CN1511538A - Use of scutellarin in inhibiting vascularization - Google Patents
Use of scutellarin in inhibiting vascularization Download PDFInfo
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- CN1511538A CN1511538A CNA021596921A CN02159692A CN1511538A CN 1511538 A CN1511538 A CN 1511538A CN A021596921 A CNA021596921 A CN A021596921A CN 02159692 A CN02159692 A CN 02159692A CN 1511538 A CN1511538 A CN 1511538A
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Abstract
The present invention discloses the new use of baicalin in inhibiting vasculariztion. Research probes the vasculariztion inhibiting effect of baicalin. The technological scheme is that baicalin is used in preparing medicine for prevention and/or treatment of inhibiting vasculariztion with the effective dosage being 6-50 mg/kg body weight/day. The present invention uses the vasculariztion as the target of treating diseases and has the advantages of treatment specificity of pointing newly formed vessel; small dosage, high treating effect and less side effect owing to the direct action of medicine to vascular endothelial cell; and less medicine resistance owing to relatively stable endothelial cell gene expression.
Description
Technical field
The present invention relates to novel application of compound, particularly relate to the new purposes of baicalin.
Background technology
Studies show that tumor self possesses and starts and promote the ability that new vessels generates, with the metabolism that satisfies self and the needs of nutrient substance supply.Tumor neovasculature generation (angiogenesis) is from existing vascular bed.If there is not angiogenesis, the growth of primary tumo(u)r can not surpass 1～2mm, can not occur soaking into and shifting yet.Suppress tumor-blood-vessel growth, closely related with generation, development, infiltration and the transfer of blocking-up tumor.Suppress tumor-blood-vessel growth, also can stop the pernicious transformation of precancerous lesion to cancer.The not only growth of entity tumor, infiltration and transfer rely on new vessels and generate, and the growth of blood system malignant tumor (as malignant lymphoma, Lymphocytic leukemia etc.) and transfer are also closely related with angiogenesis.Growth of tumor, transfer, recurrence, prognosis and angiogenesis are closely related, angiogenesis with tumor is a target spot, the exploitation angiogenesis inhibitor, not only can be used for the treatment of most of entity tumors, also can be used for the prevention of cancer and the treatment of blood system malignant tumor, simultaneously to the disease of other and associated angiogenesis as: the prevention and the treatment of diabetic renal papillary necrosis, rheumatic arthritis, psoriasis, hemangioma, atherosclerosis etc. all have important theory and realistic meaning.
Baicalin (β-D-Gluopyranosiduronicacid, 5,6-dihydroxy-4-oxo-2-phenyl-4H-1-benzopyran-7-yl) derive from the root of labiate Radix Scutellariae Scutellaria baicalensis Georgi, different name: baicalin, molecular formula are C
21H
18O
11, molecular weight is 446.35, has the structural formula of formula I:
(formula I)
This chemical compound is a faint yellow fine needle crystalline substance (methanol), fusing point: 223 ℃-225 ℃, and [α] 18D+123.(C=0.2 pyridine one water).Baicalin also can be from also head grass (extraction the leaf of leaf of the Ye Hegen of S.scordifolia Fisch. (S galericulata L.), Bignoniaceae plant Semen Oroxyli (Oroxylum indicum (L.) Vent.) and peel of stem and Plantaginaceae plant Big Semen Plantaginis (Plantago major L.).
In in the past application and research, known baicalin has antiinflammatory, antiallergic action, hepatic cholagogic, blood pressure lowering, diuresis, calmness, effect such as analgesic, and aldose reductase is had inhibitory action; At anti-tumor aspect, the experiment report is arranged, multiple animal transplanting tumor mice S180, EAC, L615, Lewis all there are inhibitory action in various degree, its anti-tumor activity and its influence to platelet aggregation are closely related.In clinical practice, baicalin is usually used in treating diseases such as infectious hepatitis, acute biliary infection, lead poisoning, heat-clearing and toxic substances removing, vomiting and nausea uncomfortable in chest, cough due to lung-heat, tumor sore and frequent fetal movement.
