CN1192357A - New use of caffeic acid and ferulic acid antagonistic endotheliolysin biological effect - Google Patents
New use of caffeic acid and ferulic acid antagonistic endotheliolysin biological effect Download PDFInfo
- Publication number
- CN1192357A CN1192357A CN98100877A CN98100877A CN1192357A CN 1192357 A CN1192357 A CN 1192357A CN 98100877 A CN98100877 A CN 98100877A CN 98100877 A CN98100877 A CN 98100877A CN 1192357 A CN1192357 A CN 1192357A
- Authority
- CN
- China
- Prior art keywords
- acid
- ferulic acid
- antagonism
- endothelin
- caffeic acid
- 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.)
- Granted
Links
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 title claims abstract description 125
- 235000004883 caffeic acid Nutrition 0.000 title claims abstract description 65
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 229940074360 caffeic acid Drugs 0.000 title claims abstract description 62
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 title claims abstract description 62
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 title claims description 67
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 title claims description 67
- 235000001785 ferulic acid Nutrition 0.000 title claims description 67
- 229940114124 ferulic acid Drugs 0.000 title claims description 67
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 title claims description 67
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 title claims description 67
- 230000004071 biological effect Effects 0.000 title abstract description 5
- 230000003042 antagnostic effect Effects 0.000 title abstract 2
- 239000003814 drug Substances 0.000 claims abstract description 30
- 230000008485 antagonism Effects 0.000 claims description 38
- 102000002045 Endothelin Human genes 0.000 claims description 22
- 108050009340 Endothelin Proteins 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 22
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 9
- 241000699670 Mus sp. Species 0.000 claims description 8
- 230000036772 blood pressure Effects 0.000 claims description 8
- 230000002792 vascular Effects 0.000 claims description 8
- 230000004663 cell proliferation Effects 0.000 claims description 7
- 230000001681 protective effect Effects 0.000 claims description 7
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 7
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 7
- 239000002253 acid Substances 0.000 abstract description 3
- 102100033902 Endothelin-1 Human genes 0.000 description 47
- 101800004490 Endothelin-1 Proteins 0.000 description 47
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000001550 time effect Effects 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- 239000002775 capsule Substances 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- FINHMKGKINIASC-UHFFFAOYSA-N Tetramethylpyrazine Chemical compound CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 239000012531 culture fluid Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 150000003440 styrenes Chemical class 0.000 description 2
- 238000009495 sugar coating Methods 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 229930182836 (R)-noradrenaline Natural products 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000006906 Vascular Ring Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002308 endothelin receptor antagonist Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- -1 methoxyl group Chemical group 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000002315 pressor effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Several new usages of caffeic acid and ferulaic acid in the prepn. of medicine are disclosed. They include the application of caffeic acid and ferulaic acid in the prepn. of medicines which possess antagonistic action against diseases caused by the biological effect of endotheliolysin.
Description
The invention relates to the pharmaceutic usage invention of caffeic acid, ferulic acid, specifically caffeic acid, the application of ferulic acid in preparing the medicine that the endothelin-1 biological effect is had antagonism belong to drug world.
Caffeic acid and ferulic acid are chemically all belonging to styrene type compounds, and the difference of the two is the group on 3 of the phenyl ring, are hydroxyls on 3 of the caffeinic phenyl ring, and are to be methoxyl group on 3 of the phenyl ring of ferulic acid.Caffeic acid and ferulic acid are the important component of promoting blood flow and remove blood stasis drug in China's tradition Chinese medicine, and be more as content in the medical materials such as Radix Angelicae Sinensis, ligustrazine.
Endothelin is a kind of bioactive substance of latest report in the world.The generation development and the Endothelin of many cardiovascular and cerebrovascular diseases have confidential relation, and as hypertension, coronary heart disease, cerebrovascular accident, heart failure etc., Endothelin participates in pathology, the physiological process of these diseases.Many countries are the pathological index of Endothelin as diseases such as hypertension, coronary heart disease, cerebrovascular accident, heart failure, and treat above-mentioned disease by the biological agent of regulating Endothelin.Endothelin is also relevant with chronic rejection, eclamposia, hepatitis etc. after other diseases such as the organ transplantation in addition.Therefore, screening is a kind of can the bioactive medicine of antagonism Endothelin be present extremely important and significant thing.
The inventor has found caffeic acid and the ferulic acid antagonism to Endothelin, thereby has finished the present invention based on a large amount of experimentatioies.
Therefore, the object of the invention provides the pharmaceutic usage of caffeic acid and ferulic acid.
