CN103435550A - Tanshinone derivative, preparation method and application thereof - Google Patents
Tanshinone derivative, preparation method and application thereof Download PDFInfo
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- CN103435550A CN103435550A CN2013102453209A CN201310245320A CN103435550A CN 103435550 A CN103435550 A CN 103435550A CN 2013102453209 A CN2013102453209 A CN 2013102453209A CN 201310245320 A CN201310245320 A CN 201310245320A CN 103435550 A CN103435550 A CN 103435550A
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Abstract
The present invention relates to a tanshinone derivative, a preparation method and an application thereof. The tanshinone derivative preparation method comprises: dissolving the total tanshinone effective fraction, benzaldehyde and ammonium acetate in ethanol, carrying out a stirring reaction at a temperature of 20-90 DEG C, taking the reactant, extracting to obtain the total tanshinone reactant dry extract, and purifying the reactant dry extract to obtain the tanshinone derivative. The present invention further discloses an application of the tanshinone derivative in preparation of angiogenesis promotion drugs and anti-tumor drugs. According to the present invention, the tanshinone derivative is provided, can be provided for treating ischemic cerebrovascular diseases, and had characteristics of rapid effect and safe medication; and the tanshinone derivative can be used for preparing treatment drugs of blood supply improvement and ischemic tissue rescue through angiogenesis, and preparing anti-lung cancer treatment drugs and other tumor disease treatment drugs.
Description
Technical field
The present invention relates to a kind of tanshinone derivative, be specially a kind of tanshinone derivative and its preparation method and application.
Background technology
Vasculogenesis (angiogenesis) is on original vasoganglion basis, goes out to form little angiogenic growth and the side Zhi Xunhuan of surrounding tissue by the stimulating endothelial cell bud, generates the complex process of new vessel.This process relates to the degraded of vascular endothelial cell epimatrix, endotheliocyte to the migration of substrate degradation place, propagation, stretching, extension and a plurality of steps such as tubular structure formation and the generation of endotheliocyte epimatrix film, mainly comprises: the degraded of active period basement membrane of blood vessel; The activation of vascular endothelial cell, propagation, migration; Rebuilding and form new blood vessel and vasoganglion, is a complex process that relates to various kinds of cell and different kinds of molecules.Vascularization is the complex process of short angiogenesis factor and supressor coordinative role, and the two,, in equilibrium state, will activate vascular system once this balance is broken under normal circumstances, makes the vasculogenesis transition or suppress vascular system blood vessel is degenerated.
Vasculogenesis refers to that endotheliocyte germinates and forms new blood vessel from existing blood vessel.Its forming process is very complicated, and is a kind of very important phenomenon of observing in all respects of life entity, for example the vasculogenesis of growth and growth, pathologic vessels generation (for example growth of tumour, diabetic retinopathy) etc.Angiogenic factor commonly used is mainly vascular endothelial growth factor (VEGF), fiber mother cell growth factor (FGF), angiogenesis factor ((Ang-1) etc.They have the effect of coordination, complementation in angiogenic process.VEGF is the specificity mitogen of endotheliocyte, and it can be by the acceptor VEGF-Rl with endothelial cell surface, the VEGF-R2 specific binding, and the migration of mediation endotheliocyte, propagation are to build the cavity configuration of blood vessel.FG-1 and FGF-2, respectively at endotheliocyte, smooth muscle cell and Fibroblast acceptor FGFR-1 and FGFR-2 combination, are playing an important role aspect vasostimulant new life and increase blood vessel strength and toughness.Ang-1 is by after its specific receptors Tie is combined, and the reconstruction of mediation vascular endothelial cell and the later stage blood vessel of sustenticular cell participation on every side thereof, protecting new vessel, and treatment of vascular seepage aspect plays active effect.
