CN108685885B - Pharmaceutical composition containing schizandrin A and application thereof - Google Patents
Pharmaceutical composition containing schizandrin A and application thereof Download PDFInfo
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- CN108685885B CN108685885B CN201810749178.4A CN201810749178A CN108685885B CN 108685885 B CN108685885 B CN 108685885B CN 201810749178 A CN201810749178 A CN 201810749178A CN 108685885 B CN108685885 B CN 108685885B
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- platelet aggregation
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- schisandrin
- platelet
- adp
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- JEJFTTRHGBKKEI-OKILXGFUSA-N deoxyschizandrin Chemical compound C1[C@H](C)[C@H](C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC JEJFTTRHGBKKEI-OKILXGFUSA-N 0.000 title claims abstract description 37
- JEJFTTRHGBKKEI-UHFFFAOYSA-N deoxyschizandrin Natural products C1C(C)C(C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC JEJFTTRHGBKKEI-UHFFFAOYSA-N 0.000 title claims abstract description 23
- FYSHYFPJBONYCQ-UHFFFAOYSA-N schisanhenol Natural products C1C(C)C(C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2O FYSHYFPJBONYCQ-UHFFFAOYSA-N 0.000 title description 8
- 239000008194 pharmaceutical composition Substances 0.000 title description 5
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 26
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 239000000178 monomer Substances 0.000 abstract description 4
- 239000003146 anticoagulant agent Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000000702 anti-platelet effect Effects 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 230000002776 aggregation Effects 0.000 description 6
- 238000004220 aggregation Methods 0.000 description 6
- 240000006079 Schisandra chinensis Species 0.000 description 4
- 235000008422 Schisandra chinensis Nutrition 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 241000283977 Oryctolagus Species 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 108091008803 APLNR Proteins 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000000001 effect on platelet aggregation Effects 0.000 description 2
- 210000003989 endothelium vascular Anatomy 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 230000010118 platelet activation Effects 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- YEFOAORQXAOVJQ-RZFZLAGVSA-N schisandrol a Chemical compound C1[C@H](C)[C@@](C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-RZFZLAGVSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 241000209524 Araceae Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 241000218377 Magnoliaceae Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100037600 P2Y purinoceptor 1 Human genes 0.000 description 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241000758724 Schisandraceae Species 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 108010015046 cell aggregation factors Proteins 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229930013686 lignan Natural products 0.000 description 1
- 150000005692 lignans Chemical class 0.000 description 1
- 235000009408 lignans Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 229930193195 schizandrin Natural products 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
- 239000001509 sodium citrate Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- YEFOAORQXAOVJQ-UHFFFAOYSA-N wuweizischun A Natural products C1C(C)C(C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
A Chinese medicinal monomer, WUWEIZI A, has effects in inhibiting ADP-induced platelet aggregation. The basic research of schisandrin A in thrombosis is used as a novel anti-platelet aggregation drug.
Description
Technical Field
The application relates to a pharmaceutical composition containing Chinese medicinal monomer schizandrin A and application thereof, which has the effect of inhibiting ADP-induced platelet aggregation.