Summary of the invention
A kind of new purposes that the purpose of this invention is to provide baicalin.
The inventor studies show that, baicalin has the effect that suppresses angiogenesis.Therefore technical scheme of the present invention is:
Baicalin suppresses the application in the medicine for the treatment of and/or preventing of angiogenesis in preparation.
Baicalin preparation suppress angiogenesis treat and/or prevent application in the medicine time, its effective dose is 6～50mg/kg body weight/day.
When needing, suppress treating and/or preventing of angiogenesis in above-mentioned formula I compound and can also add one or more pharmaceutically acceptable carriers in the medicine.Described carrier comprises diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant of pharmaceutical field routine etc., can also add flavouring agent, sweeting agent etc. in case of necessity.
Medicine of the present invention can be made various ways such as injection, tablet, powder, granule, capsule, oral liquid, unguentum, cream.The medicine of above-mentioned various dosage forms all can be according to the conventional method preparation of pharmaceutical field.
Of the present invention studies show that, except treating and/or preventing cancer, with the baicalin be active component the inhibition angiogenesis treat and/or prevent medicine, for having definite treatment and preventive effect with diseases such as the disease of associated angiogenesis such as diabetic renal papillary necrosis, retinopathy of prematurity, retinal vein occlusion, the degeneration of old plate-like speckle, rheumatic arthritis, psoriasis, hemangioma, atherosclerosiss, the spot in the wound healing is formed also significant inhibitory effect.
The present invention with the target spot of angiogenesis as the treatment disease, has the following advantages dexterously: 1, treatment is carried out at the new vessels that has started, and has specificity; 2, because vascular endothelial cell is exposed in the blood flow, and medicine directly plays a role, so dosage is little, the curative effect height, side effect is little; 3, because the endothelial cell gene expression is relatively stable, so be difficult for producing drug resistance.
Description of drawings
Fig. 1 is the dose-dependent inhibition effect curves of baicalin to human vascular endothelial cell proliferation.
Fig. 2 handles the optical microscope photograph that the human vascular endothelial cell pipe in back forms for the variable concentrations baicalin.
Fig. 3 handles the human migration of vascular endothelial cells result's in back optical microscope photograph for the variable concentrations baicalin.
The specific embodiment
Embodiment 1: baicalin is to the inhibitory action of human vascular endothelial cell proliferation.
(HUVEC available from Cascade Biologics company, Cot:C-003-5C) places the Medium 200 (available from Cascade Biologics company) that contains 10% hyclone (FBS) to cultivate (37 ℃, 5%CO with the human umbilical vein endothelial cell
2, 95% humidity), get the 4th generation cell be inoculated in 96 well culture plates by density 4000/250ul, set the medication group and the blank of matched group, each Concentraton gradient, all do 3 multiple holes for every group.Treat that the cell stand density reaches 80%, the baicalin (with the DMSO dissolving) that adds each Concentraton gradient of 5ul respectively, make final concentration be respectively 1000uM, 100uM, 10uM, 5uM and 1uM, matched group adds 5ulDMSO, continue to cultivate (M200 culture medium, 2%FBS) after 48 hours, Thiazolyl blue tetrazolium bromide salt (MTT) 20ul that adds 5mg/ml, 37 ℃ were continued to hatch 4 hours, stopped cultivating, and abandoned supernatant, every hole adds 150ulDMSO, vibration was measured each hole light absorption value at 490nm wavelength place with BIO-RAD Model 3500 microplate reader after 1 hour gently, represented the quantity of living cells in each hole with light absorption value.Above-mentioned experiment repeats 3 times.The result as shown in Figure 1, abscissa is a drug level among the figure, vertical coordinate is light absorption value (being directly proportional with living cells quantity).The result shows that baicalin is the dose-dependent inhibition effect to human umbilical vein endothelial cell's propagation, and its half amount of suppression is 100uM.