The most frequently used in current Therapeutic angiogenesis method is gene therapy and the recombinant protein treatment of exogenous Angiogensis somatomedin (as VEGF or Ang), but Angiogensis somatomedin therapeutic transgene exists immunogenicity, regulation and control difficulty; Angiogensis somatomedin recombinant protein intravenously administrable exists the aberrant angiogenesis growth whether other positions occur, even tumorigenic risk; Exogenous Angiogensis somatomedin is short because of the transformation period, is difficult to, by hemato encephalic barrier, repetitively administered, is prone to the problems such as side effect, has limited its application.
During various ischemic cardiovascular due to unstable angina pectoris, acute myocardial infarction, coronary stenosis, AS, thrombosis, collateral circulation compensation is not yet fully set up, and makes to organize serious and lasting acute anoxia, and infarct can occur.Clinical study proves; after myocardial infarction occurs; simple by self physiological revascularization; very slow to adapt to the process that ischemic changes; the myocardial ischemia generally can only the compensatory coronary occlusion of part caused; when angioplasty, cononary artery bypass are invalid, increase artificially the concentration of regional myocardial somatomedin, to alleviating so that removing myocardial ischemia, alleviate myocardial necrosis potential possibility is arranged.The method of this manually operated angiogenesis once once was called " molecular bypass art ", generally was called at present Therapeutic Angiogenesis.
The dry root that the red sage root is the Labiatae salvia red sage root (Salvia miltiorrhiza Bge.), modern medicine thinks that the red sage root has coronary artery dilator, increases coronary flow, prevents the Cardiovasculars such as myocardial ischemia and myocardial infarction, and the multiple anti-tumor activity such as Hepatoma therapy, cancer of the stomach, leukemia, cervical cancer.TANSHINONES (tanshi-none, DST) be ether or the ethanol extraction of red sage root root, the main fat-soluble effective constituent of the red sage root, by it, different chemical structures is divided into 15 kinds of compositions such as tanshinone Ⅰ, tanshinone IIA, tanshinone ⅡB, Cryptotanshinone, dihydrotanshinone, is generically and collectively referred to as TANSHINONES.
But prior art does not instruct the tanshinone derivative can be for promoting the preparation of angiogenesis drug and antitumor drug.
Summary of the invention
The object of the present invention is to provide a kind of new tanshinone derivative and the preparation method of this tanshinone derivative, and the application of this tanshinone derivative in aspect preparation promotes angiogenesis drug and antitumor drug is provided.
In order to reach the foregoing invention purpose, a kind of tanshinone derivative that at first the present invention proposes is achieved through the following technical solutions:
A kind of tanshinone derivative, is characterized in that, the structural formula of described tanshinone derivative is as follows:
Secondly, the present invention also provides the preparation method of this tanshinone derivative, by following technology, realizes:
100g total tanshinone efficient part, 500mmol phenyl aldehyde, 4mol ammonium acetate are dissolved in 1000ml ethanol, and at 20-90 ℃ of lower stirring reaction 4-16H, take out afterwards the reactant extraction and obtain total tanshinone reactant dry extract, finally described total tanshinone reactant dry extract is purified and obtained tanshinone derivative as claimed in claim 1.
In above-mentioned preparation method, the concrete steps of described purification are: get described total tanshinone reactant medicinal extract and carry out silica gel column chromatography, the eluent that is 30:1-1:1 by chloroform and methyl alcohol volume ratio afterwards carries out gradient elution, and to collect respectively chloroform and methyl alcohol volume ratio be that 30:1, chloroform and methyl alcohol volume ratio are that 20:1, chloroform and methyl alcohol volume ratio are the elutriant that 10:1, chloroform and methyl alcohol volume ratio are the 1:1 part; Get elutriant that chloroform and methyl alcohol volume ratio are 1:1 through Sephadex LH-20 column chromatography and high performance liquid chromatography separation and purification, obtain described tanshinone derivative; Wherein, the elutriant used in described high performance liquid chromatography is methanol aqueous solution, and the volume ratio of first alcohol and water is 35:100.
