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Chenodeoxycholic acid and application thereof

A kind of use, technology of compound, application field in preventing and treating arterial thrombosis disease

Inactive Publication Date: 2015-07-01
SHANGHAIMED
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of chenodeoxycholic acid in antithrombotics has not been reported

Method used

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  • Chenodeoxycholic acid and application thereof
  • Chenodeoxycholic acid and application thereof
  • Chenodeoxycholic acid and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Example 1. Inhibitory effect of chenodeoxycholic acid on ADP-induced human platelet aggregation

[0084] The purpose of this example is to prove that chenodeoxycholic acid can inhibit ADP-induced human platelet aggregation.

[0085] In this example, the platelets were prepared as follows: platelets were obtained from healthy volunteers who signed informed consent, and the volunteers did not take any antiplatelet drugs such as aspirin and clopidogrel within 20 days before blood collection. Anticoagulant ACD (85mmol L -1 Sodium citrate, 71.38mmol L -1 Citric acid, and 27.78mmol L -1 glucose). Centrifuge at 300xg for 20 minutes to obtain platelet-rich plasma, take the upper layer of platelet-rich plasma and centrifuge at 900xg for 10 minutes to obtain platelets, and finally resuspend with Tyrode's buffer (138mmol L -1 Sodium chloride (NaCl), 2.7mmol L -1 Potassium chloride (KCl), 2 mmol L -1 Magnesium Chloride (MgCl 2 ), 0.42 mmol L -1 Sodium dihydrogen phosphate (...

Embodiment 2

[0090] Example 2. Inhibitory effect of 100 μM chenodeoxycholic acid on human platelet aggregation induced by other various agonists

[0091] The purpose of this example is to prove that chenodeoxycholic acid can inhibit the aggregation of human platelets induced by thrombin and collagen.

[0092] In this example, the preparation of platelets and the aggregation induction and measurement methods of platelets are the same as those in Example 1. The results are shown in Table 2. Chenodeoxycholic acid inhibits thrombin (Chrono-log Company, Havertown, PA) (0.1 U / mL) and collagen (Chrono-log Company, Havertown, PA) (1 μg / mL) at 100 μM Induced aggregation of human platelets.

[0093] Table 2: Chenodeoxycholic acid inhibits thrombin- and collagen-induced aggregation of human platelets.

[0094] Chenodeoxycholic acid concentration (μM)

Embodiment 3

[0095] Example 3. Inhibitory effect of chenodeoxycholic acid on platelet spreading.

[0096] The purpose of this example is to demonstrate that chenodeoxycholic acid can inhibit platelet spreading.

[0097] In this embodiment, the preparation of platelets is the same as in Example 1, and the experimental process of platelet spreading is as follows:

[0098] 1) Coating of coverslips or culture plates: Coat coverslips or disposable culture plates with 20 μg / mL fibrinogen (fibrinogen, Chrono-log Company, Havertown, PA) (dissolved in PBS), 4°C Overnight, 2% bovine serum albumin blocked non-specific binding sites at 37°C for 1 hour, and washed once with PBS.

[0099] 2) Adjust the concentration of platelets in the control group or chenodeoxycholic acid treatment group to 1.8×10 with HEPES-Tyrode buffer 6 / 500 μL, inoculated on the fibrinogen-coated coverslips in a 24-well plate, 500 μL per well, and incubated at 37°C for 2 hours.

[0100] 3) Take out the above coverslip, wash once...

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Abstract

The invention relates to chenodeoxycholic acid and application thereof. Specifically, the invention provides application of a compound as shown in a formula (I) in preparation of drugs used for resisting platelet aggregation and thrombogenesis, for preventing diseases related to activation of blood platelet disorders and for treating diseases related to activation of blood platelet disorders, wherein the formula (I) is described in the specification. The chenodeoxycholic acid disclosed in the invention is capable of resisting aggregation and spreading of platelets and can be used as a novel anti-platelet aggregation and antithrombus drug in treatment of diseases related to activation of blood platelet disorders, wherein the diseases includes but are limited to thrombotic diseases, viral diseases with a hypercoagulable state, tumorous diseases, coronary heart disease, apoplexia, hypertension, leukemia, disseminated intravascular coagulation (DIC), etc.

Description

technical field [0001] The invention belongs to the technical field of medicines, in particular to the new application of chenodeoxycholic acid (CDCA) in anti-platelet aggregation and its application in the prevention and treatment of arterial thrombosis diseases. technical background [0002] With the improvement of living standards, stroke, coronary heart disease and other arterial thrombotic diseases have become the number one killer threatening the health of people in our country and developed countries. Therefore, it is very important to prevent and treat cardiovascular and cerebrovascular thrombotic diseases. Intravascular thrombosis caused by abnormal activation of platelets is the pathological basis of arterial thrombosis coronary heart disease and stroke. The process includes aggregation and spreading of platelets. Therefore, antiplatelet drugs that inhibit platelet activation are the main means of prevention and treatment of such diseases. Antiplatelet drugs curre...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/575A61P7/02A61P31/12A61P35/00A61P35/02A61P9/12A61P9/10
Inventor 张思顾建新周梅玲孙琳琳
Owner SHANGHAIMED
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