Background
Fructus Schisandrae is a dried mature fruit of Schisandra chinensis of Schisandraceae of Magnoliaceae of Araceae of perennial fallen leaves, and is called fructus Schisandrae because of its perfect sweet, sour, pungent, bitter and salty properties. Lignans are used as the most main active ingredients in schisandra chinensis, and comprise schisandra chinensis A, schisandra chinensis B and the like. The pharmacological action of schisandrin A has been widely studied, and it relates to various aspects of digestive system, cardiovascular system, central nervous system, reproductive system and urinary system. And for its novel function of anti-platelet aggregation, it has not been found so far. Platelet aggregation is an important link in the formation of thrombosis and thrombotic disorders. Platelets are one of the blood cells, but are not in nature cells, and are biologically active casts that are lysed and casted from the cytoplasm of bone marrow mature megakaryocytes. Platelets have no cell nuclei, are small in size, have a lifetime of approximately 7 to 14 days, and are in the shape of a double-sided slightly convex disk. Platelets have been considered nonfunctional cellular debris in the blood for a long period of time. Numerous studies have later found that platelets are activated by certain stimuli and undergo various changes: deformation, adhesion, aggregation and release reactions. These changes in platelets can occur sequentially, in different combinations, or alone, and are involved in vascular repair and physiological hemostasis in vivo and are closely related to diseases such as atherosclerosis, cerebral thrombosis, tumor metastasis, inflammatory response, and the like. Platelet activation and damaged vascular endothelium is involved in atheromatous plaque formation and leads to unstable atheromatous plaque, platelet activation is also an important cause of reperfusion injury. When the body is in a normal condition, the platelets are in a resting state, so that activation is not easy to occur; when the vascular endothelium in the body is damaged or inflamed, the platelets are activated and aggregated to start the coagulation process. Platelet excessive activation can form thrombus. Then, it is important to search for drugs that inhibit platelet aggregation and find corresponding action targets for thromboembolic diseases and related diseases.
Disclosure of Invention
The inventor of the present application discovers a traditional Chinese medicine, namely schisandrin A. It belongs to a peptide for inhibiting platelet aggregation and thrombosis, and is expected to inhibit platelet aggregation promotion of ADP. Wherein ADP inhibits the activity of ATPase by activating ADP receptor on platelet membrane, so that platelet is exposed out of phospholipid surface to cause platelet aggregation. ADP is a natural component in the coagulation system of the body and has a particularly important role in endogenous coagulation.
The application provides a pharmaceutical composition for treating hemorrhagic diseases, which is characterized in that: the pharmaceutical composition comprises schizandrin A.
The application also provides an application of the schisandrin A in preparing a medicament, wherein the medicament can treat diseases caused by platelet aggregation or thrombosis by acting on an APJ receptor; or to prevent platelet aggregation or to prevent thrombosis.
The application discovers the physiological function of schisandrin A, which has no effect on platelet aggregation.
The application discovers the physiological function of schisandrin A and can inhibit ADP-induced rabbit platelet aggregation.
The application relates to schisandrin A; relates to a new function research for inhibiting platelet aggregation of New Zealand rabbits. Schisandrin A was found to inhibit ADP-induced platelet aggregation in New Zealand rabbits. The application also discloses a basic research of schisandrin A in thrombosis as a novel antithrombotic drug.
In the in vitro test, the concentration gradient is 0.001mol/L,0.01mol/L,0.1mol/L, 1.0. Mu. Mol/L, preferably 1.0. Mu. Mol/L.
The beneficial technical effects of the application
1. The Chinese medicine monomer schisandrin A can treat diseases caused by platelet aggregation or thrombosis by acting on APJ receptors; or to prevent platelet aggregation or thrombosis, and thus can be used for the preparation of a medicament.
Description of the drawings:
FIG. 1 shows that schisandrin A alone has no effect on platelet aggregation
(Mean+SEM,n=4,ns vs control;ns vs DMSO group)。
FIG. 2 shows that schizandrin A inhibits ADP-induced platelet aggregation
(ADP at 5μM together with deoxyschizandrin for 5min,mean+SEM,n=5,ns vs control;***p<0.001vs DMSO group;ns vs ADP;###p<0.001vs ADP+DMSO group)。
Detailed Description
Example 1 determination of the Effect of Schisandrin A on platelet aggregation
The platelet aggregation factor analyzer (LG-PABER-I type, beijing Shidi scientific instrument Co.) was used to measure the platelet aggregation rate. The instrument adopts a photoelectric nephelometry to test platelet aggregation: platelet rich plasma (platelet rich plasma, PRP) was used as a substrate for measurement using platelet poor plasma (platelet poor plasma, PPP). Under stirring of magnetic beads, an inducer is added into PRP to cause aggregation of platelets, and the transmittance of PRP is increased or turbidity is reduced. The change of the turbidity of the light is converted into the change of the electric signal, so that the aggregation rate of the platelets is calculated.