Embodiment 2: baicalin forms the inhibitory action of ability to human vascular endothelial cell pipe.
The every hole of 24 well culture plates adds BD Matrigel
TMMatrix virgin rubber 200ul, make it to aggregate into glue, the 4th generation human umbilical vein endothelial cell (HUVEC) suspension is seeded in 24 orifice plates that scribble Matrigel glue by 30000cell/500ul density, set the medication group of matched group, each Concentraton gradient, the medication group adds 10ul respectively has the baicalin of Concentraton gradient (to dissolve with DMSO, concentration is respectively 1uM, 10uM, 100uM, 1000uM), matched group adds aseptic DMSO10ul, all does 3 multiple holes for every group.37 ℃, 5%CO
2, 95% humidity cultivated 24 hours, the formation of OLYMPUS CK40-RFL observation by light microscope vascular endothelial cell pipe, 4 low power fields countings are got in every hole, take pictures with OLYMPUS CK40 digital camera.The result shows that baicalin is dose-dependent inhibition to human vascular endothelial cell pipe formation ability as shown in Figure 2, and its half amount of suppression is 50uM.
Embodiment 3: baicalin is to the inhibitory action of human migration of vascular endothelial cells ability.
1, preparation chemotactic factor
Get the NIH3T3 cell that goes down to posterity and grew fine in back second day.The soft rinsing of serum-free DMEM 2 times.Serum-free DMEM, 5%CO
2, cultivate 24-48hours for 37 ℃.The collecting cell supernatant.Centrifugal (12000g, 4 ℃, 10min).Supernatant bacteriological filtration (0.22um filter membrane), (20 ℃) are preserved in packing.
2, Matrigel invasion and attack experiment
The Matrigel 25ul (virgin rubber is pressed 1: 2 dilution proportion with DMEM) that gets dilution adds chamber on the Transwell plate, covers whole polyester film surface, hatches 30min for 37 ℃, makes Matrigel aggregate into glue.The 4th generation human umbilical vein endothelial cell (HUVEC) suspension is seeded to the chamber by 30000/250ul density, PBS washing 3 digestion and harvestings from culture bottle.DMEM makes single cell suspension with serum-free, and 5 * 10
5Cells/ml, the medication group adds the medicine (with the DMSO dissolving, concentration is respectively 1uM, 10uM, 100uM, 1000uM) of each Concentraton gradient, and matched group adds the DMSO with volume.The chamber adds the chemotactic factor of 500ul step 1 preparation under the Transwell plate.5%CO
2, cultivated 24 hours for 37 ℃.Wipe the cell of gel and polyester film upper surface gently with the wet cotton swab of DMEM.The careful taking-up gone up the chamber, and ice-cold methanol is fixed 30 minutes.Haematoxylin dyeing 1 minute.Gradient alcohol dehydration (80%, 95%, 100%, 100%), dimethylbenzene is transparent.Carefully polyester film is cut from last chamber, place resinene mounting on the microscope slide.The cell (400 *) under high power lens that is attached to the polyester film lower surface is got 6 visuals field countings at random and is averaged and take pictures.Repeated experiments 2 times.The result shows that baicalin is the dose-dependent inhibition effect to the transfer ability of human vascular endothelial cell as shown in Figure 3, and its half amount of suppression is 50uM.
Embodiment 4: the tumor bearing nude mice in vivo test.
Results human colon cancerous cell line LOVO cell is made cell suspension with PBS, and the right side thigh portion that is seeded to big balb/c nude mice of 8 weeks with 2,000,000/200ul is subcutaneous.When treating the tumor bulk-growth, be divided into two groups at random, 5 every group to 5mm * 5mm size.Baicalin medication group dosage is 36mg/kg (medicine is to contain the PBS solution dissolving of 10%DMSO), and matched group is given the PBS solution 200ul that contains 10%DMSO, and successive administration 60 days writes down the major diameter and the minor axis of tumor body every day.During the medication, untoward reaction does not appear in mice.After putting to death mice, take out tumor, detect the microvessel density of tumor.The result shows that medication group tumor body dwindles than matched group, and growth is obviously slowed down, and microvessel density is starkly lower than matched group.Illustrate that this medical instrument has the effect that suppresses tumor in the body, and side effect is very little.
