CN102670623A - Application of tanshinlactone in preparation of anti-tumor-angiogenesis medicament - Google Patents
Application of tanshinlactone in preparation of anti-tumor-angiogenesis medicament Download PDFInfo
- Publication number
- CN102670623A CN102670623A CN2012101917447A CN201210191744A CN102670623A CN 102670623 A CN102670623 A CN 102670623A CN 2012101917447 A CN2012101917447 A CN 2012101917447A CN 201210191744 A CN201210191744 A CN 201210191744A CN 102670623 A CN102670623 A CN 102670623A
- Authority
- CN
- China
- Prior art keywords
- radix salviae
- salviae miltiorrhizae
- lactone
- angiogenesis
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 title abstract description 11
- VDYMGLBSIBHGCP-UHFFFAOYSA-N C1=CC2=C(C)C=CC=C2C(C(=O)O2)=C1C1=C2C(C)=CO1 Chemical compound C1=CC2=C(C)C=CC=C2C(C(=O)O2)=C1C1=C2C(C)=CO1 VDYMGLBSIBHGCP-UHFFFAOYSA-N 0.000 title abstract description 8
- LGZUUBFLEYOEEX-UHFFFAOYSA-N Neo-tanshinlactone Natural products C12=CC=C3C(C)=CC=CC3=C1OC(=O)C1=C2OC=C1C LGZUUBFLEYOEEX-UHFFFAOYSA-N 0.000 title abstract description 7
- 229930192675 tanshinlactone Natural products 0.000 title abstract description 7
- 150000002596 lactones Chemical class 0.000 claims description 37
- 230000002792 vascular Effects 0.000 claims description 7
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 5
- 230000033115 angiogenesis Effects 0.000 abstract description 12
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 230000004614 tumor growth Effects 0.000 abstract description 3
- 239000005557 antagonist Substances 0.000 abstract 1
- 230000003527 anti-angiogenesis Effects 0.000 abstract 1
- 230000001575 pathological effect Effects 0.000 abstract 1
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- 210000004204 blood vessel Anatomy 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 241001072909 Salvia Species 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 4
- 239000004037 angiogenesis inhibitor Substances 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 235000017276 Salvia Nutrition 0.000 description 3
- 244000295490 Salvia japonica Species 0.000 description 3
- 235000005794 Salvia japonica Nutrition 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000012447 hatching Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 241000687941 Salvia przewalskii Species 0.000 description 2
- 235000008202 Salvia przewalskii Nutrition 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002390 adhesive tape Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000003278 egg shell Anatomy 0.000 description 2
- 210000003725 endotheliocyte Anatomy 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 101710198693 Invasin Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000304195 Salvia miltiorrhiza Species 0.000 description 1
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 1
- 241000785917 Savia Species 0.000 description 1
- 238000010266 Sephadex chromatography Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical group C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960002344 dexamethasone sodium phosphate Drugs 0.000 description 1
- PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-FCJDYXGNSA-L 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- NUHSROFQTUXZQQ-UHFFFAOYSA-N isopentenyl diphosphate Chemical compound CC(=C)CCO[P@](O)(=O)OP(O)(O)=O NUHSROFQTUXZQQ-UHFFFAOYSA-N 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000000998 shell membrane Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses application of tanshinlactone in the preparation of an anti-tumor-angiogenesis medicament. According to an experimental result, by taking the tanshinlactone as an angiogenesis antagonist, an anti-angiogenesis effect can be achieved, and tumor growth, particularly pathological tumor growth related to or caused by angiogenesis is inhibited by inhibiting the angiogenesis in tumor tissues.
Description
Technical field
The present invention relates to the new purposes of Radix Salviae Miltiorrhizae lactone (tanshinlactone), the spy relates to its application in preparation antineoplastic vascular rebirth medicine fully, belongs to anti-angiogenic rebirth chemical compound field.
Background technology
Neonate tumour blood vessel is a kind of altitude mixture control process, promptly takes place in a short time, stops fully then.Tumor growth and transfer depend on angiogenesis, and first confirmation tumor produces the experiment of the theory of angiogenesis factor, are the transplanting melanoma of Greenblatt etc. or the test that uterus choriocarcinoma cell promotes vascular proliferation; The result shows that the propagation of tumor cell and vascularization are closely related, but thereby neonate tumour blood vessel is provided is the evidence of the invasin mediation that produced by tumor cell.After main vascular plexus formed, these endotheliocytes were by sprouting or forming new blood capillary from original blood vessel divisional mode.Angiogenesis relies on the multiple intermolecular balance that is discharged by host and tumor cell, through series of steps, comprises from blood vessel periphery cell and separate endotheliocyte with basement membrane that invade and shift out basement membrane, final expansion is gone in the tumor epithelial cell.Special angiogenic growth molecular energy starts this process, and special inhibition molecular energy stops this process.