Finally, the invention provides the various application of described tanshinone derivative, specific as follows:
Described tanshinone derivative promotes the application in angiogenesis drug in preparation.Comprise:
Described tanshinone derivative promotes the application in the animal blood vessels generating medicine in preparation.
Described tanshinone derivative promotes the application in the vertebrates angiogenesis drug in preparation.
Described tanshinone derivative promotes the application in the human vas generating medicine in preparation.
Described tanshinone derivative promotes the application in uriniferous tubules week capillary angiogenesis drug in preparation.
Described tanshinone derivative promotes the application in the zebra fish angiogenesis drug in preparation.
The application of described tanshinone derivative in preparing antitumor drug.Comprise,
The application of described tanshinone derivative in preparing anti-lung-cancer medicament.
In above technical scheme, described promotion angiogenesis drug comprises the medicine of making following purposes: ischemic cardiovascular or angiogenesis inhibition disease due to the brain protection of atherosclerosis, coronary heart diseases and angina pectoris, cerebral infarction, vascular occlusion thromboangiitis, coronary stenosis, myocardial infarction, myocardial ischemia, occlusive vascular disease, ischemic rat brain damage, ischemic disease, Simultaneous reconstruction of postoperative defects of mandibular osteoradionecrosis, Aristolochic acid nephropathy, thrombosis.
Compared with prior art, the present invention has following beneficial effect:
(1) tanshinone derivative provided by the invention can be used for treating ischemic cerebrovascular, and has the characteristics of instant effect, drug safety.Tanshinone derivative has outstanding security individual structure; there is multiple pharmacological effect simultaneously; by improving the level of cerebrovascular endothelial NO and PGI2; reduce intracellular calcium concentration; suppressing L-glutamic acid discharges; reduce arachidonic acid content, suppress oxyradical and improve the mechanism such as activities of antioxidant enzymes, act on a plurality of pathology links due to cerebral ischemia;
(2) tanshinone derivative provided by the invention can be used for preparing the medicine that improves blood confession redemption ischemic tissue by vasculogenesis, this curative effect of medication is definite, can need to improve by vasculogenesis the medicine of the ischemic disease of blood confession for the preparation for the treatment of, be also simultaneously the butylphthalide outer another new indication of cerebral ischemia indication that continues.
(3) tanshinone derivative provided by the invention can be used for preparing the medicine of the tumor diseases such as anti-lung cancer.
The accompanying drawing explanation
By the description of its exemplary embodiment being carried out below in conjunction with accompanying drawing, the above-mentioned feature and advantage of the present invention will become apparent and easily understand.
Fig. 1: the impact of the blood vessel disappearance that tanshinone derivative is induced VRI in zebra fish;
Fig. 2: tanshinone derivative on blood vessel endothelium injury animal intimal hyperplasia impact;
Fig. 3: tanshinone derivative is to all capillary vascular repairs of chronic nephropathy rat model uriniferous tubules and therapeutic action research.
Embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail, so that technician's of the same trade understanding:
The invention provides a kind of tanshinone derivative, called after TANSHINONES SF, its structure suc as formula under:
In the present embodiment, this tanshinone derivative preparation method is as follows:
Get total tanshinone efficient part 100.0g (35mmol), phenyl aldehyde 500mmol (60ml), ammonium acetate 4mol (about 300.0g) puts into the round-bottomed flask of 2000ml, after adding 1000ml ethanol to be heated ultrasonic dissolution, in 79 ℃ of oil baths, stirring reaction is 5 hours, takes out after reactant water and dichloromethane extraction 2 times the total tanshinone reactant dry extract that obtains 200g.Comprise this TANSHINONES SF in this total tanshinone reactant dry extract.
In this reactions steps, the temperature of reaction of phenyl aldehyde, total tanshinone efficient part and ammonium acetate should be controlled between 20-90 ℃, and the time of stirring reaction should be controlled between 4-16H.And above-mentioned concrete reaction conditions is a preferred embodiment.
