CN105687176A - Application of protocatechuic acid in preparing antithrombotic drug - Google Patents
Application of protocatechuic acid in preparing antithrombotic drug Download PDFInfo
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- CN105687176A CN105687176A CN201610047585.1A CN201610047585A CN105687176A CN 105687176 A CN105687176 A CN 105687176A CN 201610047585 A CN201610047585 A CN 201610047585A CN 105687176 A CN105687176 A CN 105687176A
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- protocatechuic acid
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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Abstract
The invention belongs to the field of natural products, and particularly relates to new antithrombotic application of protocatechuic acid. The antithrombotic activity in vivo study result shows that the protocatechuic acid has favorable antithrombotic activity and can be used for preparing an antithrombotic drug.
Description
Technical field
The invention belongs to medicine or/and field of health care products, be specifically related to the new application of protocatechuic acid, be exactly protocatechuic acid application in antithrombotic。
Background technology
Protocatechuic acid is widely present in medicinal plants, is a kind of soluble salvianolic acid composition, not only has and significantly reduce myocardial oxygen consumption, improve cardiac muscle oxygen-resistant ability, the pharmacological actions such as decreased heart rate, also have the effect of obvious anti-hepatitis B virus (hepatitisBVirus, HBV)。But there are no the report in antithrombotic。
Blood also exists blood coagulation system and the antithrombotic system (fibrinolytic system) of mutual antagonism。Under physiological conditions, the thrombin in blood is constantly activated, thus producing thrombin, forms the fibrin of trace, calm in tunica intima。But the fibrinolytic system that the fibrin of these trace has constantly been activated again is dissolved, the thrombin being simultaneously activated also constantly is swallowed by mononuclear phagocyte system。The dynamic equilibrium of blood coagulation system and fibrinolytic system, not only ensure that blood had potential solidifiable but also has been always ensured that the fluid state of blood。But, sometimes under some effect of factor that can promote process of setting, break above-mentioned dynamic equilibrium, triggered coagulation process, just form thrombosis。
Thrombosis is the basic pathology process of numerous disease such as myocardial infarction, ischemic sudden death, deep venous thrombosis etc., it severely compromises the health of the mankind, its formation and hematoblastic gathering, adhesion, endogenous is closely related with extrinsic coagulation system and fibrinous formation。Investigation report according to World Health Organization (WHO), the death that the thrombus disease caused due to atherosclerosis causes has been discharged to first。Arterial thrombus is that speckle instability there occurs breaking of speckle due to atherosclerosis, makes the platelet in blood assemble, have activated internal blood coagulation system, finally result in thrombosis。Once ischemia and the necrosis of tissue will be there is after blocking, produce serious consequence。Under the acute of arterial thrombotic disease or special state, it is necessary to auxiliary uses antithrombotic reagent, can be only achieved better antithrombotic effect。
Summary of the invention
Present invention aim to overcome that prior art defect, it is provided that a kind of protocatechuic acid new opplication in preparing antithrombotic reagent。
The commercially available common commercially available prod of protocatechuic acid, it is also possible to self-control, extracts from plant and obtains。
Protocatechuic acid, another name: PCA, molecular formula: (HO)2C6H3COOH, structural formula is as follows:
。
The internal anti thrombotic action of protocatechuic acid is investigated by the present invention, and result shows: protocatechuic acid has good anti thrombotic action, can be used for preparing antithrombotic reagent。
Detailed description of the invention
The foregoing of the present invention is described in further detail by form more by the following examples。
The anti thrombotic action experiment of embodiment 1 protocatechuic acid
Method: adopt the method for subcutaneous injection adrenalin hydrochloride and ice-water bath to prepare the acute blood-stasis model of rat。The continuous tail vein injection of rat 7 days, every day 1 time, investigates the protocatechuic acid impact on acute blood-stasis model rat blood rheological characteristic and blood coagulation four。
Instrument and material: HF6000-4 Standard for semi-Automated Blood Coagulation Analyzer, HT-100C lectin from hemolymph viscosity tester, TGL-16gR high speed desktop refrigerated centrifuger (Anting Scientific Instrument Factory, Shanghai);XIANGDAN ZHUSHEYE (Jian-Yisheng Pharmaceutical Co., Ltd., Jilin, lot number: 15062503);Prothrombin time (PT) measures test kit (105262);Activated partial thromboplastin time (APTT) measures test kit (1121781);Thrombin time (TT) measures test kit (121151);Fibrinogen (FIB) assay test kit (132079) produces by Shanghai Sun Bio-Tech Co., Ltd.。
