CN108125943A - Application of decursinol angelate in preparation of anti-atherosclerosis medicine - Google Patents
Application of decursinol angelate in preparation of anti-atherosclerosis medicine Download PDFInfo
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- CN108125943A CN108125943A CN201810046270.4A CN201810046270A CN108125943A CN 108125943 A CN108125943 A CN 108125943A CN 201810046270 A CN201810046270 A CN 201810046270A CN 108125943 A CN108125943 A CN 108125943A
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- Prior art keywords
- decursinol
- radix angelicae
- angelicae sinensis
- decursin
- atherosclerosis
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- 239000003814 drug Substances 0.000 title claims abstract description 25
- 230000000879 anti-atherosclerotic effect Effects 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims description 4
- AGABNGOXUSXQDD-XKGFZTIGSA-N [(3s)-2,2-dimethyl-8-oxo-3,4-dihydropyrano[3,2-g]chromen-3-yl] (z)-2-methylbut-2-enoate Chemical compound C1=CC(=O)OC2=C1C=C1C[C@H](OC(=O)C(\C)=C/C)C(C)(C)OC1=C2 AGABNGOXUSXQDD-XKGFZTIGSA-N 0.000 title description 2
- AGABNGOXUSXQDD-UHFFFAOYSA-N decursinol angelate Natural products C1=CC(=O)OC2=C1C=C1CC(OC(=O)C(C)=CC)C(C)(C)OC1=C2 AGABNGOXUSXQDD-UHFFFAOYSA-N 0.000 title description 2
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
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- Health & Medical Sciences (AREA)
- Emergency Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
the invention relates to an application of decursinol angelic ester in preparing antiatherosclerotic, belonging to the technical field of medicine, wherein the decursinol angelic ester is an active ingredient of angelica, and is found to have an improvement effect on blood fat in ApoE knockout mice.
Description
Technical field
The invention belongs to medicine technology fields, and in particular to decursinol Radix Angelicae Sinensis fat is used as and prepares Antiatherosclerosis medicine
Application.
Background technology
Inflammatory reaction caused by disorders of lipid metabolism is to lead to the principal element of atherosclerosis.Lipid and inflammatory factor
The inside Epithelial Cell Adhesion of monocyte is caused to lead to atherosclerosis.Oxidized low-density lipoprotein inducing macrophage
Lipid accumulation leads to progression of atherosclerosis.
Yunnan Province abounds with Radix Angelicae Sinensis, and its first-class quality, at home and abroad has long enjoyed a good reputation, and traditional place of production is West Yunnan, and with
It practises and claims cloud Radix Angelicae Sinensis when that attribution has good quality is the most famous in Dali Heqing.One of active ingredient of Radix Angelicae Sinensis is Radix Angelicae Sinensis ester
(Decursinol Angelate), Radix Angelicae Sinensis ester is the rhizome extract of Radix Angelicae Sinensis, and main component is decursinol Radix Angelicae Sinensis ester
(Decursin).
Traditional lipid-loweringing Western medicine-statins, there are some using it is upper the drawbacks of, relevant clinical trial,
Such as HPS(Simvastatin)、ASCOT-LLA(Atorvastatin)、CORONA(Rosuvastatin)And JUPITER(Rosuvastain
Spit of fland)Researchs is waited to find:Statins make diabetes risk increase about 20%, and Statins class lipid-lowering medicine has striated muscle
Dissolving, the side effect of hepatic disorder.For Chinese traditional medicine angelica after thousands of years of test, safety is secure.It finds no at present
Close report of the decursinol Radix Angelicae Sinensis fat in terms of antiatherosclerosis.
Invention content
It is an object of the present invention to solve the deficiency of the existing technology and provide decursinol Radix Angelicae Sinensis fat(Decursin)As system
The application of standby Antiatherosclerosis medicine.
To achieve the above object, the technical solution adopted by the present invention is as follows:
Decursinol Radix Angelicae Sinensis fat is as the application prepared in Antiatherosclerosis medicine.
It is further preferred that the drug includes decursinol Radix Angelicae Sinensis fat 20mg/kg therapeutically effective amounts and pharmaceutically may be used
The carrier of receiving.
It is further preferred that the drug is oral preparation.
It is further preferred that the drug is tablet, hard shell capsules or granule.
It is further preferred that the acceptable effective concentration of decursinol Radix Angelicae Sinensis fat in blood is in 12.5uM-50uM/
24h。
The present invention is not particularly limited pharmaceutically acceptable carrier, carrier such as fragrance, sweetener, liquid or solid
The common carriers substance such as body filler or diluent, and adopt and common pharmaceutical formulation, such as piece with method known in this field, is made
Agent, capsule, granule etc..
Compared with prior art, the present invention advantage is:
The present invention is studied with the active ingredient of Radix Angelicae Sinensis-decursinol Radix Angelicae Sinensis ester, has been found that it has blood in ApoE knock-out mices
The improvement result of fat.The visible apparent atherosclerotic plaque of aorta of ApoE knock out mice, by the feeding root of purple-flowered peucedanum
After alcohol Radix Angelicae Sinensis ester, atherosclerotic plaque is obviously improved.Endothelial cell adherency effect relevant with atherosclerosis simultaneously
In, decursinol Radix Angelicae Sinensis ester can inhibit the monocyte that the inside Epithelial Cell Adhesion of monocyte, LDL and oxLDL are induced to endothelium
Cell adherence.The present invention shows decursinol Radix Angelicae Sinensis fat from external, In vivo study(Decursin)Dyslipidemia can be improved,
Prevent and treat atherosclerosis.And after Decursin is used, ApoE knock out mice there are no change of blood sugar, and dynamic
Object is without death, absent renal function and dysfunction of liver.Therefore, the use of the drug has preferable safety and validity.This hair
Artery congee can be effectively prevented and treated compared with lipid-lowering statins in terms of the bright atherosclerosis for improving experimental animal models
Incidence of the sample hardening without increasing diabetes, without the damage of hepatic and renal function.
Description of the drawings
Fig. 1 is influences of the Decursin for ApoE knock-out mice atherosclerotic plaques;A) ApoE knock-out mices are fed
Eat Decursin and with solvent(Vehicle:DMSO)Feeding is reference, and feeding uses 0 coloration result of oil red after 12 weeks.B) needle
Demarcated Patch size is dyed to oil red 0, carries out plaque area ratio(0 stained positive region of oil red/angiosomes ×
100%)It measures, for wherein Decursin feedings group compared with solvent feeding group, P values are 0.0416.
Fig. 2 is the Adherence of Monocytes of Decursin confrontation inflammatory factor TNFalpha inductions in endothelial cell;A) using 10ng/
The TNF α of mL and various concentration Decursin(0th, 25,50 and 100uM)After combined stimulation endothelial cell, detection monocyte is inside
Epithelial Cell Adhesion situation, white are monocyte, and shoot picture using fluorescence microscope(Amplification factor is 20 times).B it) is directed to
Adherence of Monocytes cell number is counted(Number)And the statistical difference opposite sex, and with Decursin(0uM)Processing group is control group.
With Decursin(0uM)Processing group compares, * P<0.05, **P<0.01.(Open triangles:Decursin (0uM)Processing group;
Open circles:Decursin (25uM)Processing group;Open diamonds:Decursin (50uM)Processing group;Hollow square:
Decursin (100uM)Processing group.)
Fig. 3 is the Adherence of Monocytes of Decursin confrontation LDL inductions in endothelial cell;A) using the LDL of 50ug/mL and difference
Concentration Decursin(0th, 25,50 and 100uM)After combined stimulation endothelial cell, the inside Epithelial Cell Adhesion feelings of monocyte are detected
Condition, white are monocyte, and shoot picture using fluorescence microscope(Amplification factor is 20 times).B) for Adherence of Monocytes
Cell number is counted(Number)And the statistical difference opposite sex, and with Decursin(0uM)Processing group is control group.With Decursin
(0uM)Processing group compares, * * P<0.01, ***P<<0.01.(Open triangles:Decursin (0uM)Processing group;Open circles:
Decursin (25uM)Processing group;Open diamonds:Decursin (50uM)Processing group;Hollow square:Decursin
(100uM)Processing group.)
Fig. 4 is the Adherence of Monocytes of Decursin confrontation oxLDL inductions in endothelial cell;A) using the oxLDL of 50ug/mL and
Various concentration Decursin(0th, 25,50 and 100uM)After combined stimulation endothelial cell, the inside Epithelial Cell Adhesion of monocyte is detected
Situation, white are monocyte, and shoot picture using fluorescence microscope(Amplification factor is 20 times).B it) is glued for monocyte
Attached cell number is counted(Number)And the statistical difference opposite sex, and with Decursin(0uM)Processing group is control group.With Decursin
(0uM)Processing group compares, * * P<0.01.(Open triangles:Decursin (0uM)Processing group;Open circles:Decursin
(25uM)Processing group;Open diamonds:Decursin (50uM)Processing group;Hollow square:Decursin (100uM)Processing
Group.
Specific embodiment
With reference to embodiment, the present invention is described in further detail.
It will be understood to those of skill in the art that the following example is merely to illustrate the present invention, and it should not be regarded as limiting this hair
Bright range.In the examples where no specific technique or condition is specified, according to the described technology of document in the art or condition
Or it is carried out according to product description.Production firm person is not specified in material therefor or equipment, and being can be by buying what is obtained
Conventional products.
The present invention is unless otherwise stated, percentage sign represents percentage by volume.
Materials and methods
1. decursinol Radix Angelicae Sinensis ester
Decursinol Radix Angelicae Sinensis ester (Mahat et al, 2012a and Mahat, 2012b), (Elcom are demonstrated by column chromatography
Sci., Ltd) molecular weight be 328, in cell experiment with dromisol (DMSO) (Sigma-Aldrich, Mo, USA) it is molten
Decursinol Radix Angelicae Sinensis ester is solved, concentration is respectively 12.5uM, 25uM, 50uM and 100 uM.Cholinesterase reactivator decursinol mixes
Object (Now Foods, USA) main component is decursinol Radix Angelicae Sinensis ester, is angelica root(Angelica gigas Nakai)After air-drying
Extract.Each capsule contains 500 milligrams of decursinol Radix Angelicae Sinensis esters, raises mouse according to 20 mgs/kg of dosage daily
(SD)。
2. the foundation of ApoE knock out mice Atherosclerosis Models
The ApoE knock out mice that the present invention is sheerly using C57BL/6 is fed as material by high lipid food, successfully induces its shape
Into atherosclerotic lesion mouse model.
Materials and methods
2.2.1 reagent and instrument stereomicroscope(Jiangnan Yongxin, Nanjing), inverted microscope(TS100F, Nikon company, day
This), freezing microtome(CM1850, Leica company, Germany);Mouse basal feed is by Shanghai Communications University's Ruijin Hospital medicine
Institute's animal center provides;Yin Hong, haematoxylin are purchased from Beijing Sai Chi biotech firms;Oil red 0 is purchased from Beijing Ding Guo biotech firms;It is low close
Spend lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C)Detection kit builds up biological public affairs purchased from Nanjing
Department;Remaining reagent is that domestic analysis is pure.High lipid food is purchased from RESEARCH DIETS companies, product identification #D12492.
2. 2 .2 experimental animals C57BL/6 are sheerly the apo E-deficient mice of background(ApoE-/-)Purchased from south
Capital college mode Institute of Botany introduces a fine variety agreement [2012] 470.Animal feeding environmental condition is 20-25 DEG C of room temperature, relatively wet
Degree 40%~70%.
20 male ApoE knock-out mices(20130720 births), 20130919 weight are:24.65+1.9g 20130919
Start high lipid food to feed, 20140405 weight are:33.3+4g, blood glucose are:11.59+1.33mmol/L.
To the male of 6 week old or so(ApoE-/- mouse(n=8)Carry out high lipid food nursing(21% fat and 0.15% courage are consolidated
Alcohol), feeding is after 12 weeks, and the mouse that weight is 33.3+4g is dissected and venous blood samples for testing in next step.
2.2.3 the detection method serum total cholesterol of blood lipid level(Total cholesterol, TC), triglycerides
(Triglyceride, TG)Cholesterol oxidation enzyme process is respectively adopted in horizontal measure(C0D-PAP)And phosphoglycerol oxidase method
(GP0-PAP), finally by spectrophotometer absorption value is measured in 500nm.Low density lipoprotein cholesterol(LDL-C), it is highly dense
Spend lipoprotein cholesterol(HDL-C)Assay method builds up kit specification according to Nanjing and is operated.
2.2.4 it after the blood sampling of aorta bulk dyeing method mouse, is irrigated under anaesthesia with PBS, separation obtains whole
Aorta after removing remaining fat and connective tissue, is cleaned up with PBS, more than 12h is fixed in 4% paraformaldehyde, then indulge
To splitting.The dyeing of oil red 0 30min is carried out after 2min is impregnated in 70% ethyl alcohol of active pulse classic(0.5% mother liquor is made into isopropanol,
Again with oil red mother liquor:Ultra-pure water=3:2 dilution proportion is into working solution);70% ethyl alcohol, which is rinsed to tissue, to whiten, and is cleaned through distilled water
It takes pictures afterwards for several times, and with Image-Pro Plus 6.0.(IPP6.0)Software(Media Cybernetics)To plaque area into
Row quantitative analysis.
2.2.5 after aortic root plaque chemical analysis method takes out heart fixation 48h, master is cut from auricle lower section
Artery root, then carry out sucrose dehydration, OCT(Optimal cutting temperature compound)Embedding.Fast quickly cooling
Since aorta petal using 100 μm it is that spacing cuts continuous 5 thickness as 8 μm of slice after jelly.Slice carries out oil red dyeing.
The same 2.2.4 of colouring method.
3. cell culture
3.1 Human umbilical vein endothelial cells(HUVEC)Cell culture and person monocytic cell(THP-1)Culture
Human umbilical vein endothelial cells(HUVEC)(ATCC, USA) is in M200 culture mediums(High glucose) (Aiello et al,
1994) it is cultivated in (Invitrogen, Carlsband, CA, USA), growth additive is added in culture medium(LSGS), it is green
Mycin 100 U/ml and streptomysin 100ug/ml (Gibco, NY, USA).Human retina microvascular endothelial cells (HRMVEC)
(Cell Systems, USA), which is used, contains microvessel growth additive(MVGS)Penicillin 100U/ml and streptomysin 100ug/ml
131 culture mediums of MCDB of (Gibco, NY, USA)(High glucose culture medium).It is the 2nd for HUVEC in culture experiment
Generation.
Person monocytic cell(THP-1)Strain is originally derived from American type culture collection(ATCC).
3.2 cell countings detect the adhesion rate of HUVEC-12 cells and person monocytic cell THP-1
After HUVEC-12 cell inoculations are used MCDB131 medium cultures for 24 hours in 24 hole sterile culture plates, by following grouping
It is detected:1)TNFα(10ng/mL)+Decursin(0th, 25,50 and 100uM)Stimulation;2)LDL(50ug/mL)+Decursin
(0th, 25,50 and 100uM)Stimulation;2)oxLDL(50ug/mL)+Decursin(0th, 25,50 and 100uM)Stimulation.Stimulation 6 hours
Afterwards, it is cleaned 3 times using serum-free RPMI1640 culture solutions, adds in 5 × 106The THP-1 cells in a/hole are in 37 DEG C, 5%CO2Item
After being incubated 30min under part, unbonded THP-1 cells are removed, unbonded THP-1 cell numbers are counted under inverted microscope.
The computational methods of adhesion rate are:
Adhesion rate=[(cell number of addition THP-1-unbonded cell number)/add in the cell number of THP-1] × 100%.
4. statistical analysis
Data are represented with mean ± standard deviation, are examined by t(Two groups are compared)Or variable analysis(Two groups of > compares)Come carry out
Compare.Comparison among groups are examined with one-way analysis of variance (onewayANOVA), are thought as P < 0.05 with statistical significance.
5 results and analysis
First, research confirms that decursinol Radix Angelicae Sinensis fat can reduce the blood that atherosclerosis animal model ApoE genes knock out mouse
Lipid level(Table 1).
ApoE knock-out mices are Atherosclerosis Model by the induction of high lipid food feeding, are randomly divided into 2 groups, every group each
5,1 group of feeding Decursin(20mg/kg)(Decursin treated), 1 group of feeding drug solvent(DMSO), after 8 weeks,
It was found that two groups of glutamic-oxalacetic transaminease(AST), alanine aminotransferase(ALT), blood glucose level(Glucose), urea nitrogen(Urea
nitrogen), T-CHOL(total cholesterol), triglycerides(glyceryl ester), apolipoprotein B
(Apolipoprotein B), lipoprotein a (lipoprotein a) etc. do not have significant difference.And low-density lipoprotein(LDL)
And Apolipoprotein A1(ApoA1)There is significant difference, decursinol Radix Angelicae Sinensis ester reduces the LDL and ApoA1 of ApoE knock-out mices(It is shown in Table
1).
1. decursinol Radix Angelicae Sinensis ester of table(Decursin)Influence for ApoE knock-out mice blood fat
Note:P value are P values, and NS is no difference of science of statistics.
2nd, research confirms that decursinol Radix Angelicae Sinensis fat can reduce atherosclerosis animal model ApoE genes and knock out mouse
Atherosclerosis animal model in patch(Fig. 1).
ApoE knock-out mices are Atherosclerosis Model by the induction of high lipid food feeding, are randomly divided into 2 groups, every group each
5,1 group of feeding Decursin, 1 group of feeding placebo(Vehicle), after 8 weeks, the pathological analysis of atherosclerosis is to reality
It tests mouse to be dissected, obtains aorta, accumulation journey of the lipid on whole aorta wall is determined by the method that oil red dyes
Degree, red are atherosclerotic plaque area(Fig. 1).As a result ApoE genes knock out mouse arch of aorta bifurcation it is visible bright
Aobvious atherosclerotic plaque, the lipid in patch dye red by oil red, and positive ratio is up to 30%, same period feeding
Mouse positive ratio is 19% after Decursin8 weeks, the significant decline of atherosclerotic plaque area(P < 0.05)(Figure
1).
3rd, research confirms that decursinol Radix Angelicae Sinensis fat can inhibit the inflammatory reaction of vascular endothelial cell
The risk factor of atherosclerosis can vascular endothelial cell injury, promote the expression of adhesion molecule, make in cycle
Monocyte is adhered to endothelial cell, a series of inflammation, immune response is generated, so as to promote the formation of atherosclerosis and hair
Exhibition.Endothelial dysfunction is the earliest events of hypertension and atherosclerosis.
Tumor necrosis factor a(TNFa)After stimulating endothelial cell, the Decursin stimulating endothelial cells of various concentration are used
And observe the inside Epithelial Cell Adhesion effect of monocyte.It can be seen that(Fig. 2)With the increase of Decursin concentration(25uM、
50uM、100uM), adhesive attraction reduction of the monocyte to endothelial cell.As a result, it has been found that TNFa can conspicuousness promote monokaryon it is thin
Born of the same parents are to endothelial adhesion, and Decursin then inhibits this effect in dosage correlation.Illustrate decursinol Radix Angelicae Sinensis fat from cellular level
It can inhibit the process of vascular atherosclerosis.
4th, influences of the Decursin for the LDL and oxLDL inside Epithelial Cell Adhesions of monocyte induced
Massive epidemiology and clinical research show, the generation of low-density lipoprotein (LDL) and atherosclerosis and coronary heart disease,
Development is closely related with lesion degree.The integrality of endothelial function is of great significance to the maintenance normal physiological status of blood vessel,
Atherosclerosis is exactly using endothelial dysfunction as starting.Endothelial cell expression of adhesion molecules simultaneously occurs viscous with monocyte
Attached is the important step of one of performance that inner skin cell function is damaged and is active and atherosclerosis generation.
Oxidized low-density lipoprotein (oxidized low density lipoprotein, ox-LDL) is acknowledged as having actuating
Pulse atherosclerosis acts on, it can activate vascular endothelial cell and it is made to express various adhesion molecules, cell factor and chemotactic factor (CF)
It is a kind of chronic inflammatory reaction process in interior atherosclerosis etc. Adherence of Monocytes is promoted.Adherence of Monocytes is in blood vessel
Endothelial cell and move into it is subendothelial intake lipid be converted into foam cells be As formed earliest events.Endothelial dysfunction and
Impaired is the initiating link of earliest events.One of atharosclerosis mechanism be ox-LDL it can activate endothelial cell and make it
Various adhesion molecules are generated, promotes endothelial cell and Adherence of Monocytes, promotes the formation of foam cells.
After LDL and oxLDL stimulating endothelial cells, effects of the Decursin for the inside Epithelial Cell Adhesion of monocyte.With
The increase of Decursin concentration(25uM、50uM、100uM), as a result, it has been found that LDL(Fig. 3)Promote monocyte to endothelial cell
The effect of adherency mitigates, oxLDL(Fig. 4)The effect of the inside Epithelial Cell Adhesion of monocyte is promoted to mitigate.Again from cellular level
Illustrate that decursinol Radix Angelicae Sinensis fat can inhibit the process of vascular atherosclerosis.
Conclusion:The present invention is studied with the active ingredient of Radix Angelicae Sinensis-decursinol Radix Angelicae Sinensis ester, is all sent out in ApoE knock-out mices
Now its improvement result for having blood fat.ApoE genes knock out the visible apparent atherosclerotic plaque of aorta of mouse, pass through
After feeding decursinol Radix Angelicae Sinensis ester, atherosclerotic plaque is obviously improved.Simultaneously with the relevant endothelial cell of atherosclerosis
In adhesive attraction, decursinol Radix Angelicae Sinensis ester can inhibit the monokaryon of the inside Epithelial Cell Adhesion of monocyte, LDL and oxLDL inductions thin
The inside Epithelial Cell Adhesion of born of the same parents.The present invention shows decursinol Radix Angelicae Sinensis fat from external, In vivo study(Decursin)Blood fat can be improved
Metabolic disorder, decursinol Radix Angelicae Sinensis fat(Decursin)The hard inflammatory reaction Experiment on therapy artery congee of anti-atherogenic can be passed through
Sample hardens, and prevents and treats atherosclerosis.
To sum up, decursinol Radix Angelicae Sinensis fat can prepare Antiatherosclerosis medicine, and preferably described drug is worked as including decursinol
Return fat 20mg/kg therapeutically effective amounts and pharmaceutically acceptable carrier.Wherein, pharmaceutically acceptable carrier is this field
Conventional carrier, without particular/special requirement.
It is preferred that the drug is oral preparation, such as tablet, hard shell capsules or granule.
Experiment proves that the acceptable effective concentration of decursinol Radix Angelicae Sinensis fat in blood is in 12.5uM-50uM/24h.
Basic principle, main feature and the advantages of the present invention of the present invention has been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent thereof.
Claims (5)
1. decursinol Radix Angelicae Sinensis fat is as the application prepared in Antiatherosclerosis medicine.
2. decursinol Radix Angelicae Sinensis fat according to claim 1 is as the application prepared in Antiatherosclerosis medicine, special
Sign is that the drug includes decursinol Radix Angelicae Sinensis fat 20mg/kg therapeutically effective amounts and pharmaceutically acceptable carrier.
3. decursinol Radix Angelicae Sinensis fat according to claim 1 is as the application prepared in Antiatherosclerosis medicine, special
Sign is that the drug is oral preparation.
4. decursinol Radix Angelicae Sinensis fat according to claim 1 is as the application prepared in Antiatherosclerosis medicine, special
Sign is that the drug is tablet, hard shell capsules or granule.
5. decursinol Radix Angelicae Sinensis fat according to claim 2 is as the application prepared in Antiatherosclerosis medicine, special
Sign is that the acceptable effective concentration of decursinol Radix Angelicae Sinensis fat in blood is in 12.5uM-50uM/24h.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10874092B2 (en) | 2015-06-30 | 2020-12-29 | Regents Of The University Of Minnesota | Humanized skeletal muscle |
US10897880B2 (en) | 2015-06-30 | 2021-01-26 | Regents Of The University Of Minnesota | Humanized heart muscle |
US11673928B2 (en) | 2015-03-03 | 2023-06-13 | Regents Of The University Of Minnesota | Genetically modified pig cells with an inactivated Etv2 gene |
-
2018
- 2018-01-17 CN CN201810046270.4A patent/CN108125943A/en active Pending
Non-Patent Citations (1)
Title |
---|
TAICHI OHSHIRO ET AL.: "Molecular Target of Decursins in the Inhibition of Lipid Droplet Accumulation in Macrophages", 《BIOL. PHARM. BULL.》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11673928B2 (en) | 2015-03-03 | 2023-06-13 | Regents Of The University Of Minnesota | Genetically modified pig cells with an inactivated Etv2 gene |
US10874092B2 (en) | 2015-06-30 | 2020-12-29 | Regents Of The University Of Minnesota | Humanized skeletal muscle |
US10897880B2 (en) | 2015-06-30 | 2021-01-26 | Regents Of The University Of Minnesota | Humanized heart muscle |
US12089574B2 (en) | 2015-06-30 | 2024-09-17 | Regents Of The University Of Minnesota | Humanized skeletal muscle |
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