As mentioned above, caffeic acid and ferulic acid are chemically all belonging to styrene type compounds, and its structural formula is respectively:
The chemical structural formula of caffeinic chemical structural formula ferulic acid
The inventor studies have shown that by experiment caffeic acid, ferulic acid have good antagonism to the biological effect of endothelin-1 (ET-1), mainly show:
(1) caffeic acid, ferulic acid cause the protective effect of death of mice to endothelin-1 (ET-1).
(2) caffeic acid and ferulic acid are to the contract antagonism of vascular effect of ET-1.
(3) caffeic acid and ferulic acid rise the antagonism of blood pressure effect to ET-1.
(4) caffeic acid and ferulic acid are to the antagonism of ET-1 hyperamization pipe smooth muscle cell proliferation effect.
Caffeic acid and ferulic acid are two kinds of structurally very approaching chemical compounds, according to the pharmaceutical preparation technology of routine, can add conventional excipient with it as effective ingredient, are prepared into any pharmaceutical preparation that is suitable for using clinically.For example, pill, tablet, capsule, oral liquid, injection, powder, unguentum, aerosol etc.Preparing these pharmaceutical preparatioies is those of ordinary skills' technical activity routinely.
Because the inventor has discovered the above-mentioned new pharmacological action of caffeic acid and ferulic acid by experiment, therefore, according to the made any pharmaceutical dosage form that is suitable for clinical use of the conventional formulation technology of pharmaceutical field, all has following effect:
(1) endothelin-1 is caused the protective effect of death of mice.
(2) to the contract antagonism of vascular effect of ET-1.
(3) ET-1 is risen the antagonism of blood pressure effect.
(4) to the antagonism of ET-1 hyperamization pipe smooth muscle cell proliferation effect.
Therefore, the invention provides the following pharmaceutic usage of caffeic acid, ferulic acid:
Caffeic acid, the application of ferulic acid in preparing the medicine that Endothelin is had antagonism;
Caffeic acid, ferulic acid cause to endothelin-1 that in preparation death of mice has the application in the medicine of protective effect;
Caffeic acid, ferulic acid have application in the medicine of antagonism at preparation endothelin-1 is contracted vascular effect;
Caffeic acid, ferulic acid rise application in the medicine that blood pressure effect has antagonism in preparation to endothelin-1;
Caffeic acid, the application of ferulic acid in preparing the medicine that endothelin-1 hyperamization pipe smooth muscle cell proliferation effect is had antagonism.
Caffeic acid, ferulic acid can add the medicine excipient when being prepared into medicament, as, filler, disintegrating agent, solvent, antiseptic, correctives, thickening agent, emulsifying agent etc.
With caffeic acid, ferulic acid when being prepared into medicament, the amount of contained caffeic acid or ferulic acid effective ingredient is generally the treatment effective dose that is used for human body in the medicament.
The said pharmacy optimization of the present invention contains the caffeic acid or the ferulic acid of 0.1-99.9% weight portion;
The said pharmacy optimization of the present invention contains the caffeic acid or the ferulic acid of 10-90% weight portion;
The said pharmacy optimization of the present invention contains the caffeic acid or the ferulic acid of 15-80% weight portion;
The said pharmacy optimization of the present invention contains the caffeic acid or the ferulic acid of 20-70% weight portion;
The method of the said caffeic acid of the present invention or ferulic acid being made capsule is:
Get the pure product of caffeic acid or ferulic acid, add excipient, go into the blender mixing, encapsulated, make capsule.
The method of the said caffeic acid of the present invention or ferulic acid being made tablet is:
Get the pure product of caffeic acid or ferulic acid, add excipient, mix homogeneously, pelletize, granulate, tabletting, sugar coating gets tablet.
Following pharmacological evaluation further illustrates the pharmaceutic usage of caffeic acid or ferulic acid.
Experimental example 1 caffeic acid, ferulic acid cause the protective effect of death of mice to endothelin-1
90 of Kunming mouses (available from the department of the Chinese Academy of Sciences of laboratory animal section of Beijing Medical University), male and female half and half, body weight 20 ± 2.0g, fasting be can't help water after 16 hours, (dosage range of administration is 0.1～100mg/kg) after 30 minutes from lumbar injection caffeic acid, ferulic acid, from tail vein injection FT-1 12nmol/kg, death toll and the death time of record animal; Matched group behind the normal saline of lumbar injection and disposition of drug group equal parts 30 minutes, from tail vein injection ET-112nmol/kg, death toll and the death time of record animal, and data are done statistical procedures.
Caffeic acid and ferulic acid all effectively antagonism ET-1 cause the death of mice effect, the death time has been compared the significance meaning with matched group; In dosage was the scope of 0.1～100mg/kg, this made the apparatus dose dependent; When drug level was identical, the antagonism usefulness of ferulic acid was greater than caffeic acid.
