CN108125943A - Application of decursinol angelate in preparation of anti-atherosclerosis medicine - Google Patents

Application of decursinol angelate in preparation of anti-atherosclerosis medicine Download PDF

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Publication number
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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China
Prior art keywords
decursinol
radix angelicae
angelicae sinensis
decursin
atherosclerosis
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CN201810046270.4A
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杨莹
杨克
周太成
李奕平
陶文玉
吴丽萍
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YUNNAN SECOND PEOPLE'S HOSPITAL
Ruinjin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Co Ltd
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YUNNAN SECOND PEOPLE'S HOSPITAL
Ruinjin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Co Ltd
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Publication of CN108125943A publication Critical patent/CN108125943A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/222Esters, 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

Decursinol Radix Angelicae Sinensis fat is as the application for preparing Antiatherosclerosis medicine
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.
CN201810046270.4A 2018-01-17 2018-01-17 Application of decursinol angelate in preparation of anti-atherosclerosis medicine Pending CN108125943A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TAICHI OHSHIRO ET AL.: "Molecular Target of Decursins in the Inhibition of Lipid Droplet Accumulation in Macrophages", 《BIOL. PHARM. BULL.》 *

Cited By (4)

* Cited by examiner, † Cited by third party
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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Application publication date: 20180608

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