Aggregation ratio = (measured voltage value-PPP photovoltaic voltage value)/(PRP photovoltaic voltage value-PPP photovoltaic voltage value) ×100%.
1. Determination of the Effect of different concentrations (0.001,0.01,0.1,1. Mu. Mol/L) of Schisandrin A on platelet aggregation
Collecting blood of middle artery of New Zealand rabbit ear, anticoagulating with sodium citrate, centrifuging at 800r/min for 10min, collecting supernatant to obtain PRP, centrifuging at 3000r/min for 10min, and collecting supernatant to obtain PPP. 300 μl of PPP is precisely added into the test cup, the test channel is placed, and the substrate is measured by PPP bond and then taken out. In another test cup, 300. Mu.l of PRP was precisely added, and after 1min of pre-incubation at 37℃1 test bead was added to the test cup using a bead adder, and after starting the test, the maximum aggregation rate of platelets was recorded by adding different concentrations (0.001,0.01,0.1,1. Mu. Mol/L) of schizandrin for 5min each in three seconds (see FIG. 1).
2. Determination of different concentrations (1, 0.1.01, 0.001. Mu. Mol/L) of schizandrin A inhibiting ADP-induced rabbit platelet aggregation
PPP and PRP were collected as above, and schizandrin A was added to PRP and incubated for 5 minutes, then placed in the test zone where the baseline had been adjusted, test beads were added, and after the test was started, rapid addition or ADP test was performed for five minutes, the maximum aggregation rate of platelets was recorded, and the test results were observed to detect the inhibitory effect of schizandrin A on platelet aggregation (see FIG. 2).
In conclusion, the traditional Chinese medicine monomer has ideal effects of resisting platelet aggregation and thrombosis, and can be used for preparing related medicines.
Claims (1)
1. The application of schisandrin A in preparing the medicine for treating thrombotic diseases is characterized by being used for treating thrombotic diseases caused by platelet aggregation.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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CN201710569204 | 2017-07-11 | ||
CN2017105692040 | 2017-07-11 |
Publications (2)
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CN108685885A CN108685885A (en) | 2018-10-23 |
CN108685885B true CN108685885B (en) | 2023-11-17 |
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CN201810749178.4A Active CN108685885B (en) | 2017-07-11 | 2018-07-10 | Pharmaceutical composition containing schizandrin A and application thereof |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1970001A (en) * | 2005-11-22 | 2007-05-30 | 黄振华 | Pharmaceutical composition comprising kurarinone, magnolia vine fruit and ginseng for treating hepatitis |
CN102188486A (en) * | 2011-05-10 | 2011-09-21 | 王智森 | Pharmaceutical composition for preventing and treating fatty liver and preparation method thereof |
CN105456481A (en) * | 2015-12-07 | 2016-04-06 | 中山大学 | Application of fructus schisandrae sphenantherae extract in preparation of liver regeneration medicine |
-
2018
- 2018-07-10 CN CN201810749178.4A patent/CN108685885B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1970001A (en) * | 2005-11-22 | 2007-05-30 | 黄振华 | Pharmaceutical composition comprising kurarinone, magnolia vine fruit and ginseng for treating hepatitis |
CN102188486A (en) * | 2011-05-10 | 2011-09-21 | 王智森 | Pharmaceutical composition for preventing and treating fatty liver and preparation method thereof |
CN105456481A (en) * | 2015-12-07 | 2016-04-06 | 中山大学 | Application of fructus schisandrae sphenantherae extract in preparation of liver regeneration medicine |
Non-Patent Citations (2)
Title |
---|
罗旭灵.中国优秀硕士学位论文全文数据库医药卫生科技辑.中国优秀硕士学位论文全文数据库医药卫生科技辑.2019,(3),1-64. * |
陈恩瑜等.RP-HPLC 法同时测定补肾益脑胶囊中五味子醇甲、五味子甲素和五味子乙素的含量.海峡药学.2012,24(12),第49-52页. * |
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