Table 1. caffeic acid and ferulic acid antagonism ET-1 cause the protective effect of death of mice
Drug administration dosage number of animals death time of animal
(only) (min)
ET-1 12nmol/kg 10 2.24±1.02
Caffeic acid+ET-1 100mg/kg 10 12.72 ± 3.11
* *
10mg/kg 10 3.19±0.88
*
1mg/kg 10 2.58±0.21
*
0.1mg/kg 10 2.33±0.19
*
Ferulic acid+ET-1 100mg/kg 10 14.37 ± 1.89
* *
10mg/kg 10 5.54±1.06
**
1mg/kg 10 4.04±0.50
**
0.1mg/kg 10 3.33±1.84
*
Experimental example 2 caffeic acids and ferulic acid are to the contract antagonism of vascular effect of ET-1
Male SD rat, body weight 230 ± 10g with winning thoracic aorta fast after the rat stunning, after separating connective tissue, is cut into the wide vascular ring of 2～3mm, places Krebs-Henseleit physiological solution (K-H liquid, pH7.40 ± 0.05,95%O respectively
2+ 5%CO
2, 37.0 ± 0.5 ℃) in, add 2g basis tension force, with 10
-7The mol/L norepinephrine swash in advance secondary, balance, stable after, add ET-1 10
-9Mol/L, after waiting to reach the maximum collapse effect, (with 2%DMSO is solvent to add caffeic acid, ferulic acid and the CA-1201 of variable concentrations respectively, experiment compares with 2%DMSO), connect desk-top balance recorder (Shanghai Dahua Instrument and Meter Plant) through tonotransducer, record blood vessel isotonic contraction and diastole situation.
Caffeic acid and ferulic acid be the vascular effect that contracts of antagonism ET-1 significantly, and gives antagonism tool dose dependent; Drug dose-effect curve is after the match of sigmiodal method (referring to Fig. 1), and from the effect kinetic parameter that drawn as seen, ferulic acid antagonism ET-1 contracts the usefulness of blood vessel than caffeic acid strong (p＜0.05).
Table 2. caffeic acid and the ferulic acid antagonism ET-1 vascular effect kinetic parameter that contracts
Pharmacokinetic parameter
E
max(％) IC
50(×10
-6mol/L)
Caffeic acid 70.95 ± 6.30 1.80 ± 0.80
Ferulic acid 92.10 ± 0.81 0.063 ± 0.005
Experimental example 3 caffeic acids and ferulic acid rise the antagonism of blood pressure effect to ET-1
Male SD rat, body weight 230 ± 10g after water 18h is can't help in fasting, behind caffeic acid and the ferulic acid various dose tail vein injection, measures from tail vein injection ET-1 by 6 μ g/kg immediately, changes (SBP) with Impedance Determination rat arteria caudalis systolic pressure; Matched group is handled the ET-1 of back tail vein injection and disposition of drug group same dose with the equivalent normal saline; And with systolic pressure changing value and matched group comparison.
Caffeic acid and ferulic acid significantly after the antagonism ET-1 intravenous injection to the blood pressure effect that rises of rat; Compare with matched group, in 30 minutes, pressor effect obviously weakens after giving ET-1, and there was no significant difference (p＞0.05) (referring to Fig. 2) is compared in its effect in the later time with matched group.
Experimental example 4 caffeic acids and ferulic acid are to the antagonism of ET-1 hyperamization pipe smooth muscle cell proliferation effect
Getting rabbit aortic smooth muscle cells (RAVSMC) that the 5th generation grew up to fine and close monolayer, to adjust cell number with the culture method that goes down to posterity be 1 * 10
5Ml
-1, be inoculated in 96 well culture plates (100 μ, 1 hole
-1), 37 ℃, 5%CO
2Hatch 24h, inhale and remove culture fluid, change DMEM culture fluid, add ET-1 (10nmolL with 1% calf serum
-1) after continue to hatch different time after, obtain time-effect curve of ET 1 effect and RAVSMC; Investigate it behind adding caffeic acid and the ferulic acid and ET-1 is caused the proliferation function of smooth muscle cell.To measure each hole optical density (OD) value at the 570nm place with enzyme mark detector after the violet staining.4.1 cellular morphology is observed
After the fixing painted culture plate of crystal violet dries, directly under inverted microscope, observe, do not see that tangible cellular morphology changes.4.2 ET-1 stimulate RAVSMC propagation time-effect relation table 3.ET-1 causes the time effect of RAVSMC propagation
The time rate of increase
(d) (％)
1 33.3±25.0**
2 50.0±13.6***
7 40.0±9.28**
*p＞0.05；**p＜0.05；***p＜0.01
By table 3 as seen, ET-1 can stimulate RAVSMC propagation, and in the 2nd day peaking, the 1st, 2 compared with matched group with the 7th day numerical value, and the increase of cell proliferation rate has the significance meaning; This effect is time dependence.4.3 caffeic acid and ferulic acid antagonism ET-1 cause RAVSMC propagation
Cause time-effect relation that RAVSMC breeds, 10nmolL by ET-1
-1ET-1 and caffeic acid, ferulic acid and CA-1201 are incubated altogether and were measured OD (570nm) value on the 2nd day, the results are shown in Table 4.