By above-mentioned total tanshinone reactant medicinal extract routinely through silica gel column chromatography repeatedly, the eluent that is 30:1-1:1 by chloroform and methyl alcohol volume ratio afterwards carries out gradient elution, and to collect respectively chloroform and methyl alcohol volume ratio be that 30:1, chloroform and methyl alcohol volume ratio are that 20:1, chloroform and methyl alcohol volume ratio are the elutriant that 10:1, chloroform and methyl alcohol volume ratio are the 1:1 part; Get elutriant that chloroform and methyl alcohol volume ratio are 1:1 through Sephadex LH-20 column chromatography and high performance liquid chromatography separation and purification, wherein, the elutriant used in described high performance liquid chromatography is methanol aqueous solution, and the volume ratio of first alcohol and water is 35:100.Finally use thin layer plate (G254) to detect purity, obtain described TANSHINONES SF.
Structural Identification:
The lightpink powder, m.p.:152-153 ℃, molecular formula is C
23h
20N
2o
2, HR-FAB-MS m/z:379.4866[M+Na]+(Calcd.for C
55h
92o
21na, 379.4839), determine that compound molecular weight is 356.UV (MeOH) shows the obvious uv-absorbing of compound.Nuclear magnetic resonance data is in Table 1, table 2.
Table 1 TANSHINONES SF
1h-NMR data (C
5d
5n, δ, ppm)
Table 2 TANSHINONES SF
13c-NMR data (C5D5N, δ, ppm)
Position | C | Position | C |
1 | 29.83 | 15 | ? |
2 | 19.06 | 16 | ? |
3 | 37.63 | 17 | ? |
4 | 34.69 | 18 | 31.48 |
5 | 154.44 | 19 | 31.48 |
6 | 127.13 | 20 | ? |
7 | 127.44 | 21 | 136.5 |
8 | 131.58 | 22 | 126.75 |
9 | 137.1 | 23 | 128.98 |
10 | 135.1 | 24 | 129.03 |
11 | 128.76 | 25 | 128.98 |
12 | 168.1 | 26 | 126.75 |
13 | 182.0 | 27 | 145.28 |
14 | 180.44 | 28 | ? |
The impact of the blood vessel disappearance that embodiment 1 tanshinone derivative is induced VRI in zebra fish
Tanshinone derivative (Compound10) is at VRI(VEGFR TYR kinase inhibitor II, hereinafter referred to as VRI) blood vessel of inducing loses on zebra fish model and carries out (500 μ g/ml) blood vessel and recover test, result shows that this compound all shows recovery of blood vessels activity in various degree when different concns, the highest recovery of blood vessels rate can reach 95%, and EC50 is about 0.026 μ M.As shown in Figure 1, during the basic, normal, high dosage of tanshinone derivative, can promote recovery of blood vessels, the highest recovery of blood vessels rate can reach 95%, and EC50 is about 0.026 μ M, and is dose-dependent effect.In Fig. 1, with blank, compare & P<0.01#p<0.001; Compare * p<0.05, * * p<0.01, * * * p<0.001 with model group.
The angiogenesis promoting effect of embodiment 2 tanshinone derivatives to Human umbilical vein endothelial cells
Human umbilical vein endothelial cells (HUVE-12) adopts the F-12K substratum, wherein contains Pidolidone, the 100U/ml mycillin of 2mM, 100 μ g/ml heparin, 30 μ g/ml endothelial cell growth element and 10%FBS.Get 2-5 for cell, by every hole 1 * 105/ml, inoculate 96 orifice plates.The normal cultivation after 24 hours discards nutrient solution, changes the nutrient solution pre-treatment 24 hours of 0.5%FBS to reach cell synchronization.Test is divided into negative control group, positive controls (VEGF), tanshinone derivative group (6 dosage groups, final concentration is respectively 1,3,10,30,100,300 μ g/L), control group only adds 0.5%FBS and solvent, and the VEGF that positive controls is 20 μ g/L containing concentration establishes 6 multiple holes for every group.After cellar culture 48 hours, discard nutrient solution, microplate reader is measured the light absorption value at each hole 490nm and 690nm place according to the XTT method.Test-results shows that tanshinone derivative has thick increment effect, and IC50 is 80 μ g/L.
