES can be induced the kinds of tumor cells apoptosis, when inducing differentiation with apoptotic generation, therefore the mechanism of TANSHINONES treatment function of tumor may be the inducing cell differentiation, the while cell death inducing, or inducing tumor cell is divided into mature cell, and these mature cells finally move towards apoptosis.3. to the influence of gene expression
By cell DNA/RNA after the TANSHINONES effect is analyzed discovery, after the TANSHINONES effect, the several genes of tumor cell is expressed and is changed, wherein, the expression of c-myc oncogene obviously reduces, and c-fos gene expression strengthens, it is generally acknowledged, c-myc and c-fos expression of gene are closely related with cell proliferation and differentiation respectively, it is relevant that the amplification of c-myc gene and overexpression and malignant transformation of cells and tumor form, and the decline of its expression then changes with the form of tumor cell and differentiation has substantial connection; The c-fos gene then is the sign of cell differentiation.In addition, after the TANSHINONES effect, also change with closely-related gene p53 of apoptosis and bcl-2 expression, p53 gene and bcl-2 gene are all closely related with apoptosis, the wild type p53 gene can promote the generation of apoptosis, and mutant P 53 gene then has inhibitory action to apoptosis; The bcl-2 gene is then special relevant with apoptosis, the generation of bcl-2 gene apoptosis capable of inhibiting cell, after the TANSHINONES effect, tumor cell bcl-2 gene expression significantly reduces, and p53 gene expression strengthens, and the prompting TANSHINONES is by acting on the tumor differentiation and anticancer, cancer suppressing action is brought into play in the apoptogene expression.4. to the influence of tumor cell telomerase activation
HL60, K562 and APL cell are after 0.5 μ g/ml TANSHINONES acts on 5 days, 9 days, 5 days respectively, and Tan is respectively 30.8%, 50.8% and 37.7% (PCR-TRAP method testing result) to above cell telomerase activation suppression ratio.Telomerase is considered to major part and has the immortality cell of unlimited multiplication capacity and a New Set of tumor cell, suppresses the activity of telomerase, can suppress growth of tumour cell, so downward modulation or inhibition telomerase activation become new approaches of oncotherapy.TANSHINONES has the effect that suppresses HL60, K562 and APL cell telomerase activation, thus prompting, and TANSHINONES may be by suppressing the telomerase activation performance antineoplastic action of tumor cell.
From above result, can be the invention has the advantages that:
1. the present invention has excavated the novel medical use of TANSHINONES, has opened up a new application.
2. TANSHINONES of the present invention derives from the salviamiltiorrhizabung extract, and toxic and side effects is little, and pharmacological action is strong, has good prospect in medicine.
3. raw material of substance of the present invention source is abundant, inexpensive, and preparation technology is simple, has good commercial application prospect.
4. the medicine of material preparation of the present invention has the good result of treatment tumor, by inhibition tumor cell proliferation, inducing tumor cell differentiation and apoptosis, and inhibited to kinds of tumor cells.
5. the medicine of the material preparation of the present invention of non-toxic has differentiation of inducing and apoptosis-induced effect to tumor cell, show by experiment in vivo and vitro, but the TANSHINONES inducing tumor cell of non-toxic is to mature cell or terminal cell differentiation, and the inhibition growth of tumour cell, the new way of having opened up oncotherapy.
6. show through clinical experiment, tablet, capsule, injection and the oral liquid of TANSHINONES preparation of the present invention are evident in efficacy, relatively do not have significant difference with the differentiation agent all-trans-retinoic acid of inducing of present use, and have no side effect and the drug resistance phenomenon, good potential applicability in clinical practice is arranged.
Fig. 1 is the molecular structural formula of 15 kinds of compositions of Radix Salviae Miltiorrhizae.
Below by description, further specify but do not limit the present invention the embodiment of the invention.