Table 4. caffeic acid, 1 couple of ET-1 of ferulic acid cause the effect of RAVSMC inhibition of proliferation
Group OD value (* 10
2)
10
-11 10
-10 10
-9 10
-8
Blank 1.6 ± 0.5
ET-1 2.4 ± 0.2
ΔCaffeic acid+ET-1 1.2 ± 0.1
* *1.2 ± 0.4
* *1.2 ± 0.8
* *0.9 ± 0.1
* *Ferulic acid+ET-1 1.4 ± 0.3
* *1.5 ± 0.7
* *1.2 ± 0.2
* *1.2 ± 0.4
* *
Δ is compared with the blank group, p＜0.05;
*P＞0.05;
*P＜0.05;
* *P＜0.01
By table 4 as seen, but the RAVSMC that caffeic acid and ferulic acid significance ground antagonism ET-1 cause propagation, and this makes the apparatus dose dependent.
Infer that theoretically Endothelin may be one of cause of disease of traditional Chinese medical science stagnancy of qi and blood stasis.This experimental result can draw: caffeic acid, ferulic acid are endothelin antagonist, to the diseases related treatment of Endothelin and explore the origin cause of formation of qi stagnation blood stasis and its treatment is had very big design for development.
Embodiment 1
Get pure product 10 grams of caffeic acid, add 100 gram starch, go into the blender mixing, encapsulated, every powder charge powder 1 gram makes capsule.
Embodiment 2
Get pure product 100 grams of ferulic acid, add starch 500 grams, mix homogeneously, pelletize, granulate, tabletting, sugar coating gets tablet.
Accompanying drawing 1 is caffeic acid and the ferulic acid antagonism ET-1 blood vessel function dose-effect curve that contracts.
Accompanying drawing 2 is that caffeic acid and ferulic acid antagonism ET-1 rise blood pressure action time-effect curve.
Claims (10)
1, the application of caffeic acid in preparing the medicine that Endothelin is had antagonism.
2, caffeic acid causes to Endothelin that in preparation death of mice has the application in the medicine of protective effect.
3, caffeic acid has application in the medicine of antagonism at preparation Endothelin contracted vascular effect.
4, caffeic acid rises application in the medicine that blood pressure effect has antagonism in preparation to Endothelin.
5, the application of caffeic acid in preparing the medicine that Endothelin hyperamization pipe smooth muscle cell proliferation effect is had antagonism.
6, the application of ferulic acid in preparing the medicine that Endothelin is had antagonism.
7, ferulic acid causes to Endothelin that in preparation death of mice has the application in the medicine of protective effect.
8, ferulic acid has application in the medicine of antagonism at preparation Endothelin contracted vascular effect.
9, ferulic acid rises application in the medicine that blood pressure effect has antagonism in preparation to Endothelin.
10, the application of ferulic acid in preparing the medicine that Endothelin hyperamization pipe smooth muscle cell proliferation effect is had antagonism.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98100877A CN1073416C (en) | 1998-03-04 | 1998-03-04 | New use of caffeic acid and ferulic acid antagonistic endotheliolysin biological effect |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98100877A CN1073416C (en) | 1998-03-04 | 1998-03-04 | New use of caffeic acid and ferulic acid antagonistic endotheliolysin biological effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1192357A true CN1192357A (en) | 1998-09-09 |
| CN1073416C CN1073416C (en) | 2001-10-24 |
Family
ID=5216311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98100877A Expired - Fee Related CN1073416C (en) | 1998-03-04 | 1998-03-04 | New use of caffeic acid and ferulic acid antagonistic endotheliolysin biological effect |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1073416C (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002080355A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Antihypertensive agent |
| JP2002080356A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Preventing and treating agent for hypertension |
| JP2002080354A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Antihypertensive composition |
| JP2002080357A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Hypertension prevention / amelioration / treatment agent |
| JP2002145766A (en) * | 2000-11-08 | 2002-05-22 | Kao Corp | Hypotension prevention / treatment agent |
| JP2002154977A (en) * | 2000-09-05 | 2002-05-28 | Kao Corp | Food composition |
| JP2002363075A (en) * | 2001-06-05 | 2002-12-18 | Kao Corp | Antihypertensive agent |
| WO2011080593A3 (en) * | 2009-12-30 | 2011-08-25 | Purapharm International (Hk) Limited | Materials and methods for prevention and treatment of viral infections |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04234319A (en) * | 1990-12-28 | 1992-08-24 | Fujirebio Inc | Anti-HBV agent |
-
1998
- 1998-03-04 CN CN98100877A patent/CN1073416C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002080355A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Antihypertensive agent |
| JP2002080356A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Preventing and treating agent for hypertension |
| JP2002080354A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Antihypertensive composition |
| JP2002080357A (en) * | 2000-09-05 | 2002-03-19 | Kao Corp | Hypertension prevention / amelioration / treatment agent |
| JP2002154977A (en) * | 2000-09-05 | 2002-05-28 | Kao Corp | Food composition |
| JP2002145766A (en) * | 2000-11-08 | 2002-05-22 | Kao Corp | Hypotension prevention / treatment agent |
| JP2002363075A (en) * | 2001-06-05 | 2002-12-18 | Kao Corp | Antihypertensive agent |
| US7939563B2 (en) | 2001-06-05 | 2011-05-10 | Kao Corporation | Remedy for hypertension |
| WO2011080593A3 (en) * | 2009-12-30 | 2011-08-25 | Purapharm International (Hk) Limited | Materials and methods for prevention and treatment of viral infections |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1073416C (en) | 2001-10-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1073416C (en) | New use of caffeic acid and ferulic acid antagonistic endotheliolysin biological effect | |
| CN102370686A (en) | Pharmaceutical composition for treating chronic liver disease and its application | |
| CN1118471C (en) | Medicine containing tan matter caesalpinia extract | |
| CN1186336C (en) | Prepn and application in preparing medicine of fraxinus general coumarin | |
| CN1582952A (en) | Use of asiaticoside in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN1583803A (en) | Polysaccharose MF4 of mussel with enhancing immunity and anti-tumour activity | |
| CN101033245A (en) | Preparation method and application of pedunculoside | |
| CN101040891A (en) | Preparation method and application of tripterygium hypoglaucum alkaloids | |
| CN1163227C (en) | Application of salvianolic acid B magnesium salt in preparation of medicament for treating chronic liver disease | |
| CN1298705A (en) | Chinese medicine for treating hepatitis B and its preparing process | |
| CN1296089C (en) | Zedoary injection preparation and its preparing method | |
| CN1544429A (en) | Bee glue flavone extract preparation method, pharmaceutical preparation and its new medical uses | |
| CN103976957A (en) | 20 (S)-protopanaxadiol microsphere and preparation method and application thereof | |
| CN1055859C (en) | Application of stilbene compound and its derivative in preparation of endothelium element antagonist agent | |
| CN1660399A (en) | A medicine for treating wind-cold-damp arthralgia and weakness of muscles and bones | |
| CN1176677C (en) | Chinese medicine composition for treating cardiovascular and cerebrovascular diseases and its preparing process | |
| CN1628649A (en) | Pharmaceutical combination containing red sage root element and preparation method thereof | |
| CN1582946A (en) | Use of centellosic acid derivative in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN1155381C (en) | New pharmaceutical use of sinomenine | |
| CN100337654C (en) | Composition of Chinese medicine effective ingredients for treating cardiovascular disease | |
| CN1056748C (en) | Use of bolbostemmaoside A to prepare medicine for treatment of leukemia | |
| CN1850837A (en) | 9-(1,3-benzo dioxolyl-5_)-4-(beta-D-glucopyranosyloxy)-6,7-dimethoxy naphthale [2,3-C] furna-1(3II] ketone, and its preparing method and medicinal composition containing same | |
| CN1290510C (en) | Pharmaceutical composition containing gen-seng total saponin and astragalus root total saponin, its preparing process and application | |
| CN1309379C (en) | Asari dripping pills and its preparation process | |
| CN100342879C (en) | Liver fibrosis treating prepn and its process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Applicant after: Air Force General Hospital, PLA Applicant before: Department of Science and Technology Development General Hospital of PLA Air Force |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: SCIENCE + TECH. DEVELOPMENT DEPT. OF GENERAL HOSPITAL OF AIR FORCE, PLA TO: PLA AIR FORCE GENERAL HOSPITAL |
|
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |