CN109821008A - Medical composition and its use containing ELABELA-32 - Google Patents
Medical composition and its use containing ELABELA-32 Download PDFInfo
- Publication number
- CN109821008A CN109821008A CN201810749148.3A CN201810749148A CN109821008A CN 109821008 A CN109821008 A CN 109821008A CN 201810749148 A CN201810749148 A CN 201810749148A CN 109821008 A CN109821008 A CN 109821008A
- Authority
- CN
- China
- Prior art keywords
- elabela
- platelet aggregation
- platelet
- thrombosis
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 46
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 31
- 208000031169 hemorrhagic disease Diseases 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 210000001772 blood platelet Anatomy 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 230000002776 aggregation Effects 0.000 claims description 8
- 238000004220 aggregation Methods 0.000 claims description 8
- 239000003146 anticoagulant agent Substances 0.000 claims description 7
- 230000002785 anti-thrombosis Effects 0.000 claims description 5
- 108091008803 APLNR Proteins 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000015556 catabolic process Effects 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 abstract description 20
- 102000008186 Collagen Human genes 0.000 abstract description 16
- 108010035532 Collagen Proteins 0.000 abstract description 16
- 229920001436 collagen Polymers 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 11
- 239000003446 ligand Substances 0.000 abstract description 11
- 229940114079 arachidonic acid Drugs 0.000 abstract description 10
- 235000021342 arachidonic acid Nutrition 0.000 abstract description 10
- 230000006698 induction Effects 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 18
- 102100021667 Apelin receptor early endogenous ligand Human genes 0.000 description 14
- 101000896271 Homo sapiens Apelin receptor early endogenous ligand Proteins 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 230000002195 synergetic effect Effects 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 201000010099 disease Diseases 0.000 description 5
- 102000018746 Apelin Human genes 0.000 description 4
- 108010052412 Apelin Proteins 0.000 description 4
- 102100029057 Coagulation factor XIII A chain Human genes 0.000 description 4
- 101000918352 Homo sapiens Coagulation factor XIII A chain Proteins 0.000 description 4
- BWVPHIKGXQBZPV-QKFDDRBGSA-N apelin Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCSC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)CCC1 BWVPHIKGXQBZPV-QKFDDRBGSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 241000283977 Oryctolagus Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000005622 photoelectricity Effects 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 101800001144 Arg-vasopressin Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 102000007466 Purinergic P2 Receptors Human genes 0.000 description 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 208000014759 blood platelet disease Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000010247 heart contraction Effects 0.000 description 1
- 230000009067 heart development Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000001501 megacaryocyte Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A kind of endogenic ligand ELABELA-32, which promotees platelet aggregation and thrombosis effect by effect apj receptor, and can cooperate with ADP, collagen, the rush platelet aggregation of arachidonic acid (AA) induction and thrombosis effect.ELABELA-32 hemorrhagic disease basic research using the drug as a kind of novel rush platelet aggregation and thrombosis.
Description
Technical field
The present invention relates to the medical composition and its uses containing ELABELA-32.ELABELA-32 itself can pass through APJ
Receptor promotees platelet aggregation, and also has collaboration ADP, collagen, arachidonic rush platelet aggregation and outer thrombus shape
At effect.
Background technique
APJ is that the G-protein for the homology that a kind of and I receptor of angiotensin receptor of discovery in 1993 has 35% is coupled
Receptor has found its first endogenic ligand apelin for 1998.Apelin/APJ system is widely expressed in human body group
Knit and organ, can produce after Apelin activation apj receptor different physiological effects include: adjust vessel retraction and expansion plus
Heart tonifying myotility, adjusts energetic supersession and isohydria etc. at angiogenesis.2013, Chng etc. had found the another of apj receptor
One ligand-ELABELA (54aa) and three different ELABELA small fragments: ELABELA-32 (this can be hydrolyzed to
32 amino acid be it is highly conserved, especially last 13 are almost constant in all vertebrates.This sequence with
Apelin has 25% similitude), ELABELA-22 and ELABELA-11.This patent mainly uses ELABELA-32.ELABELA
A hot topic will be become, how it works, and can participate in what disease and how it keeps homeostasis.
ELABELA be at first found in zebra fish and find its internal differentiation of germinal layers and the development of later cardiac shape have very
Big influence.It is found in the heart of adult rodent afterwards, ELABELA also has increase cardiac contractility to play positive inotropic
Effect.ELABELA is very important embryonic development, ELABELA height be expressed in undifferentiated human embryo stem cell and
Human embryo stem cell self-renewing can be maintained by PI3K/AKT access, but human embryo stem cell does not express APJ, so speculating
ELABELA may act on another unknown receptor.Afterwards studies have reported that ELABELA can also be expressed in mammals simultaneously
It expresses and adjusts internal fluid balance by increasing the intake of diuresis and water in Adult kidney.In the ventricles of the brain of adult mouse brain
ELABELA is injected, the arginine vasopressin and rush kidney that can be activated in nucleus paraventricularis and (adjust food intake dose region in hypothalamus)
Upper gland cortin release, makes appetite stimulator.
ELABELA has a certain effect to heart development, heart contraction, Humoral immunity and nervous system, but ELABELA with
There has been no any reports for platelet function and blood coagulation dependent interaction.This patent mainly inquired into ELABELA and platelet aggregation and
The functional study of ex vivo thrombosis.It was found that ELABELA can promote platelet aggregation and external thrombus shape by apj receptor
At.Blood platelet is the biologically active cast to fall off from megacaryocyte, and main physiological function is exactly only in vivo
Blood.In vivo, blood platelet can quickly find impaired endothelium in swiftly flowing blood, and adhere to, and assemble and secrete one
Little particle slightly participates in intracorporal vascular repair and physiological haemostasis.Bleeding is a kind of common clinical manifestation, trauma surgery
And some hemorrhagic diseases usually cause to bleed profusely, or even threaten the life of patient.Blood platelet disorders are hemorrhagic diseases
The pathology cause of disease one kind, platelet aggregation obstacle can cause bleeding.So exploring the medicine for promoting platelet aggregation
Object, and find corresponding action target spot for hemorrhagic disease and its related disease and be of great significance.And inhibit ELABELA
New treatment method can be provided for antithrombus formation and its related disease.
Summary of the invention
The inventor of the present application discovered that the purposes of endogenic ligand ELABELA-32.ELABELA-32 can be by acting on APJ
Receptor promotes platelet aggregation and thrombosis peptide, and wishes to collaboration ADP, collagen, arachidonic rush platelet aggregation
It is acted on thrombosis.Wherein, ADP inhibits the activity of ATP enzyme, keeps blood platelet sudden and violent by the adp receptor on activation platelet membrane
Expose a variety of effects such as phospholipid surface and causes platelet aggregation.Collagen accounted in human body protein total amount 30 percent with
On, it is the most abundant protein of people's in-vivo content, is indispensable important composition ingredient in vascular wall.Endothelial cell by
After damage, collagen activation blood platelet makes it be adhered to wound, and ADP isoreactivity substance is promoted further to discharge, and makes platelet aggregation
Collection.Arachidonic acid is a kind of essential fatty acid of human body and can promote to discharge thromboxane A2, has and promotes platelet aggregation
With the effect of thrombosis.ADP, collagen, arachidonic acid are all the natural components in body blood coagulation system, for endogenous
Blood coagulation is even more important.
The present invention provides a kind of pharmaceutical composition for treating hemorrhagic disease, it includes endogenic ligand ELABELA-
32。
The present invention also provides the purposes that above-mentioned endogenic ligand ELABELA-32 is used to prepare drug, and wherein the drug is used for
Treat the hemorrhagic disease as caused by platelet aggregation disorder；Or the chemoprophylaxis platelet aggregation or antithrombotic.
Present invention finds the physiologic functions of above-mentioned endogenic ligand ELABELA-32, can be by acting on apj receptor
To treat the hemorrhagic disease as caused by platelet aggregation disorder；Or it is used to prevent platelet aggregation or pre- preventing thrombosis shape
At.
Present invention finds the physiologic functions of above-mentioned endogenic ligand ELABELA-32, can cooperate with ADP, collagen, flower
The rush platelet aggregation and thrombosis of raw tetraenoic acid induction act on to treat the bleeding as caused by platelet aggregation disorder
Property disease；Or this its be used to prevent platelet aggregation or antithrombotic.
Present invention finds the physiologic functions of above-mentioned endogenic ligand ELABELA-32, can pass through the ELABELA-32 that degrades
Or its target spot APJ is blocked to inhibit aggregation and the antithrombus formation of blood platelet.
In vitro in test, the gradient of concentration is 0.001mol/L, 0.01mol/L, 0.1mol/L, 1.0 μm of ol/L, preferably
For 1.0 μm of ol/L.
Advantageous effects of the invention
1, endogenic ligand ELABELA-32 of the invention has the function of preferably promoting platelet aggregation, therefore, can use
In preparing drug.
2, the rush platelet aggregation of endogenic ligand ELABELA-32 of the invention to ADP, collagen and arachidonic acid-induction
Collection has synergistic effect, therefore can be used for treating the hemorrhagic disease as caused by platelet aggregation disorder；Or this its be used to prevent
Platelet aggregation or antithrombotic.
Detailed description of the invention:
Fig. 1 is that ELABELA-32 promotes platelet aggregation；
Fig. 2 is the rush the Platelet Aggregation in Rabbit that F13A blocks ELABELA-32；
Fig. 3 is that ELABELA-32 has synergistic effect to the rush rabbit platelet aggregation that ADP is induced；
Fig. 4 is that ELABELA-32 has synergistic effect effect to collagen-induced rush rabbit platelet aggregation；
Fig. 5 is that ELABELA-32 has synergistic effect to the rush rabbit platelet aggregation of arachidonic acid-induction；
Fig. 6 is that ELABELA-32 promotes thrombosis；
Fig. 7 is that ELABELA-32 has synergistic effect to the rush ex vivo thrombosis that ADP is induced；
Fig. 8 is that ELABELA-32 has synergistic effect to collagen-induced rush ex vivo thrombosis；
Fig. 9 is that ELABELA-32 has synergistic effect to the rush ex vivo thrombosis of arachidonic acid-induction.
Specific embodiment
Preparation example 1
Its function is detected, shown in following examples.Implement below for illustrating the present invention, but should not be used to the limitation present invention
Range.
Embodiment 1 measures influence of the ELABELA-32 to platelet aggregation
It is small with platelet aggregation coagulation factor analyzer (LG-PABER-I type, Beijing Steellex Scientific Instrument Company) measurement blood
Plate aggregation rate.This instrument tests platelet aggregation using photoelectric turbidimetry: using platelet poor plasma (platelet poor
Plasma, PPP) it is used as substrate, it is measured using Platelet-rich plasm (platelet rich plasma, PRP).In magnetic
Under the stirring of power pearl, inducer is added in PRP, blood platelet is assembled, and the light transmittance of PRP increases or turbidity reduction.By light
The variation of turbidity is converted to the variation of electric signal, to calculate the aggregation rate of blood platelet.
Aggregation rate=(measurement voltage value-PPP photoelectricity voltage value)/(PRP photoelectricity voltage value-PPP photoelectricity voltage value) *
100%
1. measuring influence of the ELABELA-32 of various concentration (0.001,0.01,0.1,1 μm of ol/L) to platelet aggregation
Arterial blood drawing in new zealand rabbit ear, it is anticoagulant with sodium citrate, it is then centrifuged for, is first centrifuged 10min with 800r/min, takes
Supernatant obtains PRP, then is centrifuged 10min with 3000r/min, and supernatant is taken to obtain PPP.Accurately it is added 300 μ l's in test cup
PPP is put into TCH test channel, presses after PPP key carries out substrate measurement and takes out.In another test cup, the accurate PRP that 300 μ l are added,
At 37 DEG C after pre-temperature 1min, using adding pearl device that 1 test pearl is added in the test cup, after starting test, divide in three seconds
Not Jia Ru the ELABELA-32 of various concentration (0.001,0.01,0.1,1 μm of ol/L) test 5min, the maximum for recording blood platelet is poly-
Collection rate (referring to Fig. 1).
ELABELA-32 is blocked to promote the Platelet Aggregation in Rabbit 2. measuring F13A (apj receptor blocking agent)
PPP is acquired, PRP is same as above, and F13A is added in PRP and is incubated for 5min, is placed into the test section for having mixed up baseline,
Test pearl is added, after starting test, ELABELA-32 is added in three seconds and tests 5min, records the maximum aggregation rate of blood platelet,
It observes test result detection F13A and the Platelet Aggregation in Rabbit is promoted to ELABELA-32.Judge that apj receptor mediates with this
The rush platelet aggregation (referring to fig. 2) of ELABELA-32.
3. measuring various concentration ELABELA-32 to the association of ADP, arachidonic acid and collagen-induced rabbit platelet aggregation
Same-action
PPP is acquired, PRP is same as above, and ELABELA-32 is added in PRP and is incubated for 5min, places into the survey for having mixed up baseline
It tries in area, test pearl is added, after starting test, ADP is added in three seconds, arachidonic acid or collagen test 5min, records blood
The maximum aggregation rate of platelet, ELABELA-32 is to ADP for observation test result detection, arachidonic acid, and collagen-induced rabbit blood is small
The synergistic effect of plate aggregation (referring to Fig. 3, Fig. 4, Fig. 5).
Embodiment 2 measures influence of the ELABELA-32 to ex vivo thrombosis
Thrombosis model is established with thrombometer (LMK-12 type, Zhengzhou Ming Ju scientific & technical corporation), this instrument is used
Chandler method: blood is injected in external rotating ring, and blood flow state is in analogue body to form thrombus.
1. measuring the shadow of the ELABELA-32 to ex vivo thrombosis of various concentration (0.001,0.01,0.1,1 μm of ol/L)
It rings
Arterial blood drawing (is not added any anti-coagulants, using straight extracting vein blood 1ml, and pays attention to inject in new zealand rabbit ear
Bubble removal in device, after being handled with various concentration ELABELA-32 (0.001,0.01,0.1,1 μm of ol/L), blood sample dress fills annulus,
Slowly by 1m1 blood sample along the tube wall injection pipe of plastic hoop one end, connect into annulus at any time, be satisfied in corresponding turntable.It is put into
Middle revolving speed is 20 ± 2rpm, and at 37 DEG C, after recycling 10min, removal of thromboses measures and records the weight in wet base and length of thrombus.
The above-mentioned thrombus for having claimed weight in wet base is put into drying and processing in 60 DEG C ± 1 DEG C of baking oven, after 30min, again by the thrombus of drying
Weighing records thrombus dry weight (referring to Fig. 6).
2. measuring various concentration ELABELA-32 to ADP, arachidonic acid and collagen-induced rabbit ex vivo thrombosis
Synergistic effect
Equally thrombosis model is constructed with chandler method.By ELABELA-32 and ADP, arachidonic acid or collagen one
It rises according to the test method in 1 in the new zealand rabbit blood that 1ml is added, removal of thromboses disease records experimental result.And it observes
ELABELA-32 is to ADP, the synergistic effect of arachidonic acid and collagen-induced rabbit thrombosis (referring to Fig. 7, Fig. 8, Fig. 9).
In conclusion endogenic ligand of the invention has effects that preferably to promote platelet aggregation and thrombosis, energy
It is enough in and prepares relevant drug.
Claims (5)
1. a kind of pharmaceutical composition for treating hemorrhagic disease, it is characterised in that: the pharmaceutical composition includes ELABELA-32.
2.ELABELA-32 is used to prepare the purposes of drug, and wherein the drug is for treating as caused by platelet aggregation disorder
Hemorrhagic disease；Or the chemoprophylaxis platelet aggregation or antithrombotic.
3. ELABELA-32 according to claim 2 is used to prepare the purposes of drug, ELABELA-32 can be by acting on APJ
Receptor treats the hemorrhagic disease as caused by platelet aggregation disorder；Or it is used to prevent platelet aggregation or pre- preventing thrombosis
It is formed.
4. ELABELA-32 according to claim 2 is used to prepare the purposes of drug, ELABELA-32 can cooperate with ADP, glue
Original, the rush platelet aggregation and thrombosis of arachidonic acid-induction act on to treat as caused by platelet aggregation disorder
Hemorrhagic disease；Or this its be used to prevent platelet aggregation or antithrombotic.