The experiment of embodiment 1 animal vivo antitumor
The NIH mice, body weight 20～24 grams, male and female all have, and provide (certificate number: No. the 67th, the real moving pipe in river) by laboratory animal room of Sichuan Province's antibiotics industrial research institute.Each experiment sex is identical, every treated animal number＞10.Rat liver cancer H
22Protecting kind by the attached First Academy of Huaxi Medical Univ institute of oncology goes down to posterity.Tanshinone (TanIIA) provide standard substance by Nat'l Pharmaceutical ﹠ Biological Products Control Institute, lot number 766-9204.Be dissolved to required concentration (experiment final concentration＜0.02%) with 10% dimethyl sulfoxine (DMSO) before using.Lotus hepatocarcinoma H gets in the sterile working
22Mouse ascites is diluted to and contains 1 * 10
7/ ml oncocyte, every Corium Mus is inoculated 0.2ml down.At random be divided into 3 group with animal next day: blank group, the isopyknic DMSO of subcutaneous injection; Positive controls, lumbar injection chemotherapeutics fluorouracil (5-Fu), 3mg/kg body weight; Experimental group, subcutaneous injection Tan IIA, 20mg/kg body weight; Repeat 3 times.Each treated animal number and administration number of times see Table 1.Next day is put to death animal in drug withdrawal, dissects and peels off tumor, claims that tumor heavily reaches body weight, calculates tumour inhibiting rate and carries out statistical procedures with the t check, the results are shown in Table 2.Each organizes tumor specimen 20% formalin fixed, specimens paraffin embedding slices, HE dyeing, om observation.
Table 2 tanshinone is to rat liver cancer H
22The heavy tumour inhibiting rate P of the average tumor of inhibitory action experiment number drug dose approach number of times animal number of elements body weight change value
(mg.kg
-1.d
-1) (%) 1 DMSO 10ml SC * 5 10 10+2 1.00 ± 0.31 of (g) x+s at the whole story (g)
5-Fu????????30mg????????Ip×4????????11????11??????-0.5??????0.44±0.34????????56.0??????＜0.01
TanIIA??????20mg????????SC×5????????10????10??????+7????????0.50±0.38????????50.0??????＜0.01??2??????DMSO????????10ml????????SC×5????????14????14??????+0.5??????1.69±0.50
5-Fu????????30mg????????Ip×4????????14????14??????+3.5??????0.91±0.27????????46.2??????＜0.01
TanIIA??????20mg????????SC×5????????12????12??????+3.1??????1.04±0.47????????38.5??????＜0.01??3??????DMSO????????10ml????????SC×5????????16????16??????+4.2??????1.06±0.38
5-Fu????????30mg????????Ip×4????????16????16??????+2????????0.48±0.36????????54.7??????＜0.01
Annotate TanIIA 20mg SC * 5 12 12+4.5 0.63 ± 0.33 40.6＜0.01: SC is a subcutaneous injection; Ip is a lumbar injection
There were significant differences in P＜0.01
The result shows that tanshinone is to rat liver cancer H
22Obvious suppression effect (P＜0.01) is arranged, and the weight of animals variation and ordinary circumstance are not had obvious influence.Find that through pathological study each treated animal tumor tissues all has cancerous cell karyopycnosis, lamellar necrosis, hemorrhage and cell infiltration in various degree, experimental group obviously overweights matched group.Induce the experiment of differentiation and anti metastasis in embodiment 2 animal bodies
The BALB/C mice height of In vitro culture is shifted pulmonary carcinoma (Lewis) cell with 5 * 10
6/ ml cell number is inoculated in the subcutaneous 0.2ml in BALB/C mice back, and at random be divided into 3 group with animal next day, 10 every group: blank group, the isopyknic DMSO of subcutaneous injection; Positive controls, lumbar injection chemotherapeutics fluorouracil (5-Fu, 3mg/kg body weight); Experimental group is Tan IIA (the 20mg/kg body weight is irritated stomach) and tanshinone capsule (preparation method is stated as follows, and 20mg/kg irritates stomach), once a day, totally 10 days, continued letting animals feed again 13 days, dead until there being animal to occur.Put to death animal, dissect and peel off tumor, claim that the weight of animals, tumor weigh, lung heavily reaches and observes the lung tumors metastasis, calculate tumour inhibiting rate and neoplasm metastasis suppression ratio, and carry out statistical procedures with the t check, each organizes tumor specimen 20% formalin fixed, specimens paraffin embedding slices, HE dyeing, om observation.
PRELIMINARY RESULTS shows that TANSHINONES can suppress lung carcinoma cell and form ability in the intravital tumor of mice, and can suppress the lung transfer of primary tumo(u)r.
Human clinical's experiment
Embodiment 3 medication preparation
The preparation process of tanshinone capsule:
Material: Radix Salviae Miltiorrhizae (Salvia mltiorrhiza Bge.) is available from Chengdu Chinese crude drug company, medicinal alcohol (inland river Alcohol Plant), standard reference material tanshinone (Nat'l Pharmaceutical ﹠ Biological Products Control Institute).
