CN108685885B - Pharmaceutical composition containing schizandrin A and application thereof - Google Patents

Pharmaceutical composition containing schizandrin A and application thereof Download PDF

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Publication number
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
application
schisandrin
platelet
adp
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CN108685885A (en
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陈临溪
陆丽群
罗旭灵
李瑶
李兰芳
谢凤
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University of South China
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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
    • A61K31/075Ethers or acetals
    • A61K31/085Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • 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

Pharmaceutical composition containing schizandrin A and application thereof
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.
CN201810749178.4A 2017-07-11 2018-07-10 Pharmaceutical composition containing schizandrin A and application thereof Active CN108685885B (en)

Applications Claiming Priority (2)

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CN201710569204 2017-07-11
CN2017105692040 2017-07-11

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CN108685885B true CN108685885B (en) 2023-11-17

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Citations (3)

* Cited by examiner, † Cited by third party
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

Patent Citations (3)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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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