Claims (10)
1, baicalin suppresses the application in the medicine for the treatment of and/or preventing of angiogenesis in preparation.
2, application according to claim 1 is characterized in that: the effective dose of described baicalin in the medicine that suppresses angiogenesis is 6～50mg/kg body weight/day.
3, application according to claim 1 and 2 is characterized in that: also add one or more pharmaceutically acceptable carriers in the medicine of preparation inhibition angiogenesis.
4, application according to claim 1 and 2 is characterized in that: described medicine is the medicine that treats and/or prevents cancer.
5, application according to claim 1 and 2 is characterized in that: described medicine is to suppress the medicine that spot forms in the wound healing.
6, application according to claim 1 and 2 is characterized in that: described medicine is the medicine that treats and/or prevents diabetic retinopathy, retinopathy of prematurity and retinal vein occlusion.
7, application according to claim 1 and 2 is characterized in that: described medicine is the medicine that treats and/or prevents degeneration of old plate-like speckle and rheumatic arthritis.
8, application according to claim 1 and 2 is characterized in that: described medicine is for treating and/or preventing psoriatic medicine.
9, application according to claim 1 and 2 is characterized in that: described medicine is for treating and/or preventing angiomatous medicine.
10, application according to claim 1 and 2 is characterized in that: described medicine is for treating and/or preventing atherosclerotic medicine.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021596921A CN100430064C (en) | 2002-12-30 | 2002-12-30 | Use of scutellarin in inhibiting vascularization |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021596921A CN100430064C (en) | 2002-12-30 | 2002-12-30 | Use of scutellarin in inhibiting vascularization |
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| CN1511538A true CN1511538A (en) | 2004-07-14 |
| CN100430064C CN100430064C (en) | 2008-11-05 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106692289A (en) * | 2015-11-17 | 2017-05-24 | 上海中医药大学 | Medical application of alcohol extract of sculellaria barbata |
| CN113599416A (en) * | 2021-06-11 | 2021-11-05 | 宋坪 | New application of sculellaria barbata extract |
| CN115737661A (en) * | 2022-10-24 | 2023-03-07 | 中国人民解放军海军军医大学第一附属医院 | Application of baicalin in preparation of medicine for inhibiting retinal neovascularization |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0725761A (en) * | 1993-07-09 | 1995-01-27 | Kureha Chem Ind Co Ltd | Agent for protecting cartilage |
| US6290995B1 (en) * | 2000-02-08 | 2001-09-18 | Zhao Xinxian | Plant drug for preventing cancer II |
| CN1475219A (en) * | 2002-08-16 | 2004-02-18 | 上海凯曼生物科技有限公司 | Medicinal composition for treating blood vessel disease |
-
2002
- 2002-12-30 CN CNB021596921A patent/CN100430064C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106692289A (en) * | 2015-11-17 | 2017-05-24 | 上海中医药大学 | Medical application of alcohol extract of sculellaria barbata |
| CN106692289B (en) * | 2015-11-17 | 2020-06-26 | 上海中医药大学 | Medical application of barbat skullcap alcohol extract |
| CN113599416A (en) * | 2021-06-11 | 2021-11-05 | 宋坪 | New application of sculellaria barbata extract |
| CN115737661A (en) * | 2022-10-24 | 2023-03-07 | 中国人民解放军海军军医大学第一附属医院 | Application of baicalin in preparation of medicine for inhibiting retinal neovascularization |
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| CN100430064C (en) | 2008-11-05 |
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Granted publication date: 20081105 Termination date: 20111230 |