Method: measure 65% soak with ethanol Radix Salviae Miltiorrhizaes after 24 hours with 12 times, with flow per hour is 1/2 speed percolation of medical material weight, with the tanshinone is that standard reference material is measured the total tanshinone content in the solution that obtains, become solids with reference to the official method concentrate drying, after weighing, calculate the extract response rate, add pharmaceutically acceptable carrier or excipient and optional additional components, make and be suitable for orally such as capsule, cachet or tablet, each capsule, cachet or tablet contain the TANSHINONES of scheduled volume.
The applying high voltage chromatograph of liquid tests that tanshinone content is 2.5mg in the every capsules of clinical usefulness.
Clinical trial
Below for before the human clinical that Subsidiary Hospital No.1, Huaxi Medical Univ carries out, reaching the methodology and the result of clinical trial.The purpose of described test is to determine the effect of TANSHINONES treatment tumor and to the effectiveness and the toxic and side effects of human body.
Embodiment 4 TANSHINONES are to the treatment curative effect of acute promyelocytic leukemia (APL)
Therapeutic outcome with the early young grain leukemia patient of an example is an example:
Method 1) 1. to include standard: A. in be promyelocytic leukemia (M by the FAB standard diagnostics to patient's choice criteria
3) patient;
B. without other chemotherapeutics therapist;
C. do not alleviate or the recidivist through retinoic acid treatment.2. exclusion standard: the state of an illness is critical can not finish 3-4 week therapist.2) treat the course of treatment
Non-blind method randomized controlled trial:
Test group: TANSHINONES (capsule) 30mg.tid two months
Matched group: effectiveness retinoic acid (capsule) 20mg.tid two months 3)
Treat effectiveness according to the criterion of therapeutical effect evaluation that national leukemia meeting in 1987 is formulated.Clinical data:
Chen Youyuan, man, 30 years old.Excuse is confused, weak, the mucocutaneous hemorrhage first quarter moon, goes to a doctor in the outpatient service of hematology of the attached First Academy of Huaxi Medical Univ.The demonstration of having a medical check-up: whole skin is dispersed in petechia and purpura, anemia looks, and liver, splenic lymph nodes do not have enlargement.Be diagnosed as acute promyelocytic leukemia through hemogram and bone marrow examination.Use retinoic acid 20mg, three times on the one oral 77 days, do not have and alleviate hemoglobin (Hb): 96g/L, leukocyte (WBC): 2.3 * 10
9/ L, platelet (BPC): 209 * 10
9/ L, classification (DC): variation lymph 0.11, neutrophilic granulocyte 0.25, lymph 0.74, the bone marrow nucleated cell active proliferation, promyelocyte accounts for 0.77.Use TANSHINONES 30mg instead, three times on the one oral medications 27 days, Hb:114g/L, BPC:178 * 10
9/ L, WBC:4.1 * 10
9/ L, TANSHINONES was treated after 54 days, Hb:142 * 10
9/ L, BPC:234 * 10
9/ L, WBC:9.2 * 10
9/ L, DC: no abnormal.Bone marrow smear shows myeloblast 0.005, promyelocyte 0.025, and have a medical check-up no lymph node, liver, splenomegaly reach fully and alleviate, and do not see any toxic and side effects.
Embodiment 5 TANSHINONES are to the in vitro study of acute promyelocytic leukemia (APL) patient's APL cell induction differentiation
Gather 5 examples respectively and just send out the about 5ml of APL patient's bone marrow, separate single granulocyte through Ficoll, with 5 * 10
5/ ml cell concentration is inoculated in six orifice plates, uses 0.5 μ g/ml tanshinone (Tan IIA) and 0.5 μ g/ml all-trans-retinoic acid (ATRA) respectively and handles cell, and continuous culture is observation of cell growth and differentiation situation after 7 days, the results are shown in Table 3.