5.ELABELA-32 is used to prepare the purposes of drug, by degradation ELABELA-32 or can block its target spot APJ and inhibits
The aggregation of blood platelet and antithrombus formation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710562881 | 2017-07-11 | ||
| CN201710562881X | 2017-07-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109821008A true CN109821008A (en) | 2019-05-31 |
Family
ID=66859480
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810749148.3A Pending CN109821008A (en) | 2017-07-11 | 2018-07-10 | Medical composition and its use containing ELABELA-32 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109821008A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102241735A (en) * | 2011-06-23 | 2011-11-16 | 陕西麦科奥特科技有限公司 | Polypeptide used for prevention and treatment of acute coronary syndrome and anticoagulation antithrombotic therapy and application thereof |
| CN102617680A (en) * | 2011-02-01 | 2012-08-01 | 复旦大学 | Bi-functional antiplatelet aggregation medicine and application thereof |
-
2018
- 2018-07-10 CN CN201810749148.3A patent/CN109821008A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102617680A (en) * | 2011-02-01 | 2012-08-01 | 复旦大学 | Bi-functional antiplatelet aggregation medicine and application thereof |
| CN102241735A (en) * | 2011-06-23 | 2011-11-16 | 陕西麦科奥特科技有限公司 | Polypeptide used for prevention and treatment of acute coronary syndrome and anticoagulation antithrombotic therapy and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 刘梅青: "Pannexin1-P2X7及自噬途径介导apelin亚型和ELABELA对兔血小板聚集的影响" * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Choi et al. | The new era of the lymphatic system: no longer secondary to the blood vascular system | |
| Simonetto et al. | Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces | |
| Zubkova et al. | Regulation of adipose tissue stem cells angiogenic potential by tumor necrosis factor‐alpha | |
| CN105339007A (en) | Treatment of peripheral vascular disease using protein solutions | |
| Chen et al. | Paeonol Inhibits Proliferation of Vascular Smooth Muscle Cells Stimulated by High Glucose via Ras‐Raf‐ERK1/2 Signaling Pathway in Coculture Model | |
| CN1954825B (en) | Supermicro Tongxinluo Chinese herbal composite and its new usage | |
| CN105338990A (en) | Methods and non-immunogenic compositions for treating inflammatory disorders | |
| CN105358161A (en) | Treatment of pain using protein solutions | |
| CN105358162A (en) | Treatment of collagen defects using protein solutions | |
| Wan et al. | Galectin-3 enhances proliferation and angiogenesis of endothelial cells differentiated from bone marrow mesenchymal stem cells | |
| KR101049505B1 (en) | Blood Vessel-related Disease Therapeutic Composition Using Peptides as an Active Ingredient | |
| Lv et al. | The chinese herbal decoction danggui buxue tang inhibits angiogenesis in a rat model of liver fibrosis | |
| Guo et al. | Effects of total saponins from Rhizoma Dioscoreae Nipponicae on expression of vascular endothelial growth factor and angiopoietin-2 and Tie-2 receptors in the synovium of rats with rheumatoid arthritis | |
| Li et al. | Targeting TFE3 protects against lysosomal malfunction-induced pyroptosis in random skin flaps via ROS elimination | |
| Zhang et al. | Tetramethylpyrazine protects endothelial injury and antithrombosis via antioxidant and antiapoptosis in HUVECs and zebrafish | |
| Lu et al. | Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex | |
| CN109821008A (en) | Medical composition and its use containing ELABELA-32 | |
| Zhao et al. | Studies on single-cell adhesion probability between lymphocytes and endothelial cells with micropipette technique | |
| Lu et al. | The proresolving lipid mediator Maresin1 alleviates experimental pancreatitis via switching macrophage polarization | |
| Laurens | Development of a new extraction method for platelet-rich plasma and partial purification of platelet-derived growth factor and transforming growth factor beta | |
| Chen et al. | The mechanistic target of rapamycin complex 1 critically regulates the function of mononuclear phagocytes and promotes cardiac remodeling in acute ischemia | |
| CN105396136B (en) | CCN1（Cyr61）Application in treatment skin injury and atrophoderma relevant disease | |
| CN109395057A (en) | Medical composition and its use containing Apelin-12 | |
| CN108578464B (en) | Application of caulis spatholobi extract in preparation of antitumor drugs | |
| CN108703971B (en) | Application of anti-HIV (human immunodeficiency virus) medicament, namely, cobicistat, in preparation of antithrombotic medicament |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190531 |
|
| RJ01 | Rejection of invention patent application after publication |