The promoter action of embodiment 3 tanshinone derivatives to blood vessel endothelium injury animal intimal hyperplasia
40 Wistar rats, wherein after 30 anesthesia, the ligation of left femoral artery distal end, proximal part closes with the artery clamp, in the puncture of femoral artery far-end, inserts shaggy 0.035 inch elasticity seal wire, repeatedly pumps 5 times, then twice rotation seal wire 120 spent, and each angle repeats to pump 5 times.Layer-by-layer suture subcutis and skin, local application of penicillin after operation is with preventing infection.Animal after modeling, with being divided into 3 groups, is respectively tanshinone derivative high and low dose group and positive controls, difference intravenous injection 3mg/kg, the tanshinone derivative of 1mg/kg and the solvent of equal volume, 1 times/day, totally 14 days.Take out the inner film injury vessel segment after off-test, DAPI mark, Evans Blue are redyed, and observe intimal hyperplasia and reparation situation.After result shows that inner film injury blood vessel DAPI mark, 1% Evans Blue are redyed, the middle rete of fluorescence microscopy Microscopic observation red color visible fluorescence and the intimal hyperplasia cell of blue-fluorescence, find that the positive controls intimal hyperplasia is not obvious, the low dose group inner membrance has slight hyperplasia, and the high dose group intimal hyperplasia is obvious.As shown in Figure 2, A figure is model control group, and visible intimal hyperplasia is not obvious, and B figure is the tanshinone derivative high dose group, visible significantly intimal hyperplasia.
Embodiment 4 tanshinone derivatives are to all capillary vascular repairs of chronic nephropathy rat model uriniferous tubules and therapeutic action research
The Wstar rat, 180-200g, give Decoction of Caulis Aristolochiae Manshuriensis gavage (being equivalent to Stem of Manshurian Dutchmanspipe 30g/kg/ days), and 1 times/day, 16 weeks rear film forming of gavage, separately get 8 animals and give the water of equal volume as Normal group continuously.24 of animals after film forming, be divided into 3 groups at random, is respectively tanshinone derivative high and low dose group and positive controls, difference intravenous injection 3mg/kg, the tanshinone derivative of 1mg/kg and the solvent of equal volume, 1 times/day, totally 14 days.Put to death and respectively organize rat respectively after off-test.Get the nephridial tissue sample, 4% paraformaldehyde solution is fixed, and 4 degree are preserved.Result shows to damage capillary vessel DAPI mark, 1% Evans Blue redye after, the middle rete of fluorescence microscopy Microscopic observation red color visible fluorescence and the intimal hyperplasia cell of blue-fluorescence, find that the positive controls intimal hyperplasia is not obvious, the low dose group inner membrance has slight hyperplasia, and the high dose group intimal hyperplasia is obvious.As shown in Figure 3, A schemes positive control group, and visible intimal hyperplasia is not obvious, and B figure is the tanshinone derivative high dose group, visible significantly intimal hyperplasia, and C figure is low dose group, there is slight hyperplasia in visible internal film tissue.
The external evoked Wide colon-cancer cell of embodiment 5 tanshinone derivative apoptosis
The inoculation of Wide colon-cancer cell after recovery is gone down to posterity.The cell in vegetative period of taking the logarithm.Be inoculated in 24 porocyte culture plates with 1 * 106/ml density, be divided into 4 groups and add medicine after 12h.Be respectively Normal group, the high, medium and low intervention group of tanshinone derivative (adding respectively tanshinone derivative concentration is 5,25,125 μ g/L), separately establish the perfect medium group that does not add cell, establish 4 multiple holes for every group, put 37 degree, in the CO2 incubator, cultivate after 12,24,36 hours, the inhibiting rate experimental result that mtt assay detects tumour cell sees the following form, and calculation formula is as follows: cell mortality=[1-(experimental group OD mean value/blank group OD value)] * 100%.