At present, the tumor treatment means mainly rely on: chemotherapy, and radiotherapy, the mode of operative treatment, still, these means exist side effect big, shortcomings such as poor specificity.It is clear and definite that present the world of medicine is devoted to seek a kind of action target spot, and side effect is little, the curative effect excellent drug, and from natural product, separating the new inhibiting chemical compound of angiogenesis that has of preparation becomes the research focus of field of medicaments.
Radix Salviae Miltiorrhizae lactone molecular formula is C
17H
12O
3, white, needle-shaped crystals, molecular weight is 264, can by the Labiatae Salvia (
Salvia) various plants (for example: Radix Salviae Miltiorrhizae (
Savia miltiorrhiza), Salvia przewalskii (
Salvia przewalskii Maxim), the Yunnan Salvia japonica Thunb. (
Salvia yunnanensisC. extract in dry root H. Wright) etc.) or the rhizome and make; The chemical structural formula of Radix Salviae Miltiorrhizae lactone is following:
At present, for the research of Radix Salviae Miltiorrhizae lactone, be confined to research for its chemical constitution.Aspect pharmacologically active, the Radix Salviae Miltiorrhizae lactone is not reported as the research of pharmacological component separately.
In recent years; Along with the pathogenetic of cancer, retinopathy and systemic lupus erythematosus (sle) further discovered; Angiogenesis is a crucial physiology step that causes this type of disease, so the research of angiogenesis inhibitors also becomes a focus in medical research field.At present, more common angiogenesis inhibitors is mainly chemical medicine, as: DPTZ, Puli etc.; It is to come from biogenetic derivation that part is also arranged, like peptide class, exogenous pigment epidermal derived factors etc.
Summary of the invention
The object of the invention is to provide the new purposes of a kind of Radix Salviae Miltiorrhizae lactone (tanshinlactone); Be the application of Radix Salviae Miltiorrhizae lactone in preparation antineoplastic vascular rebirth medicine; It is used as the main active of antineoplastic vascular rebirth medicine or with other active component and processes medicine, treats cancer as angiogenesis inhibitors.
Radix Salviae Miltiorrhizae lactone of the present invention can be from extracted form natural plant, also can be chemosynthesis.
Can add one or more pharmaceutically acceptable adjuvants in the application according to the invention; Said adjuvant comprises filler, diluent, binding agent, excipient, absorption enhancer, filler, surfactant and the stabilizing agent etc. that pharmaceutical field is conventional; Also can add flavouring agent, pigment and sweeting agent etc. in case of necessity, process various ways such as capsule, pill, powder, tablet, granule, oral liquid and injection.
The present invention utilizes human hepatoma cell strain HepG-2, through the MTT experiment, tests the propagation influence of Radix Salviae Miltiorrhizae lactone to tumor cell; Experimental result shows, ester concentration can effectively suppress the propagation of tumor cell in the Radix Salviae Miltiorrhizae 0.5,1.0,2.5,5.0, during 10ug/mL.
The present invention utilizes the chick chorioallantoic membrane experimental model, tests the influence of Radix Salviae Miltiorrhizae lactone for experimental model angiogenesis in the body; Experimental result shows that the Radix Salviae Miltiorrhizae lactone can effectively suppress the chick chorioallantoic membrane vessel growth, and at the remarkable angiogenesis inhibiting of 10.0,15.0 ug/mL, its effect is better than positive drug, demonstrates good neovascularization inhibiting activity.
Above experimental result shows; The Radix Salviae Miltiorrhizae lactone can suppress the misgrowth of blood vessel; Suppress tumor cell; Can be used as the effective ingredient of angiogenesis inhibitors, use separately or share or combine, process oral agents or non-oral property is used to treat cancer and the newborn relevant disease that causes of aberrant angiogenesis according to conventional method with acceptable excipient etc.
Description of drawings
Fig. 1 is the present invention separates the Radix Salviae Miltiorrhizae lactone from the Salvia japonica Thunb. of Yunnan a process flow diagram.
Fig. 2 is the experimental result sketch map (the MTT experimental test results of different Radix Salviae Miltiorrhizae lactone administration concentration) that Radix Salviae Miltiorrhizae lactone of the present invention is used for human hepatoma cell strain HepG-2;
Fig. 3 is the experimental result sketch map (variable concentrations Radix Salviae Miltiorrhizae lactone is to the suppression ratio result of HepG-2 cell strain propagation influence) that Radix Salviae Miltiorrhizae lactone of the present invention is used for human hepatoma cell strain HepG-2;
Fig. 4 be Radix Salviae Miltiorrhizae lactone of the present invention to chick chorioallantoic membrane angiogenesis inhibitory action as a result sketch map (the Radix Salviae Miltiorrhizae lactone acts on chick chorioallantoic membrane; The experimental result that after the IPP image processing software is handled, suppresses angiogenic growth); A normal saline group wherein, b Dexamethasone group, c Radix Salviae Miltiorrhizae lactone 5 ug/mL group; D Radix Salviae Miltiorrhizae lactone 10ug/mL group, e Radix Salviae Miltiorrhizae lactone 15 ug/mL group;
Fig. 5 is a Radix Salviae Miltiorrhizae lactone of the present invention to chick chorioallantoic membrane angiogenesis inhibitory action sketch map (statistical result of angiogenic growth area data) as a result.
The specific embodiment
Below in conjunction with accompanying drawing and embodiment the present invention is done further explain; But be not limited to following embodiment at protection domain of the present invention, among the embodiment, the experimental technique of unreceipted actual conditions; According to normal condition, or the condition of advising according to manufacturer experimentizes.
Embodiment 1: the preparation of Radix Salviae Miltiorrhizae lactone (the Radix Salviae Miltiorrhizae lactone that uses among the following embodiment adopts following method to prepare)
Employing Labiatae salvia Yunnan Salvia japonica Thunb. (
Salvia yunnanensisC. 10 kilograms on dry root H. Wright) or rhizome are ground into coarse powder, extract with 25L acetone merceration, three times repeatedly, concentrate CE; The extractum water is made into suspension, uses ethyl acetate extraction, obtains the ethyl acetate section; This section adopts silica gel column chromatography to separate; The petroleum ether-ethyl acetate gradient elution obtains 5 part eluting sections, and wherein 9:1 eluting part adopts silica gel chromatographic column again; Chloroform-acetone gradient elution (adopting 8:1,5:1,3:1 eluting successively) is partly used RP-C with the eluting of 5:1
18Column chromatography methanol-water gradient elution (using 80:20,85:15 eluting successively); The 85:15 eluting is partly used sephadex chromatography (chloroform-methanol 1:1 eluting) separation and purification, use half preparative high-performance liquid chromatographic (semipre-HPLC) to prepare Radix Salviae Miltiorrhizae lactone 10mg (see figure 1) at last; Tanshinlactone such as its gained nuclear magnetic data and Radix Salviae Miltiorrhizae lactone Luo H-W, a novel seco-abietanoid from Salvia miltiorrhiza.Chem. Pharm. Bull. 1986,34, the data consistent of reporting among the 3166-3168.,
1H-NMR with
13It is following that C-NMR detects data:
1H?NMR?(400?MHz,?CDCl3)：δH
8.38?(1H,?d,?J?=?8.2,?H-1),?7.46?(1H,?dd,?J?=?8.2,?8.2,?H-2),?7.38?(1H,?d,?J?=?8.2,?H-3),?7.80?(1H,?d,?J?=?8.8,?H-6),7.74?(1H,?d,?J?=?8.8,?H-7),?7.37?(1H,?s,?H-16),?2.36?(3H,?s,Me-17),?2.66?(3H,?s,?Me-18)
13C?NMR?(100?MHz,?CDCl3)：
δC?120.6?(C-1),?126.8(C-2),?128.8?(C-3),?134.5?(C-4),?123.3?(C-5),?120.7?(C-6),?116.6?(C-7),110.2?(C-8),?107.9?(C-9),?133.1?(C-10),?158.6?(C-11),?158.6?(C-13),?149.5(?C-14),?141.0?(C-15),?120.3?(C-16),?8.5?(C-17),?19.6?(C-18)
According to above magnetic resonance spectroscopy information, confirm that its structure is Radix Salviae Miltiorrhizae lactone (Tanshinlactone), CAS No.:105351-70-0.
Embodiment 2: the Radix Salviae Miltiorrhizae lactone is to the influence experiment of human hepatoma cell strain HepG-2 propagation
With human hepatoma cell strain HepG-2 at 37 ℃, 5% CO
2Cultivated 24 hours, its inoculum concentration according to 3000 Ge ∕ holes be seeded in 96 orifice plates, cultivate 24 hours under these conditions after, with the Radix Salviae Miltiorrhizae lactone process 0.5,1.0,2.5,5.0, the variable concentrations medicinal liquid of 10.0ug/mL adds in 96 orifice plates, at 37 ℃, 5% CO
2Condition under continue to cultivate 72 hours, carefully shift out supernatant, every hole adds 150 μ LDMSO, concussion 1h, the survey absorbance A value in ELIASA 490nm place.
Show like Fig. 2 result: the absorbance of MTT experiment obviously descends when ester concentration in the Radix Salviae Miltiorrhizae is 5.0ug/mL and 10ug/mL, and the active obviously decline of tumor cell proliferation is described; According to:
Suppression ratio=1-dosing group OD value/matched group OD value
Calculate suppression ratio, show that like Fig. 3 this chemical compound significantly improved for the cell inhibiting rate when ester concentration was 5.0ug/mL and 10ug/mL in Radix Salviae Miltiorrhizae.
Embodiment 3: the chick chorioallantoic membrane experiment of Radix Salviae Miltiorrhizae lactone, and concrete operations are following:
1, buys the fresh hatching egg of producing in three days, hatching egg is carried out surperficial wiping sterilization, afterwards hatching egg is put into constant incubator, 37.8 ℃ of temperature are set, keep certain humidity (60%), hatched with this understanding 7 days with 84 disinfectant solution or bromo geramine.
2, window and administration
2.1 the preparation of ester solution in blank solution, positive control solution and the Radix Salviae Miltiorrhizae: ⑴ blank formulations prepared from solutions: compare with blank normal saline; ⑵ positive control formulations prepared from solutions: with 5 mg/mL dexamethasone sodium phosphate injections as positive control; ⑶ Radix Salviae Miltiorrhizae lactone formulations prepared from solutions: it is subsequent use with the mother solution that dehydrated alcohol is configured to 1mg/mL accurately to take by weighing Radix Salviae Miltiorrhizae lactone 2mg; Utilize above-mentioned mother solution to be configured to 5 μ g/mL with the dehydrated alcohol dilution respectively; 10 μ g/mL, the Radix Salviae Miltiorrhizae lactone alcoholic solution cold preservation of 15 μ g/mL is subsequent use;
Following 2.2 window with the administration concrete operations: ⑴ with 75% ethanol disinfection liquid to the disinfection of Embryo Gallus domesticus stub end surface; ⑵ remove eggshell, shell membrane successively with flat angle tweezers; Expose cameral mantle; ⑶ expose the chorioallantoic membrane tissue with syringe and bent angle tweezers separated gas chamber film and chorioallantoic membrane, and ⑷ is given to the sparse relatively zone of blood vessel on the chorioallantoic membrane with medicine through medicine carrying;
After the administration, seal window,, cultivated 48 hours under the condition of humidity (60%) 37.8 ℃ of temperature with adhesive tape;
3, preparation of specimen and IMAQ
3.1 preparation of specimen: open and seal adhesive tape; Dropping 2mL fixative in the administration window (methanol: acetone=1:1); Fixedly behind the 10min, treat blood vessel fixing fully after, peel off the eggshell around the air chamber; The chorioallantoic membrane of administered area is fully exposed, use operating scissors to cut with about 2.5 * 2.5cm of carrier as the center
2Chorioallantoic membrane tissue in the scope is tiled in the culture dish that the PBS buffer is housed, and it is fully launched, and then it is transferred on the microscope slide;
3.2 IMAQ: with the blank sheet of paper is background, under the available light condition, takes pictures with digital camera, and it is the chick chorioallantoic membrane photo at center that original position is taken with pharmaceutical carrier (medicine carrying);
4, date processing: the chorioallantoic membrane photo of gathering is carried out Flame Image Process with software calculate the blood vessel area, adopt the SPSS DAS that data are analyzed afterwards.
Experimental result shows that Fig. 4 is the photo of enhancing contrast ratio after the IPP software processes, from figure, can find out obviously that when the administration concentration of Radix Salviae Miltiorrhizae lactone was 10.0,15.0 ug/mL, angiogenic growth obviously was suppressed; Fig. 5 has shown the block diagram that calculates bleeding from anus pipe area through area, and as can be seen from the figure working as administration concentration is 10.0,15.0 ug/mL, and the blood vessel area obviously descends.
Claims (1)
1. the application of Radix Salviae Miltiorrhizae lactone in preparation antineoplastic vascular rebirth medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101917447A CN102670623A (en) | 2012-06-12 | 2012-06-12 | Application of tanshinlactone in preparation of anti-tumor-angiogenesis medicament |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101917447A CN102670623A (en) | 2012-06-12 | 2012-06-12 | Application of tanshinlactone in preparation of anti-tumor-angiogenesis medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102670623A true CN102670623A (en) | 2012-09-19 |
Family
ID=46803614
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012101917447A Pending CN102670623A (en) | 2012-06-12 | 2012-06-12 | Application of tanshinlactone in preparation of anti-tumor-angiogenesis medicament |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102670623A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005087225A1 (en) * | 2004-03-10 | 2005-09-22 | The University Of North Carolina At Chapel Hill | Neo-tanshinlactone and analogs as potent and selective anti-breast cancer agents |
| CN101538258A (en) * | 2009-03-04 | 2009-09-23 | 沈阳药科大学 | New composition of salvia miltiorrhiza and derivative, preparation method and medicine application thereof |
-
2012
- 2012-06-12 CN CN2012101917447A patent/CN102670623A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005087225A1 (en) * | 2004-03-10 | 2005-09-22 | The University Of North Carolina At Chapel Hill | Neo-tanshinlactone and analogs as potent and selective anti-breast cancer agents |
| CN101538258A (en) * | 2009-03-04 | 2009-09-23 | 沈阳药科大学 | New composition of salvia miltiorrhiza and derivative, preparation method and medicine application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 张伟伟: "丹参抗肿瘤活性成分研究新进展", 《中国中药杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kim et al. | Apoptosis of DU145 human prostate cancer cells induced by dehydrocostus lactone isolated from the root of Saussurea lappa | |
| CN105153084A (en) | Novel diterpene compound as well as preparation method and medicinal application thereof | |
| KR101670590B1 (en) | A Composition for inhibiting Growth of Cancer Stem Cells, containing Erk signaling activation inhibitor | |
| CN106176716B (en) | The new application of daphane diterpene compound pimelotide C | |
| Chen et al. | Growth inhibition by pennogenyl saponins from Rhizoma paridis on hepatoma xenografts in nude mice | |
| EP3339285B1 (en) | A compound isolated from isodon forrestii var. forrestii and preparation method and applications thereof | |
| AU2010206549A1 (en) | Use of pterosin compounds for treating diabetes and obesity | |
| EP2460812B1 (en) | Sterol derivatives and their synthesis and use | |
| CN101926844B (en) | Stellera chamaejasme L extract and anti-tumor action thereof | |
| CN102961384B (en) | Medical application of przewaquinone A | |
| Milani et al. | Antipromastigote and cytotoxic activities of flavonoids from Fridericia speciosa leaves | |
| CN106928299B (en) | Compound from cortex lycii radicis, preparation method and application thereof in aspect of reducing blood sugar | |
| CN102670623A (en) | Application of tanshinlactone in preparation of anti-tumor-angiogenesis medicament | |
| CN101156882A (en) | Preparation method of pseudo-ginseng protopanoxadiol saponin and its uasage | |
| CN105503984A (en) | Hedgehog signal channel inhibitor and preparation method and application thereof | |
| CN102697758A (en) | Application of cryptomeriol in preparation of anti-tumor angiogenesis medicine | |
| CN103239438B (en) | Application of kumata kenin in preparation of abnormal vascular proliferation inhibition medicines | |
| CN116947794B (en) | Eucalyptus type sesquiterpenoids rearranged by four-ring system, preparation method and application thereof, pharmaceutical composition and application thereof | |
| CN102949386B (en) | Medical application of prze-watanshinquinone B | |
| CN102670621A (en) | Application of maslinic acid in preparation of anti-tumor-angiogenesis medicament | |
| CN110204477B (en) | Diterpene alkaloid with antioxidant effect and application thereof in preparation of medicines | |
| CN103221044A (en) | Xanthanodien for the treatment of cancer | |
| CN113214154B (en) | Tribenzyl isoquinoline alkaloid, preparation method, pharmaceutical composition and application thereof | |
| KR102399872B1 (en) | Composition for inhibiting metastasis of cancer comprising benzofuran-based compounds derived from Suillus granulatus and use thereof | |
| CN109662970B (en) | A kind of application of lanostane-type |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120919 |