Table 3 TanIIA and ATRA support the comparison of APL cell differentiation influence to former being commissioned to train
-: C is untreated: negative control T:0.5 μ g/ml tanshinone R:0.5 μ g/ml all-trans-retinoic acid
| Case | Cultivate natural law | Condition of culture | Bone marrow differentiation rate (%) | Induce NBT differentiation (%) rate (%) |
| Children's grain children in evening band form nucleus neutrophil(e) cell cell cell pellets cell pellets cell in the early young grain of former grain | ||||
| ??1 ??2 ??3 ??4 ??5 | ??0 ??7 ??7 ??7 ??0 ??7 ??7 ??7 ??0 ??7 ??7 ??7 ??0 ??7 ??7 ??7 ??0 ??7 ??7 ??78 | ????- ????C ????T ????R ????- ????C ????T ????R ????- ????C ????T ????R ????- ????C ????T ????R ????- ????C ????T ????R | ????8.0????91.0????1.0 ????7.0????85.0????8.0 ???????????7.0?????15.5?????8.5?????39.0????30.0 ???????????4.0?????27.0?????2.0?????42.0????25.0 ????10.0???86.0????4.0 ????6.0????82.0????12.0 ???????????4.0?????12.0?????16.0????49.0????19.0 ???????????2.0?????13.0?????15.0????37.0????33.0 ????5.0????83.0????12.0 ????6.0????76.0????18.0?????????????????????17.5 ???????????8.0?????17.5?????20.0????37.0????19.0 ???????????4.0?????15.0?????14.0????48.0 ????4.0????72.0????24.0 ????2.0????66.0????32.0 ????2.0????6.0?????12.0?????15.0????32.0????33.0 ????1.0????8.0?????18.0?????12.5????33.0????27.5 ???????????84.0????16.0 ????1.0????75.0????22.0?????2.0 ???????????12.0????19.0?????13.0????45.0????11.0 ???????????14.0????12.0?????21.0????23.0????30.0 | ???????????4.0 ?85.9??????94.0 ?88.9??????98.0 ???????????6.0 ?87.5??????90.0 ?89.6??????96.0 ???????????7.0 ?84.1??????92.0 ?88.6??????90.0 ???????????12.0 ?78.9??????90.0 ?77.6??????90.0 ???????????10.0 ?76.1??????86.0 ?73.8??????84.0 |
The result shows: growth has obvious inhibitory action to TanII A to patient APL cell, and its growth inhibition ratio is 39.7% (comparing zero difference with ATRA 40.8%); TanIIA also can obviously promote APL cell differentiation maturation, induces differentiation rate average out to 82.5%.
By above experiment in vivo and vitro result as can be seen, TANSHINONES reaches the purpose for the treatment of tumor by killing tumor cell, inducing tumor cell differentiation and/or apoptosis, and it is evident in efficacy, toxic and side effects is little, has a good application prospect
The invention is not restricted to above embodiment, it will be appreciated by those skilled in the art that and under the prerequisite that does not break away from spirit of the present invention, can make various changes and distortion,, all fall within the scope of the invention as long as relate to the new purposes of TANSHINONES treatment tumor.
The main reference document:
1. Qian Mingkun, Yang Baojin, Gu Wenhua, etc. the research of effective component in red sage. chemical journal 1978; 36:199-205
2. Li Shizhen (1518-1593 A.D.). Compendium of Materia Medica (this second of check and punctuate). Beijing: People's Health Publisher .1977; 759
The room its year, Zhang Peiling, Xu Zongpei. the research of Radix Salviae Miltiorrhizae antibiotic effective ingredient. chemical journal 1976; 34 (3): 197-209
4. Cao's grace China, Liu Xiaoqi, Li Jingfu, etc. Natural antioxidant tanshinone is to hepatoma carcinoma cell lipid peroxidation product and the interactional influence of DNA. Acta Biophysica Sinica 1996; 12 (2): 339-344
5. open civilian army, Bao Xiaofeng, Wang Xiufeng, etc. sodium tanshinone IIA sulfate suppresses macrophage source property factors stimulated growth smooth muscle cell c-myc gene expression.Reach state's arteriosclerosis magazine 1996; 4 (4): 45-47
6. yellow prosperous, hide beneficial bright. the sodium tanshinone IIA sulfate cardiovascular pharmacological. foreign medical science Chinese medicine fascicle 1995; 17 (1): 9-12
7. the long celebrating of Xu, Wang Xiaoming, the model sturdy pines, etc. tanshinone is to the influence of single ventricular muscle cell transmembrane potential of Cavia porcellus and L-type calcium current.China's pathophysiology magazine 1997; 13 (10; 443-47
8. Gao Yugui, Song Yumei, the poplar friend, etc. PHARMACOLOGY OF TANSHINONE. Acta Pharmaceutica Sinica 1979; 14 (2): 75-81
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10.Huang?ME，Chen?YY，Weng?ZY，et?al.Use?of?all-trans?retinoic?acid?in?the?treatment?ofacute?promyelocytic?leukemia.Blood?1988；72(2)；567-572
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12.Wang?ZY，Chen?Z，Huang?W?et?al.Problems?existing?in?diffrentiation?therapy?of?acutepromyelocytic?leukemia(APL)with?all-trans?retinoic?acid(ATRA).Blood?Cell1993；19：633-641
13. Wang Zhen justice, Chen Zhu. tumor induce differentiation and leukemia and apoptosis therapy. Shanghai science tech publishing house 1998
Claims (8)
1. the application of TANSHINONES in preparation medicine for treating tumor thing.
2. application according to claim 1, wherein said treatment tumor is a killing tumor cells.
3. application according to claim 1, wherein said treatment tumor are the inducing tumor cell differentiation.
4. application according to claim 1, wherein said treatment tumor is an inducing apoptosis of tumour cell.
5. according to any one described application of claim 1～4, wherein said TANSHINONES is a tanshinone.
6. application according to claim 2, wherein said tumor are leukemia, hepatocarcinoma, pulmonary carcinoma, cerebral glioma, osteosarcoma, ovarian cancer, colorectal cancer, gastric cancer, cancer of pancreas, renal carcinoma, bladder cancer, laryngeal carcinoma or nasopharyngeal carcinoma.
7. application according to claim 3, wherein said tumor are leukemia, pulmonary carcinoma, hepatocarcinoma, cerebral glioma, osteosarcoma, gastric cancer, colorectal cancer, renal carcinoma or bladder cancer.
8. application according to claim 4, wherein said tumor are leukemia, pulmonary carcinoma, hepatocarcinoma, cerebral glioma, osteosarcoma, straight colon cancer, gastric cancer, renal carcinoma or bladder cancer.
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|---|---|---|---|
| CN 99121460 Expired - Fee Related CN1126539C (en) | 1999-10-26 | 1999-10-26 | Application of tanshinone in preparing medicine for treating tumor |
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| CN (1) | CN1126539C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004058245A1 (en) * | 2002-12-31 | 2004-07-15 | Zhongshan Univertsity | Tanshinone iia for prophylaxising or treating atherosclerosis |
| CN102579461A (en) * | 2012-01-12 | 2012-07-18 | 中国药科大学 | Application of tanshinone IIA in preparation of medicament for treating p53 mutational or deficient tumor |
| TWI401080B (en) * | 2011-04-07 | 2013-07-11 | ||
| CN103479649A (en) * | 2013-08-09 | 2014-01-01 | 大连理工大学 | Pharmaceutical composition and application thereof |
| CN110201017A (en) * | 2019-06-28 | 2019-09-06 | 曹文 | Arasaponin combines application of the tanshinone IIA in preparation prevention colorectal cancer drug |
| US10426755B2 (en) | 2015-07-01 | 2019-10-01 | Chang Gung Memorial Hospital, Chiayi | Methods for inhibiting cancer cells |
| CN113940936A (en) * | 2021-10-01 | 2022-01-18 | 浙江中医药大学 | Application of dihydrotanshinone I in preparation of Nrf2 inhibitor |
-
1999
- 1999-10-26 CN CN 99121460 patent/CN1126539C/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004058245A1 (en) * | 2002-12-31 | 2004-07-15 | Zhongshan Univertsity | Tanshinone iia for prophylaxising or treating atherosclerosis |
| TWI401080B (en) * | 2011-04-07 | 2013-07-11 | ||
| CN102579461A (en) * | 2012-01-12 | 2012-07-18 | 中国药科大学 | Application of tanshinone IIA in preparation of medicament for treating p53 mutational or deficient tumor |
| CN103479649A (en) * | 2013-08-09 | 2014-01-01 | 大连理工大学 | Pharmaceutical composition and application thereof |
| CN103479649B (en) * | 2013-08-09 | 2016-01-27 | 大连理工大学 | A kind of pharmaceutical composition and application thereof |
| US10426755B2 (en) | 2015-07-01 | 2019-10-01 | Chang Gung Memorial Hospital, Chiayi | Methods for inhibiting cancer cells |
| CN110201017A (en) * | 2019-06-28 | 2019-09-06 | 曹文 | Arasaponin combines application of the tanshinone IIA in preparation prevention colorectal cancer drug |
| CN113940936A (en) * | 2021-10-01 | 2022-01-18 | 浙江中医药大学 | Application of dihydrotanshinone I in preparation of Nrf2 inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1126539C (en) | 2003-11-05 |
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