Result shows, the tanshinone derivative effect is after 12,24 hours, with control group relatively, the increment inhibiting rate of colon-cancer cell significantly increases, statistical procedures has significant difference; And, along with each medication group of increase of dosage has increase trend to the proliferation inhibition rate of colon-cancer cell, there were significant differences for statistical procedures.Flow cytometer carries out the morphological analysis result and shows, occurs obvious apoptotic cell after the tanshinone derivative medication.Prompting tanshinone derivative cytotoxicity may realize by cell death inducing, as shown in table 3.
The restraining effect (mean ± SD) of table 3 tanshinone derivative to colon-cancer cell
The impact of embodiment 6 tanshinone derivatives on restraining effect and the cell cycle of Lewis lung cancer
The C57BL/6 mouse, male and female half and half, 18-20 gram.Right fore oxter subcutaneous vaccination Lewis lung cancer noumenal tumour.Latter the 1st day of inoculation, animal is divided into 5 groups at random, 10 every group.Be respectively the physiological saline of model group abdominal injection 0.4ml/, the high, medium and low dosage group difference of cis-platinum, the tanshinone derivative abdominal injection 3,10 of positive controls abdominal injection 1mg/kg, the tanshinone derivative of 30mg/kg.Injection is 5 days continuously, within 11st, cuts open and gets each treated animal tumour, thymus gland, spleen, takes quality.Calculate tumour inhibiting rate and organ index.And cut open and get fresh tumor tissues, prepare cell suspension, to get suspension 100ul and add the RNA enzyme, 37 degree water-baths 30 minutes, add PI500ul, 4 degree lucifuge dyeing 10 minutes.Flow cytometer obtains cell, analysis of cells cycle and apoptosis rate.
Result shows: each administration group is compared with control group, and average knurl quality significantly reduces, and difference has statistical significance, and is obvious dose-dependence, and best with heavy dose of administration group tumor killing effect, tumour inhibiting rate is 68%.The tanshinone derivative group is compared with positive controls, and thymus index significantly increases, and difference has statistical significance.Relatively, G0/G1 phase cell content increases for tanshinone derivative group and control group, and S phase cell content reduces, and difference has statistical significance, and apoptosis rate significantly increases, and is obvious dose-dependence, as shown in table 4.
Table 4 tanshinone derivative reaches the impact on dirty cell cycle and apoptosis rate to the restraining effect of Lewis lung cancer
As from the foregoing, the present invention has following beneficial effect:
(1) tanshinone derivative of the present invention can be used for treating ischemic cerebrovascular, and has the characteristics of instant effect, drug safety.Tanshinone derivative has outstanding security individual structure, there is multiple pharmacological effect simultaneously, by improving the level of cerebrovascular endothelial NO and PGI2, reduce intracellular calcium concentration, suppressing L-glutamic acid discharges, reduce arachidonic acid content, suppress oxyradical and improve the mechanism such as activities of antioxidant enzymes, act on a plurality of pathology links due to cerebral ischemia.
(2) tanshinone derivative of the present invention can be used for preparing the medicine that improves blood confession redemption ischemic tissue by vasculogenesis, this curative effect of medication is definite, can need to improve by vasculogenesis the medicine of the ischemic disease of blood confession for the preparation for the treatment of, be also simultaneously the butylphthalide outer another new indication of cerebral ischemia indication that continues.
(3) tanshinone derivative of the present invention can be used for preparing the medicine of the tumor diseases such as anti-lung cancer.
Although the present invention with preferred embodiment openly as above; but it is not for limiting claim; any those skilled in the art without departing from the spirit and scope of the present invention; can make possible change and modification, so protection scope of the present invention should be as the criterion with the scope that the claims in the present invention were defined.
Claims (12)
2. the preparation method of a tanshinone derivative as claimed in claim 1 is characterized in that preparing as follows:
100g total tanshinone efficient part, 500mmol phenyl aldehyde, 4mol ammonium acetate are dissolved in 1000ml ethanol, and at 20-90 ℃ of lower stirring reaction 4-16H, take out afterwards the reactant extraction and obtain total tanshinone reactant dry extract, finally described total tanshinone reactant dry extract is purified and obtained tanshinone derivative as claimed in claim 1.
3. the preparation method of tanshinone derivative as claimed in claim 2, it is characterized in that, the concrete steps of described purification are: get described total tanshinone reactant medicinal extract and carry out silica gel column chromatography, by chloroform and methyl alcohol volume ratio, be 30 afterwards: 1-1: 1 eluent carries out gradient elution, and to collect respectively chloroform and methyl alcohol volume ratio be that 30: 1, chloroform and methyl alcohol volume ratio are that 20: 1, chloroform and methyl alcohol volume ratio are the elutriant that 10: 1, chloroform and methyl alcohol volume ratio are 1: 1 part; Get elutriant that chloroform and methyl alcohol volume ratio are 1: 1 through Sephadex LH-20 column chromatography and high performance liquid chromatography separation and purification, obtain described tanshinone derivative; Wherein, the elutriant used in described high performance liquid chromatography is methanol aqueous solution, and the volume ratio of first alcohol and water is 35: 100.
4. the application of a kind of tanshinone derivative as claimed in claim 1 is characterized in that: described tanshinone derivative promotes the application in angiogenesis drug in preparation.
5. the application of a kind of tanshinone derivative as claimed in claim 4 is characterized in that: described tanshinone derivative promotes the application in the animal blood vessels generating medicine in preparation.
6. the application of a kind of tanshinone derivative as claimed in claim 5 is characterized in that: described tanshinone derivative promotes the application in the vertebrates angiogenesis drug in preparation.
7. the application of a kind of tanshinone derivative as claimed in claim 6 is characterized in that: described tanshinone derivative promotes the application in the human vas generating medicine in preparation.
8. the application of a kind of tanshinone derivative as claimed in claim 6 is characterized in that: described tanshinone derivative promotes the application in uriniferous tubules week capillary angiogenesis drug in preparation.
9. the application of a kind of tanshinone derivative as claimed in claim 6 is characterized in that: described tanshinone derivative promotes the application in the zebra fish angiogenesis drug in preparation.
10. as the application of the described a kind of tanshinone derivative of claim 4-9 any one; it is characterized in that, described promotion angiogenesis drug comprises the medicine of following purposes: ischemic cardiovascular or angiogenesis inhibition disease due to the brain protection of atherosclerosis, coronary heart diseases and angina pectoris, cerebral infarction, vascular occlusion thromboangiitis, coronary stenosis, myocardial infarction, myocardial ischemia, occlusive vascular disease, ischemic rat brain damage, ischemic disease, Simultaneous reconstruction of postoperative defects of mandibular osteoradionecrosis, Aristolochic acid nephropathy, thrombosis.
11. the application of a kind of tanshinone derivative as claimed in claim 1 is characterized in that: the application of described tanshinone derivative in preparing antitumor drug.
12. the application of a kind of tanshinone derivative as claimed in claim 11 is characterized in that: the application of described tanshinone derivative in preparing anti-lung-cancer medicament.
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CN102603861A (en) * | 2012-02-25 | 2012-07-25 | 中国科学院昆明植物研究所 | Tanshinone derivatives, medicine compositions thereof, and purposes thereof in medicine |
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US20070207989A1 (en) * | 2006-03-03 | 2007-09-06 | Savipu Pharmaceuticals | Diterpene derivatives for the treatment of cardiovascular, cancer and inflammatory diseases |
CN101863894A (en) * | 2010-06-01 | 2010-10-20 | 广东药学院 | Tanshinone II A derivative and preparation method and application thereof |
CN102603861A (en) * | 2012-02-25 | 2012-07-25 | 中国科学院昆明植物研究所 | Tanshinone derivatives, medicine compositions thereof, and purposes thereof in medicine |
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