Laboratory animal: the SD rat of SPF level, male and female half and half, body weight 250~300g, is provided by Henan Province's Experimental Animal Center, credit number: SCXK (Henan) 2010-0002。
Experimental technique:
The configuration of sample solution: first by a small amount of DMSO sample dissolution, add appropriate polyoxyethylene sorbitan monoleate, finally with normal saline dilution to final volume。Final DMSO: polyoxyethylene sorbitan monoleate: normal saline=10%:5%:85%, sample solution autoclaving (121.3 DEG C, 103.4 kPas) the sterilizing 15min prepared。
The SD rat of male and female half and half, is randomly divided into 4 groups, often group 6。Respectively blank group, model group, positive controls and protocatechuic acid administration group。Continuous tail vein injection is administered 7 days, every day 1 time, blank group and model group give corresponding blank solvent (DMSO: polyoxyethylene sorbitan monoleate: normal saline=10%:5%:85%), positive controls gives XIANGDAN ZHUSHEYE (3.6mL/kg), administration group gives corresponding medicine, starting modeling in the 6th day, method is as follows:
Rat skin lower injection adrenalin hydrochloride injection (0.8mg/kg) 2 times, interval time is 4h。1st time subcutaneous gives 2h after adrenalin hydrochloride, rat is placed in 0~2 DEG C of frozen water went swimming 5min, causes rat acute blood stasis model。After last subcutaneous injection adrenalin hydrochloride, Rat Fast can't help water raising, gives the 7th medicine, with 10% chloral hydrate (300mg/kg) anesthetized rat after 30min, in abdominal aortic blood, measure corresponding index after 16h。
Data process: result adopts arithmetic mean of instantaneous value and standard deviation to represent, numerical statistic adopts SPSS19.0 software one factor analysis of variance method (One-WayANOVA) to compare its significant difference。Measurement result is as follows:
The impact on acute blood-stasis model rat whole blood viscosity of table 1 protocatechuic acid
Datarepresentmean ± SD.n=6;
Compared with blank group, * * *P< 0.001;
Compared with model group,### P< 0.001;
Compared with positive control,△△△ P<0.001。
Model group compared with blank group, the whole blood viscosity under high, medium and low shear frequency all extremely significantly raise (P< 0.001), the acute blood-stasis model modeling success of rat is described。Compared with model group, the whole blood viscosity all pole under each shear frequency of protocatechuic acid administration group significantly reduce (P< 0.001), and reduce under undercut Frequency the effect of whole blood viscosity with positive control quite (P> 0.05), illustrate that it has good antithrombotic acitivity。
The impact on acute blood-stasis model rat plasma viscosity of table 2 protocatechuic acid
Datarepresentmean ± SD.n=6;
Compared with blank group, * * *P< 0.001;
Compared with model group,### P<0.001,or,# P< 0.05;
Compared with positive control,△△△ P<0.001。
Model group compared with blank group, the plasma viscosity under middle shear rate extremely significantly raise (P< 0.001), rat acute blood stasis model modeling success is described。Compared with model group, protocatechuic acid administration group can significantly reduce plasma viscosity (P< 0.05), illustrate that protocatechuic acid has good antithrombotic acitivity。
The impact on acute blood-stasis model rat blood coagulation four of table 3 protocatechuic acid
Datarepresentmean ± SD.n=5;
Compared with blank group, * * *P< 0.001;
Compared with model group,### P<0.001,or,# P< 0.05;
Compared with positive control,△△△ P<0.001or,△ P<0.05。
Model group is compared with blank group, and TT, APTT and PT all pole significantly decreases, and FIB pole raise significantly (P< 0.001), the acute blood-stasis model modeling success of rat is described。Compared with model group, protocatechuic acid administration group all can extend TT, APTT and PT significantly, and can significantly decrease FIB(P<0.001,or,P< 0.05), and protocatechuic acid extend effect and the positive control of TT quite (P> 0.05), illustrate that protocatechuic acid can suppress the solidification of blood by fibrinogenic content in intrinsic coagulation pathway and exogenous cruor pathway and reduction blood plasma, thus suppressing the formation of thrombosis。
Claims (1)
1. protocatechuic acid application in preparing antithrombotic reagent。
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CN201610047585.1A CN105687176A (en) | 2016-01-25 | 2016-01-25 | Application of protocatechuic acid in preparing antithrombotic drug |
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2016
- 2016-01-25 CN CN201610047585.1A patent/CN105687176A/en active Pending
Non-Patent Citations (1)
Title |
---|
KEUNYOUNG KIM等: "Novel Antiplatelet Activity of Protocatechuic Acid through the Inhibition of High Shear Stress-Induced Platelet Aggregation", 《THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 * |
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Application publication